Next Article in Journal
Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α1-Antitrypsin Deficiency
Previous Article in Journal
Evaluation of Four Different Analytical Tools to Determine the Regional Origin of Gastrodia elata and Rehmannia glutinosa on the Basis of Metabolomics Study

Molecules 2014, 19(5), 6309-6329; doi:10.3390/molecules19056309

Article
Bifunctionalized Allenes. Part XIII. A Convenient and Efficient Method for Regioselective Synthesis of Phosphorylated α-Hydroxyallenes with Protected and Unprotected Hydroxy Group
Ismail E. Ismailov , Ivaylo K. Ivanov and Valerij Ch. Christov *
Department of Organic Chemistry & Technology, Faculty of Natural Sciences, Konstantin Preslavsky University of Shumen, 115, Universitetska Str., BG-9712 Shumen, Bulgaria; E-Mails: ismail78@mail.bg (I.E.I.); iivanov@shu-bg.net (I.K.I.)
*
Author to whom correspondence should be addressed; E-Mail: vchristo@shu-bg.net; Tel.: +359-54-830-495; Fax: +359-54-830-371.
Received: 9 April 2014; in revised form: 1 May 2014 / Accepted: 5 May 2014 /
Published: 16 May 2014

Abstract

: The paper describes a convenient and efficient method for regioselective synthesis of phosphorylated α-hydroxyallenes using an atom economical [2,3]-sigmatropic rearrangement of intermediate propargyl phosphites or phosphinites. These can be readily prepared via reaction of protected alkynols with dimethyl chlorophosphite or chlorodiphenyl phosphine respectively in the presence of a base.
Keywords:
synthesis; hydroxy group protection; [2,3]-sigmatropic rearrangement; phosphorylated α-hydroxyallenes

1. Introduction

The synthesis and application of allene derivatives has had a great influence in preparative organic chemistry during the last three decades. The crucial structural characteristic of allenes is the presence of two π electron clouds separated by a single sp-hybridized carbon atom. Due to that very unique structural and electronic arrangement allenic compounds have an extraordinary reactivity profiles [1,2,3,4,5,6,7,8]. Moreover, functionalized allenes have also attracted growing attention due to their versatility as key building blocks for organic synthesis. The synthetic potential of functionalized allenes has been thoroughly explored in recent years. The research in that area has led to the development of novel methods for the construction of a variety of functionalized heterocyclic and carbocyclic systems [9,10,11,12,13].

There are variety of methods for the construction of hydroxyallenes that include prototropic rearrangement of propargylic alcohols [14,15,16], metal-catalyzed nucleophilic addition of propargylic derivatives to aldehydes [17,18,19,20,21,22,23,24], Cu(I)-catalyzed reaction of propargylic chlorides with Grignard reagents [25,26,27], metal-catalyzed reaction of propargylic oxiranes with organometallic compounds [28,29,30,31,32,33,34,35] and ketones [36,37], reduction of alcohols, ethers, oxiranes etc. with aluminium reagents [38,39,40], Pd(0)-catalyzed reaction of cyclic carbonates with acetylenic compounds [41,42], SN2’ [43,44] and AN [45,46,47] reactions of metalled alkoxy-allenes with oxiranes and ketones [5], and other routes [48,49].

In addition there are methods [50,51,52,53] for the synthesis of phosphorus-containing allenes (phosphonates [54,55,56,57,58,59], phosphinates [60,61], and phosphine oxides [62,63,64,65,66,67,68,69]) including reactions of α-alkynols with chloride-containing derivatives of phosphorus acids followed by [2,3]-sigmatropic rearrangement. Several diethylphosphono-substituted α-allenic alcohols were prepared by Brel [70,71] directly from alcohols by Horner-Mark rearrangement of unstable propargylic phosphites.

Since the reversible interconversion of propargylic phosphites, phosphonites and phosphinites to allenyl phosphonates, phosphinates and phosphine oxides was discovered five decades ago [60,61], it has become one of the most thoroughly investigated and synthetically applied [2,3]-sigmatropic rearrangements. Numerous synthetic applications of the rearrangement have been reported, such as its use in the synthesis of allenic steroids for substrate-induced inactivation of aromatase [72], in the efficient synthesis of (2R)-2-amino-5-phosphonopentanoic acid (AP5) as a powerful and selective N-methyl-d-aspartate (NMDA) antagonist [73], in the preparation of the phosphonate analogues of phosphatidyl derivatives [74,75], and, in the synthesis of new acyclic analogues of nucleotides containing a purine or pyrimidine moiety and an allenic skeleton [76,77].

Our research program on the chemistry of the bifunctionalized allenes requires a convenient method to introduce a phosphorus-containing group such as phosphonate or phosphine oxide group as well as a hydroxyalkyl group in the first position to the allenic system of double bonds. The above-mentioned groups attract more and more researchers’ attention as useful functionalities in organic synthesis. The emphasis is particularly on the applications of these groups as temporary transformers of chemical reactivity of the allenic system in the synthesis of eventually heterocyclic compounds.

Our scientific interest on the synthesis [78] and electrophilic cyclization reactions [79] of bifunctionalized allenes reported in our previous articles let to the discovery of a convenient and efficient method for regioselective synthesis of phosphorylated α-hydroxyallenes by an atom economical [2,3]-sigmatropic rearrangement of the mediated 4-(tetrahydro-2H-pyran-2-yloxy)-propargyl phosphites or phosphinites.

2. Results and Discussion

We based our strategy for the synthesis of the phosphorylated α-hydroxyallenes on our experience in preparation of the 4-heteroatom-functionalized allenecarboxylates [78] and relied on the well-precedented [2,3]-sigmatropic shift of propargylic phosphites to allenephosphonates [54,55,56,57,58,59] and propargylic phosphinites to allenyl phosphine oxides [62,63,64,65,66,67,68,69]. We were aware of the fact that a precedent exists for such an approach to the synthesis of the diethylphosphono-substituted α-allenic alcohols [70,71], but as far as we know, a general useful method for regioselective synthesis of phosphorylated (phosphonates and phosphine oxides) α-hydroxyallenes (primary, secondary or tertiary alcohols) with protected or unprotected hygroxy group has not been reported yet.

2.1. Synthesis of Phosphorylated α-Hydroxyallenes with Protected Hydroxy Group

The main target in our research, and namely 1,1-bifunctionalized allenes, was achieved as a range of the phosphorylated α-hydroxyallenes 7, 9, 10, and 11 were prepared by applying the following four-step procedure: (i) protection of hydroxy group in the propagylic alcohols 1; (ii) subsequent reaction with Grignard reagent to give the protected alkynols 5; (iii) interaction with dimethyl chlorophosphite or chlorodiphenyl phosphine in the presence of a base; and finally (iv) [2,3]-sigmatropic rearrangement of the protected propargyl phosphites or phosphinites.

2.1.1. Synthesis of (Tetrahydro-2H-pyran-2-yloxy)-alkynols

The first step in our investigation was to examine the hydroxy group protection in the propargylic alcohols 1 with 3,4-dihydro-2H-pyran (DHP) in the presence of pyridinium p-toluenesulfonate (PPTS) [80,81,82,83] (Scheme 1 and Table 1). Thus, the formed alkynyloxy-tetrahydro-2H-pyrans 2 were isolated by distillation in essentially quantitative yields (95%–99%). Reaction of the protected propargylic compounds 2 with ethyl-magnesium bromide and subsequent dropwise addition of propargyl magnesium bromide 3 generated in situ to ketones 4 and reflux for 24 h gave the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5 which were stable and were isolated by column chromatography in 53%–61% yields.

Molecules 19 06309 g001 1024
Scheme 1. Synthesis of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5.

Click here to enlarge figure

Scheme 1. Synthesis of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5.
Molecules 19 06309 g001 1024

Reagents and Conditions: (i) DHP (3,4-dihydro-2H-pyran) (1.5 eq), PPTS (0.1 eq), CH2Cl2, rt, 4 h, distillation; (ii) EtMgBr (1 eq), THF, reflux, 2 h; (iii) dropwise addition of 3 to R2R3C=O 4 (2 eq) (R2 = Me, R3 = Et; R2 = Me, R3 = Bu; R2 + R3 = -(CH2)5-), reflux, 24 h, column chromatography.

Table Table 1. Synthesis of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5.

Click here to display table

Table 1. Synthesis of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5.
EntryAlcoholRR1R2R3Yield a, %
15aHHMeEt61
25bHHMeBu59
35cHH-(CH2)5-58
45dHMeMeEt57
55eHMeMeBu56
65fHMe-(CH2)5-56
75gMeMeMeEt54
85hMeMeMeBu53

a Isolated yields by chromatographic purification.

2.1.2. Synthesis of Dimethyl 1-(Tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates

Once we had the required propargyl alcohols 5 with protected hydroxyl groups, we were able to investigate the proposed reactions with the corresponding chloro-containing phosphorus reagents such as dimethyl chlorophosphite and chlorodiphenyl phosphine in the presence of a base and subsequent [2,3]-sigmatropic rearrangement of the intermediate 4-(tetrahydro-2H-pyran-2-yloxy)-propargyl phosphites or phosphinites 6 and 8. Let us start with the dimethyl 1-(tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates 7a–h that can be easily prepared via an atom economical 2,3-sigmatropic rearrangement of the 4-(tetrahydro-2H-pyran-2-yloxy)-propargyl phosphites 6a–h, intermediates formed by reaction of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5a–h with dimethyl chloro-phosphite, prepared in situ from phosphorus trichloride and 2 equiv. of methanol in the presence of triethylamine, and 2 equiv. of pyridine, according to Scheme 2 and Table 2.

Molecules 19 06309 g002 1024
Scheme 2. Synthesis of the dimethyl 1-(tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates 7.

Click here to enlarge figure

Scheme 2. Synthesis of the dimethyl 1-(tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates 7.
Molecules 19 06309 g002 1024

Reagents and Conditions: (iv) PCl3(1 eq), Et3N (1.1 eq), Et2O, −70 °C, 30 min stirring, pyridine (2.2 eq), MeOH (2 eq), Et2O, [2,3-σ]-rearrangement, −70 °C, 1 h, rt, 10 h, column chromatography.

Table Table 2. Synthesis of the dimethyl 1-(tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates 7.

Click here to display table

Table 2. Synthesis of the dimethyl 1-(tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates 7.
EntryAlleneRR1R2R3Yield a, %
17aHHMeEt78
27bHHMeBu75
37cHH-(CH2)5-73
47dHMeMeEt74
57eHMeMeBu72
67fHMe-(CH2)5-75
77gMeMeMeEt71
87hMeMeMeBu70

a Isolated yields by chromatographic purification.

2.1.3. Synthesis of 2-[2-(Diphenylphosphinoyl-2,3-dienyloxy)]-tetrahydro-2H-pyrans

Next, the reaction of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5a–h with chlorodiphenyl phosphine in the presence of triethylamine at −70 °C gave the expected 2-(2-diphenylphosphinoyl-2,3-dienyloxy)-tetrahydro-2H-pyrans 9a–h in very good yields (Table 3) as a result of [2,3]-sigmatropic rearrangement of the 4-(tetrahydro-2H-pyran-2-yloxy)-propargyl phosphinites 8a–h for 8 h at room temperature, according to the reaction sequence outlined in Scheme 3.

Table Table 3. Synthesisof the 2-(2-diphenylphosphinoyl-2,3-dienyloxy)-tetrahydro-2H-pyrans 9.

Click here to display table

Table 3. Synthesisof the 2-(2-diphenylphosphinoyl-2,3-dienyloxy)-tetrahydro-2H-pyrans 9.
EntryAlleneRR1R2R3Yield a, %
19aHHMeEt86
29bHHMeBu84
39cHH-(CH2)5-81
49dHMeMeEt83
59eHMeMeBu82
69fHMe-(CH2)5-80
79gMeMeMeEt80
89hMeMeMeBu78

a Isolated yields by chromatographic purification.

Molecules 19 06309 g003 1024
Scheme 3. Synthesis of the 2-(2-diphenylphosphinoyl-2,3-dienyloxy)-tetrahydro-2H-pyrans 9.

Click here to enlarge figure

Scheme 3. Synthesis of the 2-(2-diphenylphosphinoyl-2,3-dienyloxy)-tetrahydro-2H-pyrans 9.
Molecules 19 06309 g003 1024

Reagents and Conditions: (vi) Ph2PCl (1 eq), Et3N (1.1 eq), Et2O, −70 °C; (vii) [2,3-σ]-rearrangement, −70 °C, 1 h, rt, 8 h, column chromatography.

A new family of phosphorylated α-hydroxyallenes with protected hydroxyl group 7 and 9 were synthesized via an atom economical and regioselective [2,3]-sigmatropic rearrangement of the intermediate formed propargyl phosphites or phosphinites in the reaction of protected alkynols 5 with dimethylchloro phosphite or chlorodiphenyl phosphine in the presence of triethylamine.

2.2. Synthesis of Phosphorylated α-Hydroxyallenes with Unprotected Hydroxy Group

Compounds 7 and 9 were stable enough to be handled at ambient temperature. The hydroxy group was deprotected by stirring the ethanol solution of the protected hydroxylalkyl-allenephosphonates 7 and hydroxylalkyl-allenyl phosphine oxides 9 in the presence of 0.1 equiv. PPTS at room temperature for 6 h, according to Scheme 4 and Table 4.

Molecules 19 06309 g004 1024
Scheme 4. Synthesis of the 1-hydroxyalkyl-1,2-dienephosphonates 10, the 3-diphenylphosphinoyl-2,3-dien-1-ols 11ac and the 3-diphenylphosphinoyl-3,4-dien-2-ols 11dh.

Click here to enlarge figure

Scheme 4. Synthesis of the 1-hydroxyalkyl-1,2-dienephosphonates 10, the 3-diphenylphosphinoyl-2,3-dien-1-ols 11ac and the 3-diphenylphosphinoyl-3,4-dien-2-ols 11dh.
Molecules 19 06309 g004 1024

Reagents and Conditions: (viii) PPTS (0.1 eq), EtOH, rt, 6 h, stirring.

Table Table 4. Synthesis of the 1-hydroxyalkyl-1,2-dienephosphonates 10, the 3-diphenylphosphinoyl-2,3-dien-2-ols 11ac and the 3-diphenylphosphinoyl-3,4-dien-2-ols 11dh.

Click here to display table

Table 4. Synthesis of the 1-hydroxyalkyl-1,2-dienephosphonates 10, the 3-diphenylphosphinoyl-2,3-dien-2-ols 11ac and the 3-diphenylphosphinoyl-3,4-dien-2-ols 11dh.
EntryAlleneRR1R2R3Yield a, %
110aHHMeEt80
210bHHMeBu78
310cHH-(CH2)5-77
410dHMeMeEt80
510eHMeMeBu79
610fHMe-(CH2)5-81
710gMeMeMeEt79
810hMeMeMeBu78
911aHHMeEt86
1011bHHMeBu83
1111cHH-(CH2)5-81
1211dHMeMeEt87
1311eHMeMeBu85
1411fHMe-(CH2)5-88
1511gMeMeMeEt84
1611hMeMeMeBu83

a Isolated yields by chromatographic purification.

After a conventional work-up, all allenic products 7, 9, 10, and 11were isolated as stable yellow or orange oils by column chromatography and identified by 1H-, 13C-, and 31P-NMR and IR spectra as well as by elemental analysis.

3. Experimental Section

3.1. General Information

All new synthesized compounds were purified by column chromatography and characterized on the basis of NMR, IR, and microanalytical data. NMR spectra were recorded on DRX Bruker Avance-250 (1H at 250.1 MHz, 13C at 62.9 MHz, 31P at 101.2 MHz) and Bruker Avance II + 600 (Bruker BioSpinGmbH, Karlsruhe, Germany) (1H at 600.1 MHz, 13C at 150.9 MHz, 31P at 242.9 MHz) spectrometers for solutions in CDCl3. All 1H-and 13C-NMR experiments were measured referring to the signal of internal TMS and 31P-NMR experiments were measured referring to the signal of external 85% H3PO4. J values are given in hertz. IR spectra were recorded with an FT-IRAfinity-1 Shimadzu spectrophotometer (Shimadzu, Tokyo, Japan). Elemental analyses were carried out by the Microanalytical Service Laboratory of Faculty of Chemistry and Pharmacy, University of Sofia, Bulgaria, using Vario EL3 CHNS(O) (Elementar Analysensysteme, Hanau, Germany). Column chromatography was performed on Kieselgel F254 60 (70–230 mesh ASTM, 0.063–0.200 nm, Merck, Darmstadt, Germany). Et2O and THF were distilled from Na wire/benzophenone, CH2Cl2 was distilled over CaH2, other commercially available chemicals were used without additional purification unless otherwise noted. Reactions were carried out in oven dried glassware under an argon atmosphere and exclusion of moisture. All compounds were checked for purity on TLC plates Kieselgel F254 60 (Merck).

3.2. General Procedure [80,81,82,83] for Synthesis of the Alkynyloxy-tetrahydro-2H-pyrans 2

A solution of alkynols 1 (60.0 mmol) and DHP (7.6 g, 90.0 mmol) [0.152 g/mL] in dry methylene chloride (50 mL) containing PPTS (1.5 g, 6.0 mmol) [0.03 g/mL] is stirred for 4 h at room temperature. Then the reaction was quenched with saturated NaHCO3 end extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate. After evaporation of the solvent, distillation gives an essentially quantitative yield of the alkynyloxy-tetrahydro-2H-pyrans 2 (95%–99%) which are described in the literature [80,81,82,83].

3.3. General Procedure for Synthesis of (Tetrahydro-2H-pyran-2-yloxy)-alkynols 5

Ethylmagnesium bromide [prepared from magnesium (1.2 g, 50.0 mmol) [0.024 g/mL] and ethyl bromide (5.5 g, 50.0 mmol) [0.11 g/mL] in dry THF (50 mL)] is added dropwise under stirring to substituted alkynyloxy-tetrahydro-2H-pyrans 2 (50.0 mmol) and then the mixture is refluxed for 2 h. The solution of the prepared alkynyl magnesium bromides 3 is added dropwise under stirring to the ketones 4 (100.0 mmol). The mixture is refluxed for 24 h and after cooling is hydrolyzed with a saturated aqueous solution of ammonium chloride. The organic layer is separated, washed with water, and dried over over anhydrous sodium sulfate. Solvent and the excess of ketone are removed by distillation. Purification of the residue is achieved by column chromatography (silica gel, Kieselgel Merck 60 F254) with ethyl acetate-hexane (5:1). The pure products 5 had the following properties:

3-Methyl-6-(tetrahydro-2H-pyran-2-yloxy)-hex-4-yn-3-ol (5a). Colourless oil, yield: 61%. Rf 0.53; IR (neat, cm−1): 1121 (C-O-C), 3439 (OH). 1H-NMR (600.1 MHz): δ 1.37 (t, J = 7.2 Hz, 3H, Me-CH2), 1.40 (s, 3H, Me-C-OH), 1.48, 1.67, 1.71, 3.59, 4.62 (overlapping multiplets, 9H, OTHP), 1.79 (m, 2H, Me-CH2), 3.54 (s, 1H, OH), 4.29 (m, 2H, CH2O). 13C-NMR (150.9 MHz) δ = 9.9, 19.0, 26.1, 28.4, 30.7, 37.5, 55.0, 62.3, 66.2, 81.5, 89.4, 97.7. Anal. Calcd for C12H20O3 (212.29): C 67.89, H 9.50. Found: C 67.81, H 9.44.

4-Methyl-1-(tetrahydro-2H-pyran-2-yloxy)-oct-2-yn-4-ol (5b). Colourless oil, yield: 59%. Rf 0.49; IR (neat, cm−1): 1121 (C-O-C), 3420 (OH). 1H-NMR (250.1 MHz): δ 0.87 (t, J = 6.5 Hz, 3H, Me-(CH2)3), 1.39 (s, 3H, Me-C-OH), 1.34–1.39, 1.48–1.80, 3.61, 4.72 (overlapping multiplets, 15H, OTHP + (CH2)3-Me), 2.70 (s, 1H, OH), 4.24 (m, 2H, CH2O). 13C-NMR (62.9 MHz) δ = 14.7, 19.2, 23.9, 24.7, 25.6, 29.4, 30.8, 45.5, 55.3, 60.9, 64.2, 80.1, 89.0, 97.1. Anal. Calcd for C14H24O3 (240.34): C 69.96, H 10.07. Found: C 70.03, H 10.12.

1-[3-(Tetrahydro-2H-pyran-2-yloxy)-prop-1-ynyl]-cyclohexanol (5c). Colourless oil, yield: 58%. Rf 0.48; IR (neat, cm−1): 1120 (C-O-C), 3412 (OH). 1H-NMR (250.1 MHz): δ 1.30–1.77, 1.96–2.01, 2.10–2.16, 3.54–3.72, 4.70–4.74 (overlapping multiplets, 19H, OTHP + (CH2)5), 3.51 (s, 1H, OH), 4.27 (m, 2H, CH2O). 13C-NMR (62.9 MHz) δ = 19.2, 23.2, 25.7, 26.1, 30.4, 40.0, 53.8, 62.5, 69.2, 81.0, 88.9, 96.8. Anal. Calcd for C14H22O3 (238.32): C 70.56, H 9.30. Found: C 70.65, H 9.36.

3-Methyl-6-(tetrahydro-2H-pyran-2-yloxy)-hept-4-yn-3-ol (5d). Colourless oil, yield: 57%. Rf 0.54; IR (neat, cm−1): 1122 (C-O-C), 3398 (OH). 1H-NMR (600.1 MHz): δ 1.36 (t, J = 7.4 Hz, 3H, Me-CH2), 1.38 (s, 3H, Me-C-OH), 1.46, 1.62, 1.71, 3.62, 4.71 (overlapping multiplets, 9H, OTHP), 1.49 (d, J = 7.0 Hz, 3H, Me-CH), 1.67 (m, 2H, Me-CH2), 3.24 (s, 1H, OH), 4.78 (m, 1H, CH-Me). 13C-NMR (150.9 MHz) δ = 9.4, 20.5, 22.8, 26.2, 28.7, 30.9, 36.4, 61.7, 63.0, 66.9, 84.5, 88.7, 99.1. Anal. Calcd for C13H22O3 (226.31): C 68.99, H 9.80. Found: C 69.06, H 9.75.

5-Methyl-2-(tetrahydro-2H-pyran-2-yloxy)-non-3-yn-5-ol (5e). Colourless oil, yield: 56%. Rf 0.51; IR (neat, cm−1): 1123 (C-O-C), 3432 (OH). 1H-NMR (600.1 MHz): δ 0.88 (t, J = 6.3 Hz, 3H, Me-(CH2)3), 1.36 (s, 3H, Me-C-OH), 1.33–1.40, 1.46–1.79, 3.76, 4.78 (overlapping multiplets, 15H, OTHP + (CH2)3-Me), 1.52 (d, J = 6.9 Hz, 3H, Me-CH), 2.54 (s, 1H, OH), 4.66 (m, 1H, CH-Me). 13C-NMR (150.9 MHz) δ = 14.4, 20.2, 22.4, 24.2, 24.9, 26.1, 30.2, 31.0, 45.4, 62.7, 63.0, 64.4, 84.2, 88.1, 99.4. Anal. Calcd for C15H26O3 (254.37): C 70.83, H 10.30. Found: C 70.87, H 10.23.

1-[3-(Tetrahydro-2H-pyran-2-yloxy)-but-1-ynyl]-cyclohexanol (5f). Colourless oil, yield: 56%. Rf 0.48; IR (neat, cm−1): 1119 (C-O-C), 3429 (OH). 1H-NMR (250.1 MHz): δ 1.29–1.52, 1.67–1.84, 1.95–2.12, 3.50–3.87, 4.79–4.82 (overlapping multiplets, 19H, OTHP + (CH2)5), 1.49 (d, J = 7.0 Hz, 3H, Me-CH), 3.32 (s, 1H, OH), 4.71 (m, 1H, CH-Me). 13C-NMR (62.9 MHz) δ = 20.1, 22.5, 23.0, 24.7, 26.0, 32.4, 40.6, 61.9, 62.4, 68.9, 83.2, 90.2, 98.9. Anal. Calcd for C15H24O3 (252.35): C 71.39, H 9.59. Found: C 71.30, H 9.66.

3,6-Dimethyl-6-(tetrahydro-2H-pyran-2-yloxy)-hept-4-yn-3-ol (5g). Colourless oil, yield: 54%. Rf 0.49; IR (neat, cm−1): 1120 (C-O-C), 3416 (OH). 1H-NMR (600.1 MHz): δ 1.34 (t, J = 7.4 Hz, 3H, Me-CH2), 1.38 (s, 3H, Me-C-OH), 1.43, 1.66, 1.70, 3.69, 4.91 (overlapping multiplets, 9H, OTHP), 1.51 (s, 6H, 2Me), 1.68 (m, 2H, Me-CH2), 3.22 (s, 1H, OH). 13C-NMR (150.9 MHz) δ = 9.3, 21.1, 25.4, 28.6, 30.0, 32.4, 35.7, 64.1, 66.3, 71.0, 82.3, 86.5, 96.4. Anal. Calcd for C14H24O3 (240.34): C 69.96, H 10.07. Found: C 69.89, H 10.15.

2,5-Dimethyl-2-(tetrahydro-2H-pyran-2-yloxy)-non-3-yn-5-ol (5h). Colourless oil, yield: 53%. Rf 0.45; IR (neat, cm−1): 1119 (C-O-C), 3421 (OH). 1H-NMR (600.1 MHz): δ 0.87 (t, J = 6.4 Hz, 3H, Me-(CH2)3), 1.34 (s, 3H, Me-C-OH), 1.36–1.42, 1.47–1.72, 3.59, 4.89 (overlapping multiplets, 15H, OTHP + (CH2)3-Me), 1.50 (s, 6H, 2Me), 2.542 (s, 1H, OH). 13C-NMR (150.9 MHz) δ = 14.7, 21.1, 24.3, 24.7, 25.7, 28.4, 30.0, 31.7, 44.2, 64.7, 64.9, 71.3, 82.4, 86.1, 96.7. Anal. Calcd for C16H28O3 (268.39): C 71.60, H 10.52. Found: C 71.52, H 10.58.

3.4. General Procedure for Synthesis of the Dimethyl 1-(Tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates 7

To a solution of phosphorus trichloride (2.8 g, 20.0 mmol) [0.047 g/mL] and triethylamine (2.2 g, 22.0 mmol) [0.037 g/mL] in dry diethyl ether (60 mL) at –70 °C was added dropwise with stirring a solution of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5 (20.0 mmol) in the same solvent (20 mL). After 30 min stirring at the same temperature a solution of pyridine (3.1 g, 44.0 mmol) [0.062 g/mL] and of methanol (1.3 g, 40.0 mmol) [0.026 g/mL] in dry diethyl ether (50 mL) were added. The reaction mixture was stirred for an hour at the same temperature and for 10 h at room temperature. The mixture was then washed with water, 2 N HCl, extracted with ether, washed with saturated NaCl, and dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue was chromatographed on a column (silica gel, Kieselgel Merck 60 F254) with a mixture of ethyl acetate and hexane (10:1) as eluent to give the pure products 7 as oils, which had the following properties:

Dimethyl 3-methyl-1-(tetrahydro-2H-pyran-2-yloxymethyl)-penta-1,2-dienephosphonate (7a). Yellow oil, yield: 78%. Rf 0.58; IR (neat, cm−1): 1119 (C-O-C), 1250 (P=O), 1958 (C=C=C). 1H-NMR (600.1 MHz): δ 1.07 (t, J = 7.4 Hz, 3H, Me-CH2), 1.53, 1.60, 1.71, 3.53, 4.32 (overlapping multiplets, 9H, OTHP), 1.80 (d, J = 6.7 Hz, 3H, Me-C=), 2.07 (m, 2H, Me-CH2), 3.76 (d, J = 11.2 Hz, 3H, MeO), 4.14 (m, 2H, CH2O). 13C-NMR (150.9 MHz) δ = 12.0 (J = 7.6 Hz), 18.1 (J = 6.6 Hz), 19.2, 25.5, 26.5 (J = 4.2 Hz), 30.4, 52.8 (J = 6.2 Hz), 61.9, 64.9 (J = 10.1 Hz), 90.7 (J = 191.2 Hz), 97.2, 104.6 (J = 15.6 Hz), 208.6 (J = 5.5 Hz). 31P-NMR (242.9 MHz): δ 20.3. Anal. Calcd for C14H25O5P (304.32): C 55.25; H 8.28. Found: C 55.33; H 8.19.

Dimethyl 3-methyl-1-(tetrahydro-2H-pyran-2-yloxymethyl)-hepta-1,2-dienephosphonate (7b). Yellow oil, yield: 75%. Rf 0.59; IR (neat, cm−1): 1121 (C-O-C), 1251 (P=O), 1956 (C=C=C). 1H-NMR (600.1 MHz): δ 0.90 (t, J = 7.2 Hz, 3H, Me-(CH2)3), 1.44, 1.53, 1.60, 3.53, 4.36 (overlapping multiplets, 9H, OTHP), 1.78 (d, J = 6.5 Hz, 3H, Me-C=), 1.36, 1.82, 2.05 (overlapping multiplets, 6H, Me-(CH2)3), 3.75 (d, J = 11.2 Hz, 3H, MeO), 4.09 (m, 2H, CH2O). 13C-NMR (150.9 MHz) δ = 13.9, 18.0 (J = 6.7 Hz), 19.2, 22.2, 25.5, 29.4, 30.3, 32.9, 52.7 (J = 6.3 Hz), 61.8, 64.9 (J = 10.1 Hz), 90.3 (J = 191.7 Hz), 97.3, 102.8 (J = 16.2 Hz), 208.8 (J = 5.4 Hz). 31P-NMR (242.9 MHz): δ 20.4. Anal. Calcd for C16H29O5P (332.37): C 57.82, H 8.79. Found: C 57.90, H 8.72.

Dimethyl 2-cyclohexylidene-1-(tetrahydro-2H-pyran-2-yloxymethyl)-ethenephosphonate (7c). Yellow oil, yield: 73%. Rf 0.57; IR (neat, cm−1): 1118 (C-O-C), 1252 (P=O), 1953 (C=C=C). 1H-NMR (600.1 MHz): δ 1.25–2.23, 3.55, 3.86, 4.31 (overlapping multiplets, 19H, (CH2)5 + OTHP), 3.74 (d, J = 11.1 Hz, 3H, MeO), 4.15 (m, 2H, CH2O). 13C-NMR (150.9 MHz) δ = 19.1, 25.5, 25.7, 26.5, 30.3 (J = 5.9 Hz), 30.4, 52.9 (J = 6.2 Hz), 62.0, 64.7 (J = 10.8 Hz), 88.6 (J = 190.7 Hz), 97.2, 105.1 (J = 15.6 Hz), 205.6 (J = 5.1 Hz). 31P-NMR (242.9 MHz): δ 21.2. Anal. Calcd for C16H27O5P (330.36): C 58.17, H 8.24. Found: C 58.24, H 8.18.

Dimethyl 3-methyl-1-[1-(tetrahydro-2H-pyran-2-yloxy)-ethyl]-penta-1,2-dienephosphonate (7d). Orange oil, yield: 74%. Rf 0.44; IR (neat, cm−1): 1122 (C-O-C), 1259 (P=O), 1951 (C=C=C). 1H-NMR (600.1 MHz): δ 0.95 (t, J = 7.3 Hz, 3H, Me-CH2), 1.41 (dd, J = 6.4 Hz, J = 10.2 Hz, 3H, Me-CHO), 1.51, 1.58, 1.68, 3.63, 4.38 (overlapping multiplets, 9H, OTHP), 1.74 (d, J = 6.6 Hz, 3H, Me-C=), 2.04 (m, 2H, Me-CH2), 3.77 (d, J = 11.2 Hz, 3H, MeO), 4.67 (m, 1H, CHO). 13C-NMR (150.9 MHz) δ = 12.3 (J = 7.5 Hz), 18.5 (J = 6.3 Hz), 19.4, 23.4 (J = 7.6 Hz), 25.5, 27.7 (J = 4.6 Hz), 30.5, 52.5 (J = 6.3 Hz), 62.4, 67.4 (J = 10.3 Hz), 95.8, 96.4 (J = 192.0 Hz), 104.4 (J = 15.9 Hz), 209.2 (J = 5.1 Hz). 31P-NMR (242.9 MHz): δ 20.4. Anal. Calcd for C15H27O5P (318.35): C 56.59, H 8.55. Found: C 56.64, H 8.63.

Dimethyl 3-methyl-1-[1-(tetrahydro-2H-pyran-2-yloxy)-ethyl]-hepta-1,2-dienephosphonate (7e). Orange oil, yield: 72%. Rf 0.43; IR (neat, cm−1): 1120 (C-O-C), 1254 (P=O), 1956 (C=C=C). 1H-NMR (600.1 MHz): δ 0.93 (t, J = 7.1 Hz, 3H, Me-(CH2)3), 1.43 (dd, J = 6.3 Hz, J = 10.0 Hz, 3H, Me-CHO), 1.48, 1.55, 1.64, 3.62, 4.38 (overlapping multiplets, 9H, OTHP), 1.77 (d, J = 6.6 Hz, 3H, Me-C=), 1.41, 1.74, 2.11 (overlapping multiplets, 6H, Me-(CH2)3), 3.76 (d, J = 11.2 Hz, 3H, MeO), 4.64 (m, 1H, CHO). 13C-NMR (150.9 MHz) δ = 13.8, 18.8 (J = 6.5 Hz), 19.5, 22.7, 23.5 (J = 7.5 Hz), 25.7, 29.6, 30.4, 32.8, 52.3 (J = 6.2 Hz), 62.3, 68.6 (J = 10.2 Hz), 91.4 (J = 191.7 Hz), 95.6, 103.4 (J = 16.2 Hz), 209.0 (J = 5.3 Hz). 31P-NMR (242.9 MHz): δ 20.5. Anal. Calcd for C17H31O5P (346.40): C 58.94, H 9.02. Found: C 59.01, H 8.96.

Dimethyl 1-cyclohexylidenemethylene-2-(tetrahydro-2H-pyran-2-yloxy)-propanephosphonate (7f). Dark orange oil, yield: 75%. Rf 0.42; IR (neat, cm−1): 1122 (C-O-C), 1258 (P=O), 1953 (C=C=C). 1H-NMR (600.1 MHz): δ 1.31–2.27, 3.57, 3.71, 4.34 (overlapping multiplets, 19H, (CH2)5 + OTHP), 1.42 (d, J = 6.2 Hz, 3H, Me-CHO), 3.74 (d, J = 11.1 Hz, 3H, MeO), 4.51 (m, 1H, CHO). 13C-NMR (150.9 MHz) δ = 19.6, 23.5 (J = 7.6 Hz), 25.6, 24.7, 25.8, 29.4 (J = 5.7 Hz), 30.6, 52.8 (J = 6.3 Hz), 62.6, 65.8 (J = 10.6 Hz), 93.8 (J = 189.6 Hz), 94.7, 106.0 (J = 15.5 Hz), 204.3 (J = 5.0 Hz). 31P-NMR (242.9 MHz): δ 20.2. Anal. Calcd for C17H29O5P (344.38): C 59.29, H 8.49. Found: C 59.36, H 8.43.

Dimethyl 3-methyl-1-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)-ethyl]-penta-1,2-dienephosphonate (7g). Orange oil, yield: 71%. Rf 0.44; IR (neat, cm−1): 1117 (C-O-C), 1252 (P=O), 1949 (C=C=C). 1H-NMR (600.1 MHz): δ 1.05 (t, J = 7.4 Hz, 3H, Me-CH2), 1.45 (d, J = 10.3 Hz, 6H, Me2CO), 1.47, 1.60, 1.64, 3.68, 4.35 (overlapping multiplets, 9H, OTHP), 1.79 (d, J = 6.6 Hz, 3H, Me-C=), 2.06 (m, 2H, Me-CH2), 3.76 (d, J = 11.3 Hz, 3H, MeO). 13C-NMR (150.9 MHz) δ = 12.4 (J = 7.6 Hz), 18.4 (J = 6.4 Hz), 20.4, 25.3, 31.1 (J = 8.1 Hz), 27.7 (J = 4.8 Hz), 31.3, 51.9 (J = 6.6 Hz), 63.2, 68.4 (J = 10.0 Hz), 92.4, 99.4 (J = 194.0 Hz), 103.8 (J = 15.3 Hz), 208.5 (J = 5.0 Hz). 31P-NMR (242.9 MHz): δ 21.4. Anal. Calcd for C16H29O5P (332.37): C 57.82, H 8.79. Found: C 57.76, H 8.87.

Dimethyl 3-methyl-1-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)-ethyl]-hepta-1,2-dienephosphonate (7h). Orange oil, yield: 70%. Rf 0.42; IR (neat, cm−1): 1121 (C-O-C), 1254 (P=O), 1950 (C=C=C). 1H-NMR (600.1 MHz): δ 0.91 (t, J = 7.2 Hz, 3H, Me-(CH2)5), 1.49 (d, J = 10.4 Hz, 6H, Me2CO), 1.42, 1.73, 2.06 (overlapping multiplets, 6H, Me-(CH2)3), 1.46, 1.57, 1.62, 3.64, 4.37 (overlapping multiplets, 9H, OTHP), 1.78 (d, J = 6.6 Hz, 3H, Me-C=), 3.75 (d, J = 11.2 Hz, 3H, MeO). 13C-NMR (150.9 MHz) δ = 13.9, 19.1 (J = 6.6 Hz), 20.6, 22.5, 25.4, 30.0, 30.4 (J = 8.2 Hz), 31.4, 32.9, 53.1 (J = 6.7 Hz), 63.3, 66.4 (J = 10.3 Hz), 92.7, 98.5 (J = 190.4 Hz), 104.2 (J = 15.3 Hz), 207.4 (J = 5.1 Hz). 31P-NMR (242.9 MHz): δ 22.2. Anal. Calcd for C18H33O5P (360.43): C 59.98, H 9.23. Found: C 60.05, H 9.29.

3.5. General Procedure for Synthesis of the 2-(2-Diphenylphosphinoyl-2,3-dienyloxy)-tetrahydro-2H-pyrans 9

To a solution of the (tetrahydro-2H-pyran-2-yloxy)-alkynols 5 (20.0 mmol) and triethylamine (2.2 g, 22.0 mmol) [0.037 g/mL] in dry diethyl ether (60 mL) at −70 °C a solution of freshly distilled diphenylchlorophosphine (4.4 g, 20.0 mmol) [0.22 g/mL] in the same solvent (20 mL) was added dropwise with stirring. The reaction mixture was stirred for an hour at the same temperature and for 8 h at room temperature and then washed with water, 2 N HCl, extracted with diethyl ether, and the extract was washed with saturated NaCl, and dried over anhydrous sodium sulfate. The solvent was removed using a rotatory evaporator and the residue was purified by column chromatography on a silica gel (Kieselgel Merck 60 F254) with ethyl acetate-hexane (10:1) to give the pure products 9 as oils, which had the following properties:

2-(2-Diphenylphosphinoyl-4-methyl-hexa-2,3-dienyloxy)-tetrahydro-2H-pyran (9a). Yellow oil, yield: 86%. Rf 0.58; IR (neat, cm−1): 1119 (C-O-C), 1157 (P=O), 1437, 1483 (Ph), 1949 (C=C=C). 1H-NMR (600.1 MHz): δ 0.75 (t, J = 7.4 Hz, 3H, Me-CH2), 1.27–1.82, 3.71–3.77, 4.59–4.62 (overlapping multiplets, 9H, OTHP), 1.52 (d, J = 6.2 Hz, 3H, Me-C=), 2.05 (m, 2H, Me-CH2), 4.26–4.53 (m, 2H, CH2O), 7.41–7.78 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 11.8, 17.6 (J = 5.6 Hz), 18.9, 25.4, 26.3, 30.1, 61.6, 64.2 (J = 9.5 Hz), 95.9 (J = 104.4 Hz), 97.6, 104.6 (J = 13.9 Hz), 131.7–133.8 (2Ph), 208.2 (J = 6.5 Hz). 31P-NMR (242.9 MHz): δ 29.5. Anal. Calcd for C24H29O3P (396.46): C 72.71, H 7.37. Found: C 72.63, H 7.42.

2-(2-Diphenylphosphinoyl-4-methyl-octa-2,3-dienyloxy)-tetrahydro-2H-pyran (9b). Yellow oil, yield: 84%. Rf 0.57; IR (neat, cm−1): 1120 (C-O-C), 1155 (P=O), 1438, 1482 (Ph), 1954 (C=C=C). 1H-NMR (600.1 MHz): δ 0.81 (t, J = 7.3 Hz, 3H, Me-CH2), 1.07–1.18, 3.41–3.45 (mm, 6H, (CH2)3-Me), 1.34–1.74, 3.71–3.77, 4.58–4.61 (overlapping multiplets, 9H, OTHP), 1.51 (d, J = 6.6 Hz, 3H, Me-C=), 4.25–4.52 (m, 2H, CH2O), 7.30–7.82 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 13.9, 17.7 (J = 5.6 Hz), 18.9, 22.2, 25.4, 30.1, 29.2, 32.8, 61.7, 64.3 (J = 9.6 Hz), 95.2 (J = 104.5 Hz), 97.8, 103.0 (J = 13.3 Hz), 131.5–133.4 (2Ph), 208.5 (J = 6.4 Hz). 31P-NMR (242.9 MHz): δ 29.8. Anal. Calcd for C26H33O3P (424.51): C 73.56, H 7.84. Found: C 73.64, H 7.91.

2-(3-Cyclohexylidene-2-diphenylphosphinoyl-allyloxy)-tetrahydro-2H-pyran (9c). Yellow oil, yield: 81%. Rf 0.56; IR (neat, cm−1): 1123 (C-O-C), 1169 (P=O), 1436, 1490 (Ph), 1954 (C=C=C). 1H-NMR (600.1 MHz): δ 0.97–1.06, 1.86–2.02, 3.40–3.44 (overlapping multiplets, 10H, (CH2)5), 1.27–1.57, 3.72–3.77, 4.58–4.60 (overlapping multiplets, 9H, OTHP), 4.29–4.51 (m, 2H, CH2O), 7.26–7.78 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 18.9, 21.1, 25.4, 26.3 (J = 3.8 Hz), 29.9 (J = 5.2 Hz), 30.1, 61.8, 64.1 (J = 9.6 Hz), 94.0 (J = 105.2 Hz), 97.5, 104.9 (J = 13.4 Hz), 128.1–133.0 (2Ph), 205.4 (J = 6.8 Hz). 31P-NMR (242.9 MHz): δ 31.1. Anal. Calcd for C26H31O3P (422.50: C 73.91, H 7.40. Found: C 73.83, H 7.31.

2-(2-Diphenylphosphinoyl-1,4-dimethyl-hexa-2,3-dienyloxy)-tetrahydro-2H-pyran (9d). Orange oil, yield: 83%. Rf 0.46; IR (neat, cm−1): 1119 (C-O-C), 1158 (P=O), 1440, 1489 (Ph), 1950 (C=C=C). 1H-NMR (600.1 MHz): δ 0.84 (t, J = 7.3 Hz, 3H, Me-CH2), 1.30–1.71, 3.61–3.65, 4.56–4.59 (overlapping multiplets, 9H, OTHP), 1.43 (dd, J = 6.3 Hz, J = 9.8 Hz, 3H, Me-CHO), 1.53 (d, J = 6.4 Hz, 3H, Me-C=), 2.02 (m, 2H, Me-CH2), 4.61–4.67 (m, 1H, CHO), 7.29–7.82 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 12.7, 18.6 (J = 5.5 Hz), 19.5, 22.5 (J = 7.7 Hz), 22.6, 27.5 (J = 5.4 Hz), 30.6, 62.4, 64.9 (J = 9.4 Hz), 97.6 (J = 104.1 Hz), 96.7, 104.7 (J = 13.7 Hz), 129.2–134.5 (2Ph), 204.7 (J = 6.6 Hz). 31P-NMR (242.9 MHz): δ 30.4. Anal. Calcd for C25H31O3P (410.49): C 73.15, H 7.61. Found: C 73.08, H 7.69.

2-(2-Diphenylphosphinoyl-1,4-dimethyl-octa-2,3-dienyloxy)-tetrahydro-2H-pyran (9e). Orange oil, yield: 82%. Rf 0.45; IR (neat, cm−1): 1123 (C-O-C), 1165 (P=O), 1437, 1492 (Ph), 1954 (C=C=C). 1H-NMR (600.1 MHz): δ 0.81 (t, J = 7.5 Hz, 3H, Me-CH2), 1.10–1.21, 3.50–3.55 (mm, 6H, (CH2)3-Me), 1.37–1.71, 3.62–3.67, 4.57–4.63 (overlapping multiplets, 9H, OTHP), 1.42 (dd, J = 6.4 Hz, J = 9.7 Hz, 3H, Me-CHO), 1.55 (d, J = 6.3 Hz, 3H, Me-C=), 4.52-4.57 (m, 1H, CHO), 7.28-7.84 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 13.8, 18.4 (J = 5.6 Hz), 19.6, 21.3, 22.2 (J = 7.5 Hz), 25.5, 30.5, 29.5, 32.9, 62.7, 65.2 (J = 9.7 Hz), 97.4, 97.9 (J = 105.0 Hz), 104.7 (J = 13.7 Hz), 129.7–134.6 (2Ph), 207.7 (J = 6.6 Hz). 31P-NMR (242.9 MHz): δ 29.7. Anal. Calcd for C27H35O3P (438.54): C 73.95, H 8.04. Found: C 74.03, H 7.99.

2-(3-Cyclohexylidene-2-diphenylphosphinoyl-1-methyl-allyloxy)-tetrahydro-2H-pyran (9f). Yellow oil, yield: 80%. Rf 0.45; IR (neat, cm−1): 1118 (C-O-C), 1160 (P=O), 1439, 1488 (Ph), 1949 (C=C=C). 1H-NMR (600.1 MHz): δ 1.03–1.11, 1.91–1.97, 3.33–3.45 (overlapping multiplets, 10H, (CH2)5), 1.31–1.62, 3.68–3.79, 4.56–4.70 (overlapping multiplets, 9H, OTHP), 1.44 (d, J = 6.5 Hz, 3H, Me-CHO), 4.51–4.57 (m, 1H, CHO), 7.31–7.87 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 20.0, 20.7, 21.7 (J = 7.4 Hz), 26.1, 26.7 (J = 3.6 Hz), 30.2, 30.4 (J = 5.3 Hz), 62.8, 67.8 (J = 9.6 Hz), 97.7, 99.8 (J = 105.0 Hz), 106.3 (J = 13.8 Hz), 127.7–134.2 (2Ph), 203.6 (J = 7.2 Hz). 31P-NMR (242.9 MHz): δ 31.2. Anal. Calcd for C27H33O3P (436.52): C 74.29, H 7.62. Found: C 74.33, H 7.69.

2-(2-Diphenylphosphinoyl-1,1,4-trimethyl-hexa-2,3-dienyloxy)-tetrahydro-2H-pyran (9g). Dark orange oil, yield: 80%. Rf 0.44; IR (neat, cm−1): 1119 (C-O-C), 1154 (P=O), 1436, 1487 (Ph), 1956 (C=C=C). 1H-NMR (600.1 MHz): δ 1.03 (t, J = 7.5 Hz, 3H, Me-CH2), 1.38–1.69, 3.53–3.73, 4.61–4.77 (overlapping multiplets, 9H, OTHP), 1.47 (d, J = 10.6 Hz, 6H, Me2CO), 1.53 (d, J = 6.5 Hz, 3H, Me-C=), 2.02 (m, 2H, Me-CH2), 7.41–7.85 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 12.1, 18.5 (J = 5.7 Hz), 19.4, 26.2, 28.4 (J = 5.5 Hz), 31.1, 31.2 (J = 8.0 Hz), 63.0, 68.4 (J = 9.7 Hz), 96.9, 97.8 (J = 104.7 Hz), 105.1 (J = 13.4 Hz), 127.4–133.9 (2Ph), 204.5 (J = 7.0 Hz). 31P-NMR (242.9 MHz): δ 31.7. Anal. Calcd for C26H33O3P (424.51): C 73.56, H 7.84. Found: C 73.63, H 7.92.

2-(2-Diphenylphosphinoyl-1,1,4-trimethyl-octa-2,3-dienyloxy)-tetrahydro-2H-pyran (9h). Yellow oil, yield: 78%. Rf 0.45; IR (neat, cm−1): 1119 (C-O-C), 1162 (P=O), 1440, 1486 (Ph), 1953 (C=C=C). 1H-NMR (600.1 MHz): δ 1.06 (t, J = 7.6 Hz, 3H, Me-CH2), 1.09–1.22, 3.43–3.46 (mm, 6H, (CH2)3-Me), 1.29–1.64, 3.57–3.74, 4.59–4.74 (overlapping multiplets, 9H, OTHP), 1.50 (d, J = 10.5 Hz, 3H, Me2CO), 1.55 (d, J = 6.6 Hz, 3H, Me-C=), 7.37–7.84 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 13.8, 18.1 (J = 5.7 Hz), 18.7, 21.7, 25.8, 30.0, 30.4, 30.7 (J = 8.2 Hz), 33.1, 62.0, 67.9 (J = 9.5 Hz), 97.3, 98.4 (J = 105.3 Hz), 104.8 (J = 13.5 Hz), 128.0–134.4 (2Ph), 205.4 (J = 7.2 Hz). 31P-NMR (242.9 MHz): δ 30.6. Anal. Calcd for C28H37O3P (452.57): C 74.31, H 8.24. Found: C 74.24, H 8.17.

3.6. General Procedure for Synthesis of the 1-Hydroxyalkyl-1,2-dienephosphonates 10, the 3-Diphenylphosphinoyl-2,3-dien-1-ols 11a–c and the 3-Diphenylphosphinoyl-3,4-dien-2-ols 11d–h

A solution of the dimethyl 1-(tetrahydro-2H-pyran-2-yloxy)-1,2-dienephosphonates 7 or the 2-(2-diphenylphosphinoyl-2,3-dienyloxy)-tetrahydro-2H-pyrans 9 (5.0 mmol) and PPTS (1.13 g, 0.5 mmol) [0.113 g/mL] in ethanol (10 mL) was stirred at room temperature for 6 h. The mixture was then washed with water, extracted with methylene chloride and dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue was chromatographied on a column (silica gel, Kieselgel Merck 60 F254) with a mixture of ethyl acetate and hexane (10:1) as a eluent to give the pure products 10 or 11 as oils, which had the following properties:

Dimethyl 1-hydroxymethyl-3-methylpenta-1,2-dienephosphonate (10a). Pale yellow oil, yield: 80%. Rf 0.45; IR (neat, cm−1): 1248 (P=O), 1956 (C=C=C), 3404 (OH). 1H-NMR (250.1 MHz): δ 1.06 (t, J = 7.4 Hz, 3H, Me-CH2), 1.80 (d, J = 6.7 Hz, 3H, Me-C=), 2.04–2.12 (m, 2H, Me-CH2), 2.64 (s, 1H, OH), 3.75 (d, J = 11.8 Hz, 3H, MeO), 4.30–4.36 (m, 2H, CH2O). 13C-NMR (62.9 MHz) δ = 12.0 (J = 7.7 Hz), 18.1 (J = 6.5 Hz), 26.5 (J = 9.3 Hz), 52.8 (J = 6.3 Hz), 64.9 (J = 10.1 Hz), 90.8 (J = 191.3 Hz), 104.7 (J = 15.7 Hz), 208.7 (J = 5.6 Hz). 31P-NMR (101.2 MHz): δ 21.6. Anal. Calcd for C9H17O4P (220.20): C 49.09, H 7.78. Found: C 49.17, H 7.71.

Dimethyl 1-hydroxymethyl-3-methylhepta-1,2-dienephosphonate (10b). Pale yellow oil, yield: 78%. Rf 0.43; IR (neat, cm−1): 1249 (P=O), 1958 (C=C=C), 3401 (OH). 1H-NMR (600.1 MHz): δ 0.99 (t, J = 7.3 Hz, 3H, Me-CH2), 1.32–1.46, 1.51–1.63, 2.03–2.09 (overlapping multiplets, 10H, Me-(CH2)3), 1.79 (d, J = 6.5 Hz, 3H, Me-C=), 2.64 (s, 1H, OH), 3.76 (d, J = 11.2 Hz, 3H, MeO), 4.33–4.38 (m, 2H, CH2O). 13C-NMR (150.9 MHz) δ = 13.9, 18.1 (J = 6.6 Hz), 22.2, 30.3, 32.9, 52.8 (J = 6.2 Hz), 64.9 (J = 10.1 Hz), 90.4 (J = 191.5 Hz), 103.7 (J = 15.6 Hz), 208.8 (J = 5.5 Hz). 31P-NMR (242.9 MHz): δ 21.0. Anal. Calcd for C11H21O4P (248.26): C 53.22, H 8.53. Found: C 53.30, H 8.62.

Dimethyl 2-cyclohexylidene-1-hydroxymethyl-ethenephosphonate (10c). Colourless oil, yield: 77%. Rf 0.44; IR (neat, cm−1): 1259 (P=O), 1952 (C=C=C), 3412 (OH). 1H-NMR (250.1 MHz): δ 1.22–1.37, 1.80–1.96, 3.49–3.57 (overlapping multiplets, 10H, (CH2)5), 2.67 (s, 1H, OH), 3.75 (d, J = 11.3 Hz, 3H, MeO), 4.23–4.29 (m, 2H, CH2O). 13C-NMR (62.9 MHz) δ = 25.6, 27.1, 30.4 (J = 5.8 Hz), 52.8 (J = 6.0 Hz), 64.7 (J = 10.7 Hz), 88.8 (J = 190.3 Hz), 105.1 (J = 15.3 Hz), 205.6 (J = 5.4 Hz). 31P-NMR (101.2 MHz): δ 20.8. Anal. Calcd for C11H19O4P (246.24): C 53.65, H 7.78. Found: C 53.72, H 7.73.

Dimethyl 1-(1-hydroxyethyl)-3-methylpenta-1,2-dienephosphonate (10d). Yellow oil, yield: 80%. Rf 0.58; IR (neat, cm−1): 1254 (P=O), 1956 (C=C=C), 3372 (OH). 1H-NMR (600.1 MHz): δ 0.98 (t, J = 7.5 Hz, 3H, Me-CH2), 1.42 (dd, J = 6.1 Hz, J = 10.2 Hz, 3H, Me-CHO), 1.78 (d, J = 6.6 Hz, 3H, Me-C=), 2.02–2.10 (m, 2H, Me-CH2), 2.70 (s, 1H, OH), 3.78 (d, J = 11.6 Hz, 3H, MeO), 4.67–4.72 (m, 1H, Me-CHO). 13C-NMR (150.9 MHz) δ = 12.2 (J = 7.6 Hz), 18.4 (J = 6.4 Hz), 23.2 (J = 7.5 Hz), 27.4 (J = 9.2 Hz), 52.6 (J = 6.2 Hz), 66.9 (J = 10.3 Hz), 96.3 (J = 192.3 Hz), 104.4 (J = 15.9 Hz), 208.9 (J = 5.4 Hz). 31P-NMR (242.9 MHz): δ 21.1. Anal. Calcd for C10H19O4P (234.23): C 51.28, H 8.18. Found: C 51.21, H 8.13.

Dimethyl 1-(1-hydroxyethyl)-3-methylhepta-1,2-dienephosphonate (10e). Yellow oil, yield: 79%. Rf 0.57; IR (neat, cm−1): 1248 (P=O), 1958 (C=C=C), 3437 (OH). 1H-NMR (600.1 MHz): δ 1.09 (t, J = 7.4 Hz, 3H, Me-CH2), 1.39–1.44, 1.50–1.55, 2.11–2.15 (overlapping multiplets, 10H, Me-(CH2)3), 1.40 (dd, J = 6.3 Hz, J = 10.3 Hz, 3H, Me-CHO), 1.77 (d, J = 6.9 Hz, 3H, Me-C=), 2.68 (s, 1H, OH), 3.77 (d, J = 11.5 Hz, 3H, MeO), 4.50–4.55 (m, 1H, Me-CHO). 13C-NMR (150.9 MHz) δ = 13.7, 18.7 (J = 6.4 Hz), 23.0, 23.5 (J = 7.5 Hz), 30.0, 33.0, 52.3 (J = 6.2 Hz), 68.7 (J = 10.0 Hz), 91.5 (J = 191.5 Hz), 103.2 (J = 16.1 Hz), 208.7 (J = 5.4 Hz). 31P-NMR (242.9 MHz): δ 21.2. Anal. Calcd for C12H23O4P (262.28): C 54.95, H 8.84. Found: C 55.02, H 8.78.

Dimethyl 1-cyclohexylidenemethylene-2-hydroxypropanephosphonate (10f). Orange oil, yield: 81%. Rf 0.59; IR (neat, cm−1): 1253 (P=O), 1951 (C=C=C), 3422 (OH). 1H-NMR (600.1 MHz): δ 1.33–1.48, 1.87–2.00, 3.12–3.20 (overlapping multiplets, 10H, (CH2)5), 1.38 (dd, J = 6.4 Hz, J = 9.7 Hz, 3H, Me-CHO), 2.84 (s, 1H, OH), 3.78 (d, J = 11.6 Hz, 3H, MeO), 4.64–4.69 (m, 1H, Me-CHO). 13C-NMR (150.9 MHz) δ = 23.3 (J = 7.3 Hz), 25.7, 27.0, 30.3 (J = 6.2 Hz), 53.1 (J = 6.1 Hz), 65.9 (J = 10.0 Hz), 94.7 (J = 186.1 Hz), 106.8 (J = 15.5 Hz), 202.3 (J = 5.1 Hz). 31P-NMR (242.9 MHz): δ 20.9. Anal. Calcd for C12H21O4P (260.27): C 55.38, H 8.31. Found: C 55.45, H 8.26.

Dimethyl 1-(1-hydroxy-1-methylethyl)-3-methylpenta-1,2-dienephosphonate (10g). Yellow oil, yield: 79%. Rf 0.60; IR (neat, cm−1): 1250 (P=O), 1953 (C=C=C), 3398 (OH). 1H-NMR (600.1 MHz): δ 1.11 (t, J = 7.6 Hz, 3H, Me-CH2), 1.54 (d, J = 10.7 Hz, 3H, Me2CO), 1.75 (d, J = 6.7 Hz, 3H, Me-C=), 2.04–2.13 (m, 2H, Me-CH2), 2.93 (s, 1H, OH), 3.79 (d, J = 11.5 Hz, 3H, MeO). 13C-NMR (150.9 MHz) δ = 12.3, 18.2 (J = 6.5 Hz), 27.4 (J = 9.2 Hz), 31.0 (J = 8.2 Hz), 53.0 (J = 6.6 Hz), 68.2 (J = 10.2 Hz), 99.5 (J = 190.2 Hz), 104.3 (J = 15.4 Hz), 207.4 (J = 5.2 Hz). 31P-NMR (242.9 MHz): δ 22.4. Anal. Calcd for C11H21O4P (248.26): C 53.22, H 8.53. Found: C 53.15, H 8.44.

Dimethyl 1-(1-hydroxy-1-methylethyl)-3-methylhepta-1,2-dienephosphonate (10h). Orange oil, yield: 78%. Rf 0.57; IR (neat, cm−1): 1255 (P=O), 1954 (C=C=C), 3416 (OH). 1H-NMR (600.1 MHz): δ 0.92 (t, J = 7.3 Hz, 3H, Me-CH2), 1.28–1.40, 1.53–1.66, 2.05–2.13 (overlapping multiplets, 10H, Me-(CH2)3), 1.55 (d, J = 10.8 Hz, 3H, Me2CO), 1.75 (d, J = 6.7 Hz, 3H, Me-C=), 2.95 (s, 1H, OH), 3.75 (d, J = 11.4 Hz, 3H, MeO). 13C-NMR (150.9 MHz) δ = 14.0, 19.0 (J = 6.7 Hz), 22.7, 29.8, 31.3 (J = 8.2 Hz), 33.1, 53.0 (J = 6.7 Hz), 66.6 (J = 10.3 Hz), 99.7 (J = 182.2 Hz), 104.1 (J = 15.7 Hz), 207.3 (J = 5.1 Hz). 31P-NMR (242.9 MHz): δ 22.8. Anal. Calcd for C13H25O4P (276.31): C 56.51, H 9.12. Found: C 56.59, H 9.06.

2-Diphenylphosphinoyl-4-methylhexa-2,3-dien-1-ol (11a). Colourless oil, yield: 86%. Rf 0.42; IR (neat, cm−1): 1175 (P=O), 1440, 1489 (Ph), 1955 (C=C=C), 3378 (OH). 1H-NMR (600.1 MHz): δ 0.72 (t, J = 7.4 Hz, 3H, Me-CH2), 1.54 (d, J = 6.0 Hz, 3H, Me-C=), 1.66–1.88 (m, 2H, Me-CH2), 2.66 (s, 1H, OH), 4.41–4.47 (m, 2H, CH2O), 7.28–7.82 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 11.7, 17.6 (J = 5.6 Hz), 26.4, 64.2 (J = 7.5 Hz), 97.5 (J = 103.8 Hz), 105.3 (J = 13.6 Hz), 128.2–132.5 (2Ph), 206.3 (J = 7.2 Hz). 31P-NMR (242.9 MHz): δ 33.5. Anal. Calcd for C19H21O2P (312.34): C 73.06, H 6.78. Found: C 73.14, H 6.71.

2-Diphenylphosphinoyl-4-methylocta-2,3-dien-1-ol (11b). Yellow oil, yield: 83%. Rf 0.41; IR (neat, cm−1): 1177 (P=O), 1436, 1492 (Ph), 1950 (C=C=C), 3374 (OH). 1H-NMR (600.1 MHz): δ 0.81 (t, J = 7.2 Hz, 3H, Me-CH2), 1.04–1.17, 1.34–1.50, 1.67–1.84 (overlapping multiplets, 10H, Me-(CH2)3), 1.53 (d, J = 6.2 Hz, 3H, Me-C=), 2.65 (s, 1H, OH), 4.39–4.46 (m, 2H, CH2O), 7.30–7.80 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 13.8, 17.6 (J = 5.4 Hz), 18.8, 29.2, 32.9, 64.3 (J = 7.6 Hz), 96.7 (J = 103.9 Hz), 103.6 (J = 13.5 Hz), 128.7–132.5 (2Ph), 206.5 (J = 7.2 Hz). 31P-NMR (242.9 MHz): δ 32.9. Anal. Calcd for C21H25O2P (340.40): C 74.10, H 7.40. Found: C 74.17, H 7.32.

3-Cyclohexylidene-2-diphenylphosphinoylprop-2-en-1-ol (11c). Pale yellow oil, yield: 81%. Rf 0.41; IR (neat, cm−1): 1170 (P=O), 1439, 1488 (Ph), 1947 (C=C=C), 3387 (OH). 1H-NMR (250.1 MHz): δ 0.97–1.04, 1.89–2.04, 3.38–3.54 (overlapping multiplets, 10H, (CH2)5), 2.64 (s, 1H, OH), 4.38–4.43 (m, 2H, CH2O), 7.28–7.79 (m, 10H, 2Ph). 13C-NMR (62.9 MHz) δ = 25.4, 26.4, 30.0, 62.1 (J = 7.6 Hz), 95.6 (J = 104.1 Hz), 105.4 (J = 13.3 Hz), 128.8–132.5 (2Ph), 203.6 (J = 7.3 Hz). 31P-NMR (101.2 MHz): δ 33.3. Anal. Calcd for C21H23O2P (338.38): C 74.54, H 6.85. Found: C 74.62, H 6.79.

3-Diphenylphosphinoyl-5-methtlhepta-3,4-dien-2-ol (11d). Light orange oil, yield: 87%. Rf 0.59; IR (neat, cm−1): 1174 (P=O), 1441, 1490 (Ph), 1951 (C=C=C), 3369 (OH). 1H-NMR (600.1 MHz): δ 0.86 (t, J = 7.4 Hz, 3H, Me-CH2), 1.35 (dd, J = 6.2 Hz, J = 9.4 Hz, 3H, Me-CHO), 1.58 (d, J = 6.3 Hz, 3H, Me-C=), 1.78–1.90 (m, 2H, Me-CH2), 2.70 (s, 1H, OH), 4.59–4.63 (m, 1H, Me-CHO), 7.35–7.90 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 12.4, 18.5 (J = 5.4 Hz), 22.4 (J = 7.6 Hz), 26.7, 64.2 (J = 7.4 Hz), 96.5 (J = 104.2 Hz), 105.1 (J = 13.4 Hz), 129.1–132.4 (2Ph), 204.1 (J = 7.1 Hz). 31P-NMR (242.9 MHz): δ 34.2. Anal. Calcd for C20H23O2P (326.37): C 73.60, H 7.10. Found: C 73.67, H 7.05.

3-Diphenylphosphinoyl-5-methylnona-3,4-dien-2-ol (11e). Yellow oil, yield: 85%. Rf 0.61; IR (neat, cm−1): 1168 (P=O), 1438, 1487 (Ph), 1952 (C=C=C), 3379 (OH). 1H-NMR (600.1 MHz): δ 0.92 (t, J = 7.3 Hz, 3H, Me-CH2), 1.11–1.23, 1.29–1.47, 1.69–1.96 (overlapping multiplets, 10H, Me-(CH2)3), 1.37 (dd, J = 6.3 Hz, J = 9.6 Hz, 3H, Me-CHO), 1.56 (d, J = 6.4 Hz, 3H, Me-C=), 2.72 (s, 1H, OH), 4.61–4.67 (m, 1H, Me-CHO), 7.39–7.89 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 13.7, 18.3 (J = 5.5 Hz), 18.9, 22.3 (J = 7.7 Hz), 29.5, 33.2, 65.4 (J = 7.6 Hz), 100.7 (J = 103.8 Hz), 104.8 (J = 13.5 Hz), 128.4–132.5 (2Ph), 205.3 (J = 7.3 Hz). 31P-NMR (242.9 MHz): δ 34.5. Anal. Calcd for C22H27O2P (354.42): C 74.55, H 7.68. Found: C 74.61, H 7.60.

4-Cyclohexylidene-3-diphenylphosphinoylbut-3-en-2-ol (11f). Yellow oil, yield: 88%. Rf 0.58; IR (neat, cm−1): 1168 (P=O), 1436, 1493 (Ph), 1948 (C=C=C), 3395 (OH). 1H-NMR (600.1 MHz): δ 0.99–1.07, 1.84–2.01, 3.37–3.57 (overlapping multiplets, 10H, (CH2)5), 1.34 (dd, J = 6.2 Hz, J = 9.4 Hz, 3H, Me-CHO), 2.73 (s, 1H, OH), 4.64–4.69 (m, 1H, Me-CHO), 7.32–7.84 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 22.2 (J = 7.5 Hz), 25.5, 26.5, 30.0, 66.2 (J = 7.3 Hz), 100.2 (J = 105.0 Hz), 106.6 (J = 13.6 Hz), 128.1–132.5 (2Ph), 202.6 (J = 7.4 Hz). 31P-NMR (242.9 MHz): δ 33.9. Anal. Calcd for C22H25O2P (352.41): C 74.98, H 7.15. Found: C 75.05, H 7.09.

3-Diphenylphosphinoyl-2,5-dimethylhepta-3,4-dien-2-ol (11g). Orange oil, yield: 84%. Rf 0.60; IR (neat, cm−1): 1171 (P=O), 1437, 1488 (Ph), 1954 (C=C=C), 3373 (OH). 1H-NMR (600.1 MHz): δ 1.09 (t, J = 7.3 Hz, 3H, Me-CH2), 1.49 (d, J = 10.1 Hz, 3H, Me2CO), 1.53 (d, J = 6.4 Hz, 3H, Me-C=), 1.81–1.86 (m, 2H, Me-CH2), 2.74 (s, 1H, OH), 7.28–7.88 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 12.3, 18.4 (J = 5.6 Hz), 27.2, 31.4 (J = 8.1 Hz), 67.0 (J = 7.4 Hz), 98.3 (J = 104.8 Hz), 105.3 (J = 13.5 Hz), 128.3–132.4 (2Ph), 204.7 (J = 7.2 Hz). 31P-NMR (242.9 MHz): δ 33.8. Anal. Calcd for C21H25O2P (340.40): C 74.10, H 7.40. Found: C 74.01, H 7.45.

3-Diphenylphosphinoyl-2,5-dimethylnona-3,4-dien-2-ol (11h). Dark orange oil, yield: 83%. Rf 0.56; IR (neat, cm−1): 1165 (P=O), 1439, 1486 (Ph), 1955 (C=C=C), 3394 (OH). 1H-NMR (600.1 MHz): δ 1.07 (t, J = 7.3 Hz, 3H, Me-CH2), 1.12–1.25, 1.32–1.45, 1.73–1.89 (overlapping multiplets, 10H, Me-(CH2)3), 1.50 (d, J = 10.0 Hz, 3H, Me2CO), 1.55 (d, J = 6.3 Hz, 3H, Me-C=), 2.73 (s, 1H, OH), 7.29–7.90 (m, 10H, 2Ph). 13C-NMR (150.9 MHz) δ = 13.9, 18.2 (J = 5.7 Hz), 19.0, 30.1, 31.6 (J = 8.2 Hz), 33.2, 68.1 (J = 7.5 Hz), 98.7 (J = 105.0 Hz), 105.0 (J = 13.4 Hz), 128.4–132.6 (2Ph), 205.1 (J = 7.3 Hz). 31P-NMR (242.9 MHz): δ 34.1. Anal. Calcd for C23H29O2P (368.45): C 74.98, H 7.93. Found: C 74.92, H 8.01.

4. Conclusions

In conclusion, a convenient and efficient method for regioselective synthesis of a new family of 1,1-bifunctionalized allenes has been explored. Phosphorylated α-hydroxyallenes prepared were derived from [2,3]-sigmatropic rearrangement of the intermediate propargyl phosphites or phosphinites formed in the reaction of protected alkynols with dimethylchloro phosphite or chlorodiphenyl phosphine in the presence of a base. Further investigations on this potentially important synthetic methodology are currently in progress. At the same time, the synthetic application of the prepared phosphorylated α-hydroxyallenes with protected or unprotected hydroxy group for synthesis of different heterocyclic compounds is now under investigation in our laboratory as a part of our general synthetic strategy for investigation of the scope and limitations of the electrophilic cyclization and cycloisomerization reactions of bifunctionalized allenes. Results of these investigations will be reported in due course.

Acknowledgments

Support from the Research Fund of the Konstantin Preslavsky University of Shumen (Project No. RD-08-208/2014), National Research Fund of Bulgaria (Project No. DRNF-02-13/2009) and Human Resources Development Operational Programme of the European Union (BG051PO001-3.3.06-0003/2012) is acknowledged.

Author Contributions

Valerij Ch. Christov proposed the subject, designed the study and offered necessary guidance to Ismail E. Ismailov and Ivaylo K. Ivanov. Valerij Ch. Christov and Ivaylo K. Ivanov conceived and designed the experiments. Ismail E. Ismailov and Ivaylo K. Ivanov performed the experiments under the supervision of the lead author Valerij Ch. Christov who analyzed the spectral data and wrote the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. The Chemistry of Ketenes, Allenes and Related Compounds; Patai, S., Ed.; John Wiley & Sons: New York, NY, USA, 1980.
  2. The Chemistry of the Allenes; Landor, S.R., Ed.; Academic Press: London, UK, 1982; Volume 1–3.
  3. Pasto, D.J. Recent developments in allene chemistry. Tetrahedron 1984, 40, 2805–2827. [Google Scholar] [CrossRef]
  4. Schuster, H.F.; Coppola, G.M. Allenes in Organic Synthesis; John Wiley & Sons: New York, NY, USA, 1988. [Google Scholar]
  5. Zimmer, R. Alkoxyallenes—Building blocks in organic synthesis. Synthesis 1993, 1993, 165–178. [Google Scholar] [CrossRef]
  6. Elsevier, C.J. Methods of Organic Chemistry (Houben-Weyl); Helmchen, R.W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart, Gremany, 1995; Volume E21a, pp. 537–566. [Google Scholar]
  7. Modern Allene Chemistry; Krause, N., Hashmi, A.S.K., Eds.; Wiley-VCH: Weinheim, Gremany, 2004; Volume 1–2.
  8. Brummond, K.M.; DeForrest, J.E. Synthesizing allenes today (1982–2006). Synthesis 2007, 2007, 795–818. [Google Scholar] [CrossRef]
  9. Bates, R.W.; Satcharoen, V. Nucleophilic transition metal based cyclization of allenes. Chem. Soc. Rev. 2002, 31, 12–21. [Google Scholar] [CrossRef]
  10. Ma, S. Recent advances in the chemistry of allenes. Aldrichim. Acta 2007, 40, 91–102. [Google Scholar]
  11. Hassan, H.H.A.M. Recent progress in the chemistry of allenes. Curr. Org. Synth. 2007, 4, 413–439. [Google Scholar] [CrossRef]
  12. Pinho e Melo, T.M.V.D. Allenes as dipolarophiles and 1,3-dipole precursors: Synthesis of carbocyclic and heterocyclic compounds. Curr. Org. Chem. 2009, 13, 1406–1431. [Google Scholar] [CrossRef]
  13. Back, T.G.; Clary, K.N.; Gao, D. Cycloadditions and cyclizations of acetylenic, allenic, and conjugated dienyl sulfones. Chem. Rev. 2010, 110, 4498–4553. [Google Scholar] [CrossRef]
  14. Enomoto, M.; Katsuki, T.; Yamaguchi, M. Highly regioselective isomerization of acetylenes to allenes. Tetrahedron Lett. 1986, 27, 4599–4600. [Google Scholar] [CrossRef]
  15. Oroshnik, W.; Mebane, A.; Karmas, G. Synthesis of polyenes. III. Prototropic rearrangements in β-ionols and related compounds. J. Am. Chem. Soc. 1953, 75, 1050–1058. [Google Scholar] [CrossRef]
  16. Phadtare, S.; Zemlicka, J. Nucleic acid derived allenols: Unusual analogues of nucleosides with antiretroviral activity. J. Am. Chem. Soc. 1989, 111, 5925–5931. [Google Scholar] [CrossRef]
  17. Crabbé, P.; Fillion, H.; André, D.; Luche, J.-L. Efficient homologation of acetylenes to allenes. J. Chem. Soc. Chem. Commun. 1979, 859–860. [Google Scholar]
  18. Ma, S.; Hou, H.; Zhao, S.; Wang, G. Efficient synthesis of optically active 2,3-allenols via the simple CuBr-mediated reaction of optically active propargylic alcohols with paraformaldehyde. Synthesis 2002, 2002, 1643–1645. [Google Scholar] [CrossRef]
  19. Ye, J.; Li, S.; Chen, B.; Fan, W.; Kuang, J.; Liu, J.; Liu, Y.; Miao, B.; Wan, B.; Wang, Y.; et al. Catalytic asymmetric synthesis of optically active allenes from terminal alkynes. Org. Lett. 2012, 14, 1346–1349. [Google Scholar] [CrossRef]
  20. Boldrini, G.P.; Lodi, L.; Tagliavini, E.; Tarasco, C.; TrombinI, C.; Umanl-Ronchi, A. Synthesis of enantiomerically enriched homoallylic alcohols and of 1,2-dien-1-ols using chiral tin(IV) complexes containing diethyl tartrate as an auxiliary ligand. J. Org. Chem. 1987, 52, 5447–5452. [Google Scholar] [CrossRef]
  21. Hoffman, R.W.; Weldmann, U. Stereoselective synthesis of alcohols, XIX. The sense of asymmetric induction on addition to α-chiral aldehydes. Chem. Ber. 1985, 118, 3966–3979. [Google Scholar] [CrossRef]
  22. Corey, E.J.; Imwinkelried, R.; Pikul, S.; Xiang, Y.B. Practical enantioselective Diels-Alder and aldol reactions using a new chiral controller system. J. Am. Chem. Soc. 1989, 111, 5493–5495. [Google Scholar] [CrossRef]
  23. Corey, E.J.; Yu, C.-M.; Lee, D.-H. Copper catalyzed asymmetric propargylation of aldehydes. J. Am. Chem. Soc. 1990, 112, 878–879. [Google Scholar] [CrossRef]
  24. Corey, E.J.; Jones, G.B. Enantioselective route to α-hydroxy aldehyde and acid derivatives. Tetrahedron Lett. 1991, 32, 5713–5716. [Google Scholar] [CrossRef]
  25. Li, J.; Kong, W.; Fu, C.; Ma, S. An efficient CuCN-catalyzed synthesis of optically active 2,3-allenols from optically active 1-substituted 4-chloro-2-butyn-1-ols. J. Org. Chem. 2009, 74, 5104–5106. [Google Scholar] [CrossRef]
  26. Li, J.; Zhou, C.; Fu, C.; Ma, S. Studies on Cu(I)-catalyzed synthesis of simple 3-substituted 1,2-allenes and optically active 2-substituted secondary 2,3-allenols. Tetrahedron 2009, 65, 3695–3703. [Google Scholar] [CrossRef]
  27. Deng, Y.; Jin, X.; Ma, S. Studies on Highly stereoselective addition-elimination reactions of 3-(methoxycarbonyl)-1,2-allen-4-ols with MX. An efficient synthesis of 3-(methoxycarbonyl)-2-halo-1,3(Z)-dienes. J. Org. Chem. 2007, 72, 5901–5904. [Google Scholar] [CrossRef]
  28. Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J.F. Diastereoselective synthesis of α-allenic alcohols from propargylic epoxides. Tetrahedron Lett. 1989, 30, 2387–2390. [Google Scholar] [CrossRef]
  29. Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J.F. Diastereoselective syn or anti opening of propargylic epoxides. Synthesis of α-allenic alcohols. Tetrahedron 1991, 47, 1677–1696. [Google Scholar] [CrossRef]
  30. Marshall, J.A.; Pinney, K.G. Stereoselective synthesis of 2,5-dihydrofurans by sequential SN2’ cleavage of alkynyloxiranes and silver(I)-catalyzed cyclization of the allenylcarbinol products. J. Org. Chem. 1993, 58, 7180–7184. [Google Scholar] [CrossRef]
  31. Krause, N.; Hoffmann-Röder, A.; Canisius, J. From amino acids to dihydrofurans: Functionalized allenes in modern organic synthesis. Synthesis 2002, 12, 1759–1774. [Google Scholar]
  32. Krause, N.; Hoffmann-Röder, A. Synthesis of allenes with organometallic reagents. Tetrahedron 2004, 60, 11671–11694. [Google Scholar] [CrossRef]
  33. Deutsch, C.; Lipshutz, B.H.; Krause, N. Small but effective: Copper hydride catalyzed synthesis of α-hydroxyallenes. Angew. Chem. Int. Ed. 2007, 46, 1650–1653. [Google Scholar] [CrossRef]
  34. Aksin-Artok, Ö.; Krause, N. Combined Rhodium/Gold catalysis: From propargyloxiranes to 2,5-dihydrofurans in one pot. Adv. Synth. Catal. 2011, 353, 385–391. [Google Scholar] [CrossRef]
  35. Poonoth, M.; Krause, N. Cycloisomerization of bifunctionalized Allenes: Synthesis of 3(2H)-furanones in water. J. Org. Chem. 2011, 76, 1934–1936. [Google Scholar] [CrossRef]
  36. Aurrecoechea, J.M.; Solay, M. Stereoselective samarium diiodide-promoted intermolecular coupling of alkynyloxiranes with ketones. Synthesis of 2,3-pentadiene-1,5-diols. Tetrahedron Lett. 1995, 36, 2501–2504. [Google Scholar] [CrossRef]
  37. Aurrecoechea, J.M.; Alonso, E.; Solay, M. Synthesis of allenic diols by samarium diiodide-promoted coupling between alkynyloxiranes and ketones. Tetrahedron 1998, 54, 3833–3850. [Google Scholar] [CrossRef]
  38. Cowie, J.S.; Landor, P.D.; Landor, S.R. A new method for the preparation of allenic alcohols. J. Chem. Soc. Chem. Commun. 1969. [Google Scholar] [CrossRef]
  39. Cowie, J.S.; Landor, P.D.; Landor, S.R. Allenes. Part XXIV. Preparation of α-allenic alcohols from the mono-O-tetrahydropyran-2-yl derivatives of butyne-1,4-diols. J. Chem. Soc. Perkin Trans. 1 1973. [Google Scholar] [CrossRef]
  40. Nakano, M.; Furuichi, N.; Mori, H.; Katsumura, S. Novel synthesis of the allene moiety of carotenoids via biomimetic photosensitized oxygenation. Tetrahedron Lett. 2001, 42, 7307–7310. [Google Scholar]
  41. Darcel, C.; Bruneau, C.; Dixneuf, P.H. Palladium(0), copper(I) catalysed synthesis of conjugated alkynyl α-allenols from alkynyl cyclic carbonates and terminal alkynes. J. Chem. Soc. Chem. Commun. 1994, 1845–1846. [Google Scholar] [CrossRef]
  42. Darcel, C.; Bartsch, S.; Bruneau, C.; Dixneuf, P.H. Selective catalytic transformations of alkynyl cyclic carbonates into either homopropargylic or α-allenyl alcohols. Synlett 1994, 1994, 457–458. [Google Scholar] [CrossRef]
  43. Hoff, S.; Brandsma, L.; Arens, J.F. Preparation, metallation and alkylation of allenyl ethers. Rec. Trav. Chim. Pays-Bas 1968, 87, 916–924. [Google Scholar]
  44. Hoff, S.; Brandsma, L.; Arens, J.F. Some conversions of allenyl ethers. Rec.Trav. Chim. Pays-Bas 1968, 87, 1179–1184. [Google Scholar] [CrossRef]
  45. Hormuth, S.; Reissig, H.-U. Diastereoselective additions of lithiated methoxyallene towards chiral Aaldehydes. Synlett 1991, 1994, 179–180. [Google Scholar] [CrossRef]
  46. Hormuth, S.; Reissig, H.-U.; Dorsch, D. Stereoselective synthesis of (2R,3S)-norstatine derivatives by addition of lithiated methoxyallene to amino aldehydes and subsequent ozonolysis. Liebigs Ann. Chem. 1994, 1994, 121–127. [Google Scholar] [CrossRef]
  47. Hormuth, S.; Reissig, H.-U. Stereoselective synthesis of 3(2H)-dihydrofuranones by addition of lithiated methoxyallene to chiral aldehydes. J. Org. Chem. 1994, 59, 67–73. [Google Scholar] [CrossRef]
  48. Marshall, J.A.; Tang, Y. Allene-directed diastereoselection. Additions to chiral allenyl aldehydes and ketones. J. Org. Chem. 1993, 58, 3233–3234. [Google Scholar] [CrossRef]
  49. Krause, N.; Aksin-Artok, Ö.; Asikainen, M.; Breker, V.; Deutsch, C.; Erdsack, J.; Fan, H.-T.; Gockel, B.; Minkler, S.; Poonoth, M.; et al. Combined coinage metal catalysis for the synthesis of bioactive molecules. J. Organomet. Chem. 2012, 704, 1–8. [Google Scholar]
  50. Mark, V. The Uncatalyzed Rearrangements of Tervalent Phosphorus Esters in Selective Organic Transformations; Thyagarajan, B.S., Ed.; John Wiley & Sons: New York, NY, USA, 1970; pp. 319–437. [Google Scholar]
  51. Landor, P.D. The Chemistry of the Allenes; Landor, S.R., Ed.; Academic Press: New York, NY, USA, 1982; Volume 1, pp. 174–178. [Google Scholar]
  52. Saalfrank, R.W.; Lurz, C.-J. Methoden der Organischen Chemie (Houben Weyl); Kropf, H., Scheumann, E., Eds.; Thieme: Stuttgart, Gremany, 1993; pp. 2959–3102.(In German). [Google Scholar]
  53. Hashmi, A.S.K. Synthesis of Allenes in Modern Allene Chemistry; Krause, N., Hashmi, A.S.K., Eds.; Wiley-VCH: Weinheim, Gremany, 2004; Volume 1, pp. 3–50. [Google Scholar]
  54. Macomber, R.S. Phosphorus-containing products from propargyl alcohols and phosphorus trihalides. 5. A stereochemical investigation of the formation and cyclization of allenic phosphonic acids. Preparation of 4-substituted 1,2-oxaphosphol-3-enes. J. Am. Chem. Soc. 1977, 99, 3072–3075. [Google Scholar] [CrossRef]
  55. Denmark, S.E.; Marlin, J.E. Carbanion-accelerated Claisen rearrangements. 7. Phosphine oxide and phosphonate anion stabilizing groups. J. Org. Chem. 1991, 56, 1003–1013. [Google Scholar] [CrossRef]
  56. Cai, B.; Blackburn, G.M. The syntheses and reactions of 3,4-bisphosphono-1,2,4,5-tetraenes. Synth. Commun. 1997, 27, 3943–3949. [Google Scholar] [CrossRef]
  57. Saalfrank, R.W.; Haubner, M.; Deutscher, C.; Bauer, U. Yne-allenes from 1-bromoallenes and trimethylstannylacetylenes via palladium-mediated C–C coupling reactions. Eur. J. Org. Chem. 1999, 1999, 2367–2372. [Google Scholar] [CrossRef]
  58. Bhuvan Kumar, N.N.; Kumara Swamy, K.C. The reaction of allenes with phosphorus(III) compounds bearing a P-NH-(t-Bu) group: Isolation of both enantiomers in crystalline form from an achiral system. Tetrahedron Lett. 2008, 49, 7135–7138. [Google Scholar] [CrossRef]
  59. Kumar, B.; Chakravarty, M.; Kumar, S.; Sajna, K.; Swamy, K. Allenylphosphonates with a 1,3,2-dioxaphosphorinane ring: Synthesis, structures, stability and utility. J. Chem. Sci. 2009, 121, 23–36. [Google Scholar] [CrossRef]
  60. Boiselle, A.P.; Meinhardt, N.A. Acetylene-allene rearrangements reactions of trivalent phosphorus chlorides with α-acetylenic acohols and glycols. J. Org. Chem. 1962, 27, 1828–1833. [Google Scholar] [CrossRef]
  61. Mark, V. A facile SNi’ rearrangement: The formation of 1,2-alkadienylphosphonates from 2-alkynyl phosphites. Tetrahedron Lett. 1962, 3, 281–284. [Google Scholar] [CrossRef]
  62. Nicolaou, K.C.; Maligres, P.; Shin, J.; de Leon, E.; Rideout, D. DNA-cleavage and antitumor activity of designed molecules with conjugated phosphine oxide-allene-ene-yne functionalities. J. Am. Chem. Soc. 1990, 112, 7825–7826. [Google Scholar] [CrossRef]
  63. Curfin, M.L.; Okamura, W.H. Synthetic and kinetic studies of the intramolecular Diels-Alder reactions of cycloalkenylallenylphosphine oxides. J. Org. Chem. 1990, 55, 5278–5287. [Google Scholar] [CrossRef]
  64. Grissom, J.W.; Huang, D. Low-temperature tandem enyne allene radical cyclizations: Efficient synthesis of 2,3-dihydroindenes from simple enediynes. Angew. Chem. Int. Ed. 1995, 34, 2037–2039. [Google Scholar] [CrossRef]
  65. Darcel, C.; Bruneau, C.; Dixneuf, P.H. Straightforward syntheses of dienyl- and diallenylphosphine oxides from α-allenols. Synthesis 1996, 1996, 711–714. [Google Scholar] [CrossRef]
  66. De Frutos, O.; Echavarren, A.M. An approach to the synthesis of the benzo[b]fluorene core of the kinamycins by an arylalkyne-allene cycloaddition. Tetrahedron Lett. 1997, 38, 7941–7943. [Google Scholar] [CrossRef]
  67. Schmittel, M.; Steffen, J.-P.; Maywald, M.; Engels, B.; Helten, H.; Musch, P. Ring size effects in the C2–C6 biradical cyclisation of enyne–allenes and the relevance for neocarzinostatin. J. Chem. Soc. Perkin Trans. 2 2001. [Google Scholar] [CrossRef]
  68. Guo, H.; Qian, R.; Guo, Y.; Ma, S. Neighboring group participation of phosphine oxide functionality in the highly regio- and stereoselective iodohydroxylation of 1,2-allenylic diphenyl phosphine oxides. J. Org. Chem. 2008, 73, 7934–7938. [Google Scholar] [CrossRef]
  69. Srinivas, V.; Sajna, K.V.; Kumara Swamy, K.C. Zn(OTf)2 catalyzed addition-cyclization reaction of allenylphosphine oxides with propargyl alcohol-unexpected formation of 2,5-dimethylenetetrahydrofurans and 2-substituted furans. Tetrahedron Lett. 2011, 52, 5323–5326. [Google Scholar]
  70. Brel, V.K. Synthesis and cyclization of diethylphosphono-substituted α-allenic alcohols to 4-(diethylphosphono)-2,5-dihydrofurans. Synthesis 1999, 1999, 463–466. [Google Scholar] [CrossRef]
  71. Brel, V.K.; Abramkin, E.V. Cyclization of allenyl phosphonates to 3-chloro-4-(diethylphosphono)-2,5-dihydrofurans induced by CuCl2. Mendeleev Commun. 2002, 12, 64–65. [Google Scholar] [CrossRef]
  72. Metcalf, B.W.; Wright, C.L.; Burkhart, J.P.; Johnston, J.O. Substrate-induced inactivation of aromatase by allenic and acetylenic steroids. J. Am. Chem. Soc. 1981, 103, 3221–3222. [Google Scholar] [CrossRef]
  73. Muller, M.; Mann, A.; Taddei, M. A new method for the preparation of (2R)-2-amino-5-phosphonopentanoic acid. Tetrahedron Lett. 1993, 34, 3289–3290. [Google Scholar] [CrossRef]
  74. Brel, V.K.; Stang, P.J. A new approach to phosphonate analogues of phosphatidyl derivatives. Eur. J. Org. Chem. 2003, 2003, 224–229. [Google Scholar] [CrossRef]
  75. Brel, V.K. Synthesis and intramolecular cyclization of diethylphosphono-substituted allenic glycols. Synthesis 2001, 2001, 1539–1545. [Google Scholar] [CrossRef]
  76. Brel, V.K.; Belsky, V.K.; Stash, A.I.; Zvodnik, V.E.; Stang, P.J. Synthesis and molecular structure of new acyclic analogues of nucleotides with a 1,2-alkadienic skeleton. Org. Biomol. Chem. 2003, 1, 4220–4226. [Google Scholar] [CrossRef]
  77. Brel, V.K.; Belsky, V.K.; Stash, A.I.; Zvodnik, V.E.; Stang, P.J. Synthesis and molecular structure of new unsaturated analogues of nucleotides containing six-membered rings. Eur. J. Org. Chem. 2005, 2005, 512–521. [Google Scholar] [CrossRef]
  78. Ivanov, I.K.; Parushev, I.D.; Christov, V.Ch. Bifunctionalized allenes, Part IX: An efficient method for regioselective synthesis of 4-heteroatom-functionalized allenecarboxylates. Heteroat. Chem. 2013, 24, 322–331. [Google Scholar] [CrossRef]
  79. Ivanov, I.K.; Parushev, I.D.; Christov, V.Ch. Bifunctionalized allenes, Part XI: Competitive electrophilic cyclization and addition reactions of 4-phosphorylated allenecarboxylates. Heteroat. Chem. 2014, 25, 60–71. [Google Scholar] [CrossRef]
  80. Robertson, D.N. Adducts of tert-alcohols containing an ethynyl group with dihydropyran. Potentially useful intermediates. J. Org. Chem. 1960, 25, 931–932. [Google Scholar] [CrossRef]
  81. Miyashita, M.; Yoshikoshi, A.; Griecolb, P.A. Pyridinium p-toluenesulfonate. A mild and efficient catalyst for the tetrahydropyranylation of alcohols. J. Org. Chem. 1977, 42, 3772–3774. [Google Scholar] [CrossRef]
  82. Joshi, M.C.; Joshi, P.; Rawat, D.S. Microwave assisted synthesis of symmetrically and asymmetrically substituted acyclic enediynes. ARKIVOC 2006, xvi, 65–74. [Google Scholar]
  83. Partha, B.; Pimkov, I. Composition, Synthesis, and Use of New Substituted Pyran and Pterin Compounds. US Patent 8378123 B2, 25 March 2011. [Google Scholar]
  • Sample Availability: Samples of the compounds 7, 9, 10 and 11 are available from the authors.
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert