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Molbank 2019, 2019(4), M1098; https://doi.org/10.3390/M1098

Communication
(2Sp,4R,6R,8Sp)-4,6-Dimethyl-1-phenyl-diferroceno-1-phosphines
1
Institute of Computational Biological Chemistry, University of Vienna, Währingerstraße 17, 1090 Vienna, Austria
2
Institute of Chemical Catalysis, University of Vienna, Währingerstraße 38, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Received: 19 November 2019 / Accepted: 11 December 2019 / Published: 13 December 2019

Abstract

:
Ferrocene-based compounds are powerful asymmetric ligands usable for chemical catalysis. We present the synthesis of six new homochiral diferroceno cycles potentially useful as P,O-, P,N- or P,S-ligands. Due to the stereoconservative nature of the SN1 reaction at carbons adjacent to ferrocene units, we obtained a single diastereomer of the 8-membered diferroceno[c,f]heterophosphocines in all cases.
Keywords:
ferrocene; asymmetric compound; planar chirality; macrocycle

1. Introduction

Ferrocenes have been used successfully for decades in asymmetric transition-metal catalysis [1]. Metallocenes can be planar-chiral if the same Cp ring is decorated with different substituents [2]. In addition to academic research, ferrocenes have been employed industrially as well. The homochiral P,P-ligand Xyliphos is used in the industrial asymmetric hydrogenation of a metolachlor precursor [3].
With the expectation to increase the asymmetric induction, the chiral array was extended with the introduction of two ferrocene units. To date, there have been diferrocenyl ligands reported acting as N,N-ligands for Rh(I) [4], P,S-ligands for Pd [5], P,P-ligands for Rh(I) [6] and P,P,P-ligands for Ru(II) [7], Rh(III) [8] and Ni(II) [9] catalyzed reactions.
The asymmetric capabilities may be improved further by constraining the conformational freedom of the two ferrocene moieties, e.g., by ring-closing to end up with a diferroceno cycle, which would incorporate two planar-chiral ferrocene units. Xiao et al. have developed 7-membered P,N-ligands for Pd(II) and with these complexes achieved up to 86% e.e. in asymmetric allylic amination [10]. Smith et al. [11] and Barreiro et al. [12] developed 8-membered P & P,P-ligands applied in Au(I)-catalyzed hydroalkoxylation. In this article, we report the synthesis of six 8-membered cyclic phosphine ligands with two annelated ferrocene moieties and similar structural features.

2. Results and Discussion

The synthetic route towards homoannularly bridged diferrocenes 4 is shown in Scheme 1. We obtained the enantiopure diferrocenyl precursor (R,Sp,Sp,R)-1 [13,14] according to a known efficient literature procedure [12]. The phosphorous atom was protected quantitatively as phosphine oxide 2a using hydrogen peroxide or as phosphine sulfide 2b with elemental sulfur. The preparation of precursor 2b is reported in Reference [15].
Nucleophilic substitutions at the α-carbon adjacent to a ferrocene unit proceed via a carbenium ion stabilized by the aromatic system. In constrast to typical SN1 reactions, however, these substitutions on the α-carbon take place stereo-conservatively [16]. Since preliminary experiments showed that the tertiary amino groups were inert to nucleophilic substitution, we attempted transformation of 2a and 2b to better leaving groups by methylation. Despite using a large excess (6 equiv) of methyl iodide, HRMS showed that only monoammonium salts 3a and 3b, respectively, were formed quantitatively. These salts could not be characterized by NMR, since they proved to be poorly soluble in CDCl3, D2O and DMSO-d6 and were used without further purification in the follow-up experiments.
Next, we attempted to perform a Hoffmann elimination of salts 3a and 3b using Ag2O in a water/dioxane mixture at mild conditions (50 °C) [17]. Instead of the expected mono-eliminated products, we obtained oxa-cycles 4a and 4b identified by NMR (see Supplementary Materials) in 11% and 9% yield, respectively, thus inadvertently producing 8-membered cycles potentially useful as P,O-ligands. Apparently, the Hoffmann elimination is disfavored compared to the reaction with the nucleophilic solvent. Presumably, these oxa-cycles were formed by a water molecule displacing the ammonium group intermolecularly and then displacing the amine group at the other ferrocenyl alkyl chain intramolecularly. In both cases, side products were formed as well, possibly by ring opening of the oxa cycles. In the first case, we obtained the dihydroxy hydrolytic side product 5 in 6% yield; in the latter case, we isolated the mono-eliminated decay product 6 in 6% yield.
Inspired by this finding, we attempted to cyclize mono-ammonium salts 3a and 3b with other bidentate nucleophiles. We intended to synthesize sulfur-bridged cycles 7a and 7b as well as nitrogen-bridged P,N cycles 8a and 8b by using NaHS and BnNH2 as nucleophiles. We heated the respective nucleophile and crude ammonium salts 3a or 3b dissolved in water or ACN in a Schlenk tube following standard procedures ([10,18], respectively). In both cases we detected the desired diferroceno[c,f]heterophosphocines in the crude reaction mixture by HRMS but attempted purification via SiO2 column chromatography merely yielded decay products formed by elimination.
A modified procedure (DMF, microwave heating) yielded less decomposed material and desired cycles were obtained by chromatography on the less acidic sorbens Al2O3. This allowed us to isolate and characterize all four intended cycles 7a (14%), 7b (15%), 8a (11%) and 8b (12%). In case of the N-benzyl cycles 8a and 8b, mono-eliminated side products 9 and 10 were isolated in 8% and 13% yield. In all six diferrocenocycles, impurities were detected by NMR. Repeated filtration or chromatography did not yield pure fractions.

3. Materials and Methods

3.1. General

Melting points were measured on a Reichelt Thermovar Kofler apparatus, uncorrected. Routine NMR spectra were recorded on a 400 MHz Bruker AVIII 400 spectrometer operating at 400.27 MHz (1H), 100.66 MHz (13C) and 162.04 MHz (31P) with autosampler. 1H-NMR spectra and 13C-NMR spectra used for substance characterization were recorded either on a 600 MHz Bruker AVIII 600 spectrometer operating (Bruker Biospin, Billerica, MA, USA) at 600.25 MHz (1H) and 150.95 MHz (13C) or on a Bruker AVIII 700 spectrometer at 700.40 MHz (1H) and 176.13 MHz (13C). 13C-NMR spectra were recorded in J-modulated mode. NMR chemical shifts are referenced to non-deuterated CHCl3 residual shifts: At 7.26 ppm for 1H-NMR, at 77.00 ppm to CDCl3 for 13C-NMR and at 0.00 ppm to 85% H3PO4 for 31P-NMR. HRMS were recorded by a Bruker Maxis ESI oa-RTOF mass spectrometer equipped with a quadrupole analyzer ion guide.
MeCN and DCM were distilled from CaH2. Reaction progress was monitored by TLC (SiO2 or Al2O3 sheets with F 254 fluorescent indicator). Preparative column chromatography (MPLC) was carried out by an Biotage Isolera One automated flash chromatography instrument using self-packed columns containing either SiO2–Macherey-Nagel silica gel 60 M (particle size 40–63 μm) or Al2O3–Merck aluminum oxide 90 standardized (activation grade II-III). All the other chemicals were analytical grade and used without further purification.

3.2. Synthesis

Bis{[(2Sp)-2-[(1R)-1-(dimethylamino)-ethyl]]ferrocenyl}phenyl phosphineoxide2a: [19]
Diaminophosphine 1 (630 mg, 1.02 mmol) was dissolved in MeOH (8.0 mL) and cooled in an ice bath. Aqueous H2O2 (30%; 210 μL, 1.85 mmol, 1.82 equiv.) was added to the orange solution. The solution was warmed to r.t. and stirred for 40 min. The reaction mixture was quenched by adding 10% aqueous NaHSO3 solution followed by sufficient aqueous NaHCO3 solution until pH 7 was reached. The aqueous suspension was extracted using DCM (3 × 8 mL). The combined organic fractions were dried over MgSO4 and the solvent was removed under reduced pressure to yield diaminophosphineoxide 2a (647 mg, quant.) as an orange solid. The highly polar product was pure enough for the next step.
1H-NMR (600 MHz, CDCl3) δ = 7.80 (dd, J = 11.4, 8.0 Hz, 2H, C6H5); 7.43–7.35 (m, 3H, C6H5); 4.52 (q, J = 6.8 Hz, 1H, C2H4); 4.49 (m, 1H, C5H3); 4.44 (m, 1H, C5H3); 4.36 (m, 1H, C5H3); 4.33 (m, 1H, C5H3); 4.28 (m, 1H, C5H3); 4.25 (m, 1H, C5H3); 4.23 (s, 5H, C5H5); 3.73 (s, 5H, C5H5); 3.31–3.26 (m, 1H, C2H4); 2.26 (s, 6H, NCH3); 1.53 (s, 6H, NCH3); 1.47 (d, J = 6.8 Hz, 3H, C2H4); 1.21–1.15 (m, 3H, C2H4) ppm. 13C-NMR δ = 130.07 (d, JCP = 9.2 Hz, CH, C6H5); 129.44 (CH, C6H5); 127.20 (CH, C6H5); 89.90 (Cq, C5H3); 85.23 (Cq, C5H3); 75.14 (Cq, C5H3); 73.60 (CH, C5H3); 71.89 (CH, C5H3); 71.25 (Cq, C5H3); 71.72 (d, JCP = 14.9 Hz, CH, C5H3); 70.34 (CH, C5H5); 70.20 (CH, C5H5); 69.59 (d, JCP = 9.8 Hz, CH, C5H3); 69.32 (CH, C5H3); 67.91 (CH, C5H3); 55.17 (CH, C2H4); 40.97 (CH3, NCH3); 34.66 (CH, C2H4); 14.93 (CH3, NCH3); 13.05 (CH3, C2H4); 13.04 (CH3, C2H4) ppm; 1 Cq not observed. 31P-NMR δ = 29.59 (s) ppm. HRMS: m/z calculated for C34H41Fe2N2OP [M + H]+: 637.1734, found: 637.1726.
{[(2Sp)-2-[(1R)-1-(dimethylamino)-ethyl]]ferrocenyl}{[(2Sp)-2-[(1R)-1-(trimethylammonium)-ethyl]]ferrocenyl}phenyl phosphineoxide iodide (3a): [20]
Diaminophosphineoxide 2a (642 mg, 1.01 mmol) was dissolved in 15 mL of dry MeCN and 15 mL of dry DCM in a flame-dried Schlenk tube under Ar. MeI (375 μL, 6.00 mmol, 5.94 equiv.) was added to the solution and stirred for 2 h at r.t. Precipitation of ammonium iodide 3a was induced by adding Et2O (10 mL) yielding the salt as an orange powder (780 mg, quant.). HRMS: m/z calculated for C35H44Fe2IN2OP [M − I]+: 651.1885, found: 651.1868.
{[(2Sp)-2-[(1R)-1-(dimethylamino)-ethyl]]ferrocenyl}{[(2Sp)-2-[(1R)-1-(trimethylammonium)-ethyl]]ferrocenyl}phenyl phosphinesulfide iodide (3b):
Similar procedure as given for 3a yielded 3b from 2b in quantitative yield.
HRMS: m/z calculated for C35H44Fe2IN2PS [M − I]+: 667.1662, found: 667.1644.
(2Sp,4R,6R,8Sp)-4,6-Dimethyl-1-phenyl-diferroceno-5-oxa-1-phosphineoxide (4a):
Ammonium iodide salt 3a (87 mg, 0.11 mmol) was dissolved in water (1.5 mL) and dioxane (1 mL). The solution was warmed to 50 °C and Ag2O (19 mg, 0.08 mmol, 1.5 equiv.) was added. The resulting suspension was stirred for 1 h. After complete consumption of the ammonium iodide salt 3a the mixture was cooled to r.t. and the solid material was removed by filtration. The solution was extracted with DCM (3 × 3 mL) and the combined organic fractions were washed with water (10 mL) and brine (10 mL) and dried (MgSO4). The solvent was removed under reduced pressure and the residue was purified by MPLC (SiO2, 75→100% EtOAc in heptane) yielding oxa cycle 4a (7 mg, 11%) as a glassy orange solid and dihydroxyphosphineoxide 5 (4 mg, 6%).
4a: 1H-NMR (600 MHz, CDCl3) δ = 8.02–7.95 (m, 2H, C6H5); 7.51–7.47 (m, 3H, C6H5); 5.13 (s, 1H, C5H3); 4.65 (q, J = 6.5 Hz, 1H, C2H4); 4.52 (s, 1H, C5H3); 4.45 (s, 1H, C5H3); 4.43 (s, 1H, C5H3); 4.38–4.36 (m, 1H, C5H3); 4.36–4.34 (m, 1H, C5H3); 4.24 (s, 5H, C5H5); 4.12 (q, J = 7.2 Hz, 1H, C2H4); 3.73 (s, 5H, C5H5); 1.53 (d, J = 6.5 Hz, 3H, C2H4); 1.51 (d, J = 6.4 Hz, 3H, C2H4) ppm. 13C-NMR δ = 138.11 (d, JCP = 112.4 Hz, Cq, C6H5); 131.56 (d, JCP = 10.0 Hz, CH, C6H5); 131.14 (d, JCP = 2.6 Hz, CH, C6H5); 127.79 (d, JCP = 12.3 Hz, CH, C6H5); 91.83 (d, JCP = 13.2 Hz, Cq, C5H3); 88.93 (d, JCP = 14.1 Hz, Cq, C5H3); 76.12 (d, JCP = 10.2 Hz, Cq, C5H3); 75.32 (Cq, C5H3); 74.74 (d, JCP = 10.6 Hz, CH, C5H3); 73.78 (d, JCP = 13.5 Hz, CH, C5H3); 70.44 (CH, C5H5); 70.17 (d, JCP = 11.1 Hz, CH, C5H3); 70.16 (CH, C5H5); 69.88 (d, JCP = 10.2 Hz, CH, C5H3); 69.15 (d, JCP = 9.8 Hz, CH, C5H3); 69.01 (d, JCP = 10.1, CH, C5H3); 68.31 (CH, C2H4); 66.13 (CH, C2H4); 20.93 (CH3, C2H4); 20.78 (CH3, C2H4) ppm. 31P-NMR δ = 31.13 (s) ppm. HRMS: m/z calculated for C30H29Fe2O2P [M + Na]+: 587.0502, found: 587.0507; [2M + Na]+ 1151.1106, found: 1151.1113.
5: 1H-NMR (600 MHz, CDCl3) δ = 7.95–7.90 (m, 2H, C6H5); 7.55–7.50 (m, 3H, C6H5); 5.93 (d, J = 5.4 Hz, 1H, OH); 5.22 (m, 1H, C5H3); 4.76 (m, 1H, C2H4); 4.57 (d, J = 5.4 Hz, 1H, C5H3); 4.56 (s, 1H, OH); 4.48 (pq, J = 2.4 Hz, 1H, C5H3); 4.44 (m, 1H, C5H3); 4.41 (m, 2H, C5H3, C2H4); 4.38 (pq, J = 2.4 Hz, 1H, C5H3); 4.17 (s, 5H, C5H5); 3.75 (s, 5H, C5H5); 1.64 (d, J = 6.7 Hz, 3H, C2H4); 1.21 (d, J = 6.7 Hz, 3H, C2H4) ppm. 13C-NMR δ = 136.54 (d, JCP = 110.2 Hz, Cq, C6H5); 131.55 (d, JCP = 2.9 Hz, CH, C6H5); 129.93 (d, JCP = 9.5 Hz, CH, C6H5); 128.45 (d, JCP = 12.1 Hz, CH, C6H5); 98.73 (d, JCP = 10.4 Hz, Cq, C5H3); 97.57 (d, JCP = 11.3 Hz, Cq, C5H3); 72.64 (Cq, C5H3); 71.85 (Cq, C5H3); 71.75 (d, JCP = 14.6 Hz, CH, C5H3); 70.97 (d, JCP = 15.0 Hz, CH, C5H3); 70.81 (d, JCP = 10.0 Hz, CH, C5H3); 70.46 (CH, C5H5); 70.45 (CH, C5H5); 70.27 (d, JCP = 11.0 Hz, CH, C5H3); 69.86 (d, JCP = 11.0 Hz, CH, C5H3); 69.64 (d, JCP = 9.8 Hz, CH, C5H3); 65.35 (CH, C2H4); 65.30 (CH, C2H4); 22.98 (CH3, C2H4); 21.95 (CH3), C2H4) ppm. 31P-NMR δ = 38.45 (s) ppm. HRMS: m/z calculated for C30H31Fe2O3P [M + Na]+: 605.0607, found: 605.0595; [2M + Na]+: 1187.1317, found: 1187.1295.
(2Sp,4R,6R,8Sp)-4,6-Dimethyl-1-phenyl-diferroceno-5-oxa-1-phosphinesulfide (4b):
Similar procedure as given for 4a yielded cycle 4b from 3b in 9% yield and 6% of eliminated side product 6.
4b: 1H-NMR (600 MHz, CDCl3) δ = 8.13–8.07 (m, 2H, C6H5); 7.45–7.38 (m, 3H, C6H5); 5.44 (m, 1H, C5H3); 4.61 (m, 1H, C5H3); 4.59–4.55 (m, 2H, C2H4); 4.47 (m, 1H, C5H3); 4.45–4.39 (m, 2H, C5H3); 4.37 (m, 1H, C5H3); 4.16 (s, 5H, C5H5); 4.00 (s, 5H, C5H5); 1.45 (d, J = 6.4 Hz, 3H, C2H4); 1.41 (d, J = 6.7 Hz, 3H, C2H4) ppm. 13C-NMR δ = 137.31 (d, JCP = 90.0 Hz, Cq, C6H5); 132.51 (d, JCP = 11.2 Hz, CH, C6H5); 130.82 (d, JCP = 3.0 Hz, CH, C6H5); 127.33 (d, JCP = 12.7 Hz, CH, C6H5); 92.84 (d, JCP = 9.9 Hz, Cq, C5H3); 89.73 (d, JCP = 10.2 Hz, Cq, C5H3); 77.97 (Cq, C5H3); 77.42 (d, JCP = 15.5 Hz, CH, C5H3); 76.15 (Cq, C5H3); 75.04 (d, JCP = 15.2 Hz, CH, C5H3); 70.82 (d, JCP = 8.8 Hz, CH, C5H3); 70.81 (CH, C5H5); 70.41 (CH, C5H5); 69.58 (d, JCP = 11.7 Hz, CH, C5H3); 69.41 (d, JCP = 11.5 Hz, CH, C5H3); 69.33 (d, JCP = 9.0 Hz, CH, C5H3); 65.79 (2 CH, C2H4); 21.22 (CH3, C2H4); 20.56 (CH3, C2H4) ppm. 31P-NMR δ = 43.82 (s) ppm. HRMS: m/z calculated for C30H29Fe2OPS [M + Na]+: 603.0273, found: 603.0279; [2M + Na]+ 1183.0649, found: 1183.0662.
6: 1H-NMR (600 MHz, CDCl3) δ = 8.10 (dd, J = 17.6, 10.8 Hz, 1H, C2H3); 7.87–7.81 (m, 2H, C6H5); 7.51–7.42 (m, 3H, C6H5); 5.49 (dd, J = 17.6, 1.6 Hz; 1H, C2H3); 5.23–5.17 (m, 1H, C5H3); 5.20 (dd, J = 10.8, 1.7 Hz, 1H, C2H3); 4.88 (m, 1H, C5H3); 4.49 (m, 1H, C5H3); 4.34 (s, 5H, C5H5); 4.33 (m, 1H, C5H3); 4.24 (m, 1H, C5H3); 4.17 (s, 5H, C5H5); 3.77 (m, 1H, C5H3); 3.71 (m, 1H, OH); 2.41 (d, J = 5.3 Hz; 1H, C2H4); 1.26 (d, J = 6.6 Hz, 3H, C2H4) ppm. 13C-NMR δ = 135.30 (d, JCP = 87.1 Hz, Cq, C6H5); 134.25 (CH, C6H5); 132.10 (d, JCP = 10.3 Hz, CH, C6H5); 131.38 (d, JCP = 2.8 Hz, CH, C6H5); 127.96 (d, JCP = 12.1 Hz, CH, C2H3); 111.74 (CH2, C2H3); 94.90 (d, JCP = 12.3 Hz, Cq, C5H3); 88.43 (d, JCP = 11.8 Hz, Cq, C5H3); 78.56 (d, JCP = 95.4 Hz, Cq, C5H3); 75.05 (d, JCP = 12.0 Hz, CH, C5H3); 74.97 (d, JCP = 12.6 Hz, CH, C5H3); 73.48 (d, JCP = 96.0 Hz, Cq, C5H3); 71.22 (CH, C5H5); 71.00 (d, JCP = 9.7 Hz, CH, C5H3); 70.72 (CH, C5H5); 70.10 (d, JCP = 10.4 Hz, CH, C5H3); 68.38 (d, JCP = 9.1 Hz, CH, C5H3); 68.04 (d, JCP = 10.5 Hz, CH, C5H3); 64.38 (CH, C2H4); 21.91 (CH3, C2H4) ppm. 31P-NMR δ = 40.51 (s) ppm. HRMS: m/z calculated for C30H29Fe2OPS [M]+ 580.0376, found: 580.0360; [M + Na]+ 603.0273, found: 603.0273; [M + K]+ 619.0013, found: 619.0018.
(2Sp,4R,6R,8Sp)-4,6-Dimethyl-1-phenyl-diferroceno-5-sulfa-1-phosphineoxide (7a):
Ammonium iodide salt 3a (75 mg, 0.10 mmol) and NaHS·H2O (7.5 mg, 0.10 mmol, 1.0 equiv.) were dissolved in 8 mL of DMF and heated for 8 min at 100 °C in a microwave oven. The mixture was cooled to r.t., 10 mL of DCM were added and the organic layer was washed four times with 50 mL of water each, once with 20 mL of brine and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (Al2O3; 0→100% EtOAc in heptane) yielding 14% of the intended sulfidephosphineoxide diferrocenyl cycle 7a (8 mg) as a glassy orange solid.
1H-NMR(700 MHz, CDCl3) δ = 7.92–7.85 (m, 2H, C6H5); 7.52–7.48 (m, 3H, C6H5); 5.30 (s, 1H, C5H3); 5.11 (s, 1H, C5H3); 4.52 (s, 1H, C5H3); 4.37 (s, 1H, C5H3); 4.36 (s, 1H, C5H3); 4.35 (s, 5H, C5H5); 4.24 (s, 1H, C5H3); 3.83 (s, 5H, C5H5); 3.74 (q, J = 6.9 Hz, 1H, C2H4); 3.21 (q, J = 7.1 Hz, 1H, C2H4); 1.58 (d, J = 7.2 Hz, 3H, C2H4); 1.51 (d, J = 7.0 Hz, 3H, C2H4) ppm. 13C-NMR δ = 138.59 (d, JCP = 111.7 Hz, Cq, C6H5); 131.81 (d, JCP = 9.8 Hz, CH, C6H5); 131.17 (d, JCP = 2.7 Hz, CH, C6H5); 127.66 (d, JCP = 12.1 Hz, CH, C6H5); 96.88 (d, JCP = 13.2 Hz, Cq, C5H3); 92.56 (d, JCP = 13.8 Hz, Cq, C5H3); 74.83 (d, JCP = 37.5 Hz, Cq, C5H3); 74.20 (d, JCP = 42.9 Hz, Cq, C5H3); 73.50 (d, JCP = 10.7 Hz, CH, C5H3); 73.32 (d, JCP = 13.8 Hz, CH, C5H3); 70.36 (CH, C5H5); 70.32 (d, JCP = 11.8 Hz, CH, C5H3); 70.11 (d, JCP = 10.1 Hz, CH, C5H3); 69.95 (CH, C5H5); 67.45 (d, JCP = 9.6 Hz, CH, C5H3); 67.43 (d, JCP = 10.0 Hz, CH, C5H3); 36.62 (CH, C2H4); 35.71 (CH, C2H4); 20.28 (CH3, C2H4); 20.20 (CH3, C2H4) ppm. 31P-NMR δ = 29.47 (s) ppm. HRMS: m/z calculated for C30H29Fe2OPS [M]+: 580.0376, found: 580.0369.
(2Sp,4R,6R,8Sp)-4,6-Dimethyl-1-phenyl-diferroceno-5-sulfa-1-phosphinesulfide (7b):
Similar procedure as given for 7a yielded cycle 7b from 3b in 15% yield.
1H-NMR (600 MHz, CDCl3) δ = 7.95–7.90 (m, 2H, C6H5); 7.47–7.43 (m, 1H, C6H5); 7.43–7.38 (m, 2H, C6H5); 5.38 (m, 1H, C5H3); 4.64 (q, J = 2.2 Hz, 1H, C5H3); 4.50 (m, 1H, C5H3); 4.42–4.40 (m, 1H, C5H3); 4.40–4.38 (m, 2H, C5H3); 4.28 (s, 5H, C5H5); 4.20 (s, 5H, C5H5); 3.63 (q, J = 6.8 Hz, 1H, C2H4); 2.96 (q, J = 7.3 Hz, 1H, C2H4); 1.54 (d, J = 7.3 Hz, 3H, C2H4); 1.31 (d, J = 6.8 Hz, 3H, C2H4) ppm. 13C-NMR δ = 137.96 (d, JCP = 88.8 Hz, Cq, C6H5); 132.57 (d, JCP = 11.0 Hz, CH, C6H5); 131.13 (d, JCP = 3.1 Hz, CH, C6H5); 127.45 (d, JCP = 12.5 Hz, CH, C6H5); 96.94 (d, JCP = 11.0 Hz, Cq, C5H3); 92.90 (d, JCP = 10.6 Hz, Cq, C5H3); 75.32 (d, JCP = 15.6 Hz, CH, C5H3); 75.02 (Cq, C5H3); 74.42 (Cq, C5H3); 73.75 (d, JCP = 15.0 Hz, CH, C5H3); 70.91 (CH, C5H5); 70.29 (CH, C5H5); 70.22 (d, JCP = 11.5 Hz, CH, C5H3); 70.05 (d, JCP = 11.5 Hz, CH, C5H3); 68.58 (d, JCP = 8.6 Hz, CH, C5H3); 68.34 (d, JCP = 9.1 Hz, CH, C5H3); 37.27 (CH, C2H4); 35.39 (CH, C2H4); 20.82 (CH3, C2H4); 20.79 (CH3, C2H4) ppm. 31P-NMR δ = 42.92 (s) ppm. HRMS: m/z calculated for C30H29Fe2PS2 [M]+: 596.0147, found: 596.0141.
(2Sp,4R,6R,8Sp)-4,6-Dimethyl-5-benzyl-1-phenyl-diferroceno-5-amino-1-phosphineoxide (8a):
Ammonium iodide salt 3a (77 mg, 0.10 mmol) and BnNH2 (11 μL, 0.10 mmol, 1.0 equiv.) were dissolved in 8 mL of DMF and heated for 8 min at 100 °C in a microwave oven. The reaction mixture was cooled to r.t., 10 mL of DCM were added and the organic solution was washed four times with 50 mL of water each, once with 20 mL of brine and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (Al2O3; 0→100% EtOAc in heptane) yielding 11% of the intended benzylic aminephosphineoxide diferroceno cycle 8a (7 mg) as a glassy orange solid as well as 8% of the sec. amine elimination product 9 (5 mg).
8a: 1H-NMR (600 MHz, CDCl3) δ = 8.11–8.06 (m, 2H, C6H5); 7.57–7.50 (m, 3H, C6H5); 7.41 (d, J = 7.4 Hz, 2H, C7H7); 7.28–7.24 (m, 2H, C7H7); 7.17 (pt, J = 7.3 Hz, 1H, C7H7); 4.80 (m, 1H, C5H3); 4.47 (m, 1H, C5H3); 4.39 (m, 2H, C5H3); 4.35 (m, 1H, C5H3); 4.29 (m, 1H, C5H3); 4.24 (s, 5H, C5H5); 4.04 (q, J = 6.8 Hz, 1H, C2H4); 3.94 (d, J = 16.4 Hz, 1H, C7H7); 3.90 (s, 5H, C5H5); 3.73 (q, J = 6.6 Hz, 1H, C2H4); 3.39 (d, J = 16.3 Hz, 1H, C7H7); 1.26 (d, J = 6.5 Hz, 3H, C2H4); 1.25 (d, J = 6.9 Hz, 3H, C2H4) ppm. 13C-NMR δ = 143.69 (Cq, C7H7); 137.02 (d, JCP = 110.2 Hz, Cq, C6H5); 132.35 (d, JCP = 9.38 Hz, CH, C6H5); 131.20 (d, JCP = 2.7 Hz, CH, C6H5); 127.82 (CH, C7H7); 127.63 (d, JCP = 5.5 Hz, CH, C6H5); 127.54 (d, JCP = 6.6, CH, C7H7); 126.01 (CH, C7H7); 93.20 (d, JCP = 13.2 Hz, Cq, C5H3); 93.06 (d, JCP = 13.6 Hz, Cq, C5H3); 75.38 (d, JCP = 22.2 Hz, Cq, C5H3); 74.62 (d, JCP = 18.2 Hz, Cq, C5H3); 73.65 (d, JCP = 11.4 Hz, CH, C5H3); 72.64 (d, JCP = 13.9 Hz, CH, C5H3); 70.45 (CH, C5H5); 70.39 (d, JCP = 10.6 Hz, CH, C5H3); 70.17 (CH, C5H5); 69.81 (d, JCP = 11.2 Hz, CH, C5H3); 69.58 (d, JCP = 9.6 Hz, 2 CH, C5H3); 54.66 (CH, C2H4); 53.55 (CH, C2H4); 53.12 (CH2, C7H7); 21.44 (CH3, C2H4); 20.52 (CH3, C2H4) ppm. 31P-NMR δ = 29.63 (s) ppm. HRMS: m/z calculated for C37H36Fe2NOP [M + H]+: 654.1306, found: 654.1306; [M + Na]+: 676.1126, found: 676.1129.
9: 1H-NMR (600 MHz, CDCl3) δ = 7.80–7.69 (m, 3H, C6H5); 7.55–7.34 (m, 2H, C6H5); 7.33–7.27 (m, 3H, C7H7); 7.16–7.10 (m, 2H, C7H7); 6.84–6.80 (m, 1H, C2H3); 5.46 (dd, J = 17.7, 1.6 Hz, 1H, C2H3); 5.16 (dd, J = 10.8, 10.6 Hz, 1H, C2H3); 4.86 (m, 1H, C5H3); 4.49 (m, 1H, C2H4); 4.41 (pq, J = 2.4 Hz, 1H, C5H3); 4.39 (pt, J = 2.0 Hz, 1H, C5H3); 4.36 (m, 1H, C5H3); 4.27 (s, 5H, C5H5); 4.24 (s, 1H, C5H3); 3.93 (s, 5H, C5H5); 3.89 (d, J = 4.3 Hz, 1H, C5H3); 3.20 (s, 2H, C7H7); 1.43 (d, J = 6.6, 3H, C2H4) ppm. 13C-NMR δ = 133.52 (Cq, C6H5); 131.28 (CH, C6H5); 130.29 (CH, C6H5); 128.38 (CH, C6H5); 128.26 (CH, C7H7); 128.15 (CH, C7H7); 127.95 (CH, C7H7); 111.43 (CH2, C2H3); 90.13 (Cq, C2H3); 86.08 (Cq, C5H3); 71.65 (CH, C5H3); 71.26 (CH, C5H3); 71.17 (CH, C5H3); 70.81 (CH, C5H3); 70.73 (CH, C5H5); 70.31 (CH, C5H5); 70.28 (CH, C5H3); 69.58 (CH, C5H3); 67.25 (CH, C2H4); 53.15 (CH2, C7H7); 20.56 (CH3, C2H4) ppm; 4 Cq not observed. 31P-NMR δ = 30.54 (s) ppm. HRMS: m/z calculated for C37H36Fe2NOP [M + H]+: 654.1306, found: 654.1314.
(2Sp,4R,6R,8Sp)-4,6-Dimethyl-5-benzyl-1-phenyl-diferroceno-5-amino-1-phosphinesulfide (8b):
Similar procedure as given for 8a yielded cycle 8b from 3b in 12% yield and side product 10 in 13% yield.
8b: 1H-NMR (600 MHz, CDCl3) δ = 7.91 (ddd, J = 13.6, 7.8, 1.5 Hz, 2H, C6H5); 7.47–7.41 (m, 3H, C6H5); 7.31 (d, J = 7.5 Hz, 2H, C7H7); 7.28–7.24 (m, 2H, C7H7); 7.17 (pt, J = 7.2 Hz, 1H, C7H7); 5.36 (m, 1H, C5H3); 4.65 (dd, J = 4.3, 2.4 Hz, 1H, C5H3); 4.57 (m, 1H, C5H3); 4.48 (m, 1H, C5H3); 4.46 (m, 1H, C5H3); 4.38 (m, 1H, C5H3); 4.21 (s, 5H, C5H5); 4.14 (s, 5H, C5H5); 3.98 (s, 1H, C7H7); 3.73 (q, J = 6.9 Hz, 1H, C2H4); 3.46 (q, J = 6.3 Hz, 1H, C2H4); 3.19 (d, J = 16.9 Hz, 1H, C7H7); 1.19 (d, J = 7.0 Hz, 3H, C2H4); 1.09 (d, J = 6.4 Hz, 3H, C2H4) ppm. 13C–NMR δ = 144.18 (Cq, C7H7); 138.58 (d, JCP = 89.2 Hz, Cq, C6H5); 132.79 (d, JCP = 11.3 Hz, CH, C6H5); 130.88 (d, JCP = 3.0 Hz, CH, C6H5); 127.88 (CH, C7H7); 127.32 (d, JCP = 12.4 Hz, CH, C6H5); 127.00 (CH, C7H7); 126.05 (CH, C7H7); 93.39 (d, JCP = 11.1 Hz, Cq, C5H3); 92.56 (d, JCP = 12.1 Hz, Cq, C5H3); 75.55 (Cq, C5H3); 75.47 (d, JCP = 15.6 Hz, CH, C5H3); 74.93 (Cq, C5H3); 73.93 (d, JCP = 15.0 Hz, CH, C5H3); 71.41 (d, JCP = 9.7 Hz, CH, C5H3); 71.01 (CH, C5H5); 70.35 (CH, C5H5); 70.07 (d, JCP = 11.5 Hz, CH, C5H3); 69.96 (d, JCP = 9.1 Hz, CH, C5H3); 69.85 (d, JCP = 11.4 Hz, CH, C5H3); 55.79 (CH, C2H4); 53.18 (CH2, C7H7); 52.14 (CH, C2H4); 22.12 (CH3, C2H4); 21.35 (CH3, C2H4) ppm. 31P-NMR δ = 43.41 (s) ppm. HRMS: m/z calculated for C37H36Fe2NPS [M + H]+: 670.1078, found: 670.1068.
10: M.p.: 179–180 °C (decomposition). 1H-NMR (600 MHz, CDCl3) δ = 7.82 (dd, J = 12.7, 6.5 Hz, 2H, C6H5); 7.29–7.23 (m, 3H, C6H5); 7.13–7.08 (m, 3H, C7H7); 6.80–6.76 (m, 3H, C7H7, C2H3); 5.47 (dd, J = 17.7, 1.6 Hz, 1H, C2H3); 5.17 (dd, J = 10.8, 1.6 Hz, 1H, C2H3); 4.86 (m, 1H, C5H3); 4.62 (q, J = 6.7 Hz, 1H, C2H4); 4.56 (m, 1H, C5H3); 4.33 (s, 5H, C5H5); 4.30 (m, 1H, C5H3); 4.24 (dd, J = 4.1, 2.6 Hz, 1H, C5H3); 4.12 (s, 5H, C5H5); 3.77 (m, 1H, C5H3); 3.67 (m, 1H, C5H3); 3.21 (dd, J = 23.6, 12.8 Hz, 2H, C7H7); 1.45 (d, J = 6.6 Hz, 3H, C2H4) ppm. 13C-NMR δ = 140.46 (Cq, C7H7); 135.15 (d, JCP = 86.3 Hz, Cq, C6H5); 134.47 (CH, C7H7); 131.80 (d, JCP = 10.2 Hz, CH, C6H5); 131.14 (d, JCP = 2.9 Hz, CH, C6H5); 127.85 (CH, C7H7); 127.82 (d, JCP = 11.4 Hz, CH, C6H5); 127.78 (CH, C7H7); 126.14 (CH, C2H3); 111.48 (CH2, C2H3); 95.12 (d, JCP = 12.7 Hz, Cq, C5H3); 88.55 (d, JCP = 12.0 Hz, Cq, C5H3); 77.91 (d, JCP = 95.5 Hz, Cq, C5H3); 75.03 (d, JCP = 12.2 Hz, CH, C5H3); 74.42 (d, JCP = 12.1 Hz, CH, C5H3); 73.98 (d, JCP = 95.4 Hz, Cq, C5H3); 71.15 (CH, C5H5); 71.10 (d, JCP = 10.1 Hz, CH, C5H3); 70.67 (CH, C5H5); 69.97 (d, JCP = 10.2 Hz, CH, C5H3); 68.22 (d, JCP = 9.1 Hz, CH, C5H3); 67.94 (d, JCP = 10.6 Hz, CH, C5H3); 50.71 (CH2, C7H7); 50.08 (CH, C2H4); 19.53 (CH3, C2H4) ppm. 31P-NMR δ = 39.55 (s) ppm. HRMS: m/z calculated for C37H36Fe2NPS [M + H]+: 670.1078, found: 670.1075.

Supplementary Materials

The following are available online, Figure S1: 1H-NMR spectrum of compound 2a, Figure S2: 13C-NMR spectrum of compound 2a, Figure S3: 31P-NMR spectrum of compound 2a, Figure S4: 1H-NMR spectrum of compound 4a, Figure S5: 13C-NMR spectrum of compound 4a, Figure S6: 31P-NMR spectrum of compound 4a, Figure S7: 1H-NMR spectrum of compound 4b, Figure S8: 13C-NMR spectrum of compound 4b, Figure S9: 31P-NMR spectrum of compound 4b, Figure S10: 1H-NMR spectrum of compound 7a, Figure S11: 13C-NMR spectrum of compound 7a, Figure S12: 31P-NMR spectrum of compound 7a, Figure S13: 1H-NMR spectrum of compound 7b, Figure S14: 13C-NMR spectrum of compound 7b, Figure S15: 31P-NMR spectrum of compound 7b, Figure S16: 1H-NMR spectrum of compound 8a, Figure S17: 13C-NMR spectrum of compound 8a, Figure S18: 31P-NMR spectrum of compound 8a, Figure S19: 1H-NMR spectrum of compound 8b, Figure S20: 13C-NMR spectrum of compound 8b, Figure S21: 31P-NMR spectrum of compound 8b, Figure S22: 1H-NMR spectrum of compound 5, Figure S23: 13C-NMR spectrum of compound 5, Figure S24: 31P-NMR spectrum of compound 5, Figure S25: 1H-NMR spectrum of compound 6, Figure S26: 13C-NMR spectrum of compound 6, Figure S27: 31P-NMR spectrum of compound 6, Figure S28: 1H-NMR spectrum of compound 9, Figure S29: 13C-NMR spectrum of compound 9, Figure S30: 31P-NMR spectrum of compound 9, Figure S31: 1H-NMR spectrum of compound 10, Figure S32: 13C-NMR spectrum of compound 10.

Author Contributions

P.H.: Synthesis planning, experimental synthetic work, literature search, writing of the manuscript; M.W.: Resources, spectra interpretation, proofreading of the manuscript.

Funding

This research received no external funding.

Acknowledgments

Open Access Funding by the University of Vienna is gratefully acknowledged.

Conflicts of Interest

The authors declare no conflict of interest.

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Scheme 1. Synthesis of 8-membered diferroceno[c,f]heterophosphocines. All of the shown compounds possess a (Sp,Sp)-configuration unless otherwise noted.
Scheme 1. Synthesis of 8-membered diferroceno[c,f]heterophosphocines. All of the shown compounds possess a (Sp,Sp)-configuration unless otherwise noted.
Molbank 2019 m1098 sch001
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