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Article

Enantioselective Protonation of Radical Anion Intermediates in Photoallylation and Photoreduction Reactions of 3,3-Diaryl-1,1-dicyano-2-methylprop-1-ene with Allyltrimethylsilane

by
Hajime Maeda
*,†,
Masayuki Iida
,
Daisuke Ogawa
and
Kazuhiko Mizuno
*
Department of Applied Chemisty, College of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
*
Authors to whom correspondence should be addressed.
†
Present address: Division of Material Chemistry, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
Molecules 2019, 24(14), 2677; https://doi.org/10.3390/molecules24142677
Submission received: 25 June 2019 / Revised: 17 July 2019 / Accepted: 22 July 2019 / Published: 23 July 2019
(This article belongs to the Special Issue New Insights in Photoredox Catalysis)
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Abstract

:
Photoreactions of acetonitrile solutions of 3,3-diaryl-1,1-dicyano-2-methylprop-1-enes (1a–c) with allyltrimethylsilane (2) in the presence of phenanthrene as a photoredox catalyst and acetic acid as a proton source formed photoallylation (3) and photoreduction (4) products via photoinduced electron transfer pathways. When (S)-mandelic acid was used as the proton source, the reactions proceeded with 3.4 and 4.8 %ee for formation of 3 and 4, respectively. The results of studies of the effect of aryl ring substituents and several chiral carboxylic acids suggested that the enantioselectivities of the reactions are governed by steric controlled proton transfer in intermediate complexes formed by π-π and OH-π interactions of anion radicals derived from 1a–c and chiral carboxylic acids.

Graphical Abstract

1. Introduction

Coupling reactions proceeding through photoinduced electron transfer (PET) pathways have been extensively studied from both a synthetic as well as a mechanistic viewpoint [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. Because radical ions that serve as intermediates in these processes are short-lived and highly reactive, control of the stereochemistry of these reactions is often difficult [15,16,17,18,19,20,21]. We have previously developed photoallylation and photoreduction reactions of electron deficient alkenes with allyltrimethylsilane that occur via PET pathways [22,23,24]. In addition, we also demonstrated that diastereoselectivity of this process can be achieved by steric control of allyl radical or proton addition to radical anions that are generated from electron deficient alkenes (Scheme 1) [25,26,27]. The current study was aimed at the development of enantioselective PET promoted coupling reactions, and specifically, at assessing the effect of chiral carboxylic acids on the stereochemical outcomes of photoallylation and photoreduction reactions of prochiral electron deficient alkenes. The results showed that these processes took place with maximum 3.4–4.8 %ee when (S)-mandelic acid was used as the chiral proton source.

2. Results and Discussion

Irradiation of an acetonitrile solution containing 1,1-dicyano-2-methyl-3,3-diphenylprop-1-ene (1a), 3 equiv of allyltrimethylsilane (2), a catalytic amount of phenanthrene (Phen) as a photoredox catalyst in a Pyrex vessel using a 300 W high-pressure mercury lamp was found to produce reduction product 4a in 53% yield (Scheme 2, Table 1, entry 1, supplementary). Photoreaction of 1a with 2 in the presence of acetic acid produced the allylated product 3a in addition to 4a in 34 and 31% yields, respectively (entry 2). The corresponding products 3b–c and 4b–c were produced in photoreactions of bis(p-methoxyphenyl) (1b) and bis(p-chlorophenyl) (1c) derivatives conducted under the same conditions (entries 3–6). The irradiation times used for these processes are those required for complete consumption of 1a–c. The observed efficiencies of the reactions, based on the required irradiation times, decreased in the order 1c > 1a > 1b.
Structures of photoproducts 3a–c and 4a–c were determined by using spectroscopic methods. In 1H-NMR spectra of CDCl3 solutions of 3a and 4a (Figure 1), the chemical shifts of resonances for protons that are bonded to the asymmetric carbons, i.e., Hb in 3a and Hh in 4a, were 2.97 (qd) and 3.02 (qt) ppm, respectively. Authentic samples of the photoproducts were prepared by hydrogenation of 1a using Pd/C to form 4a and ensuing allylation of 4a using allyl chloride to form 3a (Scheme 3). The spectral data for the synthesized compounds were identical to those of photoproduced 3a and 4a.
In order to explore the enantioselectivities of these photoreactions, samples of 3a and 4a were subjected to HPLC using a chiral stationary phase with the effluents being monitored by using UV and CD detectors (Figure 2a–d). The results showed that two peaks in the HPLC trace for the enantiomers of 3a and 4a were completely resolved. Unfortunately, HPLC conditions could not be found for resolution of the enantiomers of 3b and 4b. Moreover, the enantiomers of 3c and 4c can be separated by using GC with a chiral capillary column (Figure 2e).
In order to prove that these separation techniques led to the individual enantiomers, the effluents of peaks A–D in Figure 2a–d were collected, concentrated in vacuo and the residues in ethanol were subjected to UV-vis absorption and CD spectroscopic analysis (Figure 3 and Figure 4). The UV-vis absorption spectra of substances in effluents corresponding to peaks A and C were identical to those from peaks B and D, respectively. In addition, 1H-NMR and mass spectra of the respective substances in peaks A and C were also identical to those in peaks B and D, respectively. Moreover, CD spectral traces of substances comprising peaks A and B, and peaks C and D, respectively, were mirror images relative to the horizontal base line. The combined results indicated that the enantiomers of these substances can be resolved by using chromatographic methods.
To assess the potential of introducing enantioselectivity into the photoreactions described above, irradiations were carried out on solutions of 1a–c and allyltrimethylsilane (2) containing chiral carboxylic acids. The yields and percent enantiomeric excesses (%ee) of products formed in these processes are listed in Table 2. The %ee in each case was calculated using the ratio of areas under the chiral HPLC or GC peaks corresponding to the enantiomers as %ee when acetic acid was used becoming zero. A positive %ee value corresponds to a situation in which the major isomer is the second peak, while a negative value shows that the major isomer is the first peak. The absolute structures could not be decided. The data arising from photoreactions in the absence or presence of achiral acetic acid are also included in Table 2 for comparison purposes.
Use of 1 equiv of (R)-mandelic acid in photoreaction of 1a with 2 led to formation of 3a and 4a with respective +1.5 and +4.1 %ee values (entry 3). A reversal in major enantiomers of the products arose from the reaction of 1a with 2 conducted in the presence of (S)-mandelic acid (entry 4), which supports the reaction proceeding in an enantioselective manner. Also, when l-lactic acid was used in this photoreaction, the major enantiomers were the reverse of those formed in reactions in the presence of (S)-mandelic acid (entry 5). The use of C2 symmetric dibenzoyl l-tartaric acid did not promote an increase of %ee of either product (entry 6). The photoreaction of 1b with 2 also occurred when (R)- and (S)-mandelic acids were used, however the %ee of either product could not be determined (entries 9 and 10). Like in the case of 1a, photoreaction of 1c produced products 3c and 4c in which the major enantiomers were reversed when (R)- and (S)-mandelic acids were utilized (entries 13 and 14). Moreover, the results showed that the %ee improved up to 3.5 when (S)-2-(6-methoxy-2-naphthyl)propionic acid was used as a chiral acid (entry 15).
Each photoreaction described above takes place through a process termed photoredox sensitization by phenanthrene (Phen) (Scheme 4) [22,23,24,25,26,27]. In the pathway, the excited singlet state of Phen, generated by light absorption, transfers one electron (SET (single electron transfer)) to the electron-deficient alkene 1 to form the phenanthrene radical cation (Phen•+) and the alkene radical anion 1•−. The subsequent SET from allyltrimethylsilane (2) to Phen•+ generates recovered Phen and the radical cation 2•+, which undergoes nucleophile-assisted Si-C bond cleavage [28,29,30] to form the allyl radical. Also, radical anion 1•− is protonated by the carboxylic acid to produce radical 5, which upon coupling with the allyl radical generates the allylation product 3. In a competitive pathway, radical 5 undergoes hydrogen abstraction or one-electron reduction followed by protonation or disproportionation to form reduction product 4 [23]. The inefficiency of the photoreaction of the MeO-substituted substrate 1b and high efficiency of the reaction of Cl-substituted reactant 1c are likely consequences of the stabilities of the corresponding radical anions 1b•– and 1c•– which governs their rates of formation by SET from relative to unproductive decay of the excited singlet state of Phen.
Based on the results of molecular orbital calculations with related compounds, it is estimated that the radical contribution to radical anion 1•– is large at the dicyano substituted carbon (α) and that negative charge density is large at the dialkyl substituted carbon (β) [23,24,26,27]. In accord with this conclusion, the photoreaction of 1a with 2 using CH3COOD as the additive produced mainly mono-deuteriated forms of 3a and 4a in which deuterium is present at the stereogenic carbons marked with * in Scheme 4. Therefore, enantioselectivity is governed at the step where protonation of the radical anion takes place.
The stereochemistry of protonation of the radical anion 1•– can be discussed using a Felkin-Anh model (Scheme 5) [31,32,33]. Specifically, in reaction of 1a in the presence of (S)-mandelic acid, proton transfer to the Re face of 1a•– should be preferred in a complex in which a π-π stabilizing interaction occurs between the phenyl groups and the OH group of the acid is located in a sterically less hindered position. Proton transfer to the Re face of 1a leads to the eventual formation of (S)-3a and (S)-4a. On the other hand, in the reaction of 1a in the presence of l-lactic acid, an OH-π interaction between the OH group of the acid and the phenyl group of 1a•– takes place to form a complex in which proton transfer from the carboxylic acid group occurs preferentially to the Si face to minimize steric repulsion of methyl group. This process then gives rise to formation of (R)-3a and (R)-4a. In photoreaction of 1c in the presence of (S)-2-(6-methoxy-2-naphthyl)propionic acid, the main enantiomers produced were the same as those generated in reaction of 1c in the presence of (S)-mandelic acid, and %ee increased. This outcome might be a consequence of a strong π-π interaction between the chlorophenyl and the methoxynaphthyl groups.

3. Experimental Section

3.1. Materials and Equipments

THF was distilled from CaH2 and then from Na/benzophenone. CH3CN was distilled from P2O5 then from Ca(OH)2. Hexane and 2-propanol were distilled without using a drying agent. Allyltrimethylsilane (2) was prepared using a reported procedure [27]. Activated alumina was dried at 200 °C for 2 h before use. Most other chemical substances were used after purification by distillation or recrystallization.
Column chromatography was conducted by using Wakogel C-70~230 (Fujifilm Wako Pure Chemical Corporation, Osaka, Japan). Thin-layer chromatography was performed by using Merck Kiesel gel 60 F254 plates (Merck KGaA, Darmstadt, Germany). HPLC separations (achiral) were performed on a recycling preparative HPLC equipped with Jasco PU-987 pump, UV-970 UV detector, and a Chemcosorb I-5Si column (Chemco Plus Scientific Co., Ltd., Osaka, Japan) using hexane-AcOEt or hexane-2-propanol as an eluent, or a recycling preparative HPLC equipped with Jasco PU-2086 pump, RI-2031 differential refractometer (Jasco Corporation, Tokyo, Japan), and Megapak GEL 201F columns (GPC) using CHCl3 as an eluent (Jasco Corporation, Tokyo, Japan).
1H and 13C-NMR spectra were recorded using a Varian MERCURY-300 (300 MHz and 75 MHz, respectively, (Varian Inc., Palo Alto, CA, USA) spectrometer with Me4Si as an internal standard. Mass spectra (EI, achiral) were recorded on a SHIMADZU GCMS-QP5050 (Shimadzu Corporation, Kyoto, Japan) operating in the electron impact mode (70 eV) equipped with GC-17A and DB-5MS column (J&W Scientific Inc., Serial: 8696181, Folsom, CA, USA). UV-vis spectra were recorded using a Jasco V-530 spectrophotometer (Jasco Corporation, Tokyo, Japan).

3.2. Preparation of 1a

A mixture of 1,1-diphenylacetone (1.051 g, 5.0 mmol), malononitrile (0.330 g, 5.0 mmol) and activated alumina (1.5 g) was stirred at 60 °C for 1 h [34]. The solids were removed by filtration. Concentration of the filtrate gave a residue that was subjected to silica gel column chromatography followed by recrystallization from hexane to give 2-(1,1-diphenylpropan-2-ylidene)malononitrile (1a, white solid, 0.531 g, 2.06 mmol, 41% yield). Lit [35].

3.3. Preparation of 1b

A THF (50 mL) solution of 4-bromoanisole (17.53 mL, 140.0 mmol) was added dropwise to stirred Mg turnings (3.889 g, 160.0 mmol). A small amount of I2 was added to facilitate the reaction. A THF (20 mL) solution of ethyl l-lactate (4.587 mL, 40.0 mmol) was added dropwise to the solution, and the resulting mixture was stirred at reflux, cooled, and extracted with Et2O and NH4Cl aq [36]. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo, giving a residue that was subjected to silica gel column chromatography to give 1,1-bis(4-methoxyphenyl)propane-1,2-diol (5.76 g, 20.0 mmol, 50% yield, including inpurity).
25% H2SO4 aq (15 mL) was added to stirred 1,1-bis(4-methoxyphenyl)propane-1,2-diol (5.76 g, 20.0 mmol, including inpurity), and the resulting solution was stirred at reflux for 3.5 h, cooled, neutralized with Na2CO3 and extracted with Et2O [36]. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo, giving a residue that was subjected to silica gel column chromatography to give 1,1-bis(4-methoxyphenyl)propan-2-one (1.047 g, 3.87 mmol, 19% yield).
A mixture of 1,1-bis(4-methoxyphenyl)propan-2-one (1.047 g, 3.87 mmol), malononitrile (0.384 g, 5.82 mmol) and activated alumina (3.0 g) was stirred at 90 °C for 1.5 h [34]. The solids were removed by filtration. Concentration of the filtrate gave a residue that was subjected to HPLC to give 2-[1,1-bis(4-methoxyphenyl)propan-2-ylidene]malononitrile (1b, 0.728 g, 2.29 mmol, 59% yield). 1H-NMR (300 MHz, CDCl3) δ 2.21 (s, 3H), 3.82 (s, 6H), 5.59 (s, 1H), 6.89 (d, J = 8.6 Hz, 4H), 7.05 (d, J = 8.6 Hz, 4H) ppm.

3.4. Preparation of 1c

A THF (12 mL) solution of 4-bromochlorobenzene (6.647 g, 34.7 mmol) was added dropwise to stirred Mg turnings (0.729 g, 30.0 mmol). A small amount of I2 was added to facilitate the reaction. A THF (5 mL) solution of ethyl l-lactate (1.247 mL, 10.9 mmol) was added dropwise to the solution, and the resulting solution was stirred at reflux, cooled, and extracted with Et2O and NH4Cl aq [36]. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo, giving a residue that was subjected to silica gel column chromatography to give 1,1-bis(4-chlorophenyl)propane-1,2-diol (4.023 g, including inpurity).
To stirred 1,1-bis(4-chlorophenyl)propane-1,2-diol (4.023 g, including inpurity) was added 25% H2SO4 aq (12 mL), and the resulting solution was stirred at reflux for 3.5 h, cooled, neutralized with Na2CO3 and extracted with Et2O [36]. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo, giving a residue that was subjected to silica gel column chromatography to give 1,1-bis(4-chlorophenyl)propan-2-one (0.934 g, 3.36 mmol, 31% yield (two steps)). 1H-NMR (300 MHz, CDCl3) δ 2.24 (s, 3H), 5.05 (s, 1H), 7.11-7.32 (m, 8 H) ppm.
A mixture of 1,1-bis(4-chlorophenyl)propan-2-one (0.934 g, 3.36 mmol), malononitrile (0.444 g, 6.72 mmol) and activated alumina (3.0 g) was stirred at 90 °C for 1.5 h [34]. The solids were removed by filtration. Concentration of the filtrate gave a residue that was subjected to HPLC to give 2-[1,1-bis(4-chlorophenyl)propan-2-ylidene]malononitrile (1c, 0.602 g, 1.84 mmol, 55% yield). 1H-NMR (300 MHz, CDCl3) δ 2.21 (s, 3H), 5.62 (s, 1H), 7.05 (d, J = 8.4 Hz, 4H), 7.37 (d, J = 8.4 Hz, 4H) ppm; 13C-NMR (75 MHz, CDCl3) δ 21.33, 55.87, 88.80, 111.37, 111.49, 129.47, 129.94, 134.47, 135.75, 179.56 ppm; MS (EI) m/z (relative intensity, %) = 114 (52), 139 (89), 165 (59), 291 (100), 326 (62, M+).

3.5. General Procedure for Photoreactions

CH3CN (8 mL) solutions of a 3,3-diaryl-1,1-dicyano-2-methylprop-2-ene (1a–c, 0.14 mmol), allyltrimethylsilane (2, 0.42 mmol), phenanthrene (0.07 mmol), and CH3COOH (1 mL) or a chiral carboxylic acid (0.14 mmol) in Pyrex vessels were degassed by argon bubbling for 5 min and then the vessels were sealed. The solutions were irradiated by using a 300 W high pressure mercury lamp (Eikosha, EHB-W-300 or PIH-300) for 2–24 h at room temperature, maintained by using circulated cooling water. The photolysates were extracted with Et2O. The organic layer was washed with H2O, dried over Na2SO4, filtered, and concentrated in vacuo, giving a residue that was subjected to HPLC to give 3a–c and 4a–c.
2-Allyl-2-(1,1-diphenylpropan-2-yl)malononitrile (3a): 1H-NMR (300 MHz, CDCl3) δ 1.20 (d, J = 6.8 Hz, 3H), 2.42–2.59 (m, 2H), 2.91–3.02 (m, 1H), 4.16 (d, J = 9.3 Hz, 1H), 5.28 (d, J = 17.6 Hz, 1H), 5.37 (d, J = 9.6 Hz, 1H), 5.76-5.92 (m, 1H), 7.21–7.40 (m, 10H) ppm; MS (EI) m/z = 41, 65, 77, 91, 102, 115, 128, 151, 165, 167, 193, 300 (M+).
2-Allyl-2-[1,1-bis(4-methoxyphenyl)propan-2-yl]malononitrile (3b): 1H-NMR (300 MHz, CDCl3) δ 1.18 (d, J = 6.7 Hz, 3H), 2.44-2.60 (m, 2H), 2.80–2.91 (m, 1H), 3.76 (s, 3H), 3.78 (s, 3H), 4.08 (d, J = 9.2 Hz, 1H), 5.29 (d, J = 16.9 Hz, 1H), 5.36 (d, J = 10.0 Hz, 1H), 5.77–5.91 (m, 1H), 6.81–6.87 (m, 4H), 7.19–7.26 (m, 4H) ppm.
2-Allyl-2-[1,1-bis(4-chlorophenyl)propan-2-yl]malononitrile (3c): 1H-NMR (300 MHz, CDCl3) δ 1.18 (d, J = 6.7 Hz, 3H), 2.52 (dd, J = 13.8, 7.5 Hz, 1H), 2.62 (dd, J = 13.9, 6.7 Hz, 1H), 2.88 (dq, J = 8.9, 6.7 Hz, 1H), 4.15 (d, J = 9.1 Hz, 1H), 5.31 (d, J = 16.9 Hz, 1H), 5.40 (d, J = 10.2 Hz, 1H), 5.76–5.91 (m, 1H), 7.19–7.36 (m, 8H) ppm; 13C-NMR (75 MHz, CDCl3) δ 15.47, 41.40, 42.40, 42.79, 54.31, 114.18, 123.29, 128.44, 129.24, 129.27, 129.67, 129.93, 133.41, 133.76, 139.09, 139.24 ppm.
2-(1,1-Diphenylpropan-2-yl)malononitrile (4a): 1H-NMR (300 MHz, CDCl3) δ 1.30 (d, J = 6.6 Hz, 3H), 2.95–3.06 (m, 1H), 3.64 (d, J = 3.3 Hz, 1H), 3.80 (d, J = 11.7 Hz, 1H), 7.21–7.36 (m, 10H) ppm; MS (EI) m/z = 51, 63, 77, 83, 102, 128, 151, 165, 167, 193, 300 (M+).
2-[1,1-Bis(4-methoxyphenyl)propan-2-yl]malononitrile (4b): 1H-NMR (300 MHz, CDCl3) δ 1.28 (d, J = 6.6 Hz, 3H), 2.82–2.95 (m, 1H), 3.66 (d, J = 3.3 Hz, 1H), 3.69 (d, J = 11.7 Hz, 1H), 3.77 (s, 6H), 6.83–6.89 (m, 4H), 7.18–7.24 (m, 4H) ppm.
2-[1,1-Bis(4-chlorophenyl)propan-2-yl]malononitrile (4c): 1H-NMR (300 MHz, CDCl3) δ 1.29 (d, J = 6.6 Hz, 3H), 2.87-2.98 (m, 1H), 3.60 (d, J = 3.4 Hz, 1H), 3.78 (d, J = 11.8 Hz, 1H), 7.18–7.37 (m, 8H) ppm.

3.6. Resolution of Enantiomers

Resolutions of enantiomers of 3a and 4a were performed on a recycling preparative HPLC equipped with Jasco PU-980 pump, Jasco UV-970 and CD-2095 detectors (Jasco Corporation, Tokyo, Japan), Daicel CHIRALCEL OJ (3a) or OJ-H (4a) columns (Daicel Corporation, Osaka, Japan). Eluents were hexane:2-propanol = 7:3 (3a) or 9:1 (4a). [3a] = 0.068 M, [4a] = 0.078 M. Both 3a and 4a were detected by UV and CD detectors at 270 nm.
Resolutions of enantiomers of 3c and 4c were performed by using a SHIMADZU GCMS-QP5050 (Shimadzu Corporation, Kyoto, Japan) operating in the electron impact mode (70 eV) equipped with SUPELCO GAMMA DEXTM 225 column (Sigma-Aldrich Co., LLC, St. Louis, MO, USA). Detector temp = 215 °C, injection temp = 220 °C, inlet pressure = 93.7 kPa, flow rate = 1.0mL/min, linear velocity = 28.1 cm/s, split ratio = 50, carrier gas = N2.

4. Conclusions

In summary, we found that photoreactions of prochiral 3,3-diaryl-1,1-dicyano-2-methylprop-1-enes 1a–c with allyltrimethylsilane, carried in the presence of enantiomerically pure chiral carboxylic acids, generates photoallylation and photoreduction products with low but finite levels of enantioselectivity. The percent enantiomeric excesses in the products of the process was highest (4.8 %ee) when (S)-mandelic acid was used. Enantioselectivities in these reactions are a consequence of sterically governed asymmetric proton transfer in intermediate complexes formed by π-π and OH-π interactions between radical anions of the prochiral alkenes and the chiral carboxylic acids.

Supplementary Materials

The following are available online: 1H-NMR spectra of 1b, 1c, 3a, 3b, 3c, 4a, and 4c, 13C-NMR spectra of 1c and 3c.

Author Contributions

Project administration, H.M.; investigation, M.I. and D.O.; supervision, K.M.

Funding

This study was supported by Grant-in-Aids for Scientific Research on Priority Areas ‘‘Reaction Control of Dynamic Complexes (420)’’ (16033252), Scientific Research (B) (15350026), Scientific Research (C) (17K05777), and Young Scientists (B) (16750039), and the Cooperation for Innovative Technology and Advanced Research in Evolutional Area (CITY AREA) program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.

Acknowledgments

We thank Masahito Oka at Osaka Prefecture University for permission to use circular dichromism (CD) spectrometer.

Conflicts of Interest

The authors declare no conflict of interest.

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Sample Availability: Samples of the compounds are not available from the authors.
Molecules 24 02677 sch001 550
Scheme 1. Our previous works.
Scheme 1. Our previous works.
Molecules 24 02677 sch001
Molecules 24 02677 sch002 550
Scheme 2. Photoallylation and photoreduction of 1a–c by using allyltrimethylsilane (2).
Scheme 2. Photoallylation and photoreduction of 1a–c by using allyltrimethylsilane (2).
Molecules 24 02677 sch002
Molecules 24 02677 g001 550
Figure 1. 300 MHz 1H-NMR spectra of 3a and 4a in CDCl3.
Figure 1. 300 MHz 1H-NMR spectra of 3a and 4a in CDCl3.
Molecules 24 02677 g001
Molecules 24 02677 sch003 550
Scheme 3. Synthesis of authentic samples of 3a and 4a.
Scheme 3. Synthesis of authentic samples of 3a and 4a.
Molecules 24 02677 sch003
Molecules 24 02677 g002 550
Figure 2. Resolution of the enantiomers of (a,b) 3a by using chiral HPLC with UV and CD detectors both at 270 nm, (c,d) 4a by chiral HPLC with UV and CD detectors both at 270 nm, and (e) 3c and 4c by chiral GC with a MS detector.
Figure 2. Resolution of the enantiomers of (a,b) 3a by using chiral HPLC with UV and CD detectors both at 270 nm, (c,d) 4a by chiral HPLC with UV and CD detectors both at 270 nm, and (e) 3c and 4c by chiral GC with a MS detector.
Molecules 24 02677 g002
Molecules 24 02677 g003 550
Figure 3. UV-vis absorption spectra of ethanol solutions of substances from (a) peak A, (b) peak B, (c) peak C, and (d) peak D.
Figure 3. UV-vis absorption spectra of ethanol solutions of substances from (a) peak A, (b) peak B, (c) peak C, and (d) peak D.
Molecules 24 02677 g003
Molecules 24 02677 g004 550
Figure 4. Circular dichromism (CD) spectra of ethanol solutions of substances from (a) peaks A and B, (b) peaks C and D.
Figure 4. Circular dichromism (CD) spectra of ethanol solutions of substances from (a) peaks A and B, (b) peaks C and D.
Molecules 24 02677 g004
Molecules 24 02677 sch004 550
Scheme 4. Mechanism for photoallylation and photoreduction of 1.
Scheme 4. Mechanism for photoallylation and photoreduction of 1.
Molecules 24 02677 sch004
Molecules 24 02677 sch005 550
Scheme 5. Plausible explanation for the enantioselectivity.
Scheme 5. Plausible explanation for the enantioselectivity.
Molecules 24 02677 sch005
Table
Table 1. Photoallylation and photoreduction of 1a–c by using allyltrimethylsilane (2) a.
Table 1. Photoallylation and photoreduction of 1a–c by using allyltrimethylsilane (2) a.
EntrySubstrateAdditiveIrradiation Time/hYields/%
34
11a (Ar = Ph)none40 b53 b
21a (Ar = Ph)acetic acid c434 b31 b
31b (Ar = p-MeOC6H4)none240 d44 d
41b (Ar = p-MeOC6H4)acetic acid c2420 d46 d
51c (p-ClC6H4)none20 d36 d
61c (p-ClC6H4)acetic acid c233 d47 d
a Conditions: 1a–c (0.14 mmol), 2 (0.42 mmol), phenanthrene (0.07 mmol), CH3CN (8 mL), 300 W high-pressure mercury lamp, Pyrex, r.t. b Determined by using GC. c 1 mL. d Determined by using 1H-NMR.
Table
Table 2. Enantioselective photoallylations and photoreductions of 1a–c a.
Table 2. Enantioselective photoallylations and photoreductions of 1a–c a.
EntrySubstrateAdditiveIrradiation Time/hYields/% (ee/%)
34
11a (Ar = Ph)none40 b53 b
21a (Ar = Ph) Molecules 24 02677 i001acetic acidc434 b31 b
31a (Ar = Ph) Molecules 24 02677 i002(R)-mandelic acid434 b (+1.5 d,e)27 b (+4.1 d,e)
41a (Ar = Ph) Molecules 24 02677 i003(S)-mandelic acid422 b (−3.4 d,f)26 b (−4.8 d,f)
51a (Ar = Ph) Molecules 24 02677 i004l-lactic acid428b (+0.6 d,e)39 b (+3.2 d,e)
61a (Ar = Ph) Molecules 24 02677 i005dibenzoyl l-tartaric acid431 b (−2.0 d,f)16 b (−3.6 d,f)
71b (Ar = p-MeOC6H4)none240 g44 g
81b (Ar = p-MeOC6H4) Molecules 24 02677 i001acetic acid c2420 g46 g
91b (Ar = p-MeOC6H4) Molecules 24 02677 i002(R)-mandelic acid2454 g (nd h)28g (nd h)
101b (Ar = p-MeOC6H4) Molecules 24 02677 i003(S)-mandelic acid2413 g (nd h)48g (nd h)
111c (p-ClC6H4)none20 g36 g
121c (p-ClC6H4) Molecules 24 02677 i001acetic acid c233 g47 g
131c (p-ClC6H4) Molecules 24 02677 i002(R)-mandelic acid227 g (+2.0 i,j)55 g (+2.0 i,j)
141c (p-ClC6H4) Molecules 24 02677 i003(S)-mandelic acid224 g (−2.6 i,k)61 g (−0.6 i,k)
151c (p-ClC6H4) Molecules 24 02677 i006(S)-2-(6-methoxy-2-naphthyl)propionic acid20 g68g (−3.5 i,k)
a Conditions: 1a–c (0.14 mmol), 2 (0.42 mmol), phenanthrene (0.07 mmol), CH3CN (8 mL), additive (0.14 mmol), 300 W high-pressure mercury lamp, Pyrex, r.t. b Determined by using GC. c 1 mL. d Determined by using chiral HPLC. e Major isomer corresponds to the second peak in the HPLC chart. f Major isomer corresponds to the first peak in the HPLC chart. g Determined by using 1H-NMR. h Ee could not be determined. i Determined by using chiral GC. j Major isomer corresponds to the second peak in the GC chart. k Major isomer corresponds to the first peak in the GC chart.

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Maeda, H.; Iida, M.; Ogawa, D.; Mizuno, K. Enantioselective Protonation of Radical Anion Intermediates in Photoallylation and Photoreduction Reactions of 3,3-Diaryl-1,1-dicyano-2-methylprop-1-ene with Allyltrimethylsilane. Molecules 2019, 24, 2677. https://doi.org/10.3390/molecules24142677

AMA Style

Maeda H, Iida M, Ogawa D, Mizuno K. Enantioselective Protonation of Radical Anion Intermediates in Photoallylation and Photoreduction Reactions of 3,3-Diaryl-1,1-dicyano-2-methylprop-1-ene with Allyltrimethylsilane. Molecules. 2019; 24(14):2677. https://doi.org/10.3390/molecules24142677

Chicago/Turabian Style

Maeda, Hajime, Masayuki Iida, Daisuke Ogawa, and Kazuhiko Mizuno. 2019. "Enantioselective Protonation of Radical Anion Intermediates in Photoallylation and Photoreduction Reactions of 3,3-Diaryl-1,1-dicyano-2-methylprop-1-ene with Allyltrimethylsilane" Molecules 24, no. 14: 2677. https://doi.org/10.3390/molecules24142677

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