Asymmetric Photoinduced Giese Radical Addition Enabled by a Single Chiral-at-Metal Rhodium Complex

Liang Chen Liangjian Hu Yu Du Weiping Su Qiang Kang

Citation:  Chen Liang, Hu Liangjian, Du Yu, Su Weiping, Kang Qiang. Asymmetric Photoinduced Giese Radical Addition Enabled by a Single Chiral-at-Metal Rhodium Complex[J]. Chinese Journal of Organic Chemistry, 2020, 40(11): 3944-3952. doi: 10.6023/cjoc202004041 shu

中心手性金属铑配合物催化的不对称光诱导Giese自由基加成反应

    通讯作者: 苏伟平, wpsu@fjirsm.ac.cn
    康强, kangq@fjirsm.ac.cn
  • 基金项目:

    国家自然科学基金面上(No.21871261)资助项目

    国家自然科学基金面上 21871261

摘要: 报道了一种可见光驱动的双功能中心手性金属铑配合物催化的不对称自由基加成反应,由对胺基苯乙酸生成的对胺基苄基自由基对αβ-不饱和酰基咪唑进行立体选择性的1,4-加成,以中高收率和高对映选择性合成了一系列加成产物.该反应具有对映选择性高、反应条件温和、操作简单等特点.根据对双功能中心手性金属配合物催化的研究和文献报道,提出了一个合理的反应机理.

English

  • Visible-light photoredox catalysis which produces a various range of radical intermediates in a mild and convenient process has been identified as a vigorous tool in organic synthesis.[1] However, due to the involvement of open-shell radical species and quick subsequent reactions featuring low energetic barriers, the development of catalytic asymmetric photoredox reactions remains a challenging task in controlling the stereoselectivity of highly reactive intermediates.[2-3] Currently the major solutions for asymmetric catalysis promoted by visible light are typi- cally relying on two strategies: (1) dual catalysis systems[4] involving two catalysts; (2) asymmetric/photoredox bifun- ctional photocatalyst.[5] The dual catalysis systems usually contain one photocatalyst for the radical generation and an additional chiral co-catalyst for controlling the enantio- selectivity. On the other hand, single bifunctional photo- catalyst integrates visible light harvest for activation of substrates and stereocontrol during the chemical bond formation together. In a word, both strategies show the potential to overcome the inherent difficulties of visible light driven asymmetric catalysis. For instance, the Giese- type reaction[6] that is the addition of nucleophilic alkyl radicals to electron-poor alkenes has long been considered as one of the most established bimolecular radical reactions. As a paradigm, Sibi, Porter and other researchers[7] have revealed that chiral Lewis acid catalysts are capable of dominating the stereoselective conjugate addition of radicals. Inspired by these pioneering achievements, Yoon and co-workers[8] developed the first highly enantioselective intermolecular conjugate addition of α-aminoalkyl radicals generated from α-silylalkyl anilines by merging visible-light photoredox and Lewis acid catalysis. Recently, Gong group[5g] utilized a chiral nickel DBFOX complex as a single catalyst for a catalytic asymmetric conjugate radical addition.

    Oxidative decarboxylation of carboxylic acids is a substantial process in nature. Since from the seminal work by MacMillan, [9] the decarboxylation of α-amino acids via visible-light photoredox catalysis has become a powerful method to generate α-amino alkyl radicals.[10] As the 'phenylogue' of the α-amino acids, synthetic utilization of the aminoarylacetic acids with visible light has been quite limited.[11] In 2003, Miyake and co-workers[11d] succeeded in utilizing para-aminophenylacetic acids as para-amino- benzyl radical precursors in addition reactions with electron-deficient alkenes, but no enantioselectivity was observed (Scheme 1, a). As a continuation of our interest in the development of chiral-at-metal complexes[12-13] as bifunctional photocatalysts in catalytic asymmetric reac- tions, herein, we report our recent findings on a catalytic asymmetric conjugate addition of para-aminobenzyl radicals generated from para-aminophenylacetic acids to α, β-unsaturated carbonyl compounds catalyzed by a chiral-at-metal rhodium complex under visible light irradiation (Scheme 1, b).

    Scheme 1

    Scheme 1.  Photoredox catalyzed addition of para-aminobenzyl radicals to electron-deficient alkenes

    We initiated our studies with α, β-unsaturated 2-acyl imidazole 1a and 4-(N-methyl-N-phenylamino)-phenylacetic acid 2a as model substrates in the presence of 2 mol% of chiral-at-metal Rh(Ⅲ) complex Λ-Rh1 developed by Meggers' group under the irradiation with blue LEDs. To our delight, the reaction proceeded smoothly in degassed 1, 2-dichloroethane (DCE) to afford the desired product 3a in 77% yield with 82% ee (Table 1, Entry 1). Control experiments devoid of catalyst (no reaction) or performed in the dark (no reaction) reveal that it is the combination of chiral rhodium complex Λ-Rh1 and visible light that is required for an efficient reaction (Entries 2, 3). Encouraged by these promising results, other chiral-at-matal complexes were examined. Λ-Ir could lead to the formation of the target molecule 3a with an increased enantioselectivity (89% ee) but with a diminished yield (53%, Entry 4). Gratifyingly, Λ-Rh2 developed by our group gave the desired product in 70% yield with 88% ee (Entry 5). Further screening of solvents revealed that methanol was the superior one (Entries 6~10), leading to the formation of product 3a in 79% yield with 96% ee (Entry 6). These reactions could be finished in 12 h.

    Table 1

    Table 1.  Optimization of reaction conditions a
    下载: 导出CSV
    Entry Λ-M Solvent Yieldb/% eec/%
    1 Λ-Rh1 DCE 77 82
    2 Λ-Rh1 DCE
    3 None DCE
    4 Λ-Ir DCE 53 89
    5 Λ-Rh2 DCE 70 88
    6 Λ-Rh2 MeOH 79 96
    7 Λ-Rh2 Toluene 46 93
    8 Λ-Rh2 DMSO 31 60
    9 Λ-Rh2 Acetone 75 91
    10 Λ-Rh2 CH3CN 65 87
    a Unless otherwise noted, reactions were carried out by using 1a (0.1 mmol), 2a (0.15 mmol) and Λ-M (0.002 mmol, 2 mol%) in degassed solvent (0.3 mL) at room temperature under irradiation with 20 W blue LEDs. b Isolated yields based on 1a. c Determined by chiral HPLC analysis.

    With the optimal conditions established for 3a (Table 1, Entry 6), the scope of this photoinduced conjugate addition reaction was then examined. The reaction between para- aminobenzyl radical precursor 2a and α, β-unsaturated 2-acyl imidazoles 1 bearing a β-aryl substituent was first studied using the optimal conditions developed above. The results are summarized in Table 2. The introduction of electron-donating and electron-withdrawing groups on the phenyl ring had little influence on enantioselectivities. The desired products 3b~3h were obtained in moderate to high yields (58%~95%) with high enantioselectivities (91%~96% ee). Naphthyl-based substrates 1i, 1j and heteroaromatic (eg. thienyl) 1k were also well tolerated, affording 3i~3k in moderate yields (54%~72%) with high enantioselectivities (90%~95% ee). α, β-Unsaturated 2- acyl imidazole with a β-alkyl substituent (eg. isopropyl) also worked well under the optimal reaction conditions, although the conversion was incomplete even after 48 h, affording product 3l in moderate yield and high enantioselectivity (50% yield, 91% ee). The relative configuration of compound 3h was confirmed by X-ray crystallographic studies.[14]

    Table 2

    Table 2.  Substrate scope of α, β-unsaturated 2-acyl imidazolesa
    下载: 导出CSV
    a Unless otherwise noted, reactions were carried out by using 1 (0.1 mmol), 2a (0.15 mmol) and Λ-Rh2 (2 mol%) in degassed MeOH (0.3 mL) at room temperature under irradiation with 20 W blue LEDs. All isolated yields were based on substrate 1, ee values were determined by chiral HPLC analysis.

    Further examination of the substrate scope of arylacetic acids 2 was also conducted using the optimal conditions with 1a (Table 3). Phenylacetic acids bearing a tertiary amino group such as N-dimethylamino, N-methyl-N- benzylamino, N-dibenzylamino moieties at the para- position of the aryl substituent were applicable, giving the corresponding products 4a~4c in moderate yields (up to 83%) with good enantioselectivities (up to 91% ee). The phenylacetic acid bearing a secondary amino group (eg., N-benzylamino) at the para-position also reacted smoothly to give 4d in 70% yield with 95% ee. para-Primary amino phenylacetic acid also worked for this reaction, although a low yield and enantioselectivity was obtained (4e, 38% yield, 58% ee). In addition, consistent with the report of Miyake et al., [11d] 4-methoxyl-substituted arylacetic acid and phenylacetic acids with an amino group at the meta- or ortho-position of the aryl substituent (2g~2i) could not give any products under the optimal reaction conditions, probably because the radical character of their one-electron oxidized intermediate is too small to induce decarboxylation, or an intramolecular hydrogen bonding between the amino group and carboxylic acid inhibits the electron transfer oxidation.

    Table 3

    Table 3.  Substrate scope of arylacetic acidsa
    下载: 导出CSV
    Entry Ar (2) 4 Yieldb/% eec/%
    1 4-Me2NC6H4 (2b) 4a 36 90
    2 4-BnMeNC6H4 (2c) 4b 83 91
    3 4-Bn2NC6H4 (2d) 4c 60 80
    4 4-BnHNC6H4 (2e) 4d 70 95
    5d 4-H2NC6H4 (2f) 4e 38 58
    6 4-MeOC6H4 (2g)
    7 3-PhMeNC6H4 (2h)
    8 2-PhMeNC6H4 (2i)
    a Unless otherwise noted, reactions were carried out by using 1a (0.1 mmol), 2 (0.15 mmol) and Λ-Rh2 (2 mol%) in degassed MeOH (0.3 mL) at room temperature under irradiation with 20 W blue LEDs. b Isolated yields based on 1a. c Determined by chiral HPLC analysis. d DMSO was used in place of MeOH.

    To illustrate the potential application of current protocol, a large-scale reaction of α, β-unsaturated 2-acyl imidazole 1h (0.52 g, 2.0 mmol) with arylacetic acid 2a (0.72 g, 3.0 mmol) was conducted in the presence of 2 mol% of Λ-Rh2 (Scheme 2, a). Gratifyingly, the reaction proceeded smoo- thly to afford 3h in 54% yield (0.49 g) with 93% ee. Moreover, the imidazole moiety of products could be easily transferred to other functional groups.[15] For example, the removal of the imidazole moiety of 3h worked smoothly to afford ester 5 in good yield without any loss in enantiomeric excess (Scheme 2, b).

    Scheme 2

    Scheme 2.  Large-scale experiment and synthetic transformation of product 3h

    Based on control experiments and literature precedents on dual functional chiral-at-metal catalysis, [5g, 13, 16] a plausible reaction pathway is proposed in Scheme 3. Substrate 1a first coordinates with the rhodium complex Λ-Rh2 in a bidentate fashion to generate a N, O-coordinated intermediate , which could be photoexcited (I*) and then oxidizes aminoarylacetic acid 2a to generate a benzyl radical and the reduced I•– via a single electron transfer (SET) process. The benzyl radical then trapped by the intermediate in a highly stereoselective approach to form a radical intermediate . This intermediate undergoes another SET process with strong reductant I•– to regenerate and furnish an anion IV, followed by protonation to afford a neutral complex V. The substitution of complex V with 1a eventually releases the desired product 3a, and a new catalytic cycle is initiated.

    Scheme 3

    Scheme 3.  Proposed mechanism and transition-state model

    In conclusion, a highly efficient and practical catalytic enantioselective Giese radical addition of para-amino- benzyl radicals generated from para-aminophenylacetic acids to electron-deficient alkenes catalyzed by a bifunctional chiral-at-metal rhodium complex has been developed, affording the desired adducts in moderate to high yields with excellent enantioselectivities. Here the rhodium complex works not only as a chiral Lewis acid to improve the electrophilicity of substrates and control the stereoselectivity during the chemical bond formation, but also a photocatalyst to form photosensitive substrate-coordinated complex. This reaction features high enantioselectivity, mild reaction conditions and an operationally simple procedure. Further research on the development of new types of bifunctional chiral-at-metal complexes and their application in asymmetric reactions are ongoing in our laboratory.

    All reactions were performed in Schlenk tubes under an atmosphere of argon using oven-dried glassware. Commercially obtained reagents were used without further purification, unless otherwise noted. Dry DCE, toluene, CH3CN and tetrahydrofuran (THF) were obtained from solvent distillation machine (Vigor VSPS-5). Dimethyl sulfoxide (DMSO) was distilled from CaH2. Methanol and acetone (IPA) were used without further purification. Reactions were checked by thin-layer chromatography (TLC) analysis and plates were visualized with short-wave UV light (254 nm). The 1H NMR and 13C NMR and 19F NMR spectra were obtained in CDCl3 using a Bruker-BioSpin AVANCE Ⅲ HD NMR spectrometer at 400, 100 and 376.4 MHz, respectively. HPLC analyses of the compounds were done using chiralcel IA-IF columns and chiralcel AD-H, AS-H, OJ-H and OD-H columns using hexane and isopropanol as eluent. The infrared spectra were recorded on a Bruker VERTEX 70 IR spectrometer as KBr pellets. High-resolution mass spectra were recorded on a Bruker Impact II UHR TOF LC/MS mass spectrometry. Chiral-at-metal complexes Λ-Rh1, [17] Λ-Rh2[13] and Λ-Ir[18] were prepared according to reported procedure. α, β-Unsaturated 2-acyl imidazoles 1[13] and arylacetic acid (2a~2e, 2h and 2i)[11d-11e] were synthesized according to reported procedures.

    To an oven-dried 25 mL Schlenk tube equipped with a stir bar, Λ-Rh2 (2.5 mg, 2 mol%) was added along with α, β-unsaturated 2-acyl imidazoles 1 (0.1 mmol, 1.0 equiv.), 4-amino phenylacetic acid 2 (1.5 equiv.) and MeOH (0.3 mL). After degassing via three freeze-pump-thaw cycles, the Schlenk tube was sealed and positioned at a distance of 5~10 cm from 20 W blue LEDs. The reaction was stirred at room temperature for 12~48 h under argon, and then the mixture directly purified by silica gel column chromatography (EtOAc/petroleum ether, V:V=1:10 to 1:5) to afford the title products 3 or 4.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)- amino)phenyl)-3-phenylbutan-1-one (3a): Pale yellow oil, 35 mg, 79% yield, 96% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=90:10), flow rate 1 mL/min, 40 ℃, tR(minor)=8.42 min, tR(major)=9.18 min]. [α]D25+32.919 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.39~7.13 (m, 9H), 7.07 (d, J=8.3 Hz, 1H), 7.01~6.87 (m, 5H), 5.49~5.35 (m, 1H), 3.85~3.63 (m, 2H), 3.55~3.41 (m, 1H), 3.30 (s, 3H), 3.03~2.88 (m, 2H), 1.38 (d, J=6.7 Hz, 3H), 1.33 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 191.8, 149.2, 147.0, 144.4, 142.6, 133.6, 130.2, 129.4, 129.1, 128.3, 127.8, 126.2, 121.3, 120.9, 120.4, 119.2, 49.0, 44.8, 43.3, 43.0, 40.2, 23.6, 23.5; IR (KBr) ν: 2926, 2361, 2343, 1678, 1595, 1512, 1497, 1457, 1397, 1346, 1258, 982, 760, 704 cm-1; HRMS (ESI) calcd for C29H31N3NaO [M+Na]+ 460.2365, found 460.2359.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)- amino)phenyl)-3-(p-tolyl)butan-1-one (3b): Pale yellow oil, 31 mg, 68% yield, 95% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=90:10), flow rate 1.0 mL/min, 40 ℃, tR(minor)=7.58 min, tR(major)=8.49 min]. [α]D25+46.781 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.27~7.19 (m, 2H), 7.19~7.09 (m, 4H), 7.19~7.09 (m, 4H), 7.06~6.99 (m, 4H), 5.42~5.30 (m, 1H), 3.72~3.54 (m, 2H), 3.40 (dd, J=15.8, 4.7 Hz, 1H), 3.26 (s, 3H), 2.95~2.81 (m, 2H), 2.27 (s, 3H), 1.33 (d, J=6.6 Hz, 3H), 1.30 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 191.9, 149.3, 147.0, 142.5, 141.5, 135.7, 133.8, 130.2, 129.2, 129.1, 127.7, 121.5, 121.0, 120.4, 119.1, 49.2, 44.9, 43.1, 42.8, 40.3, 23.7, 23.5, 21.2; IR (KBr) ν: 2922, 2855, 2361, 2345, 1676, 1597, 1512, 1498, 1395, 1340, 1255, 981, 916, 822, 695 cm-1; HRMS (ESI) calcd for C30H33N3NaO [M+Na]+ 474.2521, found 474.2515.

    1-(1-Isopropyl-1H-imidazol-2-yl)-3-(4-methoxyphenyl)-4-(4-(methyl(phenyl)amino)phenyl)butan-1-one (3c): Pale yellow oil, 27 mg, 58% yield, 92% ee [HPLC: chiralpak IC column, 254 nm, hexane/isopropanol (V:V=75:25), flow rate 1.0 mL/min, 40 ℃, tR(minor)=6.02 min, tR(major)=6.77 min). [α]D25+37.251 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.25~7.19 (m, 1H), 7.20~7.11 (m, 4H), 7.01 (d, J=8.4 Hz, 1H), 6.95~6.84 (m, 3H), 6.77 (d, J=8.7 Hz, 1H), 5.43~5.31 (m, 1H), 3.75 (s, 1H), 3.71~3.54 (m, 2H), 3.39 (dd, J=15.9, 5.0 Hz, 1H), 3.26 (s, 3H), 2.87 (d, J=7.2 Hz, 1H), 1.34 (d, J=6.6 Hz, 1H), 1.31 (d, J=6.7 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ: 191.9, 158.0, 149.3, 147.0, 142.5, 136.5, 133.8, 130.2, 129.2, 128.8, 121.5, 121.0, 120.4, 119.2, 113.7, 55.3, 49.2, 45.1, 43.2, 42.5, 40.4, 23.7, 23.6; IR (KBr) ν: 2925, 2851, 2362, 2342, 1678, 1598, 1512, 1497, 1395, 1343, 1250, 1039, 986, 830, 697 cm-1; HRMS (ESI) calcd for C30H33- N3NaO2 [M+Na]+ 490.2470, found 490.2464.

    3-(4-Fluorophenyl)-1-(1-isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)amino)phenyl)butan-1-one (3d): Pale yellow oil, 37.1 mg, 81% yield, 91% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=90:10), flow rate 1.0 mL/min, 40 ℃, tR(minor)=8.29 min, tR(major)=8.97 min]. [α]D25+32.119 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.21~7.03 (m, 6H), 6.95~6.73 (m, 9H), 5.36~5.24 (m, 1H), 3.65~3.49 (m, 2H), 3.38~3.27 (m, 1H), 3.18 (s, 3H), 2.86~2.71 (m, 2H), 1.27 (d, J=6.6 Hz, 3H), 1.23 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 191.7, 161.5 (d, J=244.6 Hz), 149.3, 147.2, 142.6, 140.0 (d, J=3.0 Hz), 133.3, 130.2, 129.5, 129.3 (d, J=7.7 Hz), 129.2, 121.3, 121.2, 120.6, 119.4, 115.1 (d, J=21.1 Hz), 49.2, 45.0, 43.1, 42.7, 40.3, 23.7, 23.6; 19F NMR (376 MHz, CDCl3) δ: -117.12; IR (KBr) ν: 2923, 2367, 2340, 1676, 1595, 1512, 1498, 1456, 1396, 1348, 1257, 1225, 984, 917, 834, 698 cm-1; HRMS (ESI) calcd for C29H30FN3NaO [M+Na]+ 478.2271, found 478.2263.

    3-(4-Chlorophenyl)-1-(1-isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)amino)phenyl)butan-1-one (3e): Pale yellow oil, 33 mg, 70% yield, 96% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=92:8), flow rate 0.6 mL/min, 40 ℃, tR(minor)=17.35 min, tR(major)=18.17 min]. [α]D25+67.172 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.28~7.10 (m, 8H), 6.98 (d, J=8.4 Hz, 2H), 6.96~6.85 (m, 5H), 5.43~5.30 (m, 1H), 3.76~3.56 (m, 2H), 3.40 (dd, J=16.0, 4.8 Hz, 1H), 3.26 (s, 3H), 2.98~2.78 (m, 2H), 1.35 (d, J=6.6 Hz, 3H), 1.31 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 191.4, 149.2, 147.2, 142.9, 142.4, 133.0, 131.9, 130.1, 129.4, 129.3, 129.2, 128.4, 121.2, 121.1, 120.7, 119.5, 49.2, 44.8, 42.8, 42.8, 40.3, 23.7, 23.5; IR (KBr) ν: 2934, 2363, 2336, 1676, 1596, 1518, 1503, 1346, 1259, 992, 828, 762, 697 cm-1; HRMS (ESI) calcd for C29H30ClN3NaO [M+Na]+ 494.1975, found 494.1969.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)- amino)phenyl)-3-(m-tolyl)butan-1-one (3f): Colorless oil, 43 mg, 95% yield, 93% ee [HPLC: chiralpak IA column, 254 nm, hexane/isopropanol (V:V=94:6), flow rate 0.4 mL/min, 40 ℃, tR(minor)=21.32 min, tR(major)=22.55 min]. [α]D25+30.054 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.18~7.09 (m, 3H), 7.07~7.00 (m, 2H), 6.98~6.791 (m, 4H), 6.89~6.76 (m, 6H), 5.36~5.23 (m, 1H), 3.64~3.47 (m, 2H), 3.33 (dd, J=15.6, 4.8 Hz, 1H), 3.18 (s, 1H), 2.87~2.73 (m, 2H), 2.20 (s, 3H), 1.26 (d, J=6.6 Hz, 3H), 1.22 (d, J=6.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 191.9, 149.3, 147.1, 144.5, 142.7, 137.8, 133.9, 130.2, 129.4, 129.2, 128.7, 128.2, 127.1, 124.8, 121.6, 121.0, 120.4, 119.1, 49.2, 44.7, 43.2, 43.1, 40.3, 23.7, 23.5, 21.6; IR (KBr) ν: 2926, 2362, 2345, 1676, 1599, 1512, 1498, 1456, 1396, 1342, 1257, 984, 702 cm-1; HRMS (ESI) calcd for C30H33N3NaO [M+Na]+ 474.2521, found 474.2514.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)- amino)phenyl)-3-(3-(trifluoromethyl)phenyl)butan-1-one (3g): Pale yellow oil, 40 mg, 79% yield, 95% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol=(V:V=75:25), flow rate 1.0 mL/min, 40 ℃, tR(minor)= 4.25 min, tR(major)=4.62 min]. [α]D25+43.915 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.46~7.30 (m, 4H), 7.27~7.12 (m, 4H), 7.00~6.84 (m, 7H), 5.44~5.30 (m, 1H), 3.75~3.63 (m, 2H), 3.54~3.41 (m, 1H), 3.25 (s, 3H), 2.95 (dd, J=13.6, 6.6 Hz, 1H), 2.86 (dd, J=13.5, 6.7 Hz, 1H), 1.35 (d, J=6.7 Hz, 3H), 1.30 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 191.2, 149.2, 147.3, 145.2, 142.4, 132.7, 131.2, 130.4 (q, J=31.3 Hz), 130.1, 129.5, 129.5, 128.7, 124.9 (q, J=3.6 Hz), 124.3 (q, J=273.7 Hz), 123.2 (q, J=3.7 Hz), 121.3, 121.3, 120.6, 119.4, 49.3, 44.5, 43.3, 42.8, 40.3, 23.6, 23.5; 19F NMR (376 MHz, CDCl3) δ: -62.47; IR (KBr) ν: 2929, 2361, 2344, 1676, 1595, 1512, 1498, 1455, 1408, 1397, 1330, 1256, 1176, 1127, 982, 919, 707 cm-1; HRMS (ESI) calcd for C30H30- F3N3NaO [M+Na]+ 528.2239, found 528.2230.

    3-(2-Fluorophenyl)-1-(1-isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)amino)phenyl)butan-1-one (3h): Pale yellow oil, 31 mg, 68% yield, 94% ee [HPLC: chiralpak IC column, 254 nm, hexane/isopropanol (V:V=70:30), flow rate 1.0 mL/min, 40 ℃, tR(minor)=4.67 min, tR(major)=5.04 min]. [α]D25+49.312 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.28~7.19 (m, 4H), 7.17~7.07 (m, 2H), 7.05 (d, J=8.5 Hz, 2H), 7.02~6.95 (m, 2H), 6.95~6.83 (m, 5H), 5.45~5.32 (m, 1H), 4.03~3.89 (m, 1H), 3.73 (dd, J=17.2, 8.8 Hz, 1H), 3.48 (dd, J=17.2, 5.9 Hz, 1H), 3.24 (s, 3H), 3.01~2.84 (m, 2H), 1.34 (d, J=6.7 Hz, 3H), 1.31 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 191.4, 161.0 (d, J=246.4 Hz), 149.3, 147.1, 142.4, 133.4, 131.2, 131.0, 130.1, 129.4, 129.1, 129.07, 127.8 (d, J=8.4 Hz), 124.0 (d, J=3.3 Hz), 121.4, 121.1, 120.4, 119.2, 115.5 (d, J=22.8 Hz), 49.2, 43.6, 41.4, 40.3, 36.7, 23.7, 23.6; 19F NMR (376 MHz, CDCl3) δ: -117.41; IR (KBr) ν: 2921, 2363, 1676, 1595, 1512, 1497, 1457, 1409, 1395, 1346, 1258, 982, 919, 759, 704 cm-1; HRMS (ESI) calcd for C29H30FN3NaO [M+Na]+ 478.2271, found 478.2265.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)- amino)phenyl)-3-(naphthalen-2-yl)butan-1-one (3i): Colorless oil, 34 mg, 72% yield, 90% ee [HPLC: chiralpak OD-H column, 254 nm, hexane/isopropanol (V:V=95:5), flow rate 0.8 mL/min, 40 ℃, tR(minor)=13.79 min, tR(major)=18.65 min]. [α]D25+62.240 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 8.23 (d, J=8.4 Hz, 1H), 7.81 (d, J=7.9 Hz, 1H), 7.67 (d, J=8.1 Hz, 1H), 7.56~7.36 (m, 4H), 7.24~7.12 (m, 4H), 7.06 (d, J=8.1 Hz, 2H), 6.91~6.78 (m, 5H), 5.32~5.19 (m, 1H), 4.72~4.51 (m, 1H), 3.83 (dd, J=16.9, 8.0 Hz, 1H), 3.65 (dd, J=16.9, 6.5 Hz, 1H), 3.22 (s, 3H), 3.11 (dd, J=13.9, 6.6 Hz, 1H), 2.98 (dd, J=13.6, 8.2 Hz, 1H), 1.24 (t, J=6.0 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ: 191.8, 149.3, 147.1, 142.7, 142.0, 133.6, 133.6, 132.4, 130.2, 129.5, 129.2, 128.0, 127.8, 127.7, 126.5, 126.4, 125.8, 125.3, 121.5, 121.1, 120.4, 119.2, 49.2, 44.9, 43.5, 43.0, 40.3, 23.7, 23.5; IR (KBr) ν: 2924, 2363, 1675, 1597, 1510, 1497, 1457, 1396, 1340, 1255, 984, 918, 822, 750, 698 cm-1; HRMS (ESI) calcd for C33H33N3NaO [M+Na]+ 510.2521, found 510.2512.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)- amino)phenyl)-3-(naphthalen-1-yl)butan-1-one (3j): Colorless oil, 25 mg, 54% yield, 95% ee [HPLC: chiralpak OD-H column, 254 nm, hexane/isopropanol (V:V=95:5), flow rate 0.8 mL/min, 40 ℃, tR(minor)=14.09 min, tR(major)=15.41 min]. [α]D25+30.454 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.83~7.69 (m, 3H), 7.64 (s, 1H), 7.47~7.34 (m, 3H), 7.29~7.11 (m, 4H), 7.03 (d, J=7.4 Hz, 2H), 6.96~6.81 (m, 5H), 5.40~5.29 (m, 1H), 3.89~3.74 (m, 2H), 3.57~3.43 (m, 1H), 3.24 (d, J=2.1 Hz, 3H), 3.00 (d, J=6.5 Hz, 2H), 1.30 (d, J=6.6 Hz, 3H), 1.24 (d, J=6.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 191.9, 149.3, 147.1, 142.7, 140.7, 134.0, 133.8, 131.9, 130.2, 129.5, 129.1, 128.9, 126.8, 125.9, 125.6, 125.4, 123.6, 123.4, 121.7, 121.0, 120.3, 119.0, 49.1, 44.7, 42.6, 40.3, 23.6, 23.5; IR (KBr) ν: 2928, 2365, 1676, 1595, 1510, 1497, 1457, 1395, 1342, 1258, 979, 919, 779, 696 cm-1; HRMS (ESI) calcd for C33H33N3NaO [M+Na]+ 510.2521, found 510.2516.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-(4-(methyl(phenyl)- amino)phenyl)-3-(thiophen-3-yl)butan-1-one (3k): Yellow oil, 32.2 mg, 72% yield, 93% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=90:10), flow rate 1.0 mL/min, 40 ℃, tR(minor)=9.68 min, tR(major)=10.67 min]. [α]D25+23.790 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.28~7.14 (m, 4H), 7.10~7.03 (m, 3H), 6.99~6.87 (m, 3H), 6.86~6.76 (m, 2H), 5.49~5.36 (m, 1H), 4.06~3.90 (m, 1H), 3.68 (dd, J=17.0, 8.7 Hz, 1H), 3.45 (dd, J=16.9, 5.7 Hz, 1H), 3.27 (s, 3H), 3.00 (dd, J=13.6, 7.1 Hz, 1H), 2.94 (dd, J=13.6, 7.9 Hz, 1H), 1.36 (t, J=6.5 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ: 191.2, 149.2, 148.3, 147.3, 142.3, 133.0, 130.2, 129.3, 129.2, 126.6, 124.1, 123.1, 121.2, 121.1, 120.7, 119.5, 49.3, 46.0, 43.7, 40.4, 38.5, 23.7, 23.6; IR (KBr) ν: 2925, 2369, 2333, 1676, 1597, 1518, 1503, 1346, 1259, 979, 917, 695 cm-1; HRMS (ESI) calcd for C27H29N3NaOS [M+Na]+ 466.1929, found 466.1924.

    1-(1-Isopropyl-1H-imidazol-2-yl)-4-methyl-3-(4-(methyl- (phenyl)amino)benzyl)pentan-1-one (3l): Colorless oil, 20 mg, 50% yield, 91% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=92:8), flow rate 0.6 mL/min, 40 ℃, tR(minor)=9.06 min, tR(major)=9.81 min]; [α]D25-20.658 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.25~7.18 (m, 3H), 7.17~7.06 (m, 3H), 6.93 (dd, J=8.5, 2.6 Hz, 4H), 6.87 (t, J=7.3 Hz, 1H), 5.52~5.40 (m, 1H), 3.26 (s, 3H), 3.16 (dd, J=17.1, 5.5 Hz, 1H), 3.06 (dd, J=17.1, 6.8 Hz, 1H), 2.72~2.56 (m, 1H), 2.51~2.33 (m, 2H), 1.84~1.72 (m, 1H), 1.40 (dd, J=8.7, 6.7 Hz, 6H), 0.97 (d, J=6.8 Hz, 3H), 0.93 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 193.4, 149.3, 146.8, 142.9, 135.1, 130.2, 129.4, 129.2, 121.7, 121.0, 120.2, 119.0, 49.3, 41.9, 40.4, 40.2, 37.1, 29.7, 23.8, 23.7, 19.9, 18.7; IR (KBr) ν: 2958, 2925, 2855, 2365, 1675, 1597, 1512, 1500, 1457, 1340, 1257, 870, 704 cm-1; HRMS (ESI) calcd for C30H33N3NaO [M+Na]+ 426.2521, found 426.2516.

    4-(4-(Dimethylamino)phenyl)-1-(1-isopropyl-1H- imidazol-2-yl)-3-phenylbutan-1-one (4a): Colorless oil, 36% yield, 90% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=90:10), flow rate 1.0 mL/min, 40 ℃, tR(minor)=7.92 min, tR(major)=9.18 min]. [α]D25+27.322 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.22~7.00 (m, 7H), 6.91 (d, J=8.6 Hz, 2H), 6.53 (d, J=8.6 Hz, 2H), 5.32~5.26 (m, 1H), 3.64~3.46 (m, 2H), 3.30 (dd, J=15.0, 3.9 Hz, 1H), 2.86~2.68 (m, 2H), 2.80 (s, 6H), 1.24 (d, J=6.6 Hz, 3H), 1.21 (d, J=6.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 192.1, 149.2, 144.9, 142.8, 130.1, 129.4, 128.3, 127.9, 126.2, 120.9, 112.9, 49.1, 44.8, 43.5, 42.9, 41.0, 23.7, 23.6; IR (KBr) ν: 2926, 2854, 2364, 1676, 1522, 1455, 1396, 1340, 1257, 984, 948, 917, 810, 703 cm-1; HRMS (ESI) calcd for C24H29N3NaO [M+Na]+ 398.2208, found 398.2203.

    4-(4-(Benzyl(methyl)amino)phenyl)-1-(1-isopropyl-1H- imidazol-2-yl)-3-phenylbutan-1-one (4b) Colorless oil, 83% yield, 91% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=75:25), flow rate 1.0 mL/min, 40 ℃, tR(minor)=5.83 min, tR(major)=7.11 min]. [α]D25+32.986 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.26~6.98 (m, 12H), 6.88 (d, J=8.6 Hz, 2H), 6.54 (d, J=8.6 Hz, 2H), 5.33~5.21 (m, 1H), 4.38 (s, 1H), 3.67~3.47 (m, 2H), 3.29 (dd, J=15.7, 4.6 Hz, 1H), 2.85 (s, 3H), 2.81 (dd, J=13.7, 6.4 Hz, 1H), 2.73 (dd, J=13.7, 7.8 Hz, 1H), 1.24 (d, J=6.7 Hz, 3H), 1.20 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 192.1, 148.3, 144.9, 142.8, 139.3, 130.1, 129.4, 128.6, 128.3, 128.1, 127.9, 127.0, 126.9, 126.2, 120.9, 112.5, 57.0, 49.1, 44.8, 43.5, 42.8, 38.6, 23.7, 23.5; IR (KBr) ν: 2923, 2853, 2367, 2344, 1676, 1522, 1455, 1373, 1257, 1225, 984, 917, 809, 700 cm-1; HRMS (ESI) calcd for C30H33N3NaO [M+Na]+ 474.2521, found 474.2516.

    4-(4-(Dibenzylamino)phenyl)-1-(1-isopropyl-1H-imida- zol-2-yl)-3-phenylbutan-1-one (4c): Colorless oil, 60% yield, 80% ee [HPLC: chiralpak AD-H column, 254 nm, hexane/isopropanol (V:V=75:25), flow rate 1.0 mL/min, 40 ℃, tR(minor)=7.05 min, tR(major)=13.24 min]. [α]D25+37.784 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.34~7.26 (m, 4H), 7.27~7.17 (m, 10H), 7.17~7.07 (m, 3H), 6.92 (d, J=8.3 Hz, 2H), 6.60 (d, J=8.1 Hz, 2H), 5.41~5.28 (m, 1H), 4.58 (s, 4H), 3.69 (dd, J=16.5, 9.3 Hz, 1H), 3.63~3.51 (m, 1H), 3.33 (dd, J=16.5, 5.1 Hz, 1H), 2.87 (dd, J=13.7, 6.5 Hz, 1H), 2.78 (dd, J=13.7, 8.3 Hz, 1H), 1.31 (d, J=6.7 Hz, 3H), 1.27 (d, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 192.1, 147.7, 144.8, 142.7, 138.9, 130.1, 129.3, 128.7, 128.3, 128.2, 127.9, 126.9, 126.9, 126.2, 120.9, 112.5, 54.3, 49.1, 44.7, 43.3, 42.7, 23.7, 23.5; IR (KBr) ν: 2929, 2854, 2363, 1676, 1524, 1497, 1457, 1395, 1363, 1258, 959, 813, 700 cm-1; HRMS (ESI) calcd for C36H37N3NaO [M+Na]+ 550.2834, found 550.2829.

    4-(4-(Benzylamino)phenyl)-1-(1-isopropyl-1H-imidazol- 2-yl)-3-phenylbutan-1-one (4d) Pale yellow oil, 33 mg, 70% yield, 95% ee [HPLC: chiralpak IC column, 254 nm, hexane/isopropanol (V:V=70:30), flow rate 1.0 mL/ min, 40 ℃, tR(major)=6.77 min, tR(minor)=7.38 min]. [α]D25+34.052 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.37~7.05 (m, 12H), 6.91 (d, J=8.1 Hz, 2H), 6.51 (d, J=8.2 Hz, 2H), 5.41~5.28 (m, 1H), 4.26 (s, 2H), 3.66 (dd, J=16.0, 8.9 Hz, 1H), 3.63~3.52 (m, 1H), 3.37 (dd, J=16.0, 4.9 Hz, 1H), 2.86 (dd, J=13.6, 6.7 Hz, 1H), 2.80 (dd, J=13.6, 7.7 Hz, 1H), 1.32 (d, J=6.6 Hz, 3H), 1.28 (d, J=6.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 192.0, 146.0, 144.7, 142.7, 139.3, 130.2, 129.5, 129.3, 128.7, 128.3, 127.9, 127.8, 127.4, 126.2, 120.9, 113.1, 49.1, 48.9, 44.8, 43.5, 43.0, 23.7, 23.5; IR (KBr) ν: 2925, 2855, 2363, 2342, 1676, 1616, 1519, 1497, 1455, 1409, 1395, 1324, 1256, 979, 917, 702 cm-1; HRMS (ESI) calcd for C29H31N3NaO [M+Na]+ 460.2365, found 460.2359.

    4-(4-Aminophenyl)-1-(1-isopropyl-1H-imidazol-2-yl)-3-phenylbutan-1-one (4e): Pale Yellow oil, 38% yield, 58% ee [HPLC: chiralpak IC column, 254 nm, hexane/ isopropanol (V:V=75:25), flow rate 1.0 mL/min, 40 ℃, tR(major)=11.49 min, tR(minor)=16.95 min]. [α]D25+ 20.859 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.24~7.16 (m, 5H), 7.15~7.08 (m, 2H), 6.87 (d, J=8.2 Hz, 2H), 6.53 (d, J=8.3 Hz, 2H), 5.41~5.28 (m, 1H), 3.69~3.50 (m, 2H), 3.39 (dd, J=15.6, 4.8 Hz, 1H), 2.89~2.76 (m, 2H), 1.33 (d, J=6.6 Hz, 3H), 1.29 (d, J=6.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 192.0, 144.6, 144.3, 142.7, 130.3, 129.7, 129.4, 128.3, 127.9, 126.2, 120.9, 115.2, 49.1, 44.9, 43.5, 43.0, 23.7, 23.6; IR (KBr) ν: 2923, 2852, 2362, 2344, 1673, 1519, 1458, 1396, 1257, 981, 919, 830, 703 cm-1; HRMS (ESI) calcd for C22H25- N3NaO [M+Na]+ 370.1895, found 370.1890.

    Methyl-3-(2-fluorophenyl)-4-(4-(methyl(phenyl)amino)- phenyl)butanoate (5): Colorless oil, 60% yield, 97% ee [HPLC: chiralpak IC column, 254 nm, hexane/isopropanol (V:V=97.5:2.5), flow rate 0.6 mL/min, 40 ℃, tR(major)=11.23 min, tR(minor)=11.88 min]. [α]D25+ 5.888 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 7.32~6.79 (m, 13H), 3.76~3.61 (m, 1H), 3.53 (s, 3H), 3.25 (s, 3H), 2.99~2.80 (m, 2H), 2.78~2.61 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 172.7, 161.0 (d, J=244.4 Hz), 149.2, 147.3, 132.7, 130.3, 130.2, 130.0, 129.1, 128.1 (d, J=8.4 Hz), 124.0 (d, J=3.2 Hz), 121.2, 120.7, 119.5, 115.6 (d, J=22.7 Hz), 51.6, 40.7, 40.3, 38.4, 38.3; 19F NMR (376 MHz, CDCl3) δ: -117.48; IR (KBr) ν: 2363, 2345, 1736, 1637, 1595, 1510, 1492, 1384, 1341, 1254, 1152, 755, 695 cm-1; HRMS (ESI) calcd for C24H24N- FNaO2 [M+Na]+ 400.1689, found 400.1684.

    To a solution of 3h (227 mg, 0.5 mmol) in N, N-dime- thylformamide (DMF) (5.0 mL) was added MeI (710 mg, 5.0 mmol, 10.0 equiv.). The mixture was stirred at 80 ℃ for 6 h (monitored by TLC) under argon atmosphere, followed by addition of MeOH (2.0 mL) and DBU (76 mg, 2.5 mmol, 5.0 equiv.). After stirring at room temperature for 20 h, the reaction mixture was diluted with EtOAc (25 mL) and H2O (25 mL). The aqueous layer was separated and extracted with EtOAc (25 mL×2). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc/petroleum ether, V:V=2:8) to provide the compound 5 as pale yellow oil (113 mg, 60% yield).

    Supporting Information  X-ray data for compound 3h, 1H NMR, 13C NMR spectra, and HPLC chromatograms for compounds 3, 4 and 5. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.


    Dedicated to the 40th anniversary of Chinese Journal of Organic Chemistry.
    1. [1]

      For selected reviews on visible-light photoredox catalysis, see:
      (a) Xuan, J.; Xiao, W. J. Angew. Chem., Int. Ed. 2012, 51, 6828.
      (b) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322.
      (c) Douglas, J. J.; Sevrin, M. J.; Stephenson, C. R. J. Org. Process Res. Dev. 2016, 20, 1134.
      (d) Gentry, E. C.; Knowles, R. R. Acc. Chem. Res. 2016, 49, 1546.
      (e) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075.
      (f) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. J. Org. Chem. 2016, 81, 6898.
      (g) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Chem. Rev. 2016, 116, 10035.
      (h) Parasram, M.; Gevorgyan, V. Chem. Soc. Rev. 2017, 46, 6227.
      (i) Larsen, C. B.; Wenger, O. S. Chem.-Eur. J. 2018, 24, 2039.
      (j) Marzo, L.; Pagire, S. K.; Reiser, O.; Konig, B. Angew. Chem., Int. Ed. 2018, 57, 10034.
      (k) Zhao, Y. T.; Xia, W. J. Chem. Soc. Rev. 2018, 47, 2591.
      (l) Chuentragool, P.; Kurandina, D.; Gevorgyan, V. Angew. Chem., Int. Ed. 2019, 58, 11586.
      (m) Zhou, Q. Q.; Zou, Y. Q.; Lu, L. Q.; Xiao, W. J. Angew. Chem., Int. Ed. 2019, 58, 1586.
      (n) Xiao, L.; Li, J. H.; Wang, T. Acta Chim. Sinica 2019, 77, 841(in Chinese).
      (肖丽, 李嘉恒, 王挺, 化学学报, 2019, 77, 841.)
      (o) Chen, Y. L.; Chang, L.; Zuo, Z. W. Acta Chim. Sinica 2019, 77, 794(in Chinese).
      (陈奕霖, 常亮, 左智伟, 化学学报, 2019, 77, 794.)
      (p) Chen, D.; Liu, J. C.; Zhang, X. Y.; Jiang, H. Z.; Li, J. H. Chin. J. Org. Chem. 2019, 39, 3353(in Chinese).
      (陈丹, 刘剑沉, 张馨元, 蒋合众, 李加洪, 有机化学, 2019, 39, 3353.)
      (q) Zhang, H.; Yu, S. Y. Chin. J. Org. Chem. 2019, 39, 95(in Chinese).
      (张昊, 俞寿云, 有机化学, 2019, 39, 95.)

    2. [2]

      For recent reviews on asymmetric photoredox catalysis, see:
      (a) Meggers, E. Chem. Commun. 2015, 51, 3290.
      (b) Wang, C. F.; Lu, Z. Org. Chem. Front. 2015, 2, 179.
      (c) Yoon, T. P. Acc. Chem. Res. 2016, 49, 2307.
      (d) Wang, D. H.; Zhang, L.; Luo, S. Z. Acta Chim. Sinica 2017, 75, 22(in Chinese).
      (王德红, 张龙, 罗三中, 化学学报, 2017, 75, 22.)
      (e) Brenninger, C.; Jolliffe, J. D.; Bach, T. Angew. Chem., Int. Ed. 2018, 57, 14338.
      (f) Garrido-Castro, A. F.; Maestro, M. C.; Aleman, J. Tetrahedron Lett. 2018, 59, 1286.
      (g) Silvi, M.; Melchiorre, P. Nature 2018, 554, 41.
      (h) Zou, Y. Q.; Hormann, F. M.; Bach, T. Chem. Soc. Rev. 2018, 47, 278.
      (i) Jiang, C.; Chen, W.; Zheng, W. H.; Lu, H. Org. Biomol. Chem. 2019, 17, 867

    3. [3]

      For examples of deracemization enabled by visible-light photocatalysis, see:
      (a) Hoelzl-Hobmeier, A.; Bauer, A.; Silva, A. V.; Huber, S. M.; Bannwarth, C.; Bach, T. Nature 2018, 564, 240.
      (b) Shin, N. Y.; Ryss, J. M.; Zhang, X.; Miller, S. J.; Knowles, R. R. Science 2019, 366, 364.
      (c) Troster, A.; Bauer, A.; Jandl, C.; Bach, T. Angew. Chem., Int. Ed. 2019, 58, 3538.
      (d) Shi, Q.; Ye, J. Angew. Chem., Int. Ed. 2020, 59, 4998.

    4. [4]

      For selected examples of dual catalysis systems, see:
      (a) Blum, T. R.; Miller, Z. D.; Bates, D. M.; Guzei, I. A.; Yoon, T. P. Science 2016, 354, 1391.
      (b) Capacci, A. G.; Malinowski, J. T.; McAlpine, N. J.; Kuhne, J.; MacMillan, D. W. C. Nat. Chem. 2017, 9, 1073.
      (c) Lin, L.; Bai, X.; Ye, X.; Zhao, X.; Tan, C. H.; Jiang, Z. Angew. Chem., Int. Ed. 2017, 56, 13842.
      (d) Yang, Q.; Zhang, L.; Ye, C.; Luo, S. Z.; Wu, L. Z.; Tung, C. H. Angew. Chem., Int. Ed. 2017, 56, 3694.
      (e) Proctor, R. S. J.; Davis, H. J.; Phipps, R. J. Science 2018, 360, 419.
      (f) Ye, C.-X.; Melcamu, Y. Y.; Li, H.-H.; Cheng, J.-T.; Zhang, T.-T.; Ruan, Y.-P.; Zheng, X.; Lu, X.; Huang, P.-Q. Nat. Commun. 2018, 9, 410.
      (g) Zhang, H. H.; Zhao, J. J.; Yu, S. J. Am. Chem. Soc. 2018, 140, 16914.
      (h) Cheng, Y. Z.; Zhao, Q. R.; Zhang, X.; You, S. L. Angew. Chem., Int. Ed. 2019, 58, 18069.
      (i) Li, Y.; Lei, M.; Gong, L. Nat. Catal. 2019, 2, 1016.
      (j) Zhang, K.; Lu, L. Q.; Jia, Y.; Wang, Y.; Lu, F. D.; Pan, F.; Xiao, W. J. Angew. Chem., Int. Ed. 2019, 58, 13375.
      (k) Cheng, Z. M.; Chen, P. H.; Liu, G. S. Acta Chim. Sinica 2019, 77, 856(in Chinese).
      (成忠明, 陈品红, 刘国生, 化学学报, 2019, 77, 856.)

    5. [5]

      For selected examples of bifunctional photocatalysts, see:
      (a) Arceo, E.; Jurberg, I. D.; Alvarez-Fernandez, A.; Melchiorre, P. Nat. Chem. 2013, 5, 750.
      (b) Ding, W.; Lu, L. Q.; Zhou, Q. Q.; Wei, Y.; Chen, J. R.; Xiao, W. J. J. Am. Chem. Soc. 2017, 139, 63.
      (c) Silvi, M.; Verrier, C.; Rey, Y. P.; Buzzetti, L.; Melchiorre, P. Nat. Chem. 2017, 9, 868.
      (d) Skubi, K. L.; Kidd, J. B.; Jung, H.; Guzei, I. A.; Baik, M. H.; Yoon, T. P. J. Am. Chem. Soc. 2017, 139, 17186.
      (e) Li, Y.; Zhou, K.; Wen, Z.; Cao, S.; Shen, X.; Lei, M.; Gong, L. J. Am. Chem. Soc. 2018, 140, 15850.
      (f) Rigotti, T.; Casado-Sanchez, A.; Cabrera, S.; Perez-Ruiz, R.; Liras, M.; O'Shea, V. A. D.; Aleman, J. ACS Catal. 2018, 8, 5928.
      (g) Shen, X.; Li, Y.; Wen, Z.; Cao, S.; Hou, X.; Gong, L. Chem. Sci. 2018, 9, 4562.
      (h) Stegbauer, S.; Jandl, C.; Bach, T. Angew. Chem., Int. Ed. 2018, 57, 14593.
      (i) Guo, Q.; Wang, M.; Peng, Q.; Huo, Y.; Liu, Q.; Wang, R.; Xu, Z. ACS Catal. 2019, 9, 4470.

    6. [6]

      (a) Giese, B. Angew. Chem., Int. Ed. 1983, 22, 753.
      (b) Giese, B.; González-Gómez, J. A.; Witzel, T. Angew. Chem., Int. Ed. 1984, 23, 69.

    7. [7]

      (a) Wu, J. H.; Radinov, R.; Porter, N. A. J. Am. Chem. Soc. 1995, 117, 11029.
      (b) Sibi, M. P.; Ji, J.; Wu, J. H.; Gürtler, S.; Porter, N. A. J. Am. Chem. Soc. 1996, 118, 9200.
      (c) Sibi, M. P.; Porter, N. A. Acc. Chem. Res. 1999, 32, 163.

    8. [8]

      Espelt, L. R.; McPherson, I. S.; Wiensch, E. M.; Yoon, T. P. J. Am. Chem. Soc. 2015, 137, 2452. doi: 10.1021/ja512746q

    9. [9]

      (a) Zuo, Z. W.; Ahneman, D. T.; Chu, L. L.; Terrett, J. A.; Doyle, A. G.; MacMillan, D. W. C. Science 2014, 345, 437.
      (b) Zuo, Z. W.; Gong, H.; Li, W.; Choi, J.; Fu, G. C.; MacMillan, D. W. C. J. Am. Chem. Soc. 2016, 138, 1832.

    10. [10]

      For accounts on synthetic utilization of α-aminoalkyl radicals in visible-light photoredox catalysis, see:
      (a) Cho, D. W.; Yoon, U. C.; Mariano, P. S. Acc. Chem. Res. 2011, 44, 204.
      (b) Nakajima, K.; Miyake, Y.; Nishibayashi, Y. Acc. Chem. Res. 2016, 49, 1946.

    11. [11]

      (a) Cermenati, L.; Mella, M.; Albini, A. Tetrahedron 1998, 54, 2575.
      (b) Smitha, M. A.; Prasad, E.; Gopidas, K. R. J. Am. Chem. Soc. 2001, 123, 1159.
      (c) Yoshimi, Y.; Kobayashi, K.; Kamakura, H.; Nishikawa, K.; Haga, Y.; Maeda, K.; Morita, T.; Itou, T.; Okada, Y.; Hatanaka, M. Tetrahedron Lett. 2010, 51, 2332.
      (d) Miyake, Y.; Nakajima, K.; Nishibayashi, Y. Chem. Commun. 2013, 49, 7854.
      (e) Lang, S. B.; O'Nele, K. M.; Tunge, J. A. J. Am. Chem. Soc. 2014, 136, 13606.

    12. [12]

      (a) Bauer, E. B. Chem. Soc. Rev. 2012, 41, 3153.
      (b) Cao, Z.-Y.; Brittain, W. D. G.; Fossey, J. S.; Zhou, F. Catal. Sci. Technol. 2015, 5, 3441.
      (c) Zhang, L.; Meggers, E. Chem.-Asian. J. 2017, 12, 2335.
      (d) Cruchter, T.; Larionov, V. A. Coord. Chem. Rev. 2018, 376, 95.

    13. [13]

      Lin, S. X.; Sun, G. J.; Kang, Q. Chem. Commun. 2017, 53, 7665. doi: 10.1039/C7CC03650G

    14. [14]

      CCDC 1998446 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

    15. [15]

      (a) Ohta, S.; Hayakawa, S.; Nishimura, K.; Okamoto, M. Chem. Pharm. Bull. 1987, 35, 1058.
      (b) Miyashita, A.; Suzuki, Y.; Nagasaki, I.; Ishiguro, C.; Iwamoto, K.-I.; Higashino, T. Chem. Pharm. Bull. 1997, 45, 1254.

    16. [16]

      (a) de Assis, F. F.; Huang, X.; Akiyama, M.; Pilli, R. A.; Meggers, E. J. Org. Chem. 2018, 83, 10922.
      (b) Ma, J.; Lin, J.; Zhao, L.; Harms, K.; Marsch, M.; Xie, X.; Meggers, E. Angew. Chem., Int. Ed. 2018, 57, 11193.

    17. [17]

      Wang, C.; Chen, L. A.; Huo, H.; Shen, X.; Harms, K.; Gong, L.; Meggers, E. Chem. Sci. 2015, 6, 1094. doi: 10.1039/C4SC03101F

    18. [18]

      Huo, H.; Shen, X.; Wang, C.; Zhang, L.; Rose, P.; Chen, L. A.; Harms, K.; Marsch, M.; Hilt, G.; Meggers, E. Nature 2014, 515, 100. doi: 10.1038/nature13892

  • Scheme 1  Photoredox catalyzed addition of para-aminobenzyl radicals to electron-deficient alkenes

    Scheme 2  Large-scale experiment and synthetic transformation of product 3h

    Scheme 3  Proposed mechanism and transition-state model

    Table 1.  Optimization of reaction conditions a

    Entry Λ-M Solvent Yieldb/% eec/%
    1 Λ-Rh1 DCE 77 82
    2 Λ-Rh1 DCE
    3 None DCE
    4 Λ-Ir DCE 53 89
    5 Λ-Rh2 DCE 70 88
    6 Λ-Rh2 MeOH 79 96
    7 Λ-Rh2 Toluene 46 93
    8 Λ-Rh2 DMSO 31 60
    9 Λ-Rh2 Acetone 75 91
    10 Λ-Rh2 CH3CN 65 87
    a Unless otherwise noted, reactions were carried out by using 1a (0.1 mmol), 2a (0.15 mmol) and Λ-M (0.002 mmol, 2 mol%) in degassed solvent (0.3 mL) at room temperature under irradiation with 20 W blue LEDs. b Isolated yields based on 1a. c Determined by chiral HPLC analysis.
    下载: 导出CSV

    Table 2.  Substrate scope of α, β-unsaturated 2-acyl imidazolesa

    a Unless otherwise noted, reactions were carried out by using 1 (0.1 mmol), 2a (0.15 mmol) and Λ-Rh2 (2 mol%) in degassed MeOH (0.3 mL) at room temperature under irradiation with 20 W blue LEDs. All isolated yields were based on substrate 1, ee values were determined by chiral HPLC analysis.
    下载: 导出CSV

    Table 3.  Substrate scope of arylacetic acidsa

    Entry Ar (2) 4 Yieldb/% eec/%
    1 4-Me2NC6H4 (2b) 4a 36 90
    2 4-BnMeNC6H4 (2c) 4b 83 91
    3 4-Bn2NC6H4 (2d) 4c 60 80
    4 4-BnHNC6H4 (2e) 4d 70 95
    5d 4-H2NC6H4 (2f) 4e 38 58
    6 4-MeOC6H4 (2g)
    7 3-PhMeNC6H4 (2h)
    8 2-PhMeNC6H4 (2i)
    a Unless otherwise noted, reactions were carried out by using 1a (0.1 mmol), 2 (0.15 mmol) and Λ-Rh2 (2 mol%) in degassed MeOH (0.3 mL) at room temperature under irradiation with 20 W blue LEDs. b Isolated yields based on 1a. c Determined by chiral HPLC analysis. d DMSO was used in place of MeOH.
    下载: 导出CSV
  • 加载中
计量
  • PDF下载量:  0
  • 文章访问数:  63
  • HTML全文浏览量:  3
文章相关
  • 发布日期:  2020-11-25
  • 收稿日期:  2020-04-25
  • 修回日期:  2020-05-14
  • 网络出版日期:  2020-05-19
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章