Subscribe to RSS
DOI: 10.1055/s-2007-967963
Catalytic Asymmetric Alkylation of α-Cyanocarboxylates Using a Phase-Transfer Catalyst
Publication History
Publication Date:
21 February 2007 (online)
Abstract
The highly enantioselective catalytic alkylation of cyanoacetates was achieved using a chiral phase-transfer catalyst to give α,α-disubstituted α-cyanoacetates which have a chiral quaternary carbon. The product thus obtained was applied to the synthesis of an optically active oxindole.
Key words
phase-transfer catalysis - asymmetric synthesis - alkylation - halides - indoles
-
1a
Christofferrs J.Mann A. Angew. Chem. Int. Ed. 2001, 40: 4591 -
1b
Denissova I.Barriault L. Tetrahedron 2003, 59: 10105 -
1c
Douglas CJ.Overman LE. Proc. Natl. Acad. Sci. U.S.A. 2004, 101: 5363 -
1d
Corey EJ.Guzman-Perez A. Angew. Chem. Int. Ed. 1998, 37: 388 -
2a
Cativiela C.Diaz-de-Villegas MD.Galves JA.Lapena Y. Tetrahedron 1995, 51: 5921 -
2b
Abele S.Seebach D. Eur. J. Org. Chem. 2000, 1 - 3
Li H.Song J.Liu X.Deng L. J. Am. Chem. Soc. 2005, 127: 8948 -
4a
Sawamura M.Hamashima H.Ito Y. J. Am. Chem. Soc. 1992, 114: 8295 -
4b
Sawamura M.Hamashima H.Shinoto H.Ito Y. Tetrahedron Lett. 1995, 36: 6479 -
4c
Motoyama Y.Koga Y.Kobayashi K.Aoki K.Nishiyama H. Chem. Eur. J. 2002, 8: 2968 -
4d
Taylor MS.Zalatan DN.Lerchner AM.Jacobsen EN. J. Am. Chem. Soc. 2005, 127: 1313 - 5
Poulsen TB.Alemparte C.Saaby S.Bella M.Jørgensen KA. Angew. Chem. Int. Ed. 2005, 44: 2896 - 6
Sawamura M.Sudoh M.Ito Y. J. Am. Chem. Soc. 1996, 118: 3309 -
7a
Hanamoto T.Katsuki T.Yamaguchi M. Tetrahedron Lett. 1986, 27: 2463 -
7b
Cativiela C.Diaz-de-Villegas MD.Gálves JA. J. Org. Chem. 1994, 59: 2497 -
8a
Ooi T.Takeuch M.Kameda K.Maruoka K. J. Am. Chem. Soc. 2000, 122: 5228 -
8b
Ooi T.Kameda K.Maruoka K. J. Am. Chem. Soc. 2003, 125: 5139 -
11a
Ooi T.Miki T.Maruoka K. Org. Lett. 2005, 7: 191 -
11b
Ooi T.Miki T.Taniguchi M.Shiraish M.Takeuchi M.Maruoka K. Angew. Chem. Int. Ed. 2003, 42: 3796 -
11c
Ooi T.Taniguchi M.Kameda M.Maruoka K. Angew. Chem. Int. Ed. 2002, 41: 4542 -
11d
Ooi T.Doda K.Maruoka K. Org. Lett. 2001, 3: 1273 -
13a
Badorrey R.Cativiela C.Díaz-de-Villegas MD.Gálves JA. Tetrahedron: Asymmetry 2003, 14: 2201 -
13b
Badorrey R.Cativiela C.Díaz-de-Villegas MD.Gálves JA.Lapena Y. Tetrahedron: Asymmetry 1997, 8: 311 -
14a
Marti C.Carreira EM. Eur. J. Org. Chem. 2003, 2209 -
14b
Huang A.Kodanko JJ.Overman LE. J. Am. Chem. Soc. 2004, 126: 14043 -
15a
Trost BM.Zhang Y. J. Am. Chem. Soc. 2006, 128: 4590 -
15b
Trost BM.Brennan MK. Org. Lett. 2006, 8: 2027 -
15c
Bella M.Kobbelgaard S.Jørgensen KA. J. Am. Chem. Soc. 2005, 127: 3670 - 20
Yamada K.Kurokawa T.Tokuyama H.Fukuyama T. J. Am. Chem. Soc. 2003, 125: 6603
References and Notes
Although other solvents such as toluene, CH2Cl2, CHCl3, and EtOAc were investigated for the reaction, the results were inferior to the reaction using diethyl ether as solvent.
10The yield and ee using other commercially available chiral PTC’s under the same reaction conditions, were as follows: N-benzylcinchoninium chloride (trace, 19% ee), N-benzyl-cinchonidinium chloride (yield: 13%, 17% ee), N-[4-(tri-fluoromethyl)benzyl]cinchonidinium bromide (yield: 10%, 28% ee), N-benzylquininium chloride (yield: 20%, 19% ee), N-benzylquinidinium chloride (yield: 19%, 3% ee), N-(9-anthracenylmethyl)cinchonidinium chloride (yield: 10%, 0% ee), TaDiAS-[(4R,5R)-2,2-dipropyl-N,N,N′,N′-tetrakis(4-methylbenzyl)]bis(tetrafluoroborate) (yield: 42%, 4% ee).
12General procedure: A solution of tert-butyl 2-cyano-propanoate or tert-butyl 2-cyanopent-4-enoate (0.1 mmol) in Et2O (2.4 mL) was cooled to -60 °C. The PTC (1a or 1b, 0.001mmol), alkyl halide (0.12 mmol) and then CsOH (75 mg, 0.5 mmol) were added to the solution. The reaction mixture was vigorously stirred for the time indicated in Table
[2]
and then diluted with Et2O. The organic layer was washed with H2O and brine, dried over MgSO4 and the solvents evaporated. The residue was purified using flash column chromatography on silica gel (EtOAc-hexane) to give the corresponding 2-cyanocarboxylate in the yield indicated.
(R)-tert-Butyl 2-cyano-2-methyl-3-phenylpropanoate (3c)
Colorless oil; [α]D
25 -14.7 (c 2.00, CHCl3) (97% ee). 1H NMR (400 MHz, CDCl3): δ = 1.42 (s, 9 H), 1.57 (s, 3 H), 2.98-3.01 (d, J = 13.7 Hz, 1 H), 3.17-3.21 (d, J = 13.4 Hz, 1 H), 7.30-7.33 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 24.1, 28.4, 44.3, 46.7, 83.1, 121.9, 128.5, 129.2, 130.9, 135.2, 169.2. HRMS-FAB: m/z [M + H]+ calcd for C15H20O2N: 246.1493; found: 246.1494. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ, 2-propanol-hexane, 1:400).
(R)-tert-Butyl 2-cyano-2-methylpent-4-enoate (4)
Colorless oil; [α]D
25 +2.2 (c 1.67, CHCl3) (92% ee). 1H NMR (400 MHz, CDCl3): δ = 1.50 (s, 9 H), 1.54 (s, 3 H), 2.47 (dd, J = 13.8, 7.4 Hz, 1 H), 2.64 (dd, J = 13.8, 7.2 Hz, 1 H), 5.22-5.26 (m, 2 H), 5.82 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 22.7, 27.8, 42.1, 44.2, 83.9, 120.0, 120.7, 130.9, 167.8. HRMS-FAB: m/z [M + H]+ calcd for C11H18O2N: 196.1407; found: 196.1321. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ-H, 2-propanol-hexane, 1:400).
tert-Butyl 2-cyano-2-methyl-3-pyridin-2-ylpropanoate (5)
Colorless oil; [α]D
25 +8.4 (c 3.45, CH2Cl2) (70% ee). 1H NMR (400 MHz, CDCl3): δ = 1.48 (s, 9 H), 1.65 (s, 3 H), 3.21 (d, J = 14.6 Hz, 1 H), 3.45 (d, J = 14.6 Hz, 1 H), 7.19 (ddd, J = 7.6, 4.8, 1.2 Hz, 1 H), 7.27 (m, 1 H), 7.64 (td, J = 7.6, 2.0 Hz, 1 H), 8.54 (ddd, J = 4.9, 2.1, 0.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 23.6, 27.7, 44.3, 44.9, 83.6, 120.3, 122.3, 123.8, 136.4, 149.1, 155.2, 168.0. HRMS-FAB: m/z [M + H]+ calcd for C14H19O2N2: 247.1440; found: 247.1449. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ-H, 2-propanol-hexane, 1:4).
1-tert-Butyl 4-ethyl 2-cyano-2-methylbutanedioate (6)
Colorless oil; [α]D
25 +15.6 (c 2.00, CHCl3) (85% ee). 1H NMR (400 MHz, CDCl3): δ = 1.28 (t, J = 7.2 Hz, 3 H), 1.52 (s, 9 H), 1.63 (s, 3 H), 2.77 (d, J = 17.1 Hz, 1 H), 2.98 (d, J = 17.1 Hz, 1 H), 4.20 (q, J = 7.1 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 14.1, 23.7, 27.7, 41.2, 41.6, 61.4, 84.1, 120.0, 167.4, 168.7. HRMS-FAB: m/z [M + H]+ calcd for C12H20O4N: 242.1332; found: 242.1411. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ-H, 2-propanol-hexane, 1:200).
Di-tert-butyl 2-cyano-2-methylbutanedioate (7)
Colorless oil; [α]D
25 +19.3 (c 7.50, CHCl3) (92% ee). 1H NMR (400 MHz, CDCl3): δ = 1.47 (s, 9 H), 1.51 (s, 9 H), 1.60 (s, 3 H), 2.69 (d, J = 16.8 Hz, 1 H), 2.89 (d, J = 16.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 23.7, 27.7, 28.0, 41.4, 42.6, 82.3, 83.9, 120.0, 167.5, 167.8. HRMS-FAB: m/z [M + H]+ calcd for C14H24O4N: 270.1694; found: 270.1709. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ-H, 2-propanol-hexane, 1:800).
tert-Butyl 2-benzyl-2-cyanopent-4-enoate (8)
Colorless oil; [α]D
25 -18.1 (c 1.74, CHCl3) (99% ee). 1H NMR (400 MHz, CDCl3): δ = 1.29 (s, 9 H), 2.47 (dd, J = 13.6, 6.8 Hz, 1 H), 2.63 (dd, J = 13.7, 7.8 Hz, 1 H), 2.96 (d, J = 13.4 Hz, 1 H), 3.09 (d, J = 13.4 Hz, 1 H), 5.17-5.21 (m, 2 H), 5.78 (m, 1 H) 7.19-7.30 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 27.7, 41.7, 42.5, 84.2, 119.0, 120.8, 127.7, 128.4, 130.1, 130.7, 134.3, 166.9. HRMS-FAB: m/z [M + H]+ calcd for C17H22O2N: 272.1621; found: 272.1662. The ee was determined by HPLC analysis (Daicel CHIRALCEL OD, 2-propanol-hexane, 1:800).
1-tert-Butyl 4-ethyl 2-cyano-2-prop-2-en-1-ylbutane-dioate (9)
Colorless oil; [α]D
25 +13.9 (c 2.38, CHCl3) (90% ee). 1H NMR (400 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, 3 H), 1.48 (s, 9 H), 2.50 (dd, J = 13.7, 7.3 Hz, 1 H), 2.62 (dd, J = 13.9, 7.3 Hz, 1 H), 2.72 (d, J = 17.1 Hz, 1 H), 2.96 (d, J = 16.8 Hz, 1 H), 4.16 (q, J = 7.3 Hz, 2 H), 5.20-5.26 (m, 2 H), 5.80 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 14.1, 27.7, 40.0, 41.2, 45.9, 61.4, 84.3, 118.5, 121.3, 130.0, 166.6, 168.7. HRMS-FAB: m/z [M + H]+ calcd for C14H22O4N: 268.1560; found: 268.1545. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ-H, 2-propanol-hexane, 1:100).
Compound 10 was prepared from 2′-bromophenylaceto-nitrile according to a literature procedure, see: Albarella J. P.; J. Org. Chem.; 1977, 42: 2009
17
(R)-
tert
-Butyl 2-(2-bromophenyl)-2-cyanopent-4-enoate (11)
A solution of 10 (29.6 mg, 0.1 mmol) in toluene (2.4 mL) was cooled to -10 °C, and PTC 1b (1.1 mg, 0.001 mmol), allyl iodide (18 µL, 0.2 mmol) and then CsOH (75 mg, 0.5 mmol) were added to the solution. The reaction mixture was stirred vigorously for 1 d and then diluted with H2O. The mixture was extracted with CH2Cl2 and the combined organic layers were washed with brine and dried over MgSO4. After the solvent was removed by evaporation, the residue was purified by flash column chromatography on silica gel (EtOAc-hexane, 1:16) to give 11 in quantitative yield; colorless oil; [α]D
25 -9.2 (c 2.00, CHCl3) (93% ee). 1H NMR (400 MHz, CDCl3): δ = 1.48 (s, 9 H), 3.11 (dd, J = 7.6, 14.0 Hz, 1 H), 3.27 (dd, J = 6.8, 14.0 Hz, 1 H), 5.19-5.26 (m, 2 H), 5.78 (m, 1 H), 7.24 (dt, J = 1.6, 7.6 Hz, 1 H), 7.37 (dt, J = 1.2, 8.0 Hz, 1 H), 7.55 (dd, J = 1.4, 8.0 Hz, 1 H), 7.64 (dd, J = 1.6, 8.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 27.6, 39.7, 54.8, 84.7, 117.7, 120.7, 122.8, 127.7, 129.6, 130.1, 130.8, 133.9, 134.7, 165.2. HRMS-FAB: m/z [M + H]+ calcd for C16H19O2NBr: 336.0630; found: 336.0584. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ-H, 2-propanol-hexane, 1:100).
This result suggested that the Si:Re selectivity of compounds 2 and 10 in the enolate-forming step was opposite to each other. Mechanistic consideration of the asymmetric induction is now under investigation.
19
(
R
)-
N
-Benzyl-2-(2-bromophenyl)-2-cyanopent-4-enamide (12)
Compound 11 (34 mg, 0.1 mmol) was dissolved in TFA (1.0 mL) and stirred at r.t. for 12 h under an argon atmosphere. The TFA was then removed by evaporation and CH2Cl2 (1.0 mL) was added. The solution was cooled to 0 °C and EDC·HCl (38 mg, 0.2 mmol), 1-hydroxy-7-azabenzotriazole (27 mg, 0.2 mmol), and BnNH2 (16 µl, 0.15 mmol) were added. The reaction mixture was stirred overnight at r.t. under an argon atmosphere. After the addition of H2O, the mixture was extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4 and the solvents removed by evaporation. The residue was purified by flash column chromatography on silica gel (EtOAc-hexane, 1:4) to give compound 12 in 88% yield; mp 124 °C (CH2Cl2); [α]D
25 -21.9 (c 3.07, CHCl3) (93% ee). 1H NMR (400 MHz, CDCl3): δ = 3.19-3.30 (m, 2 H), 4.44 (dd, J = 5.1, 14.8 Hz, 1 H), 4.54 (dd, J = 6.0, 14.8 Hz, 1 H), 5.19-5.27 (m, 2 H), 5.75 (m, 1 H), 6.13 (br s, 1 H), 7.24-7.34 (m, 6 H), 7.39 (t, J = 7.6 Hz, 1 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 39.6, 44.8, 54.6, 118.4, 121.2, 123.0, 127.9, 128.1, 128.8, 130.3, 130.7, 130.7, 133.2, 135.3, 136.8, 165.3. HRMS-FAB: m/z [M + H]+ calcd for C19H18ON2Br: 369.0619; found: 369.0592. Anal. Calcd for C19H17ON2Br: C, 61.80; H, 4.64; N, 7.59. Found: C, 61.78; H, 4.54; N, 7.48. The ee was determined by HPLC analysis (Daicel CHIRALCEL OJ-H, 2-propanol-hexane, 1:20).
(
R
)-1-Benzyl-3-cyano-3-prop-2-en-1-yl)-1,3-dihydro-indol-2-one (13)
To a solution of compound 12 (44 mg, 0.11 mmol) in DMSO (1.1 mL) were added CuI (42 mg, 0.2 mmol) and CsOAc (106 mg, 0.5 mmol). The mixture was stirred for 10 h at 70 °C under an argon atmosphere. After the addition of Et2O, the organic layer was washed with H2O and brine, and dried over MgSO4. The solvent was removed by evaporation and the residue was purified by flash column chromatography on silica gel (EtOAc-hexane, 1:7) to give compound 13 in quantitative yield; mp 122 °C (CH2Cl2); [α]D
25 +27.3 (c 5.81, CHCl3) (93% ee). 1H NMR (400 MHz, CDCl3): δ = 2.83 (dd, J = 8.4, 13.6 Hz, 1 H), 3.05 (dd, J = 6.4, 13.2 Hz, 1 H,), 4.81 (d, J = 15.6 Hz, 1 H), 5.02 (d, J = 15.6 Hz, 1 H), 5.18-5.22 (m, 2 H), 5.65 (m, 1 H), 6.78 (d, J = 7.6 Hz, 1 H), 7.11 (t, J = 7.6 Hz, 1 H), 7.26-7.33 (m, 6 H), 7.41 (d, J = 7.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 41.1, 44.6, 46.4, 110.1, 116.7, 122.2, 123.6, 124.5, 124.7, 127.4, 128.1, 128.9, 129.0, 130.3, 134.7, 142.2, 170.1. HRMS-FAB: m/z [M + H]+ calcd for C19H17ON2: 289.1351; found: 289.1337. Anal. Calcd for C19H16ON2: C, 79.14; H, 5.59; N, 9.72. Found: C, 79.02; H, 5.52; N, 9.75. The ee was determined by HPLC analysis (Daicel CHIRALCEL IA, 2-propanol-hexane, 1:10).