Catalytic Asymmetric Alkylation of α-Cyanocarboxylates Using a Phase-Transfer Catalyst

Kazuhiro Nagata; Daisuke Sano; Takashi Itoh

doi:10.1055/s-2007-967963

LETTER

Catalytic Asymmetric Alkylation of α-Cyanocarboxylates Using a Phase-Transfer Catalyst

Kazuhiro Nagata, Daisuke Sano, Takashi Itoh*
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Fax: +81(3)37845982; e-Mail: itoh-t@pharm.showa-u.ac.jp;

Abstract

All articles of this category

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

Full Text

References

References and Notes

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

9

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.

10

The 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).

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

12

General 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).

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

16

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).

18

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).

20 Yamada K. Kurokawa T. Tokuyama H. Fukuyama T. J. Am. Chem. Soc. 2003, 125: 6603

21

( 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 MgSO_4.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).