Highly Diastereoselective Construction
of Substituted Pyrrolidines: Formal Synthesis of (-)-Bulgecinine

Biswanath Das; Duddukuri Nandan Kumar

doi:10.1055/s-0030-1260546

LETTER

Highly Diastereoselective Construction of Substituted Pyrrolidines: Formal Synthesis of (-)-Bulgecinine [¹]

Biswanath Das*, Duddukuri Nandan Kumar
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax: +91(40)27193198; e-Mail: biswanathdas@yahoo.com;

Abstract

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Abstract

A highly diastereoselective synthesis of substituted pyrrolidines has been achieved starting from nonchiral molecule, allyl bromide, or cis-but-2-ene-1,4-diol. The method involves the asymmetric epoxidation and endo-mode epoxide opening with azide nucleophile as the key steps. The method has been applied for the formal synthesis of (-)-bulgecinine.

Key words

substituted pyrrolidine - (-)-bulgecinine - diastereoselective synthesis - asymmetric epoxidation - endo-mode epoxide opening

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References

References and Notes

1

Part 45 in the series ‘Synthetic Studies on Natural Products and Bioactive Compounds’.

2a Cheng Y. Huang ZT. Wang MX. Curr. Org. Chem. 2004, 8: 325

2b Michael JP. Nat. Prod. Rep. 2005, 22: 603

3a Imada A. Kintaka K. Nakao M. Shinagawa S. J. Antibiot. 1982, 35: 1400

3b Shinagawa S. Kashara F. Wada Y. Harada S. Asai M. Tetrahedron 1984, 40: 3465

3c Shinagawa S. Maki M. Kintaka K. Imada A. Asai M. J. Antibiot. 1985, 38: 17

4a Das B. Suneel K. Satyalakshmi G. Tetrahedron: Asymmetry 2009, 20: 1536

4b Das B. Krishnaiah M. Sudhakar Ch. Bioorg. Med. Chem. Lett. 2010, 20: 2303

4c Das B. Kumar DN. Tetrahedron Lett. 2010, 51: 6011

Some earlier syntheses:

5a Wakamiya T. Yamauoi K. Nishikawa M. Shiba T. Tetrahedron Lett. 1985, 26: 4739

5b Bashyal BP. Chow HF. Fleet GWJ. Tetrahedron Lett. 1986, 27: 3205

5c Fehn S. Burger K. Tetrahedron: Asymmetry 1997, 8: 2001

5d Maeda M. Okazaki F. Murayama M. Tachibana Y. Aoyagi Y. Ohta A. Chem. Pharm. Bull. 1997, 45: 962

5e Khalaf JK. Datta A. J. Org. Chem. 2004, 69: 387

5f Chavan SP. Praveen Ch. Sharma P. Kalkote UR. Tetrahedron Lett. 2005, 46: 439

5g Toumi M. Couty F. Evano G. Tetrahedron Lett. 2008, 49: 1175

6a Izzo I. Scioscia M. Del Gaudio P. De Riccardis F. Tetrahedron Lett. 2001, 42: 5421

6b Poulard C. Carnet J. Legoupy S. Dujardiu G. Dhal R. Huct F. Lett. Org. Chem. 2009, 6: 359

7a Katsuki T. Sharpless KB. J. Am. Chem. Soc. 1980, 102: 5974

7b Gao Y. Hanson RM. Klunder JM. Ko SY. Masamune H. Sharpless KB. J. Am. Chem. Soc. 1987, 109: 5765

7c Goument B. Duchamel L. Mauge R. Tetrahedron 1994, 50: 171

8a Ma P. Martin VS. Masumune S. Sharpless KB. Viti SM. J. Org. Chem. 1982, 47: 1378

8b Finan JM. Kishi Y. Tetrahedron Lett. 1982, 23: 2719

9 Sasaki M. Tanino K. Hirai A. Miyashita MT. Org. Lett. 2003, 5: 1789

10

Spectral and Analytical Data of Selected Compounds(3-{3-(Benzyloxy)-2-[(4-methoxybenzyl)oxy]propyl}-oxiran-2-yl)methanol (4) [α]_D ^²5 -16.8 (c 0.9, CHCl₃). IR (KBr): ν_max = 3449, 1455, 1375, 1248 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.43-7.16 (7 H, m), 6.81 (2 H, d, J = 8.0 Hz), 4.65-4.43 (4 H, m), 3.79 (3 H, s), 3.74-3.63 (2 H, m), 3.62-3.42 (3 H, m), 2.99 (1 H, m), 2.82 (1 H, m), 1.92-1.73 (2 H, m). ^¹³C NMR (75 MHz, CDCl₃): δ = 158.3, 139.2, 13 2.3, 129.3, 128.8, 128.0, 121.9, 116.0, 73.2, 71.4, 70.7, 70.5, 70.3, 61.2, 56.3, 49.3, 30.7. ESI-MS: m/z = 358 [M]⁺. Anal. Calcd (%) for C₂₁H₂₆O₅: C, 70.39; H, 7.26. Found: C, 70.41; H, 7.21.
2-Azido-6-(benzyloxy)-5-(4-methoxybenzyloxy)hexane-1,3-diol (3)
IR (KBr): ν_max = 3390, 2103 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 7.38-7.16 (7 H, m), 6.81 (2 H, d, J = 8.0 Hz), 4.65-4.44 (4 H, m), 4.07 (1 H, m), 3.85 (1 H, m), 3.78 (3 H, s), 3.56-3.47 (4 H, m), 2.09 (1 H, m), 1.99-1.78 (1 H, m). ^¹³C NMR (100 MHz, CDCl₃): δ = 158.0, 137.8, 129.5, 128.5, 127.7, 126.7, 116.0, 73.2, 72.8, 70.1, 66.1, 65.5, 62.6, 55.9, 29.8. ESI-MS: m/z = 401 [M]⁺. Anal. Calcd (%) for C₂₁H₂₇N₃O₅: C, 62.84; H, 6.73. Found: C, 62.80; H, 6.75.
(4a R ,6 S ,7a S )-6-(Benzyloxymethyl)-2,2-dimethyl-hexahydro[1,3]dioxino[5,4- b ]pyrrole (16)
[α]_D ^²5 +31.3 (c 1.7, CHCl₃). IR (KBr): ν_max = 3385, 1600, 1490, 1279 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.37-7.20 (5 H, m), 4.53 (2 H, s), 4.22 (1 H, m), 4.08 (1 H, m), 3.47 (1 H, m), 3.33 (1 H, m), 2.93-2.74 (3 H, m), 2.30 (1 H, m), 1.97-1.71 (2 H, m), 1.48 (6 H, s). ^¹³C NMR (75 MHz, CDCl₃): δ = 138.8, 129.3, 128.5, 127.8, 100.9, 81.8, 72.6, 72.2, 70.0, 54.0, 36.7, 27.7. ESI-MS: m/z = 277 [M]⁺. Anal. Calcd (%) for C₁₆H₂₃NO₃: C, 69.31; H, 8.30. Found: C, 69.33; H, 8.27.
(4a R ,6 S ,7a S )-Benzyl 6-Hydroxymethyl)-2,2-dimethyl-tetrahydro[1,3]dioxino[5,4- b ]pyrrole-5(6 H )-carboxylate (2) [α]_D ^²5 -55.4 (c 1.0, CHCl₃). ^¹H NMR (300 MHz, CDCl₃):
δ = 7.32-7.13 (5 H, m), 5.05 (2 H, s), 4.40 (1 H, m), 4.24-4.00 (2 H, m), 3.96-3.65 (4 H, m), 3.07 (1 H, m), 2.63 (1 H, br s), 2.25 (1 H, m), 1.47 (6 H, s). ^¹³C NMR (75 MHz, CDCl₃): δ = 155.8, 135.5, 129.0, 128.7, 128.5, 127.8, 100.1, 72.0, 68.5, 67.0, 66.2, 61.1, 58.6, 31.4, 29.5, 19.8. ESI-MS: m/z = 321 [M]⁺. Anal. Calcd (%) for C₁₇H₂₃NO₅: C, 63.55; H, 7.17. Found: C, 63.51; H, 7.12.