키랄 보조제로서의 C<sub>2</sub>-대칭성 피로리딘 아미드의 합성과 광학 순도 결정

문홍식; 고동수

Journal of the Korean Industrial and Engineering Chemistry, Vol.9, No.6, 914-919, November, 1998

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키랄 보조제로서의 C₂-대칭성 피로리딘 아미드의 합성과 광학 순도 결정

Synthesis and Determination of Optical Purity of C₂-Symmetric Pyrrolidine Amides as Chiral Auxiliaries

문홍식, 고동수

초록

쉽게 얻을 수 있는 1,2:5,6-di-O-isopropylidene-D-mannitol (1)로부터 C₂-대칭성 피롤리딘 아미드 (8)을 합성하였다. 벤질 아민과 dimesylated hexitol (4)를 고리화 반응 시키면 트랜스 형태의 C₂-대칭성 피롤리딘 아민(5)가 주생성물로 얻어지나, 이와 함께 이성질화가 일어나 시스 이성질체인 화합물(6)도 생성된다. 피롤리딘 아민 (5,6)을 탈보호된 아민 (7)을 거쳐 아미드 (8,9)로 변형시켜 이를 순수한 형태로 분리하고, 이 C₂-대칭성 피롤리딘 아미드(8)의 광학 순도를 측정하기 위해 Mosher 유도체(13,14)를 합성하였다. ¹H 과 ¹⁹F NMR 실험으로 Mosher 유도체 (13,14)가 단일 물질임이 밝혀졌고, 이로서 피롤리딘 아미드 (8)이 광학적으로 순수한 화합물임을 확인하였다.

Optically pure C₂-symmetric pyrrolidine amides (8) were synthesized from readily available 1,2:5,6-di-O-isopropylidene-D-mannitol (1). Cyclization of dimesylated hexitol (4) with benzyl amine gave an inseparable mixture of C₂-symmetric pyrrolidine amine derivative (5) as a major product, concurring with its cis isomer (6) as a minor product. The pyrrolidine amines (5,6) were converted to separable pyrrolidine amides (8,9) via free amine (7). Optical purity of desired C₂-symmetric pyrrolidine amide (8a) was determined with its Mosher derivatives (13,14) by their ¹H and ¹⁹FNMR spectra.

Keywords:C₂-Symmetric Pyrrolidine;Mosher Derivatives;Optical Purity

[References]

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[1] Whitesell JK, Felman SW, J. Org. Chem., 45, 755 (1980)

[2] Short RP, Kennedy RM, Masamune SJ, J. Org. Chem., 54, 1755 (1989)

[3] Bjorkling F, Boutelje J, Hjalmarsson M, Hult K, Norin TJ, J. Chem. Soc.-Chem. Commun., 1024 (1987)

[4] Ito Y, Katsuki T, Yamaguchi M, Tetrahedron Lett., 25, 6015 (1984)

[5] Ikegami S, Katsuki T, Hayama T, Uchiyama T, Tetrahedron, 44, 5333 (1988)

[6] Kawanami Y, Katsuki T, yamaguchi M, Bull. Chem. Soc. Jpn., 60, 4190 (1987)

[7] Kawanami Y, Fujita I, Osawa S, Katsuki T, Chem. Lett., 25, 6015 (1984)

[8] Fuji K, Node M, Naniwa Y, Kawabata T, Tetrahedron Lett., 31, 3175 (1990)

[9] Whitesell JK, Minton MA, Chen KM, J. Org. Chem., 53, 5383 (1988)

[10] Yamamoto Y, Ohmori H, Sawada S, Synlett, 319 (1991)

[11] Whitesell JK, Felman SW, J. Org. Chem., 42, 1663 (1977)

[12] Kawanami Y, Ito Y, Kitagawa T, Tanicuchi Y, Katsuki T, Yamaguchi M, Tetrahedron Lett., 25, 857 (1984)

[13] Takano S, Moriya M, Iwabuchi Y, Ogasawara K, Tetrahedron Lett., 30, 3805 (1989)

[14] Marzi M, Misiti D, Tetrahedron Lett., 30, 6075 (1989)

[15] Watson HA, O'Neal BT, J. Org. Chem., 55, 2950 (1990)

[16] Blackman SW, Baltzly R, J. Org. Chem., 26, 2750 (1965)

[17] Corey EJ, Venkateswarlu A, J. Am. Chem. Soc., 94, 6190 (1972)

[18] Cainelli G, Manescalchi F, Synthesis, 472 (1976)

[19] Collins S, Kuntz BA, Hong Y, J. Org. Chem., 54, 4154 (1989)

[20] Jackman LM, Cotton FA, Dynamic Nuclear Magnetic Resonance Spectroscopy; Academic Press: New York (1975)

[21] Sandstorm J, Dynamic NMR Spectroscopy; Academic Press: New York (1982)