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Catalytic, asymmetric Mannich-type reactions of N-acylimino esters: reactivity, diastereo- and enantioselectivity, and application to synthesis of N-acylated amino acid derivatives.
J Am Chem Soc. 2003 Mar 05; 125(9):2507-15.JA

Abstract

In the presence of a catalytic amount of Cu(OTf)(2)-chiral diamine 3e complex, N-acylimino esters reacted with silyl enol ethers to afford the corresponding Mannich-type adducts in high yields with high enantioselectivities. A wide variety of silyl enol ethers derived from ketones, as well as esters and thioesters, reacted smoothly. In the reactions of alpha-substituted silyl enol ethers (alpha-methyl or benzyloxy), the desired syn-adducts were obtained in high yields with high diastereo- and enantioselectivities. Several intermediates for the synthesis of biologically important compounds were prepared using this novel catalytic asymmetric Mannich-type reaction, and at the same time, absolute and relative stereochemical assignments were made. In addition, it has been revealed that alkyl vinyl ethers reacted with N-acylimino esters in the presence of a catalytic amount of the Cu(II) catalyst to give the corresponding Mannich-type adducts in high yields with high enantioselectivities. This is the first example of catalytic asymmetric Mannich-type reactions with alkyl vinyl ethers. The reaction mechanism, structure of chiral catalyst-electrophile complexes, and transition states of these catalytic asymmetric reactions were assumed based on X-ray crystallographic analysis of the Cu(II)-chiral amine complex, PM3 calculations, and FT-IR analyses, etc. Finally, (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12, 1), a new inhibitor of ceramide trafficking from endoplasmic reticulum to the site of sphingomyerin (SM) synthesis, has been synthesized efficiently using the present Mannich-type reaction as a key step. The synthesis involved three steps (two-pot), and total yield was 82.9%.

Authors+Show Affiliations

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyou-ku, Tokyo 113-0033, Japan. skobayas@mol.f.u-tokyo.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12603138

Citation

Kobayashi, Shū, et al. "Catalytic, Asymmetric Mannich-type Reactions of N-acylimino Esters: Reactivity, Diastereo- and Enantioselectivity, and Application to Synthesis of N-acylated Amino Acid Derivatives." Journal of the American Chemical Society, vol. 125, no. 9, 2003, pp. 2507-15.
Kobayashi S, Matsubara R, Nakamura Y, et al. Catalytic, asymmetric Mannich-type reactions of N-acylimino esters: reactivity, diastereo- and enantioselectivity, and application to synthesis of N-acylated amino acid derivatives. J Am Chem Soc. 2003;125(9):2507-15.
Kobayashi, S., Matsubara, R., Nakamura, Y., Kitagawa, H., & Sugiura, M. (2003). Catalytic, asymmetric Mannich-type reactions of N-acylimino esters: reactivity, diastereo- and enantioselectivity, and application to synthesis of N-acylated amino acid derivatives. Journal of the American Chemical Society, 125(9), 2507-15.
Kobayashi S, et al. Catalytic, Asymmetric Mannich-type Reactions of N-acylimino Esters: Reactivity, Diastereo- and Enantioselectivity, and Application to Synthesis of N-acylated Amino Acid Derivatives. J Am Chem Soc. 2003 Mar 5;125(9):2507-15. PubMed PMID: 12603138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Catalytic, asymmetric Mannich-type reactions of N-acylimino esters: reactivity, diastereo- and enantioselectivity, and application to synthesis of N-acylated amino acid derivatives. AU - Kobayashi,Shū, AU - Matsubara,Ryosuke, AU - Nakamura,Yoshitaka, AU - Kitagawa,Hidetoshi, AU - Sugiura,Masaharu, PY - 2003/2/27/pubmed PY - 2003/5/7/medline PY - 2003/2/27/entrez SP - 2507 EP - 15 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 125 IS - 9 N2 - In the presence of a catalytic amount of Cu(OTf)(2)-chiral diamine 3e complex, N-acylimino esters reacted with silyl enol ethers to afford the corresponding Mannich-type adducts in high yields with high enantioselectivities. A wide variety of silyl enol ethers derived from ketones, as well as esters and thioesters, reacted smoothly. In the reactions of alpha-substituted silyl enol ethers (alpha-methyl or benzyloxy), the desired syn-adducts were obtained in high yields with high diastereo- and enantioselectivities. Several intermediates for the synthesis of biologically important compounds were prepared using this novel catalytic asymmetric Mannich-type reaction, and at the same time, absolute and relative stereochemical assignments were made. In addition, it has been revealed that alkyl vinyl ethers reacted with N-acylimino esters in the presence of a catalytic amount of the Cu(II) catalyst to give the corresponding Mannich-type adducts in high yields with high enantioselectivities. This is the first example of catalytic asymmetric Mannich-type reactions with alkyl vinyl ethers. The reaction mechanism, structure of chiral catalyst-electrophile complexes, and transition states of these catalytic asymmetric reactions were assumed based on X-ray crystallographic analysis of the Cu(II)-chiral amine complex, PM3 calculations, and FT-IR analyses, etc. Finally, (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12, 1), a new inhibitor of ceramide trafficking from endoplasmic reticulum to the site of sphingomyerin (SM) synthesis, has been synthesized efficiently using the present Mannich-type reaction as a key step. The synthesis involved three steps (two-pot), and total yield was 82.9%. SN - 0002-7863 UR - https://www.unboundmedicine.com/medline/citation/12603138/Catalytic_asymmetric_Mannich_type_reactions_of_N_acylimino_esters:_reactivity_diastereo__and_enantioselectivity_and_application_to_synthesis_of_N_acylated_amino_acid_derivatives_ L2 - https://doi.org/10.1021/ja0281840 DB - PRIME DP - Unbound Medicine ER -