Direct catalytic enantio- and diastereoselective aldol reaction of thioamides

Mitsutaka Iwata, Ryo Yazaki, I. Hon Chen, Devarajulu Sureshkumar, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH 3CN) 4]PF 6/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Brønsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides. Strict control of the amount of the hard Lewis base was essential to drive the catalytic cycle efficiently with a minimized retro-aldol pathway, affording syn-aldol products with high stereoselectivity. Divergent transformation of the thioamide functionality is an obvious merit of the present aldol methodology, allowing for a facile transformation of the aldol product into the corresponding aldehyde, ketone, amide, amine, and ketoester. An aldehyde derived from the direct aldol reaction was subjected to a second direct aldol reaction, which proceeded in a catalyst-controlled manner to provide 1,3-diols with high stereoselectivity.(Figure Presented)

Original languageEnglish
Pages (from-to)5554-5560
Number of pages7
JournalJournal of the American Chemical Society
Volume133
Issue number14
DOIs
Publication statusPublished - Apr 13 2011
Externally publishedYes

Fingerprint

Thioamides
Aldehydes
Stereoselectivity
Catalysts
Acids
Lewis Acids
Ketones
Amides
Lewis Bases
Condensation
Amines
phosphine
Oxides
Thioacetamide
3-hydroxybutanal

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Direct catalytic enantio- and diastereoselective aldol reaction of thioamides. / Iwata, Mitsutaka; Yazaki, Ryo; Chen, I. Hon; Sureshkumar, Devarajulu; Kumagai, Naoya; Shibasaki, Masakatsu.

In: Journal of the American Chemical Society, Vol. 133, No. 14, 13.04.2011, p. 5554-5560.

Research output: Contribution to journalArticle

Iwata, Mitsutaka ; Yazaki, Ryo ; Chen, I. Hon ; Sureshkumar, Devarajulu ; Kumagai, Naoya ; Shibasaki, Masakatsu. / Direct catalytic enantio- and diastereoselective aldol reaction of thioamides. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 14. pp. 5554-5560.
@article{4fd3e42ac11540f29810934e83e786c2,
title = "Direct catalytic enantio- and diastereoselective aldol reaction of thioamides",
abstract = "A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Br{\o}nsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH 3CN) 4]PF 6/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Br{\o}nsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides. Strict control of the amount of the hard Lewis base was essential to drive the catalytic cycle efficiently with a minimized retro-aldol pathway, affording syn-aldol products with high stereoselectivity. Divergent transformation of the thioamide functionality is an obvious merit of the present aldol methodology, allowing for a facile transformation of the aldol product into the corresponding aldehyde, ketone, amide, amine, and ketoester. An aldehyde derived from the direct aldol reaction was subjected to a second direct aldol reaction, which proceeded in a catalyst-controlled manner to provide 1,3-diols with high stereoselectivity.(Figure Presented)",
author = "Mitsutaka Iwata and Ryo Yazaki and Chen, {I. Hon} and Devarajulu Sureshkumar and Naoya Kumagai and Masakatsu Shibasaki",
year = "2011",
month = "4",
day = "13",
doi = "10.1021/ja200250p",
language = "English",
volume = "133",
pages = "5554--5560",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "14",

}

TY - JOUR

T1 - Direct catalytic enantio- and diastereoselective aldol reaction of thioamides

AU - Iwata, Mitsutaka

AU - Yazaki, Ryo

AU - Chen, I. Hon

AU - Sureshkumar, Devarajulu

AU - Kumagai, Naoya

AU - Shibasaki, Masakatsu

PY - 2011/4/13

Y1 - 2011/4/13

N2 - A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH 3CN) 4]PF 6/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Brønsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides. Strict control of the amount of the hard Lewis base was essential to drive the catalytic cycle efficiently with a minimized retro-aldol pathway, affording syn-aldol products with high stereoselectivity. Divergent transformation of the thioamide functionality is an obvious merit of the present aldol methodology, allowing for a facile transformation of the aldol product into the corresponding aldehyde, ketone, amide, amine, and ketoester. An aldehyde derived from the direct aldol reaction was subjected to a second direct aldol reaction, which proceeded in a catalyst-controlled manner to provide 1,3-diols with high stereoselectivity.(Figure Presented)

AB - A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH 3CN) 4]PF 6/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Brønsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides. Strict control of the amount of the hard Lewis base was essential to drive the catalytic cycle efficiently with a minimized retro-aldol pathway, affording syn-aldol products with high stereoselectivity. Divergent transformation of the thioamide functionality is an obvious merit of the present aldol methodology, allowing for a facile transformation of the aldol product into the corresponding aldehyde, ketone, amide, amine, and ketoester. An aldehyde derived from the direct aldol reaction was subjected to a second direct aldol reaction, which proceeded in a catalyst-controlled manner to provide 1,3-diols with high stereoselectivity.(Figure Presented)

UR - http://www.scopus.com/inward/record.url?scp=79953701354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953701354&partnerID=8YFLogxK

U2 - 10.1021/ja200250p

DO - 10.1021/ja200250p

M3 - Article

C2 - 21417332

AN - SCOPUS:79953701354

VL - 133

SP - 5554

EP - 5560

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 14

ER -