Screening of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts for the enantioselective aldol reaction of acetone with isatin

M. Kinsella, P.G. Duggan, C.M. Lennon

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

We have screened a range of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts incorporating N-pyridyl and N-quinolinyl groups in the synthetically useful aldol reaction of isatin with acetone. The 'reverse amide' N-pyridyl pyrrolidinylmethyl amide catalysts proved highly catalytically active but gave disappointing enantioselectivities. However, an N-3-pyridyl prolinamide catalyst gave the aldol adduct in high yields and high enantioselectivity with up to 72% ee of the (S)-isomer. Conditions were optimised for this catalyst and in particular an additive screen identified a link between the pKa of the acid additive and the yield and enantioselectivity. An N-arylsulfonamide prolinamide was also identified as a catalyst for this reaction giving the (R)-enantiomer in 68% ee.

Original languageEnglish
Pages (from-to)1423-1433
Number of pages11
JournalTetrahedron Asymmetry
Volume22
Issue number13
DOIs
Publication statusPublished - 15 Jul 2011

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