Synlett 2017; 28(11): 1282-1286
DOI: 10.1055/s-0036-1588964
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© Georg Thieme Verlag Stuttgart · New York

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A Stereoselective Tripeptide Catalyst for Conjugate Addition Reactions of Acetophenones to Dicyanoolefins

Tobias Schnitzer
ETH Zürich, Laboratory for Organic Chemistry, D-CHAB, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland   Email: Helma.Wennemers@org.chem.ethz.ch
,
Helma Wennemers*
ETH Zürich, Laboratory for Organic Chemistry, D-CHAB, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland   Email: Helma.Wennemers@org.chem.ethz.ch
› Author Affiliations
Further Information

Publication History

Received: 13 January 2017

Accepted after revision: 14 February 2017

Publication Date:
10 March 2017 (online)


Abstract

Peptides of the type H-Pro-Pro-Xaa-NH2 were evaluated as catalysts for conjugate addition reactions of acetophenones to cyanoolefins. Tripeptide H-d-Pro-Pro-Glu-NH2 with a carboxylic acid moiety in the side chain of Xaa was identified as a catalyst that provides γ,γ-dicyanoacetophenones in yields of up to 90% and stereoselectivies of up to 88:12 er.

Supporting Information

 
  • References and Notes

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  • 15 The peptide catalyst B (0.2 equiv, 20 μmol) was dissolved in MeOH (400 μL). The acetophenone 1 (5 equiv, 500 μmol) and dicyanostyrene 2 (1 equiv, 100 μmol) were added, and the reaction mixture was stirred for 3 d. The reaction mixture was subjected to flash chromatography (hexane–EtOAc, 20:1 to 4:1) to isolate the product after removal of all volatiles under reduced pressure. (S)-2-(3-Oxo-1,3-diphenylpropyl)malononitrile (Table 2, Entry 1) 1H NMR (300 MHz, CDCl3): δ = 8.01–7.92 (m, 2 H), 7.71–7.58 (m, 1 H), 7.51 (dd, J = 8.3, 6.9 Hz, 2 H), 7.41 (s, 3 H), 4.63 (d, J = 5.0 Hz, 1 H), 3.95 (dt, J = 8.2, 5.3 Hz, 1 H), 3.75–3.56 (m, 2 H).