A Direct Aldol Addition of Simple Thioesters Employing Soft Enolization

Abstract

Simple thioesters undergo direct aldol addition to aldehydes in the presence of magnesium bromide-diethyl ether and N,N-diisopropylethylamine using untreated, reagent grade dichloromethane under atmospheric conditions. The reactions proceed extremely rapidly and in excellent yield.

Key words

direct aldol reaction - ester - magnesium - thioester - thiol

References

• 1a Modern Aldol Reactions   Mahrwald R. Wiley-VCH; Weinheim: 2004. 
• 1b Carreira EM. In Compre-hensive Asymmetric Catalysis   Vol. 3:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Heidelberg: 1999. 
• 2a Evans DA. Tedrow JS. Shaw JT. Downey CW. J. Am. Chem. Soc.  2002,  124:  392 
• 2b Evans DA. Downey CW. Shaw JT. Tedrow JS. Org. Lett.  2002,  4:  1127 
• 2c Evans DA. Downey CW. Hubbs JL. J. Am. Chem. Soc.  2003,  125:  8706 
• 2d Lalic G. Aloise AD. Shair MD. J. Am. Chem. Soc.  2003,  125:  2852 
• 2e Magdziak D. Lalic G. Lee HM. Fortner KC. Aloise AD. Shair MD. J. Am. Chem. Soc.  2005,  127:  7284 
• 3 Yost JM. Zhou G. Coltart DM. Org. Lett.  2006,  8:  1503 
• 4 The pK _a of the thioester α-proton has been reported to be 2 units less than that of a corresponding ester, see: Bordwell FG. Fried HE. J. Org. Chem.  1991,  56:  4218 

5

All thioesters used in this work, with the exception of commercially available 7, 10, and 11, were prepared via acylation of the corresponding commercially available thiols.

6

Aldrich ACS reagent grade, ≥99.5%.