Michael Reactions of β-Keto Sulfoxides and β-Keto Sulfones

• Published in: Journal of organic chemistry 1997-09, Vol.62 (19), p.6575-6581
• Main Author: Marco, José L
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9705982

The unprecedented Michael additions of racemic or enantiomerically pure β-keto sulfoxides (1, 6, 10−12) and β-keto sulfones (23, 25, 27, 29, 30) to the highly stabilized Michael acceptors 2, 4, 8, and 21, 31, and 32 are described. The process proceeds efficiently, under very mild reaction conditions:  ethanol, piperidine (catalytic), room temperature. The reaction of the β-keto sulfoxides having the 2-pyridyl ketone moiety, with arylidenemalononitriles (2, 4) and α-cyanocinnamates (8) has given the polyfunctionalized 2-amino-4H-pyran adducts (3, 5, 7, 9), in high yield, with total diastereo- and enantioselectivity. The reaction of 2-pyridyl ketone containing β-keto sulfone 23 with arylidenemalononitrile (2) gave the polyfunctionalized 2-amino-4H-pyran 24, in high yield. Similar β-keto sulfoxides (10−12) or β-keto sulfones (25, 27), lacking the 2-pyridyl ketone moiety, underwent the same reaction, but with lower yields and poor diastereoselection. In some cases, noncyclized intermediates have been detected. The β-keto sulfones 29 and 30 did not react under the same experimental conditions. Simple Michael acceptors such as ethyl acrylate, cinnamonitrile, or methyl vinyl ketone proved also to be reluctant to react with β-keto sulfoxides 1. In summary, the powerful, strong, and particularly efficient stereodirecting properties of the 2-pyridyl ketone moiety embodied in the β-keto sulfoxides 1 and 6 or β-keto sulfone 23 have been observed for the first time. This fact coupled to the apparently critical and necessary influence of the π−π stacking interaction in the approach of reactants is discussed in depth here and used with obvious advantages in important synthetic transformations.