Tandem nitroaldol-dehydration reactions employing the dianion of phenylsulfonylnitromethane(1)
Reaction of phenylsulfonylnitromethane (1) with more than 2 molar equiv of LDA afforded the dilithium salt of phenylsulfonylnitromethane. Condensation of this dilithium salt with unbranched aldehydes occurred readily, but the initial nitroaldols dehydrated to afford unconjugated beta,gamma-unsaturated alpha-nitrosulfones in 52-88% yield. Evidence is presented that the beta,gamma-unsaturated alpha-nitrosulfones can equilibrate with the conjugated alpha,beta-unsaturated alpha-nitrosulfones at neutral pH. The normally disfavored alpha,beta-unsaturated alpha-nitrosulfones have been implicated in the formation of bis(alpha-nitrosulfones), Michael adducts of phenylsulfonylnitromethane. Three diastereomers (1R,2s,3S, 1R,2r,3S, and 1R,3R/1S,3S) have been identified for the bis(alpha-nitrosulfones) obtained in these reactions. In the case of acetaldehyde, condensation with the dilithium salt of phenylsulfonylnitromethane afforded only bis(alpha-nitrosulfones). The main product (three diastereomers) was the bis(alpha-nitrosulfone) derived from Michael addition of phenylsulfonylnitromethane and a minor product was tentatively identified as the bis(alpha-nitrosulfone) derived from dimerization. Also formed in the reaction of propanal with the dilithium salt of phenylsulfonylnitromethane was an unstable beta-amine, the formal conjugate addition product of diisopropylamine to the alpha, beta-unsaturated alpha-nitrosulfone. When tandem nitroaldol/dehydration reactions were carried out in the presence of thiols, the alpha,beta-unsaturated alpha-nitrosulfones were intercepted to provide beta-sulfides, the products of conjugate addition, in 61-83% yield.
Wade
PA
Department of Chemistry, Drexel University, Philadelphia, Pennsylvania 19104, and Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Murray
JK
Shah-Patel
S
Palfey
BA
Carroll
PJ