Tandem nitroaldol-dehydration reactions employing the dianion of phenylsulfonylnitromethane

• Published in: Journal of organic chemistry Vol. 65; no. 23; pp. 7723 - 7730
• Main Authors: Wade, PA, Murray, JK, Shah-Patel, S, Palfey, BA, Carroll, PJ
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 17.11.2000
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ACIDITIES; NITROALKANES; ALDEHYDES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0000170

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.