Domino Elimination/Nucleophilic Addition in the Synthesis of Chiral Pyrrolidines

Abstract

Polyhydroxylated pyrrolidines have been synthesized in a one-pot procedure by the addition of an organometallic reagent to isoxazolidines obtained by a 1,3-dipolar cycloaddition between nitrones and vinylsulfones. This method highlights sulfone reactivity and provides an easy approach for the preparation of chiral pyrrolidines using cyclic imines as key intermediates.

Reactions of Allylmagnesium Reagents with Carbonyl Compounds and Compounds with C═N Double Bonds: Their Diastereoselectivities Generally Cannot Be Analyzed Using the Felkin–Anh and Chelation-Control Models

“…Additions to a fused bicyclic five-membered-ring imine were also highly diastereoselective (Scheme ). These reactions required an excess of the organomagnesium reagent to generate the imine. Formation of the sulfonyl-stabilized carbanion caused a ring-opening reaction to generate the imine 955 (Scheme ).…”

Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry

“…More recently, Flores et al proposed an original synthesis of hydroxylamines 210 by the addition of an organometallic reagent to isoxazolidines 207 bearing a sulfone function on C 4 (Scheme ). They attempted moderate to good yields (35–78%) with various organo-Li reagents ( n -BuLi, MeLi, ...) and organometallics (PhMgBr, BnMgCl, ...), the best result being obtained with MeMgBr (74–78%).…”

“…Miller's research team showed that In(OTf) 3 in various alcoholic media also induced an efficient isoxazolidine ring opening to afford anti-hydroxylamides 206 (R 1 = Bn, OtBu and R 2 = Me, iPr, tBu) with good to excellent regio-and stereoselectivity. 225,226 More recently, Flores et al 227 proposed an original synthesis of hydroxylamines 210 by the addition of an organometallic reagent to isoxazolidines 207 bearing a sulfone function on C 4 (Scheme 69). They attempted moderate to good yields (35− 78%) with various organo-Li reagents (n-BuLi, MeLi, ...) and organometallics (PhMgBr, BnMgCl, ...), the best result being obtained with MeMgBr (74−78%).…”

Crystal structure of (2R*,3aR*)-2-phenylsulfonyl-2,3,3a,4,5,6-hexahydropyrrolo[1,2-b]isoxazole

“…Nitrones have been used in the synthesis of many kinds of isoxazolidines (Falkowska et al, 2015) by 1,3-dipolar cycloaddition of nitrones with sulfones (Flores, García, Garrido, Nieto et al, 2012) and have demonstrate a range of biological activities including antibiotic, gene expression regulation and cancer cell cytotoxicity (Karyakarte et al, 2012). Our research group is interested in the synthesis of isoxazolidines such as the title compound, for application in organic synthesis (Flores et al, 2011a,b;Flores et al, 2013).…”