Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone.

A rhodium-catalyzed intramolecular reductive aldol-type cyclization is described to give ß-hydroxylactones with high diastereoselectivities. The stereoselectivity of this cyclization is highly solvent dependent and can give syn- or anti-ß-hydroxylactones with high diastereoselectivity. This methodology was also applied to the synthesis of a chiral necic acid lactone which is a structural component of the pyrrolizidine alkaloid monocrotaline.

Convergent Synthesis of Fluoroalkenes Using a Dual-Reactive Unit.

Fluoroalkenes have shown importance as a metabolically stable isostere of amide compounds. To expedite the synthesis of diverse fluoroalkenes, we have developed a dual-reactive C2-unit, (Z)-1-boryl-1-fluoro-2-tosyloxyethene, containing nucleophilic and electrophilic moieties. Consecutive palladium-catalyzed cross-coupling reactions of this unit with aryl bromides and aryl boronic acids allow for the convergent synthesis of diverse trans-1,2-diaryl-substituted fluoroethenes in a chemoselective and stereoretentive manner.

Synthesis of (2,2-Diborylvinyl)arenes by Rhodium-Catalyzed Desulfanylative gem-Diborylation of 2-Arylvinyl Sulfides.

An unexpected gem-diborylation of 2-arylvinyl sulfides with bis(pinacolato)diboron proceeded efficiently with a rhodium catalyst. A wide range of (2,2-diborylvinyl)arenes are easily synthesized by this method using readily available reagents, including the alkenyl sulfides, that are prepared from general materials in one step. Mechanistic studies indicate that the reaction proceeds from either of the stereoisomers in a stepwise manner via borylative C-S bond cleavage and subsequent dehydrogenative borylation.

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe.

An effective synthesis for syn-ß-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium-hydride complex (Rh-H) derived from diethylzinc (Et2Zn) and a Rh catalyst was used for the 1,4-reduction of an α,ß-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-ß-lactam. Additionally, the reaction was applied to the synthesis of (±)-ezetimibe, a potent ß-lactamic cholesterol absorption inhibitor.

Diastereoselective Synthesis of syn-ß-Lactams Using Rh-Catalyzed Reductive Mannich-Type Reaction of α,ß-Unsaturated Esters.

The combination of Et2Zn and RhCl(PPh3)3 led to the facile generation of a rhodium-hydride complex (Rh-H) that catalyzed the 1,4-reduction of α,ß-unsaturated esters. The resulting rhodium enolate performed as a Reformatsky-type reagent and reacted with various imines to give syn-ß-lactams in good to excellent yields with high diastereoselectivity.

Asymmetric reductive aldol-type reaction with carbonyl compounds using dialkyl tartrate as a chiral ligand.

An asymmetric reductive aldol-type reaction of α,ß-unsaturated esters with carbonyl compounds using Rh catalyst and Et2Zn was investigated. A chiral zinc complex from α,ß-unsaturated ester was easily generated as the key intermediate from Et2Zn and Wilkinson's catalyst with diisopropyl L-(+)-tartrate to give a variety of enantioenriched ß-hydroxy esters. The reaction was also applied to the intramolecular reductive aldol cyclization.