J. Christopher McWilliams

Asymmetric synthesis of α-amino acid derivatives via an electrophilic amination of chiral amide cuprates with Li t-butyl-N-tosyloxycarbamate

Abstract The utility of lithium t-butyl-N-tosyloxycarbamate (LiBTOC) as a (+)NHBOC synthon in highly diastereoselective reactions with chiral cis-aminoindanol derived amide cuprates is described. The diastereoselectivities of these reactions ranged from 96% to greater than 99%. The subsequent transformation of these adducts to α-amino acids is also described.

Thiol addition to aryl propargyl alcohols under mild conditions: an accelerating neighboring group effect

Abstract Aryl alkynols provide a convenient entry into α-hydroxyketones via thiol addition followed by hydrolysis. Thiols have been added to several non-activated alkynes under mild, basic conditions. A coordinating functional group in close proximity to the triple bond facilitates this reaction.

Catalytic enantioselective hydrogenation of N-alkoxycarbonyl hydrazones: a practical synthesis of chiral hydrazines.

An enantioselective hydrogenation of hydrazones catalyzed by Rh complexes (Rh-Josiphos or Rh-Taniaphos) has been developed. The protocol can be applied to hydrazones with three different protective groups (Boc, Cbz, and methoxycarbonyl), allowing for selective deprotection and further elaboration of the hydrazine products in the presence of other functional groups.

Asymmetric Synthesis of Vabicaserin via Oxidative Multicomponent Annulation and Asymmetric Hydrogenation of a 3,4-Substituted Quinolinium Salt

An efficient, asymmetric synthesis of the 5-HT2C agonist vabicaserin in four chemical steps and 54% overall yield from commercially available benzodiazepine was achieved. The synthesis was highlighted by a novel oxidative, multicomponent reaction to affect the quinolinium ring assembly in one step followed by an unprecedented asymmetric hydrogenation of a 3,4-substituted quinolinium salt.