Indium-Induced Addition of Bromomethylacrylates to Phthaloyl-Protected Amino Aldehydes

Abstract

The indium-mediated reaction of phthaloyl-protected α-amino aldehydes 1-4 with methyl 2-(bromomethyl)acrylate in aqueous solvents was investigated. The homoallyl alcohols 5-8 were formed in 72-89% yields, the anti-isomers being the major diastereoisomers (dr 45:55-18:82). Acid-catalyzed esterification (H2SO4 in Et2O) led to α-methylene γ-butyrolactones 9,10 with yields ranging from 88 to 99%. Conjugate addition of cyanide and thiophenolate led to the addition products with improved selectivities compared with additions to carbamate-protected substrates. During the conjugate addition of a cuprate, a trapping of the intermediate enolate by a phthaloyl carbonyl group occurred, leading to tetracycle 11 in 57% yield. The configuration of all diastereo­isomers could be established by three X-ray crystallographic analyses and by NMR spectroscopy.