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 (H2 SO4 in Et2 O) 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.
Key Words
allylation - indium - Michael additions - α-amino aldehydes - α-methylene γ-butyrolactones
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