CamTHP*OH: a camphor-derived delta-lactol auxiliary for the effective desymmetrization of attached glycinamide residues. Asymmetric synthesis of alpha-amino carbonyl compounds.
Stereoselective allylation of camphor and subsequent terminal hydroformylation affords a new delta-lactol auxiliary (camTHP*OH) on multigram scale. Stereoselective condensation with glycine dimethylamide and Cbz protection affords a camTHP*-desymmetrized glycinamide building block which undergoes efficient and highly diastereoselective metal enolate alkylation reactions. Acid-mediated deprotection affords the N-Cbz-protected alpha-amino amide products which may be converted directly to alpha-amino ketones on treatment with Grignard or organolithium reagents without loss of stereochemical integrity. [reaction: see text]
Dixon
Darren J
DJ
Department of Chemistry, University of Manchester, Manchester M13 9PL, U.K. darren.dixon@man.ac.uk
Horan
Richard A J
RA
Monck
Nathaniel J T
NJ