Addition of a Reformatsky Reagent to N-Anthracene-9-sulfonyl and Related Imines: Synthesis of Protected β-Amino Acids

Article abstract of DOI:10.1016/S0040-4020(01)81815-9

The Reformatsky reagent tert-butoxycarbonylmethylzinc bromide adds in high yields to N-sulfonylimines, e.g. 1a-1d, derived by condensation of benzaldehyde dimethyl acetal with methanesulfonamide, toluene-4-sulfonamide, 4-(methoxycarbonyl)benzenesulfonamide and sulfamide: the products are protected β-amino acids 2a-2d.N-Deprotection occurs reductively (Na-naphthalene; low yields) for 2b and 2c or hydrolytically (refluxing aq. pyridine; 76percent yield of amino acid 3a after acid hydrolysis of the t-butyl ester) for the sulfamide derivatives 2d.Anthracene-9-sulfonamide (6) is readily available by sulfonation and chlorination of anthracene, and condenses with aldehydes , e.g. in the presence of TiCl4/Et3N, to yield imines 7a-7f, which after addition of tert-butoxycarbonylmethylzinc bromide give protected amino acids 8a-8f; however, 8f cyclizes to the sultam 9 via a spontaneous intramolecular Diels-Alder reaction.Reductive cleavage of the N-anthracene-9-sulfonyl group is much easier than for traditional N-sulfonyl protecting groups, as demonstrated by the deprotection of 8a and 8c using aluminium amalgam.