ADDITION OF A REFORMATSKY REAGENT TO N-ANTHRACENE-9-SULFONYL AND RELATED IMINES - SYNTHESIS OF PROTECTED BETA-AMINO ACIDS

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 beta-amino acids 2a-2d. N-Deprotection occurs reductively (Na-naphthalene; low yields) for 2b and 2c or hydrolytically (refluxing aq. pyridine; 76% 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 [RCHO; R = Ph, 4-FC6H4, 4-MeOC(6)H(4), 4-NCC6H4, 2-furyl, (E)-styryl], e.g. in the presence of TiCl4/Et(3)N, 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.