PHOTOCHEMISTRY OF N-PHTHALOYL ALPHA-AMINO-ACID ESTERS - A NEW APPROACH TO BETA, GAMMA-UNSATURATED ALPHA-AMINO-ACID, DIHYDROBENZAZEPINEDIONE, AND PYRROLIZIDINONE DERIVATIVES

The N-phthaloyl-alpha-amino acid methyl esters of 2-aminobutyric acid (2 a), valine (2 b), norvaline (2 c), tert-leucine (2 d), isoleucine (2 e), allo-isoleucine (2 f), leucine (2 g), methionine (2 h), alanine (2 i), and phenylalanine (2 k) were synthesized in enantiomerically pure form via the N-phthaloyl-alpha-amino acids (1 a - k), and their photochemistry was studied. Except 2 i and 2k, which proved to be photostable, all compounds were converted into three types of products, depending on the substitution pattern: a) isomerization products (derivatives of beta,gamma-unsaturated alpha-amino acids) 3 a, b, c, and e, b) ring expansion products (benzazepinedione esters) 4 a and c, and c) cyclization products (5 d from the tert-leucine derivative 2 d). High diastereoselectivities (d.r. > 95:5) were observed for all reactions except the transformations of the 2-aminobutyric acid derivative 2 a. The absolute configuration of the alpha-stereogenic center was retained during photolysis, as proven for the isodehydrovaline (type a product) 3 b. PCC oxidation (to give 7 b) and hydrogenation afforded 2 b with an optical rotation comparable to the starting material. Treatment of 3 b with an acid or a base led to epimerization (3 b') or isomerization of the C = C bond (6 b), respectively. The diastereomeric dihydrobenzazepinedione esters 4 a, b were formed with d,r. = 33:67 (cis:trans) and in 60% yield during photolysis of 2a. The isoleucine derivative 2 e, however, was converted into the cis isomer 4 a with high diastereoselectivity (d.r. > 95:5), whereas the corresponding allo substrate 2 f was only converted into the trans-isomer 4 b. Ethylene was extruded during irradiation of the latter substrates and during irradiation of the norvaline derivative 2 c, whereas propene extrusion from the leucine derivative 2 g led to the formation of the unsubstituted type b product 4 c. The methionine derivative 1 h was the only N-phthaloylamino acid which did not show photodecarboxylation, instead two zeta-hydrogen abstraction products were formed: the hydroxy acid 9 h and the tetracyclic lactone 10 h. The methionine ester 2 h was only converted into the ring expansion products 11 h, h' presumably by a photo electron transfer step. The chronology of the double hydrogen transfer reaction (gamma- followed by delta-H abstraction, leading to type a products) was determined by using the deuterium labeled compound (+/-)[3-D1]-2b.