Photochemistry of N ‐Phthaloyl α‐Amino Acid Esters: A New Approach to β,γ‐Unsaturated α‐Amino Acid, Dihydrobenzazepinedione, and Pyrrolizidinone Derivatives

Abstract

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