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

Abstract

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. &gt; 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. &gt;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–D 1 ]‐ 2b .