Annelative Ring Expansion via Intramolecular Photocycloaddition of α,β-Unsaturated γ-Lactones and Reductive Cleavage: Synthesis of Hydrocyclopentacyclooctene-5-carboxylates

Article abstract of DOI:10.1021/jo00140a001

A new approach for annelative, two-carbon ring expansion via intramolecular <2 + 2> photocycloaddition of fused α,β-unsaturated γ-lactones onto γ-alkenyl side chains, oxidation to γ-keto acids, and reductive cleavage of the cyclobutane ring is applied to the synthesis of hydrocyclopentacyclooctene-5-carboxylates. α,β-Unsaturated γ-lactones fused to cyclohexene and bearing 3-butenyl (4), 3-pentenyl (5), 3,4-pentadienyl (7), and 4-chloro-3-pentenyl (9) side chains in the γ-positions were prepared (Schemes II and III) either by addition of Grignard reagents to 2-bromo-1-cyclohexenecarboxaldehyde (1) followed by lihiation and carboxylation (method A) or by lithiation of N,N-dimethyl-2-bromo-1-cyclohexenecarboxamide (6) and subsequent addition to aldehydes (method B).Irradiation of the four unsaturated lactones effected mainly the fused mode of intramolecular <2 + 2> cycloaddition, forming 2-hydroxytricyclo<5.4.0.0>undecane-7-carboxylic acid lactones (13-15 and 17).Oxidation of the sodium salts of the hydroxy acids with sodium ruthenate and esterification afforded a series of tricyclic γ-keto acids (20a and 21a) and esters (20b and 22).Reduction of the keto acids or esters with lithium in ammonia lead to reductive scission of the cyclobutane ring and formation of methyl decahydro- and octahydro-1-oxo-1H-cyclopentacyclooctene-5-carboxylates (24-26).