Highly Regioselective and Diastereoselective Photooxygenation of α-Cyclogeranyl Derivatives

Abstract

Methylene blue-sensitized photooxygenation of several a-cyclogeranyl derivatives affords the exocyclic allylic hydroperoxides in 94-99% regioselectivity, while the diastereoselectivity varies from 50-97% de in favor of the cis isomer, depending on the substituents. By contrast, the ene reaction with N-phenyltriazolinedione affords significantly different regioselectivity and diastereoselectivity.The often fascinating regiochemistry and diastereoselection in the ene reaction of singlet oxygen ( 1 O 2 ) with olefins 1 provides an attractive methodology for their selective oxyfunctionalization. 2 Recently, the photooxygenation of alkenes confined in organized media, such as zeolite Y, 3 has gained significant attention due to the remarkable changes in product selectivity compared to the analogous reaction in solution. It has been recognized that for the 1 O 2 ene reactions, steric and electronic interactions contribute significantly to the stability of the product forming transition states. For example, 4 a 1 O 2 -hydroxy steering effect in combination with 1,3-allylic strain (steric effects) lead to remarkable threo diastereoselectivity in the photooxygenation of chiral allylic alcohols, while by contrast, for the analogous chiral allylic chlorides, repulsive 1 O 2 -halide atom interactions and 1,3-allylic strain as well lead to a highly erythro diastereoselective ene reaction. In addition, a highly diastereoselective and regioselective ene reaction of 1 O 2 with chiral cyclohexadienes has been reported, 5 where steric repulsions and electronic factors control substantially the product diastereoselectivity.In this communication we report a highly regioselective and diastereoselective ene reaction of 1 O 2 with a-cyclogeraniol (1) and its derivatives. Methylene blue-sensitized photooxygenation of 1 in CH 2 Cl 2 affords essentially one out of the three possible regioisomers with >97% cis-diastereoselectivity (1a), as proved by NOE experiments (Scheme 1). Irradiation of the allylic hydrogen atom next to the -OOH functionality in 1a resulted in signal enhancement of the second tertiary allylic hydrogen atom, indicative of a cis stereochemical arrangement. (1) To explore further this fascinating selectivity, we prepared the a-cyclogeranyl derivatives 2-7 6 and performed their photooxygenation reaction. The results are presented in Table 1. 7 The allylic hydroperoxides were purified and characterized after flash column chromatography of the crude reaction mixture. Alternatively, PPh 3 was added to the crude reaction mixture immediately after the photooxygenation and the corresponding allylic alcohols were subsequently purified. Scheme 1 Photooxygenation of a-cyclogeraniolThe reaction was >97% regioselective with exclusive formation of the ene adduct resulting from hydrogen atom abstraction from the allylic methyl group. The only exception was benzyl ether 5 who gave 5% of the tetrasubstituted allylic hydroperoxide formed by abstraction of the tertiary allylic hydrogen atom. The diastereoselectivity varied from 50-97% de,...