Synthetic studies on 8-deoxyserratinine type alkaloids. Selective cyclization of the 1,2-cyclohexanediacetaldehyde derivative by intramolecular aldol condensation.

Abstract

In connection with the synthesis of 8-deoxyserratinine type alkaloids, the regioselective cyclization reaction of the 1, 2-cyclohexanediacetaldehyde derivative (6) by intramolecular aldol condensation was investigated. The acetal (5) was stereoselectively prepared by two routes using the Diels-Alder reaction. The first route involved the Diels-Alder reaction of the dienophile (12), obtained from 8 via 9, 10 and 11, with butadiene in the presence of 0.5 eq. AlCl3 and acetalization of the adduct (13) to give 5 in 8% yield from 8. The second route involved conversion of the adduct (15), obtained by the Diels-Alder reaction of 8 with butadiene in the presence of 0.5 eq. BF3·Et2O, into 5 [22% yield based on the consumed dienophile (8)] via 16 and 17. The dialdehyde (6) was obtained from the cis-decalone derivative (5) via 18. Cyclization of 6 using excess morpholine-camphoric acid in dry Et2O-HMPA and subsequent treatment with (EtO)2POCH2CN gave 21, which was suitable for our purpose, and 22 in a 25 : 1 ratio.