Acetal-protected carbonyls

The successful use of acetal-protected carbonyl groups as iminium ion terminators for the construction of alkaloids is typified by Heathcock and coworkers syntheses of Lycopodium alkaloids to wit, lyco-podine and lycodine (Figure 2). A model cyclization that constructs the a-, b- and c-ring nuclei of the Lycopodium alkaloids is shown in equation (3). Treatment of diacetal (17) (a 1 1 diastereomeric mixture at C-2) with 1.3 equiv. of 3 M hydrochloric acid in methanol at room temperature for 2 d gave a single tricycle (18) in 66% yield. The authors advance that only one of the diastereomeric iminium ions will cy-clize however, enolization allows equilibration of these intermediates (Scheme 11). Thus, while dia-stereomer (19) can readily cyclize, (20) has no low energy cyclization pathway available, and must epimerize prior to cyclization. Corroborative support for this argument is found in the fact that the separated diastereomers of a related system cyclize to the same extent. ... 

Thienyl-lithium derivatives prepared through halogen-metal exchange and containing acetal-protected carbonyl groups have been used in the synthesis of di- and tri-formyl derivatives of thiophen, t-butoxy-sub-stituted thiophen aldehydes, and formylacetylthiophens. Symmetrical thienyl-substituted ketones have been obtained from thienyl-lithium derivatives and carbamates. " Mixed heterocyclic carbinols have been obtained through the reaction of thienyl-lithium derivatives with heterocyclic aldehydes. Thienyl-lithium derivatives react with cyclohexanone, and various phenylthiophens have been made by aromatization of the intermediate cyclohexenyl derivative. The reaction of thienyl-lithium derivatives with NN-dimethylacetamide, which has been used for the synthesis of... 

Selective reduction of a benzene ring (W. Grimme, 1970) or a C C double bond (J.E. Cole, 1962) in the presence of protected carbonyl groups (acetals or enol ethers) has been achieved by Birch reduction. Selective reduction of the C—C double bond of an a,ft-unsaturated ketone in the presence of a benzene ring is also possible in aprotic solution, because the benzene ring is redueed only very slowly in the absence of a proton donor (D. Caine, 1976). 

---