Concise syntheses of the natural products cavicularin (ten steps) and riccardin C (seven steps) are reported. Key features of the new synthetic route are a convergent strategy to assemble acyclic precursors and a sequence of regioselective reduction and halogenation steps to facilitate Wittig macrocyclisation and transannular ring contraction reactions.
Bridged bicyclic sulfide 1 was originally found to provide high levels of asymmetric induction in sulfur ylide-mediated epoxidations. This sulfide possesses chirality in the [2.2.1] thioether moiety and the [2.2.1] camphor-derived carbocyclic moiety. To determine whether the optimal sulfide had been used, a diastereomer of sulfide 1 in which the stereochemistry of the [2.2.1] carbocycle was reversed (sulfide 5) was prepared and studied as an epoxidation catalyst. This diastereomer gave considerably lower levels of asymmetric induction than the original sulfide 1. From computational and x-ray studies it was found that sulfide 5 gave rise to a more hindered ylide, which reacted more reversibly with aldehydes leading to lower enantioselectivity. Conditions that reduced reversibility were also tested and high enantioselectivities were returned for sulfide 5 (similar to sulfide 1). The implications for the synthesis of chiral sulfides for asymmetric epoxidations are discussed.T he reaction of sulfur ylides with carbonyl compounds to give epoxides (1-8) provides a complementary method with oxidation of alkenes (9-12) for the preparation of these valuable synthetic intermediates. Although sulfur ylide reactions have traditionally operated with stoichiometric amounts of sulfonium salts, we have recently reported a user-friendly, catalytic, and asymmetric process for epoxidation of carbonyl compounds that operated under neutral conditions by using tosylhydrazone sodium salts as diazocompound precursors and substoichiometric amounts (5 mol% in many cases) of chiral sulfide 1 and metal catalyst (Scheme 1) (13-16). This chiral sulfide could be recovered in high yield and reused without any loss of asymmetric induction. A broad range of aldehydes, including aromatic, aliphatic, and certain ␣,-unsaturated aldehydes, could be converted into the corresponding epoxides in generally high yield with high levels of enantioselectivity and diastereoselectivity (17). Sulfide 1 could also be used in a stoichiometric variant of this process, which allows access to epoxides that are difficult to form using the catalytic protocol (18).We have recently proposed a model to explain the high enantioselectivity in this system based on both experimental and computational data (Scheme 2) (19). The high enantioselectivity observed resulted from ylide 2A being strongly favored over 2B because of steric interactions between the ylide substituent and methylene unit of the [2.2.1] bicycle, and the high face selectivity in reaction of ylide conformer 2A was due to the camphor moiety effectively blocking attack from the si face. Based on this model, the camphor moiety was simply acting as a sterically large blocking group. But was it? If that was simply its role, similar levels of enantioselectivity should result from the diastereomer 5 where the carbonyl group is placed on the right of the [2.2.1] carbocycle (Fig. 1). ‡ In contrast, if the current model is too simplistic and the carbonyl group of the camphor skeleton does play a subtle role in contro...
A concise approach to the cephalotaxine CDE ring skeleton based on the intramolecular formal [5 + 2] photocycloaddition of cyclopentenyl-substituted maleimides is described. An investigation of the diastereoselectivity afforded by various protected alkoxy groups demonstrated that the best selectivity (3.5:1) was afforded by the free hydroxyl group, strongly suggesting a hydrogen-bonded excited state. Reaction: see text.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.