General Principles of Diastereoselective Reactions:Diastereoselectivity via Substrate-Directable Reactions (Internal Delivery) and Heterocyclizations

Mulzer, Johann

Comprehensive Chirality 2012, 2, 45-64.

Diastereoselective additions to unsaturated carbons may be induced by precomplexation of the reagent to polar groups in the substrate by hydrogen bridging and metal complexes (internal delivery). These additions are syn to the steering group and may attack the more hindered face of the sp² carbon. The phenomenon occurs in acyclic and cyclic systems alike (substrate-directable reactions) and is extremely valuable in view of the predictability of the stereochemical course and the magnitude of the induction. For instance, by means of substrate-directable reactions, olefinic double bonds may be epoxidized, cyclopropanated, hydrogenated, hydroformylated, or undergo cycloadditions, whereas carbonyl groups are reduced by internal delivery of hydrogen. Similarly, reagents may add to olefinic units in the substrate reversibly, and the reaction is terminated by the intramolecular intervention of a nucleophile (heterocyclization). This process effects heterocyclic ring closure under delivery of an additional functional group (e.g., halolactonization, etc.).