Enantioselective Halofunctionalization of Alkenes

Abstract

Asymmetric functionalization of alkenes is a powerful transformation to access a variety of chiral molecules. This chapter discusses strategies for the reagent‐controlled enantioselective chloro‐, bromo‐, or iodofunctionalization of alkene substrates. The resulting products from the vicinal stereoselective halofunctionalization of alkenes provide access to chiral heterocycles, synthetic building blocks, and key intermediates for the syntheses of natural products. A historical perspective with regards to both reaction development as well as the numerous mechanistic challenges for this class of transformations are discussed. The accompanying tables are a glossary of reactions that are organized by the halogen electrophile and further classified by the identity of the nucleophile. Representative protocols as well as application of asymmetric alkene halofunctionalization in kinetic resolutions, desymmetrizations, and total synthesis are also presented.

Chiral sulfide and selenide catalysts for asymmetric halocyclizations and related reactions

“…9 Herein, we summarize recent advances in chiral sulfide organocatalysis for asymmetric halocyclizations and halogenations. 10 The related chiral selenide organocatalysts for asymmetric halocyclizations are also introduced.…”

Asymmetric Intermolecular Iodinative Difunctionalization of Allylic Sulfonamides Enabled by Organosulfide Catalysis: Modular Entry to Iodinated Chiral Molecules

“…As an important branch in the field of electrophilic halogenation, electrophilic iodofunctionalization of alkenes has attracted special attention in the past decades because it possesses unique synthetic advantages. − On the one hand, this powerful transformation offers direct access to iodine-functionalized molecules by simultaneously incorporating iodine and another functional group into the double bond of the parent alkenes under mild conditions. It is known that iodine-containing molecules are of great importance because not only their structural moieties are present in bioactive molecules such as marine natural products (Scheme a) but also they can be manipulated very easily.…”

“…The obtained products could be easily transformed into various valuable chiral molecules such as α-aryl ketones, chiral secondary amines, and aziridines. This work represents the first example of organocatalytic enantioselective intermolecular iodinative difunctionalization of alkenes , and provides a convenient route for modular entry to iodine-functionalized chiral molecules. Importantly, it also exhibits the unique nature of electrophilic iodine-promoted transformation of alkenes and the advantages of the control of electrophilic iodine by chiral sulfide, which offer a basis for the design of new iodination reactions.…”

Enantioselective iodolactonization to prepare ε-lactone rings using hypervalent iodine

“…Broad interest in alkene haloesterification reactions was reignited with the advent of enantioselective variants, 6 but the intramolecular cyclizations are restricted to small ring-sizes that form β-, γ-, and δ-lactones. 7,8 The synthetic impact of these functionalizations is evident when considering ring-opening reactions of the enantioenriched lactone products that furnish, for example, enantioenriched epoxides or dihydroxy acids from unsaturated acids (Fig. 1); enantioselective carbon–oxygen bond formation with an unactivated alkene is achieved, formally, in two steps ( i.e.…”