6.20 C–X Bond Formation: α-Halogenation of Carbonyl Compounds

A Unified and Desymmetric Approach to Chiral Tertiary Alkyl Halides

“…Nevertheless, the difficulties associated with the location, identification, and collection of related marine plants have often impeded their pharmaceutical application. Conventional methods to synthesize these challenging motifs, especially chiral tertiary halides, often hinge on the enantioselective carbon–halogen bond formation of planar substrates or intermediates , (Figure A, pathway a), such as olefins, aldehydes, enolates, and metal allyl complexes, or carbon–carbon bond formation of halogen-bearing nucleophiles (pathway b). While a wide array of metal- and organocatalysts have found success in these asymmetric bond-forming reactions, synthesis of chiral tertiary alkyl halides via desymmetric functional group interconversion (FGI) of substrates with a preformed and prochiral tetrasubstituted carbon (pathway c) is underdeveloped in comparison.…”

Development of Ketone-Based Brominating Agents (KBA) for the Practical Asymmetric α-Bromination of Aldehydes Catalyzed by Tritylpyrrolidine

“…The α-bromocarbonyl compounds can serve as versatile synthetic intermediates in the formation of carbon–carbon bonds as well as various carbon–heteroatom bonds because of the high leaving group ability of the bromine atom . Asymmetric enamine catalysis is one of the powerful organocatalytic strategies for the stereoselective α-halogenation of aldehydes and ketones. − In this area, a number of catalytic asymmetric α-fluorinations and α-chlorinations of carbonyl compounds have been developed to date. − On the other hand, only a few asymmetric α-brominations have been investigated despite the high synthetic utility of the products . In the previous attempts for α-bromination of aldehydes, a high catalyst loading of ( R , R )- 2 or ( S )- 3 (20 mol %) was required, probably due to undesired side reactions such as bromination of the amine catalyst (Scheme a). , We have also developed the asymmetric α-bromination of aldehydes catalyzed by the binaphthyl-based secondary amine ( S )- 4 , in which the amount of catalyst could be reduced, since the introduction of steric bulkiness into the catalyst circumvents the catalyst deactivation by the brominating agent .…”