Organocatalytic Asymmetric -Halogenation of 1,3-Dicarbonyl Compounds

摘要

The enantioselective construction of carbon-halogen stereogenicity belongs to the topical area of current asymmetric catalysis[1] by virtue of the fact that halogen atoms attached to a chiral stereocenter can serve as a linchpin for further stereospecific manipulations.[2] Moreover, optically active halogen-containing compounds are increasingly important targets in drug discovery and material sciences.[3] Despite this, different efficient catalytic asymmetric halogenation strategies have been developed only in the last few years.[1a],[b] To date, the most notable advances have been made in the -halogenation of carbonyl compounds by using mild and stable sources of electrophilic halogens. All the reported asymmetric catalytic methodologies, from the first Lewis acid catalyzed asymmetric -fluorination of -keto esters reported by Hintermann and Togni,[4] to several highly practical metal-free (organocatalytic)[5] approaches, involve the transient formation of an enolate (enol) that can be halogenated to generate the desired product. The crucial enolization process can be efficiently promoted through 1) coordination of chiral Lewis acids with 1,3-dicarbonyl compounds;[6] 2) formation of an enamine intermediate derived from the reaction between a secondary chiral amine and enolizable aldehydes and ketones;[7] 3) attack of a chiral nucleophile on a ketene intermediate to generate a zwitterionic enolate;[8] and 4) ionic association of a phase-transfer catalyst with the enolate.[9]