A Formidable Challenge: Catalytic Asymmetric Dichlorination

Abstract

The missing piece: The long-pursued asymmetric catalytic dichlorination reaction has recently been reported (see scheme). The multiple issues faced to develop such an elusive target are discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Catalytic Chemo-, Regio-, and Enantioselective Bromochlorination of Allylic Alcohols

“…Alkene dihalogenation is a classic anti -difunctionalization reaction of carbon–carbon double bonds with few enantioselective variants . Despite impressive recent work in the stereoselective synthesis of vicinal dichlorides and polychlorinated natural products, − no general methods exist for the enantio- and regioselective addition of two halogen atoms across nonconjugated olefins. − Additionally, catalyst control over the regioselective addition of two different halogens (heterodihalogenation or interhalogenation ) to an alkene is unprecedented (Figure A). This lack of a general enantioselective method for alkene dihalogenation represents a significant gap in regio- and stereoselective methodology that remains unsolved, despite the prevalence of chiral bioactive poly- and interhalogenated compounds in nature , and the widespread use of alkyl halides as intermediates in organic synthesis.…”

Organocatalysis as a Safe Practical Method for the Stereospecific Dibromination of Unsaturated Compounds

“…Asymmetric olefin dihalogenation remains a challenge. Nicolaou et al developed a pioneering enantioselective dichlorination of allylic alcohols catalyzed by a dimeric cinchona alkaloid to yield enantio-enriched trans -dichlorinated product . The method requires preparation of aryl iododichlorides from PhI and hazardous Cl 2 gas.…”

Controlling chlorination versus cyclosulfonation of cis-diols using ionic liquid solvents

“…The reactivity of the cis diol vs. that of the trans diol towards thionyl and sulfuryl chloride and the associated dichlorination reactions were not investigated. Due to the chirality introduced by the monooxygenated sulfur atom, the cyclic sulfite (11) is present in solution as a racemic mixture of compounds having the following chirality: RRS, RRR, SRS and SRR (+4 enantiomers). It is likely that stereochemical factors combined to that of the IL/base will have an effect on the products' distribution.…”

“…In most reports, diols are reacted with PCl 3 , PCl 5 or HCl at high temperatures, or alkenes are reacted with dihalogens. 11,12 Alternatively, dichlorination can be achieved in 2 steps via a ditosyl intermediate in average yields as described by Leiris et al 13 In ILs, Villorbina et al described dichlorination reactions in a hydrophilic IL, 12 using AlCl 3 Á6H 2 O in the presence of carboxylic acids at temperatures over 100 1C, whereby starting from glycerol, chlorohydrin esters were prepared as a mixture of 1,2-and 1,3-dichloro derivatives with varying success. The variability in yields and product outcomes that are observed across the range of dichlorination reactions, both in organic and IL solvents, needs to be addressed if improved reaction conditions and scale-up protocols are to be effectively implemented.…”