Halogenation enantioselective bromination

A process of selenocatalytic a-halogenation using NBS has been reported. A catalytic enantioselective bromination of -keto esters has been achieved using a combination of NBS and TiCl2(TADDOLato) complexes as enantioselective catalyst modest enantiomeric excesses were obtained. 

RECENT PROGRESS IN ENANTIOSELECTIVE BROMINATION, CHLORINATION, AND lODINATION 1335 TABLE 43.3. Enantioselective Halogenation of 3-Ketoesters... 

In the field of asymmetric organocatalytic alkylation (see also Section 3.1) impressive examples with enantioselectivity > 99% ee have been reported by the Corey group, the Park and Jew group, and the Maruoka group [15-17]. Different types of catalyst have been used, with amounts of catalyst in the range 0.2 to 10 mol%. High enantioselectivity (99%) has also been achieved for asymmetric halogenation reactions (see also Section 3.4). This has been demonstrated for chlorination and bromination reactions by Lectka and co-workers [18]. 

Organocatalysis has led to the development of new methods for the asymmetric a-halogenation of carbonyl compounds leading to the formation of stereogenic C-X centers. Hence, details of direct enantioselective fluorination, chlorination, and bromination reactions will be presented in the following sections. 

The initial ruthenium(II) catalyst 66 abstracts a halogen (either chlorine or bromine) from the substrate forming a ruthenium(III) species 67. This is followed by pi complexation (68), radical addition (69) and halogen atom transfer to form the desired product (70). Starting from 65a, enantioselectivities of the resulting product 70a ranged from 20 to 40% ee with excellent chemical yields [28]. Reactions with a slightly different substrate bromotrichloromethane (65b) provided 70b in 32% ee, and a poor yield of 26% [29]. 

In 2001, Lectka and co-workers [52] adapted their method for catalytic asymmetric a-halogenation of acid chlorides to include bromination reactions (Scheme 13.24). Through use of the same organocatalyst and shuttle-deprotonation strategy, and a polybromoquinone as the bromine source, the catalytic enantioselective... 

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