Enantioselective a-Halogenation of Carbonyl Compounds

Molecules bearing a stereogenic center with a carbon-halogen bond are usefijl intermediates in organic chemistry, with several organocatalytic reactions being reported to perform this task [166]. 

The most extensively studied halogenation process is probably the a-fluorination of carbonyhc compounds, due to the unique properties of the fluorinated compounds [167]. ImidazoMdinones of type 91 (20mol%) could be used to promote the a-fluorination of Unear aldehydes (19a, = H) using N-fluorobenzenesulfon- 

The direct asymmetric a-iodination of linear aldehydes 19a was catalyzed by compound 72e [5mol%, = R = C(C6F )20H], in the presence of benzoic acid 

Although there has been significant development of this type of transformation during the recent past, there are stiU some unreported transformations, such as the a-iodination of ketones. Moreover, improvement of the reaction conditions, especially aiming to reduce catalyst loading and increase catalyst recyclabiUty, would enhance the possibiUties of application of these procedures to large-scale synthesis. 

2 For recent reviews, including also transition-metal catalyzed reactions see 

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A similar catalytic procedure for enantioselective formation of C-Br and C-Cl bonds has been reported recently by the Lectka group [83]. The concept of this a-halogenation of carbonyl compounds is tandem asymmetric halogenation and esterification (Scheme 3.28). Inexpensive acyl halides, 74, are used as starting... 

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. 

Reviews cover transition-metal-catalysed enantioselective a-heterofunctionalization of carbonyl compounds (103 references)," and organocatalysed enantioselective a-hetero-functionalization from 2006 to 2009, demonstrating straightforward syntheses of useful a-amino acids and alcohols, epoxides, 1,2-diols, and a-sulfenylated, a-selenenylated, and a-halogenated carbonyl derivatives." ... 

Many other electrophiles are able to react with metalated ferrocenylalkyl amines, e.g., trimethyl borate (Fig. 4-27 a), which gives, after hydrolytic workup, compounds like (S,S)-l-(iV,iV-dimethyl-l-aminoethyl)ferrocene-2-boronic acid [106]. Important intermediates for further derivatization are the halogens. For the lithiation technique, I2 (Fig. 4-27b) [151] and BrCN [106] lead to the desired compounds, but when BrCN is used, partial substitution of the dimethylamino group by cyanide occurs (see Sect. 4.3.3.2 and Fig. 4-17). For palladated amines, Brj is applicable [152]. (i ,S)-l-Iodo-2-(iV,iV-dimethyl-l-aminoethyl)ferrocene is the starting material for catalytically active zinc compounds for the enantioselective addition of zinc alkyls to carbonyl compounds [151] (see Chapter 3 for this topic). 

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