Of a-substituted carbonyls

Chapter 2 provided a general introduction to the a-alkylation of carbonyl compounds, as well as the enantioselective nucleophilic addition on carbonyl compounds. Chiral auxiliary aided a-alkylation of a carbonyl group can provide high enantioselectivity for most substrates, and the hydrazone method can provide routes to a large variety of a-substituted carbonyl compounds. While a-alkylation of carbonyl compounds involves the reaction of an enolate, the well known aldol reaction also involves enolates. 

Stork has used the addition of a,/ -unsaturated aldehydes, ketones, esters, and nitriles to enamines prepared from ketones and pyrrolidine, piperidine, or morpholine for the synthesis of a-substituted carbonyl compounds264 266 (Scheme 9). 

Asymmetric Transformation of a-Substituted Carbonyl Compounds Via Enamine or Iminazoline Formation... 

T. Varnali, V. Aviyente, B. Terryn, and M. F. Ruiz-Lopez, J. Mol. Struct. (THEOCHEM), 280, 169 (1993). Conformational Equilibria of a-Substituted Carbonyl Compounds. Study of Solvent Effects. 

Reduction of a-Substituted Carbonyl Compounds —CX-to Carbonyl Compounds... 

This chapter will provide coverage of the scope and limitations of alkylations of metal enolates of saturated and unsaturated ketones, aldehydes and carboxylic acid derivatives, together with a discussion of alkylations of various enols and enolate equivalents. Where applicable, the utility of these reactions for the diastereoselective and enantioselective synthesis of a-substituted carbonyl compounds will be described. Inevitably, the coverage of a vast research area such as this will be incomplete and in part will reflect the author s interests. However, it is hoped that most of the useful methods of carbon-carbon o-bond formation by alkylations of enolates and enols will be included. 

Enolates, or oxyallyl anions, are versatile reagents for the formation of a-substituted carbonyl compounds and are therefore important intermediates for the synthesis of complex molecules. The stereochemical outcome of an enolate reaction often depends on the geometry of the enolate and therefore the selective formation of enolates is a key step in many bond-forming processes. ... 

The so-called silyl enol ethers (enoxyorganylsilanes) are important synthones, e.g, for regiospecific preparation of enolates, aldol condensation, synthesis of a-substituted carbonyl derivatives and for thermal or photochemical cycloaddition. For the preparation of silyl enol ethers the corresponding aldehydes and ketones first have to be enolized and then treated with silylating agents in the presence of a base. Thus, from butanal (608) and Me3SiCl, cis/trans- 1-trimethylsiloxybut-l-ene (609) is obtained (equation 311)347, while 1-trimethylsiloxy-l-phenylethene (610) is the product from acetophenone (90a) (equation 312)347. 

Several Pd-catalyzed methods for the synthesis of a-substituted carbonyl compounds Method I (this section, i.e., Sect. III.2.14.1, and Sect. V.2.1 (the Tsuji-Trost reaction))... 

There are other more indirect and hence less obvious methods for the preparation of a-substituted carbonyl compounds via Pd-catalyzed or Pd-promoted C—C bond formation at a carbon center a to the carbonyl group, hi Method IV in Scheme 1, /3-hetero-substituted aUylic electrophiles serve as masked carbonyl compounds. After Pd-catalyzed cross-coupling with organometals, the hetero-substimted alkenes may be converted to the desired a-substituted carbonyl compounds, as discussed in Sect, ni.2.14.2 (Subsect F.i). For a more general discussion of Pd-catalyzed aUylation of organometals. Sect IIL2.9 should be consulted. 

The Heck reaction of hetero-substituted alkenes (Method V in Scheme 1) can also serve as an indirect method for the preparation of a-substituted carbonyl compounds, as discussed in Sect. IV.2.1. Some of the earliest examples are shown in Scheme 5. One largely unsolved difficulty is the general lack of regiospecificity. If and when its satisfactory solution is achieved, the method would provide a potentially general and useful route to a-substituted carbonyl compounds. 

Claraz A, Oudeyer S, Levacher V Deracemization of a-Substituted Carbonyl Compounds via Catal3ftic Enantioselective Protonation of their Corresponding Enolates Current Organic Chemistry, 2012 16 2192-2205. 

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