Halogenations of Enolates

Aldehydes can be converted into optically active a-chloroaldehydes through the intermediacy of chiral enamines, as reported independently in work by MacMillan and Jorgensen (Equations 22 and 23, respectively) [133-135]. MacMillan developed a procedure using hexachloride 242 [130] and the chiral imidazolidinone catalyst 243 (Equation 22) [133]. Under the mild conditions described, chlorination of aldehyde 241 proceeded to give 244 in 94 % yield and 93 % ee. 

1 Streitwieser, A. (1962) Soholytic Displacement Reactions, McGraw, New York, 

2 Fleming, I. (1976) Frontier Orbitals and Organic Chemical Reactions, Wiley, 

3 Reichardt, C. (1990) Solvents and Solvent Effects in Organic Chemistry, 2nd edn, VCH, Weinheim. 

4 Knowles, W.S. (2002) Nobel lecture, Stockholm, December 8. 2001. From Les Prix Nobel. The Nobel Prizes 2001 , Ed. Tore FrSngsmyr, [Nobel Foundation], Stockholm. 

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A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

Rate coefficients (eqn 36) for the halogenation of enols, enol ethers and enolate ions in aqueous media at 25°C... 

Halogenation of enol ethers and enol esters, leading directly to a-halo ketones is realized by use of molecular halogen or halide salts and metal oxidants. Pyridinium chlorochromate (PCC)/l2, Cr03/TMS-Cl/l2, AgOAcfi2, T10Ac/l2. ° Pb(OAc)4 and metal halides and Cu(OAc)2/l2 are useful classes of reagents for this conversion, and some examples are listed in Table 1. 

Table 1 Halogenation of Enol Ethers and Esters with Metallic Reagents...

Halo acetals have been prepared by the action of alcohol on halo ketones and halo aldehydes.An indirect application of this reaction consists in the halogenation of enol acetates with subsequent reaction of the brominated products with alcohols to give the halo acetals. ... 

Halogenation of Enolate Ions The Haloform Reaction Alkylation of Enolate Ions 917... 

Other synthetically useful reactions are allylic amination using TsN=Se=NTs and TsN=S=NTs/ photolysis of a/S-unsaturated ketones in the presence of U02Cl2-methanol [e.g. to give (6) cf. Vol. 6, p. 10], " halogenation of enol silyl ethers/ terminal double bond (e.g. geranyl cyanide, carvone) bromination with (7)... 

CFj, CCI3 0 X ClgC CCb made by halogenation of enols (Chapter 20)... 

Stereoselective a-halogenation of enolates is an important approach for the generation of synthetically versatile, chiral building blocks. By use of an auxiliary approach, the acylated oxazolidinone derivatives developed by Evans have been showcased in diastereoselective enolate brominations (Scheme 3.33) [125]. Enolization of 226 (BujBOTf, amine base) and exposure of the boron enolate to NBS affords 228 in 95 5 dr. A key application of the bromo imides is their facile conversion into azides upon treatment with tetramethylguanidinium azide (229). The resulting azides such as 230 (dr=95 5) can readily be elaborated into chiral a-amino acids (see also Chapter 10). 

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