Halogenation reaction diastereoselective

Whereas the halogen-lithium exchange is of limited importance for the generation of a-lithiated ethers, the reductive lithiation of 0/S-acetals has been applied more frequently, the versatility being enhanced by remarkable diastereoselective variants. Thus, a single diastereomer of the lithium carbenoid 52 results from the diastereomeric mixture 51 (equation 34) . Representative examples of a-lithiated ethers generated by this method and their reactions with electrophiles are given in Table 4. 

The utilization of a-amino acids and their derived 6-araino alcohols in asymmetric synthesis has been extensive. A number of procedures have been reported for the reduction of a variety of amino acid derivatives however, the direct reduction of a-am1no acids with borane has proven to be exceptionally convenient for laboratory-scale reactions. These reductions characteristically proceed in high yield with no perceptible racemization. The resulting p-amino alcohols can, in turn, be transformed into oxazolidinones, which have proven to be versatile chiral auxiliaries. Besides the highly diastereoselective aldol addition reactions, enolates of N-acyl oxazolidinones have been used in conjunction with asymmetric alkylations, halogenations, hydroxylations, acylations, and azide transfer processes, all of which proceed with excellent levels of stereoselectivity. 

The addition of an allyl metal to a-amino aldehydes has been used by Vara Prasad and Rich (Scheme 12)J23l After the addition step, the allyl group is oxidized to a carboxylic acid and lactonized. Then, the a-carbon of the lactone is alkylated stereoselectively. These investigators also systematically examined the addition reaction to determine its diastereo-selectivity. The highest diastereoselectivity was obtained when allyltrimethylsilane was used in the presence of tin(IV) chloride. An increase in the steric bulk of the protecting group and of the side chain also resulted in a better diastereoselection. Alternatively, Taddei and co-workers 24-26 used a 2-(halomethyl)allylsilane and the side chains were introduced by nucleophilic substitution of the halogen (Scheme 13). 

Application of the halogenation of y-aminoolefins preceding intramolecular cyclization has been applied to the synthesis of fused piperidines (Equation 33) <2003CC1918>. The presence of chiral substituents (e.g., via the nitrogen protecting group) generates a diastereoselective reaction (Equation 34). 

The halogen-metal exchange of one of a geminal pair of bromine atoms is readily achieved -a carbenoid is formed which may have sufficient stability to react as an organolithium before decomposing to a carbene by a-elimination.. m in cyclic systems, diastereoselectivity in this process has long been known,114116 though the outcome of reactions such as that of 137 is under a mixture of kinetic and thermodynamic control.117... 

An interesting diastereoselectivity pattern was observed when a-halogen-sub stituted allylboronates were added to aldehydes. In this reaction, (Z)-alkenes were obtained as the major products7 (Scheme 3.VII). Hoffmann and Landmann explained the results by examining two competing six-membered chairlike transition states (Scheme 3.VIII). Among the possible factors that favor the transition state A, they pointed out that dipole-dipole interactions could play a dominant... 

Peracid epoxidation and indirect epoxidation via the halohydrin route normally display opposite diastereoselectivity. In the indirect epoxidation route, the steric course is normally controlled by the first step, the formation of the most stable halonium ion, and not by the second step, the (tranx-diaxial) attack by the (nucleophilic) oxygen species. However, the relative rates and equilibria of both steps depend on the source of positive halogen and the reaction conditions which strongly influence the obtained stereoselectivity (Tables 3 and 4, and Section 4.5.1.1.3,). 

Less electronegative the halogen atom in (llla-c), higher the stereoselectivity of the addition. Addition reactions of these reagents to ketones are not reported. The enhanced diastereoselectivity of tita-nocene-like crotyl derivatives may be ascribed to the strong electron-donating nature of the cyclopentadienyl residues which reduces the Lewis acidity of the complex and, hence, its reactivity. 

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