Enolates chelation, affect

Chelation affects the stereochemistry of enolate formation. For example, the formation of the enolates from a-siloxyesters is Z for LiHMDS, but E for LiTMP.19... 

Entry 5, where the same stereochemical issues are involved was used in the synthesis of (+)-discodermolide. (See Section 13.5.6 for a more detailed discussion of this synthesis.) There is a suggestion that this entry involves a chelated lithium enolate and there are two stereogenic centers in the aldehyde. In the next section, we discuss how the presence of stereogenic centers in both reactants affects stereoselectivity. 

Summary of Facial Stereoselectivity in Aldol and Mukaiyama Reactions. The examples provided in this section show that there are several approaches to controlling the facial selectivity of aldol additions and related reactions. The E- or Z-configuration of the enolate and the open, cyclic, or chelated nature of the TS are the departure points for prediction and analysis of stereoselectivity. The Lewis acid catalyst and the donor strength of potentially chelating ligands affect the structure of the TS. Whereas dialkyl boron enolates and BF3 complexes are tetracoordinate, titanium and tin can be... 

These results are consistent with the chelated transition states depicted in Scheme 18. Steric interactions between the substituent and the carboxamide favor (AC) for ( )-allylic ethers. The R -substi-tuent of a (Z)-allylic ether, though less affected by this interaction, still experiences a certain degree of steric strain in the anti transition state (AB) thus diminishing anti selectivity. Enantioselectivity is controlled by the substituents R and R on the pyrrolidine ring. As pictured in Scheme 18, bonding occurs preferentially on the face of the enolate anti to R. For the diastereomeric secondary allylic ethers (Table 21, entries 8) transition state (AB) represents the matched arrangement for R = H and R = alkyl, whereas (AC) is matched for R = alkyl and R = H. The former arrangement would lead to an ( )-pro-duct and the latter to a (Z)-product. 

A chiral (3, (3, (3 -trifluoro-2 -propanol (14) was used for asymmetric protonation of lithium enolate (15) (Scheme 4.8) [43]. The determining factor for the product chirality in this reaction was found to be the chirality of carbinol carbon, but another chirality of the sulfinyl sulfur also affects the enantiomeric excess of the product. Thus, a binary chelation of the chiral fluorinated alcohol to the lithium was suggested. 

It is generally true that restrictions on conformational mobility minimize the number of competing transition states and simplify analysis of the factors that affect selectivity. Chelation of a metal by a heteroatom often provides such restriction and also often places the stereocenter of a chiral auxiliary in close proximity to the a-carbon of an enolate. This proximity often results in very high levels of asymmetric induction. A number of auxiliaries have been developed for the asymmetric alkylation of carboxylic acid derivatives using chelate-enforced intraannular asymmetric induction. The first practical method for asymmetric alkylation of carboxylic acid derivitives utilized oxazolines and was developed by the Meyers group in the 1970 s (Scheme 3.16a), whose efforts established the importance and potential for chelation-induced rigidity in asymmetric induction (reviews [77-79]). In 1980, Sonnet [80] and Evans [81,82] independently reported that the dianions of prolinol amides afford more highly selective asymmetric alkylations (Scheme 3.16b). 

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