Stereoselectivity in Enolate Formation

Long before the development of the enolate Claisen rearrangement, it was established theoretically [31] and with sufficient experimental precedence [6, 32] that, lacking the structural constraints in the allyl vinyl ether system, the chair-like transition state is preferred for the rearrangement. This is understandable since between the two possible transition states A and B, the transition state A is of lower energy due to the equatorial disposition of the R group. 

Ireland found this predominance of the chair like transition state in the case of the rearrangement of the enolates of the esters 18 and 19 as well, which gave respectively the U-configured acids 20 and 21 with 99% diastereoselectivity. 

The same concept was found to be applicable to the deprotonation of ketones as well. This expanded the scope of this deprotonation method still further. 

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Regioselectivity and Stereoselectivity in Enolate Formation from Ketones and Esters... 

We chose to explore the intramolecular alkylation of amide enolates as a potential stereoselective route to cis pyrethroid cyclopropane carboxylates. If the relationship between the stereoselection in enolate formation and ring closure is operable, amide enolates would be an excellent means of developing a stereoselective synthesis of cis products (8). Furthermore, recent progress in achieving enantioselection in the intermolecular alkylation of chiral amide enolates would provide a means of obtaining optically active pyrethroid acids (Figure 6) (9-13). 

The results presented here illustrate seme basic principles for achieving good measures of stereocontrol in the formation of cyclcpropanecarboxylate derivatives via intramolecular enolate alkylation. They also represent an additional example of the important role that stereoselection in enolate formation plays in stereoselective synthesis (21, 22). 

Table 9.12. Stereoselectivity in Enolate Formation and Diastereoselectivity in the Aldol Condensation...

Thioesters give trans-hoion enolates 96 when treated with dicyclopentylboron triflate in the presence of Hiinig s base, as shown in Scheme 2.27 for t-butyl propanethioate [109] — a protocol that has been applied for the generation of the chiral boron enolate 97 featuring a C2-symmetric borolane moiety [110]. However, the stereoselectivity in enolate formation can be reversed by starting from phenyl (rather than from alkyl) propanethioate so that cis-enolate 98 forms exclusively [111] - a result that might originate from thermodynamic control [100]. 

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