Ketene 0,0-acetals, formation

If HMPA is included in the solvent, the Z-enolate predominates.236,238 DMPU also favors the Z-enolate. The switch to the Z-enolate with HMPA or DMPU is attributed to a looser, perhaps acyclic TS being favored as the result of strong solvation of the lithium ion. The steric factors favoring the -TS are therefore diminished.239 These general principles of solvent control of enolate stereochemistry are applicable to other systems.240 For example, by changing the conditions for silyl ketene acetal formation, the diastereomeric compounds 17a and 17b can be converted to the same product with high diastereoselectivity.241... 

This technology has been apphed as part of the total synthesis of myx-alamide A (Scheme 56) [139]. The stereoselective aldol reaction between aldehyde 218 and the propionate 219 dehvered, after reduction, protection, and acylation, ester 220 as a single isomer. After -silyl ketene acetal formation a [3,3]-sigmatropic rearrangement accompanied by 1,3-chirality transfer took place. This, together with the uniform prochirality at the double bonds of the... 

Marshall, J. A. Stereochemical control in the ester enolate Claisen rearrangement. Stereoselectivity in silyl ketene acetal formation. Chemtracts Org. Chem. 1991,4,154-157. 

The Ireland contribution to nonactic acid synthesis, outlined in Scheme 4.32, involves a selective silyl ketene acetal formation and Claisen rearrangement in the key step. D-Mannose (209) was readily converted in a straightforward manner to dihydrofuran 212 via 210 and 211 in 36% overall yield. Esterification of the free alcohol with propionyl chloride followed by the an enolate Claisen rearrangement afforded a mixture (89 11) of tetrahydrofuryl propionates 213 after catalytic reduction. 

Warming the above a-thioiminium salt in the presence of the thiophile and base was critical in order to accomplish the sulfide-contraction process. At ambient temperature, work-up of the same reaction mixture produced the oxolactam analog of (102) as the major product (74%) along with a small amount (12%) of vinylogous carbamate (103). In order to better understand the underlying mechanism that prevailed under ambient versus elevated temperatures, NMR studies were conducted on the a-thioiminium salt (107). This intermediate, when dissolved in deuterated chloroform at ambient temperature in the presence of DBU, was converted immediately to a proposed S,N-ketene acetal (108 Scheme 23). Triphenylphosphine had no effect on the iminium salt. Aqueous work-up yielded the lactam (109), which is consistent with formation of the S,N-ketene acetal. However, wanning the intermediate (107) in the presence of the base and thiophile allowed the reaction to eventually proceed via the sulfur-extrusion pathway, due to the reversibility of the S,N-ketene acetal formation. 

After some preliminary discussion of history and nomenclature, the review will briefly cover issues of rearrangement temperature, substituent effects and catalysis. Transition state stracture as determined by isotope effects combined with theoretical studies will then be described. Stereochemical aspects of the reaction will be examined in detail with accompanying examples. The remainder of the chapter will describe the various methods of ketene acetal formation, structural variety in the allyUc ester substrates and apphcations to natural product synthesis. The presentation of the material is somewhat arbitrary, and indeed most examples could well have been placed under more than one sub-heading. 

Table 3 Effects of reaction condition on (Z) E) ratio of TBDMS silyl ketene acetal formation of ethyl propionate...

Table 3 Effects of Reaction Conditions on (Z) ( ) Ratio of TBDMS Silyl Ketene Acetal Formation of Ethyl Propionate...

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