Enolate prostereogenic

Transmetalation of lithium enolate 1 a (M = Li ) by treatment with tin(II) chloride at — 42 °C generates the tin enolate that reacts with prostereogenic aldehydes at — 78 °C to preferentially produce the opposite aldol diastereomer 3. Diastereoselectivities of this process may be as high as 97 3. This reaction appears to require less exacting conditions since similar results are obtained if one or two equivalents of tin(ll) chloride arc used. The somewhat less reactive tin enolate requires a temperature of —42 C for the reaction to proceed at an acceptable rate. The steric requirements of the tin chloride counterion are probably less than those of the diethyla-luminum ion (vide supra), which has led to the suggestion26 44 that the chair-like transition state I is preferentially adopted26 44. This is consistent with the observed diastereoselective production of aldol product 3, which is of opposite configuration at the / -carbon to the major product obtained from aluminum enolates. 

The big difference between the extent of asymmetric induction on the addition to a prostereogenic carbonyl group of simple carbanions a to a chiral sulfoxide on the one hand and enolates of sulfinyl esters on the other, can be attributed to the capacity of the ester function to chelate magnesium in the transition states and intermediates. The results already described for the addition of chiral thioacetal monosulfoxide to aldehydes (see Section 1.3.6.5.) underscore the importance of other functions, e.g., sulfide, for the extent of asymmetric induction. 

In contrast to the usual anti selectivity a remarkably high syn selectivity is observed in the addition of thioester enolates to 2-alkylidenealkanones297. The syn selectivity is probably due to a stereoselective internal autoprotonation of the resulting enolates by the dithioester a-pro-tons298 in these cases where the prostereogenic centers reside exclusively in the enone part (see also Section D.2.I.). 

Related is the reaction of prostereogenic aldehydes with enolate 2 (of known configuration) which, under the appropriate conditions in high excess, leads to the adduct 3 (for assignment, see p 477) 96. 

Enantioselective Oxygenation of Prostereogenic Enolates with Enantiomerically Pure (Camphorsulfonyl)oxaziridines... 

The intermediate in this reaction could be either the prostereogenic enolate or the chiral enamine formed in situ. In an attempt to distinguish between these pathways, the chiral enamine prepared from methyl (S)-prolinate was allowed to react with methyl A-phenylseleno-(S)-prolinate. The isolated 2-phenyl-2-phenylselenopropanal had the same enantiomeric excess as that obtained in the direct a-selenenylation of racemic 2-phenylpropanal. This result clearly indicates that the intermediacy of the chiral enamine cannot be excluded7. 

Eames, J. Weerasooriya, N. Recent Avances into the Enantioselective Protonation of Prostereogenic Enol Derivatives, Tetrahedron Asymmetry 2001,12,1-24. 

Several methodologies have been developed to generate the prostereogenic intermediate necessary to achieve enantioselective protonation but all have in common a stable or transient species, enol or enolate, which is being protonated by a chiral proton source. In specific cases, it is difficult to determine the real structure of the intermediate obtained, enolate or enol or both, because of the lack of its characterization and precise mechanistic investigations. 

N, P ] and [P, P ] Aldehydes with an a-stereocenter exhibit unusually high diastereofacial preferences for the addition of silyl enol ethers and ketene acetals with Lewis acid assistance (81). Heathcock and Uehling found good levels of facial discrimination in the addition of silyl enol ethers to chiral enones (Scheme 38, Table 11) (82). With the more substituted silyl enol ether, only one diastereomeric addition product is obtained (Eq. [1], Scheme 38). Use of a prostereogenic silyl enol ether allows control over the relative... 

In order to increase interactions between the incoming nucleophile and the ligand, a chiral functional group capable of coordinating to the carbanion has been tethered to a bidentate phosphane. The resulting enhanced steric repulsion between the enolate and the chiral phos-phane now allows efficient differentiation between the enantiotopic faces of the prostereogenic enolate in favorable cases. Furthermore, directing the nucleophile accelerates the allylation process. 

Enantioselective allylations of prostereogenic enolates have been attempted using catalytic amounts of a palladium complex incorporating (5,5)-Diop as the chiral ligand. The reactions of ketone zinc enolate 2 with allyl chloride 17 and of the sodium enolate derived from aldehyde 5 with phenyl ether 423 yield 3 and 6 of low enantiomeric excess, respectively. 

Proton transfer. Protonation of prostereogenic enolates with the y-hydroxyselenoxides, such as 1, sometimes gives excellent ee. The SnCl complex of a methyl ether of chiral BINOL can be used in catalytic amounts to protonate silyl enol ethers, affording ketones in high optical yields. A catalytic enantioselective deprotonation to form a bromoalkene is achieved by KH in the presence of A-methylephedrine. 

In this event, the addition of 2.1 equivalents of NaHMDS in THF at —78°C converted 17 into a prostereogenic cyclic enolate which then attacked the tartrate-derived dielectrophile 18 with a high level of facial selectivity to generate an intermediate of type 19. Subsequent cyclization was then biased to provide the desired pseudo meso product 20, a compound that was ultimately obtained in 92% yield. In contrast, when the conditions were changed to prevent chelation by using LiHMDS instead of NaHMDS in a solvent mixture of THF and HMPA (hexamethyl-phosphoramide), the C2-symmetric variant of this product (27, see column figures) was formed in 58 % yield. This alternate outcome presumably reflects the preliminary formation of an acyclic lithium dienolate which led to a monoalkylated product corresponding to 26. ... 

Fames J, Weerasooriya N. Recent advances into the enantioselective protonation of prostereogenic enol derivatives. Tetrahedron Asymm. 2001 12 1-24. 

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