Enolization model

With ( )-enolates model transition state A, leading to. sw-adducts, is favored for large X or Y groups. 

Detailed investigations indicate that the enolization process (LDA, THF) affords enolates 37 and 38 with at/east 97% (Z)-stereoselection. Related observations have recently been reported on the stereoselective enolization of dialkylthioamides (38). In this latter study, the Ireland-Claisen strategy (34) was employed to assign enolate geometry. Table 10 summarizes the enolization stereo selection that has been observed for both esters and amides with LDA. Complementary kinetic enolization ratios for ketonic substrates are included in Table 7. Recent studies on the role of base structure and solvent are now beginning to appear in the literature (39,40), and the Ireland enolization model for lithium amide bases has been widely accepted, A tabular survey of the influence of the ester moiety (ORj) on a range of aldol condensations via the lithium enolates is provided in Table 11 (eq. [24]). Enolate ratios for some of the condensations illustrated may be found in Table 10. It is apparent from these data that ( )-enolates derived from alkyl propionates (Rj = CH3, t-C4H9) exhibit low aldol stereoselectivity. In contrast, the enolates derived from alkoxyalkyl esters (Rj = CHjOR ) exhibit 10 1 threo diastereo-... 

The participation of enol forms of chlorophylls in primary reactions of photosynthesis is still debated. On the basis of redox potential measurements and ENDOR spectroscopy of Chi a enol models. WaslelewskI et al.,(4) favored an oxidized Chi a enol form at the C-9 of ring V for P700. Recently, from RR spectroscopy of the neutral and electrochemically-... 

Evans DA, Yang MG, Dart Ml, Duffy JL. Double stereodif-ferentiating aldol reactions of ( ) and (Z) lithium enolates. Model reactions for polypropionate assemblage. Tetrahedron Lett. 19% 37 1957-1960. 

Bernard A, A M CapeUi, A Comotti, C Gannari, J M Goodman and I Paterson 1990. Transltion-St Modeling of the Aldol Reaction of Boron Enolates A Force Field Approach. Journal of Orga Chemistry 55 3576-3581. 

Alkali alkaline earth metal enolates tend to be aggregates- complicates stereo selection models. 

Examine the enolate of acetone on Learn mg By Modeling How IS the negative charge distributed between oxygen and the a carbon" ... 

Learning By Model mg contains molecu lar models of the enolates of acetone and 2 4 pentanedione Compare the two with respect to the dis tribution of negative charge... 

Conqjutational methods can also be used to describe enolate stmcture. Most of the stmctural features of enolates are correctly modeled by B3LYP computations with dimethyl ether as the solvent molecule. Although semiempirical PM3 calculations give adequate representations of the geometries of the aggregates, the energy values are not accurate. 

It was reported that the eorresponding 2-hydroxy-3-aeetyl-benzofuran exists entirely in the enol form (73AJC1079 84H737 87CC1150) [produees deep blue eolor with ferrie ehloride (55JA1623)].This is in aeeordanee with AMI, PM3, and B3LYP/6-31G ealeulations for 3-formyl-2-hydroxybenzo [h]furan as model eompound (99UP1) (see Seheme 10, all values in keal/mol). 

These examples indicate that the (Z)-syn,(E)-antt correlation should be considered to be a rule with many exceptions. Two explanations may be given in order to rationalize the manifold stereochemical results in aldol additions. Firstly, it seems plausible that the many different reaction conditions and starting materials (e.g., various types of enolates, counterions, etc.) may cause the aldol addition to follow different reaction mechanisms, so that different types of transition states are involved. Secondly, in a single type of transition state model, the reactants may have different orientations to each other, so that the formation of different stereoisomers may result even for one and the same transition state model. 

The fact that (Z)-lithium enolatcs generally display a higher simple diastereoselectivity giving. vyn-aldols compared to (E)-enolates affording nn/i-aldols is a challenge to the Zimmer-man-Traxler model, and has become the source of extended speculation. 

The tris(diethylainino)sulfoiiium difluorotrimethylsiliconate induced aldol addition of enolsi-lancs, which delivers predominantly syw-aldols independent of the cnolate geometry (sec p 1608), calls for another mechanistic model. A.n open transition state model has been proposed which assumes that the naked" ionic oxygens are as far apart as possible28. For (Z)-enolates, one transition state is favored over the diastereomeric orientation due to the avoidance of a repulsive R /CHj interaction. 

Starting from ( )-enolates, the corresponding argument predicts that transition state 10a is lower in energy than the alternative model which suffers from mutual steric hindrance of the substituent R1 and the methyl group in a gauche orientation thus, stereoconvergence results. 

A Zimmerman-Traxler transition state model is postulated in order to rationalize the ul topicity of this aldol addition [i.e., the (S)-enolate preferentially attacks the 7 e-face of the aldehyde]33. In the two alternative transition states 3a [ul topicity (S)jRe] and 3b [Ik topicity (S)/Si, the substituents at the stereogenic center of the enolatc are oriented in such a way that... 

Once again, desilylation and oxidative cleavage33 delivers the hydroxycarboxylic acids. A chairlike transition state model, analogous to that proposed for the corresponding boron enolate33, is postulated in order to rationalize the ul topicity of the above titanium enolate. 

Thus, jyn-adducts arise predominantly, as expected, according to the Zimmerman-Traxier model. Provided that either boron or zirconium is the enolate-metal atom, high syn selectivity is achieved. The total amount of anti-adducts is lower than 2% in the case of amides 1 and 2, and it approaches zero when the other reagents arc used94 . The induced stereoselectivities are impressive for the amides and remarkable in the case of the imides. 

It must be noted that the cyclic model fails to account for the role of the additional alkyllithium and diethylaluminum that are required in precise amounts to achieve high selectivity. A simple model that recognizes a possible role for the additional reagents suggests the intermediacy of an extended, noncyclic transition state G with the aldchydic oxygen coordinated to some undefined Lewis acidic species derived from the additional components of the reaction mixture26,44. Aggregates composed of enolate, alkyllithium and dialkylaluminum species are also possible. 

The diastereoselectivity of the copper enolate 2b may be rationalized by suggesting that the chair-like cyclic transition state J is preferred which leads to the major diastereomer 4. The usual antiperiplanar enolate geometry and equatorial disposition of the aldehyde substituent are incorporated into this model. Possible transition states consistent with the stereochemistries of the observed minor aldol products are also illustrated. 

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