Ketones enolate geometry

Partial control of enolate geometry occurs also when the enol phosphate, prepared by treatment of fluoroalkyl ketones with sodium diethyl phosphite, is... 

Michael additions of ketone enolates. The stereochemistry of Michael additions of lithium enolates of ketones to a,(3-enones is controlled by the geometry of the enolate. Addition of (Z)-enolates results in anti-products with high diaster-eoselectivity, which is not changed by addition of HMPT. Reaction of (E)-enolates is less stereoselective but tends to favor syn-selectivity, which can be enhanced by addition of HMPT. 

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-... 

Most enolates can exist as two stereoisomers. Also, most aldol condensation products formed from a ketone enolate and an aldehyde can have two diastereomeric structures. These are designated as syn and anti. The cyclic-transition-state model provides a basis for understanding the relationship between enolate geometry and the stereochemistry of the aldol product. 

Enolates are a type of alkene, and there are two possible geometries of the enolate of an ester. The importance of enolate geometry is discussed in Chapter 34 and will not concern us here-More important is the question of regloselectivity when unsymmetrical ketones are deprotonated. We shall discuss this aspect later in the chapter. 

The cyclic transition state explains how enolate geometry controls the stereochemical outcome of the aldol reaction. But what controls the geometry of the enolate For lithium enolates of ketones the most important factor is the size of the group that is not enolized. Large groups force the enolate to adopt the cis geometry small groups allow the fram-enolate to form. Because we can t separate the lithium enolates, we just have to accept that the reactions of ketones with small R will be less dias ter eoselective. 

Stereoselective functionalization of enolates derived from 2-acyl-2-alkyl-1,3-dithiane 1-oxides Stereoselective enolate alkylation. There has been much interest over recent years in the enantio- and diastereocontrol of enolate alkylation.19 Most methods which do not rely on asymmetric alkylating agents hinge on a derivatization of the ketonic substrate with an enantiomerically pure auxiliary. Examples of such chiral auxiliaries include oxazolines20 and oxazolidi-nones.21 We reasoned that the sulfoxide unit present in our 2-acyl-2-alkyl-1,3-dithiane 1-oxide substrates might be expected to influence the transition-state geometry of a ketone enolate, perhaps by chelation to a metal counterion, and hence control the stereochemistry of alkylation. 

Partial control of the enolate geometry also occurs when the enol phosphate 19, prepared by treatment of fluoroalkyl ketones with sodium diethyl phosphite, is treated with a lithium aluminum hydride/copper(II) bromide reagent. " These enolates 20 react with modest diastc-reoselectivity with aldehydes to give products 21. 

Whereas deprotonation of cyclic ketones (4-7-member rings) can only lead to the (E)-(0)-enolate geometry, control of enolate stereochemistry of acyclic ketones with lithium amides is rather complicated and depends on the structure of the carbonyl compound, steric requirements of the base, and reaction conditions. 

The use of C unsubstituted and substituted stannyl enolates has been studied by Yamamoto in a series of elegant reports involving a novel bisphosphine Ag(I) complex 64 as a catalyst for C-C bond formation [30]. The addition of methyl ketone and acetate-derived enolates furnishes adducts in up to 96% ee. The use of E-stannyl enolates yields the 2-anti diastereomer as the major product in up to 96% ee. The use of acyclic Z-enol stannanes provided the complementary syn-substituted adducts as the major adduct in equally high diastereoselectivity and enantioselectivity. The observed correlation between enolate geometry and the simple diastereoselectivity of the product (E-enolates yield anti adducts while Z-enolates yield syn adducts) has led Yamamoto to postulate the involvement of a closed, cyclic transition-state structure. 

The Mukaiyama aldol reaction of ethyl ketones can lead to the controlled introduction of two adjacent stereocenters. While enolate geometry may not be trans-fened faithfully to the relative stereochemistry of the aldol product syn versus anti), stereoconvergent reactions are possible. In the example shown in Scheme 9-5, it should be noted that 7i-facial control from the chiral aldehyde is strong as both products 7 and 8 arise from Felkin selectivity [5]. 

Introduction and stereochemical control syn,anti and E,Z Relationship between enolate geometry and aldol stereochemistry The Zimmerman-Traxler transition state Anti-selective aldols of lithium enolates of hindered aryl esters Syn-selective aldols of boron enolates of PhS-esters Stereochemistry of aldols from enols and enolates of ketones Silyl enol ethers and the open transition state Syn selective aldols with zirconium enolates The synthesis of enones E,Z selectivity in enone formation from aldols Recent developments in stereoselective aldol reactions Stereoselectivity outside the Aldol Relationship A Synthesis ofJuvabione A Note on Stereochemical Nomenclature... 

So, to kick off, ketone 262 is reacted to form lruns boron enolate 266 that combines with acetaldehyde to give the intermediate 267. The 1,2-anti stereocontrol comes from the enolate geometry and the chiral centre of the original ketone imposes the 1,3-anti control in the way we have seen already in this chapter. The intermediate 267 is reduced without working the reaction up and the boron removed to give 268. 

Titanium enolates of cyclic and acyclic ketones, like their zirconium counterparts, usually give rise to syn aldol products irrespective of enolate geometry. Tri(alkoxy)- or tri(dialkylamino)-titanium enolates... 

Kinetic control. The Zimmerman-Traxler model, as applied to propionate and ethyl ketone aldol additions, is shown in Scheme 5.7 (note the similarity to the boron-mediated allyl additions in Scheme 5.3). Based on this model, we would expect a significant dependence of stereoselectivity on the enolate geometry, which is in turn dependent on the nature of X and the deprotonating agent (see section... 

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