Boron enolates model

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. 

If a chiral aldehyde, e.g., methyl (27 ,4S)-4-formyl-2-methylpentanoate (syn-1) is attacked by an achiral enolate (see Section 1.3.4.3.1.), the induced stereoselectivity is directed by the aldehyde ( inherent aldehyde selectivity ). Predictions of the stereochemical outcome are possible (at least for 1,2- and 1,3-induction) based on the Cram—Felkin Anh model or Cram s cyclic model (see Sections 1.3.4.3.1. and 1.3.4.3.2.). If, however, the enantiomerically pure aldehyde 1 is allowed to react with both enantiomers of the boron enolate l-rerr-butyldimethylsilyloxy-2-dibutylboranyloxy-1-cyclohexyl-2-butene (2), it must be expected that the diastereofacial selec-tivitics of the aldehyde and enolate will be consonant in one of the combinations ( matched pair 29), but will be dissonant in the other combination ( mismatched pair 29). This would lead to different ratios of the adducts 3a/3b and 4a/4b. 

FIGURE 2. AMI-calculated reaction path for the aldol reaction of acetaldehyde with propionalde-hyde, using complex 150b as a model for the intermediate boron enolate complex 150a. Reproduced from Y. Makino, K. Iseki, K. Fujii, S. Oishi, T. Hirano and Y. Kobayashi, Tetrahedron Lett., 36, 6527. Copyright 1995, courtesy of Elsevier... 

Bernard , A., Capelli, A. M., Gennari, C., Goodman, J. M., Paterson, I. Transition-state modeling of the aldol reaction of boron enolates a... 

In the first total synthesis of bafilomycin A by Evans and Calter [16], the syn aldol reaction between ketone 29 and aldehyde 176 was a pivotal transformation (Scheme 9-51). Using a (Z)-enolate, it could be expected that aldehyde 176 would have a small bias for the desired ann-Felkin adduct, however, control from the ketone component would be needed for high stereoselectivity. Use of common metal enolates led to poor stereocontrol however, model studies indicated that the (Z)-chlorophenyl boron enolate, in conjunction with cyclic protection of the C21-C23 diol, induced high selectivity in the desired sense. In practice, the coupling of the required aldehyde 176 and enolate 77 afforded 178 with >95%ds. Compound 178 was then successfully elaborated to give bafilomycin A]. In the second reported synthesis of bafilomycin A, Toshima et al. carried out the same aldol coupling to form the Cn-Cig bond [68]. 

Aldol and related reactions may also be chelation-controlled. Boron enolates of N-acyloxazolidinones 19 are chelated in the ground state. Their reactions with aldehydes will necessitate the coordination of the aldehyde with the boron atom at transition state, so that the initial bidentate chelate will be broken (Figure 1.26). However, the titanium atom of related titanium enolates can accommodate hexa-coordination so that the initial titanium chelate 20 does not need to be disrupted. In each case, the aldol reaction leads to different syn stereoisomers (Figure L26) via transition models 21 and 22. 

Figure 4. Prediction of stereochemistry of boron enolates 9 and 10 using chair-type six-membered transition state based on the Zimmerman model.

A similar model has been applied to aldol condensation reactions of boron enolates. O The reaction of E) enolate 369, for example, can lead to either transition state 371 or 372. Transition state 371 generates the... 

Polymeric Evans auxiliary 76 was also applied to aldol reactions2 4 (Scheme 1.6.37). In a model reaction, immobilised dihydrocinnamic acid was converted into the boron enolate and reacted with isovaleraldehyde. Products were released by treatment of the resin with NaOMe. The p-hydroxy ester 79 was obtained in a 20 1 diasteromeric ratio, along with some ester 80 derived from unreacted starting material. 

Scheme 1. Zimmerman-Traxler models for aldol stereoselectivity with boron enolates.

In practice, aldehydes bearing an adjacent stereogenic center, particularly one devoid of a bulky group, typically provide only modest aldol stereoselectivity. For example, consider the reaction of aldehyde 28 with Z boron enolate 27 as shown in Scheme 3a. According to the models just discussed, one would expect this reaction to provide only 1,2-syn products with anti-Felkin- Ahn stereoselectivity. Indeed, that conjecture proved to be true for the most part as exclusively 1,2-syn aldol adducts resulted with 29, a compound whose stereotriad reflected anti-Felkin—Ahn selectivity, constituting the predominant product. However, a fair amount of the alternate 1,2-syn Felkin- Ahn adduct (30) was also observed, such that the final ratio of 29 to 30 was a disappointing 1.75 1. 

After 124 had been converted into 125 (Scheme 14) through an ozonolysis reaction and an alcohol protection step, the Paterson group then transformed this ketone into a Z boron enolate (126, see column figure) expecting that its subsequent reaction with 88 would afford the l,2-.syn-disposed aldol product 128. Indeed, this reaction did provide primarily syn products as one would anticipate based on the Zimmerman—Traxler models shown in Scheme 1. Disappointingly, the desired syn product (128) was the minor adduct, as... 

Chiral boron enolates are effective in enantioselective aldol condensations, a transition-state model being proposed for the moderate chirality transfer exhibited (Scheme 57). ° Diastereoselection with chiral lithium enolates has also been demonstrated by a highly stereoselective synthesis of the Prelog-Djerassi lactonic acid. ... 

Scheme 2.24 Regioselective formation of boron enolates according to Mukaiyama s protocols transition-state model 91 for kinetically controlled enolate generation.

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