Evans synthesis, Mukaiyama aldol reaction

The aldehyde 157 was prepared according to the sequence in the synthesis of Evans total synthesis of callipeltoside A (Scheme 33) [75]. The vinylidene asymmetric Mukaiyama aldol reaction of a-oxy aldehyde 159 and silyl ketene acetal 160 catalyzed by Cu-pybox complex 161 [76] furnished 5-hydroxy-a, /l-unsaturated ester 162 in 95% ee, which was reduced to yield 157. 

Bolm and coworkers have developed a synthetic procedure for the efficient synthesis of enantiomerically enriched alcohols from pyruvates. As an alternative to the popular PYBOX and BUBOX complexes pioneered by Evans, new Ci-symmetric aryl-bridged aminosulfoximene ligands 71 and 72 were synthesized for use in the copper(II)-catalyzed Mukaiyama aldol reaction. By varying the stereochemistry of the sulfoximine, it is possible to... 

Evans et al. applied the Mukaiyama aldol reaction to the total synthesis of the squalene synthase inhibitor zaragozic acid C (Scheme 8.23). ° Di-f-butyl tartrate 135 was protected as acetal 137, which was converted into silyl enol ether 138. The partner aldehyde 141 was synthesized by the Evans aldol reaction (139 —> 140). The Mukaiyama aldol reaction with silyl enol ether 138 and aldehyde 141 in the presence of (i-PrO)TiCl3 gave adduct 142 as a single isomer. These transformations gave the desired stereochemistry at the C3 to C7 positions. 

In investigations of double diastereodifferentiating Mukaiyama aldol reactions, Evans demonstrated that the coupling of end silane 195 either to aldehyde 196 or to aldehyde 198 affords the Felkin products 197 and 199, respectively, with excellent diastereoselectivity (Scheme 4.21) [36]. Because of the involvement of open transition states in these aldol reactions, no direct correlation was found between the starting end silane geometry and the observed simply selectivity (syn versus anti). This contrasts with the simple diastereoselectivity typically observed for cis- and trans-metal enolates that react through cyclic Zimmerman-Traxler transition states. By this strategy, the addition of enol silane 201 to 200 provided an advanced intermediate 202 in the synthesis of 6-deoxyerythronolide B (187, Scheme 4.22) [97]. 

A vinylogous Mukaiyama reaction, similar to that utilized in our synthesis, was employed to introduce the C-, stereocenter in Nicolaou s synthesis and also in the synthesis of preswinholide A reported by the Nakata group I53k One notable reaction in Nakata s synthesis of preswinholide A was the auxiliary-controlled aldol reaction shown in Scheme 9-31. Here the Evans auxiliary is used to couple two relatively complex fragments 91 and 92 to give 93. Unusually, this reaction was best performed using the lithium enolate of imide 91. 

In a similar manner, the synthesis of the immunosuppressant (-)-pironetin (PA48153C) featured the Mukaiyama aldol as a key step in the later stages. Consistent with the experimental results and the model proposed by Evans,this reaction resulted in the preparation of the single diastereomer 25, a key intermediate in the Keck synthesis. 

Scheme 5.67 Evans Mukaiyama aldol and vinylogous aldol reactions mediated by the copper PYBOX catalyst 217 enantioselective synthesis of callipeltoside A building block 225.

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