Catalytic Asymmetric Baeyer-Villiger Reactions

In the late 20th century, chemists witnessed remarkable advancements in catalytic asymmetric synthesis. Significant efforts were devoted to the development of efficient oxidation catalysts, and a range of enantioselective metal atalyzed reactions were developed [33]. Despite the long history of the Baeyer-Villiger (BV) oxidation, the enantioselective version of the process was not studied until recently. 

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Asymmetric Baeyer-Villiger oxidation reaction In 1994, Bolm et al used chiral Cu and Ni complexes (7.23) in catalytic amount with different oxidation systems. 

Table 5. Direct catalytic asymmetric aldol reactions promoted by heteropolyme-tallic asymmetric catalyst and following Baeyer-Villiger oxidations.

An important feature of this reaction is that in contrast to most other catalytic asymmetric Mannich reactions, a-unbranched aldehydes are efficient electrophiles in the proline-catalyzed reaction. In addition, with hydroxy acetone as a donor, the corresponding syn-l, 2-aminoalcohols are furnished with high chemo-, regio-, diastereo-, and enantioselectivities. The produced ketones 14 can be further converted to 4-substituted 2-oxazolidinones 17 and /i-aminoalcohol derivatives 18 in a straightforward manner via Baeyer-Villiger oxidation (Scheme 9.4) [5]. 

Several of the aldol products obtained were readily converted to their corresponding esters by Baeyer-Villiger oxidation. These results also are summarized in Table 16. Ester 66 was further transformed into key epothilone A intermediate 69 and also a key synthetic intermediate 70 for bryostatin 7. What is the mechanism of these direct catalytic asymmetric aldol reactions using LLB-II It is apparent that self-assembly of LLB and KOH occms, because of the formation of a variety of aldol products in high ee and yields. In addition, the NMR and LDI-TOF(-i-)MS spectra of LLB KOH show the occurrence of rapid exchange between Li and K. We have already found that LPB[LaK3tris(binaphthoxide)] itself is not a useful catalyst for aldol reactions, and that the complexes LPB KOH or LPB LiOH give rise to much less satisfactory results. 

SCHEME 8.37. The Shibasaki direct catalytic asymmetric aldol reaction using heteropolymetallic asymmetric catalyst and following Baeyer-Villiger oxidation. 

After experimentation it was found that Baeyer-Villiger oxidation could be suppressed and the amount of catalyst could be reduced to 20 mol% if the reaction was carried out between pH 10 and 11 (Scheme 1.13) [33,34], Yields were increased (65-95%) and the catalytic system resulted in slightly higher ees (91-97% ee). The synthetic utility of this system has been widely explored with the successful asymmetric epoxidation of various hydroxyalkenes (90-94% ee) [35], enol ethers and enol esters (80-91% ee) [36], enynes (90-97% ee) [37], vinylsilanes (84-94% ee) [38], cis-aUcenes (84-97% ee)[39, 40], terminal alkenes (30-94% ee) [41], and mono-epoxidation of conjugated dienes (90-97% ee) [42],... 

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