Claisen condensation enantioselectivity

G-H functionalization at acetal C-H bonds generates protected forms of /3-ketoesters (Figure 4). /3-Ketoesters are often formed by Claisen condensation, but the asymmetric version is not a viable process, because the products would very likely racemize under the reaction conditions. Therefore, the C-H insertion equivalent to the Claisen condensation is very attractive, because the resulting /3-ketoester is protected, which allows for the enantioselective version to be feasible (Figure 4). 

A few years later, a new process for the (R)-HPB ester was reported by Solvias in collaboration with Ciba SC (see Figure 2.11). Claisen condensation of cheap acetophenone and diethyl oxalate was carried out, followed by chemo- and enantioselective hydrogenation of the resulting diketo ester and hydrogenolysis to the HPB ester [30]. Even though the 2,4-dioxo ester was a new substrate type, it took only a few months to develop, scale up, and implement the new process. The following aspects were the key to success (i) the low price of the diketo ester prepared via Claisen... 

Moving to a related type of [2 + 2] cycloaddition, not involving aldehydes or imines as partners, Calter and coworkers reported Cinchona alkaloid (TMSO-QN) catalysed asymmetric dimerisation of ketenes, generated in situ from the corresponding acid chlorides, yielding (3-lactones via a formal Claisen condensation (Scheme 14.29). The unstable ketene dimers were trapped with an alko>yamine to afford p-keto amides i.e. Weinreb amides) with variable yields and excellent enantioselectivities. 

Control of enantioselectivity will be discussed in the corresponding sections on carbonyl reduction (Chapter 4) alkene hydrogenation, epoxidation, and dihydroxylation (Chapter 5) aldol condensation (Chapter 6) allylation and crotylation (Chapter 7) Claisen rearrangement (Chapter 8) and the Diels-Alder reaction (Chapter 9). 

NAP-MgO acts as a bifunctional heterogeneous catalyst for the Claisen-Schmidt condensation (CSC) of benzaldehydes with acetophenones to yield chalcones, followed by asymmetric epoxidation (AE) to afford chiral epoxy ketones in moderate to good yields and impressive enantioselectivities (ee s). NAP-MgO, in combination with the chiral auxiliary (11 ,21 )-(- -)-1,2-diphenyl-1,2-ethylenediamine (DPED), catalyzed the asymmetric Michael addition of malonates to cyclic and acyclic enones. 

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