Abstract
Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols. However, to date, methods that enable control over the absolute stereochemical outcome of such a process have remained elusive. Here we report a catalytic asymmetric method for the synthesis of enantioenriched cyclohexanes from 1,5‐diols via hydrogen borrowing catalysis. This reaction is mediated by the addition of a chiral iridium(I) complex, which is able to impart high levels of enantioselectivity upon the process. A series of enantioenriched cyclohexanes have been prepared and the mode of enantioinduction has been probed by a combination of experimental and DFT studies.
Highlights
Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols
We report a catalytic asymmetric method for the synthesis of enantioenriched cyclohexanes from 1,5-diols via hydrogen borrowing catalysis. This reaction is mediated by the addition of a chiral iridium(I) complex, which is able to impart high levels of enantioselectivity upon the process
Alkylation of a substituted enolate results in the generation of a new a-stereogenic center and an abundance of methods have been developed which enable this process to be carried out in an asymmetric manner (Scheme 1 A).[2]. Whilst this approach is highly effective for alkylation with primary electrophiles, alkylation with secondary electrophiles is significantly more challenging and often results in sluggish reactivity accompanied by competing elimination processes.[1]
Summary
Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols. Hydrogen borrowing catalysis represents a powerful alternative strategy to classical enolate alkylation, enabling direct alkylation of enolates with unactivated alcohols.[4] Within this manifold, we recently reported that an achiral iridium(III) catalyst can promote alkylation of pentamethylphenyl (Ph*) ketones with alcohols leading to a- and bbranched ketones.[5] This was subsequently extended to a (5+1) annulation process in which racemic cyclohexanes could be accessed from 1,5-diols (Scheme 1 B).[6] These reactions proceed by oxidation of the alcohol by the iridium catalyst to generate the corresponding carbonyl compound in situ.
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