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. 2014 Apr 9;136(14):5225-8.
doi: 10.1021/ja500882x. Epub 2014 Mar 31.

Asymmetric fluorination of α-branched cyclohexanones enabled by a combination of chiral anion phase-transfer catalysis and enamine catalysis using protected amino acids

Xiaoyu Yang  1 , Robert J Phipps, F Dean Toste
Affiliations

Asymmetric fluorination of α-branched cyclohexanones enabled by a combination of chiral anion phase-transfer catalysis and enamine catalysis using protected amino acids

Xiaoyu Yang et al. J Am Chem Soc. .

Abstract

We report a study involving the successful merger of two separate chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate Selectfluor and an enamine activation cycle, using a protected amino acid as organocatalyst. We have demonstrated the viability of this approach with the direct asymmetric fluorination of α-substituted cyclohexanones to generate quaternary fluorine-containing stereocenters. With these two chiral catalytic cycles operating together in a matched sense, high enantioselectivites can be achieved, and we envisage that this dual catalysis method has the potential to be more broadly applicable, given the breadth of enamine catalysis. It also represents a rare example of chiral enamine catalysis operating successfully on α-branched ketones, substrates commonly inert to this activation mode.

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Figures

Figure 1
Figure 1
Proposed dual catalytic cycle for the enantioselective fluorination of ketones using (1) an enamine catalysis cycle and (2) a chiral anion phase-transfer catalysis cycle.
Scheme 1
Scheme 1. Further Transformations of Fluorinated Ketone Products
See this image and copyright information in PMC

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