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. 2016 Aug 8;55(33):9610-9614.
doi: 10.1002/anie.201603894. Epub 2016 Jun 7.

Practical and Broadly Applicable Catalytic Enantioselective Additions of Allyl-B(pin) Compounds to Ketones and α-Ketoesters

Daniel W Robbins #  1 , KyungA Lee #  1 , Daniel L Silverio  1 , Alexey Volkov  1 , Sebastian Torker  1 , Amir H Hoveyda  1
Affiliations

Practical and Broadly Applicable Catalytic Enantioselective Additions of Allyl-B(pin) Compounds to Ketones and α-Ketoesters

Daniel W Robbins et al. Angew Chem Int Ed Engl. .

Abstract

A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3 ) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well.

Keywords: enantioselective synthesis; homoallylic alcohols; homogeneous catalysis; ketones; α-ketoesters.

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Figures

Scheme 1
Scheme 1
Is high enantioselectivity feasible without a second catalyst-substrate contact point?
Scheme 2
Scheme 2
Another key question: which pathway, if any, would be preferred for allyl–B(pin) addition to α-ketoesters?
Scheme 3
Scheme 3
Screening of ligands for enantioselective allyl addition to acetophenone as the model.
Scheme 4
Scheme 4
Tertiary homoallylic alcohols obtained from catalytic enantioselective additions of allyl–B(pin) compounds to acyclic ketones. The absolute stereochemistry of the major isomer of 9 has not been determined. [a] At –15 °C, 8 h. [b] At–15 °C, 12 h.
Scheme 5
Scheme 5
Catalytic enantioselective additions to cyclic ketones.
Scheme 6
Scheme 6
Unexpected sense of selectivity in reactions of α-ketoesters and identification of an optimal aminophenol.
Scheme 7
Scheme 7
Catalytic enantioselective allyl–B(pin) addition to α-ketoesters and a representative application.
See this image and copyright information in PMC

References

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