A Cooperative Catalysis Approach to the Morita-Baylis-Hillman Reaction of Aryl Vinyl Ketones

Abstract

The Morita-Baylis-Hillman (MBH) reaction of aryl vinyl ketones has been achieved for the first time through cooperative catalysis of proline and brucine N-oxide. A unique mode of activation of the aldehydes through proline iminium intermediates has been identified as a key reaction parameter for the successful MBH reaction of aryl vinyl ketones. The reaction pathways leading to 1:2 MBH products under typical nucleophilic catalysis conditions were investigated. A systematic study revealed two different reaction pathways leading to 1:2 MBH products: (1) the second reaction of normal MBH products with aryl vinyl ketones as a dominating reaction pathway at the initial stage of the reaction, and (2) the aldol reaction pathway of Rauhut-Currier products with aldehydes (autocatalysis by alcohol products) as a major reaction pathway during the later stage of reaction.

Key words

aldol reaction - alkaloids - catalysis - ketones - nucleophiles

References

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11

Reactions in various apolar and polar solvents, including MeOH, DMF, DMSO, and 1,4-dioxane, were examined, but no MBH reaction was observed.

12

A catalytic amount of both brucine N-oxide and proline can, in principle, be used, but the catalytic turnover number (TON) remains 2-3 after five days; use of 30 mol% of both catalysts provided up to 60-70% conversion after five days at 50 ˚C.

13

No significant conversion was observed after 42 h, although the crude NMR spectrum of the reaction mixture clearly indicated that the four reaction components were present (4a, 5a, brucine N-oxide, and proline) together with the MBH product 11a.

15

After 60 h at 23 ˚C, the 1:2 MBH adduct 6 was isolated in 70-80% yield from 2 equiv phenyl vinyl ketone, see also ref. 6.