Brucine N-oxide-catalyzed Morita-Baylis-Hillman reaction of vinyl ketones: a mechanistic implication of dual catalyst system with proline.
The brucine N-oxide promoted Morita-Baylis-Hillman (MBH) reaction of vinyl ketones with aldehydes has been achieved. The corresponding asymmetric version of MBH reaction was also investigated, and the electron-deficient aryl aldehydes have emerged as suitable reaction partners for vinyl ketones; where proline was employed as a co-catalyst. In this dual catalyst system, proline is believed to form iminium intermediates with electron-deficient aryl aldehydes, while the N-oxide activates vinyl ketones to provide enolates through conjugate addition. Upon the combination of these two intermediates, the MBH products with high enantioselectivities are obtained by controlling of the rate-determining step through H-bridged chair-like transition state. Intrinsically, the resulting MBH products, alcohols, are found to interfere with the formation of both intermediates, enolates and proline iminium intermediates, thus the observed enantioselectivity of products attenuates upon further reaction conversion, possibly due to autocatalysis. This current study sheds lights on the synthetic utility of iminium species, derived from electron-deficient aryl aldehydes and proline.
Oh
Kyungsoo
K
Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202, USA. ohk@iupui.edu
Li
Jian-Yuan
JY
Ryu
Jinhyang
J
D000447:Aldehydes / Q000737:chemistry; D002384:Catalysis; D003497:Cyclic N-Oxides / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D013331:Strychnine / Q000031:analogs & derivatives* / Q000737:chemistry; D013379:Substrate Specificity
D000447:Aldehydes; D003497:Cyclic N-Oxides; D007659:Ketones; C083067:brucine N-oxide; D011392:Proline; D013331:Strychnine