Organocatalytic Conjugate Addition of Malononitrile to Conformationally Restricted Dienones

Abstract

Organocatalytic conjugate addition of malononitrile to conformationally restricted dienones has been studied. A series of chiral primary and tertiary amine catalysts were screened. A piperidine-based thiourea-tertiary amine was found to be the efficient catalyst. Chiral pyran derivatives were obtained in excellent yields and enantioselectivities via a cascade conjugate addition-intramolecular cyclization pathway. The reaction is remarkably different for the corresponding reaction of conformationally flexible dienones.

Quinine-catalyzed enantioselective tandem conjugate addition/intramolecular cyclization of malononitrile and 1,4-dien-3-ones

“…The absolute configuration of 4 was assigned as (S) except for 4r which was assigned as (R) by the comparison of the specific optical rotation with our previous report. 4 A number of other cyclic 1,5-diphenyl-1,4-pentadien-2-ones was also examined and the results are summarized in Scheme 1. Excellent yields and good enantioselectivities were achieved with 1q-s (Scheme 1).…”

“…4S,8E)-2-Amino-4-(2-chlorophenyl)-8-(2-chlorophenylmethylene)-5,6,7,8-tetrahydro-6-met hyl-4H-pyrano[3,2-c]pyridine-3-carbonitrile (4j). 4 10 H),6.96 (dd,J 15.3,11.6 Hz,1 H),6.70 (d,J 15.4 Hz,1 H),6.55 (d,J 11.8 Hz,1 H),6.51 (d,J 15.7 Hz,1 H),5.99 (dd,J 15.6,8.9 Hz, 1 H), 4.58 (s,2 H),3.62 (d,J 8.9 Hz,1 H),3.57 (d,J 14.0 Hz,1 H),3.38 (d,J 13.9 Hz,1 H),3.14 (d,J 16. 8E)-2-Amino-5,6,7,8-tetrahydro-4-phenyl-6-(phenylmethyl)-8-(phenylmethylene)-4H-p yrano[3,2-c]pyridine-3-carbonitrile (4o). 4 …”

“…Recently, we developed an enantioselective cascade reaction of malononitrile and dienones. 4 Bicyclic pyrans 4 were prepared in excellent yields and enantioselectivities. Although N- [3,5-bis(trifluoromethyl)phenyl]-N'-[(R,R)-2-(1-piperidinyl)cyclohexyl]thiourea was found to be the efficient catalyst for the transformation, it is not commercially available and requires tedious synthesis.…”

Recent Developments in Asymmetric Organocatalytic Domino Reactions

“…[76] It must be noted that these products constituted potential inhibitors against M. tuberculosis. Furthermore, the results obtained with conformationally restricted dienones 156a-e were significantly different from those obtained from the reaction of conformationally flexible dienones, which generated upon catalysis with 9-amino-9-deoxyepiquinine the corresponding cyclohexanones in moderate to high yields (35-87%), and excellent enantioselectivities (95-99% ee), as previously reported by the same authors.…”

Asymmetric Michael Addition of Malononitrile with Chalcones via Rosin-Derived Bifunctional Squaramide

“…The Michael reaction of carboanion nucleophiles to activated olefins represents a powerful type of the most remarkable transformations for the new carbon-carbon bond formation in modern organic synthesis, and has been immensely exploited over the past few decades [1][2][3][4][5][6][7]. Among the versatile nucleophiles, the employment of malononitrile for asymmetric Michael addition has received extensive attention since its nitrile group could be efficiently converted to valuable functionalities [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. To date, a few research groups have devoted their efforts to the catalytic asymmetric Michael reaction of malononitrile onto chalcones and their analogues, by either metal-catalytic [19,20] or organocatalytic [21][22][23][24][25][26][27] methods.…”