A highly enantioselective Michael addition of cyclic 1,3-dicarbonyl compounds to b,g-unsaturated a-keto esters catalyzed by amino acid-derived thiourea-tertiary-amine catalysts is presented. Using 5 mol% of a novel tyrosine-derived thiourea catalyst, a series of chiral coumarin derivatives were obtained in excellent yields (up to 99%) and with up to 96% ee under very mild conditions within a short reaction time.Keywords: 1,3-dicarbonyl compounds; Michael addition; organocatalysts; thioureas; b,g-unsaturated a-keto esters Increased focus has recently been placed on the application of organocatalysis in reactions allowing the rapid construction of functionalized molecules from simple and readily available starting materials.[1] In this field, the asymmetric Michael addition of 1,3-cyclic dicarbonyl compounds to a,b-unsaturated carbonyl systems, which could provide many chiral compounds with biological and pharmaceutical activities such as neo-flavonoids and coumarins, has attracted much attention.[2] As a class of activated a,b-unsaturated carbonyl systems, b,g-unsaturated a-keto esters sometimes are preferred electrophiles in this kind of reaction due to their high reactivity and the easy convertibility of the resultant products to other useful structures.[3] In 2003, Jørgensen et al. reported the enantioselective Michael addition of cyclic 1,3-dicarbonyl compounds to b,g-unsaturated a-keto esters catalyzed by chiral bisoxazoline-copper(II) complexes with moderate to high enantioselectivities.[4] However, it was not until very recently that an similar organocatalyzed reaction between cyclic diketones and b,g-unsaturated a-keto esters using Cinchona alkaloid-derived pyrimidines was reported by Calter et al. [5] In contrast, several organocatalysts have been developed for the Michael addition of cyclic diketones to a,b-unsaturated ketones, in which the "imine catalysis" usually controls the enantioselectivity. [6] On the other hand, following the pioneering works of Jacobsen and Takemoto, [7] remarkable advances have been made in the development and application of bifunctional chiral thiourea catalysts in catalytic asymmetric reactions. [8] Recently, the use of inexpensive and readily available amino acids as the chiral scaffold to develop novel thiourea catalysts has attracted considerable interest and proved to be effective in several asymmetric reactions.[9] Our group has been interested in the development of organocatalytic reactions utilizing b,g-unsaturated a-keto esters as a reaction partner to synthesize useful compounds. [10] We report herein the development of several amino acid-derived thiourea-tertiary amine catalysts and their applications to the asymmetric Michael addition of cyclic 1,3-dicarbonyl compounds to b,g-unsaturated a-keto esters.Using the reaction between (E)-methyl 2-oxo-4-phenylbut-3-enoate (3a) and 4-hydroxycoumarin (4a) as the model reaction, a series of thiourea-tertiary amine catalysts (Figure 1) was evaluated and the results are summarized in Table 1. Similar to Takemotos ca...

Bifunctional catalyst: Simple bifunctional N‐Acyl aminophosphines such as 1 were developed to catalyze the first asymmetric [3+2] cycloaddition between allenoates and dual activated olefins. The cycloaddition reactions afford multifunctional chiral cyclopentenes with exclusive regioselectivity, and good to excellent enantioselectivity and yields.

Abstract:The asymmetric epoxidation of electrondeficient olefins has been achieved using inexpensive and readily available prolinols as catalysts with good to excellent yields and enantioselectivities. The utility of the resulting chiral epoxides was illustrated by elaboration to several synthetically useful compounds featuring a concise synthesis of (À)-(5R,6S)-balasubramide.