A Pd(II)/Brønsted acid catalyzed migratory ring expansion for the synthesis of indene derivatives possessing a stereogenic spirocyclic carbon center was developed. This transformation is believed to mechanistically proceed via enantioselective allylic C-H activation with concomitant semipinacol ring expansion to the nascent π-allylpalladium species. Enantioselectivities as high as 98% ee were attainable.

Intramolecular hydroamination of alkynyl amides was effected by a catalytic amount of Et2Zn (20 mol %) to form indole derivatives, and a tandem cyclization/nucleophilic addition procedure involving reaction of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient approach to C3-substituted indole derivatives when an excess of Et2Zn (120 mol %) was used.

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.

A multicomponent organocatalyzed highly diastereo- and enantioselective synthesis of CF(3)-substituted aziridines is described. This reaction of in situ generated CF(3)CHN(2) and aldimines was realized by chiral Brønsted acid catalysis. The utility of the products is illustrated by easy access to β-CF(3) isocysteine and aziridine-containing dipeptides.

Try bifunctional aminophosphines! An asymmetric organocatalytic [4+2] cycloaddition between α‐substituted allenoates and tosylaldimines using bifunctional N‐acyl aminophosphine catalysts was described (see scheme). This operationally simple catalytic system could provide valuable complementary results to those of the monodentate phosphine system.

No abstract

Flavanones are a large family of natural products with many important biological activities, such as antitumor and anti-inflammatory properties. [1, 2] However, despite intensive research devoted to the synthesis of flavanone derivatives, [3] only a limited number of methods, particularly catalytic asymmetric methods, are available for the asymmetric synthesis of this class of compound.[4] Structurally, the asymmetric, intramolecular oxa-Michael addition reaction of a phenol to chalcone would provide an easy access to chiral flavanones due to the ready availability of the starting materials. However, it was not until 2007 that a breakthrough based on this strategy, by using an organocatalytic method, was accomplished, by Scheidt and co-workers, [4d] probably due to the low reactivity of the substrates. They addressed this challenge by utilizing an activated, unsaturated ketone, 1, as the substrate and bifunctional chiral thioureas as catalysts (Scheme 1). Recently, Feng and co-workers [4g] reported a metal-catalyzed version of the same reaction employing chiral N,N'-dioxide nickel(II) complexes with excellent results. In view of these results, there is still the potential for the development of new organocatalysts to effect an asymmetric intramolecular oxa-Michael addition as a route to synthesize chiral flavanones.On the other hand, the introduction of a fluorine atom into a compound often results in important changes in its biological activity, which can lead to potential applications in medicinal chemistry and the pharmaceutical industry. [5] One of the most challenging subjects in the field of synthetic fluorine chemistry is the enantioselective construction of the C À F bond at a stereogenic carbon center.[6] Since the first asymmetric fluorination reagents were reported by Differding and Lang [7a] in 1988 and the first catalytic enantioselective fluorination was disclosed by Hintermann and Togni [7b] in 2000, this intriguing field of catalytic asymmetric fluorination has been blooming. [8,9] Our group has developed a onepot tandem reaction for the synthesis of fluorinated flavanones, from b-ketoesters and aldehydes, with excellent diastereoselectivities.[10] On the basis of these results, we envisaged that by using an appropriate bifunctional catalyst, an organocatalytic, asymmetric, intramolecular oxa-Michael addition of 1 would produce enantioenriched 2, which could then be subjected to electrophilic fluorination to provide novel, chiral, fluorinated flavanone derivatives (Scheme 1). Herein, we report the details of this research.Cinchona alkaloids and their derivatives were selected as catalysts to be investigated due to their easy availability and well-documented power as bifunctional organocatalysts in