Chiral-Boron-Complex-Catalyzed Asymmetric [3 + 2] Cycloaddition of ß-Trifluoromethyl α,ß-Unsaturated Ketones with N,N'-Cyclic Azomethine Imines.

The (R)-3,3'-(3,5-(CF3)2-C6H3)2-BINOL-boron-complex-catalyzed asymmetric 1,3-dipolar cycloaddition of ß-trifluoromethyl α,ß-unsaturated ketone with N,N'-cyclic azomethine imines was developed to afford N,N'-bicyclic pyrazolidine derivatives bearing a stereogenic carbon center containing CF3 motifs in high yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, and >99% ee). This catalytic system features mild reaction conditions, high efficiency, and a broad substrate scope.

Highly Enantioselective Chiral Diol-Catalyzed Conjugate Addition of Boronic Acids to α,ß-Unsaturated Trifluoromethyl Ketones.

The (R)-3,3'-(3,5-(CF3)2-C6H3)2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to α,ß-unsaturated 1,1,1-trifluoromethyl ketones affords corresponding addition products bearing a stereogenic center at the ß-position in moderate to high yields and excellent enantioselectivities (up to 99% ee), without any 1,2-addition product formation. Moreover, this catalytic protocol features mild reaction conditions, a broad substrate scope, suitability for alkenylboronic acids and (hetero)arylboronic acids, and easy scale-up.

Chiral-Boron-Complex Catalyzed Asymmetric Inverse-Electron-Demand Aza-Diels-Alder Reaction of ß-Trifluoromethyl α,ß-Unsaturated Ketones with Cyclic N-Sulfonyl Ketimines.

A highly efficient asymmetric inverse-electron-demand aza-Diels-Alder reaction of ß-trifluoromethyl α,ß-unsaturated ketone with cyclic N-sulfonyl ketimines catalyzed by (R)-3,3'-I2-BINOL-boron-complex was developed. A broad range of fused piperidine derivatives bearing stereogenic carbon containing CF3 motifs were prepared in high yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, and >99% ee). This protocol had the characteristics of mild reaction conditions, high efficiency, and high stereoselectivity.

Enantioselective Synthesis of Chiral Organosilicon Compounds by Organocatalytic Asymmetric Conjugate Addition of Boronic Acids to ß-Silyl-α,ß-Unsaturated Ketones.

Herein, we report (R)-3,3'-(3,5-(CF3)2-C6H3)2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to ß-silyl-α,ß-unsaturated ketones, furnishing moderate to excellent yields of the corresponding ß-silyl carbonyl compounds with stereogenic centers in excellent enantioselectivities (up to 98% ee). Moreover, the catalytic system features mild reaction conditions, high efficiency, broad substrate scope, and easy scale-up.

Oxoammonium Salt-Promoted Multifunctionalization of Saturated Cyclic Amines Based On ß-Oxo Cyclic Iminium Ion Intermediates.

Herein we describe a convenient method for multiple C(sp3)-H bond functionalization of saturated cyclic amines through oxoammonium salt-promoted oxidation to afford a ß-oxo cyclic iminium ion as a key intermediate, followed by cascade addition with thiocyanate and diverse N-, O-, and S-containing nucleophiles in the green solvent and EtOH. Notably, chiral spiro azapolyheterocycles were prepared enantioselectively (>20:1 dr, up to 99% ee) when cysteine or serine esters were used as substrates. Moreover, the concise late-stage modification of several natural product derivatives was accomplished using this method.

Chiral-Boron-Complex-Catalyzed Asymmetric [3 + 2] Cycloaddition of 2'-Hydroxychalcones with N,N'-Cyclic Azomethine Imines.

We report the (R)-3,3'-I2-BINOL-boron-complex-catalyzed asymmetric 1,3-dipolar cycloaddition of 2'-hydroxychalcones with N,N'-cyclic azomethine imines, providing the corresponding N,N'-bicyclic pyrazolidine derivatives with three contiguous tertiary stereocenters in high yields with excellent diastereo- and enantioselectivities (up to >99:1 diastereomeric ratio and >99% enantiomeric excess). This catalytic system exhibits advantages of mild reaction conditions, high efficiency, and broad substrate scopes.

Enantioselective Conjugate Addition of Boronic Acids to α,ß-Unsaturated 2-Acyl Imidazoles Catalyzed by Chiral Diols.

Herein, we report the enantioselective conjugate addition of organic boronic acids to α,ß-unsaturated 2-acyl imidazoles using (R)-3,3'-I2-BINOL as the catalyst. The catalytic system shows high efficiency and tolerance to alkenylboronic acids and heteroarylboronic acids. The corresponding Michael addition products were obtained in moderate to excellent yields and with moderate to excellent enantioselectivities (up to 97% ee). A gram-scale reaction was also conducted, and the desired product was obtained in high yield with no erosion in enantioselectivity. Finally, the synthetic utility of the methodology was demonstrated by transforming the 2-acyl imidazole moiety to the corresponding aldehyde, carboxylic acid, ester, and amide derivatives.

Organocatalyzed Enantioselective Conjugate Addition of Boronic Acids to ß,γ-Unsaturated α-Ketoesters.

We report herein the (R)-3,3'-Br2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to ß,γ-unsaturated α-ketoesters to generate the corresponding Michael addition products in moderate to high yields and with moderate to excellent enantioselectivities (up to 99% ee). This catalytic system features characteristics of mild reaction conditions, high efficiency, and tolerance to alkenylboronic acids and heteroarylboronic acids.

Chiral Hydroxytetraphenylene-Boron Complex Catalyzed Asymmetric Diels-Alder Cycloaddition of 2'-Hydroxychalcones.

(S)-2,15-Cl2-DHTP-boron complex catalyst for the asymmetric Diels-Alder cycloaddition of 2'-hydroxychalcones and dienes was developed and tested. The resulting cyclohexenes with three chiral centers were obtained in high yields (up to 98%) with excellent stereoselectivities (up to >20:1 endo/exo, >99% ee). This catalytic system features high efficiency, broad substrate scopes, and mild reaction conditions. In addition, a DFT study was performed to explain the stereochemical course of the asymmetric induction.

Chiral Hydroxytetraphenylene-Catalyzed Asymmetric Conjugate Addition of Boronic Acids to Enones.

( S)-2,15-Br2-DHTP-catalyzed asymmetric conjugate addition of boronic acids to ß-trifluoromethyl α,ß-unsaturated ketones and enones was studied. The reaction afforded the corresponding Michael addition products in moderate to high yields with excellent enantioselectivities (up to 99:1 er). This catalytic system features mild reaction conditions, high efficiency, and tolerance to heteroarylboronic acids.

Synthesis and Application of Substituted 1,16-Dihydroxytetraphenylenes in Catalytic Asymmetric Allylboration of Ketones.

The synthesis and application of a newly designed C2-symmetric chiral-substituted 1,16-dihedroxytetraphenylene (DHTP) is reported. Efficient syntheses of enantiopure substituted DHTP were accomplished, and these enantiopure compounds were used as organocatalysts in asymmetric allylboration of ketones under very mild conditions. Accordingly, several tertiary alcohols were generated in moderate to good yields with up to 99% ee by using the catalyst ( S)-2,15-Br2-DHTP. A gram-scale reaction was achieved in 99% yield with 96% ee.

Asymmetric Darzens Reaction of Isatins with Diazoacetamides Catalyzed by Chiral BINOL-Titanium Complex.

An efficient catalytic asymmetric Darzens reaction of N-protected isatins with diazoacetamides using a chiral BINOL/Ti(OiPr)4 complex as the catalyst has been developed. This reaction is a straightforward method for the synthesis of spiro-epoxyoxindoles in 40-95% yields, up to >20:1 dr and up to >99% ee. A gram-scale reaction was also achieved in 95% yield with excellent stereoselectivity and enantioselectivity (>20:1 dr, >99% ee).