Catalytic Enantioselective Formation of C−C Bonds by Addition to Imines and Hydrazones: A Ten-Year Update

Recent Advances of Catalytic Asymmetric 1,3-Dipolar Cycloadditions

Phase-transfer catalysis has been recognized as a powerful method for establishing practical protocols for organic synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large-scale synthesis, and the environmentally benign nature of the reaction system. Since the pioneering studies on highly enantioselective alkylations promoted by chiral phase-transfer catalysts, this research field has served as an attractive area for the pursuit of "green" sustainable chemistry. A wide variety of asymmetric transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable organic compounds in the past several decades, especially in recent years.

Recent Developments in Asymmetric Phase-Transfer Reactions

5. Hydrosilylation 3862 5.1. Alkene Hydrosilylation 3863 5.2. Ketone Hydrosilylation 3865 6. Alkene Hydrogenation 3866 7. Aldol-, Mannich-, and Michael-Type Reactions 3867 7.1. Enantioand Diastereoselective Conversions 3867 7.2. Remarks on Stereoselective Induction 3869 8. Miscellaneous Conversions 3869 9. Analogies between Yb2+ and Ca2+ Chemistry 3871 10. Conclusions and Perspectives 3872 11. References 3873

From limestone to catalysis: application of calcium compounds as homogeneous catalysts.

Novel dipolarophiles and dipoles in the metal-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylides.

Catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3 + 2] cycloaddition occurred in the reactions with crotonate derivatives, affording substituted pyrrolidine derivatives in high yields with high enantioselectivities. On the basis of this finding, we investigated asymmetric [3 + 2] cycloadditions, and it was revealed that several kinds of optically active substituted pyrrolidine derivatives containing contiguous stereogenic tertiary and quaternary carbon centers were obtained with high diastereo- and enantioselectivities. In addition, optically active pyrrolidine cores of hepatitis C virus RNA-dependent polymerase inhibitors and potential effective antiviral agents have been synthesized using this [3 + 2] cycloaddition reaction. NMR spectroscopic analysis and observation of nonamplification of enantioselectivity in nonlinear effect experiments suggested that a monomeric calcium species with an anionic ligand was formed as an active catalyst. A stepwise mechanism of the [3 + 2] cycloaddition, consisting of 1,4-addition and successive intramolecular Mannich-type reaction was suggested. Furthermore, modification of the Schiff base structure resulted in a modification of the reaction course from a [3 + 2] cycloaddition to a 1,4-addition, affording 3-substituted glutamic acid derivatives with high diasterero- and enantioselectivities.

Development of Catalytic Asymmetric 1,4-Addition and [3 + 2] Cycloaddition Reactions Using Chiral Calcium Complexes

The fluorenone imines of glycine esters and their phosphonic acid analogues

Catalytic C−C bond-forming reactions of aminoalkanes with imines were successfully performed using 9-fluorenylidene as a protecting and activating group of the nitrogen atom. The desired products were obtained in high yields with high diastereoselectivities using KOtBu/18-crown-6 or potassium 2,6-dimethylphenoxide as a catalyst. A wide substrate scope, including simple aminoalkanes and a variety of imines, has been demonstrated. For the products obtained, selective deprotection was possible under acidic conditions to give the desired monoamine and diamine derivatives in high yields with quantitative recovery of 9-fluorenone. A preliminary study of a catalytic asymmetric variant showed promising enantioselectivity in the desired product.

Kazutaka Seki

Papers

Development of Catalytic Asymmetric 1,4-Addition and [3 + 2] Cycloaddition Reactions Using Chiral Calcium Complexes

The fluorenone imines of glycine esters and their phosphonic acid analogues

Catalytic carbon-carbon bond-forming reactions of aminoalkane derivatives with imines.

Asymmetric meso-aziridine ring-opening reactions using a chiral zirconium catalyst.

An air-stable chiral Hf-based catalyst for asymmetric Mannich-type reactions