Kohsuke Aikawa

Axial Chirality Control of Gold(biphep) Complexes by Chiral Anions: Application to Asymmetric Catalysis

In transition-metal-catalyzed reactions, the design of chiral ligands is important to achieve a high level of asymmetric induction. A dramatic increase in catalytic activity and enantioselectivity can result from a subtle change in the conformational, steric, and electronic properties of chiral ligands. Many efficient chiral phosphine ligands, especially atropisomeric (atropos) ones, have been reported to induce high enantioselectivity and yield. However, does the pursuit of atropos ligands always result in efficient asymmetric catalysis? Because of the substrate dependence of many catalyst systems, tunable and readily synthesized chiral ligands are strongly desirable. Chirally flexible (tropos) ligands, which are highly modular, versatile, and easy to synthesize without resolution, have thus been a recent topic in asymmetric catalysis; We have focused on the tropos bis(phosphanyl)biphenyl (biphep) ligands 1 to develop a new strategy for asymmetric catalysis. The biphep ligands can behave dynamically as chiral bidentate ligands for Ru, Rh, Pd, and Pt complexes when their axial chirality is controlled by chiral diamine or diene ligands. We report herein that axial chirality can be controlled in gold–biphep complexes in a highly stereospecific manner by using the binaphthol-derived phosphate anion 2, 10, 11] and that high levels of enantioselectivity can be attained in intramolecular hydroamination (Scheme 1). In contrast to our previous reports, chirality control can be attained by monodentate coordination of the chiral anion 2 as a supramolecular chiral auxiliary. The control of the axial chirality of a metal complex by a chiral anion with a high degree of stereospecificity has been a long-standing challenge. We attempted to control the axial chirality of 1-Au/(S)-2 complexes by converting the thermodynamically unfavorable diastereomer to the thermodynamically favorable one (Table 1). The combination of rac-1-AuCl and two equivalents of the silver phosphate complex (S)-2-Ag in acetone at room temperature produced a mixture of 1-Au/(S)-2 diastereomers quantitatively within 1 h. The use of anion 2a initially led to a d.r. value of 52:48, which did not change at room temperature (Table 1, entry 1). However, the isomerization proceeded in acetone at 80 8C over 14 h to give (S)-1a-Au/(S)2a (75:25) as the major diastereomer (Table 1, entry 2). No change of d.r. was observed upon heating up to 100 8C (Table 1, entry 3). Benzene or THF as a solvent resulted in lower diastereoselectivity (Table 1, entries 4 and 5). By introducing a variety of aryl substituents at the 3,3’-positions of the binaphthyl backbone, a series of chiral anions (S)-2 can be generated. When (S)-2 derivatives bearing only phenyl rings or para-substituted phenyl rings were used, remarkably high diastereoselectivity resulted (Table 1, entries 6 and 7). Additionally, the 1 a-Au complexes with chiral anions 2d,e isomerized at 100 8C over 14 h to afford exclusively the thermodynamically favored (S)-1 a-Au/(S)-2 complexes (Table 1, entries 8 and 9). As a result of the steric effect of biphep moiety, the 1b-Au complexes with the chiral anions 2c Scheme 1. Strategy of this work. a) Axial chirality control of tropos biphep–gold complexes 1 by using chiral anion 2. b) Isolation of chirally stable enantiopure biphep–gold complexes below room temperature. c) Application of enantiopure biphep–gold complexes to asymmetric catalysis.

Asymmetric hetero Diels–Alder reaction using chiral cationic metallosalen complexes as catalysts

Abstract Chiral cationic (R,S)- or (R,R)-(salen)–manganese(III) and –chromium(III) complexes served as the catalysts for asymmetric hetero Diels–Alder reaction of Danishefskys diene with aldehydes, achieving high enantioselectivity (up to 97% ee at 0°C). The reactions of aldehydes bearing no precoordinating functional group were well effected by using (R,R)-complexes as catalysts, while those of aldehydes bearing a precoordinating functionality were better effected by using (R,S)-complexes.

Highly Enantioselective Alkynylation of Trifluoropyruvate with Alkynylsilanes Catalyzed by the BINAP−Pd Complex: Access to α-Trifluoromethyl-Substituted Tertiary Alcohols

A highly enantioselective alkynylation catalyzed by the dicationic (S)-BINAP-Pd complex with a variety of alkynylsilanes and trifluoropyruvate is described. The catalytic reaction is applicable to highly enantioselective addition of polyyne to trifluoropyruvate to construct α-trifluoromethyl-substituted tertiary alcohols as enantiomerically enriched forms. The alkynyl products can be converted into a chiral allene bearing a trifluoromethyl group.

Copper(I)-catalyzed asymmetric desymmetrization: synthesis of five-membered-ring compounds containing all-carbon quaternary stereocenters.

A highly stereoselective catalytic alkylation sequence for the synthesis of highly functionalized and versatile five-membered-ring compounds bearing all-carbon quaternary stereocenters was developed. Enantioselective desymmetrization of achiral cyclopentene-1,3-diones was thus executed by chiral Cu-phosphoramidite catalysts. A variety of complicated cyclopentane derivatives can be synthesized with excellent stereoselectivities using a low catalyst loading in a one-pot operation.

Catalytic asymmetric synthesis of stable oxetenes via Lewis acid-promoted [2+2] cycloaddition.

A highly enantioselective and atom-economical [2 + 2] cycloaddition of various alkynes with trifluoropyruvate using a dicationic (S)-BINAP-Pd catalyst has been established. This is the first enantioselective synthesis of stable oxetene derivatives, whose structure has been clarified by X-ray analysis. This catalytic process offers a practical synthetic method for oxetene derivatives (catalyst loading: up to 0.1 mol %), which can serve as novel chiral building blocks for pharmaceuticals and agrochemicals and can also be transformed into a variety of enantiomerically enriched CF(3)-substituted compounds with high stereoselectivity.

Highly Enantioselective Alkenylation of Glyoxylate with Vinylsilane Catalyzed by Chiral Dicationic Palladium(II) Complexes

Chiral dicationic palladium complex-catalyzed vinylation and dienylation of glyoxylate with vinylsilanes and dienylsilanes to produce highly optical active allylic alcohols has been achieved. The advantages of this reaction are that the chiral palladium catalyst is readily employed and that vinylsilanes as nucleophiles are easily synthesized, storable, and air- and moisture-stable.

Stable but Reactive Perfluoroalkylzinc Reagents: Application in Ligand‐Free Copper‐Catalyzed Perfluoroalkylation of Aryl Iodides

The aromatic perfluoroalkylation catalyzed by a copper(I) salt with bis(perfluoroalkyl)zinc reagents Zn(RF)2(DMPU)2, which were prepared and then isolated as a stable white powder from perfluoroalkyl iodide and diethylzinc, was accomplished to provide the perfluoroalkylated products in good-to-excellent yields. The advantages of this reliable and practical catalytic reaction are 1) air-stable and easy-to-handle bis(perfluoroalkyl)zinc reagents can be utilized, 2) the reagent is reactive and hence the operation without activators and ligands is simple, and 3) not only trifluoromethylation but also perfluoroalkylation can be attained.

Catalyst self-adaptation in conjugate addition to nitroalkenes and nitroacrylates: instant chirality control in diphenylmethane-based phosphoramidite ligands.

The tropos diphenylmethane-based phosphoramidite ligand (A) provides high catalytic activity and enantioselectivity in the Cu catalysis of conjugate addition to nitroalkenes and nitroacrylate, by virtue of instant chirality control in A.

Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide

Summary The trifluoromethylation of aryl iodides catalyzed by copper(I) salt with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide and Zn dust was accomplished. The catalytic reactions proceeded under mild reaction conditions, providing the corresponding aromatic trifluoromethylated products in moderate to high yields. The advantage of this method is that additives such as metal fluoride (MF), which are indispensable to activate silyl groups for transmetallation in the corresponding reactions catalyzed by copper salt by using the Ruppert–Prakash reagents (CF3SiR3), are not required.

Achiral benzophenone ligand-rhodium complex with chiral diamine activator for high enantiocontrol in asymmetric transfer hydrogenation

The chirality of an achiral benzophenone-based rhodium complex can be controlled by chiral diamines to afford significantly high enantioselectivity in the catalytic asymmetric transfer hydrogenation of ketones (up to 99% ee, 99% yield).