Saihu Liao

Copper-Catalyzed Highly Enantioselective Cyclopentannulation of Indoles with Donor–Acceptor Cyclopropanes

A highly diastereo- and enantioselective BOX/Cu(II)-catalyzed C2,C3-cyclopentannulation of indoles with donor-acceptor cyclopropanes has been developed on the basis of asymmetric formal [3 + 2] cycloaddition of indoles. This reaction provides rapid and facile access to a series of enantioenriched cyclopenta-fused indoline products and can be further extended to the construction of tetracyclic pyrroloindolines. The synthetic potential of the reaction was demonstrated in a four-step synthesis of the core structure of borreverine.

Asymmetric Annulation of Donor-Acceptor Cyclopropanes with Dienes.

An efficient [4 + 3] cycloaddition reaction of D-A cyclopropanes with dienes has been successfully developed. The reaction proceeds well with various dienolsilyl ethers in the presence of Lewis acid, delivering a variety of cycloheptenes and [n,5,0]carbobicycles with excellent stereoselectivity. The asymmetric version of this reaction is also realized using a newly designed chiral Cy-TOX ligand, providing a new approach to access optically active cycloheptenes and [n,5,0]carbobicycles. Mechanisic study reveals that the reaction involves a stepwise pathway, which undergoes an unusual ring opening of five-membered [3 + 2] intermediate and sequential intramolecular cyclization to afford the thermodynamically stable [4 + 3] annulation product.

Highly Diastereo- and Enantioselective Cyclopropanation of 1,2-Disubstituted Alkenes†

Since Nozaki et al. reported the first enantioselective synthesis of cyclopropanes, a reaction that involved coppercatalyzed transfer of a carbene moiety from diazo compounds to alkenes, much effort has been devoted to the area of transition-metal-catalyzed asymmetric cyclopropanation reactions because it is a straightforward method for accessing optically active cyclopropanes. However, there are only a few examples where 1,2-disubstituted alkenes have been transformed through a transition-metal-catalyzed asymmetric cyclopropanation reaction with high levels of diastereoand enantioselectivity; these reactions usually involve cyclic alkenes and trisubstituted alkenes. In 1991, Masamune et al. reported a double-asymmetric-induction approach in which cis-b-methyl styrene was transformed using a Cu/BOX-catalyzed cyclopropanation reaction involving l-menthol-derived diazoacetate to give product in 92 % ee and 76% de. High enantioselectivity was achieved by Ito and Katsuki when they used chiral bipyridine ligands in the cyclopropanation of trans-b-methyl styrene, although the diastereoselectivity was low (trans/cis 40:60). Recently, Katsuki and co-workers reported the use of an aryliridium/ salen catalyst, which led to remarkably high levels of enantioand diastereoselectivity (favoring the cis product) in the cyclopropanation of terminal and cyclic alkenes. However, when cis-b-methyl styrene was used as a substrate, a relatively low yield of product (29%) was obtained and for trans-bmethyl-styrene only a trace amount of cyclopropanation product was obtained. The unsatisfactory results obtained in the cases of 1,2-disubstituted alkenes can be mainly ascribed to the high sensitivity of metallocarbenes to the steric hindrance and geometry of the alkene. Therefore, a cyclopropanation catalyst that is efficient and applicable to the highly stereoselective cyclopropanation of both cisand trans-1,2-disubstituted alkenes, especially simple trans alkenes, is still in high demand. Herein, we report that the use of bis(oxazoline) (BOX) ligands that contain C2-symmetrybreaking pendant groups in the copper-catalyzed cyclopropanation of both cisand trans-1,2-disubstituted alkenes can lead to high levels of diastereoand enantioselectivity. We commenced our study by screening copper salts in combination with several BOX ligands in the cyclopropanation reaction of cis-b-methyl styrene (Table 1). When using

A highly efficient and enantioselective intramolecular Cannizzaro reaction under TOX/Cu(II) catalysis.

An asymmetric intramolecular Cannizzaro reaction of aryl and alkyl glyoxals with alcohols has been realized with an unprecedented high level of enantioselectivity, on the basis of a newly developed congested TOX ligand and a gradual liberation protocol of active glyoxals from glyoxal monohydrates. Preliminary results suggested a mechanism of enantioselective addition of alcohols to glyoxals contributing most to the stereoselectivity, other than by the dynamic kinetic resolution of hemiacetal intermediates.

Asymmetric 1,2-Perfluoroalkyl Migration: Easy Access to Enantioenriched α-Hydroxy-α-perfluoroalkyl Esters

This study has led to the development of a novel, highly efficient, 1,2-perfluoro-alkyl/-aryl migration process in reactions of hydrate of 1-perfluoro-alkyl/-aryl-1,2-diketones with alcohols, which are promoted by a Zn(II)/bisoxazoline and form α-perfluoro-alkyl/-aryl-substituted α-hydroxy esters. With (-)-8-phenylmenthol as the alcohol, the corresponding menthol esters are generated in high yields with excellent levels of diastereoselectivity. The mechanistic studies show that the benzilic ester-type rearrangement reaction takes place via an unusual 1,2-migration of electron-deficient trifluoromethyl group rather than the phenyl group. The overall process serves as a novel, efficient, and simple approach for the synthesis of highly enantioenriched, biologically relevant α-hydroxy-α-perfluoroalkyl carboxylic acid derivatives.

A sidearm-assisted phosphine for catalytic ylide intramolecular cyclopropanation

The first phosphine-catalyzed cyclopropanation reaction via covalent ylide catalysis has been realized with high efficiency in the presence of sidearm-assisted phosphine catalysts. An ether sidearm group is found critical to turn on the catalytic activity. Crystal structures of the catalyst-derived phosphonium salts indicated a significant O⋯P+ interaction between the pendant ether oxygen and the phosphonium center, which is believed to favor the catalyst regeneration. DFT calculations rationalize the insight of the sidearm effects.