Xiu-Li Sun

Asymmetric Nazarov Reaction Catalyzed by Chiral Tris(oxazoline)/Copper(II)†

The frequent occurrence of five-membered carbocycles in natural products and other biologically active compounds has provided a major impetus for the development of efficient methods for their construction. Towards this end, the Nazarov cyclization, a stereospecific 4p electrocyclization that converts divinyl ketones into cyclopentenones through a conrotatory cyclization, has distinguished itself as a powerful tool for the synthesis of such compounds. Over several decades, great efforts have been devoted to the exploitation of the Nazarov reaction, further highlighting its synthetic utility, as demonstrated by its increasing use in total syntheses. However, the asymmetric Nazarov reaction with a catalytic amount of chiral source was not reported until the end of 2003, probably because of the complex mechanism of the reaction. Of those catalytic asymmetric reactions developed, few examples have been reported that give good to excellent enantiocontrol in good yields, except for divinyl ketones that belong to type A or B (Scheme 1).

Side-Arm-Promoted Highly Enantioselective Ring-Opening Reactions and Kinetic Resolution of Donor–Acceptor Cyclopropanes with Amines

A Ni-catalyzed asymmetric ring-opening reaction of 2-substituted cyclopropane-1,1-dicarboxylates with aliphatic amines has been accomplished using the chiral indane-trisoxazoline (In-TOX) ligand. This highly enantioselective reaction provides an efficient approach to a variety of chiral γ-substituted γ-amino acid derivatives, which are readily transformed into multifunctionalized piperidines and γ-lactams. The single-crystal X-ray structure of the TOX-Ni complex is provided, and the role of the side arm in the chiral ligand is discussed.

An Organocatalytic Asymmetric Tandem Reaction for the Construction of Bicyclic Skeletons

Cyclic ketones react with (E)-2-nitroallylic acetates in the presence of catalytic pyrrolidine-thiourea, which affords bicyclic skeletons with four or five stereocenters in one single reaction with up to 98 % ee in moderate to high yields. The cooperative effects of both enamine and the Brønsted acid are found to be crucial for the high reactivity and enantioselectivity of this cascade reaction, which is demonstrated by both theoretical calculation and experimental data.

[O−NSR]TiCl3‐Catalyzed Copolymerization of Ethylene with Functionalized Olefins

Much attention has been paid to the copolymerization of ethylene with polar alkenes catalyzed by transition-metal complexes, because it provides easy and low-cost access to functional polyethylenes (PEs) with unique properties. Since the active species in olefin polymerization are metal cations in most cases, the polar alkene monomer will poison and deactivate the catalytic species under the polymerization conditions (Scheme 1). Two strategies, either the use of late-

Tandem Michael addition/ylide epoxidation for the synthesis of highly functionalized cyclohexadiene epoxide derivatives

A highly efficient diastereoselective synthesis of cyclohexadiene epoxide derivatives with a multi-stereocenter has been developed via a tandem ylide Michael addition/epoxidation. By employing a chiral sulfonium ylide, up to 96% ee can be achieved in good yields.

Highly diastereoselective and enantioselective formal [4 + 1] ylide annulation for the synthesis of optically active dihydrofurans.

On the basis of the reactions of camphor-derived sulfur ylide with alpha-ylidene-beta-diketones, highly efficient and selective synthesis of optically active dihydrofurans has been achieved.

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

Switchable Reactions of Cyclopropanes with Enol Silyl Ethers. Controllable Synthesis of Cyclopentanes and 1,6-Dicarbonyl Compounds

Cu(SbF(6))(2)-catalyzed reaction of 2-substituted cyclopropane-1,1-dicarboxylates 1 with enol silyl ethers 2 can be readily controlled: the reaction undergoes a cycloaddition to provide substituted cyclopentane derivatives 3 in excellent yields with high diastereoselectivities in the presence of complex 8/Cu(II); however, the same substrates afford acyclic 1,6-dicarbonyl products 4 via a cycloaddition-ring-opening reaction in up to 92% yield in the absence of ligand 8. The mechanism for the ligand-switchable reactions was investigated by both control experiments and (1)H NMR studies. The substrate scope and limitation of the tunable transformation were also examined.

Highly diastereoselective construction of fused carbocycles from cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers: scope, mechanism, and origin of diastereoselectivity.

Cyclopropane rings true: By selecting the appropriate substituents on the ester and silyl groups, fused cyclopentane derivatives with multiple contiguous stereocenters can be synthesized with excellent diastereoselectivity through Cu(II)/bisoxazoline-catalyzed intermolecular [3+2] cycloaddition reactions of cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers (see scheme).

Highly enantioselective synthesis of isoxazoline N-oxides

The reaction of cinchonidine (cinchonine)-derived ammonium salts with nitroolefins in the presence of Cs2CO3 to afford optically active isoxazoline N-oxides with excellent ee and high de values has been developed.