Yan Zhang

Copper-Catalyzed C(sp3)–C(sp3) Bond Formation Using a Hypervalent Iodine Reagent: An Efficient Allylic Trifluoromethylation

An efficient copper-catalyzed allylic trifluoromethylation reaction has been developed. This reaction provides a general and straightforward way to synthesize allylic trifluoromethylated compounds under mild conditions.

Silver-mediated trifluoromethylation of aryldiazonium salts: conversion of amino group into trifluoromethyl group.

A novel strategy for aromatic trifluoromethylation by converting aromatic amino group into CF3 group is reported herein. This method, which can be considered as trifluoromethylation variation of the classic Sandmeyer reaction, uses readily available aromatic amines as starting materials and is performed under mild conditions.

Recent developments in copper-catalyzed reactions of diazo compounds.

Copper-catalyzed reaction of diazo compounds generates copper carbene intermediates that undergo diverse transformations. In recent years, the selectivity and efficiency of these important conversions have been further improved. In particular, breakthroughs have been made in catalytic asymmetric polar X-H bond insertion reactions. Moreover, novel transformations based on copper carbene, namely copper-catalyzed cross-couplings of diazo compounds, have emerged as powerful methods for carbon-carbon bond formations. This feature article summarizes the most recent developments in this area.

C(sp)–C(sp3) Bond Formation through Cu-Catalyzed Cross-Coupling of N-Tosylhydrazones and Trialkylsilylethynes

Copper-catalyzed cross-coupling of N-tosylhydrazones with trialkylsilylethynes leads to the formation of C(sp)-C(sp(3)) bonds. Cu carbene migratory insertion is proposed to play the key role in this transformation.

Palladium-Catalyzed Oxidative Cross-Coupling of N-Tosylhydrazones or Diazoesters with Terminal Alkynes: A Route to Conjugated Enynes†

Conjugated enynes have attracted considerable attention owing to their biological importance, their occurrence in various natural products, and their versatility as building blocks for the synthesis of organic conducting polymers. As a result, enormous effort has been devoted to the regioand stereoselective synthesis of conjugated enynes. Among the various methods developed in the past decades for the synthesis of enynes, the metal-catalyzed dimerization of terminal alkynes is a straightforward and atom-efficient approach (Scheme 1a, R = R’’, R’= H). However, the complicated regioand stereoselectivity of the dimerization process hampers the wide application of this method. Moreover, only in limited cases is the selective cross-coupling of two different alkynes possible. A solution to overcome this setback is the coupling of alkynes with structurally defined organometallic alkenes (Scheme 1b). However, organometallic substrates are usually difficult to handle and are toxic in general. The coupling of terminal alkynes with vinyl halides under the catalysis of palladium complexes and copper(I) iodide, namely, the Sonogashira reaction, is another option for the synthesis of conjugated enynes (Scheme 1c). This elegant process does not require a stoichiometric amount of an organometallic reagent and can produce enynes in a stereoselective manner. The major limitation of this method is that multiple steps are generally required for the preparation of the vinyl halide. In view of the limitations and shortcomings of these established methods, we conceived that it would be desirable to further develop a new type of coupling reaction that may circumvent these drawbacks. Palladium-catalyzed cross-coupling reactions involving diazo compounds as coupling partners have emerged as a new type of C=C bond-forming reaction. In pioneering studies, Van Vranken and co-workers demonstrated palladium-catalyzed coupling reactions with trimethylsilyldiazomethane. 8] Barluenga et al. first discovered a palladiumcatalyzed coupling reaction of N-tosylhydrazones with aryl bromides. We have also reported a series of palladiumcatalyzed cross-coupling reactions with a-diazocarbonyl compounds or N-tosylhydrazones as coupling partners. 14] Migratory insertion involving a palladium carbene is proposed to account for these cross-coupling reactions. Aryl, 10] benzyl, vinyl, allyl, and acyl groups have so far been used as the migratory group. As a continuation of our interest in palladium-catalyzed migratory-insertion reactions, we report the palladium-catalyzed cross-coupling of terminal alkynes with N-tosylhydrazones or diazoesters. The reaction involves an unprecedented alkynyl migratory insertion of a palladium carbene to afford conjugated enynes in a highly stereoselective manner (Scheme 1d). Initially, we chose phenylbromoethyne (2 a) as the crosscoupling partner and examined its reaction with the N-tosylhydrazone 1a in the presence of various palladium catalytic systems. However, none of the desired product was obtained. We then decided to explore an oxidative coupling process with a terminal alkyne. Li and co-workers reported a palladium-catalyzed 1,4-addition of terminal alkynes to C=C bonds in which the reactivity of the alkynyl C Pd bond could be increased by an electron-rich ligand. Enlightened by this report, we attempted the coupling of phenylacetylene (2b) Scheme 1. Synthesis of conjugated enynes. EWG =electron-withdrawing group, Ts = p-toluenesulfonyl.

Formal carbene insertion into C-C bond: Rh(I)-catalyzed reaction of benzocyclobutenols with diazoesters.

A Rh(I)-catalyzed formal carbene insertion into C-C bond of benzocyclobutenols has been realized by employing diazoesters as carbene precursors. The product indanol derivatives were obtained in good yields and in diastereoselective manner under mild reaction conditions. All-carbon quaternary center is constructed at the carbenic carbon. This catalytic reaction involves selective cleavage of C-C bond, Rh(I) carbene insertion, and intramolecular aldol reaction.

Ir(III)-Catalyzed Aromatic C–H Bond Functionalization via Metal Carbene Migratory Insertion

Ir(III)-catalyzed coupling of aromatic C-H bonds with diazomalonates has been achieved successfully via a metal carbene migratory insertion process. With different types of carbamoyl directing groups, a wide range of arenes, including heteroarenes, can be used as substrates in this Ir(III)-catalyzed C-H functionalization reaction. Mono- and bisfunctionalized products can be obtained selectively simply by changing the number of equivalents of the diazo substrate. Moreover, when diazomalonates bearing one or two tert-butyl groups are used as the substrates, the C-H bond functionalization is followed by decarboxyation, leading to products with a -CH2CO2Me or -CH2CO2H moiety at the position ortho to the directing group. This reaction demonstrates that direct C-H activation and the metal carbene migratory insertion can be merged into one catalytic cycle with an Ir(III) complex as the catalyst.

Palladium-Catalyzed Carbene Migratory Insertion Using Conjugated Ene–Yne–Ketones as Carbene Precursors

Palladium-catalyzed cross-coupling reactions between benzyl, aryl, or allyl bromides and conjugated ene-yne-ketones lead to the formation of 2-alkenyl-substituted furans. This novel coupling reaction involves oxidative addition, alkyne activation-cyclization, palladium carbene migratory insertion, β-hydride elimination, and catalyst regeneration. Palladium (2-furyl)carbene is proposed as the key intermediate, which is supported by DFT calculations. The palladium carbene character of the key intermediate is validated by three aspects, including bond lengths, Wiberg bond order indices, and molecular orbitals, by comparison to those reported for stable palladium carbene species. Computational studies also revealed that the rate-limiting step is ene-yne-ketone cyclization, which leads to the formation of the palladium (2-furyl)carbene, while the subsequent carbene migratory insertion is a facile process with a low energy barrier (<5 kcal/mol).

Synthesis of Pinacol Arylboronates from Aromatic Amines: A Metal-Free Transformation

A metal-free borylation process based on Sandmeyer-type transformation using arylamines derivatives as the substrates has been developed. Through optimization of the reaction conditions, this novel conversion can be successfully applied to a wide range of aromatic amines, affording borylation products in moderate to good yields. Various functionalized arylboronates, which are difficult to access by other methods, can be easily obtained with this metal-free transformation. Moreover, this transformation can be followed by Suzuki-Miyaura cross-coupling without purification of the borylation products, which enhances the practical usefulness of this method. A possible reaction mechanism involving radical species has been proposed.

Transition-Metal-Free Electrophilic Amination of Arylboroxines

A transition-metal-free strategy to construct C(sp(2))-N bonds using arylboroxines and O-benzoyl hydroxylamines as coupling partners has been developed. This transformation provides a useful method to access various aromatic amines.