Language：English   Publishing type：Research paper (scientific journal)  

We developed a chemoselective catalytic activation of carboxylic acid for a 1e^- radical process. α-Oxidation of a variety of carboxylic acids, which preferentially undergo undesired decarboxylation under radical conditions, proceeded efficiently under the optimized conditions. Chemoselective enolization of carboxylic acid was also achieved even in the presence of more acidic carbonyls. Extensive mechanistic studies revealed that the cooperative actions of iron species and alkali metal ions derived from 4 Å molecular sieves substantially facilitated the enolization. For the first time, catalytic enolization of unprotected carboxylic acid was achieved without external addition of stoichiometric amounts of Brønsted base. The formed redox-active heterobimetallic enediolate efficiently coupled with free radical TEMPO, providing synthetically useful α-hydroxy and keto acid derivatives.

DOI： 10.1021/jacs.0c00727

Language：English   Publishing type：Research paper (scientific journal)  

Alkylarenes, obtained from abundant hydrocarbon feedstock sources, are an attractive starting material for the formation of complex molecular architectures. Conventional activation strategies of the relatively inert sp³-hybridized benzylic C–H bonds usually require relatively harsh conditions and are difficult to apply to the synthesis of fine chemicals. The present review describes recent strategic advances for the activation of benzylic C–H bonds for the catalytic formation of C–C bonds. In particular, two activation methods, i.e., strategies that generate benzylic radicals or benzyl anions, are discussed.

DOI： 10.1016/j.tetlet.2019.151225

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acscatal.8b02361

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.orglett.8b01313

Publishing type：Research paper (scientific journal)  

DOI： 10.1021/prechem.3c00048

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ajoc.201900156

Language：English   Publishing type：Research paper (scientific journal)  

Mechanistic studies on catalytic aerobic chemoselective α-oxidation of acylpyrazoles, including control experiments, kinetic isotope effect experiments, and radical clock experiments, are described. The key to promoting the reaction was the in-situ generation of a copper(II) peroxo complex, which serves as a Lewis acid/Brønsted base cooperative catalyst for efficient enolization. The present catalysis was applicable to late-stage α-oxidation of functionalized acylpyrazoles. A preliminary diastereoselective reaction using readily available chiral acylpyrazoles demonstrated that the present catalysis provided access to optically active α-hydroxy acid derivatives.

DOI： 10.3987/COM-18-S(F)58

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.21873/anticanres.12721

Language：English   Publishing type：Research paper (scientific journal)  

A synthetic route to trans-configured tetrahydrothiophenes (THTs) through Fe(OTf)₃-promoted [3+2] cycloaddition of donor–acceptor cyclopropanes with thionoesters was developed. The cycloaddition proceeded in high yield with high diastereoselectivity, affording transient α-alkoxy THTs. Not only aromatic and aliphatic thionoesters, but also thionolactone were applicable to the present iron catalysis. Further transformation of the S,O-ketal functionality of the product was achieved in a highly trans diastereoselective manner. Moreover, the utility of our methodology was clearly demonstrated by the synthesis of enantioenriched trans-configured THTs.

DOI： 10.1002/chem.201800957

Language：English   Publishing type：Research paper (scientific journal)  

Catalytic aerobic chemoselective α-oxidation of acylpyrazoles is described. Acylpyrazoles, carboxylic acid oxidation state substrates, were efficiently oxidized under aerobic conditions using TEMPO as an oxygenating agent. The mild catalytic conditions of the present catalysis were amenable to late-stage α-oxidation of various pharmaceutical agents and natural products, leading to previously unreported α-hydroxy acid derivatives in short steps. Preliminary mechanistic studies revealed that in situ generated copper(II) peroxo species served as a Lewis acid/Brønsted base cooperative catalyst.

DOI： 10.1021/acs.orglett.7b01293

Language：English   Publishing type：Research paper (scientific journal)  

A highly chemoselective conjugate addition of amino alcohols to α,β-unsaturated ester using a soft Lewis acid/hard Brønsted base cooperative catalyst was developed. This catalysis achieved chemoselective addition of a hydroxy group over an amino group. Moreover, soft metal alkoxide generation enabled chemoselective soft conjugate addition over hard transesterification. Various amino alcohols, including unprecedented cyclic β-amino alcohol, were applicable to the present catalysis.

DOI： 10.1248/cpb.c16-00333

Language：English   Publishing type：Research paper (scientific journal)  

A chemoselective functional group installation through catalytic hydroxy group selective conjugate addition of amino alcohols to a variety of functionalized α,β-unsaturated sulfonyl derivatives was developed. Azide group installation for click chemistry and facile fluorescent labeling onto the less reactive hydroxy group demonstrated the synthetic utility of the present chemoselective catalysis. Moreover, chemo- and regioselective reaction of an unprotected amino diol was achieved for the first time.

DOI： 10.1021/acs.orglett.6b01464

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c5gc02056e

Language：English   Publishing type：Research paper (scientific journal)  

A direct copper-catalyzed highly chemoselective α-amination is described. Acylpyrazole proved to be a highly efficient enolate precursor of a carboxylic acid oxidation state substrate, while preactivation by a stoichiometric amount of strong base has been used in catalytic α-aminations. The simultaneous activation of both coupling partners, enolization and metal nitrenoid formation, was crucial for obtaining the product, and wide functional group compatibility highlighted the mildness of the present catalysis. The bidentate coordination mode was amenable to highly chemoselective activation over ketone and much more acidic nitroalkyl functionality. Deuterium exchange experiments clearly demonstrated that exclusive enolization of acylpyrazole was achieved without the formation of a nitronate. The present catalysis was applied to late-stage α-amination, allowing for concise access to highly versatile α-amino acid derivatives. The product could be transformed into variety of useful building blocks.

DOI： 10.1021/jacs.5b11773

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/adsc.201600229

Language：English   Publishing type：Research paper (scientific journal)  

A highly chemoselective and reactive μ-oxo-dinuclear iron(III) salen catalyst for transesterification was developed. The developed iron complex catalyzed acylation of aliphatic amino alcohols with nearly perfect O-selectivity, even when using activated esters, for which chemoselectivity is more difficult to control. In addition, O-selective transesterification of aromatic amino alcohols was achieved for the first time. The high activity of the iron complex enabled the use of sterically congested tertiary alcohols, including unprecedented tert-butanol.

DOI： 10.1002/chem.201602801

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ejoc.201600737

Language：English   Publishing type：Research paper (scientific journal)  

A nucleophilic amination strategy allows for expeditious access to various N-substituted α-amino carbonyl compounds. However, development of catalytic method remained unexplored in compared to an electrophilic amination strategy. The present review focused on the recent reports of a nucleophilic amination strategy for catalytic synthesis of α-amino carbonyl compounds.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ol501590n

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/anie.201309755

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ol3035609

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jo300566p

Language：English   Publishing type：Research paper (scientific journal)  

Catalytic asymmetric conjugate addition of nitroalkanes to α,β-unsaturated thioamides is promoted by a mesitylcopper/(R)-DTBM- Segphos precatalyst, affording γ-nitrothioamides in moderate to high syn-selectivity and excellent enantioselectivity. The intermediate Cu-thioamide enolate functions as a soft Lewis acid/hard Brønsted base cooperative catalyst to drive the catalytic cycle efficiently under proton transfer conditions.

DOI： 10.1021/ol202898e

Language：English   Publishing type：Research paper (scientific journal)  

Proton transfer allows efficient access to optically active five- and six-membered ring systems bearing ester and thioamide functionalities in an anti fashion; these ring systems are amenable to differential functional group manipulation. Direct catalytic, asymmetric, intramolecular conjugate addition of thioamide to α,β-unsaturated esters is described. In situ generated Cu thioamide enolate, by catalytic deprotonation, underwent the conjugate addition/protonation, to achieve the complete transformation (see scheme).

DOI： 10.1002/chem.201102332

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.tet.2011.05.109

Language：English   Publishing type：Research paper (scientific journal)  

Twice the catalyst: The simultaneous activation of an allyl cyanide (pronucleophile) and an α,β-unsaturated thioamide (electrophile) was achieved using a Cu-based soft Lewis acid/hard Brønsted base cooperative catalyst, thus resulting in the formation of enethioamides 1 in a highly enantio- and Z-selective manner (see scheme). The sequential Cu-catalyzed intramolecular cyclization gave rise to enantioenriched fused isothiazoles 2.

DOI： 10.1002/anie.201102467

Language：English   Publishing type：Research paper (scientific journal)  

A detailed study of the direct catalytic asymmetric conjugate addition of terminal alkynes to α,β-unsaturated thioamides is described. A soft Lewis acid/hard Brønsted base cooperative catalyst, comprising [Cu(CH₃CN)₄]PF₆, bisphosphine ligand, and Li(OC₆H₄-p-OMe) simultaneously activated both substrates to compensate for the low reactivity of copper alkynylide. A series of control experiments revealed that the intermediate copper-thioamide enolate functioned as a Brønsted base to generate copper alkynylide from the terminal alkyne, thus driving the catalytic cycle through an efficient proton transfer between substrates. These findings led to the identification of a more convenient catalyst using potassium hexamethyldisilazane (KHMDS) as the Brønsted base, which was particularly effective for the reaction of silylacetylenes. Divergent transformation of the thioamide functionality and a concise enantioselective synthesis of a GPR40 receptor agonist AMG-837 highlighted the synthetic utility of the present catalysis.

DOI： 10.1002/asia.201100050

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ja200250p

Language：English   Publishing type：Research paper (scientific journal)  

A concise enantioselective synthetic route to a potent GPR40 agonist AMG 837 is described. The crucial catalytic asymmetric conjugate addition of terminal alkyne was promoted by a soft Lewis acid/hard Brønsted base cooperative catalyst, allowing efficient construction of the requisite stereogenic center. The thioamide functional group is key to both activation in asymmetric alkynylation and facile transformation into carboxylic acid.(Figure Presented)

DOI： 10.1021/ol102998w

Language：English   Publishing type：Research paper (scientific journal)  

Direct catalytic asymmetric conjugate addition of terminal alkynes to α,β-unsaturated thioamides under proton transfer conditions is described. Soft Lewis acid/hard Brønsted base cooperative catalysis is crucial for simultaneous activation of terminal alkynes and thioamides, affording the β-alkynylthioamides in a highly enantioselective manner. Control experiments suggested that the intermediate copper thioamide enolate can work as Brønsted base to drive the catalytic cycle via proton transfer. The divergent transformation of the thioamide functionality highlights the synthetic utility of the alkynylation products.

DOI： 10.1021/ja105141x

Language：English   Publishing type：Research paper (scientific journal)  

We report that a hard Lewis base substantially affects the reaction efficiency of direct catalytic asymmetric γ-addition of allyl cyanide (1a) to ketones promoted by a soft Lewis acid/hard Brønsted base catalyst. Mechanistic studies have revealed that Cu/(R,R)-Ph-BPE and Li(OC ₆H₄-p-OMe) serve as a soft Lewis acid and a hard Brønsted base, respectively, allowing for deprotonative activation of 1a as the rate-determining step. A ternary catalytic system comprising a soft Lewis acid/hard Brønsted base and an additional hard Lewis base, in which the basicity of the hard Brønsted base Li(OC₆H₄-p-OMe) was enhanced by phosphine oxide (the hard Lewis base) through a hard-hard interaction, outperformed the previously developed binary soft Lewis acid/hard Brønsted base catalytic system, leading to higher yields and enantioselectivities while using one-tenth the catalyst loading and one-fifth the amount of 1a. This second-generation catalyst allows efficient access to highly enantioenriched tertiary alcohols under nearly ideal atom-economical conditions (0.5-1 mol % catalyst loading and a substrate molar ratio of 1:2).

DOI： 10.1021/ja101687p

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.tetasy.2010.04.034

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ja909758e

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/anie.200901588

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ja900001u

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ja806572b

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/anie.200801322

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.tet.2007.05.115

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/asia.200600232