記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chemoselective iron-catalyzed dehydrogenative cross-coupling using 2-acylimidazoles is described. The addition of a phosphine oxide ligand substantially facilitated the generation of tert-butoxy radicals from di-tert-butyl peroxide, allowing for efficient benzylic C-H bond cleavage under mild conditions. Extensive mechanistic studies revealed that the enolization of 2-acylimidazole proceeded through dual iron catalyst activation, followed by subsequent chemoselective cross-coupling with a benzyl radical over an undesired benzyl radical-derived homocoupling dimer that inevitably formed in earlier reported conditions. A variety of alkylarenes, aliphatic alkane, and functionalized 2-acylimidazoles were applicable, demonstrating the synthetic utility of the present catalysis. Contiguous all-carbon quaternary carbons were constructed through dehydrogenative cross-coupling. The catalytic chemoselective activation of 2-acylimidazole over bidentate coordinative and much more acidic malonate diester was particular noteworthy. Catalytic oxidative cross-enolate coupling of two distinct carboxylic acid equivalents was also achieved using acetonitrile as a coupling partner.

DOI： 10.1021/acscatal.8b02361

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A new strategy, a transient homocoupling dimer strategy, for direct catalytic oxidative cross-enolate coupling reactions is developed. Cross-enolate coupling products bearing a (contiguous) tetrasubstituted carbon center were obtained chemoselectively without the need for stoichiometric amounts of strong bases/metal oxidants, and thus, the present catalysis provides a general method for the synthesis of unnatural α,α-disubstituted amino acid motifs. The distinct transformation of azlactone and 2-acylimidazole units highlighted the synthetic utility of the present catalysis.

DOI： 10.1021/acs.orglett.8b01313

掲載種別：研究論文（学術雑誌）   出版者・発行元：Precision Chemistry  

A general protocol for the synthesis of α,β-dehydroamino acids and their peptides was developed. Proline efficiently catalyzed an aldol condensation reaction of a glycine Schiff base with a variety of aldehydes. The hydroxy group on the benzophenone imine was crucial for high Z/E selectivity and further transimination for protecting group-free α,β-dehydroamino esters. Peptide elongation of both the C- and N-terminals highlighted the usefulness of our present protocol.

DOI： 10.1021/prechem.3c00048

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The utility of thionoester as a 1,2-dipolarophile for [4+2] cycloaddition with cyclobutanones is described. The [4+2] cycloaddition reaction provided tetrahydrothiopyran, which is found in biologically active natural products, in high yield with high diastereoselectivity by using readily available TiCl
₄
. This synthetic method was applicable to a wide range of thionoesters and cyclobutanones. The ketone and S,O-ketal functionalities of the product could be reduced with excellent diastereoselectivity. Furthermore, the C−O bond was transformed into a C−C bond, affording contiguous tetrasubstituted carbon centers.

DOI： 10.1002/ajoc.201900156

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and Methods: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deaza-cytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.

DOI： 10.21873/anticanres.12721

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We designed highly active and practical bis(imidazole)/zinc complexes for transesterification reactions. X-ray crystallographic analysis was used to confirm the structures of the zinc complexes and an equivalent of bis(imidazole) ligand was crucial for high catalytic activity. The octahedral zinc complex 8c was prepared in up to a multigram scale by mixing Zn(OCOCF₃)₂·xH₂O and meta-bis(imidazolylmethyl)benzene ligand 7j (two equivalents per zinc ion) and storable under air at room temperature for at least 9 months. The stable nature of the catalyst was amenable to recovery/reuse at least five times without a significant loss of reactivity. The transesterification reaction proceeded without strict reaction conditions, and expanded substrate generalities, including sterically demanding secondary and tertiary alcohols, were applicable. Remarkably, the present zinc catalyst proved highly effective for valuable monomer synthesis from readily available methyl acrylate derivatives. Chemoselective transesterification reactions of unprotected-amino alcohols were also achieved, using not only a simple methyl ester but also an unprecedented dimethyl carbonate.

DOI： 10.1039/c5gc02056e

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report the development of a universal and recyclable heterogeneous zinc/imidazole catalyst. The catalyst is recoverable through simple filtration and can be reused at least five times, retaining its catalytic activity. Leached zinc species were not responsible for the observed catalysis based on the hot filtration test and ICP-MS analysis. The heterogeneous zinc catalyst also promotes chemoselective transesterification over amidation. (Figure presented.).

DOI： 10.1002/adsc.201600229

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A new practical method for the synthesis of functionalized acrylate derivatives with the view to prepare functional polymers was explored. Hard zinc alkoxide generation enabled the highly chemoselective transesterification of acrylate derivatives over the undesired conjugate addition, which caused polymerization. The combined use of the catalytic zinc cluster Zn₄(OCOCF₃)₆O and 4-(dimethylamino)pyridine delivered various functionalized acrylate derivatives through the transesterification of commercially available methyl acrylate derivatives with functionalized alcohols under mild conditions.

DOI： 10.1002/ejoc.201600737

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The synthesis of novel oxetanyl peptides, where the amide bond is replaced by a non-hydrolyzable oxetanylamine fragment, is reported. This new class of pseudo-dipeptides with the same H-bond donor/acceptor pattern found in proteins expands the repertoire of peptidomimetics.

DOI： 10.1021/ol501590n

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A highly chemoselective conjugate addition of alcohols in the presence of amines is described. The cooperative nature of the catalyst enabled chemoselective activation of alcohols over amines, allowing the conjugate addition to soft Lewis basic α,β-unsaturated nitriles. Divergent transformation of the nitrile functionality highlights the utility of the present catalysis. The cooperative nature of a copper catalyst enabled the highly chemoselective activation of alcohols in the presence of amines and thus the conjugate addition of the hydroxy group to soft Lewis basic α,β-unsaturated nitriles. The presented method proceeds under proton-transfer conditions, reverses the innate reactivity of the OH and NH groups, and does not require protecting groups. dppe=1,2-bis(diphenylphosphino) ethane, MeSal=3-methylsalicylate.

DOI： 10.1002/anie.201309755

記述言語：英語   掲載種別：研究論文（学術雑誌）  

An efficient protocol for direct catalytic alkynylation of ketoimines is described. The simultaneous activation of a soft Lewis basic terminal alkyne and a ketoimine bearing a thiophosphinoyl group by soft Lewis acid Cu(I) is crucial for high conversion. The reaction can be rendered asymmetric with a chiral bisphosphine ligand (S,S)-Ph-BPE.

DOI： 10.1021/ol3035609

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Direct catalytic asymmetric aldol reaction of thioamide offers a new entry to the concise enantioselective synthesis of duloxetine. The direct aldol protocol was scalable (>20 g) to afford the aldol product in 92% ee after LiAlH ₄ reduction, and 84% of the chiral ligand was recovered after recrystallization. The following four steps of transformation delivered duloxetine.

DOI： 10.1021/jo300566p

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A new catalytic system was developed for the direct catalytic asymmetric aldol reaction of thioamides. The new lithium-free Cu catalyst (second-generation catalyst) exhibited enhanced catalytic efficiency over the previously developed catalyst comprising [Cu(CH₃CN) ₄]PF₆/Ph-BPE/LiOAr (first-generation catalyst), which required a tedious catalyst preparation process. In the reaction with the second-generation catalyst, the intermediate Cu-aldolate functioned as a Brønsted base to generate thioamide enolate, efficiently driving the catalytic cycle. The present aldol methodology culminated in a concise asymmetric synthesis of atorvastatin (Lipitor^®: atorvastatin calcium), a widely prescribed HMG-CoA reductase inhibitor for lowering low-density lipoprotein cholesterol.

DOI： 10.1016/j.tet.2011.05.109

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH ₃CN) ₄]PF ₆/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Brønsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides. Strict control of the amount of the hard Lewis base was essential to drive the catalytic cycle efficiently with a minimized retro-aldol pathway, affording syn-aldol products with high stereoselectivity. Divergent transformation of the thioamide functionality is an obvious merit of the present aldol methodology, allowing for a facile transformation of the aldol product into the corresponding aldehyde, ketone, amide, amine, and ketoester. An aldehyde derived from the direct aldol reaction was subjected to a second direct aldol reaction, which proceeded in a catalyst-controlled manner to provide 1,3-diols with high stereoselectivity.(Figure Presented)

DOI： 10.1021/ja200250p

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A direct catalytic asymmetric aldol reaction of aromatic aldehydes and thioamides is described. A soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH₃CN)₄]PF ₆/Li(OC₆H₄-p-OMe) promoted the title reaction efficiently, triggered by in situ generation of the active thioamide enolate through a soft-soft interaction of Cu(I) and the thioamide. The aldol product was transformed into (R)-fluoxetine, an antidepressant agent.

DOI： 10.1016/j.tetasy.2010.04.034

記述言語：英語   掲載種別：研究論文（学術雑誌）  

(Chemical Equation Presented) A direct catalytic asymmetric aldol reaction of thioamides with a soft Lewis acid/hard Brønsted base cooperative catalytic system comprising (R,R)-Ph-BPE/[Cu(CH₃CN) ₄]PF₆/LiOAr is described. Highly chemoselective deprotonative activation of thioamides allows for a direct aldol reaction of α-nonbranched aliphatic aldehydes, which are susceptible to self-condensation. Facile reduction of the thioamide functionality and a catalyst-controlled second aldol reaction provides 1,3-diols in a highly stereoselective manner.

DOI： 10.1021/ja909758e

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Taking the reins: The title transformation of thioamides and N-diphenylphosphinoyl imines is described. By harnessing the power of cooperative catalysis between a soft Lewis acid and a hard Brønsted base, thioamide carbon pronucleophiles can furnish Mannich products (see scheme). Divergent transformation of the thioamide functionality highlights the utility of this methodology.

DOI： 10.1002/anie.200901588

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A direct catalytic asymmetric addition of allyl cyanide to ketones with a bimetallic catalytic system comprising (R,R)-Ph-BPE/[Cu(CH₃CN) ₄]ClO₄/LiOAr is described. Exclusive γ-addition of allyl cyanide was observed, affording optically enriched tertiary alcohols bearing Z-configured α,ß-unsaturated nitriles. The reaction proceeded under proton-transfer conditions, utilizing soft Lewis acid/hard Brønsted base bifunctional catalysis. The applicability of the reaction to aromatic, heteroaromatic, and aliphatic ketones demonstrates its wide substrate generality.

DOI： 10.1021/ja900001u

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Direct catalytic asymmetric addition of allylic cyanides to N-diphenylphosphinoyl ketoimines with a bimetallic catalytic system comprising Ph-BPE/[Cu(CH₃CN)₄]ClO₄/LiOAr is described. Intermediary α-adducts readily isomerized to afford synthetically useful α,β-unsaturated nitriles bearing an optically active tetrasubstituted carbon. Applicability to aromatic, heteroaromatic, and aliphatic ketoimines exemplifies wide substrate generality. Transformation of the product into densely functionalized material showcases the utility of the present protocol.

DOI： 10.1021/ja806572b

記述言語：英語   掲載種別：研究論文（学術雑誌）  

(Chemical Equation Presented) Much more reactive than the corresponding benzophenone imines, which have often been used in the synthesis of α-amino acids, the title compounds undergo Mannich-type reactions with imines in the presence of a catalytic amount of a base to afford α,β-diamino acid and α,β-diaminophosphonic acid derivatives with high syn diastereoselectivity (see scheme). An asymmetric version of the reaction is also described. Boc = tert-butoxycarbonyl.

DOI： 10.1002/anie.200801322

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A new class of isolable, air-stable, storable, and Hf-based catalyst has been developed. In the presence of 10 mol % of the powdered Hf catalyst, the asymmetric Mannich-type reactions of imines with silicon enolates derived from esters proceeded smoothly to afford the corresponding Mannich-type adducts in high yields with high enantioselectivities. Hafnium single crystals for X-ray analysis were obtained, and the crystals also showed high performance in the asymmetric Mannich-type reactions.

DOI： 10.1016/j.tet.2007.05.115

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The total synthesis of onchidin (1), a cytotoxic, C₂-symmetric cyclic decadepsipeptide from a marine mollusc, according to the published structure, is described. A novel β-amino acid, (2S,3S)-3-amino-2-methyl-7- octynoic acid (AMO), was efficiently prepared in high yield with high diastereo- and enantioselectivity based on a catalytic asymmetric three-component Mannich-type reaction with a chiral zirconium catalyst. The formation of sterically unfavorable N-methyl amide and hindered ester bonds were successfully demonstrated, and final macrocyclization was achieved at a secondary-amide site. Completion of the synthesis of 1 suggested that a revision of the structure of the natural product is required. Two diastereomers were also synthesized as candidates for the actual structure of onchidin. Furthermore, efficient solid-phase methods were employed for the combinatorial synthesis of other derivatives to clarify the real structure of onchidin. The solid-phase assembly of a pentadepsipeptide containing all the building blocks was established followed by dimeric cyclization in solution.

DOI： 10.1002/asia.200600232