Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Hiroyuki Morimoto Last modified date:2019.06.08

Lecturer / Biopharmacology, Department of Pharmaceutical Sciences / Department of Chemo-Pharmaceutical Sciences / Faculty of Pharmaceutical Sciences

1. David M. Hodgson, Philip G. Humphreys, Matthew J. Fleming, Hiroyuki Morimoto, Hisashi Mihara, Masakatsu Shibasaki, Organolithiums and lithium 2,2,6,6-tetramethylpiperidide in reductive alkylation of epoxides
Synthesis of (E)-alkenes [(E)-2-methyltetradeca-1,3-diene], Organic Syntheses, 10.15227/orgsyn.085.0001, 1-9, 2008.01.
2. Masanao Sawa, Shotaro Miyazaki, Ryohei Yonesaki, Hiroyuki Morimoto, Takashi Ohshima, Catalytic Enantioselective Decarboxylative Mannich-Type Reaction of N-Unprotected Isatin-Derived Ketimines, Organic Letters, 10.1021/acs.orglett.8b02306, 20, 17, 5393-5397, 2018.09, The first catalytic enantioselective decarboxylative Mannich-type reaction of N-unprotected ketimines is reported, directly providing N-unprotected 3-tetrasubstituted 3-aminooxindoles in high yield and ee without protection/deprotection steps. The utility of this reaction is demonstrated in the short step synthesis of (+)-AG-041R..
3. Ryohei Yonesaki, Yuta Kondo, Walaa Akkad, Masanao Sawa, Kazuhiro Morisaki, Hiroyuki Morimoto, Takashi Ohshima, 3-Mono-Substituted BINOL Phosphoric Acids as Effective Organocatalysts in Direct Enantioselective Friedel–Crafts-Type Alkylation of N-Unprotected α-Ketiminoester, Chemistry - A European Journal, 10.1002/chem.201804078, 24, 57, 15211-15214, 2018.10, Although BINOL-derived phosphoric acids are among the most widely used chiral Brønsted acid organocatalysts, their structures are mostly limited to 3,3′-disubstituted ones and simple 3-mono-substituted ones without any polar functionalities on the 3-substituent have not been used in highly enantioselective reactions. This work reports such 3-mono-substituted analogues as effective organocatalysts in direct highly enantioselective Friedel–Crafts-type alkylation of N-unprotected α-ketiminoester. The origin of the observed high enantioselectivity with the 3-mono-substituted catalyst is also discussed..
4. Megumi Noshita, Yuhei Shimizu, Hiroyuki Morimoto, Shuji Akai, Yoshitaka Hamashima, Noriyuki Ohneda, Hiromichi Odajima, Takashi Ohshima, Ammonium Salt-Accelerated Hydrazinolysis of Unactivated Amides
Mechanistic Investigation and Application to a Microwave Flow Process, Organic Process Research and Development, 10.1021/acs.oprd.8b00424, 23, 4, 588-594, 2019.04, A study of ammonium salt-accelerated hydrazinolysis of unactivated amides is described. We first studied the reaction mechanism by kinetic experiments and DFT calculations and found that cooperation of the hydrazinium salt and hydrazine is important for promoting the cleavage of unactivated amides. Next, we applied the reaction to a microwave flow process, and the amine products were isolated on a multigram scale..
5. Kazuhiro Morisaki, Hiroyuki Morimoto, Kazushi Mashima, Takashi Ohshima, Development of direct enantioselective alkynylation of αketoester and α-ketiminoesters catalyzed by phenylbis(oxazoline)Rh(III) complexes, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.76.226, 76, 3, 226-240, 2018.01, Direct catalytic enantioselective alkynylation of carbonyl compounds and imines is one of the most efficient approaches for the synthesis of propargylic alcohols and propargylamines, which are potent building blocks for synthesizing functionalized molecules. While a variety of methods for the reactions with aldehydes and aldimines have been established, the reactions with ketones and ketimines remain underdeveloped due to their reduced reactivity and difficulty in stereocontrol. In this account, we summarized our studies on direct enantioselective alkynylation reaction of α-ketoester and α-ketiminoesters catalyzed by phenylbis(oxazolinephebox)-rhodium(III) complexes, affording enantioenriched propargyl alcohols and propargylamines with a tetrasubsti-tuted carbon stereocenter under proton-transfer conditions. The catalytic system was compatible to a wide range of functional groups, including electrophilic formyl groups, and allowed for the development of an efficient method to access enantioenriched α-CF3-substituted thalidomide analogs. Mechanistic studies revealed that generation of the (alkynyl(phebox)Rh(III) complex from the (diacetatophebox)Rh(III) complex determined the overall reaction rate in the initial stages of the reaction. These results, along with the observed facile exchange of the alkynyl ligand on the (alkynylphebox)Rh(III) complexes, led us to use (trimethylsilylethynylphebox)Rh(III) complexes as a new pre-catalyst. The new catalytic system with (trimethylsilylethynylphebox)Rh (III) precatalysts exhibited enhanced catalytic performance, reduced catalyst loading to as low as 0.5 mol%, and expanded the substrate scope of the reaction with less reactive α-ketiminophos-phonate and cyclic N-sulfonyl α-ketiminoesters..
6. Masanao Sawa, Kazuhiro Morisaki, Yuta Kondo, Hiroyuki Morimoto, Takashi Ohshima, Direct Access to N-Unprotected α- and/or β-Tetrasubstituted Amino Acid Esters via Direct Catalytic Mannich-Type Reactions Using N-Unprotected Trifluoromethyl Ketimines, Chemistry - A European Journal, 10.1002/chem.201703516, 23, 67, 17022-17028, 2017.12, Direct catalytic C−C bond-forming addition to N-unprotected ketimines is an efficient and straightforward method of synthesizing N-unprotected tetrasubstituted amines that eliminates prior protection/deprotection steps and allows facile transformation of the products. Despite its advantages, however, N-unprotected ketimines have difficulties in C−C bond-forming reactions, and only a limited number of reactions and substrates are reported compared with their N-protected counterparts. Herein we report that N-unprotected trifluoromethyl ketimines are effective for C−C bond-forming reactions using Mannich-type reactions as a model case. We demonstrate that Lewis acid catalysis was effective for promoting reactions with various N-unprotected trifluoromethyl ketimines, and thiourea organocatalysis was effective for promoting highly enantioselective reactions with various carbonyl nucleophiles, providing direct access to various N-unprotected α- and/or β-tetrasubstituted amino acid esters. Furthermore, direct construction of vicinal tetrasubstituted chiral carbon stereocenters was achieved for the first time in a highly enantio- and diastereoselective manner. These results demonstrate the potential of N-unprotected ketimines as substrates applicable to many other addition reactions..
7. Amrita Das, Kenji Watanabe, Hiroyuki Morimoto, Takashi Ohshima, Boronic Acid Accelerated Three-Component Reaction for the Synthesis of α-Sulfanyl-Substituted Indole-3-acetic Acids, Organic Letters, 10.1021/acs.orglett.7b02727, 19, 21, 5794-5797, 2017.11, Boronic acid was used to accelerate a three-component reaction of indoles, thiols, and glyoxylic acids for the synthesis of α-sulfanyl-substituted indole-3-acetic acids. Boronic acid catalysis to activate the α-hydroxy group in α-hydroxycarboxylic acid intermediates and intramolecular assistance by free carboxylic acid were the keys to accelerating the product formation..
8. Toru Deguchi, Hai Long Xin, Hiroyuki Morimoto, Takashi Ohshima, Direct Catalytic Alcoholysis of Unactivated 8-Aminoquinoline Amides, ACS Catalysis, 10.1021/acscatal.7b00442, 7, 5, 3157-3161, 2017.05, Direct catalytic alcoholysis of unactivated amides is one of the most difficult challenges in organic chemistry, and an applicable method for cleaving amides used as directing groups in regioselective functionalization reactions has not been reported. Herein, we report direct catalytic alcoholysis of 8-aminoquinoline amides, which are highly effective directing groups in regioselective functionalization reactions. The reactions proceeded with a simple combination of substrates, air-stable catalysts, and alcohols, affording the corresponding esters in good yields with broad functional group tolerance. Highly chemoselective cleavage of the 8-aminoquinoline amides in the presence of related carbonyl functionalities and preliminary mechanistic studies are also described..
9. Kazuhiro Morisaki, Yuta Kondo, Masanao Sawa, Hiroyuki Morimoto, Takashi Ohshima, Synthesis of 1-tetrasubstituted 2,2,2-trifluoroethylamine derivatives via palladium-catalyzed allylation of sp3 C–H bonds, Chemical and Pharmaceutical Bulletin, 10.1248/cpb.c17-00580, 65, 11, 1089-1092, 2017.01, This note describes the construction of tetrasubstituted carbon stereocenters via palladium-catalyzed allylation of sp3 C–H bonds of 2,2,2-trifluoroethylamine derivatives. The presence of 2-pyridyl group of the imines derived from 1-substituted-2,2,2-trifluoroethylamine was key to promoting the reaction efficiently, allowing an access to a variety of 1-allylated 2,2,2-trifluoroethylamine derivatives with tetrasubstituted carbon stereocenters..
10. Kazuhiro Morisaki, Hiroyuki Morimoto, Takashi Ohshima, Direct access to
N -unprotected tetrasubstituted propargylamines via direct catalytic alkynylation of N -unprotected trifluoromethyl ketimines, Chemical Communications, 10.1039/c7cc02194a, 53, 47, 6319-6322, 2017.04, Direct catalytic alkynylation of N-unprotected trifluoromethyl ketimines is reported for the first time. A combination of catalytic amounts of diethylzinc and carboxylic acids promoted the reactions under proton-transfer conditions, allowing an unprecedented direct access to N-unprotected α-tetrasubstituted primary amines without additional deprotection steps..
11. Kazuhiro Morisaki, Hiroyuki Morimoto, Kazushi Mashima, Takashi Ohshima, Direct enantioselective alkynylation of α-ketoesters and α-ketiminoesters catalyzed by [bis(oxazoline)phenyl]rhodium(III) complexes, Heterocycles, 10.3987/REV-16-SR(S)4, 95, 2, 637-661, 2017.01, This review summarizes our studies of the direct enantioselective alkynylation of α-ketoesters and α-ketiminoesters catalyzed by [bis(oxazoline)phenyl]rhodium(III) ((phebox)Rh(III)) complexes. The reactions provide chiral α-tetrasubstituted propargyl alcohols and propargylamines under proton-transfer conditions in high yield and with high enantioselectivity. The unique nature of (phebox)Rh(III) complexes allows the reactions to occur in the presence of various functional groups, including an electrophilic aldehyde functionality. Mechanistic studies revealed that the generation of (alkynyl)Rh(III) complexes limited the overall reactivity, which led us to use (trimethylsilylethynyl)(phebox)Rh(III) complexes as efficient pre-catalysts. The use of (trimethylsilylethynyl)(phebox)Rh(III) complexes reduced catalyst loading to as low as 0.5 mol%, and expanded the substrate scope to unprecedented α-ketiminophosphonate and cyclic N-sulfonyl α-ketiminoesters..
12. Megumi Noshita, Yuhei Shimizu, Hiroyuki Morimoto, Takashi Ohshima, Diethylenetriamine-Mediated Direct Cleavage of Unactivated Carbamates and Ureas, Organic Letters, 10.1021/acs.orglett.6b03016, 18, 23, 6062-6065, 2016.12, Diethylenetriamine is effective for the direct cleavage of unactivated carbamates and ureas without additional reagents and catalysts. Various carbamates and ureas were cleaved to afford products in good yield, and the reactions were not affected by air or moisture. Unique chemoselective cleavage of carbamate and urea in the presence of amides was also achieved..
13. Kazuhiro Morisaki, Masanao Sawa, Ryohei Yonesaki, Hiroyuki Morimoto, Kazushi Mashima, Takashi Ohshima, Mechanistic Studies and Expansion of the Substrate Scope of Direct Enantioselective Alkynylation of α-Ketiminoesters Catalyzed by Adaptable (Phebox)Rhodium(III) Complexes, Journal of the American Chemical Society, 10.1021/jacs.6b01590, 138, 19, 6194-6203, 2016.05, Mechanistic studies and expansion of the substrate scope of direct enantioselective alkynylation of α-ketiminoesters catalyzed by adaptable (phebox)rhodium(III) complexes are described. The mechanistic studies revealed that less acidic alkyne rather than more acidic acetic acid acted as a proton source in the catalytic cycle, and the generation of more active (acetato-κ2O,O′)(alkynyl)(phebox)rhodium(III) complexes from the starting (diacetato)rhodium(III) complexes limited the overall reactivity of the reaction. These findings, as well as facile exchange of the alkynyl ligand on the (alkynyl)rhodium(III) complexes led us to use (acetato-κ2O,O′)(trimethylsilylethynyl)(phebox)rhodium(III) complexes as a general precatalyst for various (alkynyl)rhodium(III) complexes. Use of the (trimethylsilylethynyl)rhodium(III) complexes as precatalysts enhanced the catalytic performance of the reactions with an α-ketiminoester derived from ethyl trifluoropyruvate at a catalyst loading as low as 0.5 mol % and expanded the substrate scope to unprecedented α-ketiminophosphonate and cyclic N-sulfonyl α-ketiminoesters..
14. Makoto Ohira, Yuka Iwasaki, Chika Tanaka, Michitaka Kuroki, Naoki Matsuo, Tatsuhiko Kitamura, Masaki Yukuhiro, Hiroyuki Morimoto, Nisha Pang, Bei Liu, Tohru Kiyono, Masahide Amemiya, Kozo Tanaka, Kazumasa Yoshida, Nozomi Sugimoto, Takashi Ohshima, Masatoshi Fujita, A novel anti-microtubule agent with carbazole and benzohydrazide structures suppresses tumor cell growth in vivo, Biochimica et Biophysica Acta - General Subjects, 10.1016/j.bbagen.2015.04.013, 1850, 9, 1676-1684, 2015.05, Background The mitotic spindles are among the most successful targets of anti-cancer chemotherapy, and they still hold promise as targets for novel drugs. The anti-mitotic drugs in current clinical use, including taxanes, epothilones, vinca alkaloids, and halichondrins, are all microtubule-targeting agents. Although these drugs are effective for cancer chemotherapy, they have some critical problems; e.g., neurotoxicity caused by damage to neuronal microtubules, as well as innate or acquired drug resistance. To overcome these problems, a great deal of effort has been expended on development of novel anti-mitotics. Methods We identified novel microtubule-targeting agents with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-methylbenzohydrazide (code number HND-007) and its related compounds. We investigated their activities against cancer cells using various methods including cell growth assay, immunofluorescence analysis, cell cycle analysis, tubulin polymerization assay, and tumor inhibition assay in nude mice. Results HND-007 inhibits tubulin polymerization in vitro and blocks microtubule formation and centrosome separation in cancer cells. Consequently, it suppresses the growth of various cancer cell lines, with IC50 values in the range 1.3-4.6 μM. In addition, HND-007 can inhibit the growth of taxane-resistant cancer cells that overexpress P-glycoprotein. Finally, HND-007 can inhibit HeLa cell tumor growth in nude mice. Conclusions and general significance Taken together, these findings suggest that HND-007 is a promising lead compound for development of novel anti-mitotic, anti-microtubule chemotherapeutic agents..
15. Hiroyuki Morimoto, Direct catalytic anti-Markovnikov addition reactions of oxygen nucleophiles to simple Alkenes, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.72.1402, 72, 12, 1402-1403, 2014.12, Development of direct catalytic anti-Markovnikov addition reactions of oxygen nucleophiles to simple alkenes is a difficult challenge due to the propensity to form Markovnikov adducts under ordinary reaction conditions. Herein selected recent examples that realize these reactions with high anti-Markovnikov selectivity are summarized..
16. Ming Zhang, Kenji Watanabe, Masafumi Tsukamoto, Ryozo Shibuya, Hiroyuki Morimoto, Takashi Ohshima, A short scalable route to (-)-α-kainic acid using Pt-catalyzed direct allylic amination, Chemistry - A European Journal, 10.1002/chem.201406557, 21, 10, 3937-3941, 2014.10, An increased supply of scarce or inaccessible natural products is essential for the development of more sophisticated pharmaceutical agents and biological tools, and thus the development of atom-economical, step-economical and scalable processes to access these natural products is in high demand. Herein we report the development of a short, scalable total synthesis of (-)-α-kainic acid, a useful compound in neuropharmacology that is, however, limited in supply from natural resources. The synthesis features sequential platinum-catalyzed direct allylic aminations and thermal ene-cyclization, enabling the gram-scale synthesis of (-)-α-kainic acid in six steps and 34% overall yield..
17. Yuhei Shimizu, Megumi Noshita, Yuri Mukai, Hiroyuki Morimoto, Takashi Ohshima, Cleavage of unactivated amide bonds by ammonium salt-accelerated hydrazinolysis, Chemical Communications, 10.1039/c4cc02014f, 50, 84, 12623-12625, 2014.10, Hydrazinolysis of unactivated amide bonds is significantly accelerated by the addition of ammonium salts. The reactions proceed at 50-70 °C to give amines with broad substrate scope that outperforms existing amide bond cleavage reactions. Application to peptide and amino sugar derivatives is also demonstrated. This journal is.
18. Hiroyuki Morimoto, Risa Fujiwara, Yuhei Shimizu, Kazuhiro Morisaki, Takashi Ohshima, Lanthanum(III) triflate catalyzed direct amidation of esters, Organic Letters, 10.1021/ol500593v, 16, 7, 2018-2021, 2014.04, Lanthanum trifluoromethanesulfonate is an effective single-component catalyst for synthesizing a variety of amides directly from esters and amines under mild conditions. Highly selective amidation of esters and amines, as well as catalyst-controlled amidation of esters, demonstrated the effectiveness of the catalyst system..
19. Kazuhiro Morisaki, Masanao Sawa, Jun Ya Nomaguchi, Hiroyuki Morimoto, Yosuke Takeuchi, Kazushi Mashima, Takashi Ohshima, Rh-catalyzed direct enantioselective alkynylation of α-ketiminoesters, Chemistry - A European Journal, 10.1002/chem.201301237, 19, 26, 8417-8420, 2013.06, A green way to amino acids: α-Tetrasubstituted α-amino acid derivatives are formed in high yield and enantioselectivity by using a Rh-catalyzed enantioselective alkynylation of α-ketiminoesters. This reaction, which involves a proton transfer and can be conducted at room temperature, has high substrate scope (see scheme; Cbz=benzyloxycarbonyl, Fmoc=9-fluorenylmethyloxycarbonyl)..
20. Yuhei Shimizu, Hiroyuki Morimoto, Ming Zhang, Takashi Ohshima, Microwave-assisted deacylation of unactivated amides using ammonium-salt-accelerated transamidation, Angewandte Chemie - International Edition, 10.1002/anie.201202354, 51, 34, 8564-8567, 2012.08, Easy does it! The chemoselective oxidative ?-C(sp3)H alkylation/cyclization reaction of N-benzyl carbamates using simple mono-, di-, and trisubstituted olefins provides functionalized N-heterocycles such as oxazinones (see picture). A TEMPO oxoammonium salt serves as the oxidant, making it possible to carry out the reaction at low temperatures. Neither a metal catalyst nor preactivation in the ?-position to the nitrogen group are needed..
21. Gang Lu, Tatsuhiko Yoshino, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki, Stereodivergent direct catalytic asymmetric mannich-type reactions of α-isothiocyanato ester with ketimines, Angewandte Chemie - International Edition, 10.1002/anie.201101034, 50, 19, 4382-4385, 2011.05, Now accessible: Sterically hindered vicinal tetrasubstituted carbon stereocenters, which are not accessible by asymmetric hydrogenation, were constructed by a catalytic asymmetric C-C bond formation (see scheme; Dpp=diphenylphosphinoyl). By changing the Group 2 metal center, stereodivergent access to α,β-tetrasubstituted α,β-diamino esters was realized..
22. Hiroyuki Morimoto, Tetsu Tsubogo, Nichole D. Litvinas, John F. Hartwig, A broadly applicable copper reagent for trifluoromethylations and perfluoroalkylations of aryl iodides and bromides, Angewandte Chemie - International Edition, 10.1002/anie.201100633, 50, 16, 3793-3798, 2011.04, (Chemical Presented) Well compatible: The trifluoromethylations and perfluoroalkylations of aryl iodides and some aryl bromides with trifluoromethyl and perfluoroalkylcopper(I) phenanthroline complexes occur with broad scope at 25-50 8C (see scheme). The trifluoromethyl complex is prepared from inexpensive reagents and can be used in situ or isolated. The reactions tolerate a range of substituents and also occur with heteroaromatic systems..
23. Takafumi Yukawa, Bianca Seelig, Yingjie Xu, Hiroyuki Morimoto, Shigeki Matsunaga, Albrecht Berkessel, Masakatsu Shibasaki, Catalytic asymmetricaza-Morita-Baylis-Hillman reaction of methyl acrylate
Role of a bifunctional La(O- i Pr)3/linked-BINOL complex, Journal of the American Chemical Society, 10.1021/ja103294a, 132, 34, 11988-11992, 2010.09, The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated methyl acrylate is described. A simple Lewis acidic metal catalyst, such as La(OTf)3, was not suitable for the reaction, but rare earth metal alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Brønsted base properties efficiently promoted the reaction in combination with an achiral nucleophilic organocatalyst. The combined use of a La(O-iPr)3/(S,S)-TMS-linked-BINOL complex with a catalytic amount of DABCO promoted the aza-Morita-Baylis-Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee. It is noteworthy that isomerizable alkyl imines could be employed as well, giving products in 78-89% yield and 94-98% ee. Initial rate kinetic studies as well as kinetic isotope effect experiments using α-deuterio-methyl acrylate support the importance of both the nucleophilicity of La-enolate and the Brønsted basicity of a La-catalyst for promoting the reaction..
24. Tatsuhiko Yoshino, Hiroyuki Morimoto, Gang Lu, Shigeki Matsunaga, Masakatsu Shibasaki, Construction of contiguous tetrasubstituted chiral carbon stereocenters via direct catalytic asymmetric aldol reaction of α-isothiocyanato esters with ketones, Journal of the American Chemical Society, 10.1021/ja908571w, 131, 47, 17082-17083, 2009.12, (Chemical Equation Presented) Construction of contiguous tetrasubstituted chiral carbon stereocenters via direct catalytic asymmetric aldol reaction of α-substituted α-isothiocyanato esters with unactivated simple ketones is described. A Bu2Mg/Schiff base catalyst promoted the aldol addition/cyclization sequence at room temperature, giving protected α-amino-β-hydroxy esters with contiguous tetrasubstituted chiral carbon stereocenters in 99 to 68% yield, 98:2 to 74:26 dr, and 98 to 82% ee..
25. Keiichi Hara, Shin ya Tosaki, Vijay Gnanadesikan, Hiroyuki Morimoto, Shinji Harada, Mari Sugita, Noriyuki Yamagiwa, Shigeki Matsunaga, Masakatsu Shibasaki, Mixed La-Li heterobimetallic complexes for tertiary nitroaldol resolution, Tetrahedron, 10.1016/j.tet.2009.02.031, 65, 26, 5030-5036, 2009.06, Full details of the kinetic resolution of tertiary nitroaldols derived from simple ketones are described. Mixed BINOL/biphenol La-Li heterobimetallic complexes gave the best selectivity in retro-nitroaldol reactions of racemic tertiary nitroaldols. Using a 2:1 mixture of La-Li3-(binaphthoxide 1a)3 complex (LLB) and La-Li3-(biphenoxide 1e)3 complex, chiral tertiary nitroaldols were obtained in 80-97% ee and 30-47% recovery yield. Transformations of products were also investigated..
26. Hiroyuki Morimoto, Tatsuhiko Yoshino, Takafumi Yukawa, Gang Lu, Shigeki Matsunaga, Masakatsu Shibasaki, Lewis base assisted Brønsted base catalysis
Bidentate phosphine oxides as activators and modulators of brønsted basic lanthanum-aryloxides, Angewandte Chemie - International Edition, 10.1002/anie.200803682, 47, 47, 9125-9129, 2008.11, (Chemical Equation Presented) Dynamic Duo: A Lewis basic bidentate phosphine oxide was effective for activating and modulating the properties of Brønsted basic lanthanum aryl oxides. The Lewis base 1/lanthanum aryl oxide system was suitable for anti-selective Mannich-type reactions of trichloromethyl ketones (see scheme), affording unique building blocks for azetidine-2-carboxylic acids as well as β-amino acids..
27. Gang Lu, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki, Chiral γ-amino amide synthesis by heterobimetallic lanthanum/lithium/pybox-catalyzed direct asymmetric Mannich-type reactions of α-keto anilides, Angewandte Chemie - International Edition, 10.1002/anie.200801564, 47, 36, 6847-6850, 2008.08, (Chemical Equation Presented) Not so Mannich now: A heterobimetallic La/Li/pybox complex was key in direct catalytic asymmetric Mannich-type reactions, using α-keto anilides as synthetic homoenolate equivalents to afford γ-amino amide products in up to > 99% yield, 95% ee, and >97:3 syn-selectivity. Stereoselective reduction of the α-keto moiety afforded the β-alkyl-γ-amino-α-hydroxy amide with three contiguous stereocenters (PG=protecting group)..
28. Zhihua Chen, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki, A bench-stable homodinuclear Ni2-Schiff base complex for catalytic asymmetric synthesis of α-tetrasubstituted anti-α,β- diamino acid surrogates, Journal of the American Chemical Society, 10.1021/ja710398q, 130, 7, 2170-2171, 2008.02, Catalytic asymmetric direct Mannich-type reactions of α-substituted nitroacetates using a new bench-stable homodinuclear Ni2-Schiff base 1b complex are described. The Ni2-1b complex gave Mannich products, precursors for anti-α,β-diamino acids with an α-tetrasubstituted carbon stereocenter, in >99-91% ee. The Ni2-1b complex was also applicable to direct Mannich-type reactions of malonates and β-keto ester, giving products in high stereoselectivity (up to 99% ee, dr >97:3). Preliminary mechanistic studies suggested that the dinuclear Ni metal centers had key roles to achieve good reactivity and high stereoselectivity..
29. Hiroyuki Morimoto, Gang Lu, Naohiro Aoyama, Shigeki Matsunaga, Masakatsu Shibasaki, Lanthanum aryloxide/pybox-catalyzed direct asymmetric mannich-type reactions using a trichloromethyl ketone as a propionate equivalent donor, Journal of the American Chemical Society, 10.1021/ja073285p, 129, 31, 9588-9589, 2007.08, Direct catalytic asymmetric Mannich-type reaction of a trichloromethyl ketone as a propionate equivalent donor is described. A new lanthanum aryloxide-iPr-pybox + lithium aryloxide combined catalyst was the most effective, promoting the reaction of N-2-thiophenesulfonyl imines with the trichloromethyl ketone. syn-Mannich adducts were obtained from various aryl, heteroaryl, alkenyl, and alkyl imines in > 99-72% yield, syn/anti of > 30:1-8:1, and 98-92% ee (from a propionate equivalent donor) using 2.5-10 mol % catalyst. The Mannich adduct was converted not only into ester but also into useful building blocks..
30. So Young Park, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki, Catalytic asymmetric Michael reactions of dibenzyl malonate to α,β-unsaturated N-acylpyrroles using a La(O-iPr)3/Ph-linked-BINOL complex, Tetrahedron Letters, 10.1016/j.tetlet.2007.02.112, 48, 16, 2815-2818, 2007.04, Catalytic asymmetric Michael reactions of a malonate to acyclic α,β-unsaturated N-acylpyrroles as ester equivalent acceptors are described. A La(O-iPr)3/(S,S)-linked-BINOL complex, which is suitable for Michael addition to cyclic enones, is not suitable for acyclic α,β-unsaturated N-acylpyrroles. A new (S,S)-Ph-linked-BINOL chiral ligand was developed to improve enantioselectivity, and a La(O-iPr)3/(S,S)-Ph-linked-BINOL complex with the addition of HFIP afforded Michael adducts in good yield and enantioselectivity (up to 96% ee)..
31. Hiroyuki Kakei, Riichiro Tsuji, Takashi Ohshima, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki, Catalytic asymmetric epoxidation of α,β-unsaturated esters with chiral yttrium-biaryldiol complexes, Chemistry - An Asian Journal, 10.1002/asia.200600309, 2, 2, 257-264, 2007.01, The full details of the asymmetric epoxidation of α,β- unsaturated esters catalyzed by yttrium complexes with biaryldiol ligands are described. An yttrium-biphenyldiol catalyst, generated from Y(OiPr) 3-biphenyldiol ligand-triphenylarsine oxide (1:1:1), is suitable for the epoxidation of various α,β-unsaturated esters. With this catalyst, β-aryl α,β-unsaturated esters gave high enantioselectivities and good yields (≤99% ee). The reactivity of this catalyst is good, and the catalyst loading could be decreased to as little as 0.5-2 mol % (the turnover number was up to 116), while high enantiomeric excesses were maintained. For β-alkyl α,β-unsaturated esters, an yttrium-binol catalyst, generated from Y-(OiPr)3-binol ligand-triphenylphosphine oxide (1:1:2), gave the best enantioselectivities (≤97% ee). The utility of the epoxidation reaction was demonstrated in an efficient synthesis of (-)-ragaglitazar, a potential antidiabetes agent..
32. Zhihua Chen, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki, Catalytic asymmetric epoxidation of α-methyl α,β- unsaturated anilides as ester surrogates, Synlett, 10.1055/s-2006-956491, 20, 3529-3532, 2006.12, Catalytic asymmetric epoxidation of α-methyl α,β- unsaturated carboxylic acid derivatives was achieved using anilide as a template. The Pr(Oi-Pr)3-6,6́-Ph-BINOL complex (10 mol%) with a Ph3P(O) (30 mol%) additive promoted the epoxidation of anilides in up to 99% yield and 88% ee. For α-methyl-β-Ph α,β- unsaturated anilide, the Gd(Oi-Pr)3-6,6′-I-BINOL complex (10 mol%) with Ar3P(O) (30 mol%, Ar = 4-methoxyphenyl) was suitable, giving epoxide in 87% yield and 78% ee..
33. Shin Ya Tosaki, Keiichi Hara, Vijay Gnanadesikan, Hiroyuki Morimoto, Shinji Harada, Mari Sugita, Noriyuki Yamagiwa, Shigeki Matsunaga, Masakatsu Shibasaki, Mixed La-Li heterobimetallic complexes for tertiary nitroaldol resolution, Journal of the American Chemical Society, 10.1021/ja064858l, 128, 36, 11776-11777, 2006.09, A kinetic resolution of tertiary nitroaldols derived from simple ketones is described. Mixed BINOL/biphenol La-Li heterobimetallic complexes gave the best selectivity in retro-nitroaldol reactions of racemic tertiary nitroaldols. By using a mixture of La-Li3-(1a)3 complex (LLB 2a) and La-Li3-(1b)3 (LLB* 2b) complex in a ratio of 2/1, chiral tertiary nitroaldols were obtained in 80-97% ee and 30-47% recovery yield..
34. Hiroyuki Morimoto, Sean H. Wiedemann, Akitake Yamaguchi, Shinji Harada, Zhihua Chen, Shigeki Matsunaga, Masakatsu Shibasaki, Trichloromethyl ketones as synthetically versatile donors
Application in direct catalytic mannich-type reactions and the stereoselective synthesis of azetidines, Angewandte Chemie - International Edition, 10.1002/anie.200600227, 45, 19, 3146-3150, 2006.05, Chemical transformers! Catalytic nucleophilic activation of trichloromethyl ketones allows applications in intermolecular carbon-carbon bond-forming reactions. Mannich adducts such as azetidines can be obtained from the primary products in high yield and syn selectivity. PG = protecting group. (Chemical Equation Presented).
35. Takamasa Yoshida, Hiroyuki Morimoto, Naoya Kumagai, Shigeki Matsunaga, Masakatsu Shibasaki, Non-C2-symmetric, chirally economical, and readily tunable linked-binols
Design and application in a direct catalytic asymmetric mannich-type reaction, Angewandte Chemie - International Edition, 10.1002/anie.200500425, 44, 22, 3470-3474, 2005.05, (Chemical Equation Presented) An achiral unit is shown to be better than a chiral unit in promoting an asymmetric reaction. Non-C2-symmetric linked-binols 1 with one chiral 1,1′-bi-2-naphthol unit and one flexible achiral unit are employed as ligands in direct catalytic asymmetric Mannich-type reactions (see scheme; TON = turnover number). With as little as 0.01 mol% of ligand 1 a and 0.04 mol% of Et2Zn, the reaction proceeded smoothly to give the product in 98% ee..
36. Shigeki Matsunaga, Takamasa Yoshida, Hiroyuki Morimoto, Naoya Kumagai, Masakatsu Shibasaki, Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/linked-BINOL complex
Synthesis of either anti- or syn-β-amino alcohols, Journal of the American Chemical Society, 10.1021/ja0482435, 126, 28, 8777-8785, 2004.07, Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-β-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-β-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-β-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described..