根本 哲宏

We report the first enantioselective total syntheses of cedrelin A and methylated paralycolin B, wherein Pd-catalyzed asymmetric intramolecular Friedel-Crafts allylic alkylation of phenols was the key step. (C) 2013 Elsevier Ltd. All rights reserved.

An acid-promoted novel skeletal rearrangement is described. Using trifluoroacetic acid as the acid promoter, an intramolecular ipso-Friedel-Crafts-type addition of phenols to 3-alkylidene indolenium cations, formation of iminium cations through rearomatization of the spirocyclohexadienone units, and intramolecular Pictet-Spengler reaction proceeded sequentially, producing tricyclic indole derivatives.

We developed a novel asymmetric synthetic method for multisubstituted 9,10-dihydrophenanthrenes based on the Pd-catalyzed asymmetric intramolecular Friedel-Crafts allylic alkylation of phenols, which produces 10-vinyl or 10-isopropenyl chiral 9,10-dihydrophenanthrene derivatives in high yield with up to 94% ee.

A novel catalytic asymmetric synthetic method for making spirocyclohexadienones with an all-carbon quaternary spirocenter was developed based on the Pd-catalyzed intramolecular ipso-Friedel-Crafts allylic alkylation of phenols. When 5 mol % of the Pd catalyst and 12 mol % of (-)-9-NapBN (-)-3e were used, the spirocyclic adduct was obtained with up to 93% ee, albeit with low chemical yield. On the other hand, when using 6 mol% of the Trost ligand (R,R)-3k, the spirocyclic adducts were obtained in good yields with up to 89% ee (diastereoselectivity = 9.2:1). (c) 2012 Elsevier Ltd. All rights reserved.

We developed a novel method for the asymmetric synthesis of highly functionalized gamma-lactams through an organocatalytic aza-Michael-Michael reaction cascade using fumaric acid amide esters as multi-reactive substrates. Using chiral primary or secondary amine organocatalysts, we obtained two types of gamma-lactams with three contiguous chiral centers in moderate to good yield with excellent enantioselectivity and diastereoselectivity. (C) 2012 Published by Elsevier Ltd.

2010年度のノーベル化学賞が「有機合成におけるPd触媒を用いるクロスカップリング反応」との名の下に,Richard F.Heck博士,根岸英一博士,鈴木章博士の3名に授与された。クロスカップリング反応,聞き慣れない言葉と思われるが,医薬品や液晶化合物など,現代人の生活には欠かす事のできない機能性物質の合成に利用されている有機化学反応である。本稿では,これらの反応がどのような形で私達の実生活に関連しているか,また最先端科学研究における本反応の重要性までを含め解説する。

We developed a novel (S)-L-phenylalanine derived-bidentate chiral diaminophosphine oxide (DIAPHOX) 'preligand (S,S-P)-9b, which was successfully applied to Pd-catalyzed asymmetric allylic alkylation and amination. Using the Pd-(S,S-P)-9b catalyst system, asymmetric allylic alkylation and amination proceeded very smoothly, affording the corresponding products in excellent yield with high enantiomeric excess. It is noteworthy that both enantiomers were accessible with high enantiomeric purity using the structurally related DIAPHOX preligands (S,S-P)-9b and a monodentate chiral diaminophosphine oxide preligand (S,R-P)-10a, both of which can be prepared from a single chiral source, (S)-L-phenylalanine.

Novel chiral hydrogen bond donor catalysts based on a 4,5-diamino-9,9'-dimethylxanthene skeleton were designed and synthesized. Among the phenylurea-amide hybrid molecules prepared from various natural/unnatural chiral amino acids, the phenylalanine-derived catalyst, and the proline-derived catalyst were successfully applied to enantioselective conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes. Using 2-acetylcyclopentanone and 2-methoxycarbonylcyclopentanone as prochiral nucleophiles, asymmetric conjugate addition to beta-aryl nitroalkenes proceeded with good diastereoselectivity to provide the corresponding products bearing an all-carbon quaternary stereocenter in excellent yield with up to 95% ee. (C) 2011 Elsevier Ltd. All rights reserved.

A novel method of the enantioselective synthesis of 2-substituted hexahydroquinolin-4-ones is described. The method relies on a Pd-catalyzed asymmetric allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand and diastereoselective intramolecular Mannich reaction. The developed synthetic method could be applied to the catalytic asymmetric synthesis of (+)-2-epi-cis-195A.

This review describes the development of a new class of chiral secondary phosphine oxide preligands: Amino acid-derived P-chiral diaminophosphine oxides, DIAPHOXs, and their application to several transition metal-catalyzed asymmetric reactions. The Pd-DIAPHOX catalyst system was successfully applied to enantioselective construction of quaternary stereocenters through Pd-catalyzed asymmetric allylic alkylation with beta-keto esters as prochiral nucleophiles, asymmetric allylic substitutions with nitromethane, asymmetric allylic amination with various substrates, and enantioselective synthesis of axially chiral allenes. Ir-catalyzed asymmetric allylic amination and alkylation of terminal allylic carbonates were also examined using structurally optimized DIAPHOX preligands, and the corresponding branched products were obtained in a highly regio- and enantioselective manner. Furthermore, the developed processes were successfully applied to the enantioselective synthesis of biologically active compounds.

The first successful Pd-catalyzed intramolecular ipso-Friedel Crafts allylic alkylation of phenols, which provided a new access to spiro[4.5]cyclohexadienones, is described. The present method could be applied to catalytic enantioselective construction of an all-carbon quaternary spirocenter.

The first enantioselective total synthesis of tangutorine has been achieved, wherein a Pd-catalyzed asymmetric allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand was the key step.

An enantioselective synthesis of allenes through palladium-catalyzed asymmetric allylic alkylation using a chiral diaminophosphine oxide is described. The asymmetric allylic alkylations proceeded in the presence of a catalytic amount of lithium acetate at 4 degrees C, affording the chiral allenes in excellent yield with up to 99% ee.

This review describes the development of a new class of chiral phosphorus ligands: amino acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several transition metal-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation with cyclic β3-keto esters as prochiral nucleophiles was initially examined using P-chirogenic diaminophosphine oxide la, resulting in highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that la is activated by .N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 13, which functions as the actual ligand. Pd-catalyzed asymmetric allylic substitutions of both acyclic and cyclic substrates were also examined using various nucleophiles such as malonate derivatives, nitromethane, aliphatic amines, and aromatic amines, providing a variety of chiral compounds with good to excellent enantioselectivity. In addition, Ir-catalyzed asymmetric allylic amination and alkylation of terminal allylic carbonates were examined using structurally optimized P-chirogenic diaminophosphine oxides, and the corresponding branched products were obtained in a highly regio- and enantioselective manner. Furthermore, the developed catalytic asymmetric process was successfully applied to the catalytic enantioselective synthesis of biologically active compounds, (R)-preclamol, (R)-baclofen hydrochloride, and (-)-paroxetine. © 2008 Pharmaceutical Society of Japan.

Asymmetric allylic aminations with aromatic amine nucleophiles using Pd-DIAPHOX catalyst systems are described. The asymmetric allylic aminations of various allylic carbonates proceeded using 2-5 mol % of the catalyst and BSA, providing the corresponding N-aryl chiral allylic amines in up to 99% ee for cyclic substrates, and in up to 97% ee for acyclic substrates. (C) 2008 Elsevier Ltd. All rights reserved.

A Pd-catalyzed asymmetric allylic alkylation of 2-substituted cycloalkenyl carbonates using a chiral diaminophosphine oxide is described. Asymmetric allylic substitution of various cyclic substrates proceeded using 5 mol % of Pd catalyst, 10 mol % of (S,RP)-Ph-DIAPHOX 1, 10 mol % of LiOAc, and N,O-bis(trimethylsilyl)acetamide (BSA), to afford the corresponding products in excellent yields with up to 92% ee. (C) 2008 Elsevier Ltd. All rights reserved.

Asymmetric allylic amination of allylic carbonates prepared from racemic Morita-Baylis-Hillman adducts proceeded in the presence of Pd catalyst, chiral diaminophosphine oxide (DIAPHOX), and BSA, affording the corresponding chiral aza-Morita-Baylis-Hillman adduct derivatives in excellent yield with up to 99% ee. The cyclic reaction products could be converted into various synthetically useful compounds such as chiral cyclic beta-amino acids.

An Ir-catalyzed asymmetric allylic alkylation using chiral diaminophosphine oxide is described. Asymmetric allylic alkylation of terminal allylic carbonates proceeded using 5 mol % of Ir catalyst, 5 mol% of DIAPHOX Ii, 10 moll % of NaPF6, 10 11101 % of LiOAc, and N,O-bis(trimethylsilyl)acetamide (BSA), affording the corresponding branched products in excellent yield and in up to 95% ee. The developed catalytic asymmetric reaction was successfully applied to a formal enantioselective synthesis of paroxetine. (C) 2007 Elsevier Ltd. All rights reserved.

A Pd-catalyzed enantio selective synthesis of quaternary alpha-amino acid derivatives using a phenylalanine-derived P-chirogenic diaminophosphine oxide is described. Asymmetric allylic substitution using acyclic beta-keto esters with a nitrogen functional group at the alpha-carbon as prochiral nucleophiles proceeded in the presence of 5 mol % of Pd catalyst, 10 mol % of chiral diaminophosphine oxide 1j, BSA, and appropriate additives, affording the corresponding quaternary alpha-amino acid derivatives in excellent yield and in up to 92% ee. (c) 2007 Elsevier Ltd. All rights reserved.

The synthesis of novel P-stereogenic phenylphosphonamides 3 and 11 via an intramolecular nucleophilic substitution of P-stereogenic phosphoramide 8 is described. These compounds were used as chiral Lewis basic catalysts for the asymmetric allylation of benzaldehyde, providing the corresponding homoallylic alcohol derivatives in up to 54% ee. (C) 2007 Elsevier Ltd. All rights reserved.

This paper describes the development of a new class of chiral phosphorus ligand: aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed. asymmetric allylic alkylation was initially examined in detail using diaminophosphine oxides la, resulting in the highly enantioselecrive construction of quaternary stereocenters. Mechanistic investigations revealed that la is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 12, which functions as the actual ligand. Furthermore, asymmetric allylic amination was examined using Pd-DIAPHOX catalyst systems, providing a variety of chiral allylic amines. (c) 2007 The Japan Chemical journal Forum and Wiley Periodicals, Inc.

A Pd-catalyzed asymmetric allylic alkylation with nitromethane using an aspartic acid-derived P-chirogenic diaminophosphine oxide [(S,RP)-Ph-DIAPHOX] is described. This method was successfully applied to enantioselective synthesis of (R)-preclamol and (R)-baclofen. © 2006 Elsevier Ltd. All rights reserved.

We developed an efficient method for the synthesis of 3-substituted 2,3-dihydroquinolin-4-ones using a one-pot sequential multi-catalytic process: Pd-catalyzed allylic amination-thiazolium salt-catalyzed Stetter reaction cascade. Measurement of the initial rate of the developed sequential process revealed a significant increase in the reaction rate of the Stetter reaction in the presence of Pd(OAc)2 and AcOH·i-Pr2NEt, the constituents of the first Pd catalysis. © 2006 Elsevier Ltd. All rights reserved.

An Ir-catalyzed asymmetric allylic amination using chiral diaminophosphine oxide is described. Asymmetric allyno amination of terminal allylic carbonates proceeded in the presence of 2 mol % of Ir catalyst, 2 mol % of chiral diaminophosphine oxide, 5 mol % of NaPF6, and BSA, affording the chiral branched allylic amines in up to 95% cc. (c) 2006 Elsevier Ltd. All rights reserved.

We have successfully demonstrated that γ-acetoxy-α,β- unsaturated carbonyl compounds are useful starting materials for Pd-catalyzed asymmetric allylic alkylation to construct all-carbon quaternary stereocenters. With the use of 2-5 mol % of Pd catalyst and 4-10 mol % of P-chirogenic diaminophosphine oxides, asymmetric allylic alkylation of γ-acetoxy- α,β-unsaturated carbonyl compounds with various prochiral nucleophiles derived from cyclic β-keto esters proceeded in the presence of Zn(OAc)2, providing the corresponding products with an all-carbon quaternary stereocenter in up to 95% ee. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

(Chemical Equation Presented) A Pd-catalyzed asymmetric allylic amination using aspartic acid derived P-chirogenic diaminophosphine oxides (DIAPHOXs) is described. Asymmetric allylic amination of both linear and cyclic substrates proceeded at room temperature to give the chiral allylic amines in 72-99% ee. © 2005 American Chemical Society.

We have recently developed a new class of chiral phosphorus ligands: P-chirogenic diaminophosphine oxides. These pentavalent phosphorus compounds have been successfully applied to Pd-catalyzed asymmetric construction of tertiary and quaternary carbons. The actual ligand structure was the trivalent phosphorus species 17, which was generated in situ by BSA-induced P(V) to P(III) transformation of 6, the preligand. Detailed mechanistic studies, including asymmetric amplification and initial rate kinetics, revealed that complex 18 [Pd-17 (1:2) complex] was the active catalyst. The important function of the nitrogen atom on the sidearm in the ligands was also clarified. The source of enantioselection in the construction of asymmetric quaternary carbons was the secondary ligand substrate interaction mediated by N-Zn coordination. © 2005 American Chemical Society.

We successfully synthesized a novel P-chirogenic diaminophosphine oxide 4, which was applied to catalytic enantioselective construction of quaternary carbon centers using Pd-catalyzed asymmetric allylic substitution with various β-keto esters (up to 99% yield, 94% ee). Preliminary mechanistic studies indicated that two molecules of 8 coordinate to the Pd metal in a monodentate fashion, resulting in the formation of Pd complex 9 (Pd:8 = 1:2), which functions as the active species. Copyright © 2004 American Chemical Society.