Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram.

Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram.

[1]  V. Aggarwal,et al.  Lithiation-borylation methodology and its application in synthesis. , 2014, Accounts of chemical research.

[2]  W. Yuan,et al.  A chiral ruthenium-monophosphine catalyst for asymmetric addition of arylboronic acids to aryl aldehydes. , 2013, The Journal of organic chemistry.

[3]  T. Snape,et al.  Chiral 1,1-diaryl compounds as important pharmacophores , 2013 .

[4]  Wenjun Tang,et al.  Enantioselective Rhodium-Catalyzed Addition of Arylboronic Acids to Trifluoromethyl Ketones , 2013 .

[5]  Zhihua Cai,et al.  Design of phosphorus ligands with deep chiral pockets: practical synthesis of chiral β-arylamines by asymmetric hydrogenation. , 2013, Angewandte Chemie.

[6]  P. Jones,et al.  AT13148 Is a Novel, Oral Multi-AGC Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity , 2012, Clinical Cancer Research.

[7]  Guihua Chen,et al.  Rh(I)-catalyzed asymmetric addition of arylboronic acids to NH isatins , 2012 .

[8]  G. Pattison,et al.  Enantioselective Rh(I)-catalyzed cyclization of arylboron compounds onto ketones. , 2012, Organic letters.

[9]  Chun‐hui Xing,et al.  Rhodium(I)/diene-catalyzed addition reactions of arylborons with ketones. , 2012, Organic letters.

[10]  Tingshun Zhu,et al.  Rhodium-catalyzed, highly enantioselective 1,2-addition of aryl boronic acids to α-ketoesters and α-diketones using simple, chiral sulfur-olefin ligands. , 2012, Angewandte Chemie.

[11]  G. Lin,et al.  Rhodium-Catalyzed Asymmetric Arylation , 2012 .

[12]  Stephen P. Thomas,et al.  Enantioenriched synthesis of Escitalopram using lithiation-borylation methodology , 2011 .

[13]  Feng Cai,et al.  Chiral allene-containing phosphines in asymmetric catalysis. , 2011, Journal of the American Chemical Society.

[14]  T. Sakai,et al.  Synthesis and application of 2,6-bis(trifluoromethyl)-4-pyridyl phosphanes: the most electron-poor aryl phosphanes with moderate bulkiness. , 2011, Angewandte Chemie.

[15]  Yasunori Yamamoto,et al.  Ru/Me-BIPAM-Catalyzed Asymmetric Addition of Arylboronic Acids to Aliphatic Aldehydes and α-Ketoesters , 2011, Molecules.

[16]  Guigen Li,et al.  Catalytic asymmetric addition of arylboronic acids to isatins using C2-symmetric cationic N-heterocyclic carbenes (NHCs) Pd2+ diaqua complexes as catalysts. , 2011, Organic letters.

[17]  Shou‐Fei Zhu,et al.  Transition metal-catalyzed enantioselective hydrogenation of enamines and imines. , 2011, Chemical reviews.

[18]  V. R. Jumde,et al.  A chiral Rh–phosphite complex displaying high activity in the enantioselective Rh-catalyzed addition of arylboronic acids to carbonyl compounds: when and why atropos is better than tropos , 2010 .

[19]  C. Senanayake,et al.  Novel, tunable, and efficient chiral bisdihydrobenzooxaphosphole ligands for asymmetric hydrogenation. , 2010, Organic letters.

[20]  Hideki Miyatake-Ondozabal,et al.  Synthesis of (-)-(S,S)-clemastine by invertive N --> C aryl migration in a lithiated carbamate. , 2010, Organic letters.

[21]  Jinhua J. Song,et al.  Copper catalyzed asymmetric propargylation of aldehydes. , 2010, Journal of the American Chemical Society.

[22]  S. Morikawa,et al.  Novel axially chiral phosphine ligand with a fluoro alcohol moiety for Rh-catalyzed asymmetric arylation of aromatic aldehydes. , 2010, Organic letters.

[23]  Chun‐hui Xing,et al.  Transition metal-catalyzed addition reactions of arylboronic acids with alkyl 2-formylbenzoates: efficient access to chiral 3-substituted phthalides. , 2010, Chemical communications.

[24]  K. Kondo,et al.  Et-duphos-nickel-catalyzed asymmetric arylation of benzaldehyde derivatives bearing an ortho-Me2PhSi group with potassium aryltriolborates , 2009 .

[25]  Tamio Hayashi,et al.  The concise synthesis of chiral tfb ligands and their application to the rhodium-catalyzed asymmetric arylation of aldehydes. , 2009, Chemical communications.

[26]  K. Itami,et al.  A nickel catalyst for the addition of organoboronate esters to ketones and aldehydes. , 2009, Organic letters.

[27]  Yasunori Yamamoto,et al.  Me-bipam for enantioselective ruthenium(II)-catalyzed arylation of aldehydes with arylboronic acids. , 2009, Angewandte Chemie.

[28]  K. Kondo,et al.  Interesting Nickel-Catalyzed 1,2-Addition to α,β-Unsaturated Aldehydes with Arylborates , 2009 .

[29]  Qiongsi Wu,et al.  Synthesis of novel enantiopure biphenyl P,N-ligands and application in palladium-catalyzed asymmetric addition of arylboronic acids to N-benzylisatin. , 2009, The Journal of organic chemistry.

[30]  V. Aggarwal,et al.  Enantiodivergent conversion of chiral secondary alcohols into tertiary alcohols , 2008, Nature.

[31]  Xiyan Lu,et al.  Palladium(II)-catalyzed intramolecular addition of arylboronic acids to ketones , 2008 .

[32]  Hee-doo Kim,et al.  Stereoselective synthesis of (+)-flutriafol , 2008 .

[33]  M. Kanai,et al.  Asymmetric synthesis of tertiary alcohols and alpha-tertiary amines via Cu-catalyzed C-C bond formation to ketones and ketimines. , 2008, Chemical reviews.

[34]  Qi‐Lin Zhou,et al.  Enantioselective rhodium-catalyzed addition of arylboronic acids to alpha-ketoesters. , 2008, Angewandte Chemie.

[35]  A. Chan,et al.  Catalytic Asymmetric Alkynylation and Arylation of Aldehydes by an H8-Binaphthyl-Based Amino Alcohol Ligand , 2008 .

[36]  Kuo-Hui Wu,et al.  Highly enantioselective aryl additions of [AlAr3(thf)] to ketones catalyzed by a titanium(IV) catalyst of (S)-binol. , 2007, Angewandte Chemie.

[37]  K. Kondo,et al.  Nickel-catalyzed 1,2-addition of arylboroxines to aromatic aldehydes , 2007 .

[38]  B. Feringa,et al.  Synthesis of solution-phase phosphoramidite and phosphite ligand libraries and their in situ screening in the rhodium-catalyzed asymmetric addition of arylboronic acids. , 2007, Journal of combinatorial chemistry.

[39]  O. Riant,et al.  Asymmetric catalysis for the construction of quaternary carbon centres: nucleophilic addition on ketones and ketimines. , 2007, Organic & biomolecular chemistry.

[40]  V. T. Mathad,et al.  Substrate Modification Approach to Achieve Efficient Resolution: Didesmethylcitalopram: A Key Intermediate for Escitalopram# , 2007 .

[41]  Michael E. Laurila,et al.  Optimized Catalytic Enantioselective Aryl Transfer Process Gives Access to mGlu2 Receptor Potentiators , 2007 .

[42]  Xiyan Lu,et al.  Cationic palladium complex catalyzed highly enantioselective intramolecular addition of arylboronic acids to ketones. A convenient synthesis of optically active cycloalkanols. , 2006, Journal of the American Chemical Society.

[43]  B. Feringa,et al.  Enantioselective rhodium-catalyzed addition of arylboronic acids to trifluoromethyl ketones. , 2006, Chemical communications.

[44]  V. Martín,et al.  Asymmetric Addition to Ketones: Enantioselective Formation of Tertiary Alcohols , 2006 .

[45]  M. Kanai,et al.  Nucleophilic activation of alkenyl and aryl boronates by a chiral Cu(I)F complex: catalytic enantioselective alkenylation and arylation of aldehydes. , 2006, Chemistry, an Asian journal.

[46]  B. Feringa,et al.  Rhodium-catalyzed addition of arylboronic acids to isatins: an entry to diversity in 3-aryl-3-hydroxyoxindoles. , 2006, Organic letters.

[47]  A. Chan,et al.  Highly enantioselective addition of in situ prepared arylzinc to aldehydes catalyzed by a series of atropisomeric binaphthyl-derived amino alcohols. , 2006, Chemistry.

[48]  R. Shintani,et al.  Rhodium-catalyzed asymmetric addition of aryl- and alkenylboronic acids to isatins. , 2006, Angewandte Chemie.

[49]  Qi Zhang,et al.  Enantioselective rhodium-catalyzed addition of arylboronic acids to aldehydes using chiral spiro monophosphite ligands. , 2006, Organic letters.

[50]  B. Feringa,et al.  Rhodium/phosphoramidite-catalyzed asymmetric arylation of aldehydes with arylboronic acids. , 2006, Organic & biomolecular chemistry.

[51]  M. Paixão,et al.  Catalytic enantioselective arylation of aldehydes: boronic acids as a suitable source of transferable aryl groups. , 2005, Chemical communications.

[52]  A. Chan,et al.  Highly enantioselective phenyl transfer to aryl aldehydes catalyzed by easily accessible chiral tertiary aminonaphthol. , 2005, The Journal of organic chemistry.

[53]  C. Bolm,et al.  Highly Enantioselective Synthesis of Secondary Alcohols using Triphenylborane , 2004 .

[54]  Diego J. Ramón,et al.  Chirale tertiäre Alkohole durch katalytische enantioselektive Addition von unreaktiven Zinkreagentien an schwach elektrophile Ketone , 2004 .

[55]  M. Yus,et al.  Chiral tertiary alcohols made by catalytic enantioselective addition of unreactive zinc reagents to poorly electrophilic ketones? , 2004, Angewandte Chemie.

[56]  M. Yus,et al.  Highly enantioselective arylation of ketones , 2003 .

[57]  S. Denmark,et al.  Catalytic enantioselective addition of allylic organometallic reagents to aldehydes and ketones. , 2003, Chemical reviews.

[58]  Xumu Zhang,et al.  New chiral phosphorus ligands for enantioselective hydrogenation. , 2003, Chemical reviews.

[59]  C. Bolm,et al.  Catalyzed asymmetric aryl transfer reactions to aldehydes with boronic acids as aryl source. , 2002, Journal of the American Chemical Society.

[60]  Xumu Zhang,et al.  A chiral 1,2-bisphospholane ligand with a novel structural motif: applications in highly enantioselective Rh-catalyzed hydrogenations. , 2002, Angewandte Chemie.

[61]  L. Pu,et al.  Catalytic asymmetric organozinc additions to carbonyl compounds. , 2001, Chemical reviews.

[62]  N. Miyaura,et al.  Rhodium-Catalyzed Addition of Organoboronic Acids to Aldehydes. , 1998, Angewandte Chemie.

[63]  N. Miyaura,et al.  RHODIUMKATALYSIERTE ADDITION VON ORGANOBORONSAUREN AN ALDEHYDE , 1998 .

[64]  M. Yus,et al.  FIRST ENANTIOSELECTIVE ADDITION OF DIALKYLZINC TO KETONES PROMOTED BY TITANIUM(IV) DERIVATIVES , 1998 .

[65]  G. Plosker,et al.  Escitalopram , 2006, CNS drugs.

[66]  M. Lautens,et al.  Rhodium-catalyzed carbon-carbon bond forming reactions of organometallic compounds. , 2003, Chemical reviews.

[67]  P. Dosa,et al.  Catalytic Asymmetric Addition of ZnPh2 to Ketones: Enantioselective Formation of Quaternary Stereocenters , 1998 .

[68]  A. L. Porte,et al.  275. Lignans from Myristica otoba. The structures of hydroxyotobain and iso-otobain , 1963 .