An Asymmetric Organocatalytic Quadruple Cascade Initiated by a Friedel–Crafts‐Type Reaction with Electron‐Rich Arenes

An organocatalytic quadruple domino reaction initiated by a Friedel–Crafts-type reaction of electron-rich arenes is described. The procedure involving up to three different Michael acceptors afforded highly functionalized cyclohexenecarbaldehydes bearing an aniline moiety, which are of great pharmaceutical and agricultural interest. This diphenylprolinol trimethylsilyl ether-catalyzed reaction also generates up to 4 contiguous stereocenters. It could be shown that various functional groups are tolerated and all products were obtained with very good diastereo- and excellent enantioselectivity.

[1]  J. Alemán,et al.  Applications of asymmetric organocatalysis in medicinal chemistry. , 2013, Chemical Society reviews.

[2]  A. Mazzanti,et al.  Iminium ion catalysis: the enantioselective Friedel-Crafts alkylation-acetalization cascade of naphthols with α,β-unsaturated cyclic ketones. , 2012, Chemical communications.

[3]  D. Enders,et al.  Quadruple domino organocatalysis: an asymmetric aza-Michael/Michael/Michael/aldol reaction sequence leading to tetracyclic indole structures with six stereocenters. , 2012, Chemistry.

[4]  D. Enders,et al.  Asymmetric Synthesis of 3-Substituted Hexahydro-3H-isochromenes via an Organocatalytic Triple Cascade/Yb-Catalyzed Hetero-Diels–Alder Sequence , 2012 .

[5]  K. Shibatomi,et al.  Practical synthesis of 4,4,4-trifluorocrotonaldehyde: a versatile precursor for the enantioselective formation of trifluoromethylated stereogenic centers via organocatalytic 1,4-additions. , 2012, Chemical communications.

[6]  H. Pellissier.  Recent Developments in Asymmetric Organocatalytic Domino Reactions , 2012 .

[7]  D. Enders,et al.  Durch N‐heterocyclische Carbene katalysierte Dominoreaktionen , 2012 .

[8]  D. Enders,et al.  N-heterocyclic carbene catalyzed domino reactions. , 2012, Angewandte Chemie.

[9]  Shoulei Wang,et al.  One-pot enantioselective synthesis of functionalized pyranocoumarins and 2-amino-4H-chromenes: discovery of a type of potent antibacterial agent. , 2012, The Journal of organic chemistry.

[10]  D. Enders,et al.  Ausnutzung der elektrophilen Eigenschaften von Indol‐Intermediaten: neue Optionen in der Planung asymmetrischer Reaktionen , 2012 .

[11]  D. Enders,et al.  Exploiting the electrophilic properties of indole intermediates: new options in designing asymmetric reactions. , 2012, Angewandte Chemie.

[12]  K. Jørgensen,et al.  Taming the Friedel-Crafts reaction: organocatalytic approach to optically active 2,3-dihydrobenzofurans. , 2011, Angewandte Chemie.

[13]  W. Xiao,et al.  Enantioselective Organocatalytic Friedel-Crafts Alkylations , 2011 .

[14]  Y. Yao,et al.  Direct asymmetric hydrosilylation of indoles: combined Lewis base and Brønsted acid activation. , 2011, Angewandte Chemie.

[15]  Chandra M. R. Volla,et al.  General and Efficient Organocatalytic Synthesis of Indoloquinolizidines, Pyridoquinazolines and Quinazolinones through a One‐Pot Domino Michael Addition‐Cyclization‐ Pictet–Spengler or 1,2‐Amine Addition Reaction , 2011 .

[16]  S. You,et al.  Enantioselective Michael/Mannich polycyclization cascade of indolyl enones catalyzed by quinine-derived primary amines. , 2011, Angewandte Chemie.

[17]  V. Gouverneur,et al.  Organocatalyzed enantioselective fluorocyclizations. , 2011, Angewandte Chemie.

[18]  C. Barbas,et al.  Highly efficient hydrogen-bonding catalysis of the Diels-Alder reaction of 3-vinylindoles and methyleneindolinones provides carbazolespirooxindole skeletons. , 2011, Journal of the American Chemical Society.

[19]  R. Maggi,et al.  Update 1 of: Use of solid catalysts in Friedel-Crafts acylation reactions. , 2011, Chemical reviews.

[20]  M. Rueping,et al.  Advances in catalytic metal-free reductions: from bio-inspired concepts to applications in the organocatalytic synthesis of pharmaceuticals and natural products , 2011 .

[21]  Yi-Ju Cao,et al.  Organocatalytic Multiple Cascade Reactions: A New Strategy for the Construction of Enantioenriched Tetrahydrocarbazoles , 2011 .

[22]  S. S. Chimni,et al.  Asymmetric Organocatalytic Aza‐Friedel–Crafts Reaction of Naphthols with N‐Sulfonyl Imines , 2011 .

[23]  Hao Li,et al.  Organocatalytic enantioselective Friedel-crafts reactions of 1-naphthols with aldimines. , 2011, Organic letters.

[24]  A. Mazzanti,et al.  Organocatalytic synthesis of spiro compounds via a cascade Michael-Michael-aldol reaction. , 2010, Chemical communications.

[25]  Raquel P. Herrera,et al.  Asymmetric organocatalysis in total synthesis--a trial by fire. , 2010, Natural product reports.

[26]  D. Enders,et al.  Asymmetric Synthesis of Thiadecalinsvia an Organocatalytic Triple Cascade/Sulfa-Michael Sequence , 2010 .

[27]  D. Enders,et al.  Enantioselective Organocatalytic Synthesis of Arylglycines via Friedel-Crafts Alkylation of Arenes with a Glyoxylate Imine , 2010 .

[28]  Gang Zhao,et al.  The enantioselective, organocatalyzed Diels-Alder reaction of 2-vinylindoles with alpha,beta-unsaturated aldehydes: an efficient route to functionalized tetrahydrocarbazoles. , 2010, Chemistry.

[29]  W. Su,et al.  Imidazolethiones: novel and efficient organocatalysts for asymmetric Friedel–Crafts alkylation , 2010 .

[30]  O. Krokhin,et al.  Organocatalyzed Friedel–Crafts arylation of benzylic alcohols , 2010 .

[31]  J. Campagne,et al.  Organocatalyzed Asymmetric Friedel–Crafts Reactions , 2010 .

[32]  D. Enders,et al.  Organocatalytic asymmetric synthesis of polyfunctionalized 3-(cyclohexenylmethyl)-indoles via a quadruple domino Friedel-Crafts-type/Michael/Michael/aldol condensation reaction. , 2010, Chemical communications.

[33]  D. Enders,et al.  Organocatalytic cascade reactions as a new tool in total synthesis. , 2010, Nature chemistry.

[34]  B. Nachtsheim,et al.  A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis , 2010, Beilstein journal of organic chemistry.

[35]  Marco Bandini,et al.  Katalytische Funktionalisierung von Indolen in einer neuen Dimension , 2009 .

[36]  M. Bandini,et al.  Catalytic functionalization of indoles in a new dimension. , 2009, Angewandte Chemie.

[37]  D. Enders,et al.  Organocatalytic AsymmetricTriple Domino Reactions of Nitromethane with α,β-UnsaturatedAldehydes , 2009 .

[38]  A. Mazzanti,et al.  Targeting structural and stereochemical complexity by organocascade catalysis: construction of spirocyclic oxindoles having multiple stereocenters. , 2009, Angewandte Chemie.

[39]  D. MacMillan,et al.  Nine-step enantioselective total synthesis of (+)-minfiensine. , 2009, Journal of the American Chemical Society.

[40]  X. Companyó,et al.  Organocatalytic domino reactions , 2009 .

[41]  Kwok‐yin Wong,et al.  Organocatalytic asymmetric Friedel-Crafts alkylation/cyclization cascade reaction of 1-naphthols and alpha,beta-unsaturated aldehydes: an enantioselective synthesis of chromanes and dihydrobenzopyranes. , 2009, The Journal of organic chemistry.

[42]  W. Xiao,et al.  Asymmetric Friedel-Crafts alkylations of indoles with dialkyl 3-oxoprop-1-enylphosphonates: organocatalytic enantioselective synthesis of alpha-indolyl phosphonates. , 2009, Chirality.

[43]  J. Conrad,et al.  Enantioselective alpha-arylation of aldehydes via organo-SOMO catalysis. An ortho-selective arylation reaction based on an open-shell pathway. , 2009, Journal of the American Chemical Society.

[44]  M. Zeng,et al.  Chiral Brønsted acid catalyzed Friedel-Crafts alkylation reactions. , 2009, Chemical Society reviews.

[45]  Mohui Wei,et al.  Asymmetric organocatalytic four-component quadruple domino reaction initiated by oxa-Michael addition of alcohols to acrolein. , 2009, Chemistry.

[46]  D. Enders,et al.  Asymmetric Synthesis of Functionalized3,4-Dihydronaphthalenes via an Organocatalytic DominoNitroalkane-Michael/Aldol Condensation Reaction , 2009 .

[47]  M. Bandini,et al.  Catalytic Asymmetric Friedel–Crafts Alkylations , 2009 .

[48]  N. Shibata,et al.  Organocatalytic EnantioselectiveAza-Friedel-Crafts Alkylation of Pyrroles with N-(Heteroarenesulfonyl)imines , 2009 .

[49]  W. Xiao,et al.  Catalytic asymmetric intramolecular hydroarylations of omega-aryloxy- and arylamino-tethered alpha,beta-unsaturated aldehydes. , 2009, Chemistry.

[50]  Lei Wang,et al.  An Efficient Enantioselective Method for Asymmetric Friedel–Crafts Alkylation of Indoles with α,β‐Unsaturated Aldehydes , 2009 .

[51]  B. Hong,et al.  Enantioselective synthesis of the tetrahydro-6H-benzo[c]chromenes via Domino Michael–Aldol condensation: control of five stereocenters in a quadruple-cascade organocatalytic multi-component reaction , 2009 .

[52]  Y. Hayashi,et al.  High-yielding synthesis of the anti-influenza neuramidase inhibitor (-)-oseltamivir by three "one-pot" operations. , 2009, Angewandte Chemie.

[53]  K. Nicolaou,et al.  Enantioselective intramolecular Friedel-Crafts-type alpha-arylation of aldehydes. , 2009, Journal of the American Chemical Society.

[54]  Jun‐An Ma,et al.  Chiral Brønsted Acid‐Mediated Enantioselective Organocatalytic Three‐Component Reaction for the Construction of Trifluoromethyl‐Containing Molecules , 2008 .

[55]  Xinhong Yu,et al.  Organocatalysis: asymmetric cascade reactions catalysed by chiral secondary amines. , 2008, Organic & biomolecular chemistry.

[56]  K. Jørgensen,et al.  Catalytic asymmetric Friedel-Crafts alkylation reactions--copper showed the way. , 2008, Chemical reviews.

[57]  Canxiong Guo,et al.  9-Thiourea Cinchona alkaloid supported on mesoporous silica as a highly enantioselective, recyclable heterogeneous asymmetric catalyst. , 2008, Chemical communications.

[58]  Q. Kang,et al.  Highly enantioselective friedel-crafts reaction of 4,7-dihydroindoles with imines by chiral phosphoric acids: facile access to 2-indolyl methanamine derivatives. , 2008, Chemistry.

[59]  D. Enders,et al.  Asymmetric Synthesis of Polyfunctionalized Mono-, Bi-, and Tricyclic Carbon Frameworks via Organocatalytic Domino Reactions , 2008 .

[60]  J. Antilla,et al.  Organocatalytic enantioselective Friedel-Crafts reaction of pyrrole derivatives with imines. , 2007, Organic letters.

[61]  M. Terada,et al.  Chiral Phosphoric Acid‐Catalyzed Enantioselective Aza‐Friedel–Crafts Reaction of Indoles , 2007 .

[62]  Shou‐Fei Zhu,et al.  Chiral Brønsted acid catalyzed enantioselective Friedel-Crafts reaction of indoles and alpha-aryl enamides: construction of quaternary carbon atoms. , 2007, Angewandte Chemie.

[63]  D. Enders,et al.  Asymmetric Organocatalytic Domino Reactions of γ-Nitroketones and Enals , 2007 .

[64]  J. Perman,et al.  The highly enantioselective addition of indoles to N-acyl imines with use of a chiral phosphoric acid catalyst. , 2007, Organic letters.

[65]  M. Christmann,et al.  Organocatalytic synthesis of drugs and bioactive natural products , 2007 .

[66]  Yi-Ju Cao,et al.  Enantioselective organocatalytic intramolecular ring-closing Friedel-Crafts-type alkylation of indoles. , 2007, Organic letters.

[67]  Armando Carlone,et al.  Organocatalytic Asymmetric Friedel−Crafts Alkylation of Indoles with Simple α,β-Unsaturated Ketones , 2007 .

[68]  D. Enders,et al.  Asymmetrische organokatalytische Dominoreaktionen , 2007 .

[69]  D. Enders,et al.  Asymmetric organocatalytic domino reactions. , 2007, Angewandte Chemie.

[70]  Z. Rappoport.  The Chemistry of Anilines , 2007 .

[71]  Armando Carlone,et al.  A new approach for an organocatalytic multicomponent domino asymmetric reaction. , 2007, Angewandte Chemie.

[72]  Q. Kang,et al.  Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. , 2007, Journal of the American Chemical Society.

[73]  M. Terada,et al.  Enantioselective friedel-crafts reaction of electron-rich alkenes catalyzed by chiral Brønsted acid. , 2007, Journal of the American Chemical Society.

[74]  D. Enders,et al.  Organokatalytische, asymmetrische Eintopf‐Synthese von funktionalisierten tricyclischen Kohlenstoffgerüsten durch eine Tripelkaskade/Diels‐Alder‐Sequenz , 2007 .

[75]  D. Enders,et al.  Organocatalytic one-pot asymmetric synthesis of functionalized tricyclic carbon frameworks from a triple-cascade/Diels-Alder sequence. , 2007, Angewandte Chemie.

[76]  K. Nicolaou,et al.  Kaskadenreaktionen in der Totalsynthese , 2006 .

[77]  K C Nicolaou,et al.  Cascade reactions in total synthesis. , 2006, Angewandte Chemie.

[78]  D. Enders,et al.  Control of four stereocentres in a triple cascade organocatalytic reaction , 2006, Nature.

[79]  Jun Song,et al.  Asymmetric Friedel-crafts reaction of indoles with imines by an organic catalyst. , 2006, Journal of the American Chemical Society.

[80]  H. Pellissier.  Asymmetric domino reactions. Part B: Reactions based on the use of chiral catalysts and biocatalysts , 2006 .

[81]  H. Pellissier.  Asymmetric domino reactions. Part A: Reactions based on the use of chiral auxiliaries , 2006 .

[82]  Hongbao Guo,et al.  Katalytische asymmetrische Tandemumwandlungen mit einer konjugierten Addition als einleitendem Schritt , 2006 .

[83]  Jun‐An Ma,et al.  Catalytic asymmetric tandem transformations triggered by conjugate additions. , 2006, Angewandte Chemie.

[84]  J. Macor,et al.  Enantioselective Synthesis of a Highly Potent Selective Serotonin Reuptake Inhibitor. An Application of Imidazolidinone Catalysis to the Alkylation of Indoles with an α,β-Disubstituted α,β-Unsaturated Aldehyde , 2005 .

[85]  M. Bandini,et al.  A Journey Across Recent Advances in Catalytic and Stereoselective Alkylation of Indoles , 2005 .

[86]  Sung‐Gon Kim,et al.  Efficient total synthesis of (+)-curcuphenol via asymmetric organocatalysis , 2005 .

[87]  M. Terada,et al.  Organocatalytic asymmetric aza-Friedel-Crafts alkylation of furan. , 2004, Journal of the American Chemical Society.

[88]  W. Xiao,et al.  Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition-cyclization strategy: synthesis of (-)-flustramine B. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[89]  Marco Bandini,et al.  Neue katalytische Methoden in der stereoselektiven Friedel‐Crafts‐Alkylierung , 2004 .

[90]  M. Bandini,et al.  New catalytic approaches in the stereoselective Friedel-Crafts alkylation reaction. , 2004, Angewandte Chemie.

[91]  Z. Rappoport,et al.  The chemistry of phenols , 2003 .

[92]  Nick A. Paras,et al.  The Enantioselective Organocatalytic 1,4-Addition of Electron-Rich Benzenes to α,β-Unsaturated Aldehydes , 2002 .

[93]  D. MacMillan,et al.  Enantioselective organocatalytic indole alkylations. Design of a new and highly effective chiral amine for iminium catalysis. , 2002, Journal of the American Chemical Society.

[94]  Nick A. Paras,et al.  New strategies in organic catalysis: the first enantioselective organocatalytic Friedel-Crafts alkylation. , 2001, Journal of the American Chemical Society.