Simultaneous synthesis of both rings of chromenes via a benzannulation/o-quinone methide formation/electrocyclization cascade.

A new route to the chromene ring system has been developed which involves the reaction of an α,β-unsaturated Fischer carbene complex of chromium with a propargyl ether bearing an alkenyl group on the propargylic carbon. This transformation involves a cascade of reactions that begins with a benzannulation reaction and is followed by the formation of an o-quinone methide, and finally results in the emergence of a chromene upon an electrocyclization. This reaction was extended to provide access by employing an aryl carbene complex. This constitutes the first synthesis of chromenes in which both rings of the chromene system are generated in a single step and is highlighted in the synthesis of lapachenole and vitamin E.

[1]  Matthew E Welsch,et al.  Privileged scaffolds for library design and drug discovery. , 2010, Current opinion in chemical biology.

[2]  J. P. Harrity,et al.  Chromenes through Metal-Catalyzed Reactions of Styrenyl Ethers. Mechanism and Utility in Synthesis , 1998 .

[3]  D. Uguen,et al.  Efficient Access to (All-rac)-α-Tocopherol Acetate by a Crombie Chromene Synthesis , 2009 .

[4]  M. Adler,et al.  Direct, regioselective synthesis of 2,2-dimethyl-2H-chromenes. Total syntheses of octandrenolone and precocenes I and II , 2009 .

[5]  Soizic Prado,et al.  A simple two steps ytterbium triflate‐catalysed preparation of 2,2‐dimethyl‐2h‐chromenes from salicylaldehydes and 2‐methylpropene , 2006 .

[6]  G. Trivedi,et al.  Synthesis of 2, 2-Dimethyl-2H-chromenes via a Palladium (II) Catalysed Reaction , 1990 .

[7]  A. Aponick,et al.  A highly adaptable catalyst/substrate system for the synthesis of substituted chromenes. , 2010, Chemical communications.

[8]  Karl Heinz Dötz,et al.  Fischer carbene complexes in organic synthesis: metal-assisted and metal-templated reactions. , 2009, Chemical reviews.

[9]  Fei Liu,et al.  Synthesis of 2-substituted 2H-chromenes using potassium vinyltrifluoroborates. , 2008, Tetrahedron letters.

[10]  Y. Hayashi,et al.  Stereoselective synthesis of (.eta.6-arene)Cr(CO)3 complexes possessing a chiral center at the benzylic position , 1986 .

[11]  W. V. Otterlo,et al.  Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes , 2005 .

[12]  Yong Tang,et al.  Unexpected tandem ylide annulation reaction for controllable synthesis of 2H-chromenes and 4H-chromenes. , 2006, Organic letters.

[13]  A. Chizhov,et al.  Solvent-free cascade reaction: direct multicomponent assembling of 2-amino-4H-chromene scaffold from salicylaldehyde, malononitrile or cyanoacetate and nitroalkanes , 2010 .

[14]  Mong Liang,et al.  New organometallic polymers containing tungsten carbene complexes , 1988 .

[15]  Manish Rawat,et al.  Chromene chromium carbene complexes in the syntheses of naphthopyran and naphthopyrandione units present in photochromic materials and biologically active natural products. , 2006, Journal of the American Chemical Society.

[16]  D. Sinou,et al.  PALLADIUM(0)-CATALYZED SYNTHESIS OF 2-PHENYL-2H-CHROMENE , 2002 .

[17]  Y. R. Lee,et al.  Efficient and general method for the synthesis of benzopyrans by ethylenediamine diacetate-catalyzed reactions of resorcinols with α,β-unsaturated aldehydes. One step synthesis of biologically active (±)-confluentin and (±)-daurichromenic acid , 2005 .

[18]  R. Larock,et al.  Synthesis of 3,4-disubstituted 2H-benzopyrans through C-C bond formation via electrophilic cyclization. , 2007, The Journal of organic chemistry.

[19]  Lee M. Bishop,et al.  Mechanistic investigations of the acid-catalyzed cyclization of a vinyl ortho-quinone methide. , 2008, Chemistry.

[20]  Keith A. Korthals,et al.  Traceless stereoinduction in the one-pot assembly of all three rings of hexahydrodibenzopyrans. , 2008, Journal of the American Chemical Society.

[21]  R. Dahiya,et al.  An Expeditious and Solvent-Free Synthesis of 2-Amino-Substituted Isoflav-3-enes Using Microwave Irradiation† , 1998 .

[22]  Finn,et al.  2H-Chromenes from salicylaldehydes by a catalytic petasis reaction , 2000, Organic letters.

[23]  J. Clardy,et al.  Reactions of Group 6 Fischer carbene complexes with alkynes: effect of the metal on the product distribution and the isolation of a nontautomerized cyclohexadienone complex , 1994 .

[24]  P. T. Kaye,et al.  Application of Baylis–Hillman methodology in a chemoselective synthesis of 3-acyl-2H-1-chromenes , 2000 .

[25]  K. Dötz,et al.  A Carbene-Complex Route to Vitamin E† , 1983 .

[26]  R. Grubbs,et al.  A Highly Efficient and Practical Synthesis of Chromene Derivatives Using Ring-Closing Olefin Metathesis. , 1998, The Journal of organic chemistry.

[27]  M. Itoigawa,et al.  Cancer chemopreventive activity of naphthoquinones and their analogs from Avicennia plants. , 2001, Cancer letters.

[28]  Zhen-yuan Xu,et al.  A Novel Enantioselective Catalytic Tandem Oxa‐Michael–Henry Reaction: One‐Pot Organocatalytic Asymmetric Synthesis of 3‐Nitro‐2H‐chromenes , 2008 .

[29]  M. Rueping,et al.  Chiral organic contact ion pairs in metal-free catalytic asymmetric allylic substitutions. , 2011, Journal of the American Chemical Society.

[30]  Sangmi Oh,et al.  Construction of a polyheterocyclic benzopyran library with diverse core skeletons through diversity-oriented synthesis pathway. , 2010, Journal of combinatorial chemistry.

[31]  Seung Bum Park,et al.  Diversity-oriented synthesis of privileged benzopyranyl heterocycles from s-cis-enones. , 2008, The Journal of organic chemistry.

[32]  S. W. Youn,et al.  Facile construction of the benzofuran and chromene ring systems via PdII-catalyzed oxidative cyclization. , 2005, Organic letters.

[33]  Philip D. Campbell,et al.  Synthesis of function-oriented 2-phenyl-2H-chromene derivatives using L-pipecolinic acid and substituted guanidine organocatalysts. , 2010, Tetrahedron letters.

[34]  S. Ravichandran.  A NEW APPROACH TO THE SYNTHESIS OF CHROMENE DERIVATIVES , 2001 .

[35]  W. C. Taylor,et al.  Synthesis of 2,2-dimethylchromenes , 1969 .

[36]  T. Govender,et al.  Organocatalytic synthesis of chiral benzopyrans , 2006 .

[37]  Danqian Xu,et al.  Chiral amine/chiral acid as an excellent organocatalytic system for the enantioselective tandem oxa-Michael-aldol reaction. , 2009, Organic & biomolecular chemistry.

[38]  Ralph G. Pearson,et al.  Ionization potentials and electron affinities in aqueous solution , 1986 .

[39]  Jian Wang,et al.  One-pot approach to chiral chromenes via enantioselective organocatalytic domino oxa-Michael-aldol reaction. , 2007, Chemical communications.

[40]  S. Davies,et al.  Arene Chromium Tricarbonyl Stabilised Benzylic Carbocations , 1993 .

[41]  S. Carloni,et al.  Zeolite-Induced Heterodomino Reaction. Regioselective Synthesis of 2H-1-Benzopyrans from Phenols and α-Alkynols , 1997 .

[42]  Y. Kim,et al.  A Novel Method for the Synthesis of Substituted Benzochromenes by Ethylenediamine Diacetate‐Catalyzed Cyclizations of Naphthalenols to α,β‐Unsaturated Aldehydes. Concise Synthesis of the Natural Products Lapachenole, Dihydrolapachenole, and Mollugin , 2007 .

[43]  Jean-Yves Goujon,et al.  A new approach to 2,2-disubstituted chromenes and tetrahydroquinolines through intramolecular cyclization of chiral 3,4-epoxy alcohols , 2004 .

[44]  A. Córdova,et al.  Catalytic enantioselective domino oxa-michael/aldol condensations: asymmetric synthesis of benzopyran derivatives. , 2007, Chemistry.

[45]  T. Hanamoto,et al.  Synthesis and reactions of a-fluorovinylphosphonium salts , 2000 .

[46]  R. Ostrander,et al.  Origin of the regioselectivity in an intramolecular nucleophilic addition to arene chromium tricarbonyl complexes , 2010 .

[47]  T. Mindt,et al.  Electrocyclic ring closure of the enols of vinyl quinones. A 2H-chromene synthesis. , 2001, Organic letters.

[48]  Helen J. Mitchell,et al.  Natural Product-like Combinatorial Libraries Based on Privileged Structures. 1. General Principles and Solid-Phase Synthesis of Benzopyrans , 2000 .

[49]  P. T. Kaye,et al.  A convenient general synthesis of 3-substituted 2H-chromene derivatives , 2002 .

[50]  S. Pastine,et al.  Ru(III)-catalyzed cyclization of arene-alkene substrates via intramolecular electrophilic hydroarylation. , 2003, Organic letters.