Catalyst-Free Synthesis of α-Functionalized 2H-Chromenes in Water: A Tandem Self-Promoted pseudo-Substitution and Decarboxylation Process.

A catalyst-free decarboxylative reaction between β-keto acids and 2H-chromene acetals in water was developed. This reaction featured a broad substrate scope and facile starting materials to afford α-functionalized 2H-chromenes in high yields. The synthetic value of this protocol was also demonstrated by the scale-up synthesis and versatile coversions of the title product into other usuful compounds. In addition, control experiments indicated that the water was significantly essential for the reactivity, and mechanistic studies further revealed that the reaction proceeded through a self-promoted tandem pseudo-substitution and decarboxylation process.

[1]  Xiaoqian Liu,et al.  Scandium(III)-Catalysed Decarboxylative Addition of β- Ketoacids to para -Quinone Methides: Evidence for 1,6-Addition and Base-Assisted Decarboxylation Tandem Process , 2019, Asian Journal of Organic Chemistry.

[2]  T. Ohshima,et al.  Catalytic Enantioselective Decarboxylative Mannich-Type Reaction of N-Unprotected Isatin-Derived Ketimines. , 2018, Organic letters.

[3]  Wenhao Hu,et al.  Formal Carbene Insertion into C−O or C−N Bond: An Efficient Strategy for the Synthesis of 2‐Substituted 2H‐Chromene Derivatives from Chromene Acetals or Hemiaminal Ethers , 2018 .

[4]  Lei Wang,et al.  A catalyst-controlled switchable reaction of β-keto acids to silyl glyoxylates. , 2018, Organic & biomolecular chemistry.

[5]  Jun‐An Ma,et al.  Organocatalytic Asymmetric Decarboxylative Mannich Reaction of β-Keto Acids with Cyclic α-Ketiminophosphonates: Access to Quaternary α-Aminophosphonates. , 2018, Organic letters.

[6]  Jeonghyo Lee,et al.  Copper(II)-Catalyzed Tandem Decarboxylative Michael/Aldol Reactions Leading to the Formation of Functionalized Cyclohexenones. , 2018, Organic letters.

[7]  M. Abbas,et al.  New and improved? A review of novel antibiotics for Gram-positive bacteria. , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[8]  M. Yus,et al.  Stereoselective Coupling of N-tert-Butanesulfinyl Aldimines and β-Keto Acids: Access to β-Amino Ketones. , 2017, The Journal of organic chemistry.

[9]  Fang-Cheng Huang,et al.  A cascade Claisen rearrangement/o-quinone methide formation/electrocyclization approach to 2H-chromenes. , 2017, Chemical communications.

[10]  S. Ghosh,et al.  Organocatalytic decarboxylative aldol reaction of β-ketoacids with α-ketophosphonates en route to the enantioselective synthesis of tertiary α-hydroxyphosphonates. , 2017, Organic & biomolecular chemistry.

[11]  J. Li,et al.  Practical Access to Difluoromethyl Ketones via Straightforward Decarboxylative Difluorination of β‐Ketoacids , 2017 .

[12]  Jun‐An Ma,et al.  Organocatalytic Asymmetric Decarboxylative Amination of β-Keto Acids: Access to Optically Active α-Amino Ketones and 1,2-Amino Alcohols. , 2017, Organic letters.

[13]  Q. Kang,et al.  Chiral-at-Metal Rh(III) Complex-Catalyzed Decarboxylative Michael Addition of β-Keto Acids with α,β-Unsaturated 2-Acyl Imidazoles or Pyridine. , 2017, Organic letters.

[14]  Jun‐An Ma,et al.  Base- and metal-free decarboxylative aldol reaction of β-ketoacids with glyoxylate hydrates and glyoxal monohydrates in water , 2016 .

[15]  Jun‐An Ma,et al.  C2-Symmetric Chiral Bisoxazolines as Hydrogen-Bond-Acceptor Catalysts in Enantioselective Aldol Reaction of β-Carbonyl Acids with Trifluoroacetaldehyde Hemiacetals. , 2016, Organic letters.

[16]  A. Sutherland,et al.  Synthesis of Allylic Amide Functionalized 2H-Chromenes and Coumarins Using a One-Pot Overman Rearrangement and Gold(I)-Catalyzed Hydroarylation. , 2016, The Journal of organic chemistry.

[17]  Yanfeng Dang,et al.  Organocatalytic Enantioselective Decarboxylative Michael Addition of β-Keto Acids to Dicyanoolefins and Disulfonylolefins , 2016 .

[18]  L. Sarandeses,et al.  Transition-Metal-Free Cross-Coupling of Indium Organometallics with Chromene and Isochroman Acetals Mediated by BF3·OEt2. , 2016, Organic letters.

[19]  Hao Li,et al.  Aniline-Promoted Cyclization-Replacement Cascade Reactions of 2-Hydroxycinnamaldehydes with Various Carbonic Nucleophiles through In Situ Formed N,O-Acetals. , 2016, Chemistry.

[20]  F. Cruz,et al.  Tandem Rh-catalysis: decarboxylative β-keto acid and alkyne cross-coupling. , 2016, Chemical communications.

[21]  S. Dasgupta,et al.  Enantioselective Copper(I)-Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters. , 2015, Angewandte Chemie.

[22]  H. Lou,et al.  Indium-catalyzed oxidative cross-dehydrogenative coupling of chromenes with 1,3-dicarbonyls and aryl rings. , 2015, Organic & biomolecular chemistry.

[23]  G. Yap,et al.  Enantioselective copper-catalyzed alkynylation of benzopyranyl oxocarbenium ions. , 2015, The Journal of organic chemistry.

[24]  B. Bruin,et al.  Catalytic Synthesis of 2H-Chromenes , 2015 .

[25]  S. Schaus,et al.  Enantioselective synthesis of 1,2-dihydronaphthalene-1-carbaldehydes by addition of boronates to isochromene acetals catalyzed by tartaric acid. , 2015, Journal of the American Chemical Society.

[26]  J. Mascareñas,et al.  Rhodium-catalyzed (5+1) annulations between 2-alkenylphenols and allenes: a practical entry to 2,2-disubstituted 2H-chromenes. , 2015, Angewandte Chemie.

[27]  H. Lou,et al.  Structurally diverse α-substituted benzopyran synthesis through a practical metal-free C(sp3)-H functionalization. , 2014, Organic letters.

[28]  S. Schaus,et al.  Brønsted Acid/Lewis Acid Cooperatively Catalyzed Addition of Diazoester to 2H-chromene Acetals. , 2014, European journal of organic chemistry.

[29]  R. Pratap,et al.  Natural and synthetic chromenes, fused chromenes, and versatility of dihydrobenzo[h]chromenes in organic synthesis. , 2014, Chemical reviews.

[30]  Tiantian Wang,et al.  Proline-Catalyzed Dehydrogenative Cross-Coupling Reaction between Chromene and Aldehydes , 2014 .

[31]  Shuichi Nakamura.  Catalytic enantioselective decarboxylative reactions using organocatalysts. , 2014, Organic & biomolecular chemistry.

[32]  X. Zhang,et al.  Metalloradical approach to 2H-chromenes. , 2014, Journal of the American Chemical Society.

[33]  Thomas Knauber,et al.  Dehydrierende Kreuzkupplungen von C sp 3‐H‐Bindungen: vielseitige Verfahren zur Bildung von C‐C‐Bindungen , 2014 .

[34]  Chao‐Jun Li,et al.  The cross-dehydrogenative coupling of C(sp3)-H bonds: a versatile strategy for C-C bond formations. , 2014, Angewandte Chemie.

[35]  C. Song,et al.  Organocatalytic enantioselective decarboxylative aldol reaction of malonic acid half thioesters with aldehydes. , 2013, Angewandte Chemie.

[36]  Zu-Li Wang,et al.  Recent Advances in Catalytic Asymmetric Decarboxylative Addition Reactions , 2013 .

[37]  M. Terada,et al.  Chiral anion catalysis in the enantioselective 1,4-reduction of the 1-benzopyrylium ion as a reactive intermediate. , 2013, Chemistry.

[38]  D. Clausen,et al.  Bimolecular Coupling Reactions through Oxidatively Generated Aromatic Cations: Scope and Stereocontrol. , 2013, Tetrahedron.

[39]  Chien‐Chi Hsiao,et al.  Shedding light on organocatalysis-light-assisted asymmetric ion-pair catalysis for the enantioselective hydrogenation of pyrylium ions. , 2013, Chemistry.

[40]  Yixin Lu,et al.  Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones , 2012, Beilstein journal of organic chemistry.

[41]  D. Clausen,et al.  Aromatic cations from oxidative carbon-hydrogen bond cleavage in bimolecular carbon-carbon bond forming reactions. , 2012, The Journal of organic chemistry.

[42]  A. Doyle,et al.  Nickel-catalyzed cross-coupling of chromene acetals and boronic acids. , 2012, Organic letters.

[43]  J. C. Lima,et al.  Chemistry and applications of flavylium compounds: a handful of colours. , 2012, Chemical Society reviews.

[44]  Tejas P Pathak,et al.  Applications of ortho-quinone methide intermediates in catalysis and asymmetric synthesis. , 2011, The Journal of organic chemistry.

[45]  Prantik Maity,et al.  Copper-catalyzed enantioselective additions to oxocarbenium ions: alkynylation of isochroman acetals. , 2011, Journal of the American Chemical Society.

[46]  S. Tian,et al.  Catalytic decarboxylative alkylation of β-keto acids with sulfonamides via the cleavage of carbon-nitrogen and carbon-carbon bonds. , 2011, Chemical communications.

[47]  M. Brimble,et al.  Efficient synthesis of the spiroacetal core of paecilospirone via oxidative radical cyclisation , 2011 .

[48]  I. Lykakis,et al.  Ph3PAuNTf2 as a Superior Catalyst for the Selective Synthesis of 2H‐Chromenes: Application to the Concise Synthesis of Benzopyran Natural Products , 2011 .

[49]  R. Mahrwald,et al.  Stereoselective direct amine-catalyzed decarboxylative aldol addition. , 2011, Organic letters.

[50]  S. Schaus,et al.  Enantioselective addition of boronates to chromene acetals catalyzed by a chiral Brønsted acid/Lewis acid system. , 2010, Angewandte Chemie.

[51]  Caroline J. Scheuermann.  Beyond traditional cross couplings: the scope of the cross dehydrogenative coupling reaction. , 2010, Chemistry, an Asian journal.

[52]  A. MacGowan,et al.  Future treatment options for Gram-positive infections--looking ahead. , 2009, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[53]  Chao‐Jun Li.  Cross-dehydrogenative coupling (CDC): exploring C-C bond formations beyond functional group transformations. , 2009, Accounts of chemical research.

[54]  Jian Zhou,et al.  Characterization of key intermediates in a complex organocatalytic cascade reaction using mass spectrometry. , 2009, Angewandte Chemie.

[55]  K. Ding,et al.  Insight into the mechanism of the asymmetric ring-opening aminolysis of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane catalyzed by titanium/BINOLate/water system: evidence for the Ti(BINOLate)2-bearing active catalyst entities and the role of water. , 2008, Journal of the American Chemical Society.

[56]  S. Reisman,et al.  Enantioselective thiourea-catalyzed additions to oxocarbenium ions. , 2008, Journal of the American Chemical Society.

[57]  Weiming Zhu,et al.  Citrinin dimers from the halotolerant fungus Penicillium citrinum B-57. , 2008, Journal of natural products.

[58]  J. Metzger,et al.  Untersuchung der direkten organokatalysierten α‐Halogenierung von Aldehyden mit Elektrospray‐Ionisierungs‐Massenspektrometrie , 2007 .

[59]  J. Metzger,et al.  Electrospray Ionization Mass Spectrometric Study on the Direct Organocatalytic α-Halogenation of Aldehydes† , 2007 .

[60]  Davidr . Evans,et al.  Scope and mechanism of enantioselective Michael additions of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by nickel(II)-diamine complexes. , 2007, Journal of the American Chemical Society.

[61]  J. Metzger,et al.  Investigation of chemical reactions in solution using API-MS , 2005 .

[62]  S. Ma,et al.  ESI-MS studies on the mechanism of Pd0-catalyzed three-component tandem double addition-cyclization reaction. , 2005, Journal of the American Chemical Society.

[63]  M. Lalk,et al.  Synthesis and structure-activity relationships of 2-vinylchroman-4-ones as potent antibiotic agents. , 2005, Bioorganic & medicinal chemistry.

[64]  P. Kittakoop,et al.  Atropisomeric myristinins: selective COX-2 inhibitors and antifungal agents from Myristica cinnamomea. , 2002, The Journal of organic chemistry.

[65]  F. Rutjes,et al.  Synthesis of 2-substituted chromenes via ring-closing metathesis and stable 1-benzopyrylium ions , 2000 .

[66]  P. Wipf,et al.  Enantioselective Synthesis and Photoracemization Studies of (+)-2-Cyclopropyl-7,8-dimethoxy-2H- chromene-5-carboxylic Acid Methyl Ester, an Advanced Intermediate of a Dihydrofolate Reductase Inhibitor. , 1999, The Journal of organic chemistry.

[67]  F. S. Pashkovsky,et al.  A new approach to the synthesis of 3,6- and 5,6-dialkyl derivatives of 4-hydroxy-2-pyrone. Synthesis of rac-germicidin , 1999 .

[68]  J. Simard,et al.  (S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen. , 1997, Journal of medicinal chemistry.

[69]  R. Lahti,et al.  (S)-(-)-4-[4-[2-(isochroman-1-yl)ethyl]-piperazin-1-yl] benzenesulfonamide, a selective dopamine D4 antagonist. , 1996, Journal of medicinal chemistry.

[70]  D. J. Bauer,et al.  4′,6-Dichloroflavan (BW683C), a new anti-rhinovirus compound , 1981, Nature.

[71]  R. L. Clarke,et al.  ALPHA-BENZYLTETRAHYDROFURFURYLAMINES--A NEW SERIES OF PSYCHOMOTOR STIMULANTS. I. , 1962, Journal of medicinal and pharmaceutical chemistry.