Asymmetric Synthesis of Chiral 1,4-Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines.

A highly enantioselective synthesis of 1,4-enynes is described that proceeds through an organocatalytic reaction between propargyl alcohols and trialkenylboroxines. Our strategy relies on acid-mediated generation of the carbocationic intermediate from propargyl alcohols followed by enantioselective alkenylation with trialkenylboroxines. A range of chiral 1,4-enynes were obtained in moderate to good yields with high levels of enantioselectivity. Use of a highly acidic chiral N-triflyl phosphoramide catalyst, which has two distant Lewis basic oxygen atoms, was found to be crucial for both high reactivity and selectivity in the present reaction.

[1]  Guang-Jian Mei,et al.  Catalytic Asymmetric [4+2] Cyclization of para ‐Quinone Methide Derivatives with 3‐Alkyl‐2‐vinylindoles , 2018, Advanced Synthesis & Catalysis.

[2]  G. Hammond,et al.  Mild Base Promoted Nucleophilic Substitution of Unactivated sp 3 ‐Carbon Electrophiles with Alkenylboronic Acids , 2018, Advanced Synthesis & Catalysis.

[3]  J. Antilla,et al.  Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Hetero-triarylmethanes from Racemic Indolyl Alcohols , 2018, Angewandte Chemie.

[4]  J. Antilla,et al.  Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Hetero-triarylmethanes from Racemic Indolyl Alcohols. , 2018, Angewandte Chemie.

[5]  Guoxian Gu,et al.  Stereospecific Nucleophilic Substitution with Arylboronic Acids as Nucleophiles in the Presence of a CONH Group. , 2018, Angewandte Chemie.

[6]  J. Kikuchi,et al.  Chiral Brønsted acid-catalyzed intramolecular SN2′ reaction for enantioselective construction of a quaternary stereogenic center , 2018, Chemical science.

[7]  B. Breit,et al.  Rhodium-Catalyzed Enantioselective Decarboxylative Alkynylation of Allenes with Arylpropiolic Acids. , 2018, Organic letters.

[8]  Srinivasarao Yaragorla,et al.  Regioselective Synthesis of 1,4 & 1,5‐Enynes through a Ca(II)‐ Catalyzed Cross‐Dehydrative‐Coupling of Styrenes and Propargyl alcohols , 2018 .

[9]  S. Stavber,et al.  Molecular iodine as a mild catalyst for cross-coupling of alkenes and alcohols , 2018 .

[10]  Xin Li,et al.  Asymmetric Synthesis of Dihydrocoumarins through Chiral Phosphoric Acid-Catalyzed Cycloannulation of para-Quinone Methides and Azlactones. , 2018, The Journal of organic chemistry.

[11]  I. Ryu,et al.  Transition‐Metal‐Catalyst‐Free Cross‐Coupling Reaction of Secondary Propargylic Acetates with Alkenyl‐ and Arylboronic Acids , 2017 .

[12]  M. Tius,et al.  Catalytic Enantioselective Nazarov Cyclization , 2017 .

[13]  James R. Green,et al.  Nicholas Reactions of Alkynyl- and Alkenyltrifluoroborates , 2017, Synlett.

[14]  Qi Sun,et al.  Transition-Metal-Free Stereospecific Cross-Coupling with Alkenylboronic Acids as Nucleophiles. , 2016, Journal of the American Chemical Society.

[15]  X. Bi,et al.  Chemo- and regioselective reductive deoxygenation of 1-en-4-yn-ols into 1,4-enynes through FeF3 and TfOH co-catalysis. , 2016, Chemical communications.

[16]  Y. Bolshan,et al.  Brønsted Acid-Catalyzed Reactions of Trifluoroborate Salts with Benzhydryl Alcohols. , 2015, The Journal of organic chemistry.

[17]  F. Kwong,et al.  Pd‐Catalyzed Allylic Alkynylation of Allylic Acetates with Terminal Alkynes , 2015 .

[18]  V. Gandon,et al.  Ca(II) -catalyzed alkenylation of alcohols with vinylboronic acids. , 2015, Chemistry.

[19]  H. Ohmiya,et al.  Copper-catalyzed enantioselective allylic alkylation of terminal alkyne pronucleophiles. , 2014, Journal of the American Chemical Society.

[20]  Zhen Li,et al.  Metal‐Free and Recyclable Route to Synthesize Polysubstituted Olefins via C ? C Bond Construction from Direct Dehydrative Coupling of Alcohols or Alkenes with Alcohols Catalyzed by Sulfonic Acid‐Functionalized Ionic Liquids , 2014 .

[21]  Cong Liu,et al.  Catalytic CN Bond Alkynylation of N‐Benzylic Sulfonamides with Terminal Alkynes , 2014 .

[22]  Pu-Sheng Wang,et al.  Relay Catalytic Cascade Hydrosiloxylation and Asymmetric Hetero-Diels–Alder Reaction , 2014 .

[23]  S. Tian,et al.  Palladium-catalyzed stereospecific cross-coupling of enantioenriched allylic alcohols with boronic acids. , 2014, Chemical communications.

[24]  E. Carreira,et al.  Iridium-catalyzed enantioselective allylic alkynylation. , 2013, Angewandte Chemie.

[25]  H. Ohmiya,et al.  Copper-catalyzed γ-selective and stereospecific direct allylic alkylation of terminal alkynes: synthesis of skipped enynes. , 2013, Angewandte Chemie.

[26]  Hengshan Wang,et al.  Atom-economical chemoselective synthesis of 1,4-enynes from terminal alkenes and propargylic alcohols catalyzed by Cu(OTf)2. , 2013, The Journal of organic chemistry.

[27]  E. Carreira,et al.  Iridium-catalyzed enantioselective allylic vinylation. , 2013, Journal of the American Chemical Society.

[28]  S. Schaus,et al.  Enantioselective addition of boronates to o-quinone methides catalyzed by chiral biphenols. , 2012, Journal of the American Chemical Society.

[29]  A. Baeza,et al.  Fluorinated alcohols as promoters for the metal-free direct substitution reaction of allylic alcohols with nitrogenated, silylated, and carbon nucleophiles. , 2012, The Journal of organic chemistry.

[30]  Yoichi M. A. Yamada,et al.  Self-assembled poly(imidazole-palladium): highly active, reusable catalyst at parts per million to parts per billion levels. , 2012, Journal of the American Chemical Society.

[31]  A. Alexakis,et al.  Enyne chlorides: substrates for copper-catalyzed asymmetric allylic alkylation. , 2012, Angewandte Chemie.

[32]  Lei Wang,et al.  Iron-catalyzed ene-type propargylation of diarylethylenes with propargyl alcohols. , 2012, Organic & biomolecular chemistry.

[33]  D. Curran,et al.  Synthesis and spectroscopic analysis of a stereoisomer library of the phytophthora mating hormone α1 and derived bis-Mosher esters. , 2011, Journal of the American Chemical Society.

[34]  H. Yue,et al.  sp3‐sp2 C‐C Bond Formation via Brønsted Acid Trifluoromethanesulfonic Acid‐Catalyzed Direct Coupling Reaction of Alcohols and Alkenes , 2011 .

[35]  M. Terada,et al.  Platinum-catalyzed cycloisomerization of 1,4-enynes via 1,2-alkenyl rearrangement. , 2011, Organic letters.

[36]  M. Niggemann,et al.  Calcium-Catalyzed Direct Coupling of Alcohols with Organosilanes , 2011 .

[37]  Lei Wang,et al.  Cu(OTf)2-catalyzed arylmethylation of terminal alkynes with benzylic alcohols under ligand-, base-, and additive-free reaction conditions , 2011 .

[38]  A. Hoveyda,et al.  Enantioselective synthesis of alkyne-substituted quaternary carbon stereogenic centers through NHC-Cu-catalyzed allylic substitution reactions with (i-Bu)2(alkynyl)aluminum reagents. , 2011, Journal of the American Chemical Society.

[39]  Yuichi Kobayashi,et al.  SN2-Selective allylic substitution of chiral γ-aryl substituted allylic picolinates with alkynylcopper reagents , 2010 .

[40]  A. Fürstner,et al.  Protecting-group-free and catalysis-based total synthesis of the ecklonialactones. , 2010, Journal of the American Chemical Society.

[41]  Rai‐Shung Liu,et al.  Platinum-catalyzed cycloisomerization of 1,4-enynes via activation of a sp3-hybridized C-H bond. , 2010, Chemical communications.

[42]  Chao‐Jun Li,et al.  Copper‐Catalyzed Cross‐Dehydrogenative Coupling (CDC) of Alkynes and Benzylic CH Bonds , 2010 .

[43]  P. Iovine,et al.  Boroxine chemistry and applications: A perspective. , 2010, Dalton transactions.

[44]  G. Kabalka,et al.  Titanium(IV) halide mediated coupling of alkoxides and alkynes: an efficient and stereoselective route to trisubstituted (E)-alkenyl halides. , 2009, Organic letters.

[45]  U. Jana,et al.  New and Efficient Iron Halide Mediated Synthesis of Alkenyl Halides through Coupling of Alkynes and Alcohols , 2009 .

[46]  M. Yasuda,et al.  Direct coupling of alcohols with alkenylsilanes catalyzed by indium trichloride or bismuth tribromide. , 2008, Chemical communications.

[47]  D. Nakashima,et al.  Enantioselective 1,3-dipolar cycloaddition of nitrones with ethyl vinyl ether: the difference between Brønsted and Lewis acid catalysis. , 2008, Angewandte Chemie.

[48]  F. Gagosz,et al.  Gold(I) catalyzed isomerization of 5-en-2-yn-1-yl acetates: an efficient access to acetoxy bicyclo[3.1.0]hexenes and 2-cycloalken-1-ones. , 2006, Journal of the American Chemical Society.

[49]  D. Nakashima,et al.  Design of chiral N-triflyl phosphoramide as a strong chiral Brønsted acid and its application to asymmetric Diels-Alder reaction. , 2006, Journal of the American Chemical Society.

[50]  G. Kabalka,et al.  Substitution of hydroxyl groups with alkynyl moieties using alkynylboron dihalides: an efficient approach to secondary alkylacetylene derivatives. , 2006, Organic letters.

[51]  R. Sarpong,et al.  Pt-catalyzed pentannulations from in situ generated metallo-carbenoids utilizing propargylic esters. , 2005, Journal of the American Chemical Society.

[52]  Xiaodong Shi,et al.  Synthesis of 2-cyclopentenones by gold(I)-catalyzed Rautenstrauch rearrangement. , 2005, Journal of the American Chemical Society.

[53]  G. Kabalka,et al.  A new halopropargylation of alkynes promoted by boron trihalides. highly stereo- and regioselective syntheses of substituted (Z)-1-halo-1,4-enyne derivatives. , 2004, Organic letters.

[54]  R. J. Herr,et al.  Generation of 3-pyridyl biaryl systems via palladium-catalyzed Suzuki cross-couplings of aryl halides with 3-pyridylboroxin. , 2004, The Journal of organic chemistry.

[55]  T. Jamison,et al.  Synthesis of skipped enynes via phosphine-promoted couplings of propargylcopper reagents , 2003 .

[56]  T. Jamison,et al.  SiMe3-based homologation-epoxidation-cyclization strategy for ladder THP synthesis. , 2003, Organic letters.

[57]  Yuichi Kobayashi,et al.  Zinc Borates: Functionalized Hard Nucleophiles for Coupling Reactions with Secondary Allylic Acetates , 2000 .

[58]  M. Hirama,et al.  EFFICIENT ROUTE TO THE NINE-MEMBERED CYCLIC DIYNE SYSTEM : TUNING OF THE EXTREMELY FACILE COPE REARRANGEMENT OF 1,5-DIYNE , 1994 .

[59]  M. Isobe,et al.  Letter: A general approach to prostaglandins via methylenecyclopentanones. Total synthesis of (+/- prostaglandin F2 alpha. , 1975, Journal of the American Chemical Society.

[60]  M. Aldridge,et al.  Sex Pheromones of the Southern Armyworm Moth: Isolation, Identification, and Synthesis , 1970, Science.