Joint Experimental, in Silico, and NMR Studies toward the Rational Design of Iminium-Based Organocatalyst Derived from Renewable Sources.

An efficient organocatalyst for iminium-ion based asymmetric Diels-Alder (DA) reactions has been rationally designed. The most influential structure-activity relationships were determined experimentally, while DFT calculations and NMR studies provided further mechanistic insight. This knowledge guided an in silico screening of 62 different catalysts using an ONIOM(B3LYP/6-31G*:AM1) transition-state modeling, which showed good correlation between theory and experiment. The top-scored compound was easily synthesized from levoglucosenone, a biomass-derived chiral enone, and evaluated in the DA reaction between (E)-cinnamaldehyde and cyclopentadiene. In line with the computational finding, excellent results (up to 97% ee) were obtained. In addition, the catalyst could be easily recovered and reused with no loss in its catalytic activity.

[1]  Robert J Deeth,et al.  Is enantioselectivity predictable in asymmetric catalysis? , 2009, Angewandte Chemie.

[2]  Ming Wah Wong,et al.  β-Amino acid catalyzed asymmetric Michael additions: design of organocatalysts with catalytic acid/base dyad inspired by serine proteases. , 2011, The Journal of organic chemistry.

[3]  B. Zwanenburg,et al.  Aziridin-2-yl methanols as organocatalysts in Diels–Alder reactions and Friedel–Crafts alkylations of N-methyl-pyrrole and N-methyl-indole , 2006 .

[4]  Natalie Fey,et al.  The computational road to better catalysts. , 2014, Chemistry, an Asian journal.

[5]  P. Dalko,et al.  In the golden age of organocatalysis. , 2004, Angewandte Chemie.

[6]  Yoshiharu Yamamoto,et al.  Origin of stereocontrol in guanidine-bisurea bifunctional organocatalyst that promotes α-hydroxylation of tetralone-derived β-ketoesters: asymmetric synthesis of β- and γ-substituted tetralone derivatives via organocatalytic oxidative kinetic resolution. , 2015, Journal of the American Chemical Society.

[7]  Y. Hayashi,et al.  Asymmetric Diels-Alder reactions of alpha,beta-unsaturated aldehydes catalyzed by a diarylprolinol silyl ether salt in the presence of water. , 2008, Angewandte Chemie.

[8]  Magnus Rueping,et al.  Complete field guide to asymmetric BINOL-phosphate derived Brønsted acid and metal catalysis: history and classification by mode of activation; Brønsted acidity, hydrogen bonding, ion pairing, and metal phosphates. , 2014, Chemical reviews.

[9]  Norman L. Allinger,et al.  Conformational analysis. 130. MM2. A hydrocarbon force field utilizing V1 and V2 torsional terms , 1977 .

[10]  R. Parr,et al.  Absolute hardness: companion parameter to absolute electronegativity , 1983 .

[11]  Y. Hayashi,et al.  Diarylprolinol silyl ether as catalyst of an exo-selective, enantioselective Diels-Alder reaction. , 2007, Organic letters.

[12]  P. Geerlings,et al.  Conceptual density functional theory. , 2003, Chemical reviews.

[13]  Ariel M. Sarotti,et al.  An efficient microwave-assisted green transformation of cellulose into levoglucosenone. Advantages of the use of an experimental design approach , 2007 .

[14]  L. Domingo,et al.  Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions , 2013 .

[15]  J. Tomasi,et al.  Quantum mechanical continuum solvation models. , 2005, Chemical reviews.

[16]  A. Gervasini,et al.  Chiral hybrid inorganic-organic materials: synthesis, characterization, and application in stereoselective organocatalytic cycloadditions. , 2013, The Journal of organic chemistry.

[17]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[18]  Tian Tian,et al.  Camphor sulfonyl hydrazines (CaSH) as organocatalysts in enantioselective Diels-Alder reactions. , 2008, Organic letters.

[19]  Matthew N. Grayson,et al.  Mechanistic insights into the BINOL-derived phosphoric acid-catalyzed asymmetric allylboration of aldehydes. , 2012, Journal of the American Chemical Society.

[20]  D. MacMillan,et al.  The advent and development of organocatalysis , 2008, Nature.

[21]  Zheng Wang,et al.  Experimental and theoretical studies on the hydrogen-bond-promoted enantioselective hetero-Diels-Alder reaction of Danishefsky's diene with benzaldehyde. , 2006, The Journal of organic chemistry.

[22]  J. Platts,et al.  Solution phase, solid state, and theoretical investigations on the MacMillan imidazolidinone. , 2009, Organic letters.

[23]  F. Giacalone,et al.  Supported proline and proline-derivatives as recyclable organocatalysts. , 2008, Chemical Society reviews.

[24]  D. MacMillan,et al.  New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Diels−Alder Reaction , 2000 .

[25]  S. Mukherjee,et al.  Asymmetric enamine catalysis. , 2007, Chemical reviews.

[26]  K. Houk,et al.  Computational predictions of stereochemistry in asymmetric thiazolium- and triazolium-catalyzed benzoin condensations. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Ariel M. Sarotti.  Unraveling polar Diels-Alder reactions with conceptual DFT analysis and the distortion/interaction model. , 2014, Organic & biomolecular chemistry.

[28]  Paul Ha-Yeon Cheong,et al.  Computational prediction of small-molecule catalysts , 2008, Nature.

[29]  Paul Ha-Yeon Cheong,et al.  Quantum mechanical investigations of organocatalysis: mechanisms, reactivities, and selectivities. , 2011, Chemical reviews.

[30]  L. Curtiss,et al.  Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint , 1988 .

[31]  R. B. Sunoj,et al.  Unraveling high precision stereocontrol in a triple cascade organocatalytic reaction. , 2008, Organic & biomolecular chemistry.

[32]  Toshio Suzuki,et al.  Immobilization of MacMillan Imidazolidinone as Mac-SILC and its Catalytic Performance on Sustainable Enantioselective Diels-Alder Cycloaddition , 2010 .

[33]  Luis R. Domingo,et al.  Quantitative characterization of the global electrophilicity power of common diene/dienophile pairs in Diels–Alder reactions , 2002 .

[34]  Ariel M. Sarotti,et al.  Cellulose recycling as a source of raw chirality , 2013 .

[35]  Y. Meng,et al.  The origin of enantioselectivity in the L-threonine-derived phosphine-sulfonamide catalyzed aza-Morita-Baylis-Hillman reaction: effects of the intramolecular hydrogen bonding. , 2013, Organic & biomolecular chemistry.

[36]  A. Becke.  A New Mixing of Hartree-Fock and Local Density-Functional Theories , 1993 .

[37]  Christopher R. Corbeil,et al.  Theory and application of medium to high throughput prediction method techniques for asymmetric catalyst design , 2010 .

[38]  A. Corma,et al.  Silica-Bound Homogenous Catalysts as Recoverable and Reusable Catalysts in Organic Synthesis , 2006 .

[39]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[40]  F Matthias Bickelhaupt,et al.  The activation strain model of chemical reactivity. , 2010, Organic & biomolecular chemistry.

[41]  K. Jørgensen,et al.  A general organocatalyst for direct alpha-functionalization of aldehydes: stereoselective C-C, C-N, C-F, C-Br, and C-S bond-forming reactions. Scope and mechanistic insights. , 2005, Journal of the American Chemical Society.

[42]  A. Puglisi,et al.  Polymer-supported organic catalysts. , 2003, Chemical reviews.

[43]  Y. Takemoto,et al.  Enantioselective Michael reaction of malonates to nitroolefins catalyzed by bifunctional organocatalysts. , 2003, Journal of the American Chemical Society.

[44]  T. Kano,et al.  exo-Selective asymmetric Diels-Alder reaction catalyzed by diamine salts as organocatalysts. , 2006, Chemistry, an Asian journal.

[45]  M. Lemay,et al.  Mechanistic studies of hydrazide-catalyzed enantioselective Diels-Alder reactions. , 2006, The Journal of organic chemistry.

[46]  F. Weinhold,et al.  Natural population analysis , 1985 .

[47]  Ariel M. Sarotti,et al.  1,3-Dipolar cycloaddition reactions of azomethine ylides with a cellulose-derived chiral enone. A novel route for organocatalysts development. , 2012, Organic letters.

[48]  Ariel M. Sarotti,et al.  Recent Applications of Levoglucosenone as Chiral Synthon , 2012 .

[49]  K N Houk,et al.  Direct asymmetric anti-Mannich-type reactions catalyzed by a designed amino acid. , 2006, Journal of the American Chemical Society.

[50]  B. Martín‐Matute,et al.  CuI—Fesulphos Complexes: Efficient Chiral Catalysts for Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides. , 2007 .

[51]  K. Houk,et al.  How Cinchona Alkaloid-Derived Primary Amines Control Asymmetric Electrophilic Fluorination of Cyclic Ketones , 2014, Journal of the American Chemical Society.

[52]  Matthew N. Grayson,et al.  Understanding the mechanism of the asymmetric propargylation of aldehydes promoted by 1,1'-bi-2-naphthol-derived catalysts. , 2013, Journal of the American Chemical Society.

[53]  K N Houk,et al.  Origins of stereoselectivity in intramolecular aldol reactions catalyzed by cinchona amines. , 2015, Journal of the American Chemical Society.

[54]  R. B. Sunoj,et al.  Bicyclic proline analogues as organocatalysts for stereoselective aldol reactions: an in silico DFT study. , 2007, Organic & biomolecular chemistry.

[55]  V. Ananikov,et al.  Can Steric Effects Induce the Mechanism Switch in the Rhodium-Catalyzed Imine Boration Reaction? A Density Functional and ONIOM Study , 2005 .

[56]  K. Morokuma,et al.  A NEW ONIOM IMPLEMENTATION IN GAUSSIAN98. PART I. THE CALCULATION OF ENERGIES, GRADIENTS, VIBRATIONAL FREQUENCIES AND ELECTRIC FIELD DERIVATIVES , 1999 .

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

[58]  S. Connon,et al.  Computational study-led organocatalyst design: a novel, highly active urea-based catalyst for addition reactions to epoxides. , 2008, Journal of Organic Chemistry.

[59]  F. Dean Toste,et al.  A data-intensive approach to mechanistic elucidation applied to chiral anion catalysis , 2015, Science.

[60]  Matthew N. Grayson,et al.  Mechanistic insights into a BINOL-derived phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction. , 2015, Journal of Organic Chemistry.

[61]  A. Csámpai,et al.  Highly enantioselective conjugate addition of nitromethane to chalcones using bifunctional cinchona organocatalysts. , 2005, Organic letters.