Computational organic chemistry

COMPUTATIONAL ORGANIC CHEMISTRY COMPUTATIONAL ORGANIC CHEMISTRY Second Edition Steven M Bachrach Department of Chemistry Trinity University San Antonio, TX Copyright © 2014 by John Wiley & Sons, Inc All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River 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Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002 Wiley also publishes its books in a variety of electronic formats Some content that appears in print may not be available in electronic formats For more information about Wiley products, visit our web site at www.wiley.com Library of Congress Cataloging-in-Publication Data: Bachrach, Steven M., 1959Computational organic chemistry / by Steven M Bachrach, Department of Chemistry, Trinity University, San Antonio, TX – Second edition pages cm Includes bibliographical references and index ISBN 978-1-118-29192-4 (cloth) Chemistry, Organic–Mathematics Chemistry, Organic–Mathematical models I Title QD255.5.M35B33 2014 547.001’51–dc23 2013029960 Printed in the United States of America 10 To Carmen and Dustin CONTENTS Preface xv Acknowledgments xxi Quantum Mechanics for Organic Chemistry Approximations to the Schrödinger Equation—The Hartree–Fock Method 1.1.1 Nonrelativistic Mechanics 1.1.2 The Born–Oppenheimer Approximation 1.1.3 The One-Electron Wavefunction and the Hartree–Fock Method 1.1.4 Linear Combination of Atomic Orbitals (LCAO) Approximation 1.1.5 Hartree–Fock–Roothaan Procedure 1.1.6 Restricted Versus Unrestricted Wavefunctions 1.1.7 The Variational Principle 1.1.8 Basis Sets 1.1.8.1 Basis Set Superposition Error 1.2 Electron Correlation—Post-Hartree–Fock Methods 1.2.1 Configuration Interaction (CI) 1.2.2 Size Consistency 1.2.3 Perturbation Theory 1.2.4 Coupled-Cluster Theory 1.2.5 Multiconfiguration SCF (MCSCF) Theory and Complete Active Space SCF (CASSCF) Theory 1.2.6 Composite Energy Methods 1.3 Density Functional Theory (DFT) 1.3.1 The Exchange-Correlation Functionals: Climbing Jacob’s Ladder 1.3.1.1 Double Hybrid Functionals 1.3.2 Dispersion-Corrected DFT 1.3.3 Functional Selection 1.1 2 3 7 12 13 14 16 16 17 18 20 22 24 26 26 28 vii viii 1.4 1.5 1.6 1.7 1.8 CONTENTS Computational Approaches to Solvation 1.4.1 Microsolvation 1.4.2 Implicit Solvent Models 1.4.3 Hybrid Solvation Models Hybrid QM/MM Methods 1.5.1 Molecular Mechanics 1.5.2 QM/MM Theory 1.5.3 ONIOM Potential Energy Surfaces 1.6.1 Geometry Optimization Population Analysis 1.7.1 Orbital-Based Population Methods 1.7.2 Topological Electron Density Analysis Interview: Stefan Grimme References Computed Spectral Properties and Structure Identification 2.1 2.2 2.3 Computed Bond Lengths and Angles IR Spectroscopy Nuclear Magnetic Resonance 2.3.1 General Considerations 2.3.2 Scaling Chemical Shift Values 2.3.3 Customized Density Functionals and Basis Sets 2.3.4 Methods for Structure Prediction 2.3.5 Statistical Approaches to Computed Chemical Shifts 2.3.6 Computed Coupling Constants 2.3.7 Case Studies 2.3.7.1 Hexacyclinol 2.3.7.2 Maitotoxin 2.3.7.3 Vannusal B 2.3.7.4 Conicasterol F 2.3.7.5 1-Adamantyl Cation 2.4 Optical Rotation, Optical Rotatory Dispersion, Electronic Circular Dichroism, and Vibrational Circular Dichroism 2.4.1 Case Studies 2.4.1.1 Solvent Effect 2.4.1.2 Chiral Solvent Imprinting 28 28 29 34 35 36 38 39 40 42 45 46 47 48 51 61 61 62 66 68 69 71 73 74 76 77 77 79 80 81 81 82 85 85 86 CONTENTS 2.5 2.4.1.3 Plumericin and Prismatomerin 2.4.1.4 2,3-Hexadiene 2.4.1.5 Multilayered Paracyclophane 2.4.1.6 Optical Activity of an Octaphyrin Interview: Jonathan Goodman References Fundamentals of Organic Chemistry 3.1 3.2 3.3 3.4 3.5 3.6 Bond Dissociation Enthalpy 3.1.1 Case Study of BDE: Trends in the R–X BDE Acidity 3.2.1 Case Studies of Acidity 3.2.1.1 Carbon Acidity of Strained Hydrocarbons 3.2.1.2 Origin of the Acidity of Carboxylic Acids 3.2.1.3 Acidity of the Amino Acids Isomerism and Problems With DFT 3.3.1 Conformational Isomerism 3.3.2 Conformations of Amino Acids 3.3.3 Alkane Isomerism and DFT Errors 3.3.3.1 Chemical Consequences of Dispersion Ring Strain Energy 3.4.1 RSE of Cyclopropane (28) and Cylcobutane (29) Aromaticity 3.5.1 Aromatic Stabilization Energy (ASE) 3.5.2 Nucleus-Independent Chemical Shift (NICS) 3.5.3 Case Studies of Aromatic Compounds 3.5.3.1 [n]Annulenes 3.5.3.2 The Mills–Nixon Effect 3.5.3.3 Aromaticity Versus Strain 3.5.4 π–π Stacking Interview: Professor Paul Von RaguéSchleyer References Pericyclic Reactions 4.1 The Diels–Alder Reaction 4.1.1 The Concerted Reaction of 1,3-Butadiene with Ethylene 4.1.2 The Nonconcerted Reaction of 1,3-Butadiene with Ethylene ix 87 88 89 90 90 93 99 99 102 104 107 107 113 116 119 119 121 123 131 132 138 144 145 150 155 155 166 171 173 177 180 197 198 199 207 x CONTENTS 4.1.3 4.2 4.3 4.4 4.5 4.6 4.7 Kinetic Isotope Effects and the Nature of the Diels–Alder Transition State 4.1.4 Transition State Distortion Energy The Cope Rearrangement 4.2.1 Theoretical Considerations 4.2.2 Computational Results 4.2.3 Chameleons and Centaurs The Bergman Cyclization 4.3.1 Theoretical Considerations 4.3.2 Activation and Reaction Energies of the Parent Bergman Cyclization 4.3.3 The cd Criteria and Cyclic Enediynes 4.3.4 Myers–Saito and Schmittel Cyclization Bispericyclic Reactions Pseudopericyclic Reactions Torquoselectivity Interview: Professor Weston Thatcher Borden References Diradicals and Carbenes 5.1 5.2 5.3 5.4 5.5 Methylene 5.1.1 Theoretical Considerations of Methylene 5.1.2 The H–C–H Angle in Triplet Methylene 5.1.3 The Methylene and Dichloromethylene Singlet–Triplet Energy Gap Phenylnitrene and Phenylcarbene 5.2.1 The Low Lying States of Phenylnitrene and Phenylcarbene 5.2.2 Ring Expansion of Phenylnitrene and Phenylcarbene 5.2.3 Substituent Effects on the Rearrangement of Phenylnitrene Tetramethyleneethane 5.3.1 Theoretical Considerations of Tetramethyleneethane 5.3.2 Is TME a Ground-State Singlet or Triplet? Oxyallyl Diradical Benzynes 5.5.1 Theoretical Considerations of Benzyne 5.5.2 Relative Energies of the Benzynes 5.5.3 Structure of m-Benzyne 209 214 215 217 219 227 233 237 239 244 249 256 260 267 278 282 297 298 298 299 300 304 305 312 317 324 326 326 330 333 333 336 341 CONTENTS 5.5.4 The Singlet–Triplet Gap and Reactivity of the Benzynes Tunneling of Carbenes 5.6.1 Tunneling control 5.7 Interview: Professor Henry “Fritz” Schaefer 5.8 Interview: Professor Peter R Schreiner References 5.6 Organic Reactions of Anions 6.1 Substitution Reactions 6.1.1 The Gas Phase SN Reaction 6.1.2 Effects of Solvent on SN Reactions 6.2 Asymmetric Induction Via 1,2-Addition to Carbonyl Compounds 6.3 Asymmetric Organocatalysis of Aldol Reactions 6.3.1 Mechanism of Amine-Catalyzed Intermolecular Aldol Reactions 6.3.2 Mechanism of Proline-Catalyzed Intramolecular Aldol Reactions 6.3.3 Comparison with the Mannich Reaction 6.3.4 Catalysis of the Aldol Reaction in Water 6.3.5 Another Organocatalysis Example—The Claisen Rearrangement 6.4 Interview: Professor Kendall N Houk References Solution-Phase Organic Chemistry 7.1 7.2 Aqueous Diels–Alder Reactions Glucose 7.2.1 Models Compounds: Ethylene Glycol and Glycerol 7.2.1.1 Ethylene Glycol 7.2.1.2 Glycerol 7.2.2 Solvation Studies of Glucose 7.3 Nucleic Acids 7.3.1 Nucleic Acid Bases 7.3.1.1 Cytosine 7.3.1.2 Guanine 7.3.1.3 Adenine 7.3.1.4 Uracil and Thymine 7.3.2 Base Pairs xi 345 349 353 355 357 360 373 373 374 385 391 404 409 417 421 426 429 432 435 445 446 452 453 453 458 460 468 469 469 473 475 477 479 INDEX R-X bonds, 102 treatment of electron correlation, 101 Bond length Computed, 61–62 R–X, 102, 103 Bond path, 139 Borden, Weston, 142, 170, 228, 229, 230, 311, 315, 318, 320, 324, 325, 328, 330, 331, 332, 337, 528, 529, 535, 536 Interview, 278 Born–Oppenheimer Approximation, 3, 512 Brauman, John, 374, 383 Breslow, Ronald, 446, 447 Brillouin’s theorem, 15, 17 Brueckner orbitals, 18, 242 Bruice, Thomas, 579–584 BSSE See Basis set superposition error Butane Confomational energies, 121 Caldera, 518–520, 523–526, 535, 536, 558 Calichaemicin, 233, 234, 348 mechanism of action, 235 Canonical orbitals, Carboxylic acids Acidity of, 113–117 Carpenter, 254 Carpenter, Barry, 254, 514–518, 528, 529, 531, 532, 534, 535, 536, 555, 556 CASPT2, 20 CASSCF See Complete active space Castro, 158, 163, 164 Catechol-O-methyltransferase (COMT), 582, 583, 584, 585 X-ray crystal structure of, 583 CC See Coupled cluster theory Centauric model, 227 (+)-chaloxone OR, 85 Chameleonic model, 227 Chorismate mutase (CM), 578, 579, 580, 581, 582, 583 from Bacillus subtilis, 580 from Escherichia coli, 580 Chorismate, 578, 579, 580, 581, 583 CI See Configuration interaction Cieplak, Andrzej, 395, 396, 399, 400 cis-2-butene Reaction with dichloroketene, 547 Citrase synthase, 577 Claisen rearrangement, 578, 579 Organocatalysis of, 429–431 CM See Chorismate mutase Complete active space (CASSCF), 20 601 Composite methods, 20–22 COMT See Catechol-O-methyltransferase Configuration Interaction (CI), 14–16 Conicasterol F NMR, 81 Continuous diradical transition state, 518 Conventional ring strain energy (CRSE), 133, 135, 136, 137, 143 Cope rearrangement, 209, 215–233, 257–260, 280, 548, 549 1,2,6-heptatriene to 3-methylhexa-1,5-diene, 534–536 1,5-hexadiene, energies, 220 1,5-hexadiene, geometry, 224 active space MOs, 218 substituent effect, 225, 227 Corannulene Aromatic stabilization energy of, 149 Counterpoise, 12, 13 Coupled-cluster (CC) theory, 17, 18 CCSD, 18 CCSD(T), 18 multireference coupled cluster theory (MRCC), 20 Coupling constants, 76–77, 79, 81 Cram, Donald, 391 Cramer, Christopher 2, 23, 25, 32, 33, 35, 242, 244, 254, 383, 446, 455, 457, 461, 464, 466, 468 Interview, 493 Cremer, Dieter, 139, 140, 142, 143, 202, 241, 243, 244, 246, 336, 339, 341, 344, 347, 348 Critical assessment of methods of protein structure prediction (CASP), 574 critical points, 3, 41, 42, 44, 47, 48 CRSE See Conventional ring strain energy (CRSE) Cubane DPE, 108 Cyclobutadiene, 18, 155, 170 MO diagram of, 19 NICS, 152, 153 Cyclobutane Baeyer strain energies, 139 bond energies, 141, 142 NICS, 143 RSE, 132, 134, 138–140, 143 Cyclobutene RSE, 134 Cyclohexane, 141–143 DPE, 107 NICS, 152, 153 Cyclohexanone 1,2-Addition with lithium hydride, 398 602 INDEX Cyclohexanone (Continued) Aldol reaction, with, 413 Cyclohexene Rearrangement to vinylcyclobutane, 523 trans-Cyclohexene, 202 Cyclooctatetraene NICS, 154 Cyclopentadiene Cycloaddition with ketene, 543–547 DPE, 107 NICS, 153 NMR, 151 RSE, 148 cyclopentadienyl anion NICS, 153 cyclopentane, 143 Cyclopentene Rearrangement to vinylcyclopropane, 520–523 Cyclopropane Baeyer strain energies, 139 Bond energies, 141, 142 DPE, 107, 108 Ring current, 144 Ring strain energy (RSE), 132, 133, 138, 139, 140, 143 Stereomutation, 526–530 Cyclopropylhydroxycarbene Tunneling, 351, 354 Cyranski, Michal, 148, 172 Cysteine, 117, 118, 119, 123 Conformational energy, 124 conjugate base geometry, 118 Cytosine, 469–473, 476, 479, 483–489 gas-phase tautomer geometry, 470 Microsolvated tautomer geometry, 471 Tautomer energy, 472 Davidson correction, 16, 329, 334 Davidson-Borden rules, 324–325 Davidson, Ernest, 324, 325, 521 De novo enzyme design, 586–592 Bimolecular Diels–Alder reaction, 586 Ester hydrolases, 590 Failure of the designed proteins, 592 Intermolecular Diels–Alder reaction, 586 Kemp elimination, 590, 591 Retroaldol, 588, 589 Density functional theory (DFT), 22–28, 101, 102, 106, 119–132 Customized for NMR, 71 Errors, 123–131 Exchange-correlation functional, 23–26 Density matrix, 5, 6, 47 Deoxyribonucleic acids (DNA), 468, 469, 479, 486, 488 Deprotonation enthalpy (DPE), 100, 101, 104–113, 115–119 Acetic acid, 105 Acetone, 105 2-Butyne, 111 Amino acids, 117 Cyclopentadiene, 107 Ethane, 108 Ethene, 106 Ethyne, 107 Methanol 113 Pent-1,4-diyne, 111 Propane, 106 Propene, 105 Propyne, 111 Toluene, 107 Tyrosine, 118 Dewar resonance energy (DRE), 147 Dewar, Michael, 143, 147, 209, 219, 279 Diamagnetic susceptibility exaltation, 150, 166 Diatropic ring currents, 144, 151, 154 Dichloroketene Cycloaddition with cyclopentadiene, 544 reaction with cis-2-butene, 547 Dichloromethylene singlet-triplet energy gap, 303–304 Diels–Alder Reaction, 198–215, 232, 256, 258, 260, 261, 264, 269 1,3-butadiene with ethylene, concerted, 199–206 1,3-butadiene with ethylene, nonconcerted, 207–209 Aqueous, 446–452 Butadiene with acrolein, aqueous, 452 Butenone with cyclopentadiene, aqueous, 448–449 Cycloenones with cyclopentadiene, 215 Cyclopentadiene dimerization, in solution, 446 Fullerene with 1,3-butadiene, 206 Kinetic isotope effect, 209–214 Magnetic properties of TS, 205 Reaction dynamics, 547–550 Diffuse functions, 11, 21, 106, 151 Dirac, Paul, 2, 24 Direct dynamics, 510–512, 514, 515, 525, 534, 535, 537, 541, 545, 548, 552, 556 Dispersion, 120, 129 Chemical consequences, 131, 132 Dispersion correction, 27, 119, 130, 174 Distortion energy, 214, 215 DNA methyltransferases, 582 DNA See Deoxyribonucleic acids INDEX Doering, William, 207, 216, 217, 227, 228, 231, 279, 280 Dopamine, 582 Double hybrid functional, 26, 27, 49 dispersion corrected, spin-component-scaled (DSD-DFT), 28 Doubleday, 525, 527–529 DP4, 75, 91 Dunitz–Shomaker strain, 140, 142 Dynamic matching, 516, 519, 529, 549, 550 ECD See Electronic circular dichroism Electron correlation, 8, 11, 13–22, 23 Electronic circular dichroism (ECD), 82 Electrostatic embedding, 38 Enforced hydrophobic interaction, 448 Epoxydon OR, 85 Esperamicin, 233, 234 Ethane DPE, 108 Ethanol Atomic charges, 114 Ethylene glycol See 1,2-Ethanediol Ethene DPE, 106 Ethyne DPE, 107 Exchange-correlation functional, 23–26 Felkin, Hugh, 391–397, 401–404 Flowing afterglow spectroscopy, 107, 109 Fock matrix, 5, 6, 8, Formaldehyde Formic acid Atomic charges, 114 Deprotonation of, 114 Frenking, Gernot, 396–399 Furan ASE, 148 NMR, 151 RSE, 148 Gajewski, Joseph, 521 Gao, Jiali, 449 Gas-phase acidity, 104, 117 Gauge-including atomic orbitals (GIAO), 68 Gaussian functions, 9, 10 Gaussian-type orbital (GTO) See Gaussian function Generalized Born Approximation (GB), 31 Geometry optimization, 42–45 GIAO See Gauge-including atomic orbitals Glucose, 452, 460–468, 493 603 Gas- and solution-phase population, 465 Gas-phase energy, 463 Gas-phase geometry, 462 Microsolvation geometry, 467, 468 Glycerol See 1,2,3-Propanetriol Glycine, 489–492 IR frequencies, 68 Microsolvated energy, 491 structure of, 67 Goddard, William, 300, 301, 356 Goodman, 74, 75, 570, 571, 572, 573 Interview, 90 Gordon, Mark, 137, 490, 491 Grimme, Stefan, 13, 17, 26, 27, 84, 125, 128, 129, 130, 131, 141, 164, 174, 176, 359 Interview, 48 Gronert, Scott, 381 Group equivalent reaction (GER), 134, 136, 137, 138, 141, 142 Group equivalents (GE), 133, 135, 136, 137, 141 Guanine, 473–475, 483–489 Gas-phase tautomer geometry, 474 Microsolvated tautomer geometry, 476 Tautomer energy, 475 GX model, 21 Hajos-Parrish-Wiechert-Eder-Sauer reaction, 405, 408, 417–420, 433 Hammond Postulate, 379 Hartree–Fock (HF), 3–7, 23 Hase, William, 528, 529, 537, 538, 553 Herges, Rainer, 162, 163, 164, 165, 166 Herzberg, Gerhard, 299, 355 Heterolytic cleavage, 99, 104 Hexacyclinol NMR, 78 Hexane Conformational energies, 119, 120, 121 Hexaphenylethane, 131 HF See Hartree-Fock Hilltop, 42 Hobza, Pavel, 174, 469, 470, 473–477, 479, 485 Hoffmann, Roald, 527 Hohenberg–Kohn existence theorem, 22 Homodesmotic reaction, 134, 135, 136, 137, 147, 148, 149 Homolytic cleavage, 99, 100 Houk -List model Aldol reaction, 414–417 Houk, Kendall, 128, 175, 176, 199, 206, 207, 209, 210, 214, 228, 229, 258, 259, 267–277, 280, 383, 394–396, 398, 399, 404, 408, 410, 412–418, 420, 421, 425, 427, 428, 521, 523, 604 INDEX Houk, Kendall (Continued) 525, 527, 529, 550, 570, 578, 580, 586, 588, 590, 591 Interview, 432 Hückel topology, 161, 162 Hydroboration, 554–555 Hydrophobic effect, 447–450, 452 Hydroxymethylene Tunneling, 349–350 Implicit Solvent Models, 29–34 Individual gauge for localized orbitals (IGLO), 68 Infrared spectroscopy, 62–67 Integrating differential equations Euler’s method, 509 Runge–Kutta method, 509 Verlet algorithm, 509 Interview Chistopher Cramer, 493 Daniel Singleton, 559 Henry Schaefer, 355 Jonathan Goodman, 90 Kendall Houk, 432 Paul von Rague Schleyer, 177 Peter Schreiner, 357 Stefan Grimme, 48 Weston Thatcher Borden, 278 Intramolecular vibrational energy redistribution (IVR), 513, 515, 519, 533, 536, 542 Intrinsic reaction coordinate (IRC), 41, 505, 537, 538, 548, 549, 550, 551 ISE See Isomerization stabilization energy (ISE) Isodesmic reaction, 114, 133, 134, 135, 136, 137, 140, 142, 146, 147 Isomerization stabilization energy (ISE), 149, 162, 163 Isotropic shielding, 154 IVR See Intramolecular vibrational energy redistribution Jacob’s Ladder, 24 Jacobsen, Eric, 429–431 Jensen, Frank, 381, 387–389 Jorgensen, William, 375, 376, 386, 448–450, 580, 581, 591 Karabatsos, Gerasimos , 391 Karney, William, 158, 163, 164, 318, 320 Kass, Steven, 106, 108, 109, 110, 116, 117, 118 ketenecycloadditon with cyclopentadiene, 543–547 Kinetic isotope effect (KIE), 420, 521, 540, 544, 545, 546, 547, 559 Diels-Alder reaction, 209–214 Kirkwood–Onsager model, 31 Kollman, Peter 584, 585 Kraka, Elfi, 202, 241, 242, 243, 246, 336, 344, 348 laser ablation molecular beam Fourier transform microwave spectroscopy, 121, 123 Lazzeretti, Paolo, 151, 154 Linear Combination of Atomic Orbitals (LCAO) Approximation, 4–5 Linear synchronous transit (LST), 44 Lineberger, W Carl, 301, 303, 304, 329, 330, 332, 355, 356 List, Benjamin, 405, 408, 414–417, 421, 423, 425, 433 local density approximation (LDA), 24 Lysine, 588, 589 Magnetic shielding tensor, 154 Maitotxin NMR, 79 Mannich reaction, 421–426 Masamune, S 155, 156, 158, 159 MC See Michaelis complex (MC) MD See Molecular dynamics Mechanical embedding, 38 MEP See Minimum energy path Methanol DPE, 113 Methylene, 298–304, 305, 307, 308, 310, 326, 355, 356 MOs, 299 singlet-triplet energy gap, 301, 302 triplet geometry, 299 Methylhydroxycarbene Tunneling, 352 Tunneling control, 353 Methyloxirane OR, 86, 87 ORD, 85 Michaelis complex (MC), 570, 571, 584, 585 Microcanonical sampling, 511, 513 Microsolvation, 28, 29, 34, 451, 455–458, 464, 465, 467, 470, 471, 474–476, 479, 482, 485, 491, 492 1,2-Ethanediol, 457 Adenine, 479 Amino acids, 491 Cytosine, 471 Glycine, 491 Guanine, 476 nucleic acid base pairs, 486 Thymine, 482 Uracil, 482 Mills-Nixon effect, 145, 166, 167, 169, 170, 171 INDEX Minimum energy path (MEP), 41, 505–507, 541, 543, 545, 550, 557 Möbius topology, 161, 162, 164 Molecular dynamics (MD), 505, 507–512, 514, 516, 518, 521, 528, 529, 537, 540, 541, 544, 550, 553 Molecular Mechanics (MM), 36–38 Møller–Plesset (MP), 17 Momany, 461, 464, 466–468 Morokuma, Keiji 39, 331 Mulholland, Adrian, 577, 578, 581, 582, 592 Mulliken population, 46, 47 Multiconfiguration SCF (MCSCF), 18–20 Myers–Saito cyclization, 249–256 (4Z)-1,2,4-heptatrien-6-yne, energies, 253 (4Z)-1,2,4-heptatrien-6-yne, geometry, 252 NAC See Near attack confomers Naphthalene, 144, 160, 156, 157, 160 NICS, 152, 153 Natural population analysis (NPA), 47, 114 Near attack confomers (NAC), 579, 580, 581, 582, 583, 584 Neocarzinostatin, 233, 254, 255 mechanism of action, 250 Nicolaou, K C 360 NICS See Nuclear-independent chemical shift (NICS) NMR, 81 NMR See Nuclear magnetic resonance Nobilisitine A NMR, 75 Noradrenaline, 582 NPA See Natural population analysis Nuclear magnetic resonance (NMR), 66–82 Nuclear-independent chemical shift (NICS), 143, 150, 151, 152, 153, 154, 161, 162, 163, 164, 165, 166, 169, 170, 172 Nucleic acid base pairs, 479–489 Geometry, 483 Microsolvated geometry, 486 Stacking energy, 484 OAH See Oxyanion hole Octane, 125, 126, 130 ONIOM, 39–40 Optical rotation (OR), 82–90 Optical rotatory dispersion (ORD), 82–90 OR See Optical rotation Orbital symmetry rules See Woodward-Hoffmann rules ORD See Optical rotatory dispersion OXA See oxyallyl diradical Oxazolidinone, 416, 417 605 OxetaneRSE, 134, 135 oxyallyl diradical (OXA), 330–332 MOs, 331 Singlet-triplet energy gap, 332 Oxyanion hole (OAH), 570–573, 590 Paddon-Row, Michael, 394, 397, 399, 400 Paracylophane, 90 Para-hydroxybenzoate hydrolase, 576 Pauling paradigm, 570, 573 Pauling, Linus, 104, 147, 166, 569, 570 PBE0, 25 PBHB See para-Hydrobenzoate hydrolase PCM See Polarized continuum model Pent-1,4-diyne DPE, 111 Perdew, John, 24, 25 Perturbation theory, 16–17 MP2, 17 Petersson, George, 22 Phenanthene, 144 Phenylcarbene, 304–317, 322 MOs, 306 Ring expansion, 312–317 Ring expansion, energies, 314 singlet-triplet energy gap, 307 Phenylhydroxycarbene Tunneling, 350–351 Phenylnitrene, 304–324, 326 Bond lengths, 310 MOs, 306 Ring expansion, 312–326 Ring expansion, energies, 315 Ring expansion, geometries, 316 Ring expansion, substituent effect, 317–326 Singlet-triplet energy gap, 310 UHF MOs, 309 Phenyloxenium cation, 312 MOs, 306 Photodissociation of, 551 𝜋 –𝜋 stacking, 173, 176, 177 Pinacolyl alcohol, Protonated Rearrangement, dynamics, 550–551 Pitzer strain, 139, 140, 142 Platz, Matthew, 317–322, 365 Plumericin ECD, 87 Poisson equation, 30, 31, 32 Polarization functions, 11, 21 Polarized continuum model (PCM), 31, 33, 34, 583 Pople, John, 9, 11, 21, 64, 154, 355, 435 Population analysis, 45–48 606 INDEX Potential energy surface (PES) Chloride with methylchloride, 376 Fluoride with methylchloride, 380 Preorganization, 573, 584 Prephenate, 578, 579 Prismatomerin OR, 87 Propane, 126, 127 bond energies, 141 DPE, 106 Propyne DPE, 111 Protein structure relaxation, 572 Pseudopericyclic reactions, 260–267 Formylketene with ammonia, 264 Wolff reaction, 556 PW91, 25 Pyran-2-one MOs, 262 Pyrenophanes, 172 Pyrrole NMR, 151 Stabilization energy, 144 QM/MM, 35–40 Quadratic synchronous transit (QST), 44 quadrupole ion trap, 117 Reference configuration, 13 Restricted wavefunction, Retroaldol, 590 Rice-Ramsperger-Kassel-Marcus Theory (RRKM), 505, 507, 513, 514, 516, 517, 533, 547, 554, 555 Ring current map, 144 Ring current, 144, 151, 153, 154, 160 Ring strain energy (RSE), 99, 112, 132, 133, 134, 135, 136, 137, 138, 139, 140, 142, 143, 146, 148 evaluated using Group equivalent reactions, 137 Evaluated using isodesmic reactions, 137 Evaluated using homodesmotic reactions, 137 Roaming mechanism, 551–553 Acetaldehyde photodissociation, 552 Formaldehyde photodissociation, 551 Nitrobenzene photodissociation, 553 Roothaan Method, 5–7, 23 RosettaMatch algorithm, 587, 589, 590, 591 Roundabout mechanism, 553–554 RSE See Ring strain energy Rzepa, Henry 90 Schaefer, Henry, 22, 61, 145, 151, 156, 157, 160, 161, 298–301, 303, 334 Interview, 355 Schlegel, Bernard 64 Schleyer, Paul, 106, 114, 126, 127, 141, 142, 143, 145, 147, 148, 149, 150, 151, 153, 154, 156, 160, 161, 162, 164, 357, 394 Interview, 177 Schmittel cyclization, 249–256 (4Z)-1,2,4-heptatrien-6-yne, energies, 253 (4Z)-1,2,4-heptatrien-6-yne, geometry, 252 dynamics, 540–543 Schreiner–Pascal cyclization, 256 Schreiner, Peter 125, 127, 132, 231, 242, 246–248, 254–256, 349, 350, 352–354 Interview, 357 Schrödinger equation, 2, 3, 8, 13, 14 Secondary orbital interactions (SOIs), 258 Self-consistent field (SCF), Self-consistent reaction field (SCRF), 30 Semiclassical dynamics, 512 Sherrill, C David, 175 Shielding tensor, 154 Shikimic acid pathway, 578 SIBL See Strain-induced bond localization Siegel, Jay, 160, 169, 170 𝜎-aromaticity, 143, 144 Singleton, Daniel, 160, 169, 170, 540, 210, 254, 541, 543, 544, 547–549, 554–556 Interview, 558 Size Consistency, 16 Slater determinant, 4, 14, 15 Slater-type orbitals (STO), SN1 mechanism, 373, 374, 381 SN2 mechanism, 373–391 𝛼-Branching, 381 𝛼-Branching, energies, 382 𝛼-Branching, geometries, 383 𝛽-branching, 381 Chloride with methylchloride, energy, 377 Chloride with methylchloride, geometry, 375 Chloride with methylchloride, PES, 376 Chloride ion and methyliodide, dynamics 553–554 Fluoride with methylchloride, PES, 380 Fluoride with methylfluoride, energy, 378 Fluoride with methylfluoride, geometry, 375 Hydroxide with fluoromethane, dynamics, 536–537 Microsolvation, 388 Microsolvation, geometries, 389 Non-identity reactions energies, 380 Non-identity reactions, geometries, 379 Solvent effects, 385–391 SNF mechanism, 383, 384 geometries, 384 INDEX Solvation model (SMx), 32–34 Specific reaction parameters (SRP), 510, 511, 521, 525, 528, 534, 535 Spin projection, Spin-component scaled MP2 (SCS-MP2), 17, 28, 49 Sponer, Jiri, 479, 482, 484 Squires, Robert, 493–494 SRP See Specific reaction parameters Stanger, Amnon, 153, 167, 170, 171 STO See Slater-type orbital Strain-induced bond localization (SIBL), 166, 167, 169, 170, 171, 173, 175 Streitwieser, Andrew, 381 Subtilisin, 572 Sunoj, Raghavan, 416 Tetramethyleneethane (TME) 324–330 MOs, 325, 327 Theozyme, 586–592 Thymine, 477–482 Gas-phase tautomer geometry, 480 Microsolvated tautomer geometry, 482 Tautomer energy, 481 TME See Tetramethyleneethane TMM See Trimethylenemethane Toluene Aromatic stabilization energy of, 149 DPE, 107 Tomasi, Jacopo, 446, 473 Topological electron density analysis, 47–48 Torquoselectivity, 267–278 Electrocyclization of 1,3-cyclohexadienes, 276 Electrocyclization of cyclobutenes, 269, 271 Electrocyclization of cycloocta-1,3,5-trienes, 277 TPSS, 25 Transition state stabilization, 570 Transition state theory (TST), 505, 507, 513, 514, 517, 529, 533, 545–549, 554, 555 Tricyclopropabenzene, 166 Trimethylene diradical, 527–529 Trimethylenemethane (TMM), 324 MOs, 325 Tropylium cation, 144 NICS, 153 Truhlar, Donald, 32, 33, 35, 38, 64, 130, 383, 446, 455, 457, 461, 464, 466, 484, 492–495, 510 607 TST See Transition state theory Tunneling control, 353–355 Tunneling Carbenes, 349–355 Tyrosine, 118, 119 DPE, 118 Umbrella sampling, 575, 577 Unrestricted wavefunction, Uracil, 477–482 Gas-phase tautomer geometry, 480 Microsolvated tautomer geometry, 482 Tautomer energy, 481 Valley–ridge inflection (VRI), 42, 257–259, 541 Vannusal B NMR, 80 Variational Principle, Variational transition state theory (VTST), 514 Vibrational circular dichroism (VCD), 82–90 Vinylcyclobutane Rearrangement to cyclohexene, 523 Vinylcyclopropane Rearrangement to cyclopentene, 520–523 VRI See Valley ridge inflection VTST See Variational transition state theory Warshel, Arieh, 570, 572, 573, 584, 591, 592 Watson-Crick Base Pair, 469, 473, 474, 479, 482–487 Geometry, 483 Interaction energy, 484 𝜔B97X-D, 27 Wentzel–Kramers–Brillouin theory (WKB), 349 Wheeler, Steven, 135, 175, 176, 177 Wiberg, Kenneth 88, 106 Wiest, Olaf, 578, 580 WKB See Wentzel–Kramers–Brillouin theory Wolff rearrangement Dynamics, 555–557 Woodward-Hoffmann rules, 514, 516, 520, 521, 524, 528 Zero-point vibrational energy (ZPVE), 21, 45, 64, 123, 129, 149 ZPVE See Zero point vibrational energy Zwitterion, 472, 489, 490 Figure 1.10 Isoelectronic surface of the total electron density of ammonia and benzene Note the lack of lone pairs or a 𝜋-cloud Computational Organic Chemistry, Second Edition Steven M Bachrach © 2014 John Wiley & Sons, Inc Published 2014 by John Wiley & Sons, Inc Occupied MOs Figure 4.7 Unoccupied MOs MO 21: 7ag MO 24: 8ag MO 22: 5au MO 25: 5bg MO 23: 7bu MO 26: 8bu Representation of the active space orbitals for the Cope rearrangement MO 26 (LUMO) – 5a" MO 25 (HOMO) – 4a" MO 24 – 21a' MO 23 – 3a" MO 22 – 2a" MO 21 – 20a' MO 20 – 19a' 89 Figure 4.22 90 High lying occupied MOs and LUMO of 89 and 90 26 2a2 5a' 2a2 25 3b1 4a" 3b1 24 8b2 3a" 3b2 23 1a2 21a' 1a2 22 2b1 2a" 2b1 21 13a1 20a' 7b2 Figure 5.2 Molecular orbitals of 1, 2, and 7 α Orbitals β Orbitals 24 Energy 24 23 22 Figure 5.4 23 22 Highest lying occupied UHF orbitals of the A1 state of phenylnitrene (1) 3b1 9a1 1a2 2b1 5b2 1b1 Figure 5.11 MOs of oxyallyl diradical 40 MO 21 8b2 7b2 3b1 MO 20 2b1 11a1 1a2 1a2 11a1 MO 19 1a2 MO 18 10a1 2b1 2b1 MO 17 1b1 1b1 6b2 MO 16 9a1 10a1 1b1 Figure 5.12 High-lying molecular orbitals of 41, 42, and 44 R P4 TS1 DI TS2 P3 P2 Figure 8.4 Contour plot of the PES in Figure 8.3, looking down from above The heavy line is the direct trajectory from TS1 across DI and over TS2 to P2 The long-short dashed line is the semidirect trajectory from TS1 to P3 The dashed line is the rebound trajectory from TS1 to P3 .. .COMPUTATIONAL ORGANIC CHEMISTRY COMPUTATIONAL ORGANIC CHEMISTRY Second Edition Steven M Bachrach Department of Chemistry Trinity University San Antonio,... Chapter 9, which discusses computational enzymology This chapter extends the coverage of quantum chemistry to a sister of organic chemistry biochemistry Since computational biochemistry truly deserves... demonstrate the major impact that computational methods have had upon the current understanding of organic chemistry I present a survey of organic problems where computational chemistry has played a significant