Alkyl Halides and Nucleophilic Substitution SN2 Reaction
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Absolute and Relative Facial Selectivities in Organocatalytic Asymmetric Chlorocyclization Reactions
Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Absolute and relative facial selectivities in organocatalytic asymmetric chlorocyclization Cite this: Chem. Sci.,2018,9, 2898 reactions† Nastaran Salehi Marzijarani,a Roozbeh Yousefi,a Arvind Jaganathan,b Kumar Dilip Ashtekar,a James E. Jackson *a and Babak Borhan *a Though (DHQD)2PHAL-catalyzed chlorocyclizations of 1,1-disubstituted olefins show useful (and in some cases, reversible) asymmetric induction, stereochemically complete descriptions of these alkene additions have remained largely unknown. Herein, based on a combination of NMR, derivative, isotope labeling, and computational studies, we present detailed stereochemical analyses of chlorocyclizations of nucleophile-tethered 1,1-disubstituted styryl systems. The selectivities of the two asymmetric bond- forming processes, namely electrophilic chlorine attack and nucleophilic ring closure, are thus mapped out independently. Under the established optimal conditions, four related chlorocyclizations were + Creative Commons Attribution 3.0 Unported Licence. subjected to this analysis. All showed a strong preference for Cl delivery from the same face of the Received 12th October 2017 alkene. However, depending on reaction conditions and substrate identity (carboxylic acid, amide or Accepted 24th December 2017 carbamate), the internal nucleophiles may close with a strong net preference for either syn or anti DOI: 10.1039/c7sc04430e addition relative to the Cl atom. Studies of both uncatalyzed and (DHQD)2PHAL-catalyzed -
Organic Chemistry
Wisebridge Learning Systems Organic Chemistry Reaction Mechanisms Pocket-Book WLS www.wisebridgelearning.com © 2006 J S Wetzel LEARNING STRATEGIES CONTENTS ● The key to building intuition is to develop the habit ALKANES of asking how each particular mechanism reflects Thermal Cracking - Pyrolysis . 1 general principles. Look for the concepts behind Combustion . 1 the chemistry to make organic chemistry more co- Free Radical Halogenation. 2 herent and rewarding. ALKENES Electrophilic Addition of HX to Alkenes . 3 ● Acid Catalyzed Hydration of Alkenes . 4 Exothermic reactions tend to follow pathways Electrophilic Addition of Halogens to Alkenes . 5 where like charges can separate or where un- Halohydrin Formation . 6 like charges can come together. When reading Free Radical Addition of HX to Alkenes . 7 organic chemistry mechanisms, keep the elec- Catalytic Hydrogenation of Alkenes. 8 tronegativities of the elements and their valence Oxidation of Alkenes to Vicinal Diols. 9 electron configurations always in your mind. Try Oxidative Cleavage of Alkenes . 10 to nterpret electron movement in terms of energy Ozonolysis of Alkenes . 10 Allylic Halogenation . 11 to make the reactions easier to understand and Oxymercuration-Demercuration . 13 remember. Hydroboration of Alkenes . 14 ALKYNES ● For MCAT preparation, pay special attention to Electrophilic Addition of HX to Alkynes . 15 Hydration of Alkynes. 15 reactions where the product hinges on regio- Free Radical Addition of HX to Alkynes . 16 and stereo-selectivity and reactions involving Electrophilic Halogenation of Alkynes. 16 resonant intermediates, which are special favor- Hydroboration of Alkynes . 17 ites of the test-writers. Catalytic Hydrogenation of Alkynes. 17 Reduction of Alkynes with Alkali Metal/Ammonia . 18 Formation and Use of Acetylide Anion Nucleophiles . -
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Solvent Effects on Structure and Reaction Mechanism: a Theoretical Study of [2 + 2] Polar Cycloaddition Between Ketene and Imine
J. Phys. Chem. B 1998, 102, 7877-7881 7877 Solvent Effects on Structure and Reaction Mechanism: A Theoretical Study of [2 + 2] Polar Cycloaddition between Ketene and Imine Thanh N. Truong Henry Eyring Center for Theoretical Chemistry, Department of Chemistry, UniVersity of Utah, Salt Lake City, Utah 84112 ReceiVed: March 25, 1998; In Final Form: July 17, 1998 The effects of aqueous solvent on structures and mechanism of the [2 + 2] cycloaddition between ketene and imine were investigated by using correlated MP2 and MP4 levels of ab initio molecular orbital theory in conjunction with the dielectric continuum Generalized Conductor-like Screening Model (GCOSMO) for solvation. We found that reactions in the gas phase and in aqueous solution have very different topology on the free energy surfaces but have similar characteristic motion along the reaction coordinate. First, it involves formation of a planar trans-conformation zwitterionic complex, then a rotation of the two moieties to form the cycloaddition product. Aqueous solvent significantly stabilizes the zwitterionic complex, consequently changing the topology of the free energy surface from a gas-phase single barrier (one-step) process to a double barrier (two-step) one with a stable intermediate. Electrostatic solvent-solute interaction was found to be the dominant factor in lowering the activation energy by 4.5 kcal/mol. The present calculated results are consistent with previous experimental data. Introduction Lim and Jorgensen have also carried out free energy perturbation (FEP) theory simulations with accurate force field that includes + [2 2] cycloaddition reactions are useful synthetic routes to solute polarization effects and found even much larger solvent - formation of four-membered rings. -
Organic Chemistry Lesson 10 Reactions of Organic Molecules Combusition Reactions Substitution Reactions
Organic Chemistry Lesson 10 Reactions of Organic Molecules Combusition Reactions Substitution Reactions Physical Sciences Grade 12 1 Instructions Lesson 10 (16 April 2020) 1. Read ALL the slides in this document. 2. Homework: Just understand the theory for now. • If you have any questions, post them onto your WhatsApp group and your teacher will attend to them when (s)he has a chance. • Additional Resources: • Summary on pg.132 of your textbook. Physical Sciences Grade 12 2 Types of Reactions of Organic Compounds 1. Esterification: formation of an ester from an alcohol and a carboxylic acid. 2. Combustion Reactions (aka Oxidation): organic molecule + oxygen. 3. Substitution Reactions: one or more atoms are replaced by other atoms. (i) alkanes to alkyl halides; (ii) alcohols to alkyl halides; (iii) alkyl halides to alcohols 4. Addition Reactions: one or more atoms are added. (i) hydrogenation; (ii) halogenation; (iii) hydrohalogenation; (iv) hydration 5. Elimination Reactions: one or more atoms are removed. (i) dehydrohalogenation; (ii) dehydration; (iii) cracking of alkanes Physical Sciences Grade 12 3 1. Esterification • Already discussed (refer to earlier notes). Physical Sciences Grade 12 4 2. Combustion Reactions, i.e. Oxidation • A combustion reaction is the reaction of an organic molecule with oxygen. • Please note: “combustion” does NOT mean “explosion”. All combustion reactions release energy but most do so WITHOUT any explosion. • Alkanes – in the form of fossil fuels – are currently the main source of energy worldwide as their combustion is highly exothermic. • Examples: Burning wood for a braai. Propane combusting in a gas stove. Petrol combusting in a car engine. Physical Sciences Grade 12 5 2. -
Reaction Mechanism
Reaction Mechanism A detailed sequence of steps for a reaction Reasonable mechanism: 1. Elementary steps sum to the overall reaction 2. Elementary steps are physically reasonable 3. Mechanism is consistent with rate law and other experimental observations (generally found from rate limiting (slow) step(s) A mechanism can be supported but never proven NO2 + CO NO + CO2 2 Observed rate = k [NO2] Deduce a possible and reasonable mechanism NO2 + NO2 NO3 + NO slow NO3 + CO NO2 + CO2 fast Overall, NO2 + CO NO + CO2 Is the rate law for this sequence consistent with observation? Yes Does this prove that this must be what is actually happening? No! NO2 + CO NO + CO2 2 Observed rate = k [NO2] Deduce a possible and reasonable mechanism NO2 + NO2 NO3 + NO slow NO3 + CO NO2 + CO2 fast Overall, NO2 + CO NO + CO2 Is the rate law for this sequence consistent with observation? Yes Does this prove that this must be what is actually happening? No! Note the NO3 intermediate product! Arrhenius Equation Temperature dependence of k kAe E/RTa A = pre-exponential factor Ea= activation energy Now let’s look at the NO2 + CO reaction pathway* (1D). Just what IS a reaction coordinate? NO2 + CO NO + CO2 High barrier TS for step 1 Reactants: Lower barrier TS for step 2 NO2 +NO2 +CO Products Products Bottleneck NO +CO2 NO +CO2 Potential Energy Step 1 Step 2 Reaction Coordinate NO2 + CO NO + CO2 NO22 NO NO 3 NO NO CO NO CO 222In this two-step reaction, there are two barriers, one for each elementary step. The well between the two transition states holds a reactive intermediate. -
Activity 33. Hydrohalogenation & Hydration of Alkynes
Chem 201, Fall 2010 Activity 33, M Nov 22 Activity 33. Hydrohalogenation & Hydration of Alkynes Alkynes undergo many of the same addition reactions that alkenes do, including additions that require carbocation intermediates. Different energy and geometry changes may be required for additions to an alkyne and an alkene so some surprising outcomes may occur with alkynes. Model 1. Addition of HX Hydrogen halides (HCl, HBr, HI) add to alkynes to make vinyl halides . A carbocation mechanism is followed when the reaction is performed in the dark in a peroxide-free solvent. This addition obeys Markovnikov’s rule. A free-radical-chain mechanism is followed when HBr addition is initiated by organic peroxides. This addition gives an anti-Markonikov product. Critical Thinking Questions 1. Draw the carbocations indicated by the two bouncy curved arrows (below). Based on the observation that the carbocation mechanism yields a Markovnikov product, circle the more stable carbocation. 2. (CI) Draw the free radicals indicated by the two competing pathways (below). Based on the observation that the free-radical mechanism yields an anti-Markovnikov product, circle the more stable free radical. 3. The cations and radicals in CTQ #1 and #2 are called vinyl cations and vinyl radicals , respectively. Based on the regioselectivities reported in Model 1, what effect do alkyl substituents at the charged/radical carbon have on the energies of these species? Is this consistent with, or opposed to, their effect on R 3C+ and R 3C• species? 4. The geometry of a vinyl cation can be anticipated using VSEPR. Count electron domains in the cation below and predict all of the HCC bond angles. -
The Reactions of Alkenes
The Reactions of Alkenes The Stereochemistry of Addition Reactions 1 Diverse Reactions of Alkenes Alkenes react with many electrophiles to give useful products by addition (often through special reagents) 2 Preparation of Alkenes: A Preview of Elimination Reactions • Alkenes are commonly made by – elimination of HX from alkyl halide (dehydrohalogenation) • Uses heat and KOH – elimination of H-OH from an alcohol (dehydration) • requires strong acids (sulfuric acid, 50 ºC) 3 A Regioselective Reaction A reaction in which one structural isomer is favored over another, leading to its predominance in the mixture of products. 4 A Stereoselective Reaction A reaction in which one stereoisomer in a mixture is produced more rapidly than another, resulting in predominance of the favored stereoisomer in the mixture of products. 5 A Stereospecific Reaction A reaction in which a particular stereoisomeric form of reactant gives one specific stereoisomer of product, while a different stereoisomeric form of reactant leads to a different single pure streoisomer of product. Stereospecific reaction is also stereoselective; however, stereoselective reaction is not stereospecific. 6 An Electrophilic Addition Reaction where HX = HF, HCl, HBr, and HI Reactivity of HF << HCl < HBr < HI since HF is less acidic and HI is most acidic. The rate of addition of HI is too fast to measure. 7 The Mechanism of the Reaction 8 Relative Stabilities of Carbocations 9 Hyperconjugation Stabilizes a Carbocation 10 The Difference in Carbocation Stability Determines the Products -
Stereochemistry, Alkyl Halide Substitution (SN1 & SN2)
Chem 261 Assignment & Lecture Outline 3: Stereochemistry, Alkyl Halide Substitution (SN1 & SN2) Read Organic Chemistry, Solomons, Fryle & Snyder 12th Edition (Electronic) • Functional Group List – Learn to recognize – Please see Green Handout – also p 76 of text • Periodic Table – Inside Front Cover - know 1st 10 elements (up through Neon) • Relative Strength of Acids and Bases – Inside Front cover (reference only) • Chapter 5 – Stereochemistry • Chapter 6 –Ionic Reactions: Nucleophilic Substitution of Alkyl Halides Problems: Do Not turn in, answers available in "Study Guide Student Solutions Manual " Solomons, Fryle, Snyder • Chapter 5: 5.1 to 5.15; 5.18 to 5.21; 5.26; 5.28; 5.33a-d; 5.46 • Chapter 6: 6.1 to 6.5; 6.7 to 6.10; 6.13; 6.20; 6.26; 6.27 Lecture Outline # 3 I. Comparison of 2 Structures: Same Molecular Formula ? -> If Yes, Possibly Isomers or Identical Same Arrangement (Sequence) of Groups ? If No -> Structural Isomers If Yes -> Superposable? If Yes -> Identical Structures If No -> Stereoisomers Non-Superposable Mirror Images ? If NO -> Diastereomers If Yes -> Enantiomers II. Chirality and Stereoisomers A. The Concept of Chirality 1. Identification of chiral objects a) achiral = not chiral b) planes of symmetry within a molecule 2. Types of stereoisomers – enantiomers and diastereomers B. Location of stereogenic (chiral) centres – 4 different groups on tetrahedral atom 1. Enantiomers & diastereomers 2. Meso compounds - chiral centers with plane of symmetry within molecule 3. Molecules with more than one chiral centre 4. Recognition of chiral centers in complex molecules - cholesterol - 8 chiral centres Drawing the enantiomer of cholesterol and its potential 255 stereoisomers 5. -
Amide Activation: an Emerging Tool for Chemoselective Synthesis
Featuring work from the research group of Professor As featured in: Nuno Maulide, University of Vienna, Vienna, Austria Amide activation: an emerging tool for chemoselective synthesis Let them stand out of the crowd – Amide activation enables the chemoselective modification of a large variety of molecules while leaving many other functional groups untouched, making it attractive for the synthesis of sophisticated targets. This issue features a review on this emerging field and its application in total synthesis. See Nuno Maulide et al., Chem. Soc. Rev., 2018, 47, 7899. rsc.li/chem-soc-rev Registered charity number: 207890 Chem Soc Rev View Article Online REVIEW ARTICLE View Journal | View Issue Amide activation: an emerging tool for chemoselective synthesis Cite this: Chem. Soc. Rev., 2018, 47,7899 Daniel Kaiser, Adriano Bauer, Miran Lemmerer and Nuno Maulide * It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives. This results in a considerably reduced reactivity towards nucleophiles. Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts. Received 27th April 2018 However, a significant body of research on the selective activation of amides to achieve powerful DOI: 10.1039/c8cs00335a transformations under mild conditions has emerged over the past decades. This review article aims at placing electrophilic amide activation in both a historical context and in that of natural product rsc.li/chem-soc-rev synthesis, highlighting the synthetic applications and the potential of this approach. Creative Commons Attribution 3.0 Unported Licence. -
Chapter 14 Chemical Kinetics
Chapter 14 Chemical Kinetics Learning goals and key skills: Understand the factors that affect the rate of chemical reactions Determine the rate of reaction given time and concentration Relate the rate of formation of products and the rate of disappearance of reactants given the balanced chemical equation for the reaction. Understand the form and meaning of a rate law including the ideas of reaction order and rate constant. Determine the rate law and rate constant for a reaction from a series of experiments given the measured rates for various concentrations of reactants. Use the integrated form of a rate law to determine the concentration of a reactant at a given time. Explain how the activation energy affects a rate and be able to use the Arrhenius Equation. Predict a rate law for a reaction having multistep mechanism given the individual steps in the mechanism. Explain how a catalyst works. C (diamond) → C (graphite) DG°rxn = -2.84 kJ spontaneous! C (graphite) + O2 (g) → CO2 (g) DG°rxn = -394.4 kJ spontaneous! 1 Chemical kinetics is the study of how fast chemical reactions occur. Factors that affect rates of reactions: 1) physical state of the reactants. 2) concentration of the reactants. 3) temperature of the reaction. 4) presence or absence of a catalyst. 1) Physical State of the Reactants • The more readily the reactants collide, the more rapidly they react. – Homogeneous reactions are often faster. – Heterogeneous reactions that involve solids are faster if the surface area is increased; i.e., a fine powder reacts faster than a pellet. 2) Concentration • Increasing reactant concentration generally increases reaction rate since there are more molecules/vol., more collisions occur. -
Reaction Kinetics in Organic Reactions
Autumn 2004 Reaction Kinetics in Organic Reactions Why are kinetic analyses important? • Consider two classic examples in asymmetric catalysis: geraniol epoxidation 5-10% Ti(O-i-C3H7)4 O DET OH * * OH + TBHP CH2Cl2 3A mol sieve OH COOH5C2 L-(+)-DET = OH COOH5C2 * OH geraniol hydrogenation OH 0.1% Ru(II)-BINAP + H2 CH3OH P(C6H5)2 (S)-BINAP = P(C6 H5)2 • In both cases, high enantioselectivities may be achieved. However, there are fundamental differences between these two reactions which kinetics can inform us about. 1 Autumn 2004 Kinetics of Asymmetric Catalytic Reactions geraniol epoxidation: • enantioselectivity is controlled primarily by the preferred mode of initial binding of the prochiral substrate and, therefore, the relative stability of intermediate species. The transition state resembles the intermediate species. Finn and Sharpless in Asymmetric Synthesis, Morrison, J.D., ed., Academic Press: New York, 1986, v. 5, p. 247. geraniol hydrogenation: • enantioselectivity may be dictated by the relative reactivity rather than the stability of the intermediate species. The transition state may not resemble the intermediate species. for example, hydrogenation of enamides using Rh+(dipamp) studied by Landis and Halpern (JACS, 1987, 109,1746) 2 Autumn 2004 Kinetics of Asymmetric Catalytic Reactions “Asymmetric catalysis is four-dimensional chemistry. Simple stereochemical scrutiny of the substrate or reagent is not enough. The high efficiency that these reactions provide can only be achieved through a combination of both an ideal three-dimensional structure (x,y,z) and suitable kinetics (t).” R. Noyori, Asymmetric Catalysis in Organic Synthesis,Wiley-Interscience: New York, 1994, p.3. “Studying the photograph of a racehorse cannot tell you how fast it can run.” J. -
Development of New Domino Reactions of Alkylidene Meldrum's
Development of New Domino Reactions of Alkylidene Meldrum’s Acids Involving Friedel-Crafts Chemistry and Catalytic Conjugate Allylation of Alkylidene Meldrum’s Acids by Aaron Michael Dumas A thesis presented to the University of Waterloo in fulfilment of the thesis requirement for the degree of Doctor of Philosophy in Chemistry Waterloo, Ontario, Canada, 2009 © Aaron Michael Dumas 2009 I hereby declare that I am the sole author of this thesis. This is a true copy of my thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public. ii Abstract Alkylidene Meldrum’s acids are very reactive acceptors in conjugate additions, and are known to be significantly more electrophilic than other α,β-unsaturated carbonyl electrophiles. They also offer advantages in terms of ease of preparation, purification and storage. Despite this, they are relatively underused in organic synthesis, and have been treated as something of a curiousity in the literature. The goal of my research was to demonstrate the utility of these molecules in new reactions that are not readily available to other electrophiles. To facilitate this work, new conditions for the Knoevenagel condensation of aldehydes with Meldrum’s acid were developed. This allowed access to a broader range of monosubstituted alkylidenes than was previously possible from any single method. In a reaction that exploits the acylating ability of Meldrum’s acid, a domino addition of phenols to alkylidene Meldrum’s acids was developed. Here, Yb(OTf)3 catalyzed the addition of a phenol to the alkylidene as well as acylation through activation of the electrophile.