Organic Reaction Mechanisms, 1999 / Edition 1 available in Hardcover
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Organic Reaction Mechanisms 1999
John Wiley & SonsCopyright © 2004 John Wiley & Sons, Ltd
All right reserved.
Chapter OneReactions of Aldehydes and Ketones and their Derivatives
B. A. MURRAY
Formation and Reactions of Acetals and Related Species
Hammett plots have been constructed for the acid- and base-catalysed decomposition of methyl hemiacetals of benzaldehydes in aqueous solution. The data are analysed in terms of three-dimensional More O'Ferrall-Jencks diagrams and of Cordes interaction effects.
Diazidooxopropyl acetal (1) undergoes rhodium(II)-catalysed ring expansion to (3) in the presence of TMS chloride; the latter reagent acts as a Lewis acid-base catalyst for ring expansion of the oxonium ylid intermediate (2).
t-Butyl chloromethyl ketone forms a cyclic acetal with sucrose: the 2-hydroxy group of the sugar reacts with the carbonyl, with ring closure via the 3-position, yielding a t-butyl hydroxymethyl acetal. The results are part of a study of the relative reactivities of the hydroxy groups of (unprotected) sucrose.
An unusual case of cyclopropanol formation from a hemiacetal of a [beta]-silyl aldehyde is ascribed to an enhanced reactivity of the silicon, due to an appropriately placed oxyanion generated from the hemiacetal.
Activated N, O-acetals (4) can undergo a nucleophilic alkylation which replaces the oxygen (via an imine intermediate) to yield an amine (5a), or by replacement of the nitrogen (via an aldehyde) to yield an alcohol (5b). Such amine or alcohol products are valuable, especially if obtainable as single isomers. A catalytic, enantioselective alkylation has been reported to yield the amines (5a), using a copper-BINAP catalyst, and a variety of alkene sources for the alkylating group (enol silanes or allylsilanes, ketene silyl acetals). [sup.1]H NMR spectroscopy was used to elucidate mechanistic details concerning the transsilylations involved. For example, a simple N, O-acetal (4; X = p-Ts, [R.sup.1] = H, [R.sup.2] = Et) does not give amine (5a) with 1 equiv. of the enol silane of acetophenone; rather, O-silylation occurs. A second equivalent of enol silane is required to form (5a), and the catalyst. The paper also reports similar transformations of N, N-acetals.
Catalytic, enantioselective alkylations of N, O-acetals have been reported.
Reactions of Glucosides and Nucleosides
A theoretical study of the mutarotation of glucose has evaluated the energies of the two transition states (i.e. [alpha]-anomer to aldehyde and aldehyde to [beta]-anomer), placing n = 0-3 water molecules as part of a specific proton-transfer network. The transition states are lowered by ca 28 kcal [mol.sup.-1] with even one water, but significant further stabilizations are observed for n = 2 and 3, both of which exhibit very strong hydrogen-bonded networks. A variant with secondary hydrogen bonding (n = 2, with two 'outer' waters) is also evaluated.
A m-xylylene moiety has been used as a rigid spacer to align an intramolecular glycosylation at room temperature. The systems used, involving 15- or 14- membered ring formation, exhibit good face selectivity (i.e. towards formation of [alpha]- or [beta]-anomer). They also show promise for oligosaccharide synthesis, with a simple protocol for post-synthesis cleavage of the spacer.
Alkaline hydrolyses of p-nitrophenyl [alpha]-D-glucoside and the corresponding galactosides are accelerated by a factor of up to 110 on addition of boric, boronic, or borinic acids, relative to their [beta]-anomers. The selectivity is reversed in the case of the mannosides, indicating that a cis-relationship between the 2-hydroxy and the p-nitrophenoxy groups is central to the stereoselection. An acceleration of the hydrolysis of p-nitrophenyl-D-glucosides in the presence of [alpha]-cyclodextrins depends on this same stereochemical relationship. With [alpha]-cyclodextrin (20 mmol [dm.sup.-3]), hydrolysis of the [alpha]-D-mannoside is accelerated 7.6-fold, whereas the [beta]-anomer is unaffected. For the D-glucoside, -galactoside, and -xyloside, complexation by cyclodextrins favours hydrolysis of the [beta]-sugars, by similar factors. These selectivities are achieved without particularly strong binding (110 < K /[mol.sup-1][dm.sup.3] < 260), and are not due to binding selectivity: [K.sub.[alpha]] never differs from [K.sub.[beta]] by more than 60%.
The Maillard reaction involves condensation of an aldose with an amino function (e.g. of a protein), yielding an imine that can undergo rearrangement to an amino form (the Amadori rearrangement), followed by subsequent reactions involving both volatile and polymeric products. In the light of the increasing use of high pressure in food processing, the effect of such pressures on the formation of volatiles has been studied for a model Maillard reaction.
TMS triflate catalysis of transglycosylations between permethylated methyl D-glucopyranosides and simple alcohols has been reported.
Reactions of Ketenes and Related Species
Mechanistic investigations of additions to ketenes continue to focus on which double bond reacts first, and on the role of the solvent: many theoretical studies probe the latter by systematic incremental inclusion of a series of solvent molecules in the calculation. Experimentally, similar effects for the catalyst are often seen in its kinetic order.
Gas-phase and solution-phase calculations on the hydration of ketene to produce acetic acid, using water clusters of two, three, and four molecules to attack the ketene, show a two-step addition via the 1,1-enediol intermediate, i.e. initial addition to C=O, rather than to C=C. The preference is slight, but consistent.
Solvent isotope effects, [k.sub.HO]/[k.sub.DO], have been measured for the hydration of five ketenes, [R.sup.1][R.sup.2]C=C=O, catalysed by hydroxide ion.
Rate constants for hydration of ketene, and of carbon dioxide, have been calculated using No Barrier Theory, Marcus Theory, and a multi-dimensional Marcus treatment. The methods agree except in the case of the uncatalysed hydration of ketene, where the multi-dimensional method predicts [DELTA][G.sup.act] to be lower for addition to C=O, whereas the No Barrier results favour C=C addition. A calculation of [k.sub.HO] for ketene hydration agrees with preliminary experimental results.
Addition of amines to the silylketene [PhMe.sub.2]SiCH=C=O to form amides exhibits kinetics in acetonitrile in which the order in amine lies between second and third, as found in recent theoretical studies of the parent ketene, [H.sub.2]C=C=O, and ammonia. The result contrasts sharply with a straightforward first-order dependence found for more reactive substrates, such as diphenylketene. The influence of amine basicity is discussed for the silylketene and compared with results for hindered compounds. The reasons for the failure to observe higher order terms for the more reactive substrates are also discussed.
The amination of ketenes to produce amides (see Scheme 1) has been subjected to a variety of computational methods, including several treatments of the solvent, with explicit roles for actively participating amine and water molecules. All the results favour a two-step process with initial addition to the C=O bond, rather than a concerted reaction involving the C=C bond. The former involves a 1-amino-1-hydroxyene intermediate (6), formally the enol of the amide. Inclusion of a second amine molecule lowers the barrier to the two-step reaction. Replacing the second amine with a water molecule lowers it even further, an effect which should be even greater when water is the bulk solvent. Some experimental evidence is presented for the highly hindered substrates, bis(mesityl)ketene and bis(pentamethylphenyl)ketene. Addition of primary or secondary amines clearly shows, from IR and UV spectra, the build-up and subsequent tautomerization of the intermediate enols. The kinetics of these more hindered substrates are first order in amine; this is not inconsistent with the theoretical results, as such hindered ketenes may only react rather slowly with amine dimer, which is also in low concentration under the conditions used.
Calculations and low-temperature NMR experiments have been used to investigate the course of reactions of diphenylketene with dienes. While the reaction of cyclic (s-cis) 1, 3-dienes such as cyclopenta- and cyclohexa-1,3-diene yield 2 + 2 (Staudinger) products, the low-temperature experiments indicate initial formation of 4 + 2 (Diels-Alder) intermediates. For the open-chain reactants, 2, 3-dimethyl- and 1-methoxy-1,3-butadiene, both product types are formed initially, with conversion of the Staudinger to the Diels-Alder over time, via a retro-Claisen rearrangement.
Methyleneketene, [H.sub.2]C=C=C=O, could undergo cycloaddition at any of its double bonds. Theoretical calculations on its reaction with pyrroline-1-oxide predict an asynchronous concerted mechanism leading to (7), the 2,3-adduct, the same regioselectivity as is observed in experiment.
The mechanisms of dimerization of ketene imine and its bis(trifluoromethyl) derivative have been studied by ab initio methods. Each process identified was found to be concerted but asynchronous, with a four-membered transition state.
An isodesmic reaction has been employed to study substituent effects on the stability of ketenimines, XCH=C=NH. A (negative) correlation with the electronegativity of the substituent X was found. The sensitivity to the substituent effect is less than that for ketenes or isocyanates, but more than that found for diazomethanes or allenes. Particular stabilizing effects are found for [pi]-acceptors, e.g. X = Al[H.sub.2], B[H.sub.2], O=CH, H[O.sub.2]C, CN, N[O.sub.2], and HS[O.sub.2] (suggesting cyano-cation resonance structures are important), and for X = Li (i.e. ynamine resonance).
Keteniminium cations and imines can undergo a formal 2 + 2 thermal cycloaddition to yield 2-azetidinones [[beta]-lactams (8)]; see Scheme 2. A computational study suggests the cycloaddition occurs via a stepwise mechanism, with N-C bond formation occurring first. Stereochemistry is determined in the second step, by torquoelectronic effects. However, the nature of the anion can affect the stereochemistry, which appears to explain the change in stereochemistry found when X = Cl, i.e. when chloroenamines are used as precursors of keteniminium ions.
The chemistry of bis(trimethylsilyl)-1,2-bisketene (9) has been extended to its reaction with amines. The facile reaction occurs in two steps: the first amine gives a ketenylcarboxamide (10) and the second gives a succinamide (11); the latter can be a mixed product if the bisketene (9) is treated with two different amines successively. Phenylhydrazine reacts with (9) to give a succinimide, while treatment with an amine and then an alcohol (or vice versa) gives an ester amide. Diamines give polymeric products, unless an excess of the bisketene is employed, to give an [alpha],[omega]-bisketenyldiamide. Kinetic studies of each of the steps in the formation of the succinamide are reported. It is noted that reaction of methanol with ketenylcarboxamide (10) to give the ester amide is much faster than the formation of a diester from a ketenyl ester. This and other lines of evidence point to a coordination between the carboxamide group of (10) and incoming nucleophiles in the formation of the 'homo-' and 'hetero-' succinic acid derivatives.
Bromofluoroketene ethyl trimethylsilyl acetal [Br(F)C=COEt(Osi[Me.sub.3]), E/Z-mixture] undergoes enantioselective aldol reactions with aldehydes in the presence of Masamune's catalyst. The enantioselectivity is markedly temperature dependent, with examples of high ee at -78 and -20ºC, but of opposite rotation sign.
Lewis acid-mediated addition of silyl ketene acetals to a chiral sulfimine gives precursors of [beta]-amino acids in fair to excellent de.
Mixed diesters of both symmetrical and unsymmetrical diols have been prepared by reaction of carboxylic acids with cyclic ketene acetals of the diols, with the less substituted carbon of the cyclic dioxonium ion intermediate being attacked in most cases.
Hydration of trifluoroacetylketene is discussed later under Enolization.
Formation and Reactions of Nitrogen Derivatives
Proton affinities of imines and heats of formation of immonium ions have been calculated for the gas phase by ab initio methods. cis-Imines are more basic than their trans-isomers, reflecting the unusually high (15-17 kJ [mol.sup.-
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Table of Contents
1. Reactions of Aldehydes and Ketones and their Derivatives by B.A. Murray.
2. Reactions of Carboxylic, Phosphoric, and Sulfonic Acids andtheir Derivatives by C. T. Bedford.
3. Radical Reactions: Part 1 by A. J. Clark and J.Sherringham.
4. Radical Reactions: Part 2 by A. P. Dobbs.
5. Oxidation and Reduction by B. G. Davis and D. P. G.Emmerson.
6. Carbenes and Nitrenes by D. M. Hodgson, M. Christlieb and E.Gras.
7. Nucleophilic Aromatic Substitution by M. R. Crampton.
8. Electrophilic Aromatic Substitution by R. G. Coombes.
9. Carbocations by R. A. Cox.
10. Nucleophilic Aliphatic Substitution by J. Shorter.
11. Carbanions and Electrophilic Aliphatic Substitution by A. C.Knipe.
12. Elimination Reactions by A. C. Knipe.
13. Addition Reactions: Polar Addition by P.Kocovsky.
14. Addition Reactions: Cycloaddition by N. Dennis.
15. Molecular Rearrangements by A. W. Murray.
Cumulative Subject Index.