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ORGANIC REACTION MECHANISMS 1988

An annual survey covering the literature dated December 1987 to November 1988

Edited by A. C. Knipe and W. E. Watts University of Ulster, Northern Ireland

An Interscience' Publication

JOHN WILEY & SONS Chichester * New York Brisbane . Toronto - Singapore


An annual survey covering the literature dated December 1987 to November 1988

Edited by A. C. Knipe and W. E. Watts University of Ulster, Northern Ireland

An Interscience' Publication

JOHN WILEY & SONS Chichester * New York Brisbane . Toronto - Singapore

Copyright 0 1990 by John Wiley & Sons Ltd Baffins Lane, Chichester West Sussex PO19 IUD, England

All rights rcscrved.

No part of the book may be reproduced by any means, or transmitted, or translated into a machine language without the written permission of the publisher.

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Organic reaction mechanisms. I . Organic compounds. Chemical reactions. Mechanisma-Serials

547.13’9

ISBN 0 471 92029 0

Printed and bound in Great Britain by Courier International Ltd. Tiptree. Esres

Contributors

R. A. AITKEN

R. A. COX

M. R. CRAMPTON

G. W. J. FLEET

P. HANSON

C. D. JOHNSON

A. C. KNIPE

P. KOCOVSKP

R. B. MOODIE

R. A. MORE O’FERRALL

A. W. MURRAY

D. C. NONHEBEL

M. I. PAGE

J. SHORTER

W. J. SPILLANE

Department of Chemistry, University of St. Andrews, Purdie Building, St. Andrews, Fife KY 16 9ST, Scotland

Department of Chemistry, University of Toronto, 80 George Street, Toronto, Ontario M5S 1A1, Canada

Department of Chemistry, Durham Uni- versity, Durham DHI 3LE, UK

Dyson Perrins Laboratory, Oxford Uni- versity, South Parks Road, Oxford OX1 3QT, UK

Department of Chemistry, University of York, Heslington, York YO1 5DD, UK

School of Chemical Sciences, University of East Anglia, Norwich, UK

Department of Chemistry, University of Ulster at Coleraine, Coleraine, Co. Lon- donderry BT52 lSA, Northern Ireland

Czechoslovak Academy of Sciences, In- stitute of Organic Chemistry and Bioche- mistry, 166 10 Praha 6, Czechoslovakia

Department of Chemistry, The University, Exeter EX4 4QD, UK

Department of Chemistry, University College, Belfield, Dublin 4, Ireland

Department of Chemistry, The University, Dundee DD1 4HN, Scotland

Department of Pure and Applied Chemis- try, University of Strathclyde, Thomas Graham Building, Glasgow G1 IXL, Scotland

Department of Chemical Sciences, The Polytechnic, Queensgate, Huddersfield, West Yorkshire HDl 3DH, UK

Department of Chemistry, The University, Hull HU6 7RX, UK

Department of Chemistry, University College, Galway, Ireland

Contents

1 .

2 . 3 . 4 . 5 . 6 . 7 . 8 . 9 .

10 . 11 . 12 . 13 . 14 . 15 .

Reactions of Aldehydes and Ketones and their Derivatives by M . I . Page . . . . . . . . . . . . . . . . . . . . . . . . .

Radical Reactions: Part 1 by P . Hanson . . . . . . . . . . . . Radical Reactions: Part 2 by D . C . Nonhebel . . . . . . . . . . Oxidation and Reduction by G . W . J . Fleet . . . . . . . . . . . Carbenes and Nitrenes by R . A . Aitken . . . . . . . . . . . .

Reactions of Acids and their Derivatives by W . J . Spillane . . . . .

Nucleophilic Aromatic Substitution by M . R . Crampton . . . . . . Electrophilic Aromatic Substitution by R . B . Moodie . . . . . . .

Nucleophilic Aliphatic Substitution by J . Shorter . . . . . . . . . Carhations by R . A . Cox . . . . . . . . . . . . . . . . . .

Carbanions and Electrophilic Aliphatic Substitution by A . C . Knipe Elimination Reactions by R . A . More O’Ferrall . . . . . . . . . Addition Reactions: Polar Addition by P . Kdovskjl Addition Reactions: Cycloaddition by C . D . Johnson Molecular Rearrangements by A . W . Murray

. . . . . . .

. . . . . . . . . . . . . . . . .

1

23 95

157 223 285 305 323 335 357 387 411 435 479 525

Author Index. 1988 . . . . . . . . . . . . . . . . . . . . . . . . 663 Subject Index. 1988 . . . . . . . . . . . . . . . . . . . . . . . . 719

Preface The present volume, the twenty-fourth in the series, surveys research on organic reaction mechanisms described in the literature dated December 1987 to November 1988. In order to limit the size of the volume, we must necessarily exclude or restrict overlap with other publications which review specialist areas (e.g. photochemical reactions, biosynthesis, electrochemistry, organometallic chemistry, surface chemistry and heterogeneous catalysis). In order to minimize duplication, while ensuring a comprehensive coverage, the editors conduct a survey of all relevant literature and allocate publications to appropriate chapters. While a particular reference may be allocated to more than one chapter, we do assume that readers will be aware of the alternative chapters to which a border-line topic of interest may have been preferentially assigned.

There have been two changes of author since last year and we welcome Professor Pave1 KoEovsky (Czechoslovak Academy of Sciences) and Dr David Johnson (University of East Anglia) who have contributed reviews of Polar Addition and Cycloaddition, respectively. They replace Professor Arthur Fry and Dr Michael Paton whose expert contributions to this continuing series are gratefully acknow- ledged.

Once again we wish to thank the publication and production staff of John Wiley & Sons and our team of experienced contributors for their efforts to ensure that the standards of this series are sustained. We are also indebted to Dr N. Cully, who compiled the subject index.

A.C.K. W.E.W.

Organic Reaction Mechanisms 1988 Edited by A. C. Knipe and W. E. Watts 0 1990 John Wiley 8c Sons Ltd

CHAPTER 1

Reactions of Aldehydes and Ketones and their Derivatives

M.I. PAGE

Department of Chemical and Physical Sciences, Huddersfield Polytechnic

Formation and Reactions of Acetals, Ketals, and Orthoesters . . . . . . . . . . Hydrolysis and Formation of Glucosides, Nucleosides, Oxazines, a d Related . . . Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Non-enzymic Reactions . . . . . . . . . . . . . . . . . . . . . . . . Enzymic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . .

Reactions and Formation of Nitrogen Derivatives, Schiff Bases, Hydrazones, Oxhes,

C-C Bond Formation and Fission: Aldol and Related Reactions . . . . . . . . Other Addition Reactions. . . . . . . . . . . . . . . . . . . . . . . . . Enolization and Related Reactions . . . . . . . . . . . . . . . . . . . . . Hydrolysisand ReactionsofVinylEthersand Related Compounds . . . . . . . Other Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

and Related Species . . . . . . . . . . . . . . . . . . . . . . . . . . .

1

3 3 4 4

6 11 12 16 17 18

Formation and Reactions of Acetals, Ketals, and Orthoesters

Geminal oxygen atoms in acetals, hydrates, and orthoesters have a mutual stabilizing interaction which has a stereochemical component manifested in the anomeric effect. This interaction is not confined to oxygen and appears to be a general phenomenon with electronegative elements. A nice example has been demonstrat- ed with the iodination of methoxyacetone which kinetically yields the methyl- substituted product but thermodynamically gives 1-iodo-1 -methoxypropanone (1). The favourable geminal interaction is thought to stabilize the product by about 7 kcal mol-' .'

NMR analysis of solutions of trifluoropropan-Zone in the strong acid system HBr-CBr,F, shows the formation of the HBr adduct, a novel stable a-bromo- alcohol (2).*

Structure-reactivity correlations, including imbalances between estimates of reaction progress from the effect of substituents in different parts of the molecule, have been re~iewed.~

There is no detectable trapping of the oxocarbocation (3) by azide ion which indicates that the lifetime for this putative intermediate in aqueous solution is less than 5 x lo-" s. It is concluded that the hydrolysis of acetals cannot proceed through diffusionally equilibrated ions such as (3). The apparent slower rate of

1

2 Organic Reaction Mechanisms 1988

OMe OH I I

F,C-C-R I I

MeCO-C-H

Br

(1) (2)

I + +

RCH=OMe RCH=OH

(3) (4)

OR n

addition of water to protonated acetaldehyde (4) may be the result of using an erroneous pK, for the latter: The measurement of the acidity constants of the conjugate acids of very weak bases is usually based on acidity functions which are not very reliable. The pK, values of protonated carbonyl compounds may be estimated from keto-enol equilibria and their carbon acidity constants. This method calculates pK, values which are more negative than usually assumed; for example, that for acetone is - 7.1 and that for acetaldehyde is - 8.8.5

Protonation of 1,3-diphenyl-2-methylpropane- 1,3dione gives an intramolec- ularly hydrogen-bonded conjugate acid (5) which shows a 'H NMR signal at 621, A negative deuterium isotope effect is observed on the shift which is compatible with a very strong hydrogen bond!

The pathways of the breakdown of methyl hemiacetals of a-bromoacetophenone involve an acid, base, and pH-independent pathway similar to those observed for aldehyde derivatives. The Hammett p-values are reported for each step and are similar to those for hemiacetals of benzaldehyde. It is suggested that there may be some imbalance in the acid-catalysed reaction between deprotonation and C-0 bond-breaking so that the transition state is developing some protonated carbonyl character (6).'

A macromolecule containing basic and acidic residues is an effective catalyst for the dissociation of a glycoaldehyde dimer. Hemiacetal cleavage is suggested to be facilitated by complexation and general acid-base catalysis.*

Saturated acetals react up to 105-fold more slowly than a,p-unsaturated acetals with methyl vinyl ether, catalysed by boron trifluoride etherate. The Hammett p-value for substituted benaldehyde acetals is - 4.6 and the rates of reaction of the acetals correlate with the corresponding rates of acid-catalysed hydrolysis. It is assumed that the rate-limiting step is the addition of the reversibly formed alkoxy- carbocation to the vinyl ether.9

1 Reactions of Aldehydes and Ketones and their Derivatives 3

The rate of the acid-catalysed hydrolysis of benzaldehyde diethyl acetals in reverse micelles shows a non-linear dependence on acid concentration. It is suggested that the reaction takes place in the polar head-group region of the micelle but there is no satisfactory explanation for the acidity dependence.''

Tropone acetals complexed with tricarbonylchromium (7) undergo acid- catalysed hydrolysis to generate intermediate cations which are more stable than the uncomplexed alkoxytropylium ions. The heterolysis reactions are exo-stereo- specific.' I

There has been a report on further studies of the hydrolysis of 1,3-dio~olanes.'~ The cyclization of 2-cyanobenzaldehyde with alcohols to give isoindoles is both

acid- and basecatalysed. The most likely mechanism involves ring-closure of the intermediate hemiacetal @ ) . I 3

OR' RCH, +

77 0 0-

'H

(9)

CH,OAc

AcO Aco-J-&

OAc

The reactions of acetals with halogenosilanes leading to halogenoalkoxysilanes have been re~iewed.'~

Hydrolysis and Formation of Glucosides, Nucleosides, Oxazines, and Related Compounds

Non-enzymic Reactions

The mechanism of the hydroxide ion-catalysed hydrolysis of the glycosyl bond of /?-NAD+ has been reinvestigated. It is suggested that dissociative cleavage is facilitated by the ionized ribose diol anion stabilizing the oxocarbocation intermediate (9) but this does not involve epoxide formation."


The “0 kinetic isotope effect for the acidcatalysed hydrolysis of 4- nitropheny1[1-’*0]-~-g1ucopyranoside is temperature-dependent and is attributed to a change from specific to general acid catalysis as the temperature is lowered. At low temperature the reaction is general acidcatalysed by trifluoroacetate buffers and shows a temperature-dependent solvent deuterium isotope effect which, however, is lower than generally observed for acetal hydrolysis.16

The anomerization of methyl-D-glucofuranoside, but not the pyranoside, in acidic methanol is accompanied by the formation of the dimethyl acetal of D-

glucose (10) and it is suggested that this is an intermediate during anomerization.” The base-catalysed anomerization of 2,4-dinitrophenyl b-D-glucopyranoside is

suggested to proceed by nucleophilic aromatic substitution displacing the glycosyl oxyanion intermediate (11) which ring-opens and closes and then recombines with the aromatic residue.’*

The kinetics of the mutarotation of a-D-glucose catalysed by alumina with surface basicities are explained by a surface reaction mechanism. The adsorption of b-glucose is greater than that of the a-anorner~.’~

Diazomethane cleaves oligoglycosides at the sugar-aglycone linkage if the aglycone contains a suitably placed aldehyde group. The mechanism is thought to involve initial epoxide formation at the aldehyde centre followed by aglycone oxygen nucleophilic attack (12).M

Enzymic Reactions

The application of FAB mass spectrometry to biochemical reactions, including oligosaccharide processing, has been reviewed?’

Reactions and Formation of Nitrogen Derivatives, Schiff Bases, Hydrazones, Oxima, and Related Species

As expected, the inclusion of one or two water molecules in the calculations for the energetics of the addition of ammonia to formaldehyde dramatically decreases the activation energy. Linear rate-equilibrium relationships are found for substituted nucleophiles which are compared with experimental structure-activity correla- tiomZ2

The cyclization of a-alkylaminonitriles with trichloroacetaldehyde occurs from the carbinolamine adduct (13) to give novel 5-iminoo~azolidines.~~ ‘H NMR studies of the acid-catalysed hydrolysis of 2-substituted-3-methyl- 1,2-

oxazolidines show the presence of both the E and the 2 forms of the Schiff base intermediate (14). The carbinolamine intermediate may also be detected, the breakdown of which is rate-limiting.”

Aromatic aziridines add to aldehydes to give intermediate carbinolamines which lose hydroxide to generate iminium ions (15) which, in turn, undergo ring-opening by nucleophilic addition of another molecule of aziridine.’’

Schiff base formation between pyridoxal derivatives and n-hexylamine is sug-


gested to occur by rate-limiting dehydration of the carbinolamine involving intramolecular general acid catalysis.26

Two mechanisms have been suggested for the glutamate dehydrogenase- catalysed reductive amination of a-ketoglutarate. One involves the nucleophilic attack of ammonia on a covalently bound Schiff base in the enzyme-NADPH a-ketoglutarate complex and the other involves the reaction of ammonia with the carbonyl group of the a-ketoglutarate in the ternary complex. The latter mechanism is supported by a study of the rates of carbonyl oxygen isotopic exchange which occurs through the gem-diol intem~ediate.~’

The nitrogen and carbon isotope effects on the decarboxylation of glutamic acid catalysed by glutamate decarboxyiase indicate that decarboxylation and Schiff base formation are jointly rate-limiting. The enzyme-bound Schiff base formed between glutamate and pyridoxal 5’-phosphate partitions in a ratio of about 2: 1 between decarboxylation and return to reactants. Similar results are observed for the enzyme-catalysed decarboxylation of histidine.28

There has been a quantum-mechanical study of the mechanism of cis-trans isomerization in retinal-like protonated Schiff bases.29

The reactivity of electrophiles with diastereomeric Schiff bases is controlled largely by the stereochemistry of the reactant which could be explained by a chiral tight ion-pair.30

The pH-rate profile for the reaction of o-phenylenediamine with pyruvic acid is very complicated below pH 6. Initial imine formation is followed by ring-closure and proceeds by many intermediates, the ionization of which presumably affects the kinetic^.^'

The kinetics of the aminolysis of a,/?-unsaturated thioketones have been des- cribed3* and the aminolysis of 1,3-dicarbonyl compounds has been rep~rted.~’

Sodium hydrogen telluride, NaTeH, appears to act as both a nucleophile and a reducing agent. Its reaction with imines may be explained by nucleophilic addition to form a tellurium-containing intermediate which undergoes either homolysis of


the carbon-tellurium bond leading to a secondary amine or polar elimination of a primary amine, in which case the imino group is reduced to methylene through a tellurocarbonyl compound.34

The reduction of imines by rhodium hydride complexes occurs by initial coordination of the imine to both Rh atoms in the complex.3s

The base-catalysed and the glutathione transferase-catalysed reactions of glutathione and N-acetyl-p-benzoquinonimine have been compared. Aromatiza- tion is proposed to occur by glutathione anion addition to the imine followed by nucleophilic substitution on sulphur.36

The partitioning of the tetrahedral intermediates in their various protonic states has been used to explain the pH-rate profile and product ratio formed during the hydrolysis of iminocarbonates (16).38

There have been further reports on the hydrolysis of 1 ,Cbenzodiazepine drugs in acidic media.39

There have been numerous other reports on the formation, reactions, and hydrolysis of imine derivatives.40

As expected from previous studies, phenylhydrazone formation from substituted benzaldehydes shows rate-limiting formation and breakdown of the carbinolamine intermediate below pH 5 and above pH 6, respectively. Similar behaviour is also observed with formyl-1 ,&methano[ lO]annulenes and this is taken as evidence for the latter's aromatic ~haracter.~'

The electrophilic substitution reactions of dimethylhydrazones of aromatic aldehydes with trifluoroacetic anhydride generally occur on the azomethine carbon although competitive N-acylation also occurs:*

Regioselective hydrazone formation at C(2) in dehydroascorbic acid has been investigated :3

On the basis of dipole moments and bond lengths, n-n conjugation (17) occurs in oximino groups. This conjugation does not occur in 0-acylated oximes."

The tosylate of tropone oxime undergoes a novel stereoselective ring-opening reaction with secondary amines, alkoxides, and Grignard reagents to give 6- substituted all-Z-hexa-I ,3,5-triene carbonitriles. It is suggested that the initial addition of the nucleophile to C(2) occurs anti to the tosyl group which is then lost to generate the nitrene (18) which subsequently ring-opens stereospecifically !5

The reaction of the O-(2,4-dinitrophenyl)benzaldoximes with amines gives predominantly the substituted 2,4dinitroaniline as a result of aromatic nucleophilic substitution.46

It has been suggested that the electro-reduction by electron transfer of the C(7) side-chain oxime in cephalosporins is relevant to the antibacterial activity of fl-lactam antibiotic^.^'

C-C Bond Formation and Fission: Aldol and Related Reactions

The proline-catalysed intramolecular aldol reaction is enantioselective and under kinetic control. The kinetically important step involves both electrostatic and hydrogen-bond stabilization of the enamine intermediate ( 19).48

I Reactions of Aldehydes and Ketones and their Derivatives 7

Double-isotope fractionation factors indicate that the Claisen-type condensation catalysed by malate synthase proceeds by a stepwise mechanism. This is a warning against using the absence of enzyme-catalysed proton-exchange with solvent or the inversion of configuration at the nucleophilic centre as indicative of a concerted pathway for enzyme-catalysed Claisen-type ~ondensations.4~

The treatment of active methylene compounds and aldehydes with a catalytic amount of a secondary amine produces thermodynamically stable alkenes. The stereochemistry of this Knoevenagel reaction is determined by the elimination step from the adduct (20). Both steric and electronic effects are considered to be important.

The mechanism of the Knoevenagel reaction of aldehydes with carboxy active methylene compounds remains under discussion. In the presence of tertiary amines the fi-hydroxy adduct (21) can be isolated and identified and the decarboxylation of this intermediate is the rate-limiting step. With secondary amines it is thought that the hydroxy adduct pathway is in competition with a mechanism involving the formation of the bis(dia1kylamino) derivative (22) which gives only the condensation p r~duc t .~ '

0 &O-

I N-

N-

/ Ar-CH,

I

I I - H I

OH I

NR, Ar-C-C-

R-CH-CHXY COZ H

(20) (21)

C W H , &HR, 1 - /

Ph-CH-C, 'COCH,

The reaction of benzylideneacetylacetone with piperidine and morpholine involves initial Michael addition to generate the zwitterion (23) and its deprotonat- ed anion which accumulates. Decomposition of this intermediate occurs by protonation of the carbanion and C-C bond-cleavage to generate the iminium ion and finally benaldehyde as product.52

The intermediate alcohol resulting from carbanion addition to an aldehyde in a Knoevenagel-type condensation has been isolated, and its structure determined.


This has been taken as evidence that not all such condensations take place by the intermediate formation of the imine or iminium ion.53

A variety of transition state models has been proposed to account for the diverse stereochemistry observed in the aldol reaction. The relative preference for E and Z enolates to coordinate to metals in chair or twist-boat conformations in the transition states has been reviewed."

The mechanisms of metal enolate reactions in stereoselective carbon-carbon bond-forming reactions have been revieweds5 and, as usual, there have been numerous reports on selectivity in aldol reactions.%

The stereochemistry of the aldol addition of enantiomeric enolates to chiral aldehydes is largely determined by the configuration of the en01ate.~~

Theoretical calculations suggest that the syn isomer of the acetaldoxime carbanion is 2.6 kcal mol-' more stable than the anti form. Reactions of the syn form coordinated to metal ions with electrophiles can occur by prior coordination and ion-pair formation in the prod~ct.~'

The presence of alkaline earth metal ions changes the stereoselectivity in the triose aldol conden~ation.~~

The stereoselectivity observed in the aldol condensations of germanium enolates is changed by the presence of lithium halides.6D

An enolate of a carbohydrate adds to acetaldehyde with good diastereofacial selectivity on the enolate but with modest facial selectivity on the aldehyde.6'

Stereoselectivity is observed in the cyclization of hex- 1 -enitols in the presence of electrophiles.62

The ring-expansion and -contraction of a tricyclic keto-ester is thought to occur by an initial enolization reaction6'

A vinylogous reverse aldol reactionH and crossed-aldol reactions6s have been described.

It is generally agreed that the aldol reaction of metal enolates occurs through a chelated cyclic transition state, the structure of which is highly sensitive to the environment of the metal cation. However, the fluoride-catalysed aldol reaction of enol silyl ethers is presumed to occur by metal-free enolates with a non-chelated and extended transition statesM

The aldol reaction between silyl enol ethers and aldehydes occurs without a catalyst in aqueous neutral solution. This is attributed to the hydrophobic effect, but without a systematic study of the kinetics this suggestion remains ~peculative.~~

Cross aldol-type reactions of enol trimethylsilyl ethers with aldehydes and ketones are catalysed by rhodium complexes under neutral conditions.68

The reaction of tris(trimethylsilyl)silyllithium with aliphatic ketones generates intermediates which have been studied by 'H NMR.69

The formation of a silyl enol ether from the reaction of (trimethylsily1)tetracar- bonylcobalt with isobutyraldehyde occurs by initial formation of an acyltricar- bonylcobalt intermediate that oxidatively adds hydrosilane in the rate-limiting step. 'O

The Michael addition of trimethylsilyl enol ethers and enamines to hex- 1 - enopyran-3-uloses, catalysed by titanium@) gives, stereoselectively, C-glycosyl


compounds. This high selectivity is attributed to the formation of a cyclic transition ~ t a t e . ~ '

There have been other reports on the use of silyl enol ethers in the aldol reaction. 72

Good diastereoselectivity is achieved by the titanium tetrachloride-promoted cyclization of /I-dicarbonyl substrates using the intramolecular addition of allyl- silanes (24).73 Changing the chelating agent to tin(rv) chloride results in the reversal of diastereofacial selectivity and an intermolecular allyl-transfer mechanism.74

The formation of a-hydroxyamides from the titanium (IV) chloride-mediated addition of isocyanides to aldehydes and ketones shows no diastereoselectivity. If the alkyl group of the isocyanide (RNC) forms a stable cation, cyanohydrins are formed.7s

There continue to be reports of the selectivity observed in the aldol reaction using boron as the chelating agent.76

Aluminium enolates can be made to react with aldehydes and other electrophiles by the addition of copper (I) iodide.77

The rate of the Barbier reaction of benzaldehyde, n-heptyl bromide, and lithium depends strongly on the intensity of ultrasonic waves used for activating the reaction and the temperature. An unusual temperature dependence indicates that the reaction is mass-transport-controlled and that the cavitation phenomenon is not the only important factor in the activation

Sonication also improves the yield of epoxide from cyclization of the a-chloro- hydrin formed from the addition of chloromethyllithium to carbonyl

High selectivity (92:8) is observed for the non-chelated addition of ethyllithium, in the presence of boron trifluoride etherate, to acrolein dimer. In the chelation- controlled addition, using ethylcopper reagents in the presence of magnesium salts, high selectivity is also observed and both processes produce better stereoselectivity than that obtained with titanium reagents.*'

Organolithium reagents complexed with axially chiral biphenyl-substituted N,N,iV',N'-tetramethylethylenediamines add to aldehydes in good enantiofacial selectivity. The pattern of the stereoselection, however, is not in agreement with that of the helical choice observed for the asymmetric polymerization of triphenyl- methyl methacrylate with the same complexes.8'

Exceptionally bulky organoaluminium reagents in combination with carbon nucleophiles such as organolithiums or Grignard reagents generate amphiphilic reaction systems which can give unusual equatorial and anti-Cram selectivity in carbonyl alkylations. This is attributed to nucleophilic addition of the organometallic to an electrophilically activated carbonyl substrate.82

The role of electron transfer in the reactions of Grignard reagents with ketones has been reviewed. It is concluded that it is unnecessary to invoke extensive cage reactions in these systems or implausibly long lifetimes for cage species to explain the product yields and di~tribution.~~

The alkylation of pentane-2,4-dione through its cobalt(1r) complex proceeds by a non-radical chain mechanism initiated by an electron-transfer step induced by the metal ion.@


The rates of the sodium methoxide-catalysed condensation of substituted aromatic aldehydes with phenylacetonitrile are correlated by the Taft-Pavelich equation which takes into account by polar and steric effects.“’

The rate of the base-catalysed addition of aldehydes and ketones to acrylonitrile and acrylate esters is enhanced by high pressures.86

The fulvene anion (25) adds to aldehydes to give the exocyclic product under kinetic control, which is rationalized as a frontier-orbitalcontrolled process.87

Carbanion addition to 4-t-butylcyclohexanone in liquid ammonia occurs with axial attack when steric factors are small. Equatorial addition occurs when the enolate structure of the carbanion causes unfavourable steric interactions.88

There have been many publications concerned with diastereoselectivity in the addition of carbanions to carbonyl gr0ups.8~

The condensation of aryl bromides with 1 ,Zdiketone monoketal enolates produces benzocyclobutenols (26). Under basic conditions these derivatives may be hydrolysed to benzocyclenediones whereas under acidic conditions indanones are formed from a 1 ,Zshift involving ring-expansion and -contraction.g0

The commonly accepted mechanism for the thiazolium-catalysed benzoin condensation has been questioned. It is suggested that the thiazolium carbanion adds to undissociated salt to form a dimer (27) and that this enamine type adds to the carbonyl carbon.”

Salt effects on the rate of the cyanide-catalysed benzoin condensation have been used to support the suggested importance of hydrophobic effectsY2

The decomposition of the oxaphosphetane intermediate in the Wittig reaction has been studied by NMR under conditions where rates of formation and breakdown are similar. A significant carbon isotope effect at the carbonyl carbon excludes an electron-transfer rnechani~m.9~

The addition of pentamethyl- 1,3,2-dioxaphospholane to benzaldehyde gives an oxaphosphirane which can be


Sterically crowded allylic tributylphosphorus ylides react with aldehydes to give E alkenes with > 92% stereoselectivity. As the steric demands of the ylide are decreased, high selectivity is only obtained by using bulky aldehydes.”

Ylide anions (28) are analogues of phosphoryl-stabilized carbanions and react with benzaldehyde to give stilbenes with E-stereo~electivity.~~

Trialkyl phosphites react with a-halogenoacetophenones to give vinyl phosphites, a-hydroxyphosphonate, and acetophenone. It is suggested that all products result from a common betaine intermediate (29) resulting from phosphorus attack on the carbonyl ~arbon.~’

The intramolecular addition of a primary radical to an aldehyde to give a cycloakanoxyl radical is an irreversible process. This reaction is highly efficient and can compete with the ring-closure of a 5-hexenyl radical.’*

Deprotonation of a-chloroketimines generates anions which add to aldehydes .and ketones to give epoxides in a novel Darzens-type condensation.%

Other Addition Reactions

There has been an interesting review on the influence of water structure on reactions of carbonyl compounds.’”O

Rate and equilibrium constants for the enolization and hydration of 9-formyl- fluorene have been reported. The commonly appreciated effect of geminal oxygens on stabilization is well known through the anomeric effect but it is also manifested in the stability of carbonyl hydrates. The geminal stabilization in carbonyl hydrates is estimated to be 10” times greater than that in cyanohydrins”’ (see also p.1).

Within a restricted series, the nucleophilicity of nucleophiles towards carbonyl compounds correlates with the vertical ionization potential of the nucleophile. This may be interpreted to mean that an important aspect of the activation process is the total deformation associated with the single-electron switch from the nucleophile to the carbonyl group.”’

The potential-energy surfaces calculated for the hydration of formaldehyde using modified molecular-mechanics techniques are qualitatively similar to those obtained from ab initio methods.Io3

Theoretical studies on the water and hydroxide-ion addition to formaldehyde have been compared with that to ethene.IM

Theoretical calculations have usually indicated that, in the gas phase, there are no potential-energy maxima during the addition of anionic nucleophiles to carbonyl groups. However, if diffuse functions are included in the calculations, a local energy maximum is introduced which is sensitive to the choice of basis set.los

Theoretical calculations have also been used to support the idea of nitrogen lone-pairs facilitating hydride expulsion if they are antiperiplanar to the hydrogen bond which is broken. However, electron-correlation effects need to be included in the description of stereo-electronic effects.IM

The face selectivity observed in the addition of nucleophiles to the sterically unbiased 5-substituted adamantan-2-ones has been further investigated. Selectivity is for the syn face if the substituent is electron-withdrawing and for the anti face


if it is an electron donor. However, the selectivity may also be a function of the nature of the nu~leophi le .~~~

The stereoselectivity observed in the reduction of chiral acyclic ketones with hydride reducing agents can be correlated with a semi-empirical scale for the effective size of the reagent.Io8

Reduction of acyclic ketones initiated by electron-transfer processes produces the anti-Cram isomer preferentially.'@

The stereoselectivity of lithium aluminium hydride reductions of benzocyclohept- enones can be correctly predicted by MM2 calculations and by Felkin's torsional strain model."o

Alkali metal-ammonia reductions of enolizable ketones with a remote double bond give 1 : 1 mixtures of the corresponding enolate and alcoholate by the dis- proportionation of the radical anion intermediates and not by the previously proposed dianions."

Catalysts of the type Rh(diphosphite)+ convert 4-pentenals to cyclopentanones by intramolecular cyclization. The nett process involves the addition of the aldehyde hydrogen and the carbonyl carbon to the double bond and both of these steps are rapid and reversible. The rate-limiting step is the irreversible reductive elimination from a metallocyclohexanone to produce cyclopentanone.'

The reduction of aromatic aldehydes by benzeneselenol takes place only in the presence of oxygen. The free-radical mechanism is thought to involve the intermediate formation of a ~elenohemiacetal."~

Aldehyde dehydrogenase can catalyse the hydrolysis of esters as well as oxidize aldehydes to acids. Although both activities appear to involve a catalytically active cysteine residue there are two distinct active sites, one of which can bind aldehydes but both of which can bind and catalyse the hydrolysis of ester^."^

The use of isotope effects in enzyme-catalysed reactions, including dehyd- rogenases, has been reviewed."*

The intermediates formed during the reaction of pyrrole with formaldehyde have been studied using I3C NMR.lI6 2-Chloro-3-formylindoles react with azide ion to give 5-azido-3-cyanoindoles.

Initial displacement of chloride by azide is followed by loss of nitrogen and ring-opening to give the enolate anion (30). Azide addition to (30) is followed by ring-closure to give the product.Il7

Neighbouring carbonyl groups participate in the reactions of 2-chlorobenz- imidazoles displacing the chloride."'

Catalytic thermometric titrimetry has been applied to a study of condensation and rearrangement reactions of carbonyl compound^."^

Enolization and Related Reactions

Enols and their reactions have become very fashionable and 1988 has seen a plethora of papers published.

Many enols have been shown to be stable enough for analysis by standard spectroscopic techniques and their generation, structure, and thermodynamic and


kinetic stability have been described by Capon.'20 The chemistry of sterically crowded stable enols has also been reviewed. ''I

Some simple enols have been shown to be stable in aprotic solvents. For example, 2-methylprop-I-en-1-01 (31) has a half-life of greater than 24 hours at 25OC. Large deuterium solvent isotope effects in protic solvents are compatible with rate-limiting protonation of the

The effect of a conjugated phenyl group on enol and enolate ion stability has been examined with 2-indanone (32). Compared with acetone, the phenyl group increases carbon acidity by seven orders of magnitude and enol stability by over four orders of magnitude. The acyclic analogue, phenylacetone, displays the phenyl effect to a much smaller degree.'23

The keto-enol equilibrium constant and the acidity constants for diphenylacetaldehyde have been compared with those for sterically hindered systems. The value for pKE is 0.98 and the pK, acidity constants are 10.4 for CH ionization of the keto form and 9.4 for OH ionization of the enol, The increased stability of the enol tautomer is attributed to stabilization by the phenyl groups.'"

Both geometrical isomers of the simple enol, I-hydroxybutadiene, have been produced from silylated precursors. The ketonization gives a mixture of E-2- butenol and 3-butenol the proportions of which vary with pH. It is suggested that transmission of positive charge to the oxygen in the transition state for protonation at the 4-position is more efficient with the E-enol (33). There is no evidence for intramolecular proton transfer for the spontaneous ketonization of the Z-en01.I~'

As silicon is less electronegative than carbon, replacing a CH, by a SiH3 group may be expected to decrease the amount of enol formed in ketones. However, a-silyl substitution destabilizes carbenium ions relative to methyl and, in fact, the first silicon-substituted simple enol(34) has been prepared and found to be a stable solid at room temperature.L26

0-

dCN I yo"

R

OH H\ / ,c=c\ '€4

CH2=C H ,SiMe,

\ Me?

Mes \OH

(34)

,c=c

(33)

14 Organic Reaction Mechanisms I988

Heats of formation, proton affinities, and kinetic stabilities of simple enols in the gas phase have also been reported.”’

Homoenolization in bicyclic ketones, in which the carbonyl is a to a bridgehead position, occurs most readily when cyclohexanone structures can adopt a chair conformation. The decreased reactivity in ketones unable to adopt this conformation is very dependent on the relative orientation of the methano bridge carbon and the carbonyl group.12*

There is a linear relationship between the ”C NMR chemical shifts of the CH enol and the CH2 keto carbons in the tautomeric forms of 1,3-diketone~,’~’ and the keto-enol equilibrium constants may be correlated with the enolic methine coupling constant and are rationalized by substituent effect^.'^'

Unexpectedly, the stabilizing effect of a 1-pyridinio group on the enol is about 10-fold smaller than that of a phenyl group in a-substituted acetophenones. However, the enol content of (2-pyridy1)acetophenone is unusually large (pK, = 2.0) which is attributed to intramolecular hydrogen bonding (35).13’ By contrast, it is claimed that the almost exclusive tautomer of 2-keto-methylquinol- ines is the enaminone form (36). The only exception to this generalization is when R2 is rneth~1.l~~

The tautomeric equilibrium of Cphenylazo- 1 -naphthol favours the hydrazone form (37) by adding water to organic solvents and by applying pressure. There is not a good correlation of the equilibrium constants using Kirkwood-type equation^.'^.' This tautomeric equilibrium has also been studied theoretically, and spectroscopically.‘”

Tautomerism in the dihydropyrimidine system has been investigated as a function of substituents at the 2- and 5-po~itions.’~~

NHPh

I H

H 1 P-

CH?=C ‘Ph

(39)


Keto-enol tautomerism in B-keto-esters has been studied by 'H NMR in different solvents. In ortho-substituted benzoyl derivatives the equilibrium varies in a complex manner. For example, halogen substituents cause an increase in enol content but the degree of enolization is not dependent on resonance effects.'36

The photolysis of o-phthalaldehyde in a nitrogen matrix gives the E-enol(38).'37 Intramolecular proton transfer in o-hydroxybenzaldehyde in the gas phase

depends on the electronic state such that it occurs in the 'enol' tautomer (39) but not in the ground or other excited states.'38 The rate of the uncatalysed return to the ground state shows an unusual temperature dependence which is attributed to only the hydrogen-bonded tautomer (39) undergoing proton transfer.'3s*i39

The enol form of acetophenone can be generated from the photo-hydration of phenylacetylene and its rate of ketonization studied as a function of buffers and pH. The Brcansted a-value for the general acid-catalysed ketonization of the enol and enolate anion are 0.50 and 0.32, respectively. The uncatalysed water reaction of the enol proceeds by a stepwise rate-limiting protonation of the enolate ion by the hydronium ion (40) rather than a concerted cyclic process.'"

The ketonization of dienols unable to undergo an intramolecular 1,5-sigmatropic hydrogen shift proceeds at a slower rate.I4'

The rates of enolization of the dienones (41) are catalysed by a-cyclodextrin but the extent of catalysis is little affected by the nature of the substituent. It is suggested that debromination may occur by bromide complexed to a-cyclodextrin acting on the free uncomplexed d i e n ~ n e . ' ~ ~

The enolization of 2-decalones occurs predominantly in the direction predicted from work on steroidal ketones. However, non-steroidally locked cis-2-decalones with an angular methyl group enolize in the direction opposite to that predicted.'"

The rate of enolization of cyclohexanone at high temperatures and oxygen pressures is faster than the rate of oxidation, which supports the proposed inter- mediacy of enols during the oxidation of ketones. It is suggested that oxygen forms a transitory adduct with two enolates of cyclohexanone which then undergoes reversible oxygen-oxygen cleavage.'"

The rates of epimerization of ketones incorporated into amphiphilic ketone diastereoisomers show no diastereoselectivity below the CMC (critical micelle concentration) where rates of equilibration are rapid. Above the CMC rates are slower and the meso diastereomer is favo~red.'~'

There has been a theoretical study of the deprotonation of acetaldehyde with a variety of bases.'&

Since accurate values for the equilibrium constants for enolization are now known from methods using flash photolysis to generate the enols, reliable rate constants from the reaction of halogens with enols can be calculated. Although these rate constants are very large, 1-5 x lo9 M-' s - ' , they are less than some other values known for reactions involving halogens. It is therefore likely that the enol reactions are not completely diffusion-controlled especially since the rate constants increase as substituents become more electron-re1ea~ing.I~'

The rate of halogenation of amino-ketones is enhanced because of either intramolecular general base catalysis by the amino group, which reaches a maximum


efficiency with the b-amino-ketone corresponding to a six-membered ring in the transition state, or electrostatic stabilization by N-protonated or N-methylated derivatives of the incipient enolate anion (42), which is marked for a- and !-amino- ketones.I4

The iodination of acetophenone by iodine(m) tris(trifluoroacetate) gives both a-halogenated and aromatic ring-substituted products. The ratio of products is very dependent on solvent and aromatic ring ~ubstituent.’~~ There has also been another report on the acid-catalysed iodination of acetophenone.’”

The nitrosation of ketones to give nitroso-ketones or -oximes, in the presence of high concentrations of anions, proceeds by rate-limiting formation of the enol which is then nitrosated. With a low concentration of added anion, such as chloride, the rate-limiting step becomes the electrophilic addition of the nitrosating species to the carbon-carbon double bond of the enol(43),”’

The enolate of dimedone undergoes nitrosation in dilute aqueous acid at a rate which is limited by the diffusion-controlled encounter with the nitrosating species.15*

Cresols and 2-naphthol react with nitrogen dioxide to give nitrocyclohexadien- ones and nitrophenols. The keto tautomers of the nitrophenols (44) are the first-formed products which rapidly tautomerize to the nitrophen01.I~’

There have been some other studies of keto-enol tautomerism.’”

Hydrolysis and Reactions of Vinyl Ethers and Related Compounds

As expected, the rate of intramolecular general acid-catalysed hydrolysis of the vinyl ether in prostacyclin is significantly reduced by the introduction of an additional methylene group between the vinyl ether and the carboxyl groups.’55 Similarly, vinyl ethers with a carboxylic acid residue which is geometrically inhibit- ed from acting as an intramolecular general acid do not show an enhanced rate of hydrolysis.Is6 The slight variation in the small effective molarities observed for the intramolecular general acid-catalysed hydrolysis of vinyl ethers has been discussed without reference to differences in conformational entropy or strain effects.’”

The reaction of phenol with the vinyl ether, 3,4-dihydro-2H-pyran, results in selective ortho-substitution. The reaction proceeds in the absence of a catalyst and is thought to occur by an ene-type mechanism.’”

I Reactions of Aldehydes and Ketones and their Derivatives 17

The reactions of aroyl chlorides with vinyl ethers in the presence of a palladium catalyst and an amine base give fl-arylvinyl ethers."'

The preparation of cyclic silylated vinyl ethers has been described.'@ Trimethyl- silyl ketone acetals react with benzoyl cyanide via a six-membered cyclic transition state to give trimethylsilyl-fl-benzoyl-8-iminopropionates but in the presence of a Lewis acid the product is the corresponding or-benzoylcarboxylate.'6'

There has been a report on the acid-catalysed cyclization and hydrolysis of a y-hydroxyalkylketene dithioacetal.'62

Other Reactions

The degree of aromaticity in cyclopropenone is controversial but the "0 NMR spectrum indicates a highly shielded oxygen consistent with a negative charge on oxygen. Also compatible with a delocalized system, cyclopropenone undergoes isotopic oxygen exchange very slowly.163

If one of the carbonyl groups of a diketone, with a plane of symmetry in the ground state, is excited the excited state is chiral because of the out-of-plane geometry of one of the carbonyl groups.'"

The gas-phase reaction of hydroxy radicals with ketones is thought to proceed by the formation of a cyclic transition state involving coordination of the OH to carbonyl oxygen and a P-CH.I6'

a-Hydroxy-P-diketones rearrange, in the presence of base, to a-ketal esters and this could occur by intermediate epoxide formation or by a benzilic acid type of rearrangement. The equilibration between the anions (45) has been shown by generating the anion (46) from a-ketol esters.'"

0 0-0 0 0 II II -c-0-c-c- I I I II -c-c-c-

I I

The rearrangement of t-butyl phenyl ketone to 3-methyl-3-phenylbutan-2-one with aluminium chloride proceeds by the initial formation of a 1 : 1 complex which then gives the kinetically reactive reactant: AICI, complex of stoicheiometry 2: 5.'67

The kinetics of the bromate oxidation of oximes have been reported.'68 There has been a report of the peroxomonosulphate oxidation of ben~aldehyde.'~'

The thiophilic reactions of thiocarbonyl compounds with C- and S-nucleophiles have been reviewed.17'

A novel method for the preparation of unstable seleno- and thio-aldehydes has been reported.'"

The initial reaction of sulphur ylides with elemental sulphur gives thiocarbonyl compounds which then react with the starting ylides to give episulphides."*

The reaction of 2-hydroxyacetophenone with excess thionyl chloride in the presence of a catalytic amount of pyridine gives a thiirane. The proposed mecha-

18 Organic Reaction Mechanisms I988

nism involves the chlorination of phenol with thionyl chloride although this has never been 0b~erved.l~~

Allylic and homoallylic esters of the labile thioaldehyde, thioxoacetic acid, undergo intramolecular ‘ene’ reactions with C-C bond formation.’”

References I More OFerrall, R. A., and Murray, B. A., J. Chem. SOC., Chem. Commun.. 1988, 1098. * Clark, D. R., Emsley, J., and Hibbert, F., J. Chem. Soc., Perkin Trans. 2, 1988, 1107.

’ Toullec, J., Terrahedron Lerr., 29, 5541 (1988).

’ Sorenson, P. E., Logager, T., Kanagasabapathy, V. M., and McClelland, R. A., Bull. SOC. Chim.

’ Von der Bruggen, V., Lammers, R., and Mayr, H., J. Org. Chem., 53, 2920. lo Boyer, B., Kalfat. R.. Lamaty, G., and Roque, J. P., J . Chem. Soc., Perkin Trans. 2, 1988, 1325. I‘ Leckey, N. T., Watts, W. E., Bunton, C. A., and Moffatt, J. R., J. Chem. SOC.. Perkin Trans. 2,1988,

1909. l2 Kiyooka, S., Arita, H., Fujiyama, R. and Suzuki, K., Kochi Diagaku Rigakubu Kiyo Kagaku 8,35

(1987); Chem. A h . . 108, 130941 (1988). Sato, R., Ohmori, M., Kaitani, F., Kurosawa, A., Senzaki, T., Goto, T.. and Saito, M.. Bull. Chem. SOC. Jpn, 61, 2481 (1988).

I4 Musavirov, R. S., Nedogrey, E. P., Syraeva, I. N., Kantor, E. A., and Rakhmankulov, D. L., J. Organomer. Chem., 350, 139 (1988).

I s Johnson, R. W., Marschner. T. M., and Oppenheimer, N. J., J. Am. Chem. Soc.. 110,2257 (1988). l6 Bennett, A., Davis, A. J., Hosie, L., and Sinnott, M. L., J. Chem. Soc., Perkin Trans. 2, 1987, 581. I’ Kacmarek, J. and Szafranek, J., Finn. Chem. l a r r . , 14, 171 (1987). Is Berven, L. A., Dolphin, D. H., and Withers, S. , G., J. Am. Chem. Soc., 110,4864 (1988). l9 Ozawa, S., Nakatani, J., Sato, M., and Ogino, Y. , Bull. Chem. SOC. Jpn, 60,4273 (1987). 2o Higuchi, R., Tokimitsu, Y., and Komori, T., Liebigs Ann. Chem., 1988,249. 2’ Caprioli, R. M., Biochemisrry. 27, 513 (1988). 22 Williams, I. H., Bull. Soe. Chim., Fr. 11, 1988, 1126. 23 Lasperas, M., Taillades, J., and Commeyras, A.. Nouv. J . Chim., 12, 147 ” Parkkinen, A.. MaHinen, J., Lonnberg, H., and Pihlaja, K., J. Chem. SOC., Perkin Trans. 2, 1988,

*’ Shtelzer, S., Sheradsky, T., and Blum, J., J. Heterocycl. Chem., 24, 1581. 26 Vazquez, M. A., Donoso, J., Munoz, F., Garcia Blanco, F., Garcia del Vado, M. A., and

2’ Srinivasan, R., Viswanathan, T. S., and Fisher, H. T., J. Biol. Chem.. 263, 2304 (1988). 28 Abell, L. M. and OLeary, M. H.. Biochemistry, 27, 3325, 5927 (1988). 29 Dormans, G. J. M., Groenenboom, G. C., Van Dorst, W. C. A., and Buck, H. M., J. Am. Chem.

10 El Achqar, A., Roumestant. M. L.. and Vialltfont, P., Tetrahedron Letr.. 29, 2441 (1981).

Jencks, W. P., Bull. SOC. Chim. Fr. II, 1988,218. Amyes, T. L., and Jencks, W. P., J. Am. Chem. SOC., 110, 3677 (1988).

Clark, D. R., Emsley, J., and Hibbert, F., J. Chem. SOC., Chem. Commun., 1988, 1252.

Fr. 11, 1988, 313. Wolfe, J., Nemeth, D., Costero, A., and Rebek, J., J. Am. Chem. SOC.. 110, 983 (1988).

827.

Echevarria, G., Bull. SOC. Chim., Fr. 11, 1988, 361.

Soc., 110, 1406 (1988).

Abasolo, M. I., Gaona, C. H., and Femandez. B. M., J. Heterocycl. Chem., 24, 1771 (1987). Vsov. V. A., Timokhina. L. V.. Turchaninov, V. K., Taryashinova, D. S., and Voronokov, M. G., Zh. Org. Khim.. 23, 1221 (1987); Chem. Abs., 108. 111488 (1988). Kozlov, A. P., Ryabova, V. V., and Andreichikov, Yu, S. , Zh. Org. Khim., 23, 1665 (1987); Chem. A h . , 108, 111511 (1988). Barton, D. H. R., Bohe, L., and Lusinchi, X . , Tetrahedron Len., 29, 2571 (1988).

” Fryzuk, M. D. and Piers, W. E., Organomerallics, 7, 2062 (1988). l6 Coles, B., Wilson, I., Wardman, P., Hinson, J. A., Nelson, S. D.. and Ketterer, B., Arch. Biochem.

” Habib, A. M., Issa, R. M., Etaiw, S. H., and El-Fass, M., Egypt J . Chem., 28.29 (1985); Chem. Abs.,

38 Katzhendler, J., Goldblum, A., and Ringel, I., J . Chem. Soc., Perkin Trans. 2. 1988, 1653.

Biophys.. 264, 253 (1988).

107, 325728 (1987).

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