Comprehensive Organic Functional Group Transformations, Volume 3 (Synthesis:Carbon with One Heteroatom Attached by a Multiple Bond)

850 Pages·2003·9.07 MB·English

by  Alan R. Katritzky, Otto Meth-Cohn, and Charles W. Rees (Editors-in-Chief)

Comprehensive Organic Functional
Group Transformations, Volume 3
Elsevier, 2003

Editors-in-Chief: Alan R. Katritzky, Otho Meth-Cohn, and Charles W. Rees

Synthesis: Carbon with One Heteroatom Attached by a
Multiple Bond

Part I: Tricoordinated Carbon Functions, R2C=Y
3.01 Aldehydes: Alkyl Aldehydes, Pages 1-52, Kevin E. B. Parkes and Stewart
K. Richardson
3.02 Aldehydes: α,β-Unsaturated Aldehydes, Pages 53-79, Warren J. Ebenezer
and Paul Wight
3.03 Aldehydes: Aryl and Heteroaryl Aldehydes, Pages 81-109, Gregory J.
Hollingworth
3.04 Ketones: Dialkyl Ketones, Pages 111-204, Kevin E. B. Parkes and Stewart
K. Richardson
3.05 Ketones: α,β-Unsaturated Ketones, Pages 205-276, Warren J. Ebenezer
and Paul Wight
3.06 Ketones Bearing an α,β-Aryl or -Hetaryl Substituent, Pages 277-312,
Daryl S. Walter
3.07 Aldehyde and Ketone Functions Further Substituted on Oxygen, Pages
313-327, Donald A. Whiting
3.08 Thioaldehydes and Thioketones, Pages 329-380, William G. Whittingham

3.09 Seleno- and Telluroaldehydes and -ketones, Pages 381-401, Frank S.
Guziec and Lynn J. Guziec
3.10 Imines and Their N-Substituted Derivatives: NH, NR and N-Haloimines,
Pages 403-423, Graeme M. Robertson
3.11 Imines and their N-Substituted Derivatives: Oximes and their O-R
Substituted Analogues, Pages 425-441, Graeme M. Robertson
3.12 Imines and Their N-Substituted Derivatives: Hydrazones and Other =NN
Derivatives Including Diazo Compounds, Pages 443-490, J. Stephen Clark
3.13 Synthesis of P, As, Sb and Bi Ylides (R3P=CR2, etc.), Pages 491-500, by kmno4
Éamonn J. Coyne and Declan G. Gilheany
3.14 Doubly Bonded Metalloid Functions (Si, Ge, B), Pages 501-505, Tao Ye
and M. Anthony McKervey
3.15 Doubly Bonded Metal Functions, Pages 507-523, Tao Ye and M. Anthony
McKervey

Part II: Dicoordinated Carbon Functions, R2C=C=Y

3.16 Ketenes, their Cumulene Analogues and their S, Se and Te Analogues,
Pages 525-554, David C. Harrowven and Shelagh T. Dennison
3.17 Ketenimines and Their P, As, Sb, and Bi Analogues, Pages 555-610,
Joseph P. Michael and Charles B. De Koning

Part III: Dicoordinated Carbon Functions, R C Z

3.18 Nitriles: General Methods and Aliphatic Nitriles, Pages 611-640, Michael
North
3.19 α,β-Unsaturated and Aryl Nitriles, Pages 641-676, Milton J. Kiefel

3.20 N-Substituted Nitriles and Other Heteroanalogues of Nitriles of the Type
RCZ, Pages 677-692, R. Michael Paton

Part IV: Monocoordinated Carbon Functions

3.21 Isocyanides and their Heteroanalogues (RZC), Pages 693-726,
Ian A. O’Neil
3.22 References to Volume 3, Pages 727-856

by kmno4
3.01
Aldehydes: Alkyl Aldehydes
KEVIN E. B. PARKES
Roche Products Ltd., Welwyn Garden City, UK
and
STEWART K. RICHARDSON
University of Notre Dame, IN, USA
2[90[0 SATURATED UNSUBSTITUTED ALDEHYDES 1
2[90[0[0 From Alkanes 1
2[90[0[1 From Alkenes 1
2[90[0[2 From Alkynes 2
2[90[0[3 From Halides 2
2[90[0[4 From Alcohols and their Derivatives 2
2[90[0[4[0 By oxidation of primary alcohols 2
2[90[0[4[1 From diols 6
2[90[0[4[2 Oxidation of alcohol derivatives 7
2[90[0[4[3 Rearran‘ement of allylic alcohols 7
2[90[0[5 From Epoxides 8
2[90[0[6 From Acetals\ Enol Ethers and Enol Esters 8
2[90[0[7 From Aldehydes or Ketones 09
2[90[0[7[0 From saturated aldehydes or ketones 09
2[90[0[7[1 From unsaturated aldehydes 01
2[90[0[7[2 From a!functionalized aldehydes 01
2[90[0[8 From Carboxylic Acids and their Derivatives 02
2[90[0[8[0 Reaction of carbon nucleophiles with acids and their derivatives 02
2[90[0[8[1 Formylation reactions 03
2[90[0[8[2 Other preparations from acids and acid derivatives 04
2[90[0[09 From Sulfur!containin‘ or Other Lower!Chalco‘en!Containin‘ Precursors 04
2[90[0[00 From Nitro‘en!containin‘ Precursors 06
2[90[0[00[0 From amines 06
2[90[0[00[1 From oximes\ hydrazones and their derivatives 07
2[90[0[00[2 From nitroalkanes 07
2[90[0[01 From Or‘anosilanes 07
2[90[0[02 From Or‘anoboranes 08
2[90[0[03 Methods Involvin‘ Umpolun‘ 08
2[90[0[03[0 Formyl anion equivalents 19
2[90[0[03[1 Other anion equivalents 19
2[90[1 b AND MORE REMOTELY UNSATURATED ALDEHYDES 10
2[90[1[0 Alkyl Aldehydes with One Double Bond 10
2[90[1[0[0 From aldehydes 10
2[90[1[0[1 Preparations involvin‘ rearran‘ements 10
2[90[1[0[2 Other preparations 12
2[90[1[1 Alkyl Aldehydes with More than One Double Bond 13
2[90[1[2 Alkyl Aldehydes with Aryl or Hetaryl Substituents 13
2[90[1[2[0 From aldehydes 13
2[90[1[2[1 Other preparations 13
0
1 Alkyl Aldehydes
2[90[1[3 Alkynyl!Substituted Alkyl Aldehydes 14
2[90[1[3[0 Fra‘mentation reactions 14
2[90[2 HALOALKYL ALDEHYDES "a\ b AND MORE REMOTE HALOGEN# 15
2[90[2[0 Introduction 15
2[90[2[1 From Stable Enol Derivatives and Enamines 15
2[90[2[2 From Aldehydes 15
2[90[2[3 Miscellaneous Preparations 16
2[90[2[3[0 Functional ‘roup transformations 16
2[90[2[3[1 Carbon0carbon bond!formin‘ methods 16
2[90[3 ALDEHYDES BEARING AN OXYGEN FUNCTION 17
2[90[3[0 OH!functionalized Aldehydes 17
2[90[3[0[0 a!OH!functionalized aldehydes 17
2[90[3[0[1 b! and more remotely functionalized OH aldehydes 20
2[90[3[1 OR!functionalized Aldehydes 20
2[90[3[2 OX!functionalized Aldehydes 22
2[90[4 ALDEHYDES BEARING A SULFUR FUNCTION 23
2[90[4[0 SH! and SR!functionalized Aldehydes 23
2[90[4[1 Hi‘her!coordinated Sulfur!functionalized Aldehydes 26
2[90[5 ALDEHYDES BEARING A SELENIUM OR TELLURIUM FUNCTION 26
2[90[5[0 SeH!\ TeH!\ SeR! or TeR!functionalized Aldehydes 26
2[90[6 ALDEHYDES BEARING A NITROGEN FUNCTION 28
2[90[6[0 NH1!\ NHR! and NR1!functionalized Aldehydes 28
2[90[6[0[0 a!NH1!\ NHR! and NR1!functionalized aldehydes 28
2[90[6[0[1 b! and more remotely NH1!\ NHR! and NR1!functionalized aldehydes 33
2[90[6[1 NHX! and NX1!functionalized Aldehydes 35
2[90[6[2 NY!functionalized Aldehydes 35
2[90[7 ALDEHYDES BEARING A PHOSPHORUS\ ARSENIC\ ANTIMONY OR
BISMUTH FUNCTION 37
�
2[90[7[0 XR1\ X R2!functionalized Aldehydes 37
2[90[7[1 Hi‘her!coordinated Phosphorus!\ Arsenic!\ Antimony! or Bismuth!functionalized Aldehydes 38
2[90[8 ALDEHYDES BEARING A METALLOID FUNCTION 40
2[90[8[0 Silicon!functionalized Aldehydes*a!silyl Aldehydes 40
2[90[8[0[0 From alcohols 40
2[90[8[0[1 From aldehydes or ketones 40
2[90[8[1 b!Silyl Aldehydes 41
2[90[0 SATURATED UNSUBSTITUTED ALDEHYDES
2[90[0[0 From Alkanes
No synthetically useful methods of oxidizing totally unactivated methyl groups to aldehydes have
been reported\ although in view of the relatively high reactivity of aldehydes under oxidizing
conditions this is perhaps not surprising[
2[90[0[1 From Alkenes
Although many oxidants will cleave alkenes to aldehydes\ relatively few do so cleanly or in high
yield\ the most important and well!established exception being ozone �B!58MI 290!90�[ In cases where
ozone is not employed\ the conversion is generally achieved via the 0\1!diol by osmium"VIII# oxide!
mediated hydroxylation\ followed by periodate\ or lead"IV# acetate\ cleavage[ Isolation of the diol
intermediate is not necessary\ and hydroxylation and cleavage can be achieved in a single pot by a
mixture of osmium"VIII# oxide and sodium periodate �45JOC367�[ The cleavage can also be achieved
using potassium manganate"VIII# under phase transfer conditions with careful control of pH
�68CL332�[
Several methods have been developed for the homologative conversion of alkenes into aldehydes[
Probably the most important of these methods\ and certainly the most important industrially\ is the
hydroformylation\ or OXO reaction\ in which the alkene is treated with a mixture of hydrogen and
Saturated Unsubstituted 2
carbon monoxide in the presence of a cobalt\ rhodium or ruthenium catalyst �80COMC!I"3#802�[ In
general\ the order of reactivity is terminal alkene�straight chain internal alkene�branched alkene\
with the formyl group being delivered to the least hindered end\ although with highly polarized
alkenes\ formylation occurs at the more electron!de_cient carbon atom[ The reaction tolerates most
functional groups\ although halides usually interfere[ Recent developments include low!temperature
hydroformylation catalysts "�49>C# �67BCJ2905�\ polymer!bound ruthenium hydroformylation
catalysts �70JOC0890�\ and asymmetric versions of the reaction\ which in favourable cases give
enantiomeric excesses of over 79) "Equation "0## �76JA6011�[
H
CHO
H2, CO, SnCl2
(1)
60% conversion
78% ee
2[90[0[2 From Alkynes
Alkynes may be converted into aldehydes by hydroboration and oxidation of intermediate
vinylboranes[ Although diborane and many simple mono! and dialkylboranes give very poor
regioselectivity in the hydroboration\ excellent results can be obtained with either dimesitylborane
�72TL0322� or the thexyliodoborane�dimethyl sul_de complex �82TL4002�\ followed by a con!
ventional basic hydrogen peroxide workup "Equation "1##[
i, BHI•Me2S O O
Bun + (2)
n
– Bu n
ii, H2O2, OH Bu
99.0 : 1.0
2[90[0[3 From Halides
Primary alkyl halides may be oxidized to aldehydes by treatment with N!oxides or sulfoxides at
high temperatures in a reaction initially developed by Kornblum\ and which involves a nucleophilic
displacement of the halide as a _rst step[ Most subsequent work has concentrated on developing
modi_ed oxide reagents which may be used under less vigorous conditions^ reagents include
3!dimethylaminopyridine N!oxide in the presence of 0\4!diazabicyclo�4[3[9�undec!4!ene "dbu#
�70BCJ1110�\ a variety of pyridone N!oxide reagents �68JCS"P0#1382�\ and DMSO in the presence of
sodium hydrogen carbonate and sodium iodide �75SC0232� "Equation "2##[ The conversion may also
be achieved with more conventional oxidizing agents including tetrabutylammonium periodate
�75SC32�\ tetrabutylammonium dichromate �68CI"L#102� and iodine penta~uoride �66S308�[
0!Haloalkenes may be hydrolysed to aldehydes using mercury"II# acetate in formic acid �65BSF0830�[
Ph Ph
DMSO, NaI
O O
(3)
Br O
O 60% O
2[90[0[4 From Alcohols and their Derivatives
2[90[0[4[0 By oxidation of primary alcohols
A mild\ versatile\ selective and practically convenient reagent for the conversion of primary
alcohols to aldehydes has been a long!standing objective of many research groups[ The available
methods will be discussed in six categories] "i# metal reagents\ particularly chromium and ruthenium
salts^ "ii# activated DMSO reagents^ "iii# halogen!based oxidants^ "iv# Oppenauer!type oxidations^
"v# electrochemical and photochemical oxidations^ and "vi# miscellaneous methods[
3 Alkyl Aldehydes
Recent research on oxidation methods has often been directed to developing low!cost methods
with increased environmental acceptability[ Thus catalytic methods\ particularly those using hydro!
gen peroxide or t!butylhydroperoxide as the ultimate oxidant\ have received considerable attention[
Also of interest from this point of view are solid!supported oxidants\ which allow the reaction to
be simply worked up by _ltration[ Such oxidants\ which often vary in selectivity and reactivity when
compared with the unsupported parent reagent\ have been the subject of a review �68S390�[
"i# Usin‘ metal ion!based oxidants
"a# Chromium rea‘ents[ Most traditional chromium!based oxidants have been found to be less
than satisfactory reagents for aldehyde preparation[ They are often unstable or hazardous to
prepare\ show little selectivity\ and need to be used in quite large excesses[ In addition\ the major
product is quite often not the aldehyde but a dimeric ester formed by preferential oxidation of the
hemiacetal derived from the product aldehyde and starting material[ This discouraging picture has
been transformed by a number of new reagents\ of which perhaps the pre!eminent is pyridinium
chlorochromate "pcc#\ and which has been the subject of a review �71S134�[ Despite its now estab!
lished position\ occasional variations or improvements on the original method are still being
published\ and of particular note is an improved preparation of the reagent which is not only higher!
yielding but also less hazardous �89T3306�[ An important group of modi_cations is aimed at
simplifying the workup\ which can be complicated by di.culties separating the product from tarry
chromium!containing residues[ These modi_ed reagents include polyvinylpyridinium chloro!
chromate\ a polymeric analogue of pcc �67S423\ 70JOC0617�\ a variety of polymer!bound quaternary
ammonium chlorochromates �75JOC3905�\ and 1\1?!bipyridinium chlorochromate\ which apparently
gives more tractable residues �79S580�[ A wide range of other supported forms of chromic acid have
also been described\ including chromic acid adsorbed on silica gel �67S423\ 68T0678�\ and chromate
ion bound to an anion exchange resin �65JA5626� or to a poly"vinylpyridine# resin �67JOC1507�[
One of the few disadvantages of pcc is its mildly acidic character\ which makes it unsuitable for
the oxidation of some sensitive substrates[ Several modi_ed reagents which reduce or overcome this
problem have been reported\ the most important of which is probably pyridinium dichromate "pdc#
in dichloromethane �68TL288�\ and which\ like pcc\ is available in a resin!supported form �78SC0206�[
Other reagents with reduced acidity include pyridinium ~uorochromate �71S477�\ pcc absorbed onto
alumina\ which will oxidize citronellol to citronellal in 89) yield\ whereas pcc gives pulegone
�79S112�\ and trimethylsilyl chlorochromate\ which is prepared in situ from chromium trioxide and
chlorotrimethylsilane and allows oxidations to be performed under strictly neutral and anhydrous
conditions �72TL3256\ 74T1892�[ In addition\ the use of ultrasound in oxidations with silica gel!
supported pcc\ leading to a signi_cant reduction in the length of time and the amount of reagent
required\ has been described �78JOC4276�\ and molecular sieves have been found to assist the
oxidations of a variety of alcohols including carbohydrates and nucleosides �71JCS"P0#0856�[
Trimethylammonium chlorochromate has also been proposed as an alternative to pcc �89S016�[
Several neutral organic soluble dichromate oxidants have been developed\ and o}er a number of
advantages in comparison to pdc\ in particular allowing the oxidation of sensitive substrates\
and short reaction times[ These include the 1! and 3!benzylpyridinium dichromates �80SC308�\
bis"benzyltriethylammonium#dichromate �71S0980� and tetrakispyridinocobalt"II# dichromate
�81SC0380�[ Bisphosphonium dichromate �75TL0664� and 2!carboxypyridine dichromate "sometimes
referred to as nicotinium dichromate\ NDC# �76T2852�\ although insoluble in organic solvents\ also
appear to have advantages over pdc for some oxidations[ Lastly\ zinc dichromate has been reported
to display an unusual selectivity\ and e.ciently oxidizes primary alcohols while leaving the normally
more reactive allylic alcohols una}ected �75S174�[ This reagent is also known in a polymer!supported
form �80SC1966�[
Relatively little has been published on phase transfer!catalysed chromate oxidations\ although
the method seems to have considerable potential[ Although the earliest methods were only applicable
to acid!stable substrates �67TL0590�\ more modern methods are considerably milder �68S023\
79TL3542�\ and examples containing quite acid!sensitive functionalities\ such as an isoxazole ring are
known �72SC706�[ High yields of aldehydes can also be obtained in oxidations with preformed
quaternary ammonium chromates �68S245�[
An important early oxidant was Collins reagent\ a solution of chromium trioxide in pyridine[
The reagent is still occasionally of value\ although its preparation can be hazardous\ and a number
of variants are now known\ including solutions of chromium trioxide in DMSO �81SC656� or
hexamethylphosphoramide "HMPA# �65S283�[ A rather di}erent way of modulating the reactivity
Saturated Unsubstituted 4
of chromium trioxide is by suspending it on Celite �68S704�\ which has the additional advantage of
simplifying the workup[
Peroxychromium species such as CrO4 = C4H4N �66TL2638�\ and CrO6 �75T608�\ and a number of
chromium"V# complexes �79TL0472� have been used as reagents for primary alcohol oxidation\
although despite some advantages\ in particular being neutral\ they have not achieved widespread
use[
Lastly\ it is worth mentioning that\ despite the industrial and economic importance of the goal\
relatively little progress has so far been reported in developing catalytic chromium systems for the
oxidation of alcohols[ This area is clearly receiving some attention although\ unfortunately\ the
methods reported so far do not appear to be applicable to the oxidation of primary alcohols to
aldehydes[
"b# Man‘anese rea‘ents[ Simple manganate"VI# or manganate"VII# salts are very powerful and
unselective oxidants\ which even in simple cases are of little synthetic use for the oxidation of
primary alcohols to aldehydes since\ except in strongly basic solutions\ further oxidation to the
carboxylic acid is faster than the initial oxidation to the aldehyde[ Although a range of modi_ed
manganese reagents is now available\ which are useful for the preparation of conjugated unsaturated
aldehydes and ketones\ only occasional examples of their use for the preparation of saturated
aldehydes have been reported �72BCJ803\ 89T5758�[
"c# Ruthenium rea‘ents[ As with chromium and manganese reagents\ the challenge for chemists
wanting to develop oxidants of this class has been to moderate the reactivity and improve the
selectivity of simple ruthenium reagents[ In an interesting contrast to the other metal oxidants\
where modi_ed stoichiometric reagents have been developed\ the most successful approach has been
the development of catalytic systems[ Two distinct systems have been found to be useful[
The _rst\ and less widely used\ of these employs bis"triphenylphosphine#ruthenium"II# chloride\
which appears to have some potential as a stoichiometric\ as well as a catalytic\ oxidant of primary
alcohols[ It was _rst reported with N!methylmorpholine N!oxide as a cooxidant �65TL1492�\ although
more recent publications have used bis"trimethylsilyl#peroxide �77BCJ2596�\ phenyliodosodiacetate
�70TL1250� or m!iodosylbenzoic acid �72HCA0689� as the cooxidant[ The stoichiometric version of
the reaction is of interest since it allows the oxidation of primary alcohols in the presence of
secondary ones �70TL0594�[
Unquestionably the most important ruthenium oxidants\ and one of the most important recent
developments in oxidation methodology generally\ are the tetraalkylammonium perruthenates
developed by Gri.th and by Ley[ These use a catalytic tetraalkylammonium perruthenate\ generally
tetrapropylammonium perruthenate "TPAP#\ in the presence of 3A nm molecular sieves with
N!methylmorpholine N!oxide as a regenerating oxidant to achieve the oxidation under very mild\
neutral conditions[ The reagent is notable for the wide range of functionalities tolerated\ including
THP and silyl ethers\ alkenes\ epoxides and esters "Equation "3##\ and the fact that chiral centres a
to the newly formed carbonyl group are not epimerized �76CC0514�[ The reagent has also been the
subject of a review �89MI 290!90�[
OH O
TPAP
O O (4)
70%
O-TBDPS O-TBDPS
TBDPS = t-butyldiphenylsilyl
"d# Miscellaneous metal oxidants[ Although catalytic molybdenum! and tungsten!based systems
are well established for the oxidations of secondary alcohols\ primary alcohols are generally una}ec!
ted[ However\ two molybdenum peroxy complexes\ "0# �79TL3732� and "1# �76JOC4356�\ which are
both used stoichiometrically\ do oxidize primary alcohols to aldehydes[ Osmium tetroxide in ether
has the unusual selectivity of oxidizing primary alcohols in the presence of secondary alcohols\
although the high reactivity of the reagent to other functionalities limits the application of the
reaction �73S844�[ Nickel"II# bromide catalyses the oxidation by benzoyl peroxide of primary
alcohols to aldehydes in high yield �68JOC1844�[
A number of catalytic palladium systems for alcohol oxidation are known\ and the scope of the
method has been examined �72JOC0175�[ The optimal conditions employ 0�2 mol) of either a
palladium"9# or palladium"II# catalyst with bromobenzene as a reoxidant[ The oxidation can
also be performed under phase transfer conditions with iodobenzene as a reoxidant �74TL5146�[
5 Alkyl Aldehydes
O
O O
Mo
Ph
O O O O
N O O O
Mo
O N
O
Ph O
(1) (2)
Ytterbium"III# nitrate will catalyse the oxidation of alcohols by iodosobenzene[ Like osmium
tetroxide this reagent shows the unusual selectivity of oxidizing primary alcohols in preference to
secondary alcohols �82CL460�[
"ii# Usin‘ DMSO rea‘ents
Since P_tzner and Mo}at|s serendipitous discovery in 0852 that alcohols were oxidized at room
temperature by DMSO in the presence of dicyclohexylcarbodiimide and phosphoric acid �52JA2916�\
oxidations of alcohols by activated DMSO have become established as one of the mildest and most
general methods for the oxidation of alcohols\ although today the most commonly used variant is
that developed by Swern and co!workers which uses oxalyl chloride as the activating agent
�67JOC1379\ 67T0540�[ The method is of particular value for aldehyde preparations because of its
exceptionally mild nature and the fact that over!oxidation does not occur[
The area is well served by several good reviews[ The literature up to 0879 is covered in a classic
review by Manusco and Swern �70S054�[ This has been updated to 0878 by Tidwell �89S746�\ who
has also written an Or‘anic Reactions article on the subject\ which includes extensive tabulations of
examples\ and a good discussion of the scope of the oxidation and of potential side reactions
�89OR"28#186�[ Relatively little can be added to the coverage provided by these reviews\ although
bis"trichloromethyl#carbonate "triphosgene# recently has been reported to be a good activating
reagent\ and\ being a crystalline solid\ avoids the handling and scale!up problems associated with
the relatively toxic and corrosive reagents generally used �80JOC4837�[
N!Chlorosuccinimide and diisopropyl sul_de will oxidize alcohols in a reaction which is probably
mechanistically very closely related to the Swern�Mo}att oxidation �73CC651�[ The method shows
the curious\ and unexplained\ feature that at 9>C primary alcohols are oxidized in preference to
secondary alcohols while at �67>C the opposite selectivity is found[
"iii# Usin‘ halo‘en!based oxidants
Many electrophilic halogen"I# reagents can oxidize primary alcohols to aldehydes\ and some\
such as trichloroisocyanuric acid �81SC0478� and N!iodosuccinimide �70S283�\ do so cleanly and in
good yield[ However\ more important as oxidants are the iodine"V# reagents\ and in particular
periodinane "2#\ which was _rst reported as an oxidant for alcohols by Dess and Martin in 0872
�72JOC3044�[ An improved preparation has been described �82JOC1788�[ The oxidation occurs under
very mild conditions and is compatible with a wide range of other functionalities including secondary
amides\ sul_des\ alkenes\ furans and vinyl ethers �80JA6166�[ The related alkoxyaryltri~uoro!
periodinane "3# has also been reported to oxidize alcohols to aldehydes in moderate to high yields
�68JA4183�[
AcO OAc F F
I I
OAc F
O O
O
(3) (4)
Saturated Unsubstituted 6
"iv# Oppenauer and related oxidations
The oxidation of secondary alcohols by an aluminum alkoxide!catalysed hydrogen transfer to an
acceptor ketone\ present in excess to drive the equilibrium in the desired direction\ was _rst reported
by Oppenauer �26RTC026�[ The method was quite widely used in the older literature\ particularly
for the oxidation of steroidal alcohols\ and was the subject of an early review �40OR"5#196�[ Unfor!
tunately\ the method\ despite the mild conditions\ cannot be directly applied to the oxidation of
primary alcohols to aldehydes since the product aldehydes condense with the excess ketone present
as a hydrogen acceptor\ and until recently there was no general solution to this problem[ However\
new catalysts which do not catalyse the aldol side reaction are now becoming available[ These include
bis"cyclopentadienyl#zirconium hydride �75JOC139\ 75S663�\ zirconium oxide with benzophenone as
the hydrogen acceptor �80BCJ201�\ and a variety of lanthanide alkoxides �73JOC1934�^ they make
the method an attractive option for the oxidation of sensitive substrates with the added bene_t of
avoiding any risk of overoxidation[
"v# Electrochemical and photochemical oxidations
Since an alcohol will not lose an electron at experimentally achievable electrode potentials\ the
direct electrochemical oxidation of alcohols is an impossibility[ However\ a number of systems are
known which use an intermediary species\ often referred to as an {electron carrier|\ which can oxidize
the alcohol chemically\ the resulting reduced form of the electron carrier being reoxidized at the
anode to complete the cycle[ These include a number of traditional electron carriers such as iodonium
reagents �68TL054�\ sulfur species �68TL2750\ 79TL0756�\ molecular oxygen �78S392� and nitroxyls
�72JA3381�\ as well as established oxidants for alcohols such as ruthenium salts �89SC288�\ in what
are e}ectively electrocatalytic versions of these oxidations[ Two!stage systems in which the oxidant
is not reoxidized directly at the anode but via an electron carrier are also possible �80BCJ685�[
The photochemical oxidation of alcohols to aldehydes is a very underexplored area of meth!
odology\ although it is known that irradiation of an alcohol in the presence of a copper"II#\ iron"III#
or silver"I# salt �68JOC027� or platinum on titanium dioxide �73TL2252� can give high yields of
aldehydes[
"vi# Miscellaneous oxidations
Dimesityl diselenide catalyses the oxidation of alcohols to aldehydes by t!butyl hydroperoxide[
The method is extremely mild and is even compatible with the presence of phenylthio or phenylseleno
groups �71JOC726�[ The oxaminium salt "4# "X�OMe# has been found to be an e.cient oxidant
which shows selectivity for primary over secondary alcohols �74JOC0221�[ Variants of the reaction
in which the reagent is used catalytically with sodium hypochlorite �76JOC1448�\ sodium bromite
�89JOC351� or calcium hypochlorite �89JOC351� as a cooxidant are also known[ A similar oxidation
can be achieved with the oxaminium salt "4# "X�H# and sodium hypochlorite as the cooxidant\
and leads to less overoxidation to the corresponding carboxylic acid �89TL1066�[ Another useful
oxidant is 0\0?!"azodicarbonyl#dipiperidine\ which provides a very mild method of oxidizing alcohols
via their bromomagnesium salts �66BCJ1662�[
X
+
N Br–
O
(5)
2[90[0[4[1 From diols
Probably the most important route to aldehydes from 0\1!diols is by oxidative cleavage[ Many
oxidants\ particularly metal!based reagents\ will cleave vicinal diols\ although the major products
7 Alkyl Aldehydes
are often carboxylic acids[ However\ consistently high yields can be obtained with periodate\ lead"IV#
acetate or bismuth reagents �B!54MI 290!90\ B!58MI 290!91\ 70CC0121�[ Silica gel!supported sodium
periodate has been found to be particularly convenient for the cleavage of 0\1!diols to aldehydes
�78S53�[ Most glycol cleavages proceed by mechanisms that involve cyclic intermediates and there!
fore cannot be used for the cleavage of trans!diols[ However\ cleavages with iodine"III# or iodine"I#
acetates appear to be radical in nature and proceed equally well with cis! or trans!diols
�67JCS"P0#0372�[ Diols protected as their dibutylstannylene derivatives can also be cleaved with either
periodate or lead"IV# acetate �70TL1774�[
2[90[0[4[2 Oxidation of alcohol derivatives
"i# Ethers
A wide range of alkyl and silyl ethers of primary alcohols react with hydride!abstracting reagents
to give an oxonium ion which is hydrolysed to give the aldehyde on workup[ Thus\ methyl ethers
of primary alcohols are cleaved oxidatively by nitronium tetra~uoroborate �66JOC2986�\ or uran!
ium"VI# ~uoride �67JA4285�\ and O!trimethylsilyl derivatives of primary alcohols can be oxidized
with trityl tetra~uoroborate �65JOC0368�[ Similarly\ sodium bromate\ in the presence of a catalytic
amount of cerium"IV# ammonium nitrate\ will oxidize a wide range of ether derivatives\ including
methyl\ benzyl\ trimethylsilyl and t!butyldimethylsilyl �79S786�[
Trimethylsilyl ethers can be oxidized using DMSO:oxalyl chloride\ although the conditions
"�29>C for 29�34 minutes# are appreciably more vigorous than are normally required for alcohol
oxidations �76JCS"P0#0110�[ t!Butyldimethylsilyl ethers are inert to the reaction conditions\ and
hindered or secondary trimethylsilyl ethers react appreciably less rapidly\ allowing some interesting
selective oxidations to be achieved "Equation "4## �78S839�[ The oxidative deprotection and stability
under alcohol oxidative conditions of silyl ethers has been the subject of a very comprehensive
review\ which includes some useful tabulations of the reactivities observed �82S00�[
O O
O O
DMSO, (COCl)2
(5)
O-TMS 62% O
OSiEt3 OSiEt3
"ii# Esters
Aldehydes may be prepared under strictly neutral conditions by the photolysis of the pyruvate
esters of primary alcohols �65JOC2929\ 65SC170�\ and the reaction has been applied to good e}ect in
the preparation of a number of delicate carbohydrate aldehydes �66JOC0105�[ Alkyl nitrites are
oxidized in a Kornblum!type reaction by DMSO �75T3022�\ and alcohols can be oxidized via their
aci!nitro esters in a reaction that is probably mechanistically related �68CC292\ 70TL1184�[
2[90[0[4[3 Rearrangement of allylic alcohols
A variety of primary allylic alcohols can be isomerized to aldehydes on treatment with
N!lithioethylenediamine or N!lithioaminopropylamine in the amine as the solvent �74CC701�[ The
reaction is somewhat capricious although in favourable cases very good yields of the expected
aldehyde are obtained "Equation "5##[ The main alternative to these strongly basic conditions is a
ruthenium"II#!catalysed rearrangement[ Although the optimal conditions are substrate!dependent\