Modern Oxidation Methods

300 Pages·2004·2.69 MB·English

by  Jan-Erling B?ckvall

1
1
Recent Developments in the Osmium-catalyzed Dihydroxylation
of Olefins
UtaSundermeier,ChristianDöbler,andMatthiasBeller
1.1
Introduction
The oxidative functionalization of olefins is of major importance for both organic
synthesis and the industrial production of bulk and fine chemicals [1]. Among the
differentoxidationproductsofolefins,1,2-diolsareusedinawidevarietyofapplica-
tions.Ethylene- andpropylene-glycol areproducedona multi-million tonscaleper
annum, due to their importance as polyester monomers and anti-freeze agents [2].
A number of 1,2-diolssuch as 2,3-dimethyl-2,3-butanediol, 1,2-octanediol,1,2-hexa-
nediol, 1,2-pentanediol, 1,2- and 2,3-butanediol are of interest in the fine chemical
industry.Inaddition,chiral1,2-diolsareemployedasintermediatesforpharmaceuti-
calsandagrochemicals.Atpresent1,2-diolsaremanufacturedindustrially byatwo
stepsequenceconsistingofepoxidationofanolefinwithahydroperoxideorapera-
cid followed by hydrolysis of the resulting epoxide [3]. Compared with this process
the dihydroxylation of C=C double bonds constitutes a more atom-efficient and
shorterrouteto1,2-diols.Ingeneralthedihydroxylationofolefinsiscatalyzedbyos-
mium, ruthenium or manganese oxo species. The osmium-catalyzed variant is the
most reliable and efficient method for the synthesis of cis-1,2-diols [4]. Using os-
mium in catalytic amounts together with a secondary oxidant in stoichiometric
amounts variousolefins, including mono-,di-, and trisubstituted unfunctionalized,
as well as many functionalized olefins, can be converted into the corresponding
diols.OsO asanelectrophilicreagentreactsonlyslowlywithelectron-deficientole-
4
fins, and therefore higher amounts of catalyst and ligand are necessary in these
cases.Recentstudieshaverevealedthatthesesubstratesreactmuchmoreefficiently
whenthepHofthereactionmediumismaintainedontheacidicside[5].Here,citric
acid appears to be superior for maintaining the pH in the desired range. On the
otherhand,inanotherstudyitwasfoundthatprovidingaconstantpHvalueof12.0
leadstoimprovedreactionratesforinternalolefins[6].
SinceitsdiscoverybySharplessandcoworkers,catalyticasymmetricdihydroxyla-
tion(AD)hassignificantlyenhancedtheutilityofosmium-catalyzeddihydroxylation
(Scheme 1.1) [7]. Numerous applications in organic synthesis have appeared in re-
centyears[8].
ModernOxidationMethods.EditedbyJan-ErlingBäckvall
Copyright(cid:1)2004WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-30642-0
2 1 RecentDevelopmentsintheOsmium-catalyzedDihydroxylationofOlefins
Scheme1.1 Osmylationofolefins
Whiletheproblemofenantioselectivityhaslargelybeensolvedthroughextensive
synthesisand screeningofcinchonaalkaloid ligands by the Sharpless group, some
features of this general method remain problematic for larger scale applications.
Firstly,theuseoftheexpensiveosmiumcatalystmustbeminimizedandanefficient
recyclingofthemetalshouldbedeveloped.Secondly,theappliedreoxidantsforOsVI
speciesareexpensiveandleadtooverstoichiometricamountsofwaste.
In the past several reoxidation processes for osmium(VI) glycolates or other os-
mium(VI)specieshavebeendeveloped.Historically,chlorates[9]andhydrogenper-
oxide[10]werefirstappliedasstoichiometricoxidants,howeverinbothcasesthedihy-
droxylation often proceeds with low chemoselectivity. Other reoxidants for os-
mium(VI)aretert-butylhydroperoxideinthepresenceofEt NOH[11]andarangeof
4
N-oxides,suchasN-methylmorpholineN-oxide(NMO)[12](theUpjohnprocess)and
trimethylamineN-oxide.K [Fe(CN) ]gaveasubstantialimprovementintheenantios-
3 6
electivitiesinasymmetricdihydroxylationswhenitwasintroducedasareoxidantfor
osmium(VI) speciesin 1990 [13]. However, evenas early on as 1975 it was already
beingdescribedasanoxidantforOs-catalyzedoxidationreactions[14].Todaythe“AD-
mix”, containing the catalyst precursor K [OsO (OH) ], the co-oxidant K [Fe(CN) ],
2 2 4 3 6
thebaseK CO ,andthechiralligand,iscommerciallyavailableandthedihydroxyla-
2 3
tion reaction is easy to carry out. However, the production of overstoichiometric
amountsofwasteremainsasasignificantdisadvantageofthereactionprotocol.
Thischapterwillsummarizetherecentdevelopmentsintheareaofosmium-cata-
lyzeddihydroxylations,whichbringthistransformationclosertoa“greenreaction”.
Hence, special emphasis isgiven to the use of new reoxidantsand recycling of the
osmiumcatalyst.
1.2
EnvironmentallyFriendlyTerminalOxidants
1.2.1
HydrogenPeroxide
Ever since the Upjohn procedure was published in 1976 the N-methylmorpholine
N-oxide-basedprocedurehasbecomeoneofthestandardmethodsforosmium-cata-
lyzed dihydroxylations. However, in the asymmetric dihydroxylation NMO has not
1.2 EnvironmentallyFriendlyTerminalOxidants 3
beenfullyappreciatedsinceitwasdifficulttoobtainhigheewiththisoxidant.Some
yearsagoitwasdemonstratedthatNMOcouldbeemployedastheoxidantintheAD
reactiontogivehigheeinaqueoustert-BuOHwithslowadditionoftheolefin[15].
Inspiteofthefactthathydrogenperoxidewasoneofthefirststoichiometricoxi-
dantstobeintroducedfortheosmium-catalyzeddihydroxylationitwasnotactually
used until recently. When using hydrogen peroxide as the reoxidant for transition
metal catalysts,very often there is the big disadvantage that a large excessof H O
2 2
is required, implying that the unproductive peroxide decomposition is the major
process.
Recently Bäckvall andcoworkerswereableto improvethe H O reoxidationpro-
2 2
cess significantly by using N-methylmorpholine together with flavin as co-catalysts
in the presence of hydrogen peroxide [16]. Thus a renaissance of both NMO and
H O was induced.The mechanism of the triple catalytic H O oxidationisshown
2 2 2 2
inScheme1.2.
Scheme1.2 Osmium-catalyzeddihydroxylationofolefinsusing
HO astheterminaloxidant
2 2
The flavinhydroperoxidegeneratedfromflavinandH O recyclesthe N-methyl-
2 2
morpholine (NMM) to N-methylmorpholine N-oxide (NMO), which in turn reoxi-
dizestheOsVItoOsVIII.Whiletheuseofhydrogenperoxideastheoxidantwithout
theelectron-transfermediators(NMM,flavin)isinefficientandnonselective,various
olefins were oxidizedto diols in good to excellent yields employing this mild triple
catalyticsystem(Scheme1.3).
Scheme1.3 Osmium-catalyzeddihydroxylationof(cid:1)-methylstyrene
usingHO
2 2
By using a chiral Sharpless ligand high enantioselectivitieswere obtained. Here,
anincreaseintheadditiontimeforolefinandH O canhaveapositiveeffectonthe
2 2
enantioselectivity.
4 1 RecentDevelopmentsintheOsmium-catalyzedDihydroxylationofOlefins
Bäckvallandcoworkershaveshownthatothertertiaryaminescanassumetherole
of the N-methylmorpholine. They reportedon the firstexample of an enantioselec-
tivecatalyticredoxprocesswherethechiralligandhastwodifferentmodesofopera-
tion:(1)toprovidestereocontrolintheadditionofthesubstrate,and(2)toberespon-
sibleforthereoxidationofthemetalthroughanoxidizedform[17].Theresultsob-
tained with hydroquinidine 1,4-phthalazinediyl diether (DHQD) PHAL both as an
2
electron-transfermediatorandchiralligandintheosmium-catalyzeddihydroxylation
are comparable to those obtained employing NMM together with (DHQD) PHAL.
2
TheproposedcatalyticcycleforthereactionisdepictedinScheme1.4.
The flavin is an efficient electron-transfer mediator, but rather unstable. Several
transitionmetalcomplexes,forinstancevanadylacetylacetonate,canalsoactivatehy-
drogenperoxideandarecapableofreplacing the flavininthe dihydroxylation reac-
tion[18].
MorerecentlyBäckvallandcoworkersdevelopedanovelandrobustsystemforos-
mium-catalyzed asymmetric dihydroxylation of olefins by H O with methyltrioxo-
2 2
rhenium(MTO)astheelectrontransfermediator[19].Interestingly,hereMTOcata-
lyzes oxidation of the chiral ligand to its mono-N-oxide, which in turn reoxidizes
OsVItoOsVIII.Thissystemgivesvicinaldiolsingoodyieldsandhighenantiomeric
excessupto99%.
Scheme1.4 Catalyticcyclefortheenantioselectivedihydroxylation
ofolefinsusing(DHQD)PHALforoxygentransferandasasource
2
ofchirality
1.2 EnvironmentallyFriendlyTerminalOxidants 5
1.2.2
Hypochlorite
Apartfromoxygenandhydrogenperoxide,bleachisthesimplestandcheapestoxi-
dantthatcanbeusedinindustrywithoutproblems.Inthepastthisoxidanthasonly
beenappliedinthepresenceofosmiumcomplexesintwopatentsintheearly1970s
for the oxidation of fatty acids [20]. In 2003 the first general dihydroxylation proce-
dureofvariousolefinsinthepresenceofsodiumhypochloriteasthereoxidantwas
describedbyus[21].Using(cid:1)-methylstyreneasamodelcompound,100%conversion
and98%yieldofthedesired1,2-diolwereobtained(Scheme1.5).
Scheme1.5 Osmium-catalyzeddihydroxylationof(cid:1)-methylstyrene
usingsodiumhypochlorite
Interestingly, the yield of 2-phenyl-1,2-propanediol after 1h was significantly
higherusinghypochloritecomparedwithliteratureprotocolsusingNMO(90%)[22]
or K [Fe(CN) ] (90%) at this temperature. The turnover frequency was 242h–1,
3 6
whichisareasonablelevel[23].UndertheconditionsshowninScheme1.5anenan-
tioselectivityofonly77%eeisobtained,while94%eeisreportedusingK [Fe(CN) ]
3 6
asthereoxidant.Thelowerenantioselectivitycanbeexplainedbysomeinvolvement
oftheso-calledsecondcatalyticcyclewiththeintermediateOsVIglycolatebeingoxi-
dizedtoanOsVIIIspeciespriortohydrolysis(Scheme1.6)[24].
Nevertheless,theenantioselectivitywasimprovedbyapplyingahigherligandcon-
centration. In the presence of 5mol% (DHQD) PHAL a good enantioselectivity of
2
91% ee is observedfor (cid:1)-methylstyrene. Using tert-butylmethylether as the organic
co-solvent instead of tert-butanol, 99% yield and 89% ee with only 1mol%
(DHQD) PHALarereportedforthesamesubstrate.Thisincreaseinenantioselectiv-
2
itycanbeexplainedbyanincreaseintheconcentrationofthechiralligandintheor-
ganic phase. Increasing the polarity of the water phase by using a 10% aqueous
NaCl solution showed a similar positive effect. Table1.1 shows the results of the
asymmetricdihydroxylationofvariousolefinswithNaOClastheterminaloxidant.
Despite the slow hydrolysis of the corresponding sterically hindered OsVI glyco-
late,trans-5-decenereactedfastwithoutanyproblems.Thisresultisespeciallyinter-
estingsinceitisnecessarytoaddstoichiometricamountsofhydrolysisaidstothedi-
hydroxylationofmostinternalolefinsinthepresenceofotheroxidants.
Withthisprotocolaveryfast,easytoperform,andcheapprocedurefortheasym-
metricdihydroxylationispresented.
6 1 RecentDevelopmentsintheOsmium-catalyzedDihydroxylationofOlefins
Scheme1.6 Thetwocatalyticcyclesintheasymmetricdihydroxylation
Tab.1.1 AsymmetricdihydroxylationofdifferentolefinsusingNaOClasterminaloxidanta
Entry Olefin Time Yield Selectivity ee ee(%)
(h) (%) (%) (%) Ref.
1 1 88 88 95 99
2 2 93 99 95 97
3 1 99 99 91 95
4 1 92 94 93 97
5 1 84 84 91 97
6 2 88 94 73 88
a Reactionconditions:2mmololefin,0.4mol%K[OsO(OH)],5mol%(DHQD)PHAL,10mLHO,
2 2 4 2 2
10mLtBuOH,1.5equiv.NaOCl,2equiv.KCO,0(cid:2)C.
2 3
1.2 EnvironmentallyFriendlyTerminalOxidants 7
Tab.1.1 (continued)
Entry Olefin Time Yield Selectivity ee ee(%)
(h) (%) (%) (%) Ref.
7 2 87 93 80b
8 2 97 97 73
9 2 94 96 34b
10 2 97 >97 80b 92
b 5mol%(DHQD)PYRinsteadof(DHQD)PHAL.
2 2
1.2.3
OxygenorAir
InthepastithasbeendemonstratedbyseveralgroupsthatinthepresenceofOsO
4
and oxygen mainly non-selective oxidation reactions take place [25]. However, in
1999Kriefetal.publishedareactionsystemconsistingofoxygen,catalyticamounts
ofOsO andselenidesfortheasymmetricdihydroxylationof(cid:1)-methylstyreneunder
4
irradiationwithvisiblelightinthepresenceofasensitizer(Scheme1.7)[26].Here,
theselenidesareoxidizedtotheiroxidesbysingletoxygenandtheseleneoxidesare
able to re-oxidize osmium(VI) to osmium(VIII). The reaction works with similar
yieldsandeevaluestothoseoftheSharpless-AD.Potassiumcarbonateisalsoused,
butonlyonetenthoftheamountpresentintheAD-mix.Aircanbeusedinsteadof
pureoxygen.
Scheme1.7 Osmium-catalyzeddihydroxylationusing1O and
2
benzylphenylselenide
Thereactionwasextendedtoawiderangeofaromaticandaliphaticolefins[27].It
wasshownthatbothyieldandenantioselectivityareinfluencedbythepHofthere-
actionmedium.Theprocedurewasalsoappliedtopracticalsynthesesofnaturalpro-
ductderivatives[28].ThisversionoftheADreactionnotonlyusesamoreecological
co-oxidant,italsorequiresmuchlessmatter:87mgofmatter(catalyst,ligand,base,
8 1 RecentDevelopmentsintheOsmium-catalyzedDihydroxylationofOlefins
reoxidant) are required to oxidize 1mmol of the same olefin instead of 1400mg
whentheAD-mixisused.
Alsoin1999therewasthefirstpublicationontheuseofmolecularoxygenwith-
outanyadditivetoreoxidizeosmium(VI)toosmium(VIII).Wereportedthattheos-
mium-catalyzeddihydroxylationofaliphaticandaromaticolefinsproceedsefficiently
in the presence of dioxygen under ambient conditions [29]. As shown in Table1.2
thenewdihydroxylationprocedureconstitutesasignificantadvancementcompared
with other reoxidation procedures. Here, the dihydroxylation of (cid:1)-methylstyrene is
comparedusingdifferentstoichiometricoxidants.The yield ofthe 1,2-diolremains
goodtoverygood(87–96%),independentoftheoxidantused.Thebestenantioselec-
tivities (94–96% ee) are obtained with hydroquinidine 1,4-phthalazinediyl diether
[(DHQD) PHAL]astheligandat0–12(cid:2)C(Table1.2,entries1and3).
2
Thedihydroxylationprocesswithoxygenisclearlythemostecologicallyfavorable
procedure (Table1.2, entry 5),when the production of waste from a stoichiometric
reoxidantisconsidered.WiththeuseofK [Fe(CN) ]asoxidantapproximately8.1kg
3 6
of iron salts per kg of product are formed. However, in the case of the Krief (Ta-
ble1.2, entry 3) and Bäckvall procedures (Table1.2, entry 4) as well as in the pre-
senceofNaOCl(Table1.2,entry6)somebyproductsalsoariseduetotheuseofco-
catalysts and co-oxidants.It should be noted that only salts and byproductsformed
Tab.1.2 Comparisonofthedihydroxylationof(cid:1)-methylstyreneinthepresenceofdifferentoxidants
Entry Oxidant Yield Reactionconditions ee TON Waste(oxidant) Ref.
(%) (%) (kg/kgdiol)
1 K [Fe(CN) ] 90 0(cid:2)C 94a 450 8.1c [7b]
3 6
K [OsO(OH)]
2 2 4
tBuOH/HO
2
2 NMO 90 0(cid:2)C 33b 225 0.88d [22]
OsO
4
acetone/HO
2
3 PhSeCHPh/O 89 12(cid:2)C 96a 222 0.16e [26a]
2 2
PhSeCHPh/air 87 K [OsO(OH)] 93a 48 0.16e [26a]
2 2 2 4
tBuOH/HO
2
4 NMM/flavin/HO 93 RT – 46 0.33f [16a]
2 2
OsO
4
acetone/HO
2
5 O 96 50(cid:2)C 80a 192 – [29]
2
K [OsO(OH)]
2 2 4
tBuOH/aq.buffer
6 NaOCl 99 0(cid:2)C 91a 247 0.58g [21]
K [OsO(OH)]
2 2 4
tBuOH/HO
2
aLigand:Hydroquinidine1,4-phthalazinediyldiether. bHydroquinidinep-chlorobenzoate.
cK[Fe(CN)]. dN-Methylmorpholine(NMM). ePhSe(O)CHPh. fNMO/flavin-OOH. gNaCl.
4 6 2
1.2 EnvironmentallyFriendlyTerminalOxidants 9
from the oxidant have been included in the calculation. Other waste products have
not been considered. Nevertheless the calculations presented in Table1.2 give a
roughestimationoftheenvironmentalimpactofthereaction.
Sincetheuseofpuremolecularoxygenonalargerscalemightleadtosafetypro-
blemsitisevenmoreadvantageoustouseairastheoxidizingagent.Hence,allcur-
rent bulk oxidationprocesses,e.g., the oxidationofBTX (benzene,toluene,xylene)
aromatics or alkanes to give carboxylic acids, and the conversion of ethylene into
ethylene oxide, use air and not pure oxygen as the oxidant [30]. In Table1.3 the re-
sults of the dihydroxylation of (cid:1)-methylstyrene as a model compound using air as
the stoichiometricoxidant areshown in contrastto that with pure oxygen (Scheme
1.8;Table1.3)[31].
Scheme1.8 Osmium-catalyzeddihydroxylationof(cid:1)-methylstyrene
Thedihydroxylationof(cid:1)-methylstyreneinthepresenceof1barofpureoxygenpro-
ceeds smoothly (Table1.3, entries 1–2), with the best results being obtained at
pH10.4.Inthepresenceof0.5mol%K [OsO (OH) ]/1.5mol%DABCOor1.5mol%
2 2 4
(DHQD) PHALatpH10.4and50(cid:2)Ctotalconversionwasachievedafter16hor20h
2
dependingontheligand.Whilethetotalyieldandselectivityofthereactionareexcel-
lent(97%and96%,respectively),thetotalturnoverfrequencyofthecatalystiscom-
paratively low (TOF = 10–12h–1). In the presence of the chiral cinchona ligand
Tab.1.3 Dihydroxylationof(cid:1)-methylstyrenewithaira
Entry Pressure Cat. Ligand L/Os [L] Time Yield Selectivity ee
(bar)c (mol%) (mmolL–1) (h) (%) (%) (%)
1 1(pureO) 0.5 DABCOd 3:1 3.0 16 97 97 –
2
2 1(pureO) 0.5 (DHQD)PHALe 3:1 3.0 20 96 96 80
2 2
3 1 0.5 DABCO 3.1 3.0 24 24 85 –
4 1 0.5 DABCO 3.1 3.0 68 58 83 –
5 5 0.1 DABCO 3:1 0.6 24 41 93 –
6 9 0.1 DABCO 3:1 0.6 24 76 92 –
7 20 0.5 (DHQD)PHAL 3:1 3.0 17 96 96 82
2
8 20 0.1 (DHQD)PHAL 3:1 0.6 24 95 95 62
2
9 20 0.1 (DHQD)PHAL 15:1 3.0 24 95 95 83
2
10b 20 0.1 (DHQD)PHAL 3:1 1.5 24 94 94 67
2
11b 20 0.1 (DHQD)PHAL 6:1 3.0 24 94 94 78
2
12b 20 0.1 (DHQD)PHAL 15:1 7.5 24 60 95 82
2
aReactionconditions:K[OsO(OH)],50(cid:2)C,2mmololefin,25mLbuffersolution(pH10.4),10mLtBuOH. b10mmol
2 2 4
olefin,50mLbuffersolution(pH10.4),20mLtBuOH. cTheautoclavewaspurgedwithairandthenpressurizedtothe
givenvalue. d1,4-Diazabicyclo[2.2.2.]octane. eHydroquinidine1,4-phthalazinediyldiether.
10 1 RecentDevelopmentsintheOsmium-catalyzedDihydroxylationofOlefins
(DHQD) PHALaneeof 80%isobserved.Sharplessetal.reportedanenantioselec-
2
tivityof94%forthedihydroxylationof(cid:1)-methylstyrenewith(DHQD) PHALasthe
2
ligandusingK [Fe(CN) ]asthereoxidantat0(cid:2)C[32].Studiesoftheceilingeeat50(cid:2)C
3 6
(88% ee) show that the main difference in the enantioselectivity stems from the
higherreactiontemperature.Usingairinsteadofpureoxygengasgaveonly24%of
thecorrespondingdiolafter24h(TOF=1h–1;Table1.3,entry3).Althoughthereac-
tionisslow,itisimportanttonotethatthecatalyststaysactive,asshownbythefact
that 58% ofthe product isobtainedafter 68h (Table1.3, entry 4). Interestingly the
chemoselectivity of the dihydroxylation does not significantly decrease after a pro-
longedreactiontime.At5–20barairpressuretheturnoverfrequencyofthecatalyst
isimproved(Table1.3,entries5–11).
Fullconversionofa(cid:1)-methylstyreneisachievedatanairpressureof20barinthe
presence of 0.1mol% of osmium, which corresponds to a turnover frequency of
40h–1 (Table1.3, entries 8–11). Thus, by increasing the air pressure to 20bar, it
waspossibletoreducetheamountofosmiumcatalystbyafactorof5.Adecreaseof
theosmiumcatalystandtheligandleadstoadecreaseintheenantioselectivityoffrom
82%to62%ee.Thisiseasilyexplainedbythefactthattheligandconcentrationdeter-
minesthestereoselectivityofthedihydroxylationreaction(Table1.3,entries7and9).
Whilethereactionathighersubstrateconcentration(10mmolinsteadof2mmol)
proceedsonlysluggishlyat1barevenwithpureoxygen,fullconversionisachieved
after24hat20barofair(Table1.3,entries10and11,andTable1.4,entries17and
18).Inallexperimentsperformedunderairpressurethechemoselectivityofthedi-
hydroxylationremainedexcellent(92–96%).
Table1.4showstheresultsoftheosmium-catalyzeddihydroxylationofvariousole-
finswithair.
As depicted in Table1.4 all olefins gave the corresponding diols in moderate to
goodyields(48–89%).Applyingstandardreactionconditions,thebestyieldsofdiols
were obtained with 1-octene (97%), 1-phenyl-1-cyclohexene (88%), trans-5-decene
(85%), allyl phenyl ether (77%) and styrene (76%). The enantioselectivities varied
from53to98%eedependingonthesubstrate.Itisimportanttonotethatthechemo-
selectivityofthereactiondecreasesunderstandardconditionsinthefollowingsub-
strateorder:(cid:1)-methylstyrene=1-octene>1-phenyl-1-cyclohexene>trans-5-decene>
n-C F CH=CH > allyl phenyl ether > styrene >> trans-stilbene. A correlation be-
6 13 2
tweenthechemoselectivityofthereactionandthesensitivityoftheproduceddiolto-
wardsfurtheroxidationisevident,withthemainsidereactionbeingtheoxidativeclea-
vageoftheC=Cdoublebond.Aromaticdiolswithbenzylichydrogenatomsareespe-
cially sensitivetothisoxidationreaction.Thus,the dihydroxylationoftrans-stilbene
gave no hydrobenzoin in the biphasic mixture water/tert-butanol at pH 10.4, 50(cid:2)C
and20barairpressure(Table1.4,entry9).Insteadofdihydroxylationahighlyselec-
tivecleavageofstilbenetogivebenzaldehyde(84–87%yield)wasobserved.Interest-
ingly, changing the solvent to isobutyl methyl ketone (Table1.4, entry 12) makes it
possibletoobtainhydrobenzoininhighyield(89%)andenantioselectivity(98%)at
pH10.4.
Themechanismofthedihydroxylationreactionwithoxygenorairispresumedto
be similar to the catalytic cycle presented by Sharpless et al. for the osmium-cata-