不对称催化氢化Word文件下载.docx

不对称催化氢化Word文件下载.docx

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催化氢化都是膦配体。

有如下三种途径合成手性膦配体。

手性中心在膦上，P-手性配体；

手性中心在碳上，C-手性配体；

既有膦又有碳手性中心的配体。

常见的手性膦配体

单齿配体

PAMPCAMPMonoPhos

双齿配体

DEGPHOSDuPHOSPNNP

RROPHOSNORPHOSBPPFA

CYCPHOS（R,R）-DIPAMP（S,S）-CHIRAPHOS

（R）-BINAP（S,S）-BPPMDIOP

（R,R）-DPCP（+）-DIPMC（2R,3R）-NORPHOS

（-）-MENO

BIPHEMPSpirOPBICP

中心金属

主要限于铑（Rh）和钌（Ru）两种贵金属，另外铱（Ir）有少量的应用。

手性铑（Rh）膦催化剂只对α－酰氨基丙烯酸衍生物的催化氢化有很好的结果，对其它底物对映体选择性很低。

手性钌（Ru）膦催化剂底物适用范围广，尤其是Noyori等发展的［Ru（BINAP）（OCOR）2］催化剂能用于C=C,C=O,C=N等的不对称氢化，得到特别优异的对映体选择性。

2.1.3不对称催化机理

手性铑（Rh）膦催化剂对α－酰氨基丙烯酸衍生物的氢化催化结果如下：

PhosphineLigand

%e.e.oftheproduct

R=C6H5

R=H

（R,R）-DIPAMP

96（S）

94（S）

（S,S）-CHIRAPHOS

99（R）

91（R）

（S,S）-NORPHOS

95（S）

90（R）

（R,R）-DIOP

85（R）

73（R）

（S）-BINAP

98.5（R）a

（S,S）-BPPM

100（R）a

98（R）

（S）-BPPFA

93（S）

（S,S）-SKEWPHOS

92（R）

（S,S）-CYCPHOS

88（R）

（S,S）-Et-DuPHOS

99（S）

a.hydrogenateonofN-benzoylderivative

Halpern等人以及Brown等人对手性铑（Rh）膦催化剂的机理进行了详尽的研究。

烯烃能用Re面或者Si面与手性催化剂配位生成两个非对映体，氧化加成（K2）是速率控制步骤。

手性钌（Ru）膦催化剂催化机理

Ru（II）的配位数比Rh（I）大，可形成六配位数的八面体结构，后者只形成四面体结构。

机理更加复杂，形成单氢形式的活性中间体。

Halpern提出了机理如下

OrganicSyntheses,CV9,169

ASYMMETRICHYDROGENATIONOFALLYLICALCOHOLSUSINGBINAP-RUTHENIUMCOMPLEXES:

（S）-（−）-CITRONELLOL

[6-Octen-1-ol,3,7-dimethyl,（S）-]

SubmittedbyHidemasaTakaya1,TetsuoOhta1,Shin-ichiInoue2,MakotoTokunaga2,MasatoKitamura2,andRyojiNoyori2.

CheckedbyAndrewMadinandLarryE.Overman.

1.Procedure

Caution!

BINAP-Rucomplexesarerapidlyoxidizedinsolutioninthepresenceofair,andallproceduresshouldbecarriedoutunderanaerobicconditionsusingdegassedsolvents.

A.[（R）-2,2'

-Bis（diphenylphosphino）-1,1'

-binaphthyl]rutheniumdiacetate,Ru（OCOCH3）2[（R）-BINAP].Adry,150-mLSchlenktube（Note1）connectedtoasupplyofargon（Note2）isequippedwithaTeflon-coatedmagneticstirringbarandaglassstopper.Thevesselischargedwithbenzeneruthenium（II）chloridedimer,[RuCl2（benzene）]2,（800mg,1.60mmol）（Note3）and（R）-BINAP（1.89g,3.04mmol）（Note4）,evacuated,andthenfilledwithargon.N,N-Dimethylformamide（DMF）（30mL）（Note5）isintroducedwithahypodermicsyringeunderthestreamofargon.Thereddishbrownsuspensionisstirredat100°

Cfor10min（Note6）andtheresultingclearreddishbrownsolution（Note7）iscooled.Anotherdry,60-mLSchlenktubeischargedwithsodiumacetate（5.20g,63.4mmol）andmethanol（50mL）（Note8）andthesolutionisdegassedbythreefreeze-thawcycles.ItistransferredintotheDMFsolutionofBINAP-Ru（II）complexpreparedaboveviacannulaandthesolutionisstirredat25°

Cfor5min.Tothesolutionareaddedwater（50mL）andtoluene（25mL）underargonandtheresultingtwolayersaremixedbyvigorousstirring.Theupperorganiclayeristransferredintoanother200-mLSchlenktube（Note9）usingacannula.Theaqueouslayerisvigorouslymixedwithtoluene（25mL）andtheupperorganiclayerisagaintransferredintotheSchlenktube.Thisprocedureisrepeatedoncemore.Thecombinedorganiclayersarewashedwithfour10-mLportionsofwater（Note10）.Removalofthesolventat1mmand40°

Cfor30minwithvigorousstirring（Note11）andevacuationat0.1mmand25°

Cfor12hrgives2.54–2.67gofsolidRu（OCOCH3）2[（R）-BINAP]（99–104%crudeyieldbasedonBINAP）（Note12）.Itisdissolvedintoluene（20–25mL）withheating.Hexane（80–100mL）isaddedverycarefullytothesolutiondownthesideoftheflasktoformtwolayers.Thesolutionisleftat25°

Cfor12hrandthenat4°

Cfor3daystogivesolidmaterial.Removalofthemotherliquorisfollowedbywashingwithhexane（20mL）anddryingunderreducedpressuretoafford1.8–2.2g（71–85%yield）ofpureRu（OCOCH3）2[（R）-BINAP]asfineyellowneedlesorpowderycrystals;

mp188–190°

Cdec（Note13）.

B.（S）-（−）-Citronellol.Geraniol（12.9mL,74mmol）（Note14）and95%methanol（15mL）（Note15）areplacedinadry,80-mLSchlenktubeandthemixtureisdegassedbyfivefreeze-thawcycles.Anotherdry,80-mLSchlenktube,equippedwitharubberseptumandamagneticstirringbarandfilledwithargon,ischargedwithRu（OCOCH3）2[（R）-BINAP]（45mg,53μmol）（Note16）.Thesystemisevacuatedandrefilledwithargonthreetimes.Byuseofacannula,thesolutionofgeraniolinmethanolisintroducedintotheSchlenktubecontainingtherutheniumcomplexunderargon.Theresultinglightyellowsolution（Note17）isthentransferredwithacannulaintoa100-mL,stainlesssteelautoclaveequippedwithaglassvessel（Note18）andamagneticstirringbarbyuseofaslightpositivepressureofargon.Theautoclaveisconnectedtoahydrogensource（Note19）usingthearrangementshowninFigure1,andtheairoriginallypresentinthegas-inlettubeisreplacedbyhydrogen（Note20）.ValveAisopenedandhydrogenisintroduceduntilpressuregaugeBindicates100atm.Thesolutionisstirredat20°

Cfor8–16hr（Note21）.Duringhydrogenation,thehydrogenpressureiskeptabove90atmbytheoccasionalintroductionofhydrogenfromthecylinder（Note22）.Whenconsumptionofhydrogenceases,thegas-inlettubeisdisconnected.ExcesshydrogeniscarefullyreleasedbyopeningvalveAandthentheapparatusisdisassembled.Theyellowishbrowncontents（Note23）aretransferredtoa50-mLflaskandthesolventisremovedbyarotaryevaporator.Theresidue（Note24）isdistilledunderreducedpressuretogive10.7–11.2g（93–97%yield）of（S）-（−）-citronellolin98%ee（Note25）and（Note26）;

bp58–62°

C/0.01mm.

Figure1

2.Notes

1.Beforeuse,allapparatusisdriedovernightina120°

Coven.

2.Argon（99.998%）ispurifiedbypassingthroughaBASFcatalystRC-11columnat80°

Candthenthrough4Å

molecularsieves.

3.[RuCl2（benzene）]2,availablefromAldrichChemicalCompany,Inc.,isusedwithoutpurification.

4.BINAP[2,2'

-bis（diphenylphosphino）-1,1'

-binaphthyl]iscommerciallyavailableorcanbepreparedaccordingtoaliteratureprocedure.3Thediphosphineisslowlyoxidizedinairtogivethecorrespondingmono-anddiphosphineoxidesthatcanberemovedbycolumnchromatography（silicagel,benzene）underaninertatmosphere.

5.GuaranteedgradeDMF,availablefromNACALAITESQUE,Inc.,isdistilledover4Å

molecularsievesunderargonbeforeuseandstoredina100-mLSchlenktube.Itisdegassedbythreefreeze-thawcycles.

6.Reactionatahighertemperatureforalongerperiodleadstoformationoftherutheniumcarbonylcomplex[IR（KBr）1964cm−1].

7.ThesolutionmaybeacrudemixtureofcationicBINAP-Ru（II）complexessuchas[RuCl（BINAP）（DMF）3]Cland[Ru（BINAP）（DMF）4]Cl2.Physicalpropertiesincludeconductivity,27Scm2/mol（DMF）;

31PNMR（4:

1DMF-CDCl3）δ:

60.6（d,J=46）,61.4（d,J=46）,61.8（s）.The（R）-BINAP-Ru（II）complexobtainedbyremovalofthesolventcancatalyzehydrogenationofgeraniol（98.7%purecommercialgeraniolcontaining1.3%ofnerol,distilledfrom4Å

molecularsieves）.However,inadditionto（S）-citronellolin95–96%ee,dihydrocitronellol,anoverreductionproduct,isobtainedin3–7%yield（1.1Msubstratein95%aqueousmethanol,1.7mMcatalyst,100atmofH2,20°

C,8hr）.

8.Guaranteedgrademethanolisdistilledunderargon.

9.Thediameterisabout4cm.

10.Theextractionproceduremustbecarriedoutunderanargonatmosphere.

11.Underreducedpressure,thesolutionsometimesfoams.ThiscanbeavoidedbyheatingthetoppartoftheSchlenktubewithahotairgun.

12.CrudeBINAP-Rucomplexwithconsistentspectralcharacteristicscanbeusedforhydrogenationofgeraniol（98.7%purecommercialgeraniolcontaining1.3%ofnerol,distilledfrom4Å

molecularsieves,4.7Msubstratein95%aqueousmethanol,2.8mMRu（OCOCH3）2[（R）-BINAP],100atmofH2,20°

C,8hr）,togive（S）-citronellolin96%ee,97%isolatedyield.

13.Theproducthasthefollowingspectralproperties:

1HNMR（CDCl3）δ:

1.80（s,2OCOCH3）,6.47–7.84（m,aromaticprotons）;

31PNMR（CDCl3）δ:

65.13（s）;

13CNMR（CDCl3）δ:

23.50,125.2–138.3,188.1;

IR（CH2Cl2）cm−1:

1452,1518.Ananalyticalsampleispreparedbydryingat110°

Cand0.01mmfor12hr:

CalcdforC48H38O4P2Ru:

C,68.5;

H,4.6.Found:

C,68.4;

H,4.5.

14.Puregeraniolisobtainedbyfractionaldistillationusinga1000theoreticalplatecolumn.Thecheckersobtainedgeraniol,>

99.5%puritybyGCanalysis,fromFlukaChemicalCompanyanduseditdirectly.

15.The95%methanolispreparedbymixingdistilled,guaranteedmethanol（95mL）andwater（5mL）.Ifabsolutemethanolor90%aqueousmethanolisusedassolvent,somewhatlongerreactiontimesareneeded.

16.Thecomplexcanbestoredunderargonwithoutnoticeablelossofcatalyticactivity.Itisweighedunderanargonatmosphere.

17.Therutheniumcomplexismoderatelysolubleinmethanol.Ultrasonicstirringisemployedforcompletesolution.

18.Aglassvesselisusedforkeepingthereactionmixtureawayfromthestainlesssteelwall.Thereactionsystemisevacuatedandfilledwithargonthreetimesbeforeuse.

19.Thepurityofhydrogen（NipponSansoCo.）usedbythesubmittersis99.99999%.Thecheckersusedhydrogenof99.99%purity.

20.Thegas-inlettubeisattachedtotheautoclaveandthenthemainvalveofthecylinderisopened.Afterclosingthemainvalveofthecylinder,theconnectorofthegas-inlettubeisloosenedtoreleasehydrogenpressureandtightenedimmediately.Thisprocedureisrepeatedfivetimes.

21.To