11The Stille Reaction哈佛有机化学讲义Word格式文档下载.docx
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LL
■cistrans
Casado,A.L.;
Espinet,P.Organometallics1998,17,954-959.
•p-hydrideeliminationcanbeaserioussidereactionwithinalkylpalladiumintermediates.
iHVyd（II）L2X==+HPd（II）L2X
I
•Oxidativeadditionandreductiveeliminationstepsoccurwithretentionofconfigurationfor
sp2-hybridizedsubstrates.
•Transmetalationisproposedtobetheratedeterminingstepwithmostsubstrates.
•RelativeorderofligandtransferfromSn:
alkynyl>
alkenyl>
aryl>
allyl=benzyl>
a-alkoxyalkyl>
alkyl
•Thedetailsofthemechanismarestillbeingelucidated,andthemechanismmaychangewith
differentreactionconditions:
Espinet,P.J.Am.Chem.Soc.1998,120,8978-8985.
■StilleReactionconditions:
•Catalyst:
CommerciallyavailablePd（II）orPd（0）sources.Examples:
Pd（PPh3）4Pd（OAc）2Pd2（dba）3
O
dba=
•Ligands:
Phosphine（PR3）ligandsareoftenaddedwhenthePdsourcedoesn'
tcontainstrongligands.
Largerateenhancements（102-103）occurwithpoorlyelectron-donatingligands:
•AgeneralStillecross-couplingemployingarylchlorides（whicharemoreabundantandlessexpensivethanaryliodides,arylbromides,andaryltriflates）hasbeendeveloped.
tri-2-furylphosphine
Q
As
CPOAs
triphenylarsine
CH3O
Cl
Bu3Sn
OEt
Krishnan,B.J.Am.Chem.Soc.1991,113,9585-9595.
Pd2（dba）3（1.5mol%）
P（f-Bu）3（6.0mol%）
**
CsF（2.2equiv）
dioxane,100°
C
98%
•Additives:
CuIcanincreasethereactionrateby>
102.
Littke,A.F.;
Fu,G.C.Angew.Chem.,Int.Ed.Engl.1999,38,2411-2413.
•S^SnBus
Pd2（dba）3（5mol%）
PPh3（20mol%）
A
dioxane,50°
•1-substitutedvinylstannanescanbepoorsubstratesfortheStillereaction,probablyduetostericconstraints.However,conditionshavebeendiscoveredthataffordthedesiredStillecouplingproductinexcellentyields.
mol%CuI
relativerate
OHCH3
OMOM
（1.2equiv）
"
CH3
10
114
•TherateincreaseisattributedtothefreeligandscavengingabilityofCuI;
strongligandsinsolutionareknowntoinhibittherate-limitingtransmetalationstep.
OCT
Pd（PPh3）4（10mol%）
LiCl（6equiv）,CuCl（5equiv）
/PH3
DMSO,60°
C,45h
Kapadia,S.;
Krishnan,B.;
Wang,C.;
Liebeskind,L.S.J.Org.Chem.1994,59,5905-5911.；
Nf=n-CqFgSO?
92%
•StoichiometricCuitselfcanmediatecross-couplingreactionsundermildconditions,withoutPd.
SnBug
O
（1.5equiv）
CuO
NMP,23°
C,15min
89%
•TransmetalationofBu3SnwithCuClisproposedtoincreasetherateofthisreaction.
Isolationofthehomocouplingproductinthefollowingexperimentwastakenasevidenceforatransmetalationevent.
n-Pentyl
OH
Allred,G.D.;
Liebeskind,L.S.J.Am.Chem.Soc.1996,118,2748-2749.
NMP
N-CH3
CuCl（5equiv）,CuCl2（2equiv）
C,2h
84%
Han,X.;
Stoltz,B.M.;
Corey,E.J.J.Am.Chem.Soc.1999,121,7600-7605.
•Alkenesascouplingpartners:
+
OTBDMS
Ph
Pd2（dba）3（20mol%）
CdC*（1.8equiv）
（j-Pr）2NEt,NMP
40°
C,53h
69%
+BugSn1
OTBS
Pd（PPh3）4（10mol%）
LiCl,THF
80°
C,sealedtube
100%
N（cH3）2
CH
OCH3
I3
Ph:
（+）-A83543A,（+）-Lepicidin
•CdCl2servesasatransmetalationcocatalyst.Withoutit,homodimerizationofbothcouplingpartnerswasobserved.
Evans,D.A.;
Black,W.D.J.Am.Chem.Soc.1993,115,4497-4513.
CH34〃
HO2CH
Indanomycin（X-14547A）
Burke,S.D.;
Piscopio,A.D.;
Kort,M.E.;
:
■Matulenko,M.A.;
Parker,M.H.;
Armistead,D.M.;
Shankaran,K.J.Org.Chem.1994,59,332-347.:
Han,Q;
Wiemer,D.F.J.Am.Chem.Soc.1992,114,7692-7697.
Smith,A.B.;
Condon,S.M.;
McCauley,J.A.
Leazer,J.L.;
Leahy,J.W.;
Maleczka,R.E.J.Am.Chem.Soc.1995,117,5407-5408.
Rapamycin
1.[（2-furyl）3PbPdCl2（20mol%）（j-Pr）2NEt,DMF,THF,23°
C,7h
74%
2.TBAF,AcOH,0°
3.HF・Py,Py,THF,23°
61%
AndrewHaidle
SnBug
Pd（CH3CN）2Cl2
（20mol%）
（j-Pr）2NEtDMF,THF25°
C,24h
28%1
•Allylic,benzylichalides:
CH”.
Acerosolide
CHCI3,reflux,48h
65%
CH3OCH3CH3CH3:
Rapamycin:
Nicolaou,K.C.;
Chakraborty,T.K;
Minowa,N.;
Bertinato,P.J.Am.Chem.Soc.:
■1993,115,4419-4420.
■■
•Acidchloridescanbeusedascouplingreagents（theStillereaction,asfirstreported,used；
acidchlorides）.:
Milstein,D.;
Stille,J.K.J.A^m.Chem.Soc.1978,100,3636-3638.
OBnPdCI（PPh3）2（2.5mol%）o
CH^Cl+3H°
C"
5%）ACH^^oj
3H2n4、OTHF,50c15min3:
93%H2NO
Paquette,L.A.;
Astles,P.C.J.Org.Chem.1993,58,165-169.
TBSO
H
O八OCH3
PdCl2（CH3CN）2（3mol%）
PPh3（5mol%）
DME,reflux
75%
Liebeskind,L.S.;
Yu,M.S.;
Fengl,R.W.J.Org.Chem.1993,58,3543-3549.
MonocillinI
・.、O
OOCH3
Lampilas,M.;
Lett,R.TetrahedronLett.1992,33,777-780.
Pd2（dba）3-CHCl3（15mol%）AsPhg（0.6equiv）/Pr2NEt（10equiv）
DMF,25°
C,36h
62%
Pd2（dba）3・CHCl3（10mol%）
AsPh3（0.2equiv）
/PrzNEt（10equiv）
DMF,40°
C,5h
45%
2NH2SO4（2.0equiv）
THF:
H2O4:
1,25°
33%（plus50%startingmaterial）
•InthefirstStillecoupling,noneoftheregioisomericcouplingproductwasisolated.
Murphy,F.;
Barluenga,S.;
Ohshima,T.;
Wei,H.;
Xu,J.;
Gray,D.L.F.;
Baudoin,O.J.Am.Chem.Soc.2000,122,3830-3838.
Examplesinvolvingcopper（I）:
•Thecopper（I）-mediatedcouplingofavinylstannaneandavinylbromidesucceededwhenpalladiumcatalysisfailed.Notetheselectivetransformationofthevinyltriflatetothevinylstannaneinthepresenceofthevinylbromide.
•Liebeskind'
scopper（I）thiophene-2-carboxylatepromotedcouplingreactionwasusedforthetotalsynthesisofconcanamycinF.Thisreactionfailedintramolecularlywhenthetwocouplingpartnershadalreadybeenjoinedviatheesterlinkage.
OTf
CH3CH3
CuCl（3equiv）
DMF,60°
C,1h
Pd（Ph3）4（2mol%）
LiCl（6equiv）
（CH3）3SnSn（CH3）3（2equiv）
THF,reflux,16h
^^Sn（CH3）3
L-CH3
Br
Et
TESO
CH3CH3OCH3
•”otCS
ConcanamycinF
R=DEIPS
Huang,A.X.;
Xiong,Z.;
Corey,E.J.J.Am.Chem.Soc.1999,121,9999一10003.
Paterson,I.;
Doughty,V.A.;
McLeod,M.D.;
Trieselmann,T.Angew.Chem.,Int.Ed.Engl.2000,39,1308-1312.AndrewHaidle
SynthesisofArylandVinylStannanes:
Bu3SnCl（0.85equiv）►BugSn，
Li•NH2CH2CH2NH2THF,0°
Ct25°
C,18h
33%
•Directedorthometalationfollowedbyadditionofastannylchlorideisastandardmethod.
Snieckus,V.Chem.Rev.1990,90,923-924.
Bu3SnH（1.2equiv）
AIBN（2.4mol%）
90°
C,6h
Bu3Sn，SnBu3
t-BuLi（3.8equiv）
Et2。
，23°
C,2h;
>
Bu3SnCl（4.3equiv）
SnBu
90%
Renaldo,A.F.;
Labadie,J.W.;
Stille,J.K.Org.Synth.1988,67,86-97.
Tius,M.A.;
Gomez-Galeno,J.;
Gu,X.;
Zaidi,J.H.J.Am.Chem.Soc.1991,113,5775-5783.
Bu3Sn"
snBu3
CH3Li（1.2equiv）,THF,-78°
ClCO2Et（1.2equiv）,2.5h;
CH3OH
[（CH3）3Sn]2
Pd（PPh3）4（5mol%）
DME,80°
C,15h
97%
（CH3）3Sn
59%
Benaglia,M.;
Toyota,S.;
Woods,C.R.;
Siegel,J.S.TetrahedronLett.1997,38,4737-4740.
CH3OH
I人O
Bu3SnOCH3,Et2O,23°
C;
OTHP
RSnR3
Bu3SnH（1.1equiv）
AIBN（3mol%）
95°
C,3h
+r«
：
^YCH3
BugSnOTHP
92%85:
15
•Theadditionofstannylradicalstoalkynesisreversibleundertheseconditions.Theproductratioreflectsthethermodynamicequilibrium.
Corey,E.J.;
Ulrich,P.;
Fitzpatrick,J.M.J.Am.Chem.Soc.1976,98,222-224.
Bu3SnSsnBu3
PdCl2（CH3CN）2（5mol%）
BugSnO
Thibonnet,J.;
Abarbi,M.;
Parrain,J.-L.;
Duchene,A.Synlett1997,771-772.
Bu3Sn（Bu）CuCNLi2
THF,-40°
C,20min;
NHQ
SnBu3
95%
97:
3E:
Z
Aksela,R.;
Oehlschlager,A.C.Tetrahedron1991,47,1163-1176.
CH3（2-Th）CuCNLi2（1equiv）
►
-10°
Ct23°
C,THF,Et2。
30min
Bu3SnCuCNLi2
6
CrCZ/BusSnCHZ
C,2.5h;
H2O
SriBug
82%
1998,39,6419-6420.
Hodgson,D.M.;
Foley,A.M.;
Lovell,P.J.TetrahedronLett.
n-Bu
HB（c-C6H“）2
——612n-BuB（c-Hex）2
THF
NaOH（1equiv）,THF,23°
C,0.5h;
Cu（acac）2（5mol%）;
BusSnCI,-15°
n-BuSnBu3
Behling,J.R.;
Ng,J.S.;
Babiak,K.A.;
Campbell,A.L.;
Elsworth,E.;
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