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Rhodium(III)‐CatalyzedDehydrogenativeHeckReactionof
SalicylaldehydesShi,Z.;Schröder,N.;Glorius,F.Angew.Chem.Int.
Ed.2012,EarlyView,DOI10.1002/anie.201203224
CurrentLiteraturePresentedbyMelissaSprachmanJuly28,2012
H
OH
R1
O 2.5 mol% [(Cp*RhCl2)2]
10 mol% C5H2Ph4
Cu(OAc)2, DCE
R
R1
O
O
R
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FunctionalizationofAldehydeC‐HBondsUmpolungofAldehydeswithNHeterocyclicCarbenes(NHCs):
O
HAr1
Ar2
O
Ar3+
NN
N
PhTBDPSO
BF4
(10 mol%)
DBU (10 mol%)
THF, 0 °C, 6 hAr3
Ar2
O
Ar1
O
43-98%; 56-78% ee
Bugaut,X.;Glorius,F.Chem.Soc.Rev.2012,41,3511‐3522.
O
O
H
Ar
RO
O
R
Me
Ar
O
NN
N
Ph
Mes
Cl
(10 mol%)
DBU (20 mol%)
dioxane, 80 °C, 20 h
8-99%; 96-99% ee
Piel,I.;Steinmetz,K.;Hirano,R.;Fröhlich,R.;Grimme,S.;Glorius,F.Angew.Chem.Int.Ed.2011,50,4983‐4987.
O
HAr+
R2
R1
O
NN
N
Ph(20 mol%)
K3PO4 (1.5 equiv)
dioxane, 40 °C, 24 h
MeO
MeOBF4
R1
R2
O
Ar
up to 95% yield> 20 : a drup to 96% ee
Liu,F.;Bugaut,X.;Schedler,M.;;Fröhlich,R.;Glorius,F.Angew.Chem.Int.Ed.2011,50,12626‐12630.
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FunctionalizationofAldehydeC‐HBondsStartingPoint:IntramolecularAlkeneHydroacylation:
O
H
RhCl(PPh3)3 (10 mol%)
CHCl3, C2H4, rt, 86 h
72%
O
Lochow,C.F.;Miller,R.G.J.Am.Chem.Soc.1976,98,1281‐1283
Willis,M.C.ChemRev.2010,110,725‐748.
[RhI]
O
H
[RhIII]
OH [RhIII]
CO
H H2C
+
[RhI]
CO
H
Decarbonylation Pathway
[RhIII]
OH
[RhIII]
O
O
H
syn-addition
H
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IntermolecularAlkeneHydroacylationO
H
RhCl(PPh3)3 (10 mol%)
CHCl3, C2H4, rt, 86 h72%
O
O
H
Rh(acac)(C2H4)2 (10 mol%)
CHCl3, C2H4, rt, 16 h
O
+
O
+
O
1% 6% 39%
Nohydroacylationproductswereformedwhensaturatedaldehydeswereusedassubstrates.
Itwashypothesizedthatinternalalkenecoordinationwasrequiredforreactivity.
Useofheteroatomchelationasastrategyforintermolecularhydroacylation
Lochow,C.F.;Miller,R.G.J.Am.Chem.Soc.1976,98,1281‐1283.Vora,K.P.;Lochow,C.F.;Miller,R.G.J.Organomet.Chem.1980,192,257‐264.
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HydroacylationviaHeteroatomChelation
H
OH
O Pr
Pr
+
[RhCl(COD)]2 (1.0 mol%)dppf (1 mol%)
Na2CO3 (5 mol%)PhMe, reflux, 20 h OH
O
Pr
Pr
H
OH
O
+SiEt3
[RhCl(COD)]2 (0.5 mol%)dppf (1 mol%)
Na2CO3 (5 mol%)PhMe, reflux, 20 h
OH
O
SiEt3
87%
H
OH
O
+
[RhCl(COD)]2 (0.5 mol%)dppf (1 mol%)
Na2CO3 (5 mol%)PhMe, reflux, 5 h OH
O
quant.
O
Rh H
O
Kokobu,K.;Matsumasa,K.;Nishinaka,Y.;Miura,M.;Nomura,M.Bull.Chem.Soc.Jpn.1999,72,303‐311.
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DehydrogenativeHeckReaction(DHR)
TraditionalMizoroki‐HeckReaction:
Ar-X + ZPd
0
ZAr
DehydrogenativeHeckReaction:
Ar-H + Z ZArPd(II) (cat.)
oxidant
Pd0
ArPdX
Z
Z
PdX
Ar
ZAr
HPdX
base
base HX
ArPdX
Z
Z
PdX
Ar
ZAr
HPdX
PdX2
ArH
HX
Pd0
HX
oxidant
reduced oxidant
Bras,J.L.;Muzart,J.Chem.Rev.2011,111,1170‐1214.
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Rh(III)‐MediatedC‐HOleeinationUseofanoxidizingdirectinggroup:
R1 NH
O
OMe +
R2
[Cp*RhCl2]2 (1.0 mol%)
CsOAc (30 mol%)
MeOH (0.2 M)60 °C, 3-16 h
R1 NH2
O
R2
52%-99%
NH
O
OMe
H
+ Ph
NH
O
OPiv
H
[Cp*RhCl2]2, CsOAc
MeOH, 60 °C
[Cp*RhCl2]2, CsOPiv
PivOH, EtOH, 80 °C
Rh(III)N
OOR1
HPh
!-hydride elimination
R1 = Me
R1 = Piv
C-N reductive
elimination
N-O bond cleavage and (re)oxidation of the Rh catalyst
NH
O
OMe
Ph
NH
O
Ph
Rakshit,S.;Grohmann,C.;Besset,T.;Glorius,F.J.Am.Chem.Soc.2011,133,2350‐2353.
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InspirationfortheTitlePaper
Lu,Y.;Wang,D.‐H.;Engle,K.M.;Yu,J.‐Q.J.Am.Chem.Soc.2010,132,5916‐5921
Me
HOH
+ CO2Et
Pd(OAc)2 (10 mol%)Li2CO3 (1 equiv)AgOAc (2 equiv)
C6F6, 80 °C, 48 hO
CO2Et
Me
O NH
O
CO2H
(20 mol%)
Me
85%
Electron deficientOlefin
H
MeO
Pd(OAc)2 (10 mol%)Li2CO3 (1 equiv)AgOAc (2 equiv)
C6F6, 80 °C, 48 h
Me
O NH
O
CO2H
+OH
MeO
OH
Ph49%
(20 mol%)Electron neutralOlefin
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Rh‐CatalyzedSynthesisofChromones
OH
O
H +
Ph
Ph
[{RhCl(cod)}2]/C5H2Ph4
Cu(OAc)2•H2OO
O
Ph
Pho-xylene, 140 °C, 2 h
86%
Shimizu,M.;Tsurugi,H.;Satoh,T.;Miura,M.Chem.AsianJ.2008,3,881‐886.
O
O
H
RhX2-HX
RhIIIX3
OH
O
H
-HX O
RhX
O
R2
R1
O RhX
OR2
R1
O
O
R2
R1
RhIX
2 CuIIX2
2 CuIX
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Rh(III)‐CatalyzedDHRofSalicylaldehydes
OH
O
H + CO2Et
[catalyst]
oxidant
solvent, 120 °C, 18 h O
O
CO2Et
CatalystandOxidantOptimization:
Entry Catalyst(mol%) Oxidant(equiv)
Solvent Yield
1 [RuCl2(p‐cymene)]2(2.5) Cu(OAc)2(2) t‐amylOH 0%
2 [Cp*RhCl2]2(2.5) Cu(OAc)2(2) t‐amylOH 12%
3 [Cp*RhCl2]2(2.5) Cu(OAc)2(4) t‐amylOH 48%
4a [Cp*RhCl2]2(2.5) Cu(OAc)2(4) DCE 76%
A10mol%1,2,3,4‐tetraphenyl‐1,3‐cyclpentadienewasusedasaligand
SelectedexamplesfromtheSIfromtheTitlepaper.Cp* =
cymene
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SalicylaldehydeSubstrateScope
O
O
CO2Et
R1
R1
H
Yield Z/E ratio
76% 98:2
Me 80% 98:2
OMe 82% 95:5
SMe 85% 100:0
NO2 44% 100:0
Ph 71% 99:1
CO2Me 68% 99:1
R1
F
Yield Z/E ratio
70% 98:2
62% 96:4
70% 95:5
33% 95:5
Cl
Br
I
O
O
CO2Et
O
O
CO2Et
O
O
CO2Et
63% (97:3) 75% (100:0)
O
76% (93:7)
H
OH
R1
O [(Cp*RhCl2)2] (2.5 mol%)
C5H2Ph4 (10 mol%)
Cu(OAc)2 (4 equiv)
DCE, 120 °C, 18 h
CO2Et R1
O
O
R+
(Z/E)
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SalicylaldehydeSubstrateScope
H
OH
R1
O [(Cp*RhCl2)2] (2.5 mol%)
C5H2Ph4 (10 mol%)
Cu(OAc)2 (4 equiv)
DCE, 120 °C, 18 h
CO2Et R1
O
O
R+
(Z/E)
H
O
Et2N OH
[(Cp*RhCl2)2] (2.5 mol%)
C5H2Ph4 (10 mol%)
Cu(OAc)2 (4 equiv)
DCE, 120 °C, 18 h
CO2Et
+
O
O
CO2EtEt2N30%
+
O
Et2N OH
CO2Et
28%
resubjected
O
O
CO2EtEt2N40%
+
O
Et2N OH
CO2Et
36%
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OleeinSubstrateScope
H
OH
R1
O [(Cp*RhCl2)2] (2.5 mol%)
C5H2Ph4 (10 mol%)
Cu(OAc)2 (2 equiv)
DCE, 120 °C, 18 h
Ph R1
OH+
orR1Ph
O
O
O
Ph
orR1
O
O
Ph
OH
Ph
O
R1
R1 Yield
H
Me
F
Cl
CO2Me
66%
71%
47% + < 10% chromone
43% + < 10% chromone
64% + < 10% chromone
O
O2N
O
Ph
44% (4 equiv Cu(OAc)2
O
O
Ph
34% (2 equiv Ag2CO3
was used as the oxidant)
O OH
O
Ph
57% (lonchocarpin)
O OH
O
54% (4-methoxylonchocarpin)
OMe
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MechanisticInsights
H
O
H + CO2Et
[(Cp*RhCl2)2] (2.5 mol%)
C5H2Ph4 (10 mol%)
Cu(OAc)2 (4 equiv)
DCE, 120 °C, 18 hH
O
CO2Et
not detected
OMe
O
H + CO2Et
[(Cp*RhCl2)2] (2.5 mol%)
C5H2Ph4 (10 mol%)
Cu(OAc)2 (4 equiv)
DCE, 120 °C, 18 hOMe
O
CO2Et
not detected
OMe
O
H
CO2Et
28%
OH
NTs
+ CO2Et
[(Cp*RhCl2)2] (2.5 mol%)
C5H2Ph4 (10 mol%)
Cu(OAc)2 (4 equiv)
DCE, 120 °C, 18 h
OH
NTs
CO2Et
not detected
+
O
N Ts
CO2Et
not detected
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ProposedMechanism
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Salicylaldehyde‐BasedNaturalProducts
O
O
Ph O
O
Ph OH
O
Ph
O
O
aurone flavone 2'-hydroxychalcone flavanone
Alternativesynthesisofaurones:
Harkat,H.;Blanc,A.;Weibel,J.‐M.;Pale,P.J.Org.Chem.2008,73,1620‐1623.
OH
OH
Ph
AuCl/K2CO3
(10 mol%)
MeCN, rt
84% O
OH
Ph
MnO2
CH2Cl2, rt, 1 hO
O
Ph90%
OH
O
H
Ph H (3 equiv)Cy3AgCl (10 mol%)
i-Pr2NEt (20 mol%)
H2OO
OH
Ph
MnO2
CH2Cl2, rt, 2 hO
O
Ph75% (2 steps)
Yu,M.;Skouta,R.;Zhou,L.;Jiang,H.‐f.;Yao,X.;Li,C.‐J.J.Org.Chem.2009,74,3378‐3383.
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SummaryandOutlook
AcatalyticDHRreactionusingsalicylaldehydeshasbeendeveloped.
Themethodologyforformingauronederivativesmaybelimitedtocaseswhereelectron‐deeicientoleeinsareusedassubstrates.
Theauthorsdemonstratedthenecessityofheteroatomchelationforthereactiontoproceed.
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