cyanomethylation jian-zhou huang 2013-07-06. intrduction basic phosphine and nhc catalyted by...
Post on 17-Jan-2018
218 Views
Preview:
DESCRIPTION
TRANSCRIPT
Cyanomethylation
Jian-Zhou Huang2013-07-06
IntrductionBasic phosphine and NHCCatalyted by metal
Ruthenium Copper Palladium Nickel
Decarboxylative ReactionCross-couplingConclusion
Contents
Intrduction: pKa
alkyl CN
H
Ph CN
H
pKa = 21.9pKa ~ 31.3
CNH
pKa ~ 21.1 in DMSO
OH
Ph
H2O2 aq, Na2CO3acetone, rt
74 % yield
OH
PhCN O NH2
PhCN
NHTs
Ph
1) NiCl2H2O( 1.0 equiv) (Boc)2O( 2.0equiv) NaBH4(7 equiv)
2) diethylenetriamine(1 equiv) MeOH, 0oC to rt, 15h
Ph
NHTs
PhNHBoc
Ph
NHSO2PyCN
conc HCl, dixoxane,reflux,12hPh
NHSO2PyCOOH
Basic phosphine and NHC
TMSCH2CN PR3+ Si CN
PR3
SiPR3
CH2CN RCHOR
OHCN
Cl
CHO
+ TMSCH2CN1, NHC 5 mol%, DMF, RT
2, H+ Cl
OHCN
83 % yield
NN Ar
Ar
NHC
Ph
O
HTMSCH2CN+
TTMPP(20 mol%)
DMPU, 8h, 50 oC Ph
OHCN
92 %
TTMPP[2,4,6-(OMe)3C6H2]3P
Ph
O
HTMSCH2CN+ 1, cat (2 mol%), THF, 0oC
Ph
OHCN2, H+
PNN
N
N
i-Pri-Pr
i-Pr
89% yield
S, Matsukawa, Tetrahedron Letters 2008, 49, 2982
J. G. Verkade, J. Org. Chem. 2009, 74, 5683L. He, Tetrahedron Letters 2012, 53, 2231
RutheniumRCHO
+ CH3CN
CpRu(PPh3)(CH3CN)2PF6 5 mol%DBU 5 mol%, NaPF6 10 mol%
CH3CN/HMPA 3/1, 4Å MS
R
OHCN
NR2
R1 R1
NHR2
CN
yield 72 - 93 %
yield 79 -91 %
RuPh3P NCCH3
NCCH3
PF6DBU DBU•H
PF6
R
ONaCN
R
OHCN
NaPF6
RuPh3P
NCCH3
N CH2
RuPh3PCH3CN
O
R CN
RuPh3PCH3CN
DBUPF6
DBU•HPF6 R
OHCN
Shibasaki, J. Am. Chem. Soc. 2004, 126, 13632-13633
decomp without NaPF6
CH2CN
Ph3P=ORu black P
ONN
N
HMPA
H
OR
HH
CN
H
pKa 15.7-16.9(H2O)
pKa ~28.9(H2O)
+ nitrile selectivedeprotonation
ROH
CN
RuPh3P NCCH3
NCCH3
PF6Ru
Ph3P NCCH3PPh3
PF6
1a 1b
CH3CN CHOR+
[Ru] 10 %mol, DBU 50 % mol
4 Å MS, CH3CN/HMPA 3/150 0C
38 % yield 64 % yield
2a was added slowly over 7 h, yield = 82 %
ROH
CN
Shibasaki, Chem. Commun., 2005, 3600-3602
Copper
R1 R2
O+ TMSCH2CN
CuF3PPh32EtOH(2.5%)(EtO)3SiF(120 mol%)
3HFNEt3R1
OHCN
R2
O
93 %
Ph
O
75%
O
79%
Ph H
O
92 %
CHO
86 %
CuF·3PPh3 ·2EtOH+
(EtO)3SiF
Si OEtF
EtO
EtO
TMSCH2CN TMSF
Cu(PPh3)3
(EtO)3SiCH2CNF
Cu(PPh3)3
N Cu(PPh3)3
+(EtO)3SiF
NR
H
NSiMe3
CutBuO Si OEt
EtOEtO
FCu
hard interation
soft interation
F
Ph H
OCH3CN
CuOtBu(10 mol%)/dppe(15 %)
DMSO,RT+
Ph
OHCN
95 % yield
H
OCH3CN
CuOtBu(10 mol%)/L*(15 %)
DMSO,500C+
OHCN
72 % yield74 % ee
Masakatsu Shibasaki, Org. Lett, 2005, 7, 3757-3760
5 5PP
tBuO
tButBu
OtBu
O
O
O
O
2
2L*
Masakatsu Shibasaki, Org. Lett, 2003, 5, 3147-3150
2 -Naph
NDpp
+CN [Cu(CH3CN)4]ClO4/L*
Li(OC6H4-p-OPh)
CH2Cl2/THF, -20oC,40h2 -Naph
HN Dpp
CN
2 -Naph
HN Dpp
CN
isomerization
2 -NaphCN
91% yield90 % eeZ/E = 93/7
Masakatsu Shibasaki, J. Am. Chem. Soc. 2008 , 130 , 14477-14479
P P
Ph
Ph
Ph
Ph
CNH
pKa ~ 21.1 in DMSO
Lewis acid/hard Brønsted base/hard
Shibasaki. J. Am. Chem. Soc. 2009,131, 3195
O
+CN [Cu(CH3CN)4]ClO4/L*
Li(OC6H4-p-OPh)
THF, -20oC,40h
P P
Ph
Ph
Ph
Ph
Ph
OH
CN81 % yield97 % ee
CN
Cu*
CN*Cu
C-copper C-copper
PhCOCH3
CuO
NH
Ph
PP
*
*Cu(OC6H4-o-OMe)
Lewis acid/hard Brønsted base/hardLewis base
O
+CN
[Cu(CH3CN)4]ClO4/L*Li(OC6H4-p-OPh)
LB
THF, -40oC,40h
P P
Ph
Ph
Ph
Ph
Ph
OH
CN86 % yield99 % ee
P
P
O PhPh
O PhPh
LB
Shibasaki, M. J. Am. Chem. Soc. 2010,132, 5522
2 -Naph
NDpp
+CN
Mesitylcopper(10 mol%)L*(10 mol %)HOC6H4-p-OMe(10 mol%)
CH2Cl2/THF, -20oC,40h2 -Naph
HNDpp
CN
1) Li free
2) Li free + LiClO4
yield: < 5%, 88% ee
2 -Naph
NDpp
+CN
Mesitylcopper(10 mol%)L*(10 mol %)HOC6H4-p-OPh(10 mol%)
CH2Cl2/THF, -20oC,40h2 -Naph
HNDpp
CN
yield: < 78%, 83% ee
LiClO4(10 mol %
3) without [Cu(CH3CN)4]ClO4 yield 8%
2 -Naph
NDpp
+CN
LiOC6H4-p-OPh(10 mol%)
CH2Cl2/THF, -20oC,40h2 -Naph
HNDpp
CNLiClO4(10 mol %
mechanism
[Cu(CH3CN)4]ClO4
+(R,R)-Ph-BPE
LiOAr
+
THFCu
P L
P L* +LiOAr Cu
P L
P OAr* + LiClO4
inactiveNC
CuP L
P N*
HO
Li
O
soft lewis acid hard bronsted base
31P NMR spectra
Bn2N Ph
S CN+
[Cu(CH3CN)4PF6/L*Li(OC6H4-p-OMe) 5 mol%
Toluene ,0oCBn2N
S Ph
CN
O
O
O
O
PAr2PAr2
L*
P
P
O PhPh
O PhPh
Ph2P PPh2
OO
5
without Phosphine oxide
9 % (83 % ee) 76 % (95 % ee) 81 % (95 % ee)
Ph3PO
74% (95 % ee)Ar = 3,5-(tBu)2-4-MeOC6H2
CN
Cu*
CN*CuBn2N Ph
S
CuSP
P
NBn2
NC H H
* Bn2N
S Ph
CN
Plausible transition state
Masakatsu Shibasaki, Angew. Chem. Int . Ed. 2011 , 50 , 7910 -7914
C-copper C-copper
CNO O
PdPh2P PPh2OCOCF3
NTs
Ph+
cat, 20oC, 5hNaHCO3(1.0 eq), THF
PhCN
NHTs
dr = 3:2yield = 90%
O OPdPh2P PPh2
CNH
O OPdPh2P PPh2
HNC
O OPdPh2P PPh2
CN
O OPdPh2P PPh2NC
HE = 0 kcal/mol E = 1.2 kcal/mol E = 1.2 kcal/mol E = 6.7 kcal/mol
O OPdPh2P PPh2
NCH NTs
PhK. J. Szabo, Org. Lett. 2008 , 10 , 2881
Palladium-pincer ligand
PhCH2CN +Ph H
NTs cat(5 mol%)
NaHCO3( 1equiv)TsHN
PhCN
Phdr = 2:1yield = 99%
O OPdPh2P PPh2OCOCF3
PhCH2CN NTs+
dr = 1.3:1yield = 71%ee = 33 %
O OPdP PTFA
OO
O
O
TsHN
CyCN
Ph
K. J. Szabo, Org. Lett. 2008 , 10 , 5175-5178
20oC, THF, 15h
cat(5 mol%)NaHCO3( 1equiv)
20oC, 15h
N
Ph
Ts+
Ph CN
cat (5 mol%)AgOAc(5 mol%)K2CO3(1.0eq)
THF, MS 5Å,-20oC
HN
Ph
Ts
CN
Ph
97 % yielddr = 93:7er = 95: 5
Pd
N
N N
NCOPh
Ph
PhPh
Ph
PhOC
OAc
PhCH2CN
OAC
Pd
N
N N
NCOPh
Ph
PhPh
Ph
PhOC
N
PhHOAC
HOAC
Pd
N
N N
NCOPh
Ph
PhPh
Ph
PhOC
NC
PhH
Pd
N
N N
NCOPh
Ph
PhPh
Ph
PhOC
N Ts
PhPh
CN
N
Ph
Ts
HN
Ph
Ts
CN
Ph
Pd
N
N N
NCOPh
Ph
PhPh
Ph
PhOC
Brcat
Norio Shibata, Adv. Synth. Catal. 2011, 353, 3385
aza-MBH
NTs
Ph CN
cat(5 mol%), DABCO(5 mol%)AgOAc(5 mol%)
iPrCN, 4Å MS,-10oC
NHTs
Ph CN
93 %, (94 % ee)
+
Pd
N
N N
N
Ph
Ph
Ph
Ph
OAc
Ac Ac
Pd
N
N N
N
Ph
Ph
Ph
Ph
N
Ac AcPd
N
N N
N
Ph
Ph
Ph
Ph
NTs
Ac Ac
Pd
N
N N
N
Ph
Ph
Ph
Ph
N
Ac Ac
CDABCO+
DABCO
NTs
Ph
CN
DABCO+
Ph
AcO-
NHTs
Ph CN CN
OAc-
N. Shibata, Angew. Chem. Int . Ed. 2012 , 51, 10337
Nickel
NPiPr22
iPrP NiOTf
O
H
F
CH3CNsolv, cat
DBU(100 mol%), 45 oC, 24 h
OH
F
CN
75 % yield
[Ni]-DBU-DBU
+DBU[Ni] N CH3 [Ni] N CH2
DBUDBU-H+ RCHO
[Ni] N CH2
O H
R[Ni] N CH2
HO H
R
NCR
OH
+
O
H
F
CH3CNsolv, cat
DBU(100 mol%), 45 oC, 24 hNR(PNP)Ni-OTf
LiCH2CN
CH3CN
LiN(TMS)2
(PNP)Ni-CH2CN
Chem. Commun., 2005, 4450
Base-Free Conditions
PhCHO+ CH3CNcat, rt, CH3CN
Ph
OHCN
cat 1 mol % yield = 91 %cat 0.01mol % yield = 72 %, TON = 10 000
138 mL(1.36 mol)
150 mL(2.87 mol)
cat(5 ppm)(3.0 mg)
TON = 82 00041% conversion
M N C CH2
B: BHM N C CH3
RCHOM O CN
R
CH3CN+BH+
HOR'+B:
O
Ni
O
PiPr2
PPiPr2
CH2CN
O
Ni
O
PiPr2
PPiPr2
O CH2CN
R
H
RCHO RCHO
CH3CN
R
OHCN cat
with base
base free
H. Guan, Angew. Chem . Int. Ed. 2013 , 52 ,ASAP
VS
Decarboxylative MannichReaction
Ph
NSO2Py
+ HO
OCN
cat(5% mol), AgOTf(5 mol%)
THF, 4Å MS, RT Ph
NSO2PyCN
82 % yield, 88 % ee
Pd
N
N N
NCOMe
Ph
PhPh
Ph
MeOC
Brcat
S. Nakamura, Chem. Eur. J. 2013, 19, 4128
H2CC
N [Pd]
VS O
OC
NPd
decarboxylation deprotonation
NP(O)Ph2
HPh+ CNHOOC
Ph2.5 eq
CuOAc-L*(5 mol%)
THF, 0oC, 12 h
NP(O)Ph2
PhPh
CN
dr = 7.1:1yield = 94 %ee = 87 %
O
O
O
O
P
P
OMe
tBu
tBu
tBu
OMetBu
2
2DTBM-SEGPHOSM, Shibasaki, J. Am. Chem. Soc. 2009 , 131 , 9610
Pd
N
N N
NAc
Ph
PhPh
Ph
Ac
OTf
Pd
N
N N
NAc
Ph
PhPh
Ph
Ac
Pd
N
N N
NAc
Ph
PhPh
Ph
Ac
O
Pd
N
N N
NAc
Ph
PhPh
Ph
Ac
N SO2Py
PhCOO-
CN
N
Ph
NSO2Py
HN
Ph
NSO2Py
CNHO
OCN
HOTf
O
ON
base
base• H+
OCN
H
HOTf
APCI mass (positive, 792.2)exact mass: 792.2 [M+H+]
NH
O
O
HOCN
O
+NH
O
HOEt3N(20mol%), DMF, 70oC
72h95 %
CN
J. Wang, ACS Catal. 2012, 2, 2622 - 2625
N
N CF3
O
CN
COOH
pyridine(solv),70oC
12h N
N CF3
OH CN
70 % yield
D. M. Volochnyuk, Synthesis 2009, 7, 1099
CN
PhO2S NHBoc
SO2TolPh+
1) cat 20 mol%) CsOHH2O(130 mol%) toluene/CH2Cl2 = 9:1
2) Mg, TMSCl MeOH, RT, 3h
NHBoc
Ph CN
90 % yield, 76 % ee
N
O2N
OH
N
O
Cl
CN
PhO2S NBoc
Ph+
1)(DHQ)2PYR (20 mol %) DCM, -40oC, 20h
2) Mg, TMSCl, MeOH,RT,3h
NHBoc
Ph CN
92 % yield 73 % ee
CN
PhO2SCN
C. Palomo, J. Org. Chem. 2010, 75, 3920
Cross coupling
Br+ NC TMS
2 mol% Pd2dba3/Xantphos0.5 eq ZnF2, DMF, 90oC
John F. Hartwig, J. Am. Chem. Soc., 2005, 127, 15824
CN
Cl +NC COONa
tBu 87 % yield
2 mol%[Pd2(allyl)2Cl2]6 mol% S-Phos140oC, 5h, mesitylene
CN
tBu
86% yiled
Lei Liu, Angew. Chem. Int . Ed. 2011 , 50 , 4470
+ CO2
Conclusion
(1) 反应类型比较少，大部分仍需要加入强碱；(2）不对称的反应较少(3) 反应体系复杂，添加剂多(4) 需要活化基团活化，原子经济性差。
Thank You!
top related