Post on 30-Nov-2018
Group Meeting12/7/2005
Narendra Ambhaikar Electrochemistry in Organic Synthesis
BrH
N
R2
COR1
N
COR1
CO2H
R2CO2H
R2=CH3, C5H11, (CH2)4CO2CH3
+
R1=H, CH3
NR
O
NR
O
anodic oxid.MeOH
!e!, !H+ +NuH, !H+N
R
O
NR
O
Nu
i) Kolbe and non-Kolbe oxidations of carboxylic acids
ii) Oxidation of amides
HNO
O
CH2Cl
C anodeconst. currentMeOH
HNO
O
CH2ClMeO
"-methoxy amide
NO
O
CH2Cl
HO
HO H
3 steps
NNH
N
O
Me N NC anodeEt4NOTsMeOH
(100%)
NNH
N
O
Me N N
OMe
s-BuLithen O2
(10-35%)
NNH
N
O
Me N NH
O
NNH
N
O
Me N NH
OOMe
C anodeNaOMeMeOH
(97%)
iv) Anodic oxidation of thioethers
N
SPh
Ph
O
N
SPh
Ph
OF
Pt anodeEt4NF.3HFMeCN
(70%)
N
N
S CO2Et
F
N
N
S CO2Et
Pt anodeEt4NF•3HFDME
(78%)
v) Introduction of F into biologically active molecules
OR
HO
OR
O
( )n
( )n
vi) Oxidation of alcohols and ethers
sproketal
Pt anodeLiBF4
NaOEt / EtOH
NH
HMe CO2H
O
!e!, Pt anodeNaOAc,MeOH/AcOH(84%)
NH
HMe OAc
ONH
CO2H
NCbz
CO2Me
MeO
protectionthen
-2e-,MeOHCu( )3
BF3•OEt2(80%)
NCbz
CO2Me
iii) Functionalization of proline
Celimene, C.; Dhimane, H.; La Bail, M.; Lhommet, G. Tetrahedron Lett. 1994, 35, 6105-6106.
(69%, 3 steps)
N
Me
H
n-Bu
ANODIC OXIDATIONS
Danielmeier, K.; Schierle, K.; Steckhan, E. Tetrahedron 1996, 52, 9743-9754.
!e!
(45-67%)
Becking, L.; Schafer, H. J. Tetrahedron Lett. 1988, 29, 2797-2800.
Mori, M.; Kagechika, K.; Sasai, H.; Shibasaki, M Tetrahedron 1991, 47, 5315-5340.
N
Me
O
H
S
CO2H
NHAc
(+)-PS-5 (antibiotic)
( )3
Butora, G.; Reed, J. W.; Hudlicky, T.; Brammer, L. E. Jr.; Higgs, P. I.; Simmons, D. P.; Heard, N. E.J. Am. Chem. Soc. 1997, 119, 7694-7701.
Shono, T. Tetrahedron 1984, 40, 811-850.
Synthesis of O-alkyl, N-acyl hemiaminals
Electrochemical oxygenation versus anionic oxygenation
'' The anionic oxygenation protocol was abandoned for safety considerations and the general unpredictability of hazards, as well as complexity of the reaction mixtures'' - Hudlicky and coworkers
pymetrozine O-alkyl, N-acyl hemiaminal
SO
O
R
SO
O
R
F(66-80%)
Pt anodeEt4NF•3HFDME
Hou, Y.; Higashiya, S.; Fuchigami, T. J. Org. Chem. 1997, 62, 8773-8776.
Dawood, K. M.; Higashiya, S.; Hou, Y.; Fuchigami, T. J. Org. Chem. 1999, 64, 7935-7939.
Higashiya, S.; Narizuka, S.; Konno, S.; Maeda, T.; Momota, K.; Fuchigami, T. J. Org. Chem. 1999,64, 133-137.
Marko, I. E. Tetrahedron Lett. 2000, 41, 4383-4387.
Group Meeting12/7/2005
Narendra Ambhaikar Electrochemistry in Organic Synthesis
BrH
O
Me
Me
Me
OTBS
OTBS
TBDPSO
Me
O
TBDPSO
Me
O
Me
HOTBS
Me
Me
RVC anode (0.2 mA)2,6-lutidine, LiClO420% MeOH/CH2Cl22.44 F/mol(70%)
O
R1
O
Br
TMSO
R1
O OO
R1
R2
Mg, CuITMSCl
C anode, LiClO4
i-PrOH/MeCN2,6-lutidineconst. current
+
Sythesis of [6-7-5] guanacastepene core (Trauner, 2005)
Total synthesis of (±)-alliacol A (Moeller, 2003)
Me
O OH
O
Me
Me
O
Alliacol A
Me
O
TBSO
MeMe
TBSO
Me
O
Me
Me
TBSO
O
MeO
HRVC anodecarbon cathode0.4 M LiClO4
MeOH/CH2Cl2 (1:4)2,6-lutidine, RT15-20 mA, 2.2 F/mole
TsOH, RT(88%)
Me
O
Me
Me
HO
O HMe
O
Me
Me
O
MeO
H a) I2, PPh3, Im
DCM/Tol, 85 oC (87%)
b) AgNO3
THF/MeOH, RT (92%)
Nuc-H
X
( )nNuc-H
X
( )nNuc
X
( )n
Nuc
X
( )n Y
[O]
+ solvent (YH)
!H+!H+[O]
Intramolecular anodic olefin coupling reactions
These reactions reverse the polarity of the electron rich olefin to be oxidized, transforming it into an electrophile
(70%)O
TBDPSO
Me
O
Me
HOTBS
Me
Me
MeO
H
HCl, H2O, THF (85%)
O
MeO
MeO
OMe
NMe
OMe
MeO
MeO
OMe
NMe
OMe
MeO
MeO
OMe
NMe
OMe
MeO
MeO
OMe
NMe
H- e-
H2O
Electrooxidative cyclization of (±)-Laudanosine (Miller, 1971)
1.1 VLiClO4
Na2CO3
(52%)
-e-
- ROH
- 2H+
ANODIC OXIDATIONS
Mihelcic, J.; Moeller, K. J. Am. Chem. Soc. 2003, 125, 36-37.Asymmetric synthesis: Mihelcic, J.;Moeller J. Am. Chem. Soc. 2004, 126, 9106-9111.
Hughes, C. C.; Miller, A. K.; Trauner, D. Org. Lett. 2005, 7, 3425-3428.Whitehead, C. R.; Sessions, E. H.; Ghiviriga, I.; Wright. D. L. Org. Lett. 2002, 4, 3763-3765.
Miller, L.; Stermitz, F. R.; Falck, J. R. J. Am. Chem. Soc. 1971, 93, 5941-5942. Miller, L. L.; Stermitz, F. R.; Falck, J. R. J. Am. Chem. Soc. 1973, 95, 2651-2656.
O
MeMe
TBSO
P(OEt)2
O
O
O
+
i) NaH (92%)
ii) Me2Cu(CN)Li2 TBSCl, (91%)
( )n( )n( )n
n = 1 R1 = H, R2 = Me (64%)n = 1 R1 = Me, R2 = H (78%)n = 1 R1 = H, R2 = Me (64%)n = 2 R1 = Me, R2 = H (76%)n = 2 R1 = H, R2 = Me (65%)
R2 R2
OO
R1
R2
( )n
Two-step annulation for assembly of polycyclic systems
1N HCl Oi-Pr
H
BrH
Group Meeting12/7/2005
Narendra Ambhaikar Electrochemistry in Organic Synthesis
BrH
I OMe
O
+
Pd(OAc)2n-Bu4NBr
DMF/H2O/Et3N
RT, 3.5 hOMe
O
(82%)
Electrochemical Heck Reaction
- Requires no ligand and no high temperatures
Trapping of N-centered radicals and radical cations
NH Ph
MeR
i) n-BuLi, THFii) Pt anode, THF, HMPA0.25 M LiClO4
1.2 F/mole, !10oCNMeR
Ph
(66-85%)R = H, Me, Ph
Anodic oxidation of NO3-: Nitrate radical formation
R2
R1
R3
Pt anodeLiNO3
CH3CN/H2O/Et2ON O
R2
R1
R3
Me
(69-77%)
Generation of NO3•, then its addition to olefin to form the most substituted radical, then further
oxidation to carbocation and finally trapping by MeCN to form oxazole after loss of NO2+
Oxidation of ethers using an 'Electroauxiliary'
Y EA!e!
Y EA- EA+
!e!Y -EA
+
Nu Y Nu
Y = heteroatom, EA = electroauxiliary, a group that is attached to a substrate to reduce its oxidation potential. Enables oxidation of the substrate. It also avoids over-oxidation of the product.
Electrochemical Nozaki-Hiyama-Kishi coupling
Catalytic amounts of chromium (7%) and nickel (3%) are generated from a pre-electrolysis of a stainless steel rod make it environmentally friendly.
OX
FGA
OH
A FG+
3% bipy, DMFe-, Fe/Cr/Ni anode(50-80%)
A = H, CF3, CO2Me, CNX = Cl, Br, FG = electron donating or withdrawing
O
EA
C7H15
C anode
Bu4NBF4
O
C7H15 F
EA = TMS (68%, cis/trans 55:45)
EA = SnBu3 (83%, cis/trans 74:26)
EA = SMe (64%, cis/trans 87:13)
Y
SnBu3
R
Y
R
Y = O, R = H (55%)
Y = O, R = F (80%)
Y = NCO2Me, R = H (54%)
electrolysisBu4NClO4
A
Br
A = F, CF3, MeO, CN, Me,COMe
R = H, Me
Cl CO2Me
R
+ ACO2Me
RNi cathodeZn/Al anodeBu4NBF4NiBr2Bipy
(51-85%)
Durandetti, M.; Nedelec, J.-Y.; Perichon, J. J. Org. Chem. 1996, 61, 1748-1755.
Durandetti, M. I.; Nedelec, J.-Y.; Perichon, J. Org. Lett. 2001, 3, 2073-2076.
Tian, J.; Moeller, K. D. Org. Lett. 2005, 7, 5381-5383.
Electrochemical Ni catalyzed coupling between aryl halides and "-chloroestersTokuda, M.; Fujita, H.; Miyato, T.; Suginome, H. Tetrahedron 1993, 49, 2413-2426.
Shono, T.; Chuankamnerkarn, M.; Kaekawa, G.; Ishifune, M.; Kashimura, S. Synthesis 1994, 895-897.
Yoshida, J.; Maekawa, T.; Murata, T.; Matsunaga, S.; Isoe, S. J. Am. Chem. Soc. 1990, 112, 1962-1970. Yoshida, J.; Ishichi, Y.; Isoe, S. J. Am. Chem. Soc. 1992, 114, 7594-7595.
Electrochemistry in organometallic reactions
Group Meeting12/7/2005
Narendra Ambhaikar Electrochemistry in Organic Synthesis
BrH
Electrochemical Reductions
O
Me
e-, Sn/C, i-PrOH, Et4NOTs4 F/mol (70%)
OHMe
Br CO2Me
CO2Me-1.85 V, DMF, n-Bu4NBr(65-80%)
CH(CO2Me)2
+2e-, CH2(CO2Me)2n-Bu4NBr, MeCN (89%)
quadrone
CHO
EWG
+e-CHO
EWG
cyclization
EWG
O
H
EWG
O
+e-
EWG
O
H
EWG
OH
overall transformation
Me
H
Me
Me
H
1-sterpurene
Total synthesis of 1-sterpurene (Little, 1986)
Me
Me
HMe
OH
[2+2]Me
H
Me
Me
H
OH
CO2Me
CO2Mee-, Cu electrode CH2(CO2Et)20.9 M Et4NOTsMeCN/H2O CO2Me
CO2Me Na, TMSCl (4.9 eq)PhMe, !
Me
Me
H
HOH
O
58% (11.6:1 trans:cis)
Me
Me
H
H
O
i) MsCl, Et3Nii) LiBr, Li2CO3
(58%)
(75%)
i) MeLiii) PCC (2 eq)
(71%)
Me
Me
HMe
OH
H2C CH2
Me
H
Me
Me
H
OH
Me
i) MeLiii) SOCl2, Py
(60%)
Me
H
Me
Me
H
1-sterpurene
Me
H
Yield and selectivity of the electroreductive cyclization increased
in the presence of CeCl3 (73%, 14.8:1).
h"
Moens, L.; Baizer, M.; Little, D. J. Org. Chem. 1986, 51, 4497-4498.
Formal total synthesis of quadrone (Little, 1990)
OO
Me Me
O
O
CO2Me
Me Me
HO
CO2Me
MeMe
i) LAH (95%)
ii) TBDPSCl (96%)
iii) PCC (100%)
iii) (EtO)2POCH2CN (76%)
MeMe
NC
OTBDPS
MeMe
NC
OTBDPS
H
O
i) 9-BBNii) PCC
(85%)
+2e-, CH2(CO2Me)2n-Bu4NBr, MeCN (90%)
MeMe
NC
OTBDPS
Me Me
HO
OH
CN
OTBDPS
Me Me
OO
quadrone
Sowell, G. C.; Wolin, R. L.; Little, R. D. Tetrahedron Lett. 1990, 31, 458-485. Group Seminar by Carlos Guerrero on 'Quadrone'
Little, R. D. Chem. Rev. 1996, 96, 93-114.Kende's intermediate