Baran Lab
Stephen Buchwald
Tom Maimone
-This presentation will try to cover the work of professor Buchwald in somewhat chronological order until 2007.
-It is fairly comprehensive, with ~ 125 papers referenced.
main topics:
I. Zirconium Chemistry (1986-1999)
II. Titanium Chemistry (1991-2000)
III. Copper Hydride Chemistry (1999-2005)
III. Cross-Coupling (Pd, Cu) (1994-present)
Biographical:
-Born 1955 in Bloomington, IN
-Sc.B Brown University 1977:
(Kathlyn Parker and David Cane)
-Ph.D Harvard 1982:
(Jeremy Knowles)
-Postdoc Caltech 1982-1984:
(Robert Grubbs)
-hobbies include sports, food,
and cats (as of 1988)
Professional Appointments:
1984 assistant professor MIT
1989 associate professor MIT
1993 full professor MIT
1997 Camille Dreyfus Professor
over 300 publications
over 35 patents
Selected Awards:
Arthur C. Cope Scholar
ACS Organometallic Chemistry Award (2000)
Siegfried Medal Award (2006)
ACS Creative Work in Synthetic Chemistry (2006)
National Academy of Science (2008)
I. Zirconium Chemistry
The chemistry of Zirconium-alkyne complexes: JACS, 1986, 108, 7441.
Li
Me
ZrCP2
Cl
Cp2Zr
Cp2Zr
Me
Bond length 1.295 A
(between double and triple)
PMe3
Cp2Zr
air and moisture
sensitive
THF
Cp2Zr
O
Cp2Zr
and acylic alkynes:
JACS, 1987, 109, 2544
N
CN
O
PMe3
R
Cp2Zr
PMe3
PMe3
O
Cp2Zr
O
PMe3
R
ZrCp2
R
Cp2Zr
R
R
R
and acylic alkenes:
JACS, 1987, 109, 2544.
PMe3
Cp2Zr
Cp2Zr
Cp2Zr
R
an excellent review:
Chem. Rev. 1988, 88, 1047
1
Stephen Buchwald
Baran Lab
I. Zirconium Chemistry
Cyclopentenone synthesis: JACS, 1989, 111, 9113
Zirconocene-Thioaldehyde complexes: JACS, 1987, 109, 1591.
JACS, 1988, 110, 3171
R
Cp2ZrMe2
CO
SH
R
benzene
80 °C
PMe3
Cp2Zr
ZrCp2
R
C
H
N
also see benzyne complexes: JACS, 1986, 108, 7411.
Cp2ZrPh2
PMe3
ZrCp2
Δ
S
(-CH4)
R
(-CH4)
PMe3
R
Me3P
Me
O
Cp2
Zr
R
Cp2Zr
Tom Maimone
R
PMe3
N
N
ZrCp2
Cp2Zr
S
ZrCp2
S
R
S
Butenolide Synthesis: TL, 1988, 29, 3445
O
Similar elaboration is possible: TL, 1987, 28, 3245.
R
Cp2Zr
C
Cp2
Zr
N
H3O+
N
O
OH
1. Cp2Zr(H)Cl
O
Cp2Zr
CO
OH
I2
O
Cl
R
R
Cis Difunctionalization of Cyclic olefins: Organomettalics, 1991, 10, 537.
Double complexes can be prepared: JACS, 1987, 109, 4396
O
Cp2
Zr
ZrCp2
CO
Me
Li
ZrCp2
Cp2Zr(Me)Cl
ZrCp2
PMe3
THF
+ other
isomers
Δ
Li
Me
ZrCp2
Cp2Zr
MeOH
80 °C
E+
E
SCl2
S
2
Stephen Buchwald
Baran Lab
Tom Maimone
I. Zirconium Chemistry
Application to Natural Product Synthesis:
Pyrrole Synthesis: JACS, 1989, 111, 776.
Duocarmycin pharmacophore: JOC, 1992, 57, 6380.
SiMe3
Cp2Zr
CH3 R
Cl
N
Li
SiMe3
Cp2Zr
THF
SiMe3
N
R
Cp2Zr
CH3
N
R
I
Br
N
O
I2
t-BuLi
Cp2Zr(Me)Cl
R2
R1
R2
CO
Cp2Zr
R
N
H
R1
R1
R2
R
Zr
R
SCl2
TMS
THF
R
R
N
Bn
I
N
O
R
Cp2
Zr
N
Bn
Bn
I
Cp2Zr
MeO
2. BBr3
3. MeI
N
N
N
Bn
Bn
Bn
N
H
Dehydrobufotenine
DG
DG
X
R
t-Buli
Cp2Zr(Me)Cl
1. H3O+ or I2
2. H3O+
Me
ZrCp2
N
N
Regioselective, Directed Meta Acylation: JACS, 1998, 120, 9119.
DG
I2
Me
1. Pd(PPh3)4
Me
NHMe K2CO3
HO
Et3N
CO2Et
N
I
as
before
I
NH2
R
R
ZrCp2
Cp2Zr(Me)Cl
Br
S
Me
t-BuLi
MeO
TMS
Indole Synthesis: JACS, 1991, 113, 4685., JACS, 1994, 116, 11797
Br
2. NaH
Tetrahydropyrroloquinolines: JACS, 1996, 118, 1028.
R
SiMe3
N
MeO
R
N
Benzothiophene Synthesis: JOC, 1989, 54, 2793
R
1. BBr3
OMe
SiMe3
Cp2Zr
I
I
DG
DG
Δ
ZrCp2
R-CN
X=H
X=I
O
Cp2
Zr
N
R
3
Stephen Buchwald
Baran Lab
I. Zirconium Chemistry
Interesting Organometallic Structures:
cyclic 7-membered cumulene: JACS, 1993, 115, 10394.
Use of Zirconocene in Biaryl Synthesis: JACS, 1999, 121, 9469.
R
R
Br
1. n-BuLi
TMS
ZrCp2(X)
Cp2Zr
TMS
R
I2
ZrCp2(X)
Ar
TMS
Cp2Zr(Me)Cl
TMS
product formed
Ar
TMS
Me
t-BuLi
TMS
Double alkyne Zirconocene Complex: JACS, 1994, 116, 5471
ZrCp2
Me
Cp2Zr
TMS
ZrCp2
MeO
OMe
ZrCp2
H3
C
Cp2Zr
ZrCp2
TMS
desired product
Cp2ZrCl2
TMS
80°C
PhH
TMS
Cp2ZrCl2
bimetallic Zirconium complex containing an in-plane briding aromatic ring:
JACS, 1989, 111, 397-398.
OMe
ZrCp2
desired product
Interesting Organometallic Structures:
MeO
TMS
R
I
Br
Cp2
Zr
PdAr
SiMe3
Br
TMS
TMS
Cp2Zr
ligand
ZrCp2
2. Cp2Zr(Me)Cl
SiMe3
R
ArBr,
Pd2(dba)3
Tom Maimone
TMS
TMS
ZrCp2
TMS
TMS
ZrCp2
TMS
actually formed
MeO
OMe
4
Stephen Buchwald
Baran Lab
Tom Maimone
II. Titanium Chemistry
Catalytic Reduction of Esters to Alcohols: JACS, 1991, 113, 5093
JOC, 1992, 57, 3751
O
n-BuLi
Cp2TiCl
(10%)
(5%)
R
OEt
HSi(OEt)3
(2 eq.)
R
NaOH
or HCl
OSI(OEt)3
R
OH
Asymmetric Hydrogenation of imines: JACS, 1992, 114, 7562.
JOC, 1993, 58, 7627.
JACS, 1994, 116, 8952 (scope and limitations)
JACS, 1994, 116, 11703 (Kinetic and mech. analysis)
X Ti
X
(2 - 10 %)
N
1) n-BuLi
(2 eq)
2) PhSiH3
(2.5 eq)
thought to
stablize active
catalyst
Ti
H
R
R
R
H2 (2000 psi)
65 °C
HN
R
R
R
presumed
active
catalyst
5
Stephen Buchwald
Baran Lab
II. Titanium Chemistry
Kinetic Resolution of Racemic pyrrolines: JACS, 1994, 116, 9373.
Asymmetric Hydrogenation of Unfunctionalized trisubstituted
olefins: JACS, 1993, 115, 12569.
usual
suspects
R3
X Ti
X
(2 - 10 %)
R3
1) n-BuLi
(2 eq)
2) PhSiH3
(2.5 eq)
thought to
stablize active
catalyst
Ti
H
R1
Tom Maimone
R
Ar
N
R
Ar
N
R
Ar
N
H
R2
H2 (2000 psi) R1
65 °C
R2
Asymmetric Enamine Hydrogenation: JACS, 1994, 116, 5985
usual
suspects
N
presumed
active
catalyst
N
Enantioselective Ketone Hydrosilylation: JACS, 1994, 116, 11667.
O
X Ti
X
1) n-BuLi
(2 eq)
3)
2)
4) TBAF
or HCl
Me
OSiMe3
OH
Ar
R2
Ar
R2
aromatic ketone
give best ee's
SiMe3
H n
(5 eq)
polymethyl hydrosiloxane
5%
Catalytic Reduction of Lactones to Lactols: JACS, 1995, 117, 12641
JOC, 1997, 62, 8522.
Cp2Ti
O
O
O
Cl
2 mol%
2
O
OH
TBAF/Alumina (1%)
PMHS (5 eq)
6
Stephen Buchwald
Baran Lab
II. Titanium Chemistry
One-pot conversion of amides to aldehydes: ACIEE, 1996, 35, 1515.
O
R
Ti(O-iPr)4 (1 eq)
NR2 Ph2SiH2 (1.1 eq)
R
NR2
possibly
via
HTi(O-iPr)3
O
H3O+
R
H
Tom Maimone
Reductive Enyne Cyclizations with a practical Titanocene reaent: JOC, 1992, 57, 5803.
JOC, 1996, 61, 2713.
JACS, 1996, 118, 9450
JACS, 1999, 121, 5881
X
Cp2TiCl2
EtMgBr
R
X = O, C(CO2Et)2
MgBr
air and
moisture
stable
R
Cl
Ti
Cp2
R
Me
Ti
Cp2
R
R
R
TiCp2
Ti
Cp2
Br
R
R
N
H
X
Cp2Ti(CO)2
PhMe
100 °C
X
N
X
C
low effective concentration
of isocyanide
X
via:
Ph2SiH2
2. Work up
H
Me
X
Ph2SiH2
Ph2(H)Si
H
Me
Cp2Ti(PMe3)2
CO
X
Cp2Ti
γ−Butyrolactone synthesis: JACS, 1996, 118, 5818.
JACS, 1997, 119, 4424
O
Me
O
HO Me
1. Cp2Ti(PMe3)2 (10%)
PMe3 (80%)
Enyne and Dienyne Cycloisomerization: JACS, 1999, 121, 1976.
R
N
Reductive Enone Cyclization: JACS, 1995, 117, 6785.
JACS, 1996, 118, 3182
R
R
NC
> 5%
O
R
1) BnNH2
Pd(dba)3
NaOt-Bu
2) Pd/C
CO2NH4
R
R
Br2
R3Si
CN
> 95%
Δ
Br
X
can be troublesome,
R
reacts with catalyst
Use of R3SiCN as the carbon monoxide equivalent: JACS, 1993, 115, 4912.
JACS, 1994, 116, 8593.
MeMgBr
R3Si
R
O
Me
Titanocene-based Indole Synthesis: JACS, 1998, 120, 3068.
Cp2TiCl2
CO
X
Cp2Ti
Me
O
X
Cp2Ti
O
O
H
H
Enantioselective Titanium-mediated Pauson-Khand: JACS, 1996, 118, 11688.
JOC, 1999, 64, 5547
JACS, 1999, 121, 7026 - 7033
OC Ti
CO
E
E
R
R
CO
E
O
E
typical ee's = 70 - 90
7
Stephen Buchwald
Baran Lab
III. Copper Hydride Chemistry
Asymmetric Ester Conjugate Reduction: JACS, 1999, 121, 9473.
Me
R
O
CuCl (5%)
NaOt-Bu (5%)
OEt (S)-p-tol-BINAP (10%) R
PMHS (4 eq.)
Me
Asymmetric reduction of cyclic enones: JACS, 2000, 122, 6797.
O
Me3Si
OEt
O
Si
O
H
SiMe3
O
CuCl (5%)
NaOt-Bu (5%)
Me
O
Tom Maimone
R
(S)-p-tol-BINAP (10%)
PMHS (1.05 eq.)
R
n
PMHS
(E) and (Z) isomers give opposite
enantiomers of similar ee
One-pot Synthesis of 2,3 disubstituted cyclopentanones. OL, 2001, 3, 1129.
O
Asymm.
con. red.
Ph2
Si
O
O
O
TBAT
Ph2SiH2
Bn
BnBr
R
R
R
R
TBAT = (Bu4N)Ph3SiF2
8
Stephen Buchwald
Baran Lab
III. Copper Hydride Chemistry
Tom Maimone
Conjugate Reduction by Copper carbene complex: OL, 2003, 5, 2417.
Dynamic Kinetic Resolution via conjugate reduction: JACS, 2002, 124, 2892.
iPr
N
Me
iPr
R
CuCl
N
O
Me
A
NaOt-Bu
OEt
iPr
iPr
A
OEt
R
PHMS
t-BuOH
O
O
O
R
R
yields typically ~ 90%
Total synthesis of Eupomatilone -3: ACIEE, 2005, 44, 6177.
B(OH)2
Br
1) Pd
MeO
CO2Me 2) BH3 THF
MeO
O
OMe
O
3) MnO2
MeO
OMe
4) MgCl OEt MeO
O
OMe
O
O
Me
MeO
Enantioselective Lactam/lactone conjugate Reduction: JACS, 2003, 125, 11253.
O
O
usual
suspects
X
R
O
X = O, N-PMP
usual
suspects
R
CO2R
R
N
O
R
N
O
ee's 80 - 99
MeO
CO2R
CO2R
Me
N
Me
N
O
Me
O
Me
CO2R
(S) - BINAP
PMHS
air
O
OMe
Asymmetric Reduction of enamides: PNAS, 2004, 101, 5821.
Cu(OAc)2 H2O
CuCl2 2H2O
(R)-MeO-BIPHEP PMHS
NaOt-Bu
X
R
R
O
O
X
X
O
OMe
NaHMDS
MeI
MeO
MeO
O
O
MeO
O
Me
MeO
MeO
85%
93%ee
O
O
9
Stephen Buchwald
Baran Lab
Tom Maimone
IV. Cross-Coupling Chemistry
Migita: Chem Lett, 1983, 927
Palladium catalyzed Aromatic Amination with in Situ Generated Aminostannanes:
JACS, 1994, 116, 7901.
ArBr + Bu3SnN(Et)2
Bu3Sn-NEt2
HNRR'
80°C
Br
Bu3Sn-NRR'
Argon
PdCl2(P(o-tolyl)3)2
purge
(1-2%)
(-Et2NH)
or
Pd(dba)2
P(o-tolyl)3
Tin-Free Amination: ACIEE, 1995, 34, 1348.
HNRR' (1.2 eq)
ArBr
ArNRR'
t-BuONa (1.4 eq)
Pd(dba)2
P(o-tolyl)3
PhMe
65 °C
for aryl iodides: JOC, 1996, 61, 1133
intramolecular: Tett., 1996, 52, 7525.
structure of Pd/amine complexes: OM,
1996, 15, 2745. OM, 1996, 15, 2755.,
OM, 1996, 15, 3534
ArNRR
Key Precedent:
PdCl2(P(o-tolyl)3)2 (cat)
ArN(Et)2
Boger: JOC, 1985, 50, 5782.
MeO2C
N
H2N
CO2Me
MeO2C
Pd(PPh3)4(stoich.)
Br
N
CO2Me
HN
BINAP TO THE RESCUE:
Improved catalytic system with bidentate phosphines: JACS, 1996, 118,
7215.
primary amines can now be used (β−hydride elim. supressed)
ex. ArBr
n-HexNH2
as low as 0.05% Pd
can be utilized
Pd2(dba)3 (0.5%)
BINAP (0.75%)
NaOt-Bu (1.4 eq)
PhMe
80 °C
ArNHR
use of pyridyl bromides: JOC,1996, 61, 7240
use of aryl triflates: JOC, 1997, 62, 1264
TL, 1997, 38, 6363
mechanistic study: JACS, 1997, 119, 6787.
use of aryl iodides (room temp): JOC, 1997, 60, 6066.
use of optically active amines: JACS, 1997, 119, 8451.
Amination/Fischer indole synthesis: JACS, 1998, 120, 6621.
JACS, 1999, 121, 10251.
double amination (2 different ArX): JOC, 1999, 64, 6019.
Ammonia equivalent: TL, 1997, 38, 6367
Review: ACR, 1998, 31, 805.
JOMC, 1999, 576, 125.
aminations With Ni(COD): JACS, 1997, 119, 6054.
scope: JOC, 2000, 65, 1144
10
Stephen Buchwald
Baran Lab
Tom Maimone
IV. Cross-Coupling Chemistry (Pd)
Intramolecular C-O bond formation: JACS, 1996, 118, 10333.
mechanistic studies: JACS, 1997, 119, 6787
JACS, 1998, 120, 6504
optically active: JACS, 2001, 123, 12202
X
Pd(OAc)2 (5%)
Tol-BINAP (6%)
n
Br
A Highly active Catalyst for Pd-catalyzed cross coupling reactions: JACS, 1998, 120, 9722.
The Introduction of the biaryl ligands ("Buchwald ligands"), mild conditions now possible for
many reaction types.
OH
K2CO3 (1.2 eq)
PhMe
100 °C
-5,6,7 membered rings formed
-alcohol must normally be 3°
DPPF can
also be used
HNRR'
Cy2P
O
NMe2
X = Br, I
X = Cl
L
Br
OH
R
R
Tol-BINAP (3.5%)
NaH (2 eq)
O
PhB(OH)2
R
R
O
Br
Palladium-Catalyzed α−Arylation of Ketones: JACS, 1997, 119, 11108
JACS, 2000, 1222, 1360
Br
O
Pd2(dba)3 (1.5%)
O
BINAP (3.5 %)
NaOt-Bu (1.3 eq)
THF
70 °C
Cy2P
Cy2P
Ar
Pd(OAc)2 (0.75%)
L (1.5%)
CsF (3 eq)
dioxane
rt
Ph
O
Pd2(dba)3 (3%)
L
NaHMDS
rt
Highly active catalyst for the room-temperature Amination and Suzuki Coupling of Aryl Chlorides:
ACIEE, 1999, 38, 2413. JACS, 1999, 121, 9550. JOC, 2000, 65, 1158.
NMe2
Asymmetric Arylation of Ketone Enolates: JACS, 1998, 120, 1918.
With Ni: JACS, 2002, 124, 3500.
O
ArBr
O
Pd2(dba)3 (10 - 20%)
(S)-BINAP
NaOt-Bu (2 eq)
PhMe
100°C
limited substrate scope
NRR'
L (1.5 %)
NaOtBu (1.4 eq)
room temp for X=Br,I
80 °C for x =Cl
Cl
Intermolecular C-O bond formation: JACS, 1997, 119, 3395.
Pd2(dba)3 (1.5%)
or
Pd(OAc) (5%)
Pd2(dba)3 (0.5 mol%)
1
(tBu)2P
3
(tBu)2P
-More ligands introduced
- 1 effective for room temp Suzuki rxns of both electron rich
and poor aryl chlorides. Not good for rt amination of ArCl
- 2 better than 1 for C-O bond formation.
- 3 good for very low cat. loadings, and suzuki of hindered
substrates.
-4 better than 3 for many room temp applications
ligand synthesis: JOC, 2000, 65, 5334.
Adv.Synth.Cat., 2001, 343, 789.
NMe2
2
4
11
Stephen Buchwald
Baran Lab
Tom Maimone
IV. Cross-Coupling Chemistry (Pd)
Aryl Halide/Amide coupling: OL, 2000, 2, 1101.
Diaryl ether formation: JACS, 1999, 121, 4369.
X
OH
O
Pd(OAc)2
L
NaH
or
K3PO4
100 °C
RHN
Cs2CO3
R
O
O
PPH2
100 °C
PPh2
Xantphos
Indole N-arylation: OL, 2000, 2, 1403.
H
N
X
NMe2
R
X = Br, OTf, I
some new ligands:
R
N
Pd(OAc)2 (1%)
xantphos (1.5%)
O
X
Ph
P(t-Bu)2
P(t-Bu)2
P(adamantyl)2
N
Pd2(dba)3
L
NaOtBu
PhMe
80 - 100°C
X = Br, Cl, I
Ester arylation: JACS, 2001, 123, 7996.
Asymmetric Biaryl synthesis: JACS, 2000, 122, 12051.
Br
B(OH)2
P(O)(OEt)2
Br
Me
Pd2(dba)3
L*
K3PO4
40 - 70°C
Improved intramolecular C-O Bond Formation: JACS, 2000, 122, 12907.
L (6%)
O
P(O)(OEt)2
OtBu
OtBu Pd(OAc)2 (3%)
2.3 eq
O
LHMDS (2.5 eq)
rt - 80°C
Intermolecular Aryl ether synthesis: JACS, 2001, 123, 10770
Biaryl Ligands now allow primary alcohols to be used:
X
Pd(OAc)2
X
X = Br, Cl
OH
L
Cs2CO3
PhMe
80°C
OH
O
P(t-Bu)2
Me2N
PCy2
X = Br,Cl
Pd(OAc)2
L
Cs2CO3
PhMe
70 °C
O
P(t-Bu)2
NMe2
P(t-Bu)2
L
12
Stephen Buchwald
Baran Lab
T-$
IV. Cross-Coupling Chemistry (Pd)
catalytic Asymmetric Vinylation of Ketone Enolates: OL, 2001, 3, 1897.
O
Ph
Good Further reading for ligand design:
O
Pd2(dba)3 (2.5%)
R
N
Me
Br
Ph
L (6.5%)
NaOtBu
PhMe
N
Me
Aryl Trifluoroborate couplings: OL, 2004, 6, 2649.
Pd(OAc)2
BF3
Cl
PCy2
L
K2CO3
MeOH
MeO
Ligand Design, development, study papers: JACS, 2002, 124, 1162.
Xantphos: JACS, 2002, 124, 6043.
overview: ACIEE, 2004, 43, 1871.
Insight into high kinetic activity : JACS, 2003, 125, 13978
Negishi catalyst: JACS, 2004, 126, 13029.
Suzuki/sonagashira cat: ACIEE, 2005, 44, 6173.
Suzuki catalyst: JACS, 2005, 127, 4685.
Ligand effects: ACIEE, 2006, 45, 4321.
Ligand Stability: JACS, 2007, 129, 5096.
OMe
C-H Functionalization: oxindole Synthesis: JACS, 2003, 12084.
Pd(OAc)2 (3%)
O
Cl
N
R
PtBu2
N
R
O
Et3N, PhMe, 80°C
C-H Functionalization: Carbazole synthesis: JACS, 2005, 127, 14560.
O
N
H
O
Me
Pd(OAc) (5%)
N
Me
Cu(OAc)2, O2
PhMe
120 °C
13
Stephen Buchwald
Baran Lab
Tom Maimone
IV. Cross-Coupling Chemistry (Cu)
Aromatic Finkelstein Reaction: JACS, 2002, 124, 14844.
Imidazole aryl halide coupling: TL, 1999, 40, 2657.
H
N
I
N
Cu(OTf)
dba
Br
N
Cs2CO3
xylenes
110 - 125 °C
N
N-Arylation of Nitrogen Heterocycles: JACS, 2001, 123, 7727.
O
JACS, 2002, 124, 7421.
Ph
N
H
NH2
O
RHN
N
NHR
RHN
I
H
N
R
key ligand
Cu(OAc)2
Hydrazide coupling: OL, 2001, 3, 3803.
I
NH2
CuI
Cs2CO3
1,10
phenanthroline
80°C
DMF
RO
O
OR
CuI, L ,Cs2CO3
O
Copper Coupling of Thiols: OL, 2002, 4, 3517
Copper Cyanation of aryl bromides: JACS, 2003, 125, 2890.
Copper C-O coupling/claisen: JACS, 2003, 125, 4978.
Copper C-P Bond formation: OL, 2003, 5, 2315.
Copper Amide/ vinyl halide: OL, 2003, 5, 3667.
Room temp Cu C-N: JACS, 2006, 128, 8742.
N Vs. O-arylation: JACS, 2007, 129, 3490
hydroxypyridine Coupling: OL, 2007, 9, 643,
Benzimidazole synthesis: OL, 2007, 9, 4749.
oxazole synthesis: OL, 2007, 9, 5521.
C-H Functionalization: ACIEE, 2008, 47, 1932
NRR'
2,6-Lutidine
air
rt
R
RO
O
Copper amino alcohol coupling: OL, 2002, 4, 3703
Boronic acid coupling: OL, 2001, 3, 2077.
O
O
Copper Coupling of alcoholsL OL, 2002, 4, 973.
typically CuI (1%), L (10%), K3PO4 (2 eq), 110 - 130 °C
RNHR'
Malonate Arylation: OL, 2002, 4, 269.
Copper Amination of aryl Iodides: OL, 2002, 4, 581.
HN
B(OH)2
NHMe
MeHN
RO
O
H
N
indole N-arylation:
JACS, 2002, 124, 11684
JOC, 2004, 69, 5579
NaI (2 eq)
Dioxane
110 °C
I
RNHR'
HN
I
CuI (5%)
L (10%)
O
N
R
NH2
14