José Barluenga
A. Mendoza
José Joaquin Barluenga Mur was born in Tardienta 07/27/1940
1963 BS from the University of Zaragoza
1963 - 1966 PhD with Prof. Vicente Gomez Aranda (Zaragoza)
1967 - 1970 Postdoc with Prof. Heinz Hoberg at Max-Planck.
Institute für Kohlenforshung an der Rühr (Germany)
1970 - 1972 Scientific collaborator CSIC (Zaragoza)
1972 - 1975 Associate professor (Zaragoza)
1975 - 2010 Professor at the University of Oviedo. 1993 - Director
of the University Institute for Organometallic Chemistry
"Enrique Moles" (Oviedo)
2011 - today Emeritus Professor (Oviedo)
Oviedo
Baran Lab GM 2011-02-19
Gijón
Tardienta
Zaragoza
Numbers
632 Publications (SciFinder)
35 Reviews
Research interests
1963 - 1966 PhD in organomercury chemistry
1967 - 1970 Postdoc in organoaluminium chemistry
1970 - 1984 Addition of nitrogen nucleophiles to alkenes and alkynes (thallium, mercury)
1978 - 1988 Substituted organolithium compounds
1979 - 1992 Azabutadiene cycloadditions
1984 - 2008 Bis(pyridine)iodonium tetrafluoroborate [IPy2]BF4
1994 - 2010 Fischer carbene complexes. Recently unstabilized carbenes.
1995 - 2007 Organozirconium chemistry
2005 - 2011 Late transition metal catalysis (palladium, gold, platinum, silver, nickel...)
2009 - 2011 Metal-free reductive coupling
Awards
12 major awards
1989 Alexander von-Humboldt Foundation
1999 1st Gold Medal from the Spanish Royal Society of Chemisrty
2005 Rey Jaime I Research Award
2009 Silver Medal of the Principality of Asturias
2 Doctor Honoris Causa (Alcala de Henares and La Rioja)
The Group
4 Full professors (Fañanás, Aznar, Tomás and González)
11 Professors
~ 19 Graduate students
~ 2 Visiting students
~ 2 Postdocs
Angewandte profile: Angew. Chem. Int. Ed. 2010, 49, 6250.
The Barluenga group outside the Faculty of Chemistry in 2004.
"Where there's a will there's a way"
"Draw it!! kid..."
"The straws don't let you see the forest!!"
"You must always try to undertake your daily work with passion, dedication and cope
with standards of intellectual innovation and significance"
"If you continue to repeat experiments you're going to graduate in 10 years"
"For that trip no need to bring that saddlebag..."
"Is that the way you want to be scientists?!?"
1
José Barluenga
A. Mendoza
Mercury and thallium: Amination reactions.
Addition of anilines across alkynes
Background - Seminal Publications
Hg(OAc)2 then NaBH4/NaOH/H2O
or
NAr
Tl(OAc)3, 80ºC
+ HNRAr
Ph
XHg
+ HgX2 + HY
X = AcO, Cl, Br
Y = OH, OR
+ HX
Y
Baran Lab GM 2011-02-19
Ph
A. N. N. Deniges, Chem. Pharm. 1889, 18, 394.
NRAr
Synthesis 1975, 704.
or
Ph
XHg
+ HNRAr
Ph
NR2
Aminomercuration of dienes
Ph
XHg
N
Ar
N
Ar
62-99%
Ar
N
N
Ar
ArN
R2
HgX
X
R1
O
R1
with TlIII: Synthesis 1974, 504.
with HgO: Synthesis 1979, 962.
NHPh
NHPh
N
Ph
PhN
Ph
R2
HNR1R2
NAr
O
O
Os
tBuN
NtBu
R
O
tBuN
NtBu
LiAlH4
R3
tBuHN
R1
R1R2N
if R1,R2≠H
Hg2+=Hg(OAc)2
R5
R4
O
NH2
= alkyl, aryl, H, OR, NH2, NHR.
R1, R2, R3, R4= alkyl, aryl, H.
R
+
Ts
NH2
R1 R2
R5
R5
NHtBu
R
R
B. Sharpless et al. J. Am. Chem. Soc. 1977, 99, 3420. ---> only cited aminopalladation by J.E.-Backvall :)
O
JCS, Chem. Commun. 1985, 1375.
J. Org. Chem. 1991, 56, 6166.
1) Hg(NO3)2
2) NaBH4
O
+
O
Os
R2
NHPh
Hg(BF4)
40ºC
R1
Hydro(sulf)amidation of alkenes
HNRAr
NHPh
[3,3]
R1
if R1=Ar,R2=H
Hg2+=HgCl2
ArRN
NHPh
50-60%
or
Diamination of alkenes
PhHN
NR4R5
R3
NR4R5
R2
Hg2+
R2
NRAr
55-93%
R3
R1
cyclodimerization
of allylanilines
ArRN
O
R3
JCS, Chem. Commun. 1984, 1427.
Anales RSEFQ 1972, 68, 221; Tetrahedron Lett. 1972, 3621; Synthesis 1978, 911; Synthesis
1979, 896; J. Heterocyclic Chem. 1979, 16, 1017; J. Heterocyclic Chem. 1980, 17, 917.
Tl(OAc)3
or
+
+ HNRAr
HgO•2HBF4
R2
R2
HgCl2
HNR4R5 R1
N
Ar
X = CH2, O, NR
PhHN
Ph
Conjugated and deconjugated enynes
+ HgX2 + H2NAr
NHPh
NRAr JCS Perkin Trans. I 1980, 2732.
Catalytic TlIII: Synthesis 1977, 195.
or
A. Lattes, J. J. Périe Bull. Soc. Chim. Fr. 1971, 1378.
N
Ar
NAr
5 mol% HgCl2
+ R2NH2+X-
+ HgX2 + HNR2
N
H
R3
R3
JCS, Chem. Commun. 1981, 671.
JCS, Perkin Trans. I 1983, 591.
1) Hg(NO3)2
2) NaOH, NaBr, H2O
Na+ NTs
HgBr
R
69-83%
NHTs
Br2
Br
R
76-96%
NaBH4 quench: JCS, Chem. Commun. 1981, 1178.
Br2 quench: JCS, Perkin Trans. I 1984, 721.
2
José Barluenga
A. Mendoza
Baran Lab GM 2011-02-19
Lithiation and direct coupling with aryl and vinyl bromides: The differential reactivity of
dianionic intermediates.
Oxygenated nucleophiles
ArHN
+ HgO•2HBF4 + H2NAr
ArHN
ROH
THF, -10ºC
Hg(BF4) THF, 66ºC
R=H, alkyl
1) BuLi, -78ºC
2) Li[C10H8], -78ºC
3) RX, -78ºC to rt
O
OR
Ph
NH
54-80%
Synthesis 1981, 376.
RO
O
Ph
NH
70-95%
X
Hg(BF4)
+ HgO•2HBF4 + 2ROH
THF, 66ºC
R
O
R=H, alkyl
BF4
RO
ROH
ArRN
R1
PhLi
R2
YLi
R2MgBr
or
LiAlH4/AlCl3
YH
E
OM
R1
R2
R3
Cl
Li
E
THF, -78ºC R
THF, -78ºC R
R
R
Y= O, NPh.
61-83%
E = H, D, OH, CO2H, C(OH)R2, SiMe3.
Tetrahedron Lett. 1978, 2015; J. Org. Chem. 1979, 44, 4798.
R
YLi
BuLi
Cl
THF, -78ºC
R
YLi
Li[C10H8]
Cl
THF, -78ºC
R
R
Cl
-60ºC
R3
R1
R2
R1
Li
R3
-60ºC to rt R
R3
Seminal work on β-oxide elimination: J. J. Eisch et al. J. Am. Chem. Soc. 1976, 98, 4646;
From chloroketones: J. Org. Chem. 1981, 46, 2721;
From chloroacyl chlorides: J. Org. Chem. 1983, 48, 609; J. Org. Chem. 1983, 48, 3116;
(Chloromethyl)lithium: JCS, Chem. Commun. 1988, 536; JCS, Perkin Trans. I 1990, 417;
JCS, Perkin Trans. I 1989, 77; J. Org. Chem. 1999, 2843;
J. Org. Chem. 1997, 5974; Synthesis 1988, 234.
YH
E
Li
OM
Li
46-99%
R3
β-Functionalized organolithiums from alkyl chlorides. Lithium naphthalenide.
YH
R3
1) R1MgBr, THF, -78 to -60ºC
2) R2MgBr or LiAlH4/AlCl3, -60ºC
3) Li, -60ºC
Cl
HgBr
R1
R2
-60ºC to rt
Et2O, -60ºC
O
Li
if M=Li
+ ClCH2Li
Cl
R1
Li
YLi
HgBr
Bu
(α and β)
O
O
ArRN
H
68-86%
Seminal: Synthesis 1974, 135; Improvement in presence of aniline: Synthesis 1975, 116;
same with Mg: Synthesis 1975, 467.
YH
I
Ph
O
+ HgX2 + HNRAr
R=H, alkyl
Br
β-Elimination of β-functionalized organolithium compounds: Synthesis of olefins.
50-90%
+ Hg0
N
X=Br, I
Mercury - Lithium exchange: An entry to β-functionalized organolithiums
PhNH2, rt
R1
OR
Tetrahedron 1984, 2563.
Li / THF
Br
RX:
-
Tetrahedron Lett. 1992, 6183.
Cl
E
γ,δ,ε-functionalized organolithium compounds. δ,ε-functionalized compounds behave
normally but the γ ones undergo a different elimination process...
1) 2RMgX
2) H2O
3) BuLi
Only 1ary RLi
Y=O, NPh, N(CO)Ph.
E = H, D, OH, CO2H, C(OH)R2, SiMe3, C(NHR1)R2, SMe.
with Na and K: J. Org. Chem. 1981, 46, 1281;
imines, sulphides and alkyl halides: J. Org. Chem. 1982, 47, 1560;
Li[C10H8] (-100ºC β-elimination): JCS, Chem. Commun. 1982, 1153; JCS Perkin Trans. I 1983, 3019.
Cl
O
Cl
Li
X
X = Cl, OMe
H
OH
O
R
R
THF, 66ºC
~55%
R
R
Synthesis 1983, 378; Synthesis 1983, 736;
Synthesis 1985, 846; Synthesis 1987, 819.
3
José Barluenga
A. Mendoza
Baran Lab GM 2011-02-19
Lithiation of allylamines
R
R
R
1) BuLi
2) tBuLi
H
NH
Li
NLi
NH
E
R1
Br
Br
E
or R
N
N
R
Li
R
N
NHR
R1
N
H
Li
Li
R1
1) tBuLi,
THF, -78ºC
R
N
ZrCp2
2) Cp2Zr(Me)Cl,
-78 to 0ºC
R1
Cyclic enol ethers
OR
R2
THF, -78ºC
H
R3
OH
ZrCp2
Et
ZrCp2
Cp2Zr(Me)Cl
Li
R1
R1
H
THF, -78ºC to 66ºC
O
H
Ar
H
ZrCp2
R1
via:
Ar
R1
R1
H
ZrCp2
Me
CH4
R1
ZrCp2
70-82%
Ar
O
H
δ+ Cp
2
Zr
72-86%
H
OH
R1
E
Angew. Chem. Int. Ed. 2004, 43, 3932; Angew. Chem. Int. Ed. 2007, 46, 2607.
PhLi or PhMgBr
Cp2Zr(Me)Cl
O
R1
H
THF, -78 to 0ºC
64-96%
R2
R1
Et
R1
ZrCp2
R1
R1
via:
ZrCp2
ZrCp2
NHR
O
Chem. Soc. Rev. 2005, 34, 762.
Cp2ZrCl2
R2
R3
JCS, Chem. Commun. 1994, 989; J. Org. Chem. 1997, 62, 5953; Chem. Eur. J. 2004, 10, 109.
J. Am. Chem. Soc. 1998, 120, 4865; Chem. Eur. J. 2001, 7, 2896; Eur. J. Org. Chem. 2003, 771.
Organozirconium chemistry using Cp2Zr(Me)Cl
Vinyl bromides as alkyne equivalents. Enol ethers as efective cross-coupling counterparts.
68-82%
then I2/NaHCO3
Li
2BuLi
E
RN
R2
N
H
Li
Li
R1
Imino-zirconocene complexes
E
Et2O, -78ºC 1h@-78ºC
(-50ºC or rt)
R
64-91%
Z. Naturforsch B, 1995, 50, 312; Chem. Commun. 1995, 1009; Chem. Eur. J. 1997, 3, 1324;
Chem. Eur. J. 2004, 10, 101; Synlett 2005, 2513; Org. Lett. 2008, 10, 4469.
E
N
R2
then E+
E+
E
Br
R2
Carbolithiation of lithiated double bonds.
R
55-88%
R1
ZrCp2
2) Cp2Zr(Me)Cl, R1
-78 to 0ºC
H
R2
then E+
1) tBuLi,
Br
THF, -78ºC
JCS, Chem. Commun. 1988, 1135; Tetrahedron Lett. 1988, 4859; Tetrahedron Lett. 1992, 7573;
J. Org. Chem. 1994, 59, 602; J. Org. Chem. 1994, 59, 1586.
tBuLi
OR
R2
Cp2Zr(Me)Cl
Li
N
Catalytic vinyl-magnesation of unactivated olefins.
R
MgCl
Cp2ZrCl2 cat.
R
N
-78 to 0ºC
R1
R
ZrCp2
O
PrMgCl (3 eq.)
1) E+
2) H2O
E
R
R
OMgCl
OH
56-93%
Angew. Chem. Int. Ed. 2006, 45, 6362; Org. Lett. 2007, 9, 3081.
4
José Barluenga
A. Mendoza
The serendipitous birth of [IPy2]BF4 - Barluenga's reagent
Y
+ HgO•2HBF4 + I2
Y
DCM/SiO2
rt
Hg(BF4)2 + I2
IBF4 source?
Direct iodination of Phe residues in peptides - Iodine radiolabelling in proteins.
H
H
N
HO2C
CO2Me [IPy2]BF4 (1.0 eq.) HO2C
N
CO2Me
HBF4 (2.0 eq.)
Y= H; 54%
Y=tBu; 78%
Y=OMe; 87%
Y=CO2H; 35%
Y=NO2; 12%
I
Baran Lab GM 2011-02-19
NH2
O
NH2
DCM:TFA (10:1), rt
92%
"IBF4" + HgIBF4
I
JCS, Perkin Trans. I 1984, 2623.
o:p (40:1)
with TfOH o:p (1:2)
Pyridine as stabilizer of iodonium...
HgO.2BF4-SiO2 + I2 + pyridine
AgBF4-SiO2 + I2 + pyridine
[IPy2]BF4
DCM, rt
6ppm Hg co-precipitates (ICP-MS)
[IPy2]BF4
DCM, rt
Davis et al. Org. Synth. 2010, 87, 288
In
Y=H; 97%
Y Y=2-MeO; 97%
90%
I
NO2
I
I
NH2
NH2
Me
I
HO
I
HO
I
I
Me
99%
Cl
99%
AcHN
99%
H2N
CO2Me
CO2Me
93% (in water)
93%
N
H
O
O
NH2
I
O
O
O
R1
93%(in water)
ROH
I
R2
O
X
X=O,S,NMe
R
I
Mechanism?
CO2H
Nu
R
R
H
N
TMS
O
R1
R1
O
BocHN
H
N
Nu
R2
analogously:
Br
HO
R2
I
HO
N
H
O
O
H
N
Iodonium as C-C (or C-X) bond forming promoter
I
I
NH2
n=2; 79%
n=3; 42%
n=4; 81%
n=5; 99%
n=6; 97%
I
O
CO2H
O
H
N
CO2H
o:p (7:1)
o:p (8:1)
Ac-Ala-Asp-Ala-Thr-Phe-NH2
For-Nle-Leu-Phe-OH
Angew. Chem. Int. Ed. 2004, 43, 325. Peptides in solid phase: Tetrahedron Lett. 1999, 7279.
OH
NH2
H
N
N
H
O
For activated arenes, the reagent is reactive enough. For non-activated ones, 1-2 eq. HBF4 or TfOH is needed.
Y=H; 85%
Y=4-tBu; 99%
Y=4-OMe; 96%
Y Y=3-CO2H; 86%
Y=3-NO2; 82%
O
H
N
H
Electrophilic iodination of activated and unactivated arenes
I
O
Nu
R
R
I
[IPy2]BF4 / xHBF4
BF4-
20g scale (indole synthesis)
JCS, Chem. Commun. 1992, 1016; J. Org. Chem. 1993, 58, 2058; Tetrahedron Lett. 1993, 34, 3893;
J. Org. Chem. 1996, 61, 5804; JCS, Chem. Commun. 1996, 1505; Chem. Commun. 2000, 1307.
X
X
Ph
R2
R3
I
Directed aromatic iodination...Does it remind you of something?
DCM:TFA (10:1), rt
85%
NHCOCF3
I
o:p (14:1)
Y-
N
90%
I
catalytic dimerization
O
R2
I
I
R
R
I
NR1
R
H
Angew. Chem. Int. Ed. 1988, 27, 1546; Angew. Chem. Int. Ed. 1993, 32, 893;
J. Am. Chem. Soc. 1997, 119, 6933; Angew. Chem. Int. Ed. 1998, 37, 3136;
I
Angew. Chem. Int. Ed. 2003, 42, 2406; J. Am. Chem. Soc. 2003, 125, 9028; Org. Lett. 2003, 5, 4121;
X
J. Am. Chem. Soc. 2004, 126, 3416; Chem. Commun. 2005, 2008; Chem. Eur. J. 2006, 12, 5790;
Angew. Chem. Int. Ed. 2007, 46, 1281.
Angew. Chem. Int. Ed. 2006, 45, 3140; Chem. Eur. J. 2009, 15, 8946.
F
o:p (25:1)
Ph
NHCOCF3
NHCOCF3
R3
I
NHCOCF3
R
I
X
X
o:p (12.5:1)
I
R
NHR1
R
Ph
CO2Me
I
NHCOCF3
I
R
[IPy2]BF4 (1.0 eq.)
HBF4 (2.0 eq.)
CO2Me
.
F
F
5
José Barluenga
A. Mendoza
4-amino-1-aza-1,3-butadienes - Synthesis.
Mining the gold of enyne hydroamination... 2-amino-1,3-butadienes
R1
O
H
R1
Hg(OAc)2
R2N
N
NEt3
R2
R3
O
Ar
R2
NHR1
Ar
if
R1
Ph
R4
R2
R2N
R2
R3
NH
R2
H
NHR1
Chiral 2-amino-1,3-butadienes
Highlight: K. Krohn, Angew. Chem. Int. Ed. 1993, 32, 1582
R4
OR
OR
NHR1
R4
NH
Synthesis 1970, 142
4-amino-1-aza-1,3-butadienes - Basic reactivity.
CO2R
R2N
OR
Me
Me
N
Ar
if
R3
R2≠H
Ar
R1
CO2R
O
R2
R2=H
R2
N / AlCl3
1) R4
2) NaOH, H2O
G. Wittig et al. Liebigs Ann. Chem. 1973, 1075.
Ph
NO2
NR1
NPh
R2N
Me
1) LDA
N
2) R4
3) NaOH, H2O
H
R2
R1
Baran Lab GM 2011-02-19
NH2
Ar
O
R3
NH
O
OH
[H]
OH
OH
R4
R2
OH
R4
R2
R4
O
76-94%
NaBH4
or
Na/iPrOH
NH
R2
1) BuLi
2) R3-X
R3
R3
up to 97:3:>1
up to 92:4:4
[LiAlH(OtBu)3]
[LiAlH4]
J. Org. Chem. 1985, 50, 802; J. Org. Chem. 1987, 52, 1425
LiAlH4
NH2
NH2
O
NaBH4
or
Na/iPrOH
NH2
OH
R2
MsCl, NEt3
R3
R2
R4
DCM
NH
R3
R4
JCS, Chem. Commun. 1988, 1247; J. Org. Chem. 1991, 56, 6166; J. Org. Chem. 1983, 48, 2255;
J. Org. Chem. 1983, 48, 2255; J. Org. Chem. 1985, 50, 4052;
J. Am. Chem. Soc. 1993, 115, 4403; J. Org. Chem. 1993, 58, 3391; Chem. Eur. J. 1996, 2, 805; Tetrahedron Lett. 1983, 34, 1981. J. Org. Chem. 1992, 57, 1219; JCS, Chem. Commun. 1988, 410;
J. Org. Chem. 1997, 62, 6746; J. Org. Chem. 1998, 63, 3918; J. Org. Chem. 1999, 64, 3736.
J. Org. Chem. 1993, 58, 5972.
up to 98% ee
up to 95% ee
OMe
R2
R4
R2
R4
R3
2-aza-1,3-butadienes - Normal and inverse demand [4+2] cycloadditions.
R1
R1
N
TMS 1) DMAD
2) CsF
R1
NR2
HN
N
MeO2C
MeO2C
HCl
R2
N
R3
MeO2C
H
CO2Me
CO2Me
4-amino-1-aza-1,3-butadienes - cycloaddition en route to heterocycles.
R1
NR2
R2
R2
NH
+ R2CH2MgX
R1
O
E
R1
TFA
R1
N
Z
X
N
-NH3
R1
R2
R1
X
Z
R1
R2
R2
NC
CN
R4
R2
[5+1] [3+2] [4+2]
NHR1 with with with
CO2Me
JCS, Chem. Commun. 1987, 1195; JCS, Chem. Commun. 1989, 267.
N
R3
NH
+X+
N
X
X
C
R3
R3
NR1
R4
R2
R2
R3
X
X
X
N
R4
N
R5
N
H
H
H
Review: Advances in Heterocyclic Chemistry 1993, 57, 1.
R4
NPh
X
E
NC
CN
O
Z
O
E
E
S
O
S
S
NR
NR
. . .
Chem. Ber. 1985, 36, 52; JCS, Chem. Commun. 1986, 1179;
JCS, Perkin Trans. I, 1988, 1739; Tetrahedron Lett. 1989, 30, 2685.
[5+1] - Dihydropyrimidines: Synthesis 1974, 720; Synthesis 1979, 346; Synthesis 1989, 230; Synlett 1992, 563;
JCS, Chem. Commun. 1988, 410. Pyrimidones: JCS, Chem. Commun. 1979, 675; J. Org. Chem. 1980, 45, 2592.
Thiadiazines: JCS, Chem. Commun. 1979, 675; JCS, Perkin Trans I 1981, 1891. Diazaphosphorines: Synthesis
1983, 370; Synthesis 1985, 309. Diazasilines: Angew. Chem. Int. Ed. 1986, 25, 181. Diazagermines:
Organometallics 1992, 11, 2348.
[3+2] - Pyrazoles: JCS, Chem. Commun. 1979, 891; JCS, Perkin Trans I, 1981, 1891. Isoxazoles: J. Org. Chem.
1983, 48, 1379. Pyrroles: J. Org. Chem. 1982, 47, 1696.
[4+2] - Pyrimidines: Synthesis 1970, 363. Pyridines: Synthesis 1975, 191.
6
José Barluenga
A. Mendoza
Palladium catalysis - new entry to amino and azadienes?
2 mol% Pd2dba3.CHCl3
4 mol% DavePhos
R2
X
+ R2NH
R1
TMS
N
+
Application of the olefination reaction to cases of special interest...
R2
R2N
X
+
R4
1st α-arylation
N
Maria Escribano's work...
N
R1
N
1 mol% Pd2dba3
4 mol% XPhos
+ ArX
R1
LnPd0
R4
N2
R4
R1
R2
Ar
60-99%
-HX
R4
+
Ph
94%
NHMe
N
N
Me
NHTs
+
R4
R1
H
R3
B(OH)2
R2
R1
R4
K2CO3 or K2PO4
dioxane, 110ºC, 2h
R3
R2
62-99%
R1
N2
R
Olefin
R2
Angew. Chem. Int. Ed. 2007, 46, 5587; Org. Lett. 2011, 13, 510.
Ph
1) Pd cat.
2) H+
Br
4
Ar R
LnPd
R1
NHTs
Metal-free reductive coupling of tosylhydrazones and boronic acids...
LnPdHX
LnPd
Ar'
Ar'
Chem. Eur. J. 2009, 15, 13291 (VIP paper).
R1
LnPd
X
N
MeO
R2
Ar
H+
O
63-97%
Ar
LiOtBu, dioxane, 110ºC
R2
X= Br, Cl, ONf
+ArX
MeO
LiOtBu, dioxane, 110ºC
Ar'
Ar
Ar
R2
Tosylhydrazones... Efforts in fundamental research finds a neat reward!!
R4
1 mol% Pd2dba3
4 mol% XPhos
NHTs
+ ArX
MeO
R3
Angew. Chem. Int. Ed. 2007, 46, 1529; J. Am. Chem. Soc. 2009, 131, 4031.
NHTs
N
H
70-94%
R3
61-90%
2nd amination
N
H
R2
R4
R3
X = Cl, Br, I;
Y = ONf, Br, I.
Chem. Eur. J. 2008, 14, 4792.
LiOtBu, dioxane, 110ºC
N
R2 NaOtBu, dioxane, 110ºC
X
Ar
Ts-NHNH2
1 mol% Pd2dba3
4 mol% XPhos
+ ArX
R1
2 mol% Pd2dba3
4 mol% XPhos
R1
Chem. Eur. J. 2010, 16, 12801
CO2Et
O
R
Chem. Commun. 2005, 4891; Angew. Chem. Int. Ed. 2004, 43, 343.
N
Ar
CO2Et
A general approach to the indole ring...
Y
1) TsNHNH2, dioxane, 70ºC
2) ArBr, 1 mol% Pd2dba3/XPhos,
LiOtBu, 110ºC
O
R1
NaOtBu, toluene, 80ºC
Adv. Synth. Catal. 2004, 1697; Chem. Commun. 2004, 1400.
2 mol% Pd2dba3.CHCl3
4 mol% DavePhos or BINAP
N
NaOtBu, toluene, 80ºC
R
Baran Lab GM 2011-02-19
B
R1
R2
One-pot conditions
1) TsNHNH2 / dioxane, 80ºC, 1.5h
2) R3B(OH)2, K2CO3, 110ºC, 1-5h
R3
OH
OH
Nat. Chem. 2009, 1, 494.
Phenol insertion: Angew. Chem. Int. Ed. 2010, 49, 4993.
7
José Barluenga
A. Mendoza
Synthesis of furo[3,2-c]quinolines
Ar 5 mol% PtCl2COD
OH
10 mol% AgSbF6
N
+
R
slow addition
R1
MeCN, rt
From Fischer carbene complexes to π-electrophilic catalysis
1) BuLi, THF, 0ºC
OMe
OTMS
2)
(OC)5Cr
R
THF, -78ºC
O
Baran Lab GM 2011-02-19
HO
Et
>98% ee
3) allyl-Li, -78ºC
4) HClO4, -78ºC to rt
5) 90ºC, THF
H
R
acetone, rt
Et
10 mol% W(CO)6, hν (350nm)
2 mol% NEt3, THF, rt
OH
R
O
Nu
+ Nu
Me
O
DCM, rt
O
R3
OH
88-96%; >97% de
O
Synthesis of chroman-spiroketals
O
5 mol%
OH
HC(OR3)3 [Pd(MeCN)4](BF4)2
OH +
+
or
R1
MeCN, rt
H2NR
R2
72-96%; >97%de
R
R1
O
O
R2
R1
Y
X X= R3O, Y=H
Gram-scale total synthesis of (-)-berkelic acid
O
R
M(H)
MeO2C
R
N
EWG
X= H, Y=NHR
The pursuit of the catalytic generation of exocyclic enol ethers. Proof-of-concept: Povarov.
+
60-98%;
>97% de
EWG
R1
OH
Angew. Chem. Int. Ed. 2006, 45, 2019; Chem. Eur. J. 2009, 15, 11660;
Chem. Eur. J. 2009, 15, 8121; Chem. Eur. J. 2010, 16, 9758.
OH
R3
O
Angew. Chem. Int. Ed. 2009, 48, 1644.
R
Ar
3 mol% AuCl3
R
Nu = ROH, AcOH, MeCN/H2O
R
R2
R2
H
Development of cycloisomerization-Prins cascade...
R
Chem. Eur. J. 2008, 14,
10892; Chem. Eur. J. 2010,
16, 7110.
R1
2 mol% PtCl2COD
70-87%; >97% de
R1
Cycloisomerization - [4+2] cycloaddition
+
Angew. Chem. Int. Ed. 2005, 44, 126.
OH
H
H
R
81-95%
R1
O
R Et
90-92%; >98% ee
J. Am. Chem. Soc. 2002, 124, 9056.
Angew. Chem. Int. Ed. 2006, 45, 4848.
72-84%
R
O
NH
O
HCl aq.
R1
5 mol% PtMe2COD
HBF4 (1 eq.)
MeCN, -30ºC to rt
+
HO
Angew. Chem. Int. Ed. 2008, 47, 7044.
Me
MeO2C
OH
C5H11
HO
OH
Et
H
MeO2C
O
H
C5H11
C5H11
HO
EtO2C
O
MeO2C
N
H
O
O
99%; 98% ee
2:1 dr
CO2Et
NH
O
O
H
OH
C5H11
OH
OH
[gram-scale]
OHC
1
72-88% R
R1
O
98% ee
HO2C
O
1) 5 mol% Ag+
2) H+
HO
O
R
MeO2C
OH
MeI
CO2Me
EtI
OH
CH2O
A. Mendoza, PhD Thesis, U. Oviedo 2009
8
José Barluenga
A. Mendoza
Activated propargylic esters: A new scaffold with new interesting reactivity to explore.
Indolizine synthesis by means of pyridine/diazocompound cross-coupling.
CO2Et
R3
R2
O
Baran Lab GM 2011-02-19
O
O
R2
DCM, rt
OEt
R1
PtCl2
[Cu(MeCN)4]BF4
R2
OEt
R1
R1=Ar,
R1
OEt
R2
O
vinyl, alkyl
not good)
R2=Ar, vinyl, alkyl, OR
R2
N
R2
CuIIIX
N
CuX
R2
CO2Et
CO2Et
R3
O
J. Am. Chem. Soc. 2010, 132, 13200.
E
OEt
Some radical iodine reactions you could be interested in...
R1
(1ary
I
J. Am. Chem. Soc. 2007, 129, 7772.
New rearrangement to (2-furyl)carbenes. Hydrosilylation and hydrogermanation.
hν
I2 + PhI(OAc)2 + tBuOH
85-98%
cyclohexane, rt
I
R2
5 mol%
[Cu(MeCN)4]BF4
O
O
+ HXR3
R3
EtO2C
I2 + PhI(OAc)2 + tBuOH
R2
O
H
OEt
XR3
53-82%
R2
I
tBuOI
+ AcOI
X= Si, Ge
OAc
OAc
CO2Et
OEt
I
O
[Cu]
R1
+
R3
R3
O
60ºC, 15h
I
O
5 mol%
[Cu(MeCN)4]BF4
N2
CO2Et +
R2
R2
O
N3
33-79%
R1
1/2 I2
R
RI
I
I
O
IN3
CO2H
CO2Et
O
R1
OAc
CO2Et
R3
RH
1/2 I2
R3
DCM, rt
R3
R2
R1=alkyl, H
R2=ester, ketone, Ar
R3=Ar, H
I
J. Am. Chem. Soc. 2008, 130, 13528.
R1
O
R1
Angew. Chem. Int. Ed. 2002, 41, 2556.
I2 (1.1 equiv)
10 mol% TMSN3
Diazo-heterocoupling
N2
OAc
I
PhI(OAc)2
R2
O
O
47-92%
cyclohexane, 40ºC
R1
DCM, rt
R3
R1
R3
N
R1
R1
R3
[Cu]
[Cu] OEt
R1
DCM, rt
28-94%
N2
O
O
5 mol% CuBr
CO2Et
N
1-30
90-99
.
R2
R1= alkyl, vinyl, aryl, CN,
ester, ketone, aldehyde,
halogen, OTs.
R2,R3= alkyl, H
R2
O
.
51-88%
OEt
:
:
O
[Pt]
R1 +
R1
70-99
1-10
Z
E
O
R2
R2
O[Pt]
O
R1
or
R1
OEt
Z
O
catalyst
O
AcOI
N2
Angew. Chem. Int. Ed. 2009, 48, 7569.
I
O
O
Angew. Chem. Int. Ed. 2005, 44, 5851.
9