Justine deGruyter
Robert G. Bergman
• 
Born:
Chicago,
IL.
1942
Educa&on
• 
B.A.:
Carleton
College,
1963
• 
Ph.D.:
University
of
Wisconsin,
Mad.,
1966
NIH
Fellow,
Jerome
A.
Berson
• 
Post‐doc:
Columbia
University,
1967
NATO
Fellow,
Ronald
Breslow
Independent
Career
• 
California
InsRtute
of
Technology
‐
1967:
Noyes
Research
Instructor
‐
1969:
Assistant
Professor
‐
1971:
Associate
Professor
‐
1973:
Professor
of
Chemistry
• 
University
of
California,
Berkeley
‐
1977:
Professor
of
Chemistry
‐
2002:
G.
E.K.
Branch
DisRnguished
Professor
Lawrence
Berkeley
NaRonal
Laboratory
Honors
and
Awards
• 
1969:
Alfred
P.
Sloan
Fellowship
• 
1984:
NaRonal
Academy
of
Sciences
• 
1984:
American
Academy
of
Arts
and
Sciences
• 
1986:
ACS
Award
in
Organometallic
Chemistry
• 
1987:
ACS
Arthur
C.
Cope
Award
(1996)
• 
1994:
DOE
E.O.
Lawrence
Award
in
Chemistry
• 
2003:
ACS
James
Flack
Award
in
Phys.
Org.
Chemistry
• 
2007:
NAS
Award
in
Chemical
Sciences
Commi6ee
Memberships
• 
Editorial
Boards
(JOC,
Organomet.,
Chem
Rev.,
IJCK,
JACS,
OL.
• 
ACS
ExecuRve
Commi^ees
(Org,
Inorg.,
Organometallic)
• 
Department
Review
Commi^ees
(Caltech;
UN,
Reno;
UM,
Ann
Arbor;
Harvard;
Rutgers;
NC
State;
UCSB
Baran Group Meeting
02/07/2015
Research
Interests
by
Decade
• 
1960s:
ReacRvity
of
methylnorbornyl
derivaRves
and
cyclopropyl‐
carbinyl
caRons
• 
1970s:
mechanisms
of
organic
reacRons;
“unusually
reacRve”
molecules
(e.g.
1,3‐diradicals
and
vinyl
caRons);
Bergman
cyclizaRon;
organometallic
chemistry
• 
1980s:
synthesis
and
chemistry
of
organo‐TMs,
migratory
inserRon
and
oxidaRve
addiRon
reacRons,
chemistry
of
dinuclear
complexes,
organo‐TM
enolates,
• 
1990s‐present:
C−H
acRvaRon,
Green
Chemistry
‐
>577
papers
published
to
date
‐
Mentored
over
200
undergraduates,
graduate
students
and
postdocs
‐
Numerous
teaching
awards
Public
Outreach
Efforts
• 
Outspoken
advocate
for
the
advancement
of
ethics
in
science
• 
Created
the
Community
in
the
Classroom
(CIC)
Program
at
UCB
Top
Cited
Papers
1.
“Rhodium‐Catalyzed
C‐C
Bond
FormaRon
via
Heteroatom‐
Directed
C‐H
Bond
AcRvaRon.”
Chem.
Rev.
2010,
110,
624.
2.
“SelecRve
Intermolecular
Carbon‐Hydrogen
Bond
AcRvaRon
by
SyntheRc
Metal
Complexes
in
Homogeneous
SoluRon.”
Acc.
Chem.
Res.
1995,
28,
154.
3.
“ReacRve
1,4‐dehydroaromaRcs.”
Acc.
Chem.
Res.
1973,
6,
25.
4.
“C‐H
AcRvaRon
in
Completely
Saturated‐Hydrocarbons‐
Direct
ObservaRon
of
M
+
R‐H

M(R)(H).”
JACS.
1982,
104,
352.
5.
“Para
Benzyne‐
GeneraRon
as
an
Intermediate
in
a
Thermal
IsomerizaRon
ReacRon
and
Trapping
Evidence
for
1,4‐
Benzenediyl
Structure.”
JACS.
1972,
94,
660.
Robert G. Bergman
Justine deGruyter
1‐Cyclopropylvinyl
Carboca1ons
Reac1ve
1,4‐Dehydroaroma1cs
Me
AgNO2
H2O
I
Baran Group Meeting
02/07/2015
RH
O
AgOAc
HOAc
OAc
AgOTs
MeCN
OTs
150-200°C
PhH, CHD
NR2
R1
NR4
H
R3
NR4
H
R1
NR1
R
[Zr] NR
R1
N
[Zr]
N
R
R1
Bergman Cycloaromatization
H
HS R
NR1
H
R
N
H
R
N
R1
Enediyne drugs: "smart bombs"
- delivery system
- warhead
- safety catch
2
S S SR'
HO
NtBu
Me Zr
THF
Me
Me
H
R
[Zr]
Me
Bergman Cyclization
HO
H
O
Me
S
OR
NHAc
O
[Zr] NR1
NR
R1
H
S OR
O
NHAc
H
JACS.
1998,
120,
11828.
CHO
OK
tBu
R
H
OC
Me
Me3P
Rh
O
Ph
Ph
O
O
S OR
R1
O
1 (1-4%)
OTMS
Ph
R1
R2
NHAc
“Controlling
the
ReacRvity
of
Bergman
and
Myers‐Saito
CyclizaRons.”
D.A.
Ryan,
UIUC
(2002).
OTMS
H
Ph
- TONmax= 100
- syn:anti ratios dependent on reaction
conditions
JACS.
1989,
111,
938.
H
H
H
H
1
OTMS
R2 PhCHO
O
89:11 syn:anti
Me3P
CO
Rh
O
PMe3
Me
Ph
cd. ca. 2.98-3.02Å
Me
R
Me
DMSO
HO
cd. 4.12Å
tBu
tBu
R
OTMS
Me
TMS
TMSCl
PhH, rt
O
PhMe, —40°C
R= H, Me
Me3P
CO
Rh
O
PMe3
PMe3
O2
cleaved
DNA
vs.
Metal
Enolates
PMe3
OC Rh Cl
PMe3
NHAc
dsDNA
NR
H
HO
OR
Calicheamycin
R
CH2OH
Enediyne
Drugs
NR2
H
R1
H
Cl
MeOH
JACS.
1969,
91,
2115.
JACS.
1971,
93,
1925.
Imine
Metathesis
Cl
CCl4
H
*
H
H
H
- H2
H
H
*
H
H
O
400°C
O
slow
O
O
H
*= +, —, •
Acc.
Chem.
Res.
1973,
6,
25.
(and
references
therein)
Robert G. Bergman
Justine deGruyter
C−H
Ac1va1on:
The
“Holy
Grail”
• 
Bond
strength:
90‐100
kcal/mol
• 
Ubiquitous,
but
difficult
to
differenRate
• 
MechanisRc
insight
allows
for
opRmizaRon/scope
expansion
Baran Group Meeting
02/07/2015
Me
Me
Me
Me
Me
P
Me2
H
[Ir]
H
Me
h!
P
Me2
Iridium(I)
"We now wish to report the discovery of an organotransition-metal system capable of
intermolecular oxidative addition to single C—H bonds in saturated hydrocarbons...in
high yield at room temperature in homogeneous solution."
Me
[(Me5C5)IrCl2]2
H
[Ir]
h!/PhH
1. PMe3
2. LiEt3BH
CHBr3
Me
Me
Me
Me
Me
h!/C6H12
H
Ir H
PMe3
Me
Me
Me
R
Ir H
PMe3
Me
Me
H
[Ir]
Me
Me
Me
Br
Ir R
PMe3
Me
Me
P
Me2
Al2O3
PhH
Me
Me
LnM
C6H5
Ir H
PMe3
Me
L + Ln-1M
M—R1 + R2—H
+ R—H
(L)
Cp* [Ir]
Cl
h!
tBuX
Cp*
Me
Me
NH2
L
Me
Ir
X
Me
Me
metathesis
CO2
(X=O)
tBuNC
Me
Me
L
Ir
Cp*
X
N
tBu
Cp*
Ir
O
Me
L
O
Ir
Me
N
HO
O
1a + 1b
(1)
M—R2 + R1—H
H
R2
(2)
Science.
1995,
270,
1970.
H
[Ir]
H2C
CH2
OTf
Me
Me4C
no reaction
Cp*(PMe3)Ir(CH3)(OTf)
[Ir]
TfO
Cp*
L
M
Me
X= NH
X= OH
Me
X
R
H
C2H6
tBuNCO
(X=NH)
Cp*
X
Me
Ir
Ln-1M
H
OTf
OTf
Cp*
L
CO2
(X=NH)
Me Me
L
(TMS)2NK
R
[Ir]
H2C
H H
Me
Me
OH
H
150°C
C6H11
[Ir]
R1
!-bond
(TMS)2NK
(L)
Cp* [Ir]
Cl
Me
Me
Ln-1M
ox. add'n
Me
CHCl3
2b (X=Cl)
P
Me2
R—H
[Ir]
Me
N
CHCl3
(L)
X= NH2
X= OH Cp* [Ir]
H
1b (X=H)
JACS.
1998,
120,
3253.
JACS.
1982,
104,
352.
Cp*(L)IrH2
X
C6H11
H
[Ir]
Ph
X
Iridium(III)
Me
h!/Me4C
Me
X
[Ir]
P
Me2
2a (X=Cl)
+ CH2Br2
Me
[Ir]
H
h!
Me
150°C
1a (X=H)
h!
Me
+
X
[Ir]
Ph
Me
+ 13CH4
+ CH4
Me
Ir
tBu N
H
Me
N
Me
O
JACS.
1988,
110,
3704.
[Ir]
TfO
13CH
3
[Ir]
OTf
JACS.
1993,
115,
10462.
Robert G. Bergman
Justine deGruyter
Me
ClH2CCl
[Ir]
ClCH2Cl
Ir Me
PMe3
Me
Me
Me
Cp2Zr(CH3)(X)
Me
Me
Baran Group Meeting
02/07/2015
B(Arf)4
CH2Cl2
ClCH2Cl
[Ir]
13CH
3
NHR
Cp
Zr
Cp
Ph
NHR
Cp
Zr
Cp
Me
[Cp2Zr=NR]
H
H
O
Me
H
Me RhH2
Me3P
H
[Rh]
X
H H
I
[Rh]
O
0°C
O
H
h!, —50°C
H O
H
H2O/Silica Gel
H H
CHI3
H
H O
[Rh] —78°C H
H
[Rh]
H
[Rh]
O
X
X
[Rh]
I
X
[Rh]
JACS.
1988,
110,
8729.
Y
X
[Rh]
Liquid
Noble
Gases
1,2-H Migration
H
[Ir]
Zirconium‐Mediated
[Ir]
[Zr] NHtBu
X
[Zr]
X
THF
X
BuHtN
NtBu
THF
H
Cp
Zr
NHtBu
H
Me
-THF
X
[Ir]
75°C
H
O
Me
EtOH
NHtBu
[Zr]
BuHtN
[Zr]
BuHtN
[Zr]
H
Ir H
PMe3
Me
[Ir]
H
MeOH
CpMn(CO)3, cy.
NHtBu
[Zr]
Fe
Re(CO)3
Me
Me
75°C
CpRe(CO)3, cy.
[Ir]
Me
[Cp2Zr=NtBu]
Cp2Fe, cy.
H
[Ir]
Me
CH4
Zr
Cp
75°C
JACS.
1995,
117,
5877.
- Interaction energy between M
and Kr or Xe ! 5-10 kcal/mol
- Interaction energy between M
and liquid alkanes ! 8-12 kcal/mol
JACS.
1989,
111,
7628.
NHtBu
[Zr]
R2
H2O
R2
R1
O
O
H
R1
Y
1,2-[Rh] Migration
25°C
H
X
X
[Rh]
O Y
X
X
RHN
O
O Y
X
CHI3,—78°C
1,3-enamine
R1 dianion synthons
Zr
R2
Possible Mechanistic Pathways
Me
Cp
R
N
R
Cp
N
Zr
Cp
O
Rhodium‐Mediated
Me
Cp
Cp
Cp
Science.
1995,
270,
1970.
Me
R1C CR2
THF
Cp2Zr(NHR)2
Zr
N
R
- CH4
CH2Cl2
[Ir]
Zr
Cp
RNH2
[Ir]
R
N
Cp
Re(CO)3
[Ir]
BuHtN
[Zr]
Mn(CO)3
H
OMe
iPrOH
H Me
[Ir]
OH
tBuOH
[Ir]
H
H Me Me
[Ir]
OH
JACS.
1989,
111,
6841.
Robert G. Bergman
Justine deGruyter
Bergman‐Arnold
Niobium(III)
Imido
Complexes
1 atm CO (12 equiv)
1 equiv. H2
20% molar 1
Me
Ph
PhH
N
N
Ar
Me
N
Me
CO
Nb
L
Ar
Me
N
Nb
N
R
1 atm H2
12 h, rt
- 2 CH4
Me
Ta
Me
Ta
N
N
Me
N
Cl3(py)2Ta
3 PhCH2MgCl
Ph
NCMe3
Ta
Ph
N
Me
Ar
Ta
Ph
R2
N
N
Ta
Me
R=H, CH3
H2NPh 135°C, C6D5Cl
N
Ph
R2
R1
Markovnikov
N
+
Ph
R2
R1
anti-Markovnikov
Ar
Ph
N
N
tBu
Me
N
Ph + H2NPh
Ar
N
N
= Me
Ph
Ph
Ph
Ta
B(C6F5)4
1 (5 mol%)
N
C6D5Cl, 135°C
Ph
Ph
Ph
H
N
+
Ph
HN
Ph
Ph
H2N
Ph
+
H2N
N
O
Ta
Me
Me
+
Me
R
N
Me
N
N
B(C6F5)4
2
Ph
135°C, C6D5Cl
N
N
NCMe3
Ar
Nb
NtBu
R1
[Ta] (5 mol%)
Tantalum
Complexes
N
O
Me
Ph
Ph
NtBu
F
N
+
Ar
Ph3CB(C6F5)4-
2 (5 mol%)
R
Me
Ta
Ph
JACS.
2013,
135,
8145.
Ar
NCMe3
JACS.
2014,
136,
2994.
N
I
N
1
Ar
Me
N
Me
R=Tol, Me
N
MeI
N
N
F
Nb
F
N
N
- THF, - N2
Ar
Ar
Me
neat
Nb
N
Me
N
RCN
R
NtBu
ArN3
!
NtBu
N
R
1
Ar
Me
N
Me
Me
Ar
Me
Me
N
-
CN
S
Me
Ta
Dalton
Trans.
2006,
203.
CF3
Me
Me
NtBu
JACS.
2011,
133,
14904.
Ar
N
N
CO
NtBu
N
S
Me
N
Ar
Me
N
Me
Me
N
N
Me
Ta
N
Ph
N
Nb
Me
N
N
Nb
N
N
N
For
further
reading
on
recent
RGB
collaboraRons
see:
Burns
Group
MeeRngs−
Ma^
Landry
(Stanford)
H
H
Z-!-methylstyrene
75%
Ph
Ar
Me
Me
Baran Group Meeting
02/07/2015
Me
TMS
NH2
NH2
2 (5 mol%)
Me 135°C
N
Me
Me
Me
H
•
2 (5 mol%)
H
135°C
N
Me
NH2
NH2
TMS
Organometallics.
1999,
18,
4465.
Org.
Le6.
2006,
8,
2445.
Org.
Le6.
2004,
6,
2519.
Robert G. Bergman
Justine deGruyter
Bergman‐Toste‐Raymond
Bergman‐Toste
Nitroso
Cobalt
Complexes
Me
Me
Me
Me
Co
N
O
R1
R2
R4
X
R2Me
R3
R1
2N
LiAlH H
Me
O
R
R 1OH
N
R2
Co
Me
H
N
R
X
2
R4
Me
R4N 3
1=
Me
O
Co
N
E+, Sc(OTf)3, LHMDS
Me
5:1 THF:HMPA, rt
Me
LiAlH
Me
O
H
OH
Me
Me
Me
Me
X
Me
OH
Me
Me
trans preference
Path B
Co
N
Me
OH
O
N
+ H2O
Me
Me
OH
- H+
Me
E
Me
+ 1 - H2O
Me
OH
Me
O
Me
Me
O
- 1 + H2O
Me
Me Me
cis preference
Me
Co
Me
Me
N
O
O
H2N
Co Cp R OH
Me
Path A
JACS.
1980,
102,
5676.
Me
O
N
OH
Me
H+
Me
Me
E+= Michael acceptor
H2N HO
O
N
O
N R
O
X
Organometallics.
1983,
2,
787.
Me
Cp Co
X
O
Me
Me
O
Me
O
1, NO
N
O
Cp Co
R
0°C
N
X
O
R3
O
N
Baran Group Meeting
02/07/2015
O
N
HO
O
OH
125°C, µwave
O
H
JACS.
2008,
130,
3777.
Org.
Le6.
2009,
11,
3698.
JACS.
2012,
134,
17873.
JACS.
2013,
135,
18802.
Polymers
Ms
N
1 equiv.
Bn
Ms
N
Me
4 equiv.
Ms
N
Bn
Me
N
H
23
Ms Me
Mn= 3300, PDI=1.04
DMF, 45°C
Ms
N
Bn
DMF, 45°C
N
Ms
Ms
N
Me
Me
H
Me
107
Mn=14,700, PDI=1.01
Me
JACS.
2005,
127,
17616.
TMS
NH
1/2 [Al(NMe2)3]2 +
NH 100°C, 60 min
- HNMe2
TMS
O
X
1
neat, 25-75°C
m
O
H
O
m
X
Me
O
NMe2
n
O
Me
O
1
PhMe, 75°C
1:1 D2O:[D6]DMSO
45°C, pD= 8.0
Unbuffered D2O
rt
Me
O
H
N
Me
O
Me
Me
Me
Me
NH
Me
Me
O
O
kcat (s-1)
kuncat (s-1)
a
2.9(4) x 10-2
4.0(3) x 10-8
(730,000)
b
1.6(1) x
10-2
7.7(8) x 10-9
2,100,000
c
5.7(1) x 10-2
3.3(1) x 10-8
1,700,000
kcat/kuncat
Chem.
Eur.
J.
2014,
20,
3966.
Me
H
7% Ga-host
a or b
O
O
Me
a= E,E
b= Z,Z
c= Z,E
Me
7% Ga-host
TMS
N
NMe2
Al
NHMe2
N
TMS
1
PhMe
OH
Me
O
O
O
O
NMe2
Me
n
Organometallics.
2011,
30,
3217.
Robert G. Bergman
Justine deGruyter
Bergman‐Ellman
Heterocyclic
C−H
Ac&va&on
N
Baran Group Meeting
02/07/2015
N
R1
N
THF, 160°C
N
N
X
R2
[RhCl(coe)2]2 (5 mol%)
PCy3 (7.5 mol%)
[RhCl(coe)2]2 (5 mol%)
PCy3 (40 mol%)
I
EtN3 (4 equiv)
THF, 150°C
R3
n
N
N
N
N
N
N
N
N
N
N
Ph
N
H
R1
N
X
R2
N
Ph
R3
n
Ph
N
Ph
N
O
O
Org.
Le6.,
2004,
6,
35.
N
BnN
N
Me
[RhCl(coe)2]2 (5 mol%)
JACS.
2001,
123,
2685.
BnN
Me
Ligand (15 mol%), PhMe
BnN
R1
1. (PPh3)3RhCl
125 or 150°C, PhMe
R3
R2
X
2. I N HCl (aq.)
n
O
R1
R2
O
n
R1
R2
R3
or
R3
R
R
X
n
X
BnN
Me
BnN
X= CH2, O, NR
n= 0,1
Me
BnN
Me
BnN
Me
Ph
SiMe2Ph
Me
BnN
Me
Me
N
O
Me
Me
O
O
Me
O
Me
H
O
Me
Me
O
Me
O
JACS.
2004,
126,
7192.
Me
O
mechanism?
N
R
Me
R=Me, Ac, SO2Ph
Me
N
JACS.
2001,
123,
9692.
[RhCl(coe)2]2 (5 mol%)
(p-NMe2)PhPEt2
Me
N
Me
PhMe, 100°C
H
JACS.
2008,
130,
2452.
[RhCl(coe)2]2 (5 mol%)
PCy3 (7.5 mol%)
H
N
H
N
MgBr2 (5 mol%)
150°C, THF
N
(PhO)2PO2H
Me4NBH(OAc)3
N
R5
NR4
R1
H
N
N
R
R
R
S
N
O
N
H
O
N
N
R
Me
N
N
H
R
R5
R=
N
H
R
R1
Me
O
N
S
Me
R3
R2
OtBu
OiBu
TMS
[RhCl(coe)2]2 (2.5 mol%)
NR4 4-Me2N-C6H4-PEt (5 mol%)
N
N
S
O
O
N
Me
N
CN
Me
PhMe, heat
(PhO)2PO2H
TMS
R5
R7
NR4
R1
R3
S
Me
JACS,
2002,
124,
13964.
R7
R5
N
R1
R2
not isolated
N
R6
R3
R2
R2
1. PhSO3H
—78°C
2. Me4NBH(OAc)3
R
Me
Bn
R6
R3
NR
Me 4
Me
H
JACS.
2013,
135,
2478.
Robert G. Bergman
Justine deGruyter
Baran Group Meeting
02/07/2015
Total
Synthesis
of
Vasicoline
Total
Synthesis
of
(+)‐Lithospermic
Acid
CO2Me
CHO
MeO2C
CHO
1. CBr4, PPh3, 88%
isovanillin, Na, MeOH
OMe
OH
O
OMe
Cl
OH
2. DiBAl-H, CH2Cl2
—78°C, 96%
CO2Me
CO2H
O
CO2Me
OMe
O
F3C
OH
O
piperidine, py.
100°C, 85%
O
OMe
OMe
OMe
NH2
N
NHMe
NHMe
NH
(2 equiv) (50 mol%)
CuI (25 mol%)
K2CO3, 1,4-dioxane
140°C
2. HCl, H2O, 52% brsm
3. KHFe(CO)4, CH2O,
5 bar CO, EtOH, 105°C
58%
OMe
OMe
K2CO3, DMF
0°C to rt
>20:1 regioselectivity, 65%
[RhCl(coe)2]2 (5 mol%)
2 (15 mol%)
CO2Me
CO2Me
O
O
OMe
OMe
Me3SnOH
Cl
Cl
N
o-Cl2C6H4
N
N
CO
CO22Me
H
N
TMS
CO2Me
CO2Me
O
O
Cl
N
75% ee
56%, 99% ee after recryst.
OMe
OMe
Br
Cl
1.
CHO CO Me
2
O
HO
OMe
EDC, DMAP
CHCl3, 80%
MeO
MeO
Br
CCl4, 0°C
(96:4), 96% (mix)
OMe
OH
O
O
Cl
PBr3
OMe
1. (R)-(-)-aminoindane
PhH, reflux, 99%
2. i. [RhCl(coe)2]2, FePCy2
PhMe, 75°C
ii. HCl, H2O, 88%
MeO
1. H2SO4, MeOH
85°C, 94%
O
OMe
MeOH: py. (1:1), 120°C
59%
OMe
2. i. nBuLi
ii. ClCO2Me
93%
OMe
Cl
OMe
OMe
OMe
OMe
O
O
HO
HO
O
O
P
OH
OH
neat, 100°C
sealed tube
35%
CO
CO22Me
H
N
O
O
OH
2=
NMe2
N
OH
OH
Cy
OH
OH
R= Me
JACS.
2005,
127,
13496.
R= H
Cl
JOC.
2006,
71,
1969.
Total
Synthesis
of
Biologically
Ac&ve
Dihydropyrroloindoles
O
N
PG
H
1. RNH2, 3 Å ms
PhH, rt,
2. i. [RhCl(coe)2]2 (10 mol%)
20% L, PhMe, 90°C
ii. 10% AcOH/THF
OMe 61%, 90% ee
O
N
H
O
OMe
PG
N
O
O
O
RhCl(dppp)2 (5 mol%)
xylene, reflux, 86%
N
Br
N
Br
OMe K2CO3, THF, 85°C
75%
Br
1. Pd(OAc)2 (5 mol%)
(R)-BINAP (7.5 mol%)
Cs2CO3, PhMe, 105°C
62%
H
N
O
O
N
H
2. CH3SO3H, CH2Cl2, 61%
N
N
OMe
OMe
Org.
Le6.
2006,
8,
1745.