Baran Lab
Group Meeting
The Career of Paul G. Gassman
Biography
- Born June 22, 1935
- Died April 21, 1993 (Aged 57)
Education
- B.S. (1957) from Canisius
College in Buffalo, New York
- Ph.D. (1960) from Cornell
University under Jerrold
Meinwald
- Post-Doc in same Ph.D. lab
Academic Career
1960s - Assistant Professor of Chemistry at Ohio State
University
1966 - Associate Professor
1969 - Full Professor
1974 - Move to University of Minnesota
1974-1976 - remain as Adjunct Professor at Ohio
State
1973 - R.J. Reynolds Professor at Duke University
1988 - Regent’s Professor
Awards and Honors
Fellow of the Alfred P. Sloan Foundation (1967-69), ACS Award in Petroleum
Chemistry (1972), Fellow of the Japan Society for the Promotion of Science (1981),
Fellow of the American Association for the Advancement of Science (1982),
Minnesota Award from the Minnesota Section of the ACS (1983), ACS James Flack
Norris Award in Physical Organic Chemistry (1985), ACS Arthur C. Cope Scholar
Award (1986), University of Minnesota George Taylor/Institute of Technology Award
for Service (1987), Fulbright Scholar (1988), Member of National Academy of
Sciences (1989), Chemical Pioneers Award of the American Institute of Chemists
(1990), National Catalyst Award of the Chemical Manufacturers Association (1990),
Member of the American Academy of Arts and Sciences (1992), and, from his
undergraduate college: the James R. Crowdle Alumni Award (1971), Distinguished
Alumni Award (1985), and the President's Medal (1991)
Yiyang See
04/25/2015
Important Professional Appointments
1976-88 - ACS Division of Organic Chemistry as a member of the Executive
Committee
1980 - Chairman-elect
1981 - Chairman
1983-88 - Councilor
1990 - ACS President
Research Interest
mechanisms of catalysis (hydrocarbon metathesis)
X-ray photoelectron spectroscopy (XPS)
chemistry of highly strained molecules
neighboring group participation in carbocation chemistry
cycloaddition reactions
enzyme mechanisms
organoelectro-chemistry,
carbanion chemistry
synthesis of heterocyclic molecules
nitrenium ion chemistry
300 publications in scientific journals, 32 patents, and 11 books
Trained 72 Ph.D., 13 M.S. and many post-docs
Paul G. Gassman Distinguished Service Award (by ACS)
Gassman Lectureship in Chemistry (University of Minnesota)
Lessons from Gassman:
“I feel that anyone desiring to become a good organic chemist should be
putting in a minimum of 60 hours per week in improving their knowledge and
ability in the area of organic chemistry. At least ten hours of this time should be
spent reading.”
“Postdoctorals are supposedly accomplished chemists who can carry their own
weight in any research group….I expect a great deal from post doctoral
associates.”
“…I also feel that doing good chemistry is a matter of pride… Pride also entails
keeping equipment running and clean, never leaving a mess for your lab mates
to clean up, making sure that anything that is broken gets fixed…”
Baran Lab
Group Meeting
The Career of Paul G. Gassman
Commentaries:
13 in total from 1987 to 1992
The Reactivity of strained "bent" bonds
- NO DIVINE RIGHT OF CHEMISTS (1990)
- GRADUATE-EDUCATION IN CHEMISTRY - WHERE HAVE WE BEEN AND WHERE ARE WE
GOING (1988)
- WILL CHEMISTRY EXIST IN THE FUTURE (1987)
Energy release for
breaking central
bond/ Kcal per mol
At the Beginning:
N
R
O
chloramine
OH
NH 2
N
OH
R
R
O
N
R
R
N
Me
NOCl;
Na tBuO;
ozone
Me
Me
O
OH
chloramine
N
85%
Me
O
Me
radical
mechanism
N2
Me
light,
aq. dioxane
Me
attack from
concave face
normal σ
0.3%
0.4%
88.7%
2.2%
1.2%
2.1%
3.0%
O
+
D
O
H
H
D
O
O
+
attack
from
less
hindered
face
H
H
H
a
b
H
symmetrical
known & studied
"twist" bent
unknown in 1967
Top view
Side view
Chem. Comm. 1967, p793
Ph
JACS, 1968, p5637
CO2H
H
NC
CN
H
H
a
a
a
H
H
H
H
b
H
H
b
b
H
NC
NC
NC
NC
b
H
D
D
b
H
H or
D
H
61%
N 2+
H
H
O
H
CH2Cl2, reflux
4h
a
Me
6.7%
D
1:18
Types of strained bonds
CN
CN
H
6.2%
O
JOC, 1965, p2262
a
H
80.0%
oxidation
O
H
H
H
CN
CN
H
H
CN
Me
Me
+
Me
H
H
D
D
JACS, 1960, p2857
a
b
CN
JACS, 1968, p4746
> 80%
hυ
no filters
no reaction
CO2H
60%
Y
O
CN
NC
Me
X = OH, NH 2, H
X Y = OH, NH 2, H
rapid
CN
Me
H
α-pinene
- Nature of reaction mechanism?
- Stereochemical requirements?
32-34
NC
Bicyclo [2,1,1 ]hexanes
Me
47
rapid
Rate of reaction with
H 3COOC
COOCH 3
R
JACS, 1959, p4751
Me
41
Mechanism of attack of olefins on "bent" σ bonds
CN
CN
2 days
H
160°C
CN
CN
H
the Forster reaction
O
Yiyang See
04/24/2015
H
H
NC
NC
Acc. Chem. Res. 1971, p128
Baran Lab
Group Meeting
The Career of Paul G. Gassman
The "Twist" Bent Bonds
Norbornyne
Dauben:
Me
Me
hυ
H
Me
EtOH
H
+
OEt
Me
hυ
H
H
Me
H
H
OEt
O
38%
O
H
H
Cl
22%
H
HO 2C
MeO
H
O
Me
H
H
H
Me
Me
H
H
Br
H
1.Na 2S
2. NCS, CCl 4
3. mcpba
28%
- prepared in similar way
- highly acid sensitive
- E1/2 1.34V
- easily photo-isomerized
H
H
H
KO tBu
D
S
O O
Cl
Photolactonization
hυ
1-cyanonaphthalene/
biphenyl, MeCN/H 2O
H
8h
Me
18%
Me
O
O
+
O
H
Me
42%
Me
H
CH2
5%
- yields ranges froom 36 to 69%
- high propensity to form 5-member
lactones
-1e
O
OH
O
O
HO
H
Me
The Chemistry of electron deficient carbocations
- detailed studies on the solvolysis of electron deficient systems
- plenty of kinetic studies
- please consult: Acc. Chem. Res., 1983, 16 (8), pp 279–285
O
Me
- easily isomerized to cis
- low oxidation potential
(E1/2 1.52V)
JACS, 1983, p667
JOC, 1986, p2397
Computational studies: JACS, 1988, p2309
JACS, 1975, p4768
AH
H
HO
H
n-Bu
n-Bu
O
Br
insertion
-LiCl
H
HO
Preparation of trans-bicyclo[4.1.0]octanes
OMe
Li
n-Bu
D 2O
H
JACS, 1968, p6895
O
n-Bu
BuLi
Li
n-Bu
OMe
1. CH2I 2, Zn
2. LAH
3. TsCl,pyr
4. LiBr
49%
∗
BuLi
H
1.TsNHNH 2
H 2. NaOH, cold
3. hυ, aq. dioxane
1. CH2I 2, Zn
2. Na, xylenes
O
3. Cu(OAc)2, O2
H
B
Cl
BuLi
H
Preparation of trans-bicyclo[5.1.0]octanes
OMe
O
AH
Proposed Mechanism:
Chem. Comm. 1967, p795
40%
n-Bu
+
1:1.6
- Quenched with D2O --> only starred H in B was labelled
- Using C3 deuterated SM, product ratio was 16:1
- Starting with enatiopure SM, A was opp. enantiomer and B was racemic
Cl
cholestadiene
n-Bu
80%
H
OEt
alumina
column
Me
EtOH
nBuLi (4 -5 eq), THF
2h, RT; H 2O
Cl
Me
H
H
cholestadiene
Gassman:
Me
Yiyang See
04/24/2015
Me
Me
H
Me
HO
Me
H
Me
JACS, 1987, p7547
Baran Lab
Group Meeting
The Career of Paul G. Gassman
Transition Metal induced rearrangements
Retrocarbene Addition to cyclopropanes
Me
Me
Me
Ph
Me [Rh(CO) Cl] , 2h;
2
2
chloranil, PhH, 2h
1. dibromocarbene
2. MeLi
Me
Ph
7%
PhWCl 3.AlCl3
JACS, 1976, p6057
azulene product
Cyclopropane-Olefin Cross Metathesis
Ph
Hypothesis: a divalent carbon fragment can be transferred from an alkyl-substituted cyclopropane to an
electron-deficient, conjugated olefin to yield an alkene and an electron-deficient cyclopropane
Ph
C-H
insertion
1,2 vinyl shift to
give diene product
+
70%
Rh
Ph
Ph
35%
H
R
1a, R = Et
b, R = nBu
c, R = i-Pr
Me
Me
PhWCl 3.AlCl3
+
Ph +
19%
H
Ph
Me
Mechanism:
Rh(I)
R
Ph
Ph
Ph
Ph
Me
Yiyang See
04/24/2015
Ph
Me
naphthalene product
General Scheme:
JACS, 1971, p5897
H
R
H
Synthesis of small [n]paracyclophanes
+
R1
R1
H
+
R
Catalyst loading: ~1% pf PhWCl 3/EtAlCl2
O
1. H 2O
2. LTA or electrochem.
H decarboxylation
O
O
H
H
H
H
1. mcpba
2. H +, heat
(CH 2)n
H
O
O
O
JOC, 1980, p2923
Cyclobutane Diene Interconversion
CF 3
CF 3
CF 3
CF 3
hυ
0.1 eq. PhWCl 3.AlCl3
hυ
0.1 eq. PhWCl 3.AlCl3
CF 3
CF 3
CF 3
CF 3
JACS, 1976, p6058
JACS, 1976, p861
Baran Lab
Group Meeting
Yiyang See
04/24/2015
The Career of Paul G. Gassman
The Chemistry of Nitrenium ions
- well studied species in 1962
R1
R2
C R3
vs
carbonium ions
R1
R2
N
Application of Nitrenium ion theory to synthetic problems
π route to azabicycles
MeO
H
- virtually unknown in 1962
nitrenium ions
Ag+, MeOH
Me
Me
Me
MeOH, heat
N
Cl
Me
Me
Me
N
+
Cl
H
59%
- accelerated by Ag+
Me
Me
Me
N
+
MeO
H
20%
77%
Me
Me
7%
8%
N
H
Me
Me
Ag
60%
N
Me
Ring expansion & contractions
Cl
Ar
N
Ar
Cl+
NH
Distinguishing between divalent nitrogen species with a positive charge (nitrenium) vs δ+ nitrogen in TS
H
Ag+, H 2O
Me
Me
4%
Cl
43%
N
Me
N Me
HO
O
Ar
Ag+, MeOH
N Cl
Me
Ag
N Cl
Me
Ar
Me
OMe
O
Ar
NHMe
> 65% mass balance
Chem. Comm. 1969, p495
R1
Me
Me
Cl
N R2
ionization
-
R1
N R2
relaxation
R1
N R2
Ph Me
N
Cl
Cl-
Me
singlet state
carbonium like reactivity
Me
Me
Me
triplet state
radical cation like reactivity
Me
Me
Me
Me
Ag+, MeOH
Ph
Me
Me
Ag+, MeOH
N
Cl
Me
Me
Me
N
N
spin inversion
catalyzed by
heavy atom
solvents
Me
Me
N
Cl
H
Ph
NaBH 4
N Me
36%
Ph
BzCl
Ph
N
N
N Me
H 2N
H 2N
H
N
Cl
N
Ph
Ph Me
N
+ 24% RSM
O
Me
OH
combined 75%
N
H
Tet. Lett. 1971, p109
SN Ar reactions of anilines
Me
Me
Me
Me
Me
N
H
R1
Me
R
N
Cl
Ag+,
MeOH
R
N
R1
R1
R
NH
39 - 77%
Me
MeO
N H
H
R1
R
N
Cl
Ag+,
R1
MeOH
N
R1
R
Me
Me
Me
R
N
MeO
R1 = EDG
62 - 70%
JACS, 1972, p3884
5-hydroxyl oxindoles
O
N
OH
Acc. Chem. Res 1970, p262
ArSO2Cl, TEA
-78°C
Ar = 4-Me-Ph
4-NO2-Ph
O
N
O SO Ar
2
MeOH
N
OH
30-34%
MeO
O +
O
N
H
42-54%
Chem Comm. 1971, 1437
Baran Lab
Group Meeting
The Career of Paul G. Gassman
On the chlorination of indoles - Gassman's proposal
R
R
NaOCl
R
cold
N
H
N
Cl
R
Yiyang See
04/24/2015
MeOH
cold
Cl
N
R
Ag+,
R
N
R
Welcome to heterocycle land!!
OMe
'Gassman' - type alkylation
R
R
Cl+
rapidly to 25°C;
rapidly to -10°C
X
NH 2
X
N
H
R
R
R
S
Cl
X
N
H
R
R
NaOMe or
Tl(OAc)
Cl
N
H
R
R
R
N
OH
R1
X
R
R
R1
N
O
R
O
R
OR1
N
H
R
OH
O
S
S
base
R
X
R
R
S
base
R
NH 2
products
OH
R
NH 2 R
R1
Tetrahedron, 1972, p2749
X
R1
R3
X
N
R1
R2
+
NH
X
R1
R
R
+
O
Cl
OH
S
R2
R
Me
S
O
R
O
OEt
R1
Me
S
O
+
NH 2 O
R
R1
R2
NH 2
S
+
S
R
Miscellaneous:
- Se can be used instead of S (lower yields)
Ph
S
O
EtO
OH
R
SMe
+
O
R
R
NH
S
LG
R2
O
N
R1
or air oxidation
R1
R
OH O
+
R
O
R
+
R3
NH
O
N
R1
Me
S
O
R
S
LG
S
+
N
R1
N
R1
OH
R
R
R
X = CH or CR1
R
R
R
R
R
OH R
NH 2
X
R
N
R
S LG
S
R
Baran Lab
Group Meeting
Yiyang See
04/24/2015
The Career of Paul G. Gassman
The Ultimate Dienophile
The Ionic Diels Alder Reaction
R
Suitable dienophiles
R
H
R
R
H
Me
Me
H
Me
OH
HSbCl 6
TfOH
pTSA
R = tBu
R
H
64%
65%
74%
13%
3%
8%
JACS, 1984, p6086
CH2
Control of regiochemistry - introduction of Lewis basic groups
Ph
Me
Me
HO
Me
S
S
80%
Me
H
D 3C
CD 3 +
H
CH 3
H
HS
CD 3
Me
Me
+
3%
JACS, 1989, p2319
using allenes
O
R
R
H 3C
+
R
R
R
R
O
R
R
O
O
O
R
20-71% yields
22-65% yields
Tet. Lett.1991, p6473
D 3C CD CH
3
2
H 3C
H
CH 3
D D
D 3C
CH 3
D C
CH 3 3
CD 3
H 3C CH CD
3
2
DD
CD 3
CD 3
CH 3
H 3C CH CH
3
2
- protonation do not produce the same allyl cation; allyl cations involved are asymmetrical
- starting alkenes do not interconvert significantly by other pathways
- resulting asymmetric allyl cations do not interconvert under reaction conditions
(or slower than cycloaddition)
X
[2+2]
O
HO
5 steps from glutaraldehyde
diene, Lewis acid
H
CH 3
H
CH2
CD 3
CD 3
46%
D 3C
CH2 +
Proposed:
Me
Me Me
D 3C CD CD
3
2
CD 3
CD 3
CH 3
68:32
JACS, 1986, p3075
H
Me
H
CD 3
CD2
S
S
S
Me
1 mol% TfOD D 3C
3min, -78°C
CH 3
H
CH 3
H C
CH 3 3
CD 3
H 3C
H
D 3C
CD 3
CD2
Me
More complex examples:
macrocyclization
OMe 2% TfOH, 25°CMe
Me
0.001M, 3min
O
H 3C
27:73
31%
S
O
CH 3
CH2
CD 3
S
56%
S
Me
CD 3
H
1 mol% TfOH H 3C
3min, -78°C
S
S
For mechanistic studies:
JACS, 1990, p8624
yields: 46-78%
50 mol% TMSOTf
HO
S
Ph
Me
OMe
Me
Me
OEt
An Unsymmetrical 1,1,3,3-Tetramethylallyl Cation
H 3C
Me
OR
OR
yields: 53-83%
50 mol% TMSOTf
yields: 56-84%
2 mol% TfOH
H
17%
23%
12%
RO
OR
OEt
OEt
yields: 70%
R
H
R1
R
R
10% acid
R
RO
Tet. Lett.1992, p157
H 2C
HX
H
CH 3
CD 3
CD 3
tight ion pair
- since both terminal position could be attacked, only
differentiating factor is nature of counterion
- different acid (X-) therefore should result in different ratios
- HSbCl6 (9:91); H2SO4 (19:81); TFA (25:75); pTSA (35:65)
- all interconversion was determined to be <10%
JACS, 1991, 6271