Baran Lab Group Meeting Yiyang See 04/25/2015 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) 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…”
Transcript
Baran LabGroup Meeting
Yiyang See04/25/2015The 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 Career1960s - 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 HonorsFellow 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)
Important Professional Appointments1976-88 - ACS Division of Organic Chemistry as a member of the Executive Committee 1980 - Chairman-elect 1981 - Chairman 1983-88 - Councilor 1990 - ACS President
Research Interestmechanisms 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 booksTrained 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 LabGroup Meeting
Yiyang See04/24/2015The Career of Paul G. Gassman
Commentaries:13 in total from 1987 to 1992 - 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)
At the Beginning:the Forster reaction
R
ON
ROH
chloramineR
ON
ROH
NH2
R
ON
R
N
JACS, 1959, p4751Bicyclo [2,1,1 ]hexanes
Me MeMe
α-pinene
NOCl;NatBuO;ozone
Me MeO
NOH chloramine
Me MeO
N285%
Me Me
CO2H
H
light,aq. dioxane
oxidationMe Me
O> 80%
JACS, 1960, p2857
60%
Me Me
X
Y
X = OH, NH2, HY = OH, NH2, H
Types of strained bonds
HHa
bMe
Meab
H H
H H
ba
H
Hor
normal σ symmetrical "twist" bent
Top view
Side view
known & studied unknown in 1967
Chem. Comm. 1967, p793
HH
CN
NC
CNNC
2 days160°C CN
CN
CN
CNCN
HH
CN
CN
HCN
H
H
CNH
CN
80.0% 6.2% 6.7% 0.3% 0.4%
88.7% 2.2% 1.2% 2.1% 3.0%
HHD
D OOO+
HHD
D
OOO
JACS, 1968, p4746
Mechanism of attack of olefins on "bent" σ bonds
N2+
CO2-
+CH2Cl2, reflux
4h H
Ph61% D
D
D
DH
H
JACS, 1968, p5637
The Reactivity of strained "bent" bonds
Energy release for breaking central bond/ Kcal per mol
41 47 32-34
Rate of reaction with rapid rapid no reactionCOOCH3H3COOC
- Nature of reaction mechanism?- Stereochemical requirements?
radicalmechanism
attack fromconcave face
H
Ha
b
CNNC
H
Ha
bH
NC
NC
H
H
Ha
b
NC
NC
H
H
H
H
NC
NC
H
H
a
b
attack from less
hindered face
Acc. Chem. Res. 1971, p128
Ohυ
no filters +
1:18
JOC, 1965, p2262
Baran LabGroup Meeting
Yiyang See04/24/2015The Career of Paul G. Gassman
Preparation of trans-bicyclo[5.1.0]octanes
1. CH2I2, Zn2. Na, xylenes3. Cu(OAc)2, O2
38%
H
H
O
O
1.TsNHNH22. NaOH, cold3. hυ, aq. dioxane
22%
H H
HO2COMe
O
O
OMeH H
HOJACS, 1968, p6895
Preparation of trans-bicyclo[4.1.0]octanes
1. CH2I2, Zn2. LAH3. TsCl,pyr4. LiBr
49%
1.Na2S2. NCS, CCl43. mcpba
28% S
H H
MeO
OMe
JACS, 1983, p667JOC, 1986, p2397
Computational studies: JACS, 1988, p2309
O
O Br
Br
H
H
ClO O
KOtBuH
H18%
- easily isomerized to cis- low oxidation potential (E1/2 1.52V)
H
H
MeMeH
H
MeH
- prepared in similar way- highly acid sensitive- E1/2 1.34V- easily photo-isomerized
The "Twist" Bent BondsDauben:
Me
H
cholestadiene
hυ Me
HEtOH
Me
H
Me
H
OEtOEt
Me
H
cholestadiene
hυ Me
HEtOH Me
H
OEt40%
aluminacolumn Me
H
+
Chem. Comm. 1967, p795
Gassman:
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
Norbornyne
Cl
H
nBuLi (4-5 eq), THF2h, RT; H2O
80%+
n-Bu
H∗∗Hn-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
A B
Proposed Mechanism:
Cl
H
Cl
Li
n-Bu
Li
BuLiBuLi n-Bu
D
D2O
BuLi
Cl
Hn-Bu
-LiCl
Hn-Bu
insertion
Hn-Bu
AJACS, 1975, p4768
Photolactonization
H
MeMe
O
HO
hυ1-cyanonaphthalene/biphenyl, MeCN/H2O
8hO
O
MeMe H
O
O
CH2
Me H
+
42% 5%
- yields ranges froom 36 to 69%- high propensity to form 5-member lactones
H
MeMe
O
HO
-1e
O
OH
MeMe H
HO
O
MeMe H JACS, 1987, p7547
Baran LabGroup Meeting
Yiyang See04/24/2015The Career of Paul G. Gassman
Transition Metal induced rearrangements
Ph
PhMe
Me1. dibromocarbene2. MeLi
Me
PhPh
[Rh(CO)2Cl]2, 2h;chloranil, PhH, 2h
Me
Ph
Ph
PhMe Me
Ph+ +
19% 35% 7%Mechanism:
Me
PhPh
Rh(I)Me
Ph
Rh
Me
Phazulene product
1,2 vinyl shift to give diene product
C-Hinsertion
Me Ph
H
naphthalene product
JACS, 1971, p5897
Synthesis of small [n]paracyclophanes
HH
OOO
O OO
H H
1. H2O2. LTA or electrochem. decarboxylation H
H
1. mcpba2. H+, heat (CH2)n
JOC, 1980, p2923
Cyclobutane Diene Interconversion
CF3
CF3
CF3
CF3
hυ
0.1 eq. PhWCl3.AlCl3
CF3
CF3
CF3
CF3
hυ
0.1 eq. PhWCl3.AlCl3JACS, 1976, p861
Retrocarbene Addition to cyclopropanes
R H PhWCl3.AlCl3 H
R+
1a, R = Et b, R = nBu c, R = i-Pr
PhWCl3.AlCl3
70% JACS, 1976, p6057Cyclopropane-Olefin Cross MetathesisHypothesis: 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
R
HR1
+R1
HR
+
General Scheme:
JACS, 1976, p6058
Catalyst loading: ~1% pf PhWCl3/EtAlCl2
Baran LabGroup Meeting
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The Chemistry of Nitrenium ions
CR1
R2R3
carbonium ions
NR1
R2
nitrenium ions
vs- well studied species in 1962 - virtually unknown in 1962
N
Me MeMe
Cl
MeOH, heat
N
MeMeMe
ClH
N
MeMeMe
MeOH
N
Me MeMe
H+ +
59% 20% 7%- accelerated by Ag+ 77% 8% 4% N
Me MeMe
ClAg
Distinguishing between divalent nitrogen species with a positive charge (nitrenium) vs δ+ nitrogen in TS
R1 NCl
R2
ionization
- Cl-R1 N R2
singlet state
R1 N R2
triplet state
relaxation
carbonium like reactivity radical cation like reactivity
N
Me MeMe
ClN
Me MeMe
N
Me MeMe
N
MeMeMe N
MeMeMe
ClH
N
Me MeMe
H
N
Me MeMe
HHN
Me MeMe
H
spin inversion catalyzed by heavy atom
solvents
Acc. Chem. Res 1970, p262
5-hydroxyl oxindoles
NO
OH
ArSO2Cl, TEA-78°C
NO
O SO2ArAr = 4-Me-Ph 4-NO2-Ph
MeOHN
O
OHNH
O+
MeO
42-54%30-34%Chem Comm. 1971, 1437
Application of Nitrenium ion theory to synthetic problemsπ route to azabicycles
N MeCl
Ag+, MeOH
NMe
MeO HAg+, H2O
NMe
HO H
43% 60%
Ring expansion & contractions
Tet. Lett. 1971, p109
PhN
Cl
Me Ag+, MeOH PhN
Me
N
Ph
Me
NaBH4N
Ph
Me+ 24% RSM
36%
N
Ag+, MeOH
N
BzCl
Cl
Ph PhN
H
Ph H2NO Me
H2NOH
combined 75%
SNAr reactions of anilines
N Cl
RAg+, MeOH N
RR1 R1 NH
RR1
MeO
39 - 77%
N Cl
RAg+, MeOH N R
R1 R1 NR
R1 = EDG62 - 70%Me Me Me
MeO
R1
JACS, 1972, p3884
Ar
NHMe
Cl+Ar
NMe
ClAg+, MeOH
Ar
NMe
ClAg
Ar OMe
O
Ar NHMe
O
> 65% mass balanceChem. Comm. 1969, p495
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Yiyang See04/24/2015The Career of Paul G. Gassman
Welcome to heterocycle land!!
X NH2
Cl+
X NH
ClX N
HS
S
R RR
Rbase
X NH2
R
SR
OH O S
SR
RR
Rbase
OH
R
SR
LG
'Gassman' - type alkylation
X
NH2
X
NH2R
S
R R+
R R
X NR2
R1X = CH or CR1
X
NHS
Me
+
R
R
R1
O
R2
NO
R1
NHS
Me
+
R
R
R1
O
OEt
OH OHR
S
R R+
R R LG
OH OHO
S
S+
R R LG
NH2 NH2O
S
S+
R R
R3
R3
OR1
OHS
Me
+
R
R
O
R1
R2
R2
NO
R1
R O
NO
R1
Cl SMe
NHS
Ph
+
R
R
R1
N OR1
OEtO
products
or air oxidation
Miscellaneous:- Se can be used instead of S (lower yields)
On the chlorination of indoles - Gassman's proposal
NH
R
R N
R
R
NaOCl
Cl
cold
N
R
R
Cl Ag+, MeOHcold
N
R
R
OMe
rapidly to 25°C;rapidly to -10°C
NH
R
R
Cl
NH
R
R
OR1NaOMe or
Tl(OAc)
NR
R
OH
R1 XN
R
R
OR1
NR
RO R1
Tetrahedron, 1972, p2749
Baran LabGroup Meeting
Yiyang See04/24/2015The Career of Paul G. Gassman
The Ionic Diels Alder Reaction
R R10% acid
H
H
R
R
H
H
R
R
H
HR
MeMeMe
HSbCl6TfOHpTSA
64% 17% 13%65% 23% 3%74% 12% 8% JACS, 1984, p6086
R = tBu
Control of regiochemistry - introduction of Lewis basic groups
MeHO
Ph
S
S
MeMe Me
S
S
Me
S
SHO
Me
MeOMe
H
SS
Ph
Me
80%
H
H
SS
Me
Me
56% 31%
SS
Me
H
H
Me
JACS, 1986, p3075
Me OMe
5 steps from glutaraldehyde
2% TfOH, 25°C0.001M, 3min
Me MeMe Me Me
Me+
46% 3%HO
JACS, 1989, p2319
More complex examples:macrocyclization
using allenes
OO diene, Lewis acid OOR 22-65% yields
Tet. Lett.1991, p6473
20-71% yields
[2+2]
O
O +RR
RR
RR
RR O
O
Tet. Lett.1992, p157
Suitable dienophiles
OH
RR
RO ORR1
yields: 56-84%2 mol% TfOH
yields: 70%
RO OROR
yields: 53-83%50 mol% TMSOTf
OEt
OEtOEt
yields: 46-78%50 mol% TMSOTf
For mechanistic studies:JACS, 1990, p8624
An Unsymmetrical 1,1,3,3-Tetramethylallyl Cation
CH2H3C
H CD3
CD3
1 mol% TfOH3min, -78°C
CH2H3C
H CD3
CD3
H3CCH3
HD3C
CD3
+H3C
D3C CD3
CH3CH3
CD3
CD2
H3C
D3C CD3
CD3CD3
CH3
CH2
27:73
CD2D3C
H CH3
CH3
1 mol% TfOD3min, -78°C
CD2D3C
H CH2
CH3
D3CCD3
HH3C
CH3
+D3C
H3C CH3
CH3CH3
CD3
CD2
D3C
H3C CH3
CD3CD3
CH3
CH2
68:32
D D D D
- 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)
Proposed:
CH2H3C
H CD3
CD3
HXCH3H2C
H CD3
CD3
X
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%
