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hard way. In my case they certainly were.
These lessons also of course could not be learned without
dedicated teachers that one encounters along the way.
My High School Chemistry teacher, Mr. Schwartz, was actually a
biologist filling in because of a retirement.
Although he did not know a lot of chemistry, he was dedicated to
helping students learn. He
once picked me up at 4:00 AM and drove me across the state for a High
School Chemistry fair. I
had prepared a talk on an experiment that I had repeated from a
Chemistry book. I was
embarrassed to find that everyone else’s talk involved original
experiments. The lesson
learned from this is that science is about doing something new.
 The next important lesson came as an
undergraduate at the University of Wisconsin at Eau Claire.
As a freshman, I was recruited to do research with Dr. Larry
Schnack. He was interested
in the cyclopropyl carbinyl cation problem having received his Ph. D.
with Charles DePuy. We
planned a detailed Hammet study of a number of substituted cyclopropyl
carbinyl tosylates, which took me the next three years to do.
In my second year Dr. Schnack moved into administration but I
continued the project. He
was too eventually become Chancellor of the University, a position he
served with great distinction for almost two decades.
In my four years as an undergraduate I made a lot of compounds
and measured a lot of rate constants.
In my senior year we assembled all the data for publication when
much to my horror we discovered that Ken Wiberg at Yale published the
same study with the same compounds.
The only consultation was that our rate constants matched his.
There was no point to publish our work.
The lesson learned here is that having a good idea is not enough,
you have to do it and do it before anybody else
does.
Having batted zero for my professional career
up to this point, I was ready for graduate school.
However, the United States Military had other plans for me at this time.
Due to an unfortunately low draw in the lottery, I was forced into
military service and served in the US Army for three years at Fort Meade
Maryland. I work in a reference medical laboratory that serviced all
branches of the armed services on the east coast. We did tests ranging
from simple cholesterol and triglycerides to toxicological studies of
drug overdoses. The latter was important because if an active
military personnel died of a drug overdose, then the family would be
denied all benefits. The most important event to occur during this time
was the meeting of the woman who was to become my wife. Mary and I met
on a blind date arranged by someone we knew who worked with me on a
moon-lighting job at a local hospital. Mary's support of my goals in
academia is the biggest factor responsible for the success I have had in
my professional career.
I
thought it was exceedingly kind of the Department of Chemistry at Iowa
State University to hold open my graduate position until I finished
my military service. In July of 1974, I enrolled at Iowa State University and was fortunate enough to
work for Professor Thomas Barton who was a truly inspirational scientist
and personality. His wit
was faster than a speeding bullet and he had endless capacity to produce
great ideas. He liked risky
projects and was a master at mechanistic deduction.
I tackled a flurry of high-risk ideas in my first three and a
half years in graduate school but nothing worked.
Everything in my thesis comes from the last seven months in the
lab. Nonetheless, since we had several projects that all worked at
once, we ended up with eight publications together on the study of
organosilicon reactive intermediates including silanones, silylenes,
silenes and disilenes. This
was an incredibly intense seven months during which I did not sleep more
that five hours a night. I
finally found out what doing good science was.
It was an exhilarating and joyful period.
I will always be indebted to Thomas Barton for showing me how to
do science right. It is a
debt that I can never repay, but showing new graduate students the joy
of chemical research is at least a small effort in this regard not to
mention a lot of
fun.
Although not a synthetic chemist, Professor Barton
is at least partly responsible for my career in synthetic chemistry.
He did not like synthetic chemistry and forbade anyone in his lab
from pursuing any leads that would have any possible applications in
synthetic organic chemistry. Synthetic
chemistry was thus the forbidden fruit of which I was not allowed to
partake and it had for me the allure of the unknown.
My decision to pursue a career in synthetic organic chemistry was
cemented upon taking an organometallic course with Professor Robert
Angelici and when Peter Vollhardt’s synthesis of estrone with
organocobalt chemistry was published in the Journal of the American
Chemical Society in 1979. Professor
Angelici’s course was so well done and properly suited for those who
were not inorganic majors that everyone in the course came away with a
real and profound sense that they could do organometallic chemistry.
Professor Vollhardt’s one-pot synthesis of estrone was a great
inspiration to many a young chemist at the time since it seemed to
crystallize a sense of what the power of the burgeoning new field of
organometallics in organic synthesis could do.
The field of organometallics in organic
synthesis was just taking off when I was finishing grad school I was
fortunate enough to land a postdoctoral position with one of the
pioneers of the field, Martin Semmelhack at Princeton.
He had spent a decade or so exploring the scope and applications
to organic synthesis of nucleophilic additions to arene chromium
tricarbonyl complexes. His charge to me was to explore the same reactions of
naphthalene chromium tricarbonyl complexes and apply this to a total
synthesis. A number of
these compounds were known, but their preparation usually gave mixtures
of regioisomers with unsymmetrical naphthalenes having two benzene rings
of different substitution patterns.
In preparation for writing my thesis, I decided that I needed to
read the entire Journal of Organometallic Chemistry since at the time
all the most important organosilicon papers were to be found in that
Journal, along with JACS. Much
to my amazement, I came across a paper describing the selective
formation of a naphthalene chromium tricarbonyl complex from the
reaction of an aryl chromium carbene complex with an acetylene.
This reaction comprised the key step of a total synthesis
deoxyfrenolicin that I proposed in an NIH postdoctoral fellowship
application which was funded. It
was also pleasing to see the total synthesis appear in the literature
two years after I finished my postdoctoral stay which was due to the
talented efforts of four colleaques in the Semmelhack group.
In the Fall of 1980 I accepted my first
academic position as Assistant Professor at the University of Chicago. I will never forget the first time I sat in my own lab
and put my feet up on the desk. The
thought still gives me goose-bumps.
All of the projects that we started at Chicago involved the
reactions of Fischer carbene complexes and their applications in organic
synthesis. My mentor,
Martin Semmelhack, was kind enough to allow me to pursue this area on my
own since I had brought the idea to his group.
This gesture was greatly appreciated and vital to establishing my
own career. This was an area that was ripe since a large number of
reactions of Fischer carbene complexes with potential in organic
synthesis had been discovered by inorganic chemists but synthetic
organic chemists had not yet began working in the area.
My only competition when I started was Karl Heinz Dötz in
Munich who had discovered the benzannulation reaction with alkynes.
In the US, Charles Casey at Wisconsin had done some early work
put had stopped just before I began.
It was a great opportunity for us and it kept us so busy that we
had no time to pursue any other ideas.
To get a sense of how rapidly this area was to grow from that
point on one can look at a textbook of the time.
The first edition of “Principles and Applications of
Organotransition Metal Chemistry” by Collman and Hegedus was published
in 1980 and it tersely concludes that Fischer carbene complexes “are
of little use in organic synthesis”. The second edition appeared in 1986 and had an entire chapter
devoted to the subject. We
have continued to work in the area and there are now dozens of groups
around the world that have made contributions to the field. Thirty-nine years after their discovery, Fischer carbene
complexes are clearly one of the most important organometallic reagents
in synthetic organic chemistry. We
have just recently completed a comprehensive review on the reaction of
Fischer carbene complexes with alkynes.
For just this reaction alone, all of the known examples were
assembled to give a Table that is over 600 pages
long.
Just as actors often get typecast into certain
roles, chemists can become pigeonholed into defined fields and even
sub-fields. In the early
nineties we began to work in an area of catalytic asymmetric synthesis,
an area that was completely new for us.
With no track record in the area, we found that people were
reluctant to open doors for us. We have been pummeled mercilously by reviewers for the last
six years trying to get this work funded.
We thus realized that we would have to get this program off the
ground by subversive means, using funds from other grants as seed money.
This can only be done for so long since in the long run it can
jeopardize existing programs. We had pushed this about as far as we could at the University
of Chicago and probably would not have been able to continue this
program if we had not moved to Michigan State University.
The move here provided the funds necessary to move this program
forward to the point where just recently we have obtained independent
funding from the NIH to continue this program.
It wasn’t until we had solved a problem that no one else could
solve that we were accepted into the catalytic asymmetric community. While many methods have been developed over the years
for the catalytic asymmetric synthesis of epoxides, related methods for
the preparation of aziridines provided more elusive.
In the last 2-3 years we have developed the first general
catalytic asymmetric synthesis of aziridines and now are beginning to be
accepted as an established group in the field of catalytic asymmetric
synthesis. In the future we will examine catalyst designs for other
important reactions in organic synthesis.
The research group is now at eighteen members
and is flourishing here at Michigan State University in both the areas
of Fischer carbene complexes in organic synthesis and in catalytic
asymmetric synthesis. My
family and I enjoy living in the East Lansing area and are glad that we
made the move. I like to
take advantage of the summer and play tennis (when it’s not raining)
and in the winters I like to drink wine (when it’s not raining).
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