Chemical Synthesis: Gnosis to Prognosis

619 Pages·1996·28.705 MB·English

by  H. B. Kagan (auth.), Chryssostomos Chatgilialoglu, Victor Snieckus (eds.)

Chemical Synthesis
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Series E: Applied Sciences· Vol. 320
Chemical Synthesis
Gnosis to Prognosis
edited by
Chryssostomos Chatgilialoglu
Consiglio Nazionale delle Ricerche,
I.Co.C.E.A.,
Bologna, Italy
and
Victor Snieckus
Department of Chemistry,
University of Waterloo,
Waterloo, Ontario, Canada
Kluwer Academic Publishers
Dordrecht / Boston / London
Published in cooperation with NATO Scientific Affairs Division
Proceedings of the NATO Advanced Study Institute on
Chemical Synthesis: Gnosis to Prognosis
Ravello, Italy
May 8-19,1994
A C.I.P. Catalogue record for this book is available from the Library of Congress.
ISBN-13: 978-94-0lO-6598-6 e-ISBN-13: 978-94-009-0255-8
DOl: lO.lO07/978-94-009-0255-8
Published by Kluwer Academic Publishers,
P.O. Box 17,3300 AA Dordrecht, The Netherlands.
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Softcover reprint of the hardcover 1st edition 1996
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Table of Contents
Preface ................................................ vii
Dedication ................................................ xi
Asymmetric Synthesis: I -Fundamentals and Recent Advances. II -Some Aspects
of Asymmetric Catalysis with Transition-Metal Complexes ................................. 1
H. B. Kagan
Addition of Enolates and Metalloalkyls to Imines. Stereospecific Synthesis of
f3-Lactams, Amines, Aziridines and Aminols ................................................ 25
G. Cainelli, M. Panunzio, D. Giacomini, G. Martelli, G. Spunta and
E. Bandini
Target-Driven Organic Synthesis: Reflections on the Past, Prospects for the Future ... 61
S. Hanessian
Optically Active Transition Metal Compounds Containing Chiral Transition Metal
Atoms ............................................................................................ 91
H. Brunner
Biomimetic Chemistry. Bifunctional Binding and Catalysis ............................ 113
R. Breslow
Design of Enzyme Inhibitors. Answering Biological Questions Through Organic
Synthesis ..................................................................................... 137
P. A. Bartlett
Enantioselective Catalysis with Transition Metal Complexes ........................ 175
H. Brunner
Directed Aromatic Metalation: A Continuing Education in Aatland Chemistry ........ 191
V. Snieckus
Panel Discussion 1. As We Head Into the 21st Century, is There Still Value in
Total Synthesis of Natural Products as a Research Endeavor? ........................ 223
C. H. Heathcock
Convergent Strategies For Synthetic Receptors ......................................... 245
P. Timmerman, W. Verboom and D. N. Reinhoudt
The Advancement of Radical-Based Synthetic Strategies: From Reagent Design
to Pol ymer Modification .................................................................... 263
C. Chatgilialoglu
Templated Synthesis of Enzyme Mimics: How Far Can We Go? ................... 277
S. Anderson and J. K. M. Sanders
Towards a Chemical Etiology of the Natural Nucleic Acids' Structure ............. 293
A. Eschenmoser
vi
Principles of Antibody Catalysis ......................................................... 341
D. Hilvert
New Homocalixarenes and Catenanes: From Molecular Recognition to
Mechanical Bonds .......................................................................... 361
S. Meier, S. Ottens-Hildebrandt, G. Brodesser and F. Vogtle
Self-Assembly in Chemical Synthesis .................................................... 381
S. 1. Langford and J. F. Stoddart
Oligonucleotide-Directed Recognition of Double-Helical DNA ....................... .403
C. HelEme and T. Garestier
Can Enzyme Mimics Compete With Catalytic Antibodies? .............................. 419
C. 1. Walter, L. G. Mackay and J. K. M. Sanders
Panel Discussion II. Synthesis of Giant Modular Structures: Supramolecular
Assemblies and Well-Defined Macro-molecules ........................................ .429
J. Michl
Polymer Synthesis and Stereochemistry with Transition Metal Catalysts ............ .453
R. Waymouth, G. W. Coates, F. Ciardelli, C. Carlini and A. Altomare
Making Unnatural Products by Natural Means ......................................... 475
S. J. Langford and J. F. Stoddart
Supramolecular Chemistry and Chemical Synthesis. From Molecular Interactions
to Self-Assembly ............................................................................. 511
J-M. Lehn
Synthetic Approaches to Functional Polymers ......................................... 525
F. Ciardelli, M. Aglietto, o. Pieroni, G. Ruggeri, R. Waymouth,
M. Kesti and K. Stein
Transduction of Molecular Interactions into Macroscopic Properties ................... 549
H. C. Visser, R. J. W. Lugtenberg, J. F. J. Engbersen and D. N. Reinhoudt
Approaches to Synthesis Based on Non-Covalent Bonds .............................. 565
G. M. Whitesides, E. E. Simanek, and C. B. Gorman
The Functionalization of Saturated Hydrocarbons by Gif Chemistry. Part 1. Use
of Superoxide and of Hydrogen Peroxide. Part. 2. Use of t-Butylhydroperoxide ... 589
D. H. R. Barton
Panel Discussion III. Organic Synthesis and the Life Sciences ...................... 601
D. Arigoni
INDEX ......................................................................................... 621
PREFACE
Chemical Synthesis: Gnosis to Prognosis
(XTUllKtl ~uv8eoTr ana TT) rVWOT) OTT) npaYVWOT))
" .... other things being equal, that field has the most merit which contributes most
heavily to, and illuminates most brightly, its neighbouring scientific disciplines[l]
One hundred scientists, a blend of students, industrialists, and academics from
twenty countries gathered to circumscribe, understand, and elaborate this topic in the
magical setting of Ravello, Italy. The mandate of this workshop? To survey existing
knowledge, assess current work, and discuss the future directions of chemical synthesis
as it impinges on three exciting interdisciplinary themes of science in the 1990's: bioactive
molecules, man-made chemical materials, and molecular recognition. This tempting but
inexact menu summoned diverse students and scientists who wished to seriously reflect
upon, dissect, and eject ideas and own experiences into open debate on this topic, which
is at a crossroad in internal evolution and impact on the life and material sciences.
The group arrived from many directions and in various forms of transportation,
matters soon forgotten, when it found itself in the village which nurtured Wagner's
inspiration and set to work immediately to ponder the question which has received
extensive thought, prediction, and caveat from illustrious chemists over a period of time
[2], two of which, to the delight of all, in presence among the Lectures.
During the intense ten days of activities, the three themes were addressed in a
deliberate potpourri fashion which, from the outset, provided the desired response:
enthusiastic, unbridled, and open-ended questions and discussion. It continued outside
of the Chapel, at breakfast, over lunch and dinner, and was buoyantly evident in the
garden coffee breaks hosted by the congenial staff and management.
Lectures on chemical synthesis at its fundamental levels, indicative of the vibrant
health of the science, ranged from specific modern methods (Barton, Cainelli, Snieckus),
to asymmetric catalysis (Brunner, Kagan), to target-oriented strategies (Hanessian). The
disappearing biology-organic synthesis boundaries were clearly evident from
contemplation of biomimetic catalysis (Breslow), design of enzyme mimics (Sanders) and
inhibitors (Bartlett), catalytic antibodies (Hilvert), and a tour de force "why" topic
(Eschenmoser). Molecular recognition and function delivered a range of stimulating
salvos on receptors, self-assembly and -organizaton, and sequence-specific modification
of nucleic acids (Htm~ne, Reinhoudt, Stoddart, Vogtle). The material science theme saw
the interdisciplinary bridges shrink further with presentations par excellence on
macroscopic non-covalent bond interactions (Lehn, Whitesides) and molecular electronic
devices (Wrighton[3]). The sophisticated synthetic chemistry ongoing in the polymer
arena was masterfully illuminated from perspectives of radical (Chatgilialoglu) and
transition metal catalyzed (Ciardelli and Waymouth) reaction perspectives.
vii
viii
Three Panel Moderators posed provocative questions concerning the value of total
synthesis in the 21st Century (Heathcock), the relationship between synthesis and the life
sciences (Arigoni), and the construction of giant molecular modules (Michl). These
sessions, unharassed by time limitations and suit-and-tie formality (and once assisted by
rain), became playing fields for delving deeper into the three themes but never losing sight
of prognosis. As hopefully evident from the taped transcripts, the multilogue ranged
from serious to mirthful, all resolved to place quality substance in front of the audience
and the readers of the workshop proceedings.
For this event, we warmly thank the Lecturers, the Panel Coordinators and
Members, the Discussion Leaders, and, most of all, the participants. The Lecturers
covered a broad range of subjects in excellent fashion, with careful attention to the diverse
experience of the audience, including students. They orchestrated their talks with a view
to establish interconnecting links among speakers in related areas, overcoming internal
chemtalk barriers. The Discussion Leaders set the atmosphere by initiating and
encouraging relaxed inquiry. The Panel Coordinators took full control of their difficult
tasks, prepared an agenda, and catalyzed broad-ranging response; the Panel Members
provided food for thought and unhesitently went into unknown territories for the same
end result. Finally, all participants, by their questions, interaction, suggestions, and
overall attentiveness made the our tasks easy and happy ones.
In summary, the Ravello NATO ASI was a very special workshop which we
remember as an intense but collegial scientific discussion, a forum for interaction among
individuals from broadly different cultures and languages, and the reinforcement or
initiation of cameraderie which continues. We hope that this volume reflects all of these
aspects, provides current status reports in diversified fields, and, most significantly, acts
as a benchmark for the discipline of organic synthesis as it surveys and reaches towards
its central contributions in the 21st Century.
Behind (usually in front) of all named conference organizers are the truly responsible
individuals. From this viewpoint, we wish to thank most warmly Carla Ferreri and Barb
Weber who, although distanced geographically, brought it to fruition. Another assumed
task, the operation of projection, was carried out with great attention to detail by Massimo
Capobianco, Thanasis Gimisis and Marco Lucarini. The Organizing Committee (H.J.
Bestmann, A. Eschenmoser, C.H. Heathcock, and J-M. Lehn) not only reinforced our
plans for this unusual program but also vigorously partook in discussion and panel
deliberation. Our special thanks are due to NATO, Ente Provinciale del Turismo di
Salerno and Area della Ricerca di Bologna (CNR) who kindly provided the financial
support.
Chryssostomos Chatgilialoglu Victor Snieckus
IX
1, Weinberg, A.M. Minerva 1963,2, 159.
2 Inter alia, "Synthesis must always be carried out by plan, and the synthetic frontier can
be defined only in terms of the degree to which realistic planning is possible, utilizing all
of the intellectual and physical tools available." [Woodward, R.B. In Perspectives in
Organic Chemistry; Todd, A.R., Ed.; Interscience: New York, 1956]. "What the
synthetic target provides is stimulation and direction. Challenged by the necessity of
moving towards a given structure, the synthesis often leads to problems that are
complementary to those chosen in open-ended preparative research on reactivity."
[Eschenmoser, A.; Wintner, C.E. Science (Washington, D.C.) 1977, 196, 1410]. We
have travelled far since 1828 and the interest attached to 'total synthesis' has
disappeared." [Robinson, R. 1. Chem. Soc. 1936, 1079]; "This statement was not
really true in 1936. It will still not be true in a hundred years." G. Stork, Prix Roussel
Lecture, 8 juin, 1978. "The best industrial synthesis may attain average yields of over
90% for a 30-40 step synthesis. It is clear, therefore, that the synthesis of natural
products remains an objective of great scientific value and of great social and economic
significance." [Barton, D.R.H. Pure Appl. Chem. 1977,49, 1241]. " ... it will still be
the chemists skilled in synthesis who will succeed in preparing the most interesting targets
and exploring the most challenging themes ... " [Seebach, D. Angew. Chem. Int. Ed.
Eng/. 1990, 29, 1320].
3. Wrighton, M. article not published.
DEDICATION
Dear Professor Prelog,
We were overjoyed to read your concurrence to be our Honorary Chairman but then
downcast when we received your hesitant second letter. As the opening day approached,
we realized and then accepted that we would not delight in the benefit of your broad
knowledge, deep insight, and personal warmth and humor in a workshop at which all of
these characteristics would have found expression.
". .. we believed that it was not worthwhile to compete ... , but rather, given
sufficient trust, that we should communicate our results to each other. Unnecessary
duplication, priority arguments, and disappointments are thus avoided, and one also
learns much from one's partners. [1]
II
Although to quote you this briefly is to do injustice, to quote is to convey to you and
to the readers that the spirit of these words, in context of interaction and discussion,
prevailed at Ravello. That spirit, we hope, is also transmitted in the essays and panel
discussions of this volume where you will find themes which reflect your multifaceted
achievements and interests in organic chemistry.
We did miss you. Because through your insight, the self-assembly vs self
recognition definition argument would have been clarified; through your wisdom, the
uncertain impact of combinatorial chemistry would have received prognosis; through your
humor, the repartee on the term "chemzymes" would have, we are confident, taken
another twist.
We know you are well because we saw you at Linde Oberstrass near the ETH
recently. And so we offer this volume, dear colleague, with the sincere wish that you
will, without multimedia distraction, delight in the ongoing changes in organic synthesis
for whose foundations you have been a major architect.
u,/j
cy,l
V~d",,~~L
L,--
Chryssostomos Chatgilialoglu Victor Snieckus
1. Prelog, V. My 132 Semesters of Chemistry Studies; Seeman, J.J., Ed.; American
Chemical Society: Washington, D.C., 1991; P 37.
xi