REACTIONS IN CRYSTALS: DESIGN, DISCOVERY AND UNDERSTANDING
Bruce M. Foxman, Department of Chemistry, Mail Stop 015, Brandeis University, Waltham,
MA 02454-9110, USA Email: foxman1@brandeis.edu
Web: http://www.xray.chem.brandeis.edu
The presentation opens with a brief introduction/tutorial on solid-state reactivity; a few specific
examples and ideas are given to help the audience place the talk in context. When a new solidstate reaction is reported, we may well be impressed with the unusual stereo- and/or chemospecific process before us. Ideally, such a new discovery might represent a preview of a larger
set, an entire new class of reactions. As our quest to discover new solid-state reactions
progresses, this is a most desirable goal. Thus, “discovery” should represent more than the
collection of an “odd gem” from time to time; rather, the discovery should present an opportunity
to both elaborate and develop new general syntheses, and to understand their mechanisms. Our
discovery some time ago, that irradiation of solid bis(trans-2-butenoato)calcium 1 with 60Co γrays leads to only one of four possible diastereomers of the calcium salt
H
CH3
of cis, trans-nepetic acid 2, provides just such an opening. In that study,
CO2M
we proposed a radical mechanism which involved bond rotation in order
to bring a radical intermediate to a position where 5-endo-cyclization
could occur. The presentation will review the structural and mechanistic
aspects of this reaction, and will demonstrate how the process may be
CO2M
modified − using design guidelines for the structure of molecular crystals H H
− to synthesize either an alternative diastereoisomer or different, but
nonetheless mechanistically-related compounds. Important structural
2, M = Ca
modifications that will alter the relative orientation of the butenoates
include: (A) Head-to-head assembly of trans-2-butenoates in a metal complex, with shorter
distances than those observed in 1; this material also undergoes a cyclodimerization reaction, and
provides an excellent, novel one-pot synthesis of a second diastereoisomer of nepetic acid. (B)
Head-to-tail assemblies of trans-2-butenoates in two different metal complexes. In these
compounds, which react by the same mechanism, certain of the C atoms are > 5Å from each
other, and the final step of the mechanism, i.e., ring closure, is precluded. Instead of a
cyclodimerization reaction, a solid-state Michael addition is observed. In order to further
understand these reactions we developed syntheses for the 2-deutero- and 3-deutero-trans-2butenoic acids and the corresponding metal complexes. The results clearly demonstrate
stereospecific hydrogen atom transfer in these intermolecular, γ-ray-induced radical reactions;
no scrambling of hydrogen or deuterium atoms occurs. Further, we also will show that, in the
presence of deuterium-labeled butenoate, the Michael additions are also stereospecific.
[Research supported by the National Science Foundation, Grant DMR-0089257].
BRUCE M. FOXMAN
Department of Chemistry, Mail Stop 015, Brandeis University, Waltham, MA 02454-9110
Telephone: +1-781-736-2532 (voice); +1-781-736-2516 (fax)
email: foxman1@brandeis.edu; web page : http://www.xray.chem.brandeis.edu
EDUCATION
Institution
Major
Degree and Year
Iowa State University
(Senior Research Thesis Advisor :
Professor John G. Verkade)
Chemistry
B. S., 1964
with distinction
Massachusetts Institute of Technology
(Ph. D. Thesis Advisor:
Professor F. Albert Cotton)
Inorganic Chemistry
Ph. D., 1968
The Australian National University
(Postdoctoral Advisor:
Professor Alan M. Sargeson)
Inorganic Chemistry
Research Fellow,
1968-1972
PROFESSIONAL APPOINTMENTS
Research Fellow, The Australian National University, 1968-1972
Assistant Professor, Brandeis University, 1972-1978
Visiting Professor, IBM Thomas J. Watson Research Center, 1975
Associate Professor, Brandeis University, 1978-1985
Professor, Brandeis University, 1985Visiting Professor, Oxford University, 1987
Visiting Professor, Max-Planck-Institut für Polymerforschung, 1995-1996
Honorary Professor, University of Birmingham, 2001
Professeur Invité, Université Louis Pasteur, 2002