The scientific work of John G. Verkade—A retrospect

GRAPHICAL ABSTRACT

Dr. John G. Verkade

Photo courtesy of Iowa State University

ABSTRACT

Presented is a retrospective view of the scientific work of Dr. John G. Verkade, who served, with distinction, as the Associate Editor for Phosphorus, Sulfur, and Silicon and the Related Elements from 1988 to 2006.

With the passing of John G. Verkade on April 6, 2016, main group element chemistry worldwide has mourned the loss of a very distinguished protagonist who made significant contributions to this branch of science, both as very productive and excellent researcher, and as teacher, for more than a half century. Even at the time of my own start as an active scientist some 30 years ago, his name was already well-known and highly recognized among phosphorus chemists, and in particular the discovery of the “Verkade's superbases” and their applications later enhanced his reputation especially over the last two decades.

John Verkade obtained his basic scientific education at the University of Illinois, where he received his bachelor's degree with high honors in 1956, and at Harvard University where he graduated with an A. M. in 1957. He then returned to the University of Illinois to complete his Ph.D. in 1960 under the supervision of T.S. Piper, a disciple of Sir Geoffrey Wilkinson. In the same year, John joined the faculty at Iowa State University where he was promoted to full professor in 1971 and to university professor in 1997. Iowa State University remained the base of his scientific activities until he sadly passed away earlier this year following a 15 month illness. John Verkade motivated an impressive number of graduate and Ph.D. students and postdoctoral researchers to give their best in doing excellent research, and their joint efforts resulted in an imposing scientific oeuvre comprising more than 360 scientific papers, some 100 meeting abstracts and proceedings papers, and more than 20 patents. He also authored, co-authored, or co-edited five books, and acted as an associate editor for Phosphorus, Sulfur, and Silicon and the Related Elements and as chair of the editorial board of Chemical and Engineering News. Of importance to Phosphorus, Sulfur, and Silicon and the Related Elements were John's 18 years (1988–2006) of outstanding and dedicated service as Associate Editor, working with Editor-in-Chief, Professor Bob Holmes to receive manuscripts, distribute them for review and develop an Editorial Board that reflected the expertise needed in main group chemistry. Being an active member of the American Chemical Society (ACS), John served in a number of committees and was an elected member of the ACS board of directors from 1987 to 1994. His scientific excellence was well recognized by the chemical community and honored by a number of awards including an Alfred P. Sloan Fellowship, the Harry and Carol Mosher ACS Section Award, a BF Goodrich Collegiate Inventors Program Award, Election to the Tilden Technical High School Hall of Fame, Department of Chemistry/Ames National Laboratory Outstanding Mentor Award, Iowa State University Award for Outstanding Achievement in Research, the Midwest ACS Award for Meritorious Contributions to Chemistry, and—in 2010—American Chemical Society Fellow and Fellow of the American Association for the Advancement of Science.

As a researcher, John Verkade showed a great interest in the coordination chemistry of phosphite (and arsenite) ligands in the early years of his career. His Ph.D. supervisor, T. S. Piper, had a reputation for the application of physical—and in particular spectroscopic—techniques to study the structure and electronic nature of coordination compounds, and the ambience of his group offered John a superb opportunity to get acquainted with new physical methods and learn using them for the solution of chemical problems. A long-term project, which began already with his Ph.D. thesis entitled Compounds of Transition Metals with a Phosphite Ester and earned him a name in the scientific community, entailed a series of detailed and comprehensive studies on two bicyclic phosphites, viz. the newly synthesized 4-methyl-2,6,7-trioxa-1-phospha-bicyclo-[2.2.2]-octane and 1-phospha-2,8,9-trioxa-adamantane, and their complexes with transition metal- and boron-based Lewis acids. The incorporation of the phosphite donor moieties into highly rigid bicyclo-[2.2.2]-octane or adamantane cages was considered to minimize conformational changes and rehybridization upon coordination of the Lewis acid, which should in turn facilitate the interpretation of coordination-induced changes in spectroscopic properties and render these compounds ideal objects for elucidating the nature of the metal-ligand bonding in the complexes formed.

One of the main workhorses for conducting these investigations became NMR spectroscopy which emerged around 1960 as a rather new analytical tool for chemists. The method seemed perfectly suitable for the Verkade research since ³¹P chemical shifts and phosphorus-metal coupling constants (where available) provide a local and rather direct probe for the phosphorus metal interactions. These studies were eventually extended to include also nitrogen and sulfur analogues of the cage phosphites and other types of P-donor ligands, and their outcome was published in various papers during the 60s and early 70s and summarized in 1972 in a review entitled Spectroscopic Studies of the Nature of the Metal-Phosphorus Bonding in Coordination Complexes. Some important issues addressed in this work, which remains today John Verkade's most cited paper, are experimental approaches to the determination of ligand basicity, structural trends in ligands and metal complexes, the connection between stereochemistry of complexes and inter-ligand spin coupling, the analysis of the observed trends using theoretical concepts, and—last but not least—some basic considerations on the influence of π-back donation effects on spectroscopic properties. Since phosphites continue to be important ligands in coordination chemistry and catalysis, topics like the evaluation of stereochemistry and the analysis of σ-donor/π-acceptor interactions remain scientific evergreens until today.

The 1970s and 1980s saw a continuation of the earlier structural and spectroscopic studies on phosphite complexes but also a widening of the research interests (as evidenced e. g. by a paper on the application of hydrido nickel phosphites as homogeneous catalysts). The state-of-the art knowledge on the interpretation of trends in phosphorus-metal coupling constants in coordination compounds with P-donor ligands was later summarized in a chapter of a book entitled Phosphorus-31 NMR Spectroscopy in Stereochemical Analysis which was published in 1987 by the co-editors Louis D. Quin and John G. Verkade and soon became a standard work for phosphorus chemists (a second book by the same editors published some 7 years later contained recent updates reporting on the characterization of various classes of phosphorus compounds).

In addition to these activities, the Verkade group began to develop a serious interest in organophosphorus chemistry. The obvious entry point into this field was marked by studies on mono- and bicyclic derivatives featuring a six-membered 1,3,2-dioxaphosphorinane ring which had first been observed as early as 1964 as the products of reactions involving cleavage of one bond in the framework of the familiar cage phosphites (e. g. a Michaelis–Arbuzov reaction of a phospha-trioxa-adamantane). In the wake of the strong interest in conformational and stereochemical analysis of organic compounds in the early 60s, the expertise in physical methods was now also used for a more systematic analysis of the stereochemistry of 1,3,2-oxaphosphorinane derivatives and their chemical implications. Some fundamentally important topics addressed are the ste-reospecific course of Michaelis–Arbuzov or oxidation reactions, and the influence of conformational constraints on the basicity and nucleophilicity of phosphate esters. These studies were soon extended to include biologically or medically active heterocyclic amidophosphates (cyclophosphamide, isophosphamide, triphosphamide) with similar topological structures as 1,3,2-oxaphosphorinanes. An evident interest in establishing possible connections between the conformational preferences and biological activity (which was also studied in collaboration with other researchers) led to a comprehensive investigation of the impact of stereoelectronic influences on basicity and nucleophilicity of monocyclic and bicyclic phosphate esters. Some insular papers dealing with the optical resolution of cyclophosphamide and triphosphamide attest further the first incidences of chirality as a new phenomenon in the Verkade research.

Beginning from the mid-70s, the Verkade group began also exploring new types of polycyclic frameworks. Nitrogen analogues of the familiar phosphites started moving more into the foreground as is evident from coherent studies of the spectroscopic properties of [2,2,2]bicyclooctane frameworks featuring one or two triamido-substituted phosphorus atoms in the bridgehead positions. An important point in retrospection was reached in 1976 with a report on the investigation of a condensation reaction of P(NMe₂)₃ with triethanolamine. The resulting unstable bicyclic phosphite P(OCH₂CH₂)₃N could be trapped by oxidation, complexation, or protonation of the phosphorus atom to give isolable (thio)phosphates, borane complexes, or phosphonium salts, respectively. Crystal structural studies allowed the Verkade group to establish that the individual products showed remarkable differences in their molecular structures. The (thio)phosphates exhibit bicyclic 2,8,9-trioxa-1-phospha-5-azabicyclo[3.3.3]undecane structures with an essentially trigonal planar coordination at the nitrogen atoms, whereas the cation features a tricyclic structure consisting of three five-membered rings that share a common “transannular” phosphorus-nitrogen bond and a penta-coordinate phosphorus atom with a formal valence electron count of ten (10-P-5). In regard of the topological equivalence of the tricyclic structure with that of the isoelectronic silicon compounds and triethanolamine esters of other inorganic acids, which were known as “atranes”, the phosphonium cation was referred to as the first example of a phosphatrane. In order to enable a clear distinction between molecules with and without a transannular bond, molecules featuring the “open” bicyclic structure were later named as “pro-phosphatranes.” Closer investigation of the chemical properties revealed an unusually high phosphorus basicity for the unstable pro-phosphatrane P(OCH₂CH₂)₃N, and the corresponding chalcogenides YP(OCH₂CH₂)₃N (Y = O, S) showed both significant basicity and nucleophilicity in adding one or two electrophiles R⁺ to give mono- and dicationic phosphatranes [RYP(OCH₂CH₂)₃N]⁺ and [R₂YP(OCH₂CH₂)₃N]²⁺, respectively. The origin of this remarkable reactivity was attributed to a stabilizing effect arising from formation of a 3-center-4-electron bond in the axis of the resulting atrane structure.

The discovery of the very special properties of phosphatranes paved the way for a shift in focus of the research interests of the Verkade group which set on at the beginning of the last decade of the 20^th century and eventually entailed results that are to date rated as the probably most important achievements in John Verkade's work. The start of this development may be related to two JACS papers and a conference report in this journal (entitled Novel Properties of New Phosphatranes and Silatranes) from 1989 describing new findings on the triaza-analogues of silatranes and phosphatranes, respectively. These papers already revealed two of the three “curious features” which made, according to John's own words, “these aesthetically attractive species exceedingly interesting to study” (J. G. Verkade, Acc. Chem. Res. 1993, 26, 483; the allusion to aesthetics refers to a comparison of the molecular shape of pro-azaphosphatranes with that of an (American) football, which probably also testifies to John's ability to recognize a snappy selling point), viz. the possibility to induce a continuous variation of the transannular contact from a simple van-der-Waals interaction to a genuine bond by tuning the steric demand of the peripheral substituents, and the fact that the donation of electron density from the bridgehead nitrogen to E may strongly enhance the basicity and nucleophilicity on the E or terminal Y atoms in a molecule Y–E(NRCH₂CH₂)₃N. The third “curious” feature—the possibility to convert one atrane framework into another one by formally replacing the central atom—was somewhat later realized in the development of a transmetalation route that proved synthetically extremely useful to access previously unknown metallatranes. In my opinion, it is one of John Verkade's greatest accomplishments that he managed not only to condense a large body of experimental findings into these concise hypotheses, but was also able to realize the potential of these maxims for generating new chemical reactivity, and finally managed to find suitable applications which allowed him to exploit this potential.

The motivation to study azasilatranes came from the realization that these species might make potentially interesting precursors for silicon nitride ceramics and was the first step to develop a wealth of further metallatranes and aza-metallatranes with previously unknown core elements. These included beside silicon other main group elements such as tin and the group-13 elements boron to gallium as well as early transition metals like the group-4 elements (titanium, zirconium, hafnium), vanadium and molybdenum. An example of a peculiar chemical reactivity beyond the transmetalation reactions is the reported dimerization of two azasilatranes in a dehydrocoupling reaction. Smart optimization of sterically shielding substituents led to the characterization of a monomeric alumatrane containing a coordinatively unsaturated metal atom with trigonal pyramidal coordination. The high Lewis acidity of this species (allegedly exceeding that of BF₃) was demonstrated by the characterization of a complex which exhibits an additional axial aqua ligand and was considered an isolable representative of an intermediate in the hydrolysis of aluminum alkoxides.

While John Verkade's contributions to metallatrane chemistry must be considered excellent science, they have not yet resulted in obvious applications (although he very well realized the potential, as is evident from a patent on the use of metallatranes as CVD precursors and a note on his website which mentions the elaboration of alumatranes into “New Types of Lewis acid catalysts” as a project in development). This is different for pro-azaphosphatranes which the Verkade group turned in the last two decades into highly versatile reagents for applications in organic synthesis and catalysis. The key to this amazing development was the recognition of the unusually high Brønsted and Lewis basicity of pro-azaphosphatranes—their Brønsted basicity by far exceeds that of conventional phosphites and pro-phosphatrane and comes close to that of “Schwesinger” phosphazene bases which are currently considered the strongest neutral bases known. Even if the discovery of this property was serendipitous, it initiated nonetheless a rapid and purposeful exploration of chemical properties of both pro-azaphosphatranes and their chalcogenides and imino derivatives. A breakthrough in 1999 was finding that pro-azaphosphatranes cannot only be employed as strong non-ionic bases in stoichiometric reactions, but may also act as nucleophilic organocatalysts which can promote a reaction even if only a sub-stoichiometric quantity of the reagent is present. The discovery of the first reaction of this type—a pro-azaphosphatrane-catalyzed variant of the addition of nitroalkanes to carbonyl compounds (Henry reaction)—stimulated an intensive research for further applications, and a review dating from only four years later contains a list of more than 30 synthetically useful transformations which benefit from the use of pro-azaphosphatranes as stoichiometric reagent, nucleophilic organocatalyst, or ligand for the stabilization of catalytically active metal centers, respectively. The relevance and potential of these reactions for organic synthesis is illustrated by the facts that several of them were patented, and that pro-azaphosphatranes were soon commercialized and, being promoted under the name of “Verkade's superbases”, are until to date available in the catalogues of leading fine chemicals manufacturers. Although the pace slowed down somewhat after 2005, the Verkade group continued to develop their pro-azaphosphatrane chemistry and to publish results with interesting prospects for applications like the synthesis of the first chiral azaphosphatranes, or the preparation of heterogeneous catalysts based on immobilized azaphosphatranes.

Right from the start, John Verkade's research approach disclosed not only a strong motivation to improve the conceptual understanding of the structures and electronic nature of main-group element compounds and their complexes (which may in today's terminology be labeled as an inclination to fundamental or pure research), but he took also vital interest in the development of new applications that put his experience or findings into practical use. The persevering elaboration of pro-azaphosphatrane chemistry, which widened the scope of the Verkade research to incorporate aspects of organic chemistry and catalysis, offers possibly the most spectacular (at least for academic chemists) illustration of this inclination. Other projects linked his activities to analytical chemistry and chemical engineering. One of these undertakings was based on the exploitation of the long standing experience of the Verkade group in the NMR characterization of phosphorus compounds and resulted in the development of analytical methods for the characterization of hydroxylic and phenolic functionalities in coal extracts, condensates, and liquefaction products after appropriate derivatization with suitable phosphorus reagents. A further line of interest aiming at the improvement of the quality of fuels and energy carrier materials started in the 1990s with efforts to utilize phosphines and phosphites for the desulfurization of coal, and culminated in more recent activities aiming at an enhancement of methods for the conversion of animal fat and vegetable oils into biodiesel. Apart from their potential practical benefits, these activities highlight that John Verkade's scientific curiosity crossed the borders between chemical sub-disciplines and gave his scientific approach a true interdisciplinary touch.

A reflection on John Verkade's scientific work would remain incomplete without mentioning at least shortly his contributions to the advancement of teaching chemistry and the development of the community of phosphorus chemists. The pedagogical concepts are laid down in several articles in the Journal of Chemical Education and two books focusing on a pictorial approach to explain molecular orbital concepts and their use to describe structure and bonding in molecules, polymers, and even solids. The relation to John Verkade's own research activities is immediately clear if one recollects that comprehending the connections between structure, electronic nature, and chemical reactivity—which formed a principal guideline for much of his work—needs a sound conceptual and theoretical background. Nonetheless, John's foresight is admirable if one realizes that even today—where computers and quantum chemical software are readily available even for students—a concise yet nonmathematical approach to rationalize the bonding in a large variety of molecules makes an eminently powerful and generally applicable tool for teaching descriptive chemistry at all levels.

It is beyond doubt that John Verkade's published scientific work is of outstanding merit and value to main group chemistry, both because of its impact on the development of this chemical discipline in the past half century, and its potential to provide present and future readers with the inspiration and practical tools to develop further exciting research. Considering that a notable number of his former students or postdocs (including myself) are still active in academic research, I am confident that also his personality and his personal approach to do science—of which I myself remember above all his readiness to look beyond his own nose and meet new challenges, his clarity of thought which enabled him to put even complicated issues in a nutshell, and his distinct dedication to get to the bottom of a problem—will be remembered and passed as example to future generations of students and scientists.