Heteroatom Chemistry Volume 6, Number 4, 1995

n

Tribute to Professor Shigeru Oae

This issue of HETEROATOM CHEMISTRY is dedicated to Shigeru Oae on the occasion of his seventy-fifth birthday. This is particularly appro- priate, not only because of his eminence as a re- search worker in the field of main group chemis- try, but also because he has been the Far East Editor of HETEROATOM CHEMISTRY since its inception five years ago. Many of the outstanding articles that have appeared in this Journal arrived through Pro- fessor Oae's influence, and, indeed, many of the outstanding articles were written by him and his colleagues.

Sig, as he is known to his many friends, was born in Okayama, Japan, on January 18, 1920. Af- ter the usual early period of education, he received the B.Sc. degree in 1943 with a major in chemistry from Waseda University, and he was the valedic-

torian of his graduating class. After two years of industrial research at Hodogaya Chemical Works in Yokohama, and military service, he entered the Institute for Scientific and Industrial Research at Osaka University, and he was awarded the D.Sc. degree and was appointed to the position of As- sociate Professor in 1955. In the meantime, he had broken with the feudalistic tradition of the old Ja- pan by moving to the United States in 1950, work- ing as a research associate with Professor Calvin A. VanderWerf at the University of Kansas in Law- rence, Kansas, for a two-year period. (I was an As- sistant Professor at KU at that time, and I first be- came acquainted with Sig there.) He returned to Osaka University for the period 1953-1955, and then returned to the United States to work with Profes- sor Charles C. Price at the University of Pennsyl-

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viii McEwen

vania in Philadelphia for two years. Then he moved to the Drexel Institute of Technology (now Drexel University) as a faculty member in the Depart- ment of Chemistry. He next worked as a Visiting Chemist at Brookhaven National Laboratory in Upton, Long Island, New York, where he was as- sociated with Dr. Alfred P. Wolf‘s group from 1958- 1960 before he accepted the appointment as Chair- man of the Chemistry Department at the Radia- tion Center of Osaka Prefecture for the period 1960- 1962. In 1962, he moved to Osaka City University as Professor of Organic Chemistry and remained there until the University of Tsukuba asked him to become the Chairman of the Department of Chem- istry in 1973. He also served as Dean of the Uni- versity for a period of two years, before he “re- tired” in 1983 at the age of 63.

Professor Oae was given the Asahi Science Re- search Award in 1969 and the Japan Chemical So- ciety Award in 1972 for his achievements in the field of Organic Sulfur Chemistry. He was also the recipient of the Toray Science Research Award in 1980. During this period of his life, he was invited to 22 foreign countries and more than 100 univer- sities and colleges, including many in Japan, to de- liver various lectures.

A t the time of his retirement from the Univer- sity of Tsukuba, Professor J. C. Martin (then at the University of Illinois) wrote: “It is difficult for me to adjust to the idea that Sig has really reached an age which could justify his retirement. ‘Retire- ment’ can of course have many different meanings and I am sure that in Sig’s case it will be multi- dimensional in a way calculated to take maximum advantage of the new degrees of freedom which it affords.” This has certainly turned out to be true. Sig soon resumed his scientific activity by means of an arrangement with the Okayama University of Science, by establishing the Institute of Hetero- atom Chemistry in Osaka, by becoming the found- ing editor of REVIEWS ON HETEROATOM CHEMISTRY with the aid of Professors Atsuyoshi Ohno and Naomichi Furukawa as associate edi- tors, by organizing ICHAC (The International Con- ference on Heteroatom Chemistry that will be holding its fourth meeting in Seoul, Korea, July 30- August 4, 1995), by becoming the Far East Editor of HETEROATOM CHEMISTRY, by carrying out cooperative research work with many Japanese chemists, and by visiting many laboratories throughout the world to give lectures on “Ligand Coupling Reactions within Hypervalent Species,” and, at the same time, to function as an ambas- sador to chemists worldwide.

A s with all famous research chemists, Sig will be remembered by future generations for his con-

tributions to chemistry. These have included his studies on the following:

(1) Acid-Enhancing Effect of Dicoordinate Sulfur Groups A series of studies of the acid-enhancing effect of a-alkylthia or a-arenethia groups on adjacent methylene group protons were reported for the first time in 1960 on the basis of quantitative kinetic evidence. In subsequent years, the effect was shown to be multiplied in a logarithmic manner by fur- ther substitution of a second or third alkylthia or arylthia group at the a-carbon, and the effect was found to be insensit ve to the steric bulk of the at- tached carbon g roux in accord with the concept of 3d-orbital resonance effects. This carbon acid- enhancing effect of an a-thia group led to appli- cations by many chemists, e.g., in the synthetic uses of 1,3-dithiane-2-1ithio derivatives and to the ra- tionalization of the >markedly high catalytic reac- tivity of Co-enzyme A. Similarly, the a-thia group was shown to stabilize free radicals, apparently by an electron-sharing conjugative resonance effect.

(2) Chemistry of Chiral Tricoordinate Organic Sulfur Compounds In 1957, Professor Oae initiated a research pro- gram to study the nature of tricoordinate organic sulfur compounds of general formula

. .

where X = 0, N or C

The chiral nature of the compounds was exten- sively exploited in mechanistic studies of isotopic oxygen exchange of sulfoxides, in substitution and rearrangement reactions of sulfoxides and sulfili- mines, and in thermal racemization of these and related compounds. Convenient methods to incor- porate ’‘0 into sulfoxides were utilized to open the way to study the stereochemistry of nucleophilic substitution at tricoordinate sulfur in sulfoxides. Sulfoxides were found to undergo oxygen ex- change in sulfuric, phosphoric, and carboxylic acids, in N2O4, in carboxylic acid anhydrides, with alkali metal alkoxides, and with sulfoxides themselves. Especially interesting was the demonstration that optically active methyl phenyl sulfoxide under- went the oxygen exchange reaction with retention of configuration. This was the first demonstration of an SN2 reaction on tricoordinate sulfur occur- ring with retention of configuration.

A Tribute to Professor Shigeru Oae ix

As an extension of the work with tricoordinate sulfur compounds, the chemistry of several seleno analogs has been explored. Among other findings, the first example of an optically active selenonium ylide was prepared.

(3) Ligand Coupling within a Hypervalent Intermediate In 1984, S. Oae, T. Kawai, and N. Furukawa re- ported that the reaction of optically active a-phen- ylethyl a-pyridyl sulfoxide occurred with an alkyl or aryl Grignard reagent to give, in quantitative yield, optically active 2-( 1 -phenylethyl)-pyridine with 100% retention of the configuration of the chiral carbon atom. This has led, extending up to the present time, to numerous additional studies of ligand coupling reactions within hypervalent in- termediates. It is probable that such reactions have been observed with compounds of more than two dozen different hetero atoms. In all of these cases, attack of a nucleophilic reagent at the central het- ero atom occurs to give a hypervalent intermedi- ate that subsequently undergoes intramolecular coupling of an electron-withdrawing ligand lo- cated at an apical position with an electron-do- nating or 7~ ligand located at an equatorial posi- tion, these ligands having attained the necessary geometrical sites by prior pseudorotation, as re- quired. In such reactions, ligand exchange is usu- ally a competing reaction with ligand coupling from within the hypervalent intermediate. For ex- ample, in 1992, Uenishi, Yamamoto, Takeda, Wa- kabayashi, and Oae reported in HETEROATOM CHEMISTRY that the reactions of (+)-(1R)-phen- ylethyl 2-quinolyl (R)-sulfoxide and (-)-( 1 R)-phen- ylethyl 2-quinolyl (S)-sulfoxide with methylmag- nesium bromide gave (R)-2-( 1 -phenylethyl)quinoline as a ligand coupling product and a mixture of methyl (1R)phenylethyl (R)- and (S)-sulfoxides as ligand exchange products. Both the ligand cou- pling and ligand exchange reactions had occurred with retention of configuration at the chiral car- bon. This result is consistent with the general mechanism described above. Much additional work will undoubtedly be forthcoming during future years to determine the scope and boundaries of these fascinating reactions. Many chemists in ad- dition to Professor Oae and his colleagues are working in this area.

(4) The Pumrnevev Reaction Treatment of a sulfoxide bearing an a-hydrogen with acetic anhydride produces an a-acetoxy sul- fide, which, in turn, can readily be hydrolyzed to an aldehyde plus a thiol. The mechanism of the

rearrangement step was studied by Itoh, Numata, Yoshimura, and Oae in the early 1980s by use of D and ’‘0 tracers and optically active or geomet- rically isomeric sulfoxides, kinetics studies also being of paramount importance. The following four- step mechanism was proposed for the rearrange- ment:

step 1 + step 2. -H’ + - R - S- CH? - X + ( R CO) 20 W R- S- CHz - X R COO- = R- S- CH - X +

0 0-C-R 0-C-R b 8

sieo 3 step d -R-S=CH-X-R -S-m-Y

-0- C- R’ 6

0-C-R’ a It was demonstrated that the 1,2-acyloxy shift pro- ceeds in an intramolecular manner, with forma- tion of an intimate ion pair, with sulfoxides in which X represents an electron-withdrawing substituent, whereas the rearrangement proceeds primarily in an intermolecular manner when X is a simple al- kyl group.

(5) Sulfilimines and Sulfoxirnines Sulfilimines are the nitrogen analogs of sulfoxides. Professor Oae and his coworkers developed a con- venient synthetic procedure for the conversion of a sulfide to an N-tosylsulfilimine. Such sulfili- mines, by analogy to the behavior of sulfoxides, were found to undergo stereospecific cis-elimina- tion by simple pyrolysis. Facile Pummerer-type rearrangements, reductions, and halide-catalyzed rearrangements were similarly discovered. A pro- cedure to prepare “free sulfilimines” was devel- oped next, and this led to the development of a new field of sulfilimine chemistry. Their acylation and subsequent cleavage reactions gave isocyanates. Their addition to a$-unsaturated ketones gave a- carbonylaziridines. Their oxidation gave sulfoxi- mines that previously could be prepared only by a hazardous procedure. Their halogenation afforded N-halosulfilimines that undergo reaction with soft nucleophiles at nitrogen, but with hard nucleo- philes at sulfur to give sulfoximines or sulfonedi- imines.

Optically active free sulfilimines were pre- pared for the first time, and these were found to be useful in establishing stereochemical reaction cycles. A facile synthesis of an optically active free diarylsulfilimine was achieved, and it could be uti- lized to prepare an optically active aziridine and an optically active sulfoximine. Also, a free diar- ylsulfilimine was found to react with an aldehyde to form a nitrile in quantitative yield. See the fol- lowing scheme for examples.

x McEwen

R\ .

R.'

S-NH -

\. ? cox .-* ,s-.N-c-R.&R-s-R, + R--N=C=O R

R'

(6) Chemical and Enzymatic Oxidation and Reduction of Organosulfur Compounds After some years of studies on the syntheses of sulf- oxides from sulfides, and the synthesis of sulfonic anhydrides from disulfides and N204. Professor Oae began to investigate modes of oxidation of divalent sulfur compounds. In the oxidation of thiols, di- sulfides, and thiolsulfinates with N204, interme- diate thionitrites (-S-N=O) were isolated and found to be excellent diazotization agents. In the electro- philic oxidation of a thiolsulfinate with a peracid, evidence for the formation of an "a-disulfoxide" intermediate was shown by use of 'sO-labeled methylthiolbenzenesulfinate.

Enzymatic oxidation of sulfides was carried out successfully with purified cytochrome P-450. This oxidation involves an initial one-electron transfer from sulfur, similar to that with the Undenfriend system (ferrous ascorbate mixture).

Sodium metaperiodate was shown to oxidize unsymmetrical thiolsulfinates selectively to the corresponding thiolsulfonates, suggesting the metal oxides to be nucleophilic oxidizing agents. The modes of base-catalyzed air oxidation of thiols, di- sulfides, and thiolsulfinates were shown to involve both peroxysulfinates and peroxysulfenates and

were similar to oxidations with the superoxide an- ion. Also, nucleophilic attack of hydroxide ion on thiolsulfinates was shown by the use of an "0 tracer to take place on the sulfinyl sulfur in the oxidative S-S bond cleavage.

On the basis of these and similar studies with various sulfur compounds, Professor Oae sug- gested that there are three different modes of ox- idation of such compounds, viz., electrophilic, nu- cleophilic, and those involving SET (single-electron transfer), depending on the oxidants and media. The action of the cytochrome P-450 system, or of Fen- ton's reagent on a sulfide, with S-oxidation or de- alkylation, was thought to involve the initial for- mation of a sulfenium cation-radical (A) by the SET mechanism.

0 R-s-cH2R, Cy10.P-150 c o t + (0 ) t

[ R- S- CHzR']-R- S- CHz R' OT OH radical '

R-S-CHR'*RSSR + R'CHO I OH

(A) l -H* to),

Peracids, singlet oxygen, N204, and FAD-mono- oxygenase are electrophilic oxidants, and KIO,, KMnO,, peracylates, and the superoxide anion are typical nucleophilic oxidants. The assumption that peroxysulfonates -sulfinates and -sulfenates are formed in the alkaline autoxidation of thiols and disulfides, and in the reaction of compounds con- taining the s-S linkage with the superoxide anion, was confirmed by trapping experiments.

Some new and interesting one-pot reductions of sulfonic and sulfuric acids were also developed by Professor Oae and his coworkers. Also, new methods of reduction of sulfoxides, sulfoximines, and sulfilimines were developed.

(7) Miscellaneous Studies Professor Oae and his colleagues have also carried out extensive studies on reactions of elemental sul- fur, mechanisms of reactions of phenols and phe- nolic esters, rearrangements of tertiary amine ox- ides, decomposition of diacyl peroxides, anchimeric assistance in nucleophilic substitution reactions of organic halides, and radiation and photochemistry of organosulfur compounds. Details of these stud- ies can be found in the open literature and also in a private printing of a book by Professor Oae in 1983, entitled, Seeking Beyond the Horizon of Sci- ence. This book was published by a group of Sig's former students under the management of Nao- michi Furukawa. Much of the material for this Tribute to Professor Shigeru Oae was adapted from this book.

Impressive as it is, a summary of Sig's re- search does not do full justice to his position in

A Tribute to Professor Shigeru Oae xi

science. He is unique in his role as an Ambassador- at-Large to chemists throughout the world. It was therefore no surprise that he was elected the first President of ICMGC, Inc. (International Council on Main Group Chemistry, Inc.) in 1994. Some of the reasons for his stature as a humanitarian are pre- sented in the following abstracts of letters that are contained in a chapter entitled “Dear Sig” in the book mentioned previously, Seeking Beyond the Horizon of Science.

“The prophets have said, ‘blessed are the peacemakers,’ and Professor Oae is truly a peacemaker, between individuals and nations. He came to the United States, alone, at a time when the relations between our two nations were still strained. Almost at once, he won, not only the heads, but also the hearts, of all who were privileged to know him. He taught us that, not alone the language of science, but also the language of respect and love is universal.”

- C . A. VanderWerf

“. . . He has been a real scientific statesman- as an administrator at Osaka, in his role in the founding and organization of the University of Tsukuba, and in his great contributions to the development of communication and under- standing between chemists in Japan and the United States.”

- Cheves Walling

“. . . You have every right to be proud of the Department of Chemistry at Tsukuba. As its first Chairman, you built the Department from the ground up-you planned the buildings, brought in the funds for the equipment, found the staff and persuaded them to join you in the new

venture, and by example set the standards for research. Not many scientists have been able to leave so great an imprint on science, or on the organization of science in any country.

“But as an American, I should like to honor you in addition for your contributions to the international nature of science, and to the good- will of the international scientific commu- nity.”

- Frank H. Westheimer “No picture of Sig could be complete without a mention of his outstanding human qualities. Sig’s cordiality, breadth of interests, and re- fined taste earned him the friendship of col- leagues all over the world.”

- Kurt Mislow “Sig is my first and oldest Japanese friend. His friendly ways, his wisdom and good judgment both in scientific and other matters has made him an outstanding ambassador for Japan and Japanese chemistry.”

- S. Gronowitz Although I have known Sig for nearly half a cen- tury, my closest interactions with him (also with Alfred Schmidpeter) have been in the founding and development of HETEROATOM CHEMISTRY. Hardly a week has passed during the past five years when we haven’t exchanged fax messages or let- ters. Throughout this period, Sig has been a tower of strength and wisdom. His consistent good hu- mor and optimism have been of inestimable value in keeping the journal and me alive and well. I am happy to have this opportunity to give him my sin- cere thanks.

- William E. McEwen Edi tor-in-Chief