Chemistry of Heterocyclic Compounds, Oxazoles: Synthesis, Reactions, and Spectroscopy, Part A
Ed. David C. Palmer, Wiley-Interscience, Hoboken, NJ, 2003, 640 pp., price $325.00, ISBN: 0-471-39494-7
The arrival of the distinct burgundy jacketed volume in the continuing series of Chemistry of Heterocyclic Compounds in the library is always a welcome sight especially to a graduate student. It invites browsing in order to initiate appreciation of the rich chemistry of some obscure heterocycle that he or she would not face during a graduate career unless by chance involvement in a specialized research problem. Setting aside the fact that library browsing is increasingly uncommon in our on-line world, appreciation of π-excessive and π-deficient heterocyclic reactivity and synthesis is a rude awakening to most graduate students on their first day of work at a pharmaceutical company when they are asked to prepare a pyrrolopyrazolopyrimidinoindole.From this viewpoint, the current volume, Part A of a two-part work, represents the new bible for the oxazoles, which may be perused to allow appreciation or deep insight into this ring system whose history, as noted in the informative foreword by Al Meyers, a chemist with major contributions to this area, is deeply infused in organic chemistry by way of azlactones (“cyclic amino acids”, tautomeric oxazolones) first reported in 1883. It constitutes an update of the Turchi volume 45 in this series from 1983, covering synthesis, reactions, spectroscopic properties and the special topics of oxazole Diels–Alder reactions and mesoionic oxazoles. The vast advances since 1983, evident in all chapters, are a testament to the now established significance of this heterocycle in organic synthesis, asymmetric catalysis, natural products with potent and diverse bioactivity and hence, not unexpectedly, in medicinal and agrochemical programs. The editor, Dr Palmer, noting that comprehensive coverage of the 10,000 references which appeared in the 20-year period would constitute a Herculean task, has confined the two-volume scope to significant advances in mononuclear oxazoles, oxazolones, oxazolines, and chiral bis-oxazolines and exclusion of fully reduced and benzofused systems. This is a wise decision since, in the time frame indicated, detailed searches for specific compounds are easily achieved through electronic databases.
Chapter 1, by far the longest (390 pp.), by editor David Palmer and S. Venkatraman dealing with the Synthesis and Reactions of Oxazoles, attests to the significance of this heterocycle in natural products, medicinal agents, and materials science substances. Rational divisions of methods of oxazole synthesis are presented, beginning with oxidation of oxazolines, continuing with rearrangement of aziridine and other heterocyclic rings, Rh, Te, and Hg reagent-mediated processes, and terminating with methods of de novo ring forming reactions, e.g. from α-leaving group-containing ketones, oximes, hydrazones, azides and isocyanides (especially van Leusen's TosMIC reagent). Included in this journey are the venerable and the still widely used Cornforth and Robinson–Gabriel methods which have assumed new variations. Mechanistic aspects are briefly given to encourage understanding and hence potential application. Solid support oxazole syntheses reflect the currency of the volume. Illustrations of key oxazole ring forming reactions in the context of natural product synthesis allow some judgment concerning the tolerance of chiral sites and certain functional groups to a host of conditions.
In the section on oxazole reactions, the major themes of electrophilic substitution, disruption of aromatic character at the C4–C5 bond, nucleophilic, hydrolytic cleavage to various functionalized derivatives, singlet oxygen reactions, and Diels–Alder and [2 + 3] cycloaddition (see also below) processes are systematically covered. The use of oxazoles as masked functionality is delineated. Methods of heterocyclic interconversion of oxazoles into pyrroles, pyrazoles, imidazoles, thiazoles and pyrimidine, among others, are updated and recall the excellent early volumes by van der Plas on this interesting topic (H. C. van der Plas, Ring Transformation of Heterocycles, Academic Press, New York, London, 1973, vols 1 and 2). The intriguing and frustrating metalation chemistry, which involves equilibrium ring opening reactions is also updated from the time of the excellent review by Iddon (B. Iddon, Heterocycles, 1994, 37, 1321). The advantages gained by lithium for organozinc, magnesium and tin transmetalation, followed by the new wave of Kumada–Corriu, Negishi, and Stille cross coupling reactions are clearly evident; however, conspicuously missing are boronated oxazoles and hence Suzuki coupling processes. Silylated oxazoles, which are of advantage for the induction of carbodesilylation reactions under mild conditions, oxazolium salts and miscellaneous reactions conclude this chapter of rich oxazole chemistry.
The oxazole natural product section begins with a very useful display of representative natural products which incorporate oxazole rings in their overall structure. The excitement in this field is due to the potential of finding therapeutic agents for antibacterial, analgesic, antitumor, antiviral, and antifungal indications, which have been discovered in certain natural products. Representative structural types arranged according to the number of oxazole rings are presented in overview before separate sections concerning the synthetic work on streptogramine antibiotics, thiangazole and tantazole HIV inhibitors, calyculin protein phosphatase inhibitors, hennoxazole anti herpes simplex viral inhibitors, the now celebrated diazonamides (reviewed slightly in advance of the structural revision, see T. Ritter and E. M. Carreira, Angew. Chem. Int. Ed. 2002, 41, 2489), and finally the multi-bioactive ulupualide, are summarized. An addendum brings this most valuable review to an early 2001 dateline. Excellent concise summaries of the arduous synthetic work are presented.
A short (24 pp.) Chapter 2 on Spectroscopic Properties by D. Lowe provides extensive NMR (including N, O, and F nuclei), MS, IR, and UV spectroscopic data in tabular format for browsing and correlation purposes.
Chapter 3, Oxazole Diels–Alder Reactions, by J. L. Levin and L. M. Laakso is a 1985 update on this important reaction which constitutes a commonly traveled route for the synthesis of furans, pyridines, and other heterocycles. The behavior of oxazoles, both as dienes and dienophiles in inter- and intra-molecular processes, should be required material in graduate courses in synthetic organic chemistry to allow students a head start in the appreciation of heterocyclic chemistry of value in the pharmaceutical industry. Particularly useful and, at the time, unique, methods leading to substituted pyridines and furans, although with the proviso of availability of starting isoxazoles with proper appendages, are reviewed. The synthesis of diverse heterocyclic systems (e.g. benzonaphthyridines) and natural products further convincingly illustrate the power of this methodology.
The final Chapter 4 (100 pp.), Mesoionic Oxazoles, by G. W. Gribble, provides coverage for the period since the exhaustive 1983 review in the oxazole volume of The Chemistry of Heterocyclic Compounds series. The telling name of munchnones (1,3-oxazolium 5-oxides) and, more recently, isomunchnones has become integrated into the mindset of aware organic chemists for 1,3-dipolar cycloaddition reactions. After brief sections on the synthesis (including new Ugi four-component and solid support methodology) and spectroscopic properties of munchnones, electrophilic, nucleophilic, and cycloaddition reactivity are delineated with the last reaction occupying most coverage thus reflecting the greatest synthetic significance. While cycloaddition with archetypical acetylenic dipolarophiles provides a general route to pyrrole derivatives, the corresponding reaction with olefinic partners also leads to diverse products, including those in which the elimination of CO2 has not occurred. Other dipolarophiles, from carbonyl to phosphorus-containing systems, are reviewed, clearly documenting the rich playground in heterocyclic synthesis that is presented by the munchnone 1,3-dipolar reactivity. As stated by the author, the corresponding, usually unisolable, isomunchnones “undergo 1,3-dipolar cycloaddition…with alacrity.” Hence, largely through the thorough investigations of Padwa, a broad picture of cycloaddition reactivity emerges, which shows potential for the construction of pyridones, furans, and a considerable number of non heteroaromatic bicyclic adducts, including some that serve as intermediates to alkaloid synthesis. As expected, especially considering the treacherous problems of multi-authored volumes and the fact that publication occurred in the same year, the chapter on Mesoionic Oxazoles in Synthetic Applications of 1,3-Dipolar CycloadditionChemistry Toward Heterocycles and Natural Products (Ed. A. Padwa and W. H. Pearson, The Chemistry of Heterocyclic Compounds, Wiley-Interscience, New York, vol 59, 2003) by the same author, overlaps in the cycloaddition sections with that of the present volume. However, Professor Gribble has taken great care to rewrite, update and reorganize the Padwa and Pearson chapter; furthermore, the Palmer chapter naturally contains much broader coverage as indicated above. Considering the specialized nature of the Padwa and Pearson volume and the price differential, the market reached by the two volumes will be quite separate.
Almost 20 years have passed since the publication of the Turchi edited volume on oxazoles in The Chemistry of Heterocyclic Compounds series. This volume by David Palmer will serve easily for the next 20 years as the reference source for this class of heterocycles, since its rise to prominence owing to appearance in natural product, polymer, dye, and bioactive molecular structures, cannot be ignored by the teacher and researcher in organic chemistry. The writing is clear, the (several thousand) structures are visually friendly, the tabular data is representative, the index, which includes a separate listing of classes of oxazoles, is useful, and the references include patents. Dr. Palmer and his authors deserve our deep gratitude for this major work. We eagerly await Part B of this volume set.
Victor Snieckus
Queens University, Kingston, Canada
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