Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200400655

Controlled microwave heating in modern organic synthesis.

Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

Asymmetric 1,3-Dipolar Cycloaddition Reactions

The Diels-Alder reaction has both enabled and shaped the art and science of total synthesis over the last few decades to an extent which, arguably, has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Diels-Alder cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.

https://www.ch.ic.ac.uk/local/organic/pericyclic/DA.pdf

The Diels--Alder reaction in total synthesis.

Introduction Cationic domino reactions Anionic domino reactions Radical domino reactions Pericyclic domino reactions Photochemically induced domino processes Transition metal catalysis Domino reactions initiated by oxidation or reduction Enzymes in domino reactions Multicomponent reactions Special techniques in domino reactions

Domino Reactions in Organic Synthesis

Nitrilimines: thermal production, direct observation, and capture reaction

The study of pyrolysis (thermolysis) reactions has a long tradition in Australia. In the 1950s, G. M. Badger and his students at the University of Adelaide carried out extensive studies on the gasphase pyrolysis of aromatic hydrocarbons under flow conditions at atmospheric pressure. Experiments with low-pressure gasphase pyrolysis, later to be known as flash vacuum thermolysis (FVT) or flash vacuumpyrolysis (FVP) – a term coined byEddie Hedaya – were started by Wilfred D. (Bill) Crow and R. F. C. (Roger) Brown in the Chemistry Department, School of General Studies, at the ANU in 1965. At that time, there were two places in Canberra where one could do chemical research: the Medical Chemistry Department in the John Curtin School of Medical Research under Professor Adrien Albert, and the Chemistry Department in the School of General Studies. The Research School of Chemistry was being built in 1966 and it opened for business in 1967withArthur Birch as FoundationDean. Nobody liked the name ‘School of General Studies’, which authors abbreviated SGS or dropped entirely in their publications, and in 1979 this unhappy name was changed to ‘The Faculties’. Roger Brown arrived at the SGS as a young lecturer in 1961, and Bill Crow from CSIRO (Melbourne) accepted an associate professorship at about the same time. At the SGS, Bill Crow purchased a Lindberg tube furnace for hisM.Sc. student from Western Australia, Richard K. (Dick) Solly to commence FVP experiments in 1964. He later purchased a mass spectrometer in order to pursue the then-popular line of research on analogies (or differences) between thermal and mass spectrometric fragmentations. Other researchers, inter alia M. P. Cava, E. K. Fields, and S. Meyerson in the USA had similar interests. However, Bill Crowwent on study leave with Nelson J. Leonard at the University of Illinois, Urbana-Champaign, in 1965 and left it to Roger to supervise Dick, which led to a series of very topical papers on the formation of benzyne and hetarynes, a subject that remained close to Roger’s heart throughout his career. After his move to Monash University in 1968, methyleneketenes and methylenecarbenes became a major research topic in collaboration with Frank. W. Eastwood, and this is where the ‘Roger Brown rearrangement’, viz. 1,2-dyotropic shifts in acetylenes, R–C1 C2–R0 #R0–C1 C2–R, taking place via transient vinylidene intermediates, was discovered. According to Richard Johnson (University of New Hampshire, USA), during the Gordon Conference on Physical Organic Chemistry in Holderness, New Hampshire, in 2001 he and Roger Brown discussed this chemistry as they hiked up Rattlesnake Mountain, and later that afternoon, Richard and Maitland Jones, Jr (Princeton University) decided (over a beer) to name the rearrangement after Roger. During the evening session, Maitland drew the alkyne-vinylidene rearrangement on a chalkboard in the centre of the stage and suggested to the assembled crowd to honour Roger by naming the reaction after him. The August issue of Aust. J. Chem. is dedicated to the memory of Roger Brown, who passed away on 1 September 2013. Many scientists from all over the world have contributed papers to this issue, which thereby becomes a celebration of FVP and the chemistry of reactive intermediates and unusual molecules as well as organic synthesis, structure determination, and inorganic chemistry. The apparatus and techniques used in flash (vacuum) pyrolysis are reviewed. Anna Chrostowska and Stanislaw Lesniak from Pau, France, and Lodz, Poland, respectively, review the use of photoelectron spectroscopy in the study of pyrolysis reactions. Ian Rae, Roger’s first Ph.D. student, reveals some of Roger’s first research projects at the SGS in Canberra, which were concerned with 1,2-dithiole chemistry and nitrones. Carl Th. Pedersen (Odense, Denmark) with colleagues in Belgium, Japan, and Singapore describe the elusive ethene diselone, Se1⁄4C1⁄4C1⁄4Se. Oliver Kappe (Graz, Austria) reports on the (non-)existence of special microwave effects, Hassan Sheibani (Kerman, Iran) on new reactions of chlorocarbonylketenes, and Wolfram Sander et al. (Bochum, Germany) on matrix-isolation of pyridyl radicals formed by FVP of azopyridines as well as the pyridylperoxy radicals derived from them. Arvid Kuhn and Curt Wentrup (UQ) with co-workers from Japan report on the characterisation of 1,2-dehydroheptafulvene (heptafulvyne) and rearrangements of C8H6 hydrocarbons under FVP conditions, which includes a Roger Brown rearrangement. Joel Hooper, J. W. White, and Andrew Holmes (Melbourne) describe the use of a Claisen rearrangement with an organocatalytic, intramolecular Diels-Alder reaction in natural product synthesis, Mary Garson et al. (UQ) report the isolation of a new 3-alkylpiperidine from Indonesian waters, and John Bremner and Z. Wu (Wollogong) detail annulation of eightto ten-membered oxaza rings to benzo[b] thiophene. ChrisMoody (Nottingham, UK) reports the use of Rh-catalyzed carbene insertion in the synthesis of indoxylic acid esters. Jonathan White, Ken Ghiggino and co-workers (Melbourne) elucidate solvatochromism in diketopyrrolopyrrole derivatives with the aid of calculations, Jason Smith (UTas), Rolf Prager (Flinders) and co-workers report on the synthesis of heterocyclic fused imidazoles by FVP of isoxoazol-5(2H)ones, and Ross McGeary (another former Roger Brown student) and his co-workers (UQ) use ethyl (benzothiazol-2ylsulfonyl)acetate in malonic ester-type syntheses of carboxylic acids and esters. Roger Brown spent an extended period on sabbatical at Nijmegen University, The Netherlands, in Binne Zwanenburg’s group, and two papers from this laboratory report CSIRO PUBLISHING

/pdf/roger-f-c-brown-memorial-issue-3sktri6omh.pdf

Roger F. C. Brown Memorial Issue

Flash vacuum thermolysis (FVT) of 6-aryl-1,3-dioxine-4-thiones 9 leads to the formation of acylthioketenes 10, which are characterized by Ar matrix IR spectroscopy as well as on-line tandem mass spectrometry. The thioketenes 10 undergo a 1,3-shift of the aryl group to generate thioacylketenes 11. Ketenes 11 cyclize to 3-aryl-thiet-2-ones 12, which are also characterized by matrix IR spectroscopy and tandem mass spectrometry. The thiet-2-ones 12 undergo two kinds of eaction under the FVT conditions: (i) cheletropic CO extrusion with formation of arylthioketenes 13, and (ii) cycloreversion to COS and arylacetylene

Acylthioketene—Thioacylketene—Thiet-2-one Rearrangements.

Benzyne, cyclohexyne, and 3-azacyclohexyne have been obtained by flash vacuum pyrolysis of phthalic anhydride, 4-cyclopentylidene-3-methylisoxazol-5(4H)-one (34), and 3-methyl-4-(2-pyrrolidinylidene)isoxazol-5(4H)-one (37), respectively, isolated at 77 K and observed by IR spectroscopy. Trapping and fragmentation reactions are described, and the implications for the mechanism of benzyne formation from phthalic anhydride via cyclopentadienylideneketene (9) are discussed.

Benzyne, Cyclohexyne, and 3-Azacyclohexyne and the Problem of Cycloalkyne versus Cycloalkylideneketene Genesis.

Carboxy(vinyl)ketenes, alkylideneketenes, and vinylketenes have been obtained selectively, sequentially, and isomerically pure for the first time by flash vacuum pyrolysis of 2,2-dimethyl-5-alkylidene-1,3-dioxane-4,6-diones (Meldrum's acid derivatives) under controlled conditions. Each of the ketenes was directly observed by IR spectroscopy and trapped with methanol or aniline. Highly unstable compounds believed to be the hydroxyacetylene isomers of the alkylidene- and vinylketenes have been observed for the first time.

Curt Wentrup

Papers

Nitrilimines: thermal production, direct observation, and capture reaction

Roger F. C. Brown Memorial Issue

Acylthioketene—Thioacylketene—Thiet-2-one Rearrangements.

Benzyne, Cyclohexyne, and 3-Azacyclohexyne and the Problem of Cycloalkyne versus Cycloalkylideneketene Genesis.

Interrelationship Between Carboxy(vinyl)ketenes, Methyleneketenes, Vinylketenes, and Hydroxyacetylenes.