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 The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction.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

Synthesis of α-Cyano Carbonyl Compounds by Flash Vacuum Thermolysis of (Alkylamino)methylene Derivatives of Meldrum′s Acid. Evidence of Facile 1,3-Shifts of Alkylamino and Alkylthio Groups in Imidoylketene Intermediates.

The photoelectron spectroscopic study of the thermolysis of amino-substituted Meldrum's acids confirms the formation of several intermediates in the gas phase: their structure depends on the amine function being either secondary or tertiary. In the first case, imidoylketene is clearly characterized, while in the second case cyclic end-products are identified. In both cases, the electronic structure characterization of unstable methylketene is not obvious from PE data.

Contribution of Photoelectron-Spectroscopy to the Study of the Flash Vacuum Pyrolysis of Amino-Substituted Meldrum Acid-Derivatives

N-Sulfides. Dinitrogen Sulfide, Thiofulminic Acid, and Nitrile Sulfides

This review describes the methods of generation of alpha-oxoketenes and their use in synthesis. While the ketenes are often generated in situ without direct proof for their existence, methods used for their direct observation are also emphasized. The most important classes of precursor molecules are 2-diazo-1,3-diketones, 1,3-dioxin-4-ones, 2,3-dihydrofuran-2,3-diones, and beta-ketoacid derivatives. Synthetically useful reactions are nucleophilic additions to give carboxylic acid derivatives which can be subjected to further functional group manipulation, [2 + 2] cycloadditions to give four-membered rings, and [2 + 4] cycloaddition chemistry with a wide variety of double-and triple-bonded dienophiles, resulting in numerous six-membered heterocyclic ring systems.

α‐Oxoketenes ‐ Preparation and Chemistry

Iminoacetonitrile (1) has been prepared by two methods: (i) thermal decomposition of the tosylhydrazone salts 13 at 200-degrees-C and (ii) Ar matrix photolysis of azidoacetonitrile (15). Ab initio calculations indicate that 1Z is of slightly lower energy than 1E, and this is confirmed by the IR spectra with use of the thermal methods. 1E/1Z undergo photochemical interconversion, giving a ca. 3:1 photostationary E:Z ratio. 1E and 1Z are fully characterized by their gas-phase, matrix, and thin-film IR spectra, which are in excellent agreement with ab initio calculations, by H-1 and C-13 NMR spectroscopy in solution, and by mass spectrometry. 1 polymerizes in solution above -40-degrees-C; pyrolysis produces HCN, and matrix photolysis produces HNC and van der Waals complexes containing HNC. N-tert-Butyliminoacetonitrile thermally fragments to tert-butyl isocyanide and HCN. N-Cyanomethanimine (3) has also been prepared by two methods: (i) pyrolysis of trimethylenetetrazole (20) at 500-800-degrees-C and (ii) pyrolysis of ditetrazolopyrazine 22 at 600-850-degrees-C. Both methods are extremely clean. 3 is fully characterized by its IR spectrum in agreement with ab initio calculations and, in conjunction with other work, by its mass and millimeter-wave spectra. 3 is thermodynamically stable in the gas phase up to ca. 800-degrees-C at low pressure and short contact times but polymerizes in the solid state above -100-degrees-C.

Curt Wentrup

Papers

Synthesis of α-Cyano Carbonyl Compounds by Flash Vacuum Thermolysis of (Alkylamino)methylene Derivatives of Meldrum′s Acid. Evidence of Facile 1,3-Shifts of Alkylamino and Alkylthio Groups in Imidoylketene Intermediates.

Contribution of Photoelectron-Spectroscopy to the Study of the Flash Vacuum Pyrolysis of Amino-Substituted Meldrum Acid-Derivatives

N-Sulfides. Dinitrogen Sulfide, Thiofulminic Acid, and Nitrile Sulfides

α‐Oxoketenes ‐ Preparation and Chemistry

HCN Dimers: Iminoacetonitrile and N-Cyanomethanimine.