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 The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction.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

Formation of Cumulenes, Triple‐Bonded, and Related Compounds by Flash Vacuum Thermolysis of Five‐Membered Heterocycles

Flash vacuum pyrolyses or pulsed pyrolysis of azole esters 1b and 20 and their carboxylic acids 1a and 19 or acid chloride 1c give five-membered ring ketenes (azafulvenones) 2 and 24 which dimerize to diketopiperazines 3 and 21 but also undergo efficient rearrangement to (cyanovinyl)- and (o-cyanophenyl)ketene (6 and 27). The same products are obtained by elimination of alcohol from esters of these (cyanovinyl)ketenes. Both types of ketenes are observed directly by IR spectroscopy and are trapped by alcohols to give the corresponding azole esters or (cyanovinyl)acetates. 1-Carbonyl-1H-isoindole (34) is a highly reactive ketene, dimerizing at 50 K. All ketene IR spectra are in good accord with ab initio calculations. The mechanism of this apparent retro-Wolff rearrangement is discussed.

(Cyanovinyl)ketenes from azafulvenones. An apparent retro-Wolff rearrangement

Photolysis of 3-pyridyldiazomethane in an Ar matrix at 7-10 K gives 3-pyridylcarbene. Further photolysis causes ring opening to nitrile ylide 26 (formonitrile pent-2-en-4-ynylide) as the major reaction together with a minor amount of ring expansion to 1-azacyclohepta-1,3,4,6-tetraene, 27. Matrix photolysis of 3-azidopyridine leads to ring opening to formonitrile N-cyanovinylmethylide, 33.

Curt Wentrup

Papers

Formation of Cumulenes, Triple‐Bonded, and Related Compounds by Flash Vacuum Thermolysis of Five‐Membered Heterocycles

(Cyanovinyl)ketenes from azafulvenones. An apparent retro-Wolff rearrangement

3-pyridylcarbene and 3-pyridylnitrene: ring opening to nitrile ylides.

Nitrile Imines: Thermal Generation, Direct Observation, and Subsequent Trapping

Acyl‐ and Thioacylketenes: Synthesis of 3‐Benzoly‐4‐phenylthiet‐2‐one