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 The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction.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

6. C-Sulfur-Substituted Aziridines 2110 6.

Synthesis and reactivity of C-heteroatom-substituted aziridines.

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/microwave%20enhanced%20synthesis%20Caddick%202009.pdf

Microwave enhanced synthesis

Recent advances in the stereoselective synthesis of aziridines.

Recent Advances in the Stereoselective Synthesis of Tetrahydrofurans.

The reaction of ring-closing metathesis-derived cyclic allylsiloxanes 3 with aldehydes in the presence of a Lewis acid gives 2,3,4-trisubstituted tetrahydrofurans related to the furanolignan family of natural products. The reactions proceed with complete 3,4-trans stereoselectivity, whereas the C-2 stereochemistry depends on both the aldehyde and Lewis acid used. When boron trifluoride etherate is used with aliphatic or electronically neutral aryl aldehydes, the reactions favor the production of the 2,3-cis isomer 8, whereas electron-rich aryl aldehydes lead to the 2,3-trans isomer 9 by Lewis acid-mediated isomerization of the kinetically favored cis isomer. The isomerization can be avoided by use of TMSOTf as a promoter, and hence, the stereochemistry can be tuned by appropriate choice of reagent. Cleavage of the pendant 3-ethenyl group installs the 3-hydroxymethyl group common to the furanolignans.

Reagent-controlled stereoselective synthesis of lignan-related tetrahydrofurans.

The scope of dimerization and isomerization reactions of α-lithiated terminal aziridines is detailed. Regio- and stereoselective deprotonation of simple terminal aziridines with lithium 2,2,6,6-tetramethylpiperidide (LTMP) or lithium dicyclohexylamide (LiNCy2) generates trans-α-lithiated terminal aziridines. These latter species can then undergo dimerization or isomerization reactions depending on the nature of the N-protecting group. α-Lithiated terminal aziridines bearing N-alkoxycarbonyl (Boc) protection undergo N- to C-[1,2] migration to give N−H trans-aziridinylesters. In contrast, aziridines bearing N-organosulfonyl [tert-butylsulfonyl (Bus)] protection undergo rapid dimerization to give 2-ene-1,4-diamines or, if a pendant alkene is present, diastereoselective cyclopropanation to give 2-aminobicyclo[3.1.0]hexanes. All of these reactions were used as key steps in the preparation of synthetically and biologically important targets.

Dimerization and Isomerization Reactions of α-Lithiated Terminal Aziridines

Dimerization of Lithiated Terminal Aziridines

Bowman–Birk inhibitor analogues containing 2, 3 and 4-carbon analogues of the natural disulfide were synthesised via solid phase microwave-assisted RCM and found to have Ki values against chymotrypsin in the low to sub-micromolar range, the best replacement for the disulfide arising from the linkage by RCM of two L-homoallylglycine residues.

Synthesis and bio-assay of RCM-derived Bowman–Birk inhibitor analogues

Organolithium-induced deprotonation of terminal epoxides in the presence of appropriate diamine ligands allows trapping with a range of electrophiles, yielding functionalised di- and tri-substituted epoxides in good yields and with control of stereochemistry at the epoxide.

Steven M. Miles

Papers

Reagent-controlled stereoselective synthesis of lignan-related tetrahydrofurans.

Dimerization and Isomerization Reactions of α-Lithiated Terminal Aziridines

Dimerization of Lithiated Terminal Aziridines

Synthesis and bio-assay of RCM-derived Bowman–Birk inhibitor analogues

Deprotonation–electrophile trapping of terminal epoxides