2,5-Dihydro-1,3,4-oxadiazoles and Bis(heteroatom-substituted)carbenes.

2,5-Dihydro-1,3,4-oxadiazoles with heteroatom substituents at C-2 (also known as corresponding Delta(3)-1,3,4-oxadiazolines) are very useful materials for the thermal generation of acetoxy(alkoxy)-, dialkoxy-, alkoxy(aryloxy)-, diaryloxy-, alkoxy(alkylthio)-, bis(alkylthio)- and alkoxy(amino)-carbenes. Such carbenes are relatively nucleophilic and react with a variety of electrophilic functional groups. This Account reviews our work to prepare 2,5-dihydro-1,3,4-oxadiazoles and apply them to the synthesis of other target molecules.

Reactions of dimethoxycarbene with dimethyl 2,3-dicycanomaleate and fumarate.

Dimethoxycarbene, in 2-fold or larger excess, reacts with dimethyl 2,3-dicyanomaleate and fumarate to afford an unstable dihydrofuran 1:1 adduct that was shown to react further with the carbene to afford a 2:1 adduct reported previously. In an astonishing process, the dihydrofuran reacts with water to afford a mixture of (d,l and meso) dimethyl 2,3-dicyanosuccinates in which both hydrogen atoms of water were used to hydrogenate a C=C bond.

Zwitterion from a cyclopropane with geminal donor and acceptor groups.

2,2-Dimethoxy-3,3-dicyanospiro[cyclopropane-1,9'-[9H]fluorene] reacted fast with methanol to afford 9-trimethoxymethyl-9-dicyanomethyl-9H-fluorene. Reaction with benzaldehydes also gave products of cyclopropane ring opening. Strong electron-donor p-substituents or a strong attractor enhanced the rate.

Density functional theory computational study on the thermal cycloreversion of 2-acetoxy-2-methoxy-5,5-dimethyl-Delta3-1,3,4-oxadiazoline: evidence for a carbonyl ylide intermediate.

Three [3 + 2] cycloreversions of 2-acetoxy-2-methoxy-5,5-dimethyl-Delta(3)-1,3,4-oxadiazolines were examined by computation at the density functional level of theory. The lowest activation energies are those for cycloreversion to 2-diazopropane and acetic methylcarbonic anhydride and for cycloreversion to N(2) and a carbonyl ylide. Those are the reactions that are observed experimentally.

New thermal source of dimethoxycarbene leading to zwitterionic intermediates and 2:1 stoichiometry in reaction with electrophilic alkenes.

[reaction: see text] At 50 degrees C, dimethyl dicyanofumarate and maleate react with 2 equiv of dimethoxycarbene to generate the products shown.

Relative reactivities of carbonyl and thiocarbonyl groups toward dimethoxycarbene: two new dimethoxythiiranes.

Reaction of dimethoxycarbene (DMC), generated by thermolysis of a 2,5-dihydro-1,3,4-oxadiazole, with 2,2,4,4-tetramethyl-3-thioxocyclobutanone afforded primarily 2,2-dimethoxy-3,3,5,5-tetramethyl-4-thioxocyclopentanone from ring expansion by overall insertion into the C-CO bond. 4,4-Dimethoxy-2,2,5,5-tetramethyl-3-thioxocyclopentanone, from overall insertion into a C-CS bond, was a minor product. Thus the carbene had reacted preferentially at the carbonyl group, rather than the thiocarbonyl group of the four-membered ring.