Synthesis of α-Cyano and α-Sulfonyl Cyclic Ethers via Intramolecular Reactions of Peroxides with Sulfone- and Nitrile-Stabilized Carbanions.

The intramolecular reaction of carbon nucleophiles with oxygen-centered electrophiles has been little explored outside of nucleophilic epoxidation. We now report the synthesis of sulfonyl- and cyano-substituted oxacycles via intramolecular reaction of sulfone- and nitrile-stabilized carbanions with dialkyl peroxides, triethylsilyl/alkyl peroxides, and monoperoxyacetals. The cyclizations are successfully applied to synthesize oxetanes, tetrahydrofurans, and tetrahydropyrans but fail for oxepanes. Cyclizations involving the relatively stabilized anion derived from a benzylic nitrile proceed in high yields for a variety of peroxides, including those in which the electrophilic oxygen is formally isobutyl or neopentyl. Corresponding cyclizations of an alkanenitrile are successful with both dialkyl and alkyl silyl peroxides but demonstrate much greater variability in yields. Reactions of sulfone-containing substrates are successful only with dialkyl peroxides. The success of reactions appears to be strongly influenced by the rate of peroxide decomposition, which appears to be highest for reactions involving poorly stabilized anions. The significant variation in diastereoselectivity observed for different classes of peroxide on a common framework suggests the possibility of substrate-dependent reaction mechanisms.

A click-based modular approach to introduction of peroxides onto molecules and nanostructures.

Copper-promoted azide/alkyne cycloadditions (CuAAC) are explored as a tool for modular introduction of peroxides onto molecules and nanomaterials. Dialkyl peroxide-substituted alkynes undergo Cu(i)-promoted reaction with azides in either organic or biphasic media to furnish peroxide-substituted 1,2,3-triazoles. Heterolytic fragmentation of the peroxide to an aldehyde, a side reaction that appears to be related to the formation of the triazole, can be suppressed by use of excess alkyne, the presence of triethylsilane, or by use of iodoalkyne substrates. Complementary reactions of simple alkynes with azido-substituted peroxides are much less efficient. Click reactions of alkynyl peroxyacetals are also reported; reductive fragmentation can be minimized by increasing the distance between the peroxyacetal and the alkyne. The strategy enables modular introduction of dialkyl peroxides and peroxyacetals onto gold nanoparticles, the first such process to be reported.