Tunable Reaction Mode of Bifunctional Peroxides with Ketones to Access α-Oxacyclic Ketones and Enals

Abstract

A new annulation reaction between allylic/benzylic peroxides and ketones has been developed to provide the αoxacyclic ketones in moderate yields under the KO t Bu basic conditions. Mechanistic studies reveal that these peroxides undergo the Kornblum-DeLaMare rearrangement to release the aldehyde intermediates and subsequently initiate the aldol/etherification tandem process to deliver the final products. Accordingly, these peroxides serving as "masked" enals have also been utilized to prepare the previously hard-to-achieve α-enal-tethered ketones in one step.

A formal (3 + 2) annulation–Cannizzaro cascade of bifunctional peroxides for the synthesis of dihydrofurans

“…These bielectrophilic peroxides, which possess the merits of good stability and reactivity, could cyclize with a diverse array of carbon nucleophiles to forge five- and six-membered oxacycles under very mild basic conditions. 11 For instance, we applied 2-iodomethylallyl peroxides as (4 + 1) annulation synthons to couple with the active methylene compounds to make 2,2-disubstituted tetrahydrofurans in good yields under the Cs 2 CO 3 or KOH basic conditions (Scheme 1C). 11 a…”