Oxodealkenylative Cleavage of Alkene C(sp³)−C(sp²) Bonds: A Practical Method for Introducing Carbonyls into Chiral Pool Materials

Abstract

Reported herein is a one‐pot protocol for the oxodealkenylative introduction of carbonyl functionalities into terpenes and terpene‐derived compounds. This transformation proceeds by Criegee ozonolysis of an alkene, reductive cleavage of the resulting α‐alkoxy hydroperoxide, trapping of the generated alkyl radical with 2,2,6,6‐tetramethylpiperidin‐1‐yl (TEMPO), and subsequent oxidative fragmentation with MMPP. Using readily available starting materials from chiral pool, a variety of carbonyl‐containing products have been accessed rapidly in good yields.

Photoinduced C−O Bond Formation through C−C Bond Cleavage of Alcohols by Suppressing Alcohol Oxidation

“…Under reductive conditions, the Ezetimibe‐derived alkoxyamine ( 38 ) was successfully converted to the corresponding primary alcohol 41 with an 88% yield. On the other hand, oxidative cleavage conditions resulted in the formation of the aldehyde 42 with a yield of 51% [25a] . Importantly, the key cyclic structure and chiral centers were retained throughout these transformations.…”

“…Recently, the Kwon group demonstrated significant advancements in dealkenylative transformations by employing Criegee hydroperoxide intermediates, generated by bubbling ozone into a methanol solution [30] . Notably, they successfully achieved a one‐pot oxodealkenylative cleavage of alkene C( sp 3 )−C( sp 2 ) bonds, involving a radical trapping procedure with TEMPO (Scheme 1C) [25a] . These findings highlight the potential of C−C bond fragmentation as a valuable tool in synthetic chemistry for constructing complex molecular architectures.…”

Dealkenylative Functionalizations: Conversion of Alkene C(sp3)–C(sp2) Bonds into C(sp3)–X Bonds via Redox-Based Radical Processes

“…After dealkenylative thiylation, the next logical step was to use (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), a well-known persistent radical reagent, to achieve aminoxylation (Figure 10 ). 11 The reaction conditions for dealkenylative aminoxylation were similar to those for hydrodealkenylation. First, ozonolysis of the alkene in methanol yielded a hydroperoxide, which was subjected to reduction mediated by iron(II) sulfate, leading to an alkyl radical that was terminated by TEMPO to form a C(sp 3 )–O bond.…”

“…Gratifyingly, methods have been developed recently to strategically cleave alkenyl C(sp 3 )–C(sp 2 ) σ-bonds to expand the existing potential of olefinic compounds. Indeed, several examples of fragmenting these ‘inert’ bonds and installing useful synthetic motifs in their wake—including C(sp 3 )–H, 8 9 C(sp 3 )–S, 10 C(sp 3 )–O, 11 C(sp 3 )=O, 11 C(sp 3 )–C(sp 2 ), 12 and C(sp 3 )–C(sp) 13 functionalities—have been explored since 2018.…”