Synthesis of Functionalized α‐Vinyl Aldehydes from Enaminones

Abstract

An efficient RhII‐catalyzed synthesis of functionalized α‐vinyl aldehydes with high E/Z stereoselectivity was developed. The reaction mediates the cyclopropanation of enaminones with vinyl carbenoids that are generated from cyclopropenes in situ to give the aminocyclopropane intermediates. Selective C−C bond cleavage of the cyclopropane intermediates leads to formation of α‐vinyl aldehyde derivatives with high E/Z selectivity. This method proceeds at room temperature under very mild reaction conditions and works with a broad substrate scope.

Stereoselective cyclopropanation of enamides via C–C bond cleavage of cyclopropenes

“…Cyclopropylamines with electron-withdrawing groups are prone to hydrolysis in situ to provide carbonyl compounds via proximal C-C bond cleavage. [39][40][41] However, vinylcyclopropylamides are much more stable even under harsh high temperature or acidic conditions (ESI, Table S1 †). The reaction proceeded efficiently and led to oxidative 1,3-deneyl aldehydes in the presence of AgTFA and CuCl 2 as co-metal catalysts.…”

“…1c). [39][40][41] The cyclopropylamine moiety is a key constituent of a variety of natural and non-natural compounds that exhibit important biological activities. [42][43][44][45] It is a general building block as well to prepare valuable architectures via ringopening reactions.…”

C–C Bond Cleavages of Cyclopropenes: Operating for Selective Ring-Opening Reactions

“…The rhodium-catalyzed reaction of cyclopropenes 31 with enaminones 32 to prepare α-vinyl aldehyde derivatives 33 was disclosed by Loh and co-workers (Scheme 6.B). 62 This protocol relied on the consecutive use of Rh 2 (OAc) 4 as catalyst and p-toluenesulfonic acid (TsOH). Specifically, the rhodium species is able to induce the cyclopropene-to-carbene rearrangement to generate a rhodium carbene, which is responsible for the cyclopropanation of the enamine.…”

“…The rhodium-catalyzed reaction of cyclopropenes 31 with enaminones 32 to prepare α-vinyl aldehyde derivatives 33 was disclosed by Loh and co-workers (Scheme .B) . This protocol relied on the consecutive use of Rh 2 (OAc) 4 as catalyst and p -toluenesulfonic acid (TsOH).…”

Metal-free synthesis of gem-difluorinated heterocycles from enaminones and difluorocarbene precursors

“…[41][42][43] In our continuing research on enaminone chemistry. [44][45][46][47][48][49] We envisioned employing a suitable CF 2 carbene precursor [50][51][52][53][54][55][56] to cyclopropanation with the C-C double bond of enaminone to generate an aminocyclopropane intermediate, [57][58][59] which will further induce a regioselective C-C bond cleavage in situ to afford gem-difluorinated 5-heterocycles (Fig. 1B).…”