Regio- and Stereoselective Electrochemical Alkylation of Morita–Baylis–Hillman Adducts

Abstract

Electrosynthesis is effectively employed in a general regio- and stereoselective alkylation of Morita–Baylis–Hillman compounds. The exposition of N -acyloxyphthalimides (redox-active esters) to galvanostatic electroreductive conditions, following the sacrificial-anode strategy, is proved an efficient and practical method to access densely functionalized cinnamate and oxindole derivatives. High yields (up to 80%) and wide functional group tolerance characterized the methodology. A tentative mechanistic sketch is proposed based on dedicated control experiments.

Electrochemical Allylic Alkylation of Morita-Baylis-Hillman Adducts and N-Hydroxyphthalimide Esters towards C(sp3)—C(sp3) Bond Formation

“…Based on previous reports and the above experimental results, [10,12] a possible mechanism for electrochemcial allylic alkylation was shown in Scheme 3. This reaction was initiated by the formation of a radical anion through cathode reduction, which further releasing CO 2 and phthalimide anion to form the corresponding alkyl radical (Scheme 3).…”

Catalyst- and Additive-Free Electrochemical CO2 Fixation into Morita–Baylis–Hillman Acetates

“…Paper / PSP / Special Topic Template for SYNTHESIS Thieme Indeed, eChem, using electricity alone as a sufficient power supply, can effectively generate transient nucleophilic species, capable of trapping CO2 for the subsequent conversion into value-added functionalized carboxylic acids (Figure 1a). 7 In continuation with our ongoing interest addressing the synthetic valorization of CO2 8 and the electrochemical manipulation of Morita-Baylis-Hillman (MBH) acetates 1, 9 we envisioned the possibility to merge these approaches documenting a cathodic reduction 10 of MBH derivatives 1 and subsequent CO2 trapping. 11 Therefore, the electrophilic profile of MBH acetates 1, previously serving for the capture of nucleophilic radicals 12 generated by cathodic reduction (Figure 1b), is twisted into a nucleophilic character.…”

Alkoxy Radical Induced Transformations from N‐Alkoxyphthalimides Under the Photoredox Catalysis

“…Meanwhile, in view of the enormous transformations from its carboxylic acid analogous, it is surprising to note that the chemistry of alkoxy radicals, has not attained the same degree of importance [12–15] . The analogous radical chemistry of carboxylic acid and its derivatives has been investigated much more widely, and this topic has been extensively reviewed [16–24] . Mechanistically, the radical pathway for carboxylic acid counterpart was mainly the decarboxylative process followed by cross‐coupling for diverse carbon‐carbon and carbon‐heteroatom bond construction with extruding carbon dioxide as a traceless leaving group.…”

“…Under electrical condition, single electron transfer occurred from the cathode to the substrate, leading to decomposition of intermediate radical anion via the N−O bond cleavage. Interestingly, a few reports realized synthetic useful transformations based on N ‐acyloxyphthalimides via electrochemistry, enabling the alkylation of MBH adducts and C5‐substituted azomethine imines [59,60] . Indeed, a review on photochemical synthesis through alkoxy radicals was recently published by Zuo and coworkers during the preparation of this review, covering the recent progress in alkoxy radical‐mediated transformations under visible light irradiation [25] .…”

“…[12][13][14][15] The analogous radical chemistry of carboxylic acid and its derivatives has been investigated much more widely, and this topic has been extensively reviewed. [16][17][18][19][20][21][22][23][24] Mechanistically, the radical pathway for carboxylic acid counterpart was mainly the decarboxylative process followed by crosscoupling for diverse carbon-carbon and carbon-heteroatom bond construction with extruding carbon dioxide as a traceless leaving group. Alkoxy radical chemistry is undoubtedly an increasingly active area of research, and notably the chemistry of oxygen radical has received much attention recently, attributed to its versatile transformation induced by highly reactive and tunable oxygen radicals such as 1,2-, 1,5-hydrogen atom transfer (HAT), and β-fragmentation (deformylation) process, with the resurgence of this area linked to the rapid development of photoredox catalysis in the past decade (Scheme 1).…”