Transition metal-free phosphonocarboxylation of alkenes with carbon dioxide via visible-light photoredox catalysis

Abstract

Catalytic difunctionalization of alkenes has been an ideal strategy to generate structurally complex molecules with diverse substitution patterns. Although both phosphonyl and carboxyl groups are valuable functional groups, the simultaneous incorporation of them via catalytic difunctionalization of alkenes, ideally from abundant, inexpensive and easy-to-handle raw materials, has not been realized. Herein, we report the phosphonocarboxylation of alkenes with CO 2 via visible-light photoredox catalysis. This strategy is sustainable, general and practical, providing facile access to important β-phosphono carboxylic acids, including structurally complex unnatural α-amino acids. Diverse alkenes, including enamides, styrenes, enolsilanes and acrylates, undergo such reactions efficiently under mild reaction conditions. Moreover, this method represents a rare example of redox-neutral difunctionalization of alkenes with H-P(O) compounds, including diaryl- and dialkyl- phosphine oxides and phosphites. Importantly, these transition-metal-free reactions also feature low catalyst loading, high regio- and chemo-selectivities, good functional group tolerance, easy scalability and potential for product derivatization.

Photocatalytic Umpolung ofN- andO-substituted alkenes for the synthesis of 1,2-amino alcohols and diols

“…17 Due to their innate nucleophilicity, they are excellent traps for electrophilic radicals, leading to the formation of a nucleophilic aamino radical I (Scheme 1A, a). The latter can then react with a radical trap, 18 undergo oxidation to the a-amino cation, [19][20][21] reduction to the a-amino anion, 22 or addition to an organometallic species followed by reductive elimination. 23 Despite the efficiency associated to such transformations, all enamide difunctionalizations reported so far are based on the initial addition of a highly reactive electrophilic radical, limiting functional group tolerance and the structural diversity of the obtained products.…”

“…It is important to stress that such an approach would completely change the type of transformations accessible, as the rst step would involve reaction with a nucleophile, in opposition to the electrophilic radical already intensively investigated. [17][18][19][20][21][22][23] Although this strategy appears highly attractive to answer current limitations in enamide functionalization, only one example of ene-carbamate hydroacetoxylation has been reported by Nicewicz and co-workers. 29 When considering the importance of nitrogen-containing compounds, a difunctionalization of enamides via photocatalytic Umpolung would be highly desirable.…”

Utilization of CO2 Feedstock for Organic Synthesis by Visible‐Light Photoredox Catalysis

“…In 2019, Yu and co‐workers demonstrated that phosphonocarboxylation of activated alkenes 44 (e.g., styrenes, acrylates, enolsilanes, and enamides) with di(aryl‐ or alkyl)phosphine oxides 45 and phosphites, and CO 2 under metal‐free photoredox catalytic conditions (Scheme 10 a). [23] The direct quenching of excited photocatalyst by phosphine oxide in combination with base warranted the generation of phosphorous‐centered radical 47 , which engaged in the difunctionalization of styrenes, acrylates, and enamides to finally furnish β‐phosphonocarboxylic and β‐phosphonoamino acids 46 (Scheme 10 b). However, alkyl enamides and unactivated alkenes remained unreactive under these reaction conditions.…”

Visible‐Light Photoredox‐Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

“…For example, Iwasawa [5e,s] and König [5n] both realized regioselective hydrocarboxylations of alkenes via visible‐light photoredox and transition‐metal dual catalysis. Martin, [5h] Wu, [5r] Li [5z] and our group [5j,x,ab] have developed different visible light‐driven difunctionalizing carboxylations of alkenes. These previously reported methods, however, are limited to activated alkenes, including styrenes and acrylates.…”