Synthesis through C(sp3)–C(sp2) Bond Scission in Alkenes and Ketones DOI
Michal Šimek,

Jeremy H. Dworkin,

Ohyun Kwon

et al.

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

ConspectusThe homolytic cleavage of C-C bonds adjacent to functional groups has recently become a popular strategy for restructuring the skeletons complex organic molecules. In contrast traditional reactivity profiles polar bond disconnections, scission furnishes carbon-centered free radicals primed controlled termination with diverse range radicophiles. Beyond standard radical capture, transition-metal catalysis facilitates sophisticated and C-heteroatom bond-forming reactions. Intensive efforts have been focused over many years into neighboring carboxylic acids alcohols. Despite ubiquity alkenes ketones in natural products, feedstock chemicals, common synthetic intermediates, much less attention paid exploiting their potential diversifying chiral pool materials, such as terpenes terpenoids. Defunctionalization this manner is powerful approach synthesizing high-value chemicals advanced intermediates because possibility reconstruct further decorate chirality-bearing carbon skeletons. Motivated by necessity, since 2018 our group on developing ozonolysis-based dealkenylative molecular diversification, we expanded deacylation 2025. Account, chronicle initial motivation, describe historical background, summarize research deacylative synthesis. Our capitalizes ozonolysis MeOH generate α-methoxyhydroperoxides reaction reducing agents. Their reduction through single electron transfer, mediated transition metal, leads formation an alkoxyl that undergoes rapid β-scission, furnishing both ester derived from acetal atom. The produced can be strategically terminated radicophiles, thereby delivering remodeled Using concept, developed hydrodealkenylation (through hydrogen atom transfer benzenethiol), thiylation thiyl diaryl disulfides), alkenylation addition/elimination nitrostyrenes), oxodealkenylation treatment TEMPO followed oxidation). Furthermore, kinetic analysis enabled development catalytic FeII/vitamin C system alkynylation halodealkenylation. Synergizing copper aminodealkenylation net-redox-neutral C-N formation. Although high oxidation ozone relative compounds makes alkene-to-peroxide conversion possible, it also limits applicability techniques substrates featuring ozone-sensitive groups. We overcame constraint first applying Isayama-Mukayiama peroxidation olefins then using novel system─catalytic FeIII PhSH stoichiometric γ-terpinene─for ozone-free hydrodealkenylation. alkenes, straightforward methodology well, including cycloalkanones. This process applicable total syntheses late-stage modifications ketone-containing products.

Language: Английский

Synthesis through C(sp3)–C(sp2) Bond Scission in Alkenes and Ketones DOI
Michal Šimek,

Jeremy H. Dworkin,

Ohyun Kwon

et al.

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

ConspectusThe homolytic cleavage of C-C bonds adjacent to functional groups has recently become a popular strategy for restructuring the skeletons complex organic molecules. In contrast traditional reactivity profiles polar bond disconnections, scission furnishes carbon-centered free radicals primed controlled termination with diverse range radicophiles. Beyond standard radical capture, transition-metal catalysis facilitates sophisticated and C-heteroatom bond-forming reactions. Intensive efforts have been focused over many years into neighboring carboxylic acids alcohols. Despite ubiquity alkenes ketones in natural products, feedstock chemicals, common synthetic intermediates, much less attention paid exploiting their potential diversifying chiral pool materials, such as terpenes terpenoids. Defunctionalization this manner is powerful approach synthesizing high-value chemicals advanced intermediates because possibility reconstruct further decorate chirality-bearing carbon skeletons. Motivated by necessity, since 2018 our group on developing ozonolysis-based dealkenylative molecular diversification, we expanded deacylation 2025. Account, chronicle initial motivation, describe historical background, summarize research deacylative synthesis. Our capitalizes ozonolysis MeOH generate α-methoxyhydroperoxides reaction reducing agents. Their reduction through single electron transfer, mediated transition metal, leads formation an alkoxyl that undergoes rapid β-scission, furnishing both ester derived from acetal atom. The produced can be strategically terminated radicophiles, thereby delivering remodeled Using concept, developed hydrodealkenylation (through hydrogen atom transfer benzenethiol), thiylation thiyl diaryl disulfides), alkenylation addition/elimination nitrostyrenes), oxodealkenylation treatment TEMPO followed oxidation). Furthermore, kinetic analysis enabled development catalytic FeII/vitamin C system alkynylation halodealkenylation. Synergizing copper aminodealkenylation net-redox-neutral C-N formation. Although high oxidation ozone relative compounds makes alkene-to-peroxide conversion possible, it also limits applicability techniques substrates featuring ozone-sensitive groups. We overcame constraint first applying Isayama-Mukayiama peroxidation olefins then using novel system─catalytic FeIII PhSH stoichiometric γ-terpinene─for ozone-free hydrodealkenylation. alkenes, straightforward methodology well, including cycloalkanones. This process applicable total syntheses late-stage modifications ketone-containing products.

Language: Английский

Citations

0