Photochemical C–H Activation Enables Nickel-Catalyzed Olefin Dicarbofunctionalization

Abstract

Alkenes, ethers, and alcohols account for a significant percentage of bulk reagents available to the chemistry community. The petrochemical, pharmaceutical, and agrochemical industries each consume gigagrams of these materials as fuels and solvents each year. However, the utilization of such materials as building blocks for the construction of complex small molecules is limited by the necessity of prefunctionalization to achieve chemoselective reactivity. Herein, we report the implementation of efficient, sustainable, diaryl ketone hydrogen-atom transfer (HAT) catalysis to activate native C−H bonds for multicomponent dicarbofunctionalization of alkenes. The ability to forge new carbon−carbon bonds between reagents typically viewed as commodity solvents provides a new, more atom-economic outlook for organic synthesis. Through detailed experimental and computational investigation, the critical effect of hydrogen bonding on the reactivity of this transformation was uncovered.

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…For this process, the authors used a bulky titanium catalyst, by which a desirable regioselectivity could be achieved (Scheme 7B and C). The obtained N-substituted anilines resemble some important compounds already known for their biological activities, such as antimalarial ( 17) [69] and anticancer (18) [70,71] properties (Scheme 7A).…”

“…One of the key synthetic methodologies is the C-H bond activation process that enables a straightforward access to several important and innovative compounds [14][15][16][17][18]. In the last few years, metals such as ruthenium [19][20][21], rhodium [22][23][24], palladium [25][26][27], and iridium [28][29][30] have been widely applied as catalysts for this matter, including in the synthesis of bioactive substances.…”

Light-Mediated Cross-Coupling of Anomeric Trifluoroborates

“…Because the proposed activation method proceeds through a radical species, we also wondered if C1 trifluoroborates can be enaged in C-S 21c and C-Se 25 bond-forming reactions (Scheme 5). To our delight, the formation of both ethers 26 and 28 proceeded smoothly from 15a and eletrophilic sulfur (25) or selenium (27) sources without a nickel co-catalyst. The high axial selectivities in reactions with 2-deoxysaccharides (and a mixture of anomers in the case of "regular" saccharides) are consistent with the metallo-anomeric effect operational for high-oxidation state nickel complexes 26 combined with the kinetic preference of the C1 radicals.…”

“…The high axial selectivities in reactions with 2-deoxysaccharides (and a mixture of anomers in the case of "regular" saccharides) are consistent with the metallo-anomeric effect operational for high-oxidation state nickel complexes 26 combined with the kinetic preference of the C1 radicals. 27 To rationalize the high selectivities, we propose a mechanism of C-arylation shown in Scheme 6. The anomeric radical intermediate 29 generated from α-trifluoroborates 9 enters the catalytic cycle through a recombination with Ni(II) intermediate 31.…”

“…Furthermore, the radical 29 generated from axial trifluoroborates is already in the preferred axial configuration. 27 We next analyzed the reaction pathways for the axial and equatorial isomers for tetrahydropyran (THP) and 2-deoxy-D-glucose (2dGlc). Recombination of bipyNiPhBr with both radicals in either pathway is a highly favorable process with substantial gain in free energy regardless of the configuration of the intermediates.…”