Ruthenium-Catalyzed P^III-Directed Remote ε-C–H Alkylation of Phosphines

Abstract

The ruthenium-catalyzed remote ε-C–H alkylation of phosphines with tertiary alkyl halides has been developed. This novel PIII-directed C–H activation strategy tolerated various functional groups and delivered a wide variety of modified phosphines with excellent meta-site selectivity. Preliminary mechanistic studies indicated that a PIII-assisted ortho-cyclometalation/remote σ-activation pathway might be involved in this methodology.

Cooperative Ligand-Promoted P(III)-Directed Ruthenium-Catalyzed Remote Meta-C–H Alkylation of Tertiary Phosphines

“…Recently, P (III) -assisted ortho -C­(sp 2 )–H functionalizations of phosphines were accomplished by Clark, Shi, Soule, Takaya, and our group, respectively (Scheme a) . Compared with these advances gained in ortho -C–H functionalization, selective meta -C­(sp 2 )–H functionalization of phosphines remains unsolved and seems rather challenging, especially for tertiary phosphines in virtue of its strong coordination ability . Herein, we report a ruthenium-catalyzed meta -C­(sp 2 )–H alkylation of tertiary phosphines by using intrinsic P III as a directing group (Scheme c), which provides an efficient and rapid access to a variety of synthetically useful phosphines from commercially available precursors.…”

Sterically Controlled Late‐Stage Functionalization of Bulky Phosphines

“…Previously reported arylphosphine C−H borylation reactions, which are catalyzed by rhodium, ruthenium or iridium, or mediated by boron bromide reagents, all rely on the directing effect of the phosphine substituent to achieve high regioselectivity (Scheme 1). [6c,7] Directed arylation, [8] alkylation, [9] alkenylation [9b,10] and silylation [11] provide efficient access to additional substituents, but the use of a directing group strategy still limits functionalization to the C−H bond that lies closest to a catalyst engaged in dative bonding with the phosphorus lone pair, [8,9b,e,f,10–12] or the C−H bond para to this position [9a,c,d] . Here we report an undirected C−H borylation reaction of bulky phosphines, where the most sterically accessible position(s) of the scaffold undergo functionalization, so that a distinct regioisomer is obtained compared with phosphorus directed C−H borylation reactions.…”

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

“…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. Although catalysts based on these metals, are known to be efficient in C-H bond activation reactions affording the products in good yields and mild conditions, they are also known to be usually expensive.…”