Palladium-Catalyzed Remote meta-Selective C–H Bond Silylation and Germanylation

Abstract

Selective meta-C−H activation of arenes to date has met with a limited number of functionalizations. Expanding the horizon of meta-C−H functionalization, herein we disclose an unprecedented meta-silylation and -germanylation protocol by employing a simple nitrile-based directing template. Longer linkers between the target site and the directing template were successfully explored for meta-silylation (sp 2 -ε and sp 2 -ζ). Additionally, synthetic utility was demonstrated with several postsynthetic elaborations and with a formal synthesis of TAC101, a promising drug for the treatment of lung cancer.

Accessing Remote meta‐ and para‐C(sp2)−H Bonds with Covalently Attached Directing Groups

“…[31] phenethyl sulfonate (R = H) meta-olefination [32] aryl alcohol and acid (R = OMe) meta-olefination [33] aryl sulfonates (R = OMe) meta-silylation meta-germanylation [34] benzylsulfonyl esters phenylacetic acids meta-olefination [36] benzyl sulfonyl esters meta-olefination [41] benzyl sulfonates meta-cyanation meta-alkylation [43] [44] aryl sulfonates meta-cyanation meta-alkylation meta-alkenylation [43] [44] [44] phosphonate benzyl phosphonates meta-olefination meta-acetoxylation meta-hydroxylation [37] Angewandte Chemie Reviews…”

“…Thep otential of this procedure was demonstrated by sequential ortho-and meta-olefination of phenethylamine derivatives (31)(32)(33)(34)(35)(36). Finally,the directing group was removed under acid hydrolysis to afford meta-substituted phenylethylamine 37.…”

“…[34] Directing group assisted meta-C À Hf unctionalization had previously involved the construction of only CÀCa nd CÀO bonds,s ot his was an ontrivial example of CÀSi bond formation. In 2017, our group reported as et of examples for the metasilylation of phenylalkanesulfonic acids (Scheme 20).…”

Recent Progress in the Transition‐Metal‐Catalyzed Activation of Si−Si Bonds To Form C−Si Bonds

“…Much more challenging than the ortho ‐C(sp 2 )−H silylation of arenes via a five‐ or six‐membered metallacyclic intermediate is meta ‐C(sp 2 )−H silylation, which involves a large strain energy because the cyclic intermediates contain more than 11 members. Inspired by the pioneering work of the Yu group, Maiti and co‐workers have realized a method for the palladium‐catalyzed remote meta ‐selective C(sp 2 )−H silylation of benzylsulfonates 62 containing 2‐cyanophenol as a directing group (Scheme ) . Both mono‐ and disilylated products 63 a and 63 b are obtained in moderate ratios if symmetric benzylsulfonates possessing two available meta ‐C−H bonds are used.…”

“…Inspired by the pioneering work of the Yu group, [25] Maiti and co-workers have realized am ethod for the palladium-catalyzed remote meta-selective C(sp 2 )ÀHs ilylation of benzylsulfo-nates 62 containing 2-cyanophenol as ad irecting group (Scheme17). [26] Both mono-and disilylated products 63 a and 63 b are obtainedi nm oderate ratios if symmetric benzylsulfonates possessing two available meta-CÀHb onds are used. Substratesw ith two unsymmetrical meta positions produce monosilylatedp roduct 63 d,f avoring silylation at the sterically lesshinderedp osition.…”