Ortho-alkylation of acetanilides using alkyl halides and palladium acetate

Transition‐Metal‐Catalyzed Direct Arylation of (Hetero)Arenes by CH Bond Cleavage

“…[108,109] More recently, Sanford and co-workers investigated the use of iodonium salts, such as [Ph 2 I][BF 4 ] (153), for the direct arylation of 2-aryl pyridines (Scheme 59). [27] Here, detailed mechanistic studies indicated that a palladium(II)/palladium(IV) catalytic cycle [110][111][112] was operative rather than a palladium(0)/palladium(II) cycle, which had generally been proposed for direct arylations with aryl (pseudo)halides as electrophiles. [27] Importantly, the same method enabled the regioselective direct arylation of indoles at the C2-position to proceed at ambient temperature.…”

“…In this way, anilide, [114,115] benzylamine, [116] pyridine, and pyrazole [117] derivatives were regioselectively functionalized with aryl iodides (Scheme 60). Based on competition experiments, as well as, literature precedent for the formation of palladium(IV) species in reactions with alkyl halides, [110][111][112] a palladium(II)/palladium(IV) mechanism was proposed to be operative in these arylations. [114] With respect to organic synthesis, it is noteworthy that Corey and co-workers and employed this approach for the selective arylation of C(sp 3 ) À H bonds in a-amino acid derivatives.…”

Stereoselective Synthesis of Chiral α‐Amino‐β‐Lactams through Palladium(II)‐Catalyzed Sequential Monoarylation/Amidation of C(sp3)H Bonds

“…Previously, Tremont and Rahman found that the use of coordinating solvents, such as DMF, DMA, and acetonitrile, promoted exclusive monomethylation in the palladium-catalyzed ortho methylation of acetanilides with MeI. [17] Shabashov and Daugulis also found that reactions run in acetonitrile cleanly afforded the monoarylation product.…”

“…[17] After further optimization, we were pleased to find that the monoarylation of 1 with PhI (1.5 equiv) occurred [b] Ratio (mono/di) [c] A wide range of aryl iodides were found to be compatible with this protocol, and the desired products were furnished in good yields under the optimized reaction conditions (Scheme 2). Many different functional groups, such as alkoxy (products 2 f and 2 g, 77 and 74 %, respectively), fluoro (product 2 h, 71 %), chloro (product 2 i, 71%), bromo (product 2 j, 70 %), nitro (product 2 m, 62 %), and acetylamino groups (products 2 k and 2 l, 79 and 35 %, respectively), were tolerated under the reaction conditions.…”

Construction of indole nucleus through C-H functionalization reactions

“…71 Tremont and coworkers demonstrated that with a stoichiometric amount of Pd(OAc) 2 , the ortho position of acetanilides can be activated to form aryl palladium species which can then be alkylated with alkyl halides such as allyl iodide (Scheme 55). Addition of triethylamine into the same pot promoted the Heck cyclization to form an indole product in 23% yield.…”