Palladium‐Catalyzed Selective Carbofunctionalization of Inert γ‐C(sp³)−O Bonds with 4‐Hydroxypyridin‐2(1H)‐ones and 4‐Hydroxy‐2H‐pyran‐2‐ones

Abstract

The palladium-catalyzed selective carbofunctionalization of inert γ-C(sp 3)À O bonds of aliphatic amides by using the strategy of sp 3 CÀ H activation/β-O elimination/hydrocarbofunctionalization with the assistance of 8-aminoquinolyl directing group is presented here. This method features a broad scope of both 4-hydroxypyridin-2(1H)-ones and 4-hydroxy-2H-pyran-2-ones, providing a versatile method for the synthesis of corresponding γsubstituted amide derivatives.

Pd(II)‐Catalyzed Selective Amination of Inert γ‐C(sp3)−O Bonds of Aliphatic Amides with Hydrazines

“…Based on previous reports [14][15][16] and the above experimental results, a plausible catalytic cycle for this palladium-catalyzed selective amination of inert γ-C(sp In summary, we have reported the palladium-catalyzed selective amination of inert γ-C(sp 3 )À O bond of aliphatic amide with hydrazines by using the strategy of 8-aminoquinolinedirected sp 3 CÀ H activation/β-O elimination/hydro-carbofunctionalization for the first time. This method features a broad scope of hydrazines, providing a versatile method for the synthesis of corresponding γ-hydrazines substituted carboxylic acids.…”

“…Based on previous reports [14–16] and the above experimental results, a plausible catalytic cycle for this palladium‐catalyzed selective amination of inert γ‐C(sp 3 )−O bond of aliphatic amide with hydrazines is shown in Scheme 3. First, under the action of 8‐aminoquinyl directing group, the palladacycle intermediate A was formed through the cleavage of C(sp 3 )−H.…”

“…Pd(II)‐catalyzed functionalization of inert sp 3 C−O bonds of aliphatic amides by using the strategy of 8‐aminoquinoline‐directed C(sp 3 )−H activation [13] /β‐O elimination/hydrofunctionalization was reported by Engle. [14] By employing the same strategy, our group subsequently achieved the palladium‐catalyzed carbofunctionalization of inert sp 3 C−O bonds of aliphatic amides, which gave rise to the γ‐4‐hydroxypyridin‐2( 1H )‐one and 4‐hydroxy‐ 2H ‐pyran‐2‐one‐substituted amide derivatives in moderate to good yields [15] . Meanwhile, Engle group disclosed the 8‐aminoquinoline‐directed, palladium‐catalyzed amination of alkenes with N−H nucleophiles, including amides, imides, carbamates, sulfonamides and hydroxylamine derevatives [16] .…”

“…[14] By employing the same strategy, our group subsequently achieved the palladium-catalyzed carbofunctionalization of inert sp 3 CÀ O bonds of aliphatic amides, which gave rise to the γ-4-hydroxypyridin-2(1H)-one and 4-hydroxy-2H-pyran-2-one-substituted amide derivatives in moderate to good yields. [15] Meanwhile, Engle group disclosed the 8-aminoquinoline-directed, palladium-catalyzed amination of alkenes with NÀ H nucleophiles, including amides, imides, carbamates, sulfonamides and hydroxylamine derevatives. [16] However, to the best of our knowledge, the utilization of hydrazines as NÀ H nucleophiles in the amination of unactivated C(sp 3 )À O bonds remains an unexplored challenge.…”

“…Control experiments indicated that the reaction did not occur in the absence of Pd catalyst or acid additives, respectively (Table 1, entries 9-10). Further optimization towards the solvents revealed that DCM was superior to other solvents (Table 1, entries [11][12][13][14][15][16]. Thus, the optimal reaction conditions were Pd(OAc) 2 (10 mol%) and CyhÀ COOH (50 mol%) in DCM (1.0 mL) at 120 °C for 24 h.…”