Cascade Reaction for the Synthesis of Carbolines from O‐Methylketoximes and Styrenes via Palladium‐Catalyzed C–H Activation and Sequential Annulation

Abstract

A novel cascade reaction has been described for the synthesis of Carbolines via palladium‐catalyzed successive C–C/C–N formation from O‐methylketoximes and styrenes. The oxime ether auxiliary not only serves as a traceless directing group, but is also partly transformed into the value‐added pharmacophore in a two‐step, one‐pot fashion.

Pd-Catalyzed Intermolecular Dehydrogenative Heck Reactions of Five-Membered Heteroarenes

“…Reaction of N-phenylindole with 3-chloro-1-phenylpropan-1-one provided high yield of the C3 alkenylation, via in situ generation of the enone from the β-chloro ketone (Equation (53)) [95]. (Under these conditions, N-alkyl, N-benzyl, and N-allylindoles led mainly to annulation products, like those of Equation (61) C2 alkenylation may be followed by annulation with the C3 substituent (Equations (56) [98] and (57) [99]). The lactonization depended on the N-substituent of the indole and did not occur with N,Ndimethylacrylamide as the alkenylating reagent (Equation 56).…”

“…Regarding the lactone (Equation (56)), Liu, Zeng, and coworkers proposed the activation of an olefinic C−H bond of the DHR product 11A, leading to the seven-Most reports of selective C2 alkenylations are due to substrates already C3 substituted, as exemplified with Equation(54) [96], Equation(55) [97], Equation(56) [98], and Equation (57)[99]. be followed by annulation with the C3 substituent (Equations (56)[98] and (57)[99]). The lactonization depended on the N-substituent of the indole and did not occur with N,Ndimethylacrylamide as the alkenylating reagent (Equation(56)).…”

“…The aza-heterocycle (Equation(57)) would be formed as depicted in Scheme 4. Regarding the lactone (Equation (56)), Liu, Zeng, and coworkers proposed the activation of an olefinic C−H bond of the DHR product 11A, leading to the seven-(55) C2 alkenylation may be followed by annulation with the C3 substituent (Equations (56)[98] and (57)[99]). The lactonization depended on the N-substituent of the indole and did not occur with N,N-dimethylacrylamide as the alkenylating reagent (Equation(56)).…”

“…8.5. BenzimidazoleC2-styrenylation of 1-methyl-1H-benzo[d]imidazole was also performed using Ong's procedure (Equation (99))[114] (99).…”

Palladium-Catalyzed β-Arylation of Cyclic α,β-Unsaturated <i>O</i>-Methyl Oximes with Aryl Iodides

“…[16][17][18][19][20][21][22][23] Oxime species are easily prepared from carbonyl compounds, and play an important and versatile role in organic synthesis. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] In metal-promoted direct β-functionalization of acyclic oxime species, the oxime group usually behaves as a directing Ncoordinating functionality [16][17][18][19][20][21][22][23] (Chart 1B). On the other hand, metal-promoted direct β-functionalization of cyclic oxime spe-cies such as 2-cyclohexen-1-one oxime, whose oxime group is not effective as a directing N-coordinating functionality, has not been reported yet (Chart 1C).…”