Copper‐Catalyzed Chemoselective Divergent Carbene Insertion into the N−H bonds of Tryptamines

Abstract

Easy access to divergent products with chemoselectivity is of great importance in organic synthesis. Herein, we have developed a chemoselective copper‐catalyzed carbene insertion protocol onto N‐H bonds of tryptamine derivatives. Divergent insertion products are obtained by varying the nucleophilicity of the aliphatic NH of tryptamine with electron‐donating or electron‐withdrawing groups. The reaction provided N‐H insertion products with broad substrate scope in good yields.

Facile access to C-substituted piperazin-2-ones and mianserin derivative enabled by chemoselective carbene insertion and cyclization cascade

“…Surprisingly, the piperazinone derivative 3aa is obtained in 53% isolated yield with our previous reaction conditions (Cu(hfacac) 2 · x H 2 O/ rac -BINOL in THF, entry 1). 8 The structure of 3aa has been unambiguously confirmed by XRD (CCDC †). 9 The simple insertion products are not observed, and the other expected isomer, 3′aa , was also not detected.…”

“…3 c ,7 Recently, our group successfully achieved the chemo-selective carbene insertion onto NH bonds of tryptamines in which relatively highly nucleophilic amine is preferred in chemo-selective insertion. 8 Inspired by this result, we focused our attention on realizing the chemo-selective carbene insertion onto more challenging NH bonds of 1,2-diamines (Fig. 1b).…”