Cleavage of the carbon–carbon bond in biphenylene using transition metals

Synthesis of Tetrahydrobiphenylene <i>via</i> Pd(0)-Catalyzed C(<i>sp</i>²)–H Functionalization

“…1) This class of compounds possesses an interesting aromaticity 2) and the aryl-aryl C-C bond can be cleaved to give metallocyclic complexes. [3][4][5] In contrast, the synthesis of partially hydrogenated biphenylenes, including tetrahydro-and hexahydrobiphenylenes has received little attention, despite these compounds showing interesting bioactivity. Caubère and colleagues have reported that di-and tetrahydrobiphenylenes showed cytotoxicity against human lymphoblasts and L1210 murine leukemia cell lines.…”

“…[13][14][15][16][17][18][19][20] Methods for the formation of benzocyclobutenes based on intramolecular C-H functionalization have been developed by the Catellani, Baudoin, Wolfe, and Martin groups. [21][22][23][24][25][26][27] Recently, we have investigated Pd(0)-catalyzed benzylic C(sp 3 )-H functionalization for the synthesis of various heterocycles and tetrahydro-2H-fluorenes. [28][29][30][31][32][33][34][35][36][37][38][39][40][41] In the synthesis of oxindoles, C(sp 3 )-H activation was favorable over competitive C(sp 2 )-H activation because of the presence of the sp 2 nitrogen linkage 29) (Chart 2a).…”

“…[21][22][23][24][25][26][27] Recently, we have investigated Pd(0)-catalyzed benzylic C(sp 3 )-H functionalization for the synthesis of various heterocycles and tetrahydro-2H-fluorenes. [28][29][30][31][32][33][34][35][36][37][38][39][40][41] In the synthesis of oxindoles, C(sp 3 )-H activation was favorable over competitive C(sp 2 )-H activation because of the presence of the sp 2 nitrogen linkage 29) (Chart 2a). In contrast, two methyl groups were required for the synthesis of tetrahydro-2H-fluorene through C(sp 3 )-H activation in the presence of the sp 3 carbon linkage (Chart 2b).…”

“…[28][29][30][31][32][33][34][35][36][37][38][39][40][41] In the synthesis of oxindoles, C(sp 3 )-H activation was favorable over competitive C(sp 2 )-H activation because of the presence of the sp 2 nitrogen linkage 29) (Chart 2a). In contrast, two methyl groups were required for the synthesis of tetrahydro-2H-fluorene through C(sp 3 )-H activation in the presence of the sp 3 carbon linkage (Chart 2b). 39) These results indicated that molecular flexibility is important for selectivity in this reaction.…”

“…Use of an electron rich ligand, such as (2-furyl) 3 P, was not effective for suppression of the side reaction (entry 3). The reaction using bulky triaryl-and trialkyl-phosphine ligands, including (o-tolyl) 3 P, Ad 2 PnBu, and Cy 3 P·HBF 4 , hardly proceeded (entries 4-6), despite reports that bulky trialkylphosphine ligands were effective for C(sp 3 )-H functionalization. 29) Using 5 mol% of 1,1′-bis(diphenylphosphino) ferrocene (dppf), a bidentate ligand, resulted in poor conversion (entry 7).…”