Synthesis and Stereochemical Properties of "Extended" Biphenols Bridged by ortho-, meta-, and para-Phenylene Spacers

A series of isomeric biphenols based on para- (1), meta- (2), and ortho- (3) terphenyl backbones was synthesized. Suzuki cross-coupling methodology was employed for the construction of the terphenyl backbone of their methyl-protected precursors (respectively 8, 13, and 16). Using K2CO3 as the base, the best reaction conditions involved DMF at 100 degrees C as solvent. Anhydrous conditions greatly improved the yields of the sterically crowded systems (particularly 16). ortho-Terphenyls 3 and 16 exist as mixtures of syn/anti atropisomers in solution. Compound 16 crystallizes in the anti-in form. DFT calculations at the B3LYP/6-311+G(d,p) level indicate that for both compounds the anti-in form is more stable than the syn form by 6.07 and 2.07 kJ mol(-1) for 16 and 3, respectively. These Delta Delta G(0) values are higher by the same factor (of two) than those obtained in solution at 240 K (3.17 and 0.93 kJ mol(-1)). The atropisomeric properties of 16 and 3 are finally discussed in the context of ortho-terphenyls in the literature. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)