B Values as a Sensitive Measure of Steric Effects

Abstract

Someone who says "A" should be prepared to also say "B": In contrast to cyclohexane model-based A values, biphenyl model-derived B values are powerful tools to quantify steric repulsion in and conformational behavior of ortho-substituted aromatic compounds.Torsional barriers of 15 ortho-substituted biphenyls have been determined computationally using the B3LYP density functional and experimentally by variable-temperature ("dynamic") nuclear magnetic resonance. Taking advantage of the 3'-isopropyldimethylsilyl group as a novel and superior diastereotopicity probe and tracking coalescence temperatures down to -173 degrees C (100 K), activation energies of aryl-aryl rotation as small as 5 kcal mol(-1) can be assessed. The 2-X/2'-H repulsion increments thus derived are powerful parameters for rationalizing and predicting the conformational behavior of aromatic compounds carrying ortho substituents.

The biphenyl-monitored effective size of unsaturated functional or fluorinated ortho substituents

“…6 A typical series of spectra taken of 2-ethynyl-3¢-(isopropyldimethylsilyl)biphenyl (3) is reproduced below (Fig. 1).…”

“…Therefore, as there is no conjugation energy from the beginning there is no penalty for sacrificing it either. 6 The dependence of conjugation on conformation is without doubt the origin of the higher B values of vinyl (B 8.2) and formyl (B 10.2) in comparison with phenyl (B 7.5) and hydroxymethyl (B 7.9), respectively.…”

“…The corresponding energy of conjugation is lost at the coplanar transition state where steric hindrance forces the amino group into a skew position. 6 In contrast, the dimethylamino (B 6.9) entity is twisted out-of-resonance with respect to the adjacent aryl ring in both the ground state and the transition state. Therefore, as there is no conjugation energy from the beginning there is no penalty for sacrificing it either.…”

“…11 2-Ethynyl-3¢-(isopropyldimethylsilyl)biaryl (3) was obtained from 1-bromo-2-(trimethylsilylethynyl)benzene in 72% yield. The inverse combination (with respect to Scheme 4) of the Suzuki-Miyaura components, 2-R-substituted phenylboronic acids coupled with 1-bromo-3-(isopropyldimethylsilyl)benzene, had been explored previously 6 in an attempt to get hold of large amounts of 2-bromo-3¢(isopropyldimethylsilyl)biphenyl (2-R = Br). Unfortunately this product, conceived to act as a turntable intermediate on the way to whole a series of model compounds, was almost more rapidly consumed than formed.…”

“…Therefore, we had to resort to the equally unclean coupling between 1,2-dibromobenzene and 3-(isopropyldimethylsilyl)-phenylboronic acid. 6 A satisfactory result was now achieved by merely replacing the coupling unit 1-bromo-3-(isopropyldimethylsilyl)benzene by its iodo analog. 2-Bromo-3¢-(isopropyldimethylsilyl)biphenyl was isolated in 89% yield.…”