Atropisomerization barriers of configurationally unstable biaryl compounds, useful substrates for atroposelective conversions to axially chiral biaryls

Configurationally unstable biaryl lactones of type (M)-1 reversible arrow ( P)-1 and ring-opened 2-acyl-2'-hydroxy biaryl compounds of type (M)-4 rever sible arrow (P)-4 are versatile precursors for the atroposelective preparat ion of axially chiral biaryls. The activation barriers of their atropisomer ization process, which constitutes a fundamental precondition for the dynam ic kinetic resolution, were determined by dynamic NMR spectroscopy for rapi d processes and by HPLC-monitored racemization of enantiomerically enriched material for smaller interconversion rates. For the lactones, the free act ivation energies Delta G(298)(double dagger) increase with the steric deman d of the substituent R ortho to the biaryl axis in the series H < OMe (t(1/ 2) approximate to ms) < Me (t(1/2) approximate to s) < Et < i-Pr (t(1/2) ap proximate to min) < t-Bu (t(1/2) approximate to d). The formally ring-opene d 2-acyl-2'-hydroxy biaryls, which interconvert via the lactol isomers 5 as the cyclic (and thus configurationally less stable) intermediates, have a significantly slower atropisomerization rate as a result of the high loss i n activation entropy Delta S-double dagger as a consequence of the required intermediate ring closure 4 --> 5.