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

Abstract

The size of a series of typical substituents has been probed by dynamic NMR measurements of the barriers to aryl-aryl rotation of the corresponding biphenyls. The resulting B values are meaningful because only mono-ortho substituted compounds were investigated and thus the results are not compromised by the non-additivity of multiple steric effects. On the basis of the chosen model system ethynyl and cyano groups were found to be slightly smaller than a phenyl ring. In contrast, vinyl and, in particular, formyl groups proved to be larger than phenyl. The latter difference is due to the loss of conjugation forces at the planar transition state. a-Hydroxyhexafluoroisopropyl is slightly more bulky than tert-butyl. Pentafluorophenyl and trifluoromethoxy exhibit nearly the same effective size as phenyl and methoxy, respectively. Trifluoromethyl is somewhat smaller than isopropyl.

Rotational barriers of biphenyls having heavy heteroatoms as ortho-substituents: experimental and theoretical determination of steric effects

“…the B value) of the substituted biphenyl. A number of diasterotopic probes in the 3′-position of 2-substituted biphenyls were tested for this purpose: Me 2 CH, 7 (i-Pr) 3 Si, 8 i-PrMe 2 Si, 8,10 (CF 3 ) 2 COH 9 and it was demonstrated that the rotational barrier was found to remain the same, within the experimental uncertainty of ±0.15 kcal mol , regardless of the choice of probe. For instance the barriers determined using the isopropyl group as a probe were found 7 to be 15.4, 8.75 and 9.9 kcal mol −1 for biphenyls bearing, as an ortho substituent, t-Bu, Br and I, respectively.…”

Are carboxylic esters really refractory to DAST? On the fluorination of α-hydroxyesters with DAST

“…8C Time, h 6 7 8 9 10 b 1 H 1 25 3 55 36 4 5 -2 4 25 3 50 42 4 4 -3 4 25 144 8 72 4 16 -4 4 a 80 16 29 51 -20 -5 Me 1 25 16 64 5 13 18 0 6 2 25 16 52 7 13 21 5 7 5 25 144 49 6 9 25 11 8 n Pr 1 25 5 83 3 13 1 0 9 1 25 48 82 2 12 4 0 10 5 25 144 42 6 22 24 6 11 1 40 5 44 10 8 23 9 neither trifluoroester from 8 nor pentafluoro diethers from 9 were formed by OH/F permutation, even in the presence of a large excess of DAST or at longer reaction times. This means that, although the ethoxydifluoromethyl group is less electron-withdrawing than the ethoxycarbonyl group, it is bulky enough [31,32] to divert the attack exclusively at the second carbonyl group.…”

“…Here, both steric and electronic effects play a synergic role in promoting the carbonyl fluorination. Though CF 3 group exerts an inductive electron-withdrawing effect comparable, if not slightly lower, to that of -CO 2 Et group, its steric requirements are substantially larger [32] and the attack of DAST to OH group becomes all the more difficult.…”

“…Diethyl 2-[(1-tert-butoxycarbonylindol-3-yl)methyl]-2-hydroxymalonates 15c,d, ethyl 2-[(1-tert-butoxycarbonylindol-3-yl)methyl]-2-hydroxy-3,3,3-trifluoropropionates 16a,c,d were prepared by the same procedure reported in ref [32]. starting from commercial 2-bromo-4-chloroaniline (for 15c and 16c) and 2-bromo-4-methylaniline (for 15d and 16d).…”

How Space‐Filling Is a Pyridine Lone Pair?

“…[31] Up to now, such "B values" have been determined for more than two dozen substituents. [31][32][33] The measurements were accomplished by variable-temperature ("dynamic") NMR spectroscopy, monitoring the flip of the axially chiral biphenyl conformer into its mirror image by means of diastereotopicity probes such as an isopropyl, [34] isopropyldimethylsilyl, [31] or hexafluoro-α-hydroxyisopropyl [32] group located at the 3Ј-position. [35] …”