Clathrates of TETROL: Further Aspects of the Selective Inclusion of Methylcyclohexanones in Their Energetically Unfavorable Axial Methyl Conformations

(+)-(2R,3R)-1,1,4,4-Tetraphenylbutane-1,2,3,4-tetraol
(TETROL) functions as a highly efficient host for the inclusion of
cyclohexanone and 2-, 3-, and 4-methylcyclohexanone, all with 1:1
host/guest ratios. Most extraordinarily, the 3- and 4-methyl isomers
are uniquely included in their higher energy axial methyl conformations
rather than as their more energetically favorable equatorial analogues.
In contrast, 2-methylcyclohexanone is included more conventionally
in the equatorial methyl conformation. During recrystallization of
TETROL from racemic 2- and 3-methylcyclohexanone, some preference
is shown by the host for the (R)-enantiomer. In the
latter case, this is attributed to a much stronger H-bond between
a hydroxyl group of TETROL and the carbonyl group of the (R)-enantiomer (O···O 2.621(2) Å) compared
with a significantly weaker H-bond to the (S)-enantiomer
(3.125­(8) Å). In the former instance, hydrogen-bond strengths
to both enantiomers are similar, but the (R)-enantiomer
engages in three (guest)­CH···π­(host) and three
(guest)­H···Car(host) contacts, whereas fewer
interactions of these types are observed for the (S)-enantiomer. Calculations of geometries of the guest cyclohexanones
were determined at the MP2/6-311++G­(2df,2p) level and compared with
those obtained at the G3­(MP2) level. Finally, an interesting correlation
between crystal packing indices for the three methylcyclohexanone
clathrates and their respective desolvation onset temperatures was
identified.