198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

Supramolecular Synthons and Pattern Recognition 63
atom, the cluster approximates to a super-CBr 4 molecule. In retrosynthetic
terminology, cluster 17 is easily understood then as the combination of two
tetrahedral moities, the tetraphenylmethane molecular synthon 15 and the Br 4
supramolecular synthon 18. Now, if one interchanges the molecular and supramolecular
synthons by replacing the Br 4-cluster 18 with covalently bonded CBr 4
and the C-Br covalent bonds with the Br◊◊◊Ph interaction 19, the result is complex
20. In 20, four molecules of 14 are linked to a CBr 4 molecule through
synthon 19 (Br◊◊◊Ph centroid 3.67 Å) and the central carbon atoms of CBr 4 and
tetraphenylmethane may be treated as spheres and joined to form a distorted
diamondoid network. The crystal structures 17 and 20, derived from single- and
two-components respectively, bear close and striking similarities at the supramolecular
level and have similar diamondoid networks mediated by Br 4 and
Br◊◊◊Ph supramolecular synthons.
To continue, the crystal structure of tetrakis-(4-iodophenyl)methane (16) is
isomorphous with 17 having an I◊◊◊I distance of 3.95 and 4.16 Å in the corresponding
I 4-synthon. In this family of halo-substituted tetraphenylmethanes
with S 4- or pseudo-S 4-symmetry, the molecules exhibit similar columnar
packing in the solid state [14]. In summary, if a supramolecular structure is
defined as a network and analysed retrosynthetically, general connectivity
strategies can be systematically derived.
4
From Organic Synthesis to Crystal Engineering
A smooth and logical progression from molecular synthesis to crystal engineering
follows if functional groups are replaced with supramolecular synthons and
target molecules with networks. The functional group approach for defining
covalent bond connections is suited to the goals of molecular synthesis where
carbon-carbon bonds are formed between atoms with unlike polarisations, as
between nucleophiles (enolates, carbanions) and electrophiles (ketones, halides)
[15, 16]. In traditional organic synthesis, the molecule is assembled in a stepwise
and sequential manner such that carbon atoms in two functional groups react to
form a covalent bond while the others are deliberately made to stand as innocuous
spectators. In cases of potential competition between two or more functional
groups, protection of the more reactive group is necessary. The development
of mild and selective reagents and reaction conditions has been motivated
by the need to minimise the number of steps and improve the stereoselectivity
in covalent synthesis.
This approach has served synthetic organic chemistry for close to five decades
and has led to the total synthesis of a large number of molecules [17].
Complex natural products such as quinine, cortisone, strychnine, cedrol and
reserpine were the landmark syntheses of the 1940s and 1950s. The period from
1960 to 1990 was one of intensive research encouraged by the advent of modern
spectroscopic techniques and the ready availability of a large storehouse of
starting chemicals. A number of natural [10,16–19] and non-natural [20, 21]
target molecules were successfully tackled during this period. The total synthesis
of vitamin B 12 completed by Woodward [22] and Eschenmoser and Winter