472
M. Akazome and S. Matsumoto
asymmetric unit consisted of two hosts and two guests, while the space group was
P1.
The three crystal structures mentioned above have the same cyclic hydrogen
bonding network to form 2:2 clusters (Tr-Tyr·tBuNH 2 ).
Figure 22.16 shows the difference between phenylalanine and tyrosine. In the
case of Tyr, a one-dimensional hydrogen bonding network of ammonium carboxylate
was broken and terminated by a phenolic hydroxy group of Tyr. As a result, larger
secondary alcohol guests settled between hosts with the distance expanded from 9.27
to 11.15 Å. Although the phenyl group of Phe interacted with one phenyl group of
a trityl group by a C-H· · · π interaction, the phenyl group of Tyr interacted with one
hydrogen atom of the ammonium group by a N-H· · · π interaction, and the phenolic
HO group also made a hydrogen bond with an oxygen atom of the guest alcohol.
The conformational change of the side chain induced a new 2:2 cluster structure
(Tr-Tyr·tBuNH 2 ).
As mentioned above, we found that Tr-Tyr·tBuNH 2 salt included 1-arylethanols
to form the similar 2:2 clusters (Tr-Tyr·tBuNH 2 ). The structure of these inclusion
crystals had the generality to become a great potential inclusion host. However, the
statistic disorder must be suppressed and high enantiomeric excesses must be gained.
22.4 Conclusion
We reviewed the recent progress of the molecular recognition by inclusion
phenomena regarded as a useful application of organic crystals.
In the first half of this review, we covered recent examples of molecular recognition by inclusion crystalline hosts: a dumb-bell type host [9], TETROL [10, 11]
and TADDOL [14], and amino-acid-based hosts [15–17]. Some chiral hosts have
achieved high enantioselective inclusion for cyclic ketones (up to 97% ee), sulfoxides
(up to 98% ee), and nitriles (up to 92% ee).
In the latter half, we focused on the installation of trityl and related bulky
groups, which enable compounds to settle guest molecules to form inclusion crystals. In fact, some hosts of amines [26–32] having trityl or 9-phenyl-9-xanthenyl
groups included several neutral guests to construct inclusion crystals. In particular,
we demonstrated that salts between N-trityl-tyrosine and tert-butylamine include
1-(1-naphthyl)ethanol in 96% ee (R) [33].
Inclusion crystal methods are still being refined to achieve structural isomer separation and optical resolution for neutral compounds. The trityl and related bulky
groups might be recognized as crystal engineering tools that have the inclusion
ability to host candidates. However, single-crystal X-ray analyses of these inclusion
crystals showed us that inclusion with low enantioselectivity was often owing to
statistically disordered structures, meaning both enantiomers settled in one recognition site. Therefore, the method of suppressing this statistic disorder with low
enantioselectivity remains unknown.
M. Akazome and S. Matsumoto
asymmetric unit consisted of two hosts and two guests, while the space group was
P1.
The three crystal structures mentioned above have the same cyclic hydrogen
bonding network to form 2:2 clusters (Tr-Tyr·tBuNH 2 ).
Figure 22.16 shows the difference between phenylalanine and tyrosine. In the
case of Tyr, a one-dimensional hydrogen bonding network of ammonium carboxylate
was broken and terminated by a phenolic hydroxy group of Tyr. As a result, larger
secondary alcohol guests settled between hosts with the distance expanded from 9.27
to 11.15 Å. Although the phenyl group of Phe interacted with one phenyl group of
a trityl group by a C-H· · · π interaction, the phenyl group of Tyr interacted with one
hydrogen atom of the ammonium group by a N-H· · · π interaction, and the phenolic
HO group also made a hydrogen bond with an oxygen atom of the guest alcohol.
The conformational change of the side chain induced a new 2:2 cluster structure
(Tr-Tyr·tBuNH 2 ).
As mentioned above, we found that Tr-Tyr·tBuNH 2 salt included 1-arylethanols
to form the similar 2:2 clusters (Tr-Tyr·tBuNH 2 ). The structure of these inclusion
crystals had the generality to become a great potential inclusion host. However, the
statistic disorder must be suppressed and high enantiomeric excesses must be gained.
22.4 Conclusion
We reviewed the recent progress of the molecular recognition by inclusion
phenomena regarded as a useful application of organic crystals.
In the first half of this review, we covered recent examples of molecular recognition by inclusion crystalline hosts: a dumb-bell type host [9], TETROL [10, 11]
and TADDOL [14], and amino-acid-based hosts [15–17]. Some chiral hosts have
achieved high enantioselective inclusion for cyclic ketones (up to 97% ee), sulfoxides
(up to 98% ee), and nitriles (up to 92% ee).
In the latter half, we focused on the installation of trityl and related bulky
groups, which enable compounds to settle guest molecules to form inclusion crystals. In fact, some hosts of amines [26–32] having trityl or 9-phenyl-9-xanthenyl
groups included several neutral guests to construct inclusion crystals. In particular,
we demonstrated that salts between N-trityl-tyrosine and tert-butylamine include
1-(1-naphthyl)ethanol in 96% ee (R) [33].
Inclusion crystal methods are still being refined to achieve structural isomer separation and optical resolution for neutral compounds. The trityl and related bulky
groups might be recognized as crystal engineering tools that have the inclusion
ability to host candidates. However, single-crystal X-ray analyses of these inclusion
crystals showed us that inclusion with low enantioselectivity was often owing to
statistically disordered structures, meaning both enantiomers settled in one recognition site. Therefore, the method of suppressing this statistic disorder with low
enantioselectivity remains unknown.