21 Asymmetric Synthesis Involving Dynamic Enantioselective …
453
21.4 Conclusion and Future Prospects—The Fascination
of Organic Crystals and the Prospect for New
Asymmetric Reactions
Asymmetric chemistry using chirality that is naturally expressed by crystallization
of organic compounds was introduced from the viewpoint of asymmetric synthesis.
More than 160 years have passed since Pasteur separated sodium ammonium tartrate
crystals by hand to obtain optically pure compounds, but the attractiveness of such
crystals has yet to be exhausted, with new chemistry being developed every day.
Optical resolution of racemates utilizing the properties of conglomerates is important as a simple and inexpensive resolution method. Furthermore, in the case of rapid
racemization in the process of crystallization, total resolution by deracemization
from a racemate to one enantiomer becomes possible. We introduced examples of
incorporating synthetic processes for amino acids, medicines and agrochemicals, and
applications to axially asymmetric compounds. Deracemization by dynamic crystallization includes liquid–solid dynamic preferential crystallization, which promotes
crystallization from a supersaturated solution, and Viedma ripening by asymmetric
amplification in solid–solid form, which is being developed in new reaction systems.
In addition, the asymmetric synthetic process combining a reaction that generates a
chiral center from a prochiral substrate with dynamic crystallization is a phenomenon
in which chirality is manifested and amplification occurs only by reaction in solution
and crystallization. This method is expected to be developed for a variety of reaction
systems. However, the above-mentioned methods are only applicable to chiral crystals and conglomerates, and chiral crystallization is the largest bottleneck. Future
developments such as technology that can arbitrarily control the crystal structure
and chirality, and prediction of crystal structure due to advances in computational
chemistry are eagerly anticipated.
References
1. Sheldon, R.A.: Chirotechnology: Industrial Synthesis of Optically Active Compounds. CRC
Press, New York (1993)
2. Collins, A.N., Sheldrake, G.N., Crosby, J.: Chirality in Industry: The Commercial Manufacture
and Applications of Optically Active Compounds. Wiley, New York (1992)
3. Polenske, D., Lorenz, H., Seidel-Morgenstern, A.: Potential of different techniques of preferential crystallization for enantioseparation of racemic compound forming systems. Chirality
21, 728–737 (2009)
4. Collet, A.: Separation and purification of enantiomers by crystallisation methods. Enantiomer
4, 157–172 (1999)
5. Yoshioka, R.: Optical resolution and crystallization-induced asymmetric transformation of
amino acids and pharmaceutical intermediates. Top. Curr. Chem. 269, 83–132 (2007)
6. Sakamoto, M, Mino, T.: Asymmetric reaction using molecular chirality controlled by spontaneous crystallization. In: Y. Mastai (ed) Advances in Crystallization Processes, InTech,
pp. 59–80, (2012)
453
21.4 Conclusion and Future Prospects—The Fascination
of Organic Crystals and the Prospect for New
Asymmetric Reactions
Asymmetric chemistry using chirality that is naturally expressed by crystallization
of organic compounds was introduced from the viewpoint of asymmetric synthesis.
More than 160 years have passed since Pasteur separated sodium ammonium tartrate
crystals by hand to obtain optically pure compounds, but the attractiveness of such
crystals has yet to be exhausted, with new chemistry being developed every day.
Optical resolution of racemates utilizing the properties of conglomerates is important as a simple and inexpensive resolution method. Furthermore, in the case of rapid
racemization in the process of crystallization, total resolution by deracemization
from a racemate to one enantiomer becomes possible. We introduced examples of
incorporating synthetic processes for amino acids, medicines and agrochemicals, and
applications to axially asymmetric compounds. Deracemization by dynamic crystallization includes liquid–solid dynamic preferential crystallization, which promotes
crystallization from a supersaturated solution, and Viedma ripening by asymmetric
amplification in solid–solid form, which is being developed in new reaction systems.
In addition, the asymmetric synthetic process combining a reaction that generates a
chiral center from a prochiral substrate with dynamic crystallization is a phenomenon
in which chirality is manifested and amplification occurs only by reaction in solution
and crystallization. This method is expected to be developed for a variety of reaction
systems. However, the above-mentioned methods are only applicable to chiral crystals and conglomerates, and chiral crystallization is the largest bottleneck. Future
developments such as technology that can arbitrarily control the crystal structure
and chirality, and prediction of crystal structure due to advances in computational
chemistry are eagerly anticipated.
References
1. Sheldon, R.A.: Chirotechnology: Industrial Synthesis of Optically Active Compounds. CRC
Press, New York (1993)
2. Collins, A.N., Sheldrake, G.N., Crosby, J.: Chirality in Industry: The Commercial Manufacture
and Applications of Optically Active Compounds. Wiley, New York (1992)
3. Polenske, D., Lorenz, H., Seidel-Morgenstern, A.: Potential of different techniques of preferential crystallization for enantioseparation of racemic compound forming systems. Chirality
21, 728–737 (2009)
4. Collet, A.: Separation and purification of enantiomers by crystallisation methods. Enantiomer
4, 157–172 (1999)
5. Yoshioka, R.: Optical resolution and crystallization-induced asymmetric transformation of
amino acids and pharmaceutical intermediates. Top. Curr. Chem. 269, 83–132 (2007)
6. Sakamoto, M, Mino, T.: Asymmetric reaction using molecular chirality controlled by spontaneous crystallization. In: Y. Mastai (ed) Advances in Crystallization Processes, InTech,
pp. 59–80, (2012)