Crystallization-driven dynamic

Synthesis of Cell Adhesion Inhibitors via Crystallization-Driven Dynamic Transformations... 

Two approaches to BIRT-377 (1) are discussed. The focus is the stereoselective synthesis of tran -imidazolidinones such as 16 and cu-oxazolidinones such as 29d. The kinetic and thermodynamic factors governing the cis/trans selectivity in the formation of 16 and 29d were studied, and it was found that neither can assure complete selectivity in favor of either form. It was then found in both cases that a crystallization-driven dynamic transformation can produce, in a very efficient manner, the desired cis isomer in virtually 100% selectivity in the case of 29d, whereas only the tmns isomer is obtained in the case of 16. Self-regeneration of stereocenters is then applied to the alkylation of the enolates derived from 16 and 29d with p-bromobenzyl bromide, followed by routine transformations, to produce 1 in >99.9% ee via two separate processes. 

Angelin, M. Fischer, A. Ramstrom, O. Crystallization-induced secondary selection from a tandem driven dynamic combinatorial resolution process. J. Org. Chem. 2008, 73, 3693-3595. 

Chow, C.-E Fujii, S. Lehn, J.-M. Crystallization-driven constitutional changes of dynamic polymers in response to neat/solution conditions. Chem. Commun. 2007,42, 4363 365. 

Angelin M, Vongvilai P, Fischer A, Ramstrom O (2010) Crystallization driven asymmetric synthesis of pyridine P-nitroalcohols via discovery-oriented self-resolution of a dynamic system. Eur J Org Chem 6315-6318... 

Figure 2-122, The first dynamic molecular display of small molecules by Levinthal was driven by the Crystal Ball" [193, ...

For configurationally unstable carbanions , a (thermodynamically driven) equiUbration between diastereomeric isomers is the method of choice, if the difference in free energy is large enough (>2 kcabmol ). In rare cases, a dynamic kinetic resolution is possible by preferential crystallization of one diastereomer. 

In Fig. 11.3, we made a comparison between the binodals obtained from dynamic Monte Carlo simulations (data points) and from mean-field statistical thermodynamics (solid lines). First, one can see that even with zero mixing interactions B = 0, due to the contribution of Ep, the binodal curve is still located above the liquid-solid coexistence curve (dashed lines). This result implies that the phase separation of polymer blends occurs prior to the crystallization on cooUng. This is exactly the component-selective crystallizability-driven phase separation, as discussed above. Second, one can see that, far away from the liquid-solid coexistence curves (dashed lines), the simulated binodals (data points) are well consistent... 

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