Organized media inclusion complexes

The enantioselective inclusion complexation of the reaction product with lOa-c in aqueous medium is more efficient than that by the recrystallization method. For example, inclusion complexation of rac-65e with 10a,b did not occur by recrystallization from an organic solvent however, enantioselective complexation occurred efficiently in aqueous medium to give finally optically active 65e [12]. 

When a mixture of acetophenone 59a (1.0 g, 8.3 mmol), NaBH4 (0.94 g, 24.9 mmol), and water (10 ml) was stirred at room temperature for 2 h, rat-60a was produced. To the water suspension medium of rac-60a was added powdered 8a (3.87 g, 8.3 mmol), and the mixture was stirred for 3 h to give a 2 1 inclusion complex of 8a with (-)-60a.25 Inclusion complex formed was filtered and dried. Heating of the complex in vacuo gave (-)-60a of 95% ee (0.42 g, 85%). From the filtrate left after separation of the inclusion crystals, (+)-60a of 77% ee (0.35 g, 70%) was obtained by extraction with ether. By the same procedure, optically active 60a and 60c-g were prepared (Table 5). Solid state and solvent-free organic reactions have been well established25,263 0. Host-guest inclusion complexation in the solid state has also been reported.260... 

Host-guest inclusion complexations are usually carried out in organic solvents. As a green process, inclusion complexation can be performed in a water suspension medium or in the solid state. When the solid-state reaction in a water suspension medium is combined with an enantioselective inclusion complexation in the same water medium, a one-pot green preparative method for obtaining optically active compounds can be designed. In all these cases, enantiomers separated as inclusion complexes are recovered by distillation of the inclusion complex. When enantioselective inclusion complexation in the solid state is combined with the distillation technique, a unique green process for enantiomeric separation can result. 

Enantiomeric separations of bicyclic acid anhydride 69, lactones 70 and 71 and carboximides 72 and 73 by complexation with la-c in organic solvents were also successful (Table 3.3-3) [26]. These complexations can probably be carried out in a water suspension medium and hence be described as green processes. rac-Panto-lactone (74) was separated to produce (S)-(-)-74 of 99% ee in 30% yield by complexation with Ic [27]. Enantiomerically impure monoterpenes were purified by inclusion complexation with a chiral host compound. For example, (lS,5S)-(-)-verbe-none (75a) of 78% ee gave 99% ee enantiomer by complexation with la. By similar treatment of 75b of 91% ee with la as above, (lR,5R)-(-i-)-75b of 98% ee was obtained [28]. 

As mentioned before, the situation with MM calculations for large and very flexible molecules and their inclusion complexes, especially those involving CyDs, is different from that of the calculations for small and medium organic molecules. As discussed in Section 1.3, the former systems are highly flexible, and in the majority of cases they are studied either in the solid state (discussed in Chapter 7) crystallized with, even more mobile, solvent molecules or in solution. Therefore, all the objections raised in Sections 11.1 and 11.2 concerning comparison of the calculated MM results with the corresponding experimental data are also valid. 

Photocycloadditions are currently carried out in organic solvent" the study in pure water is stiU at an infancy stage even if there is great interest fi-om an environmental point of view. Most of the investigations carried out in aqueous medium concern [2 - - 2] processes and have been performed in the presence of micelles, CD, or in inclusion complexes, with the scope of favoring the molecular aggregation and therefore the regio- and stereoselectivity of the reaction. ... 

It was found that polar enantiomers could be separated with CDs in nonaqueous polar medium (e.g., 99% acetonitrile with 1% methanol). In this situation, inclusion complexation is unlikely, the solvent molecules occupying the CD cavity. The chiral mechanism involves H-bonds with the spatially oriented hydroxyl groups at the rims of the cavity and other interactions with the numerous asymmetric carbons of the glucopyranose units [36]. Polar organic mobile phases were tried with other CSPs and greatly extended their usefulness enhancing the role of H-bond interactions that were screened by water molecules. 

Unique inclusion behavior in reflection of the induced-fit binding mechanism is observed when an organic stock solution of octopus cyclophane 3 is injected into an aqueous medium containing ANS for the host-guest complexation study [17], A circular dichroism (CD) spectrum does not undergo any change for 3 upon complexation with ANS, indicating that the conformation around l-... 

Indeed, no substrate selectivity or increase in aldehydes ratio was observed when the reactions were conducted in the presence of a free / -CD analogous catalyst [PhN(CH2PPh2)2Rh(cod)]BF4. It must be pointed out that the reactions were performed in an aqueous organic two-phase system with an aqueous phase containing 30% DMF. The presence of an aqueous phase is supposed to force inclusion of the substrate in the cavity during the catalysis. In one-phase medium composed of DMF, the formation of transient adducts between substrate and a rhodium complex modified by a phosphinite /3-CD ligand also seems possible (Figure 19). ... 

---