Inclusion crystals reactions

When a solution of 10a and 11 in ether was kept at room temperature for 12 h, a 2 1 inclusion complex of 10a and 11 was obtained as colorless prisms (m.p. 134-137 °C) in 72% yield. When a powdered mixture of the inclusion crystal and 7 was kept at room temperature in the solid state for 3 days, (+)-trans-1,2-dibromocyclohexane (12) of 12% ee was obtained in 56% yield by distillation of the reaction mixture [3]. Much more efficient enantioselective reactions in the solid state are described in Sect. 6. 

Similar irradiation of the 1 1 complex of tropolone ether 10b and host compound 8 led to photoproducts 11b (100% ee) and 12b (72% ee) in 12 and 14% yields, respectively. The authors interpreted these reactions as follows disrotatory electrocyclic closure of tropolone derivative 10 to afford photoproduct 11 in the inclusion crystals occurs in only one direction owing to the steric hindrance of host 8. This interpretation appeared to be reasonable based on an examination of the X-ray crystal structure study of the inclusion complex [18]. Formation of keto-ester 12 takes place by a more complex mechanism... 

Scheme 3 illustrates intriguing enantioselection in organic reactions that proceed in chiral crystalline lattices (5). When inclusion crystals of a ketone and an optically active diol host are treated with BH3-ethyl-enediamine complex, the optically active alcohol is obtained in... 

Intramolecular [2 + 2] photocyclization reactions of 2- /V-(2-propcnyl)amino]cy-clohex-2-enones (67) are also controlled enantioselectively by carrying out irradiation in inclusion complex with a chiral host compound. When inclusion crystals of 67 with 12 are irradiated in the solid state, optically active 9-azatricyclo[5.2.1.0]-decan-2-ones (68) were obtained in the chemical and optical yields indicated in Table 3 [30],... 

Photocyclization reaction of the V-(aryloylmcthyl)-8-valerolactams (80) occur stereoselectively and enantioselectively in their inclusion crystals with optically... 

When chemical reactions are carried out in inclusion complexes, reactions can proceed selectively due to template control effects caused by the host compound. In some cases, reaction occurs only in the inclusion complex, but not in solution, since molecules can be arranged in the appropriate positions for reaction in an inclusion crystal. When an optically active host compound is used, enantiose-lective reactions can be accomplished. For some time we have been studying such selective reactions in inclusion complex crystals in the solid state. However, these reactions have already been published in the book Organic Solid State Reactions [1], In this present chapter, some representative topics and some recent new results of selective thermochemical and photochemical reactions in inclusion crystals are briefly summarized. 

When a mixture of powdered ketone and NaBH4 is kept at room temperature, reduction of the ketone occurs to give the corresponding alcohol [2], When the reaction is carried out in inclusion crystals containing a chiral host compound, the optically active alcohol can be obtained by enantio-control of the reaction by the chiral host. For example, treatment of inclusion crystals of acetophenone (2a) or o-methylacetophenone (2b) and (S,S)-(-)-1,6-bis(o-chlorophenyl)-1,6-diphenylhexa-2,4-diyne-l,6-diol (1) [3] with powdered BH3-ethylenediamine complex (3) in the solid state gave 4a of 44 % ee (96 % yield) or 4b of 59 % ee (57 % yield), respectively [4],... 

Urbanczyk-Lipkowska, Zofia, Inclusion Complexation as a Tool in Resolution of Racemates and Separation of Isomers, 8, 1 see also Selective Reactions in Inclusion Crystals, 8, 173. 

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... 

Tanaka, K., Fujimoto, D., Oeser, T., Imgartinger, H., and Toda, F. (2000) Chiral Inclusion Crystallization of Tetra(p-bromophenyl)ethylene by Exposure to the Vapor of Achiral Guest Molecules A Novel Racemic-to-Chiral Transformation Through Gas-Solid Reaction, Chem. Commun., 413-414. 

Irradiation of the inclusion crystals of 2a (— )-4 suspended in H20 (containing hexadecyl trimethylammonium bromide) with stirring for 30 h gave a crude reaction product, photocyclization products (+ )-3a, as crystalline materials. This was... 

Reactions using chiral crystals of 2a were carried out using one single crystal in order to avoid the mixture of crystals with opposite chirality. The ee of several independent reactions was 56% on average [53]. The smaller value compared with that seen for the inclusion crystals must be due to weaker confinement of molecules in the crystal lattice compared with the case of the inclusion crystal, which has hydrogen bonds between host and guest molecules. 

In contrast to the number of intramolecular asymmetric hydrogen abstraction reactions using supramolecular approaches (Sec. IV.D.), intermolecular asymmetric hydrogen abstraction reactions have been scarcely reported. Only two examples are presented these occur in inclusion crystals of deoxycholic acid with ketones and crystals of cyclodextrin with acetophenone. 

Lahav, Leiserowitz and their coworkers have used inclusion complexes of deoxycholic acid to carry out asymmetric photochemical reactions. The authors reported that acetophenone forms a 2 5 crystalline channel inclusion complex with deoxycholic acid 22 as the host and that irradiation of the complex in th4 solid state leads to abstraction of a hydrogen atom by the acetophenone 23a from C5 of the steroid followed by coupling of the resulting radical pair to produce1 photoproduct 24 (Scheme 9) [216,219]. The authors were able to follow the course of the reaction by x-ray crystallography. Only one diastereomer of the product was obtained in the reaction. Aoyama et al. have studied the reaction of AT,N-dialkylpyruvamides in deoxycholic acid inclusion crystals (Scheme 10) [246], Solid-state irradiation of the inclusion complex of 22 and 25 gave the... 

Photocyclization of A -alkylfuran-2-carboxyanilides conducted in inclusion crystals with optically active tartaric acid-derived hosts led to the formation of tricyclic /ra r-dihydrofuran compounds with up to 99% ee <1996JOC6490, 1999JOC2096>. 2-(/>-Alkoxystyryl)furans underwent photocyclization to give 5-(3-oxo-(/ )-butenyl)benzo[ ]furans as the predominant isomers in undehydrated dichloromethane as shown in Equation (59). The intermediate alkyl enol ether could be obtained by performing the reaction in anhydrous benzene <1999OL1039>. 

Table 15-3. Yield, optical purity, and absolute configuration of the alcohol 9 obtained by solid-solid reaction of a 1 1 inclusion crystal of 8 and 10 with 2BHrNH2CH2CH2NH2.

Enantioselective Michael addition of thiols to enones is a useful reaction for the synthesis of sex pheromones [26] and terpenes [27]. For example, enantioselective Michael additions of thiols to 2-cyclohexenone (64) and maleic acid esters in the presence of chiral bases such as cinchona alkaloids [28, 29] and optically active amino alcohols [30, 31] have been reported. It has also been found that the enantioselective Michael addition reaction proceeds efficiently in an inclusion crystal... 

Although cis- (89) and tran. -7-hydroxy-l-azabicyclo[4.2.0]octan-2-one (90) can easily be obtained by photocyclization of V-(aryloylmethyl)-f5-valerolactam (88), this reaction proceeds nonstereoselectively to give a mixture of rac-89 and rac-90 [48]. Stereocontrol of this reaction is, however, easily accomplished by carrying out the reaction in an inclusion crystal with an optically active host compound such as 2 or 3. 

A suspension of powdered 1 1 inclusion complex of 88a with 2c (3.21 g) in water (120 ml) containing sodium alkylsulfate as a surfactant was irradiated under stirring at room temperature for 12 h. The reaction mixture was filtered to give optically active 89a in the optical and chemical yields indicated in Table 15-21 [49]. From aqueous solution, additional (+)-89a was isolated (Table 15-21). By the same procedure, 88b and 88c gave optically active 89b and 89c, respectively (Table 15-21) [49]. However, 88d was inert to irradiation in its inclusion crystal with 2c. 

Enantioselective intramolecular photocyclization reactions of enones as inclusion crystals with chiral host compounds proceeds very efficiently. Several examples of such reactions are described in this Chapter. 

Although the very useful synthetic route to rran.s-dihydrofuran derivatives (131) by photoreaction of the furan-2-carboxanilides (130) in MeOH has been established, the reaction gives rac-131 together with some other by-products [76]. To control the reaction and to produce optically active 131, the photoreaction of 130 was carried out in an inclusion crystal with 2. Although 130a did not form an inclusion crystal with 2a-c, 130b-f formed inclusion crystals in the ratios indicated in Table 15-24. Irradiation of these powdered inclusion crystals in the water sus-... 

Organic inclusion crystals are attractive substances from the viewpoint of the dynamics of molecular assemblies. The inclusion crystals comprise nanocomposites between host and guest molecules and exhibit supramolecular properties through non-covalent bonds [1], The host molecules provide molecular-level cavities where the guest molecules undergo intercalations and reactions. We have elucidated such dynamics by using the inclusion crystals of steroids and primary ammonium salts (Figure 26.1). 

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