Solid enantioselective reaction

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. 

Enantioselective Br2 addition to cyclohexene (11) was accomplished by the solid-state reaction of a 2 1 inclusion complex of 10b and 11 with 7, although the optical yield was low (Sect. 2.1). However, some successful enantioselective solid-state reactions have been reported. For example, reaction of a 1 1 complex of 68 and acetophenone (64a) with borane-ethylenediamine complex (130) in the solid state gave the (i )-(+)-2-hydroxyethylbenzene (65a) of 44% ee in 96%... 

An enantioselective Wittig reaction was accomplished by the solid-state reaction of a 1 1 complex of 10b and 122 or 10c and 143 with 141, which gives... 

Much more efficient enantioselective solid-state reactions can be accomplished by photochemical reactions. Some new results are summarized in the following section. 

The most exciting enantioselective photochemical conversion of a a-oxoamide to a P-lactam has been found in the case of N,N-diisopropylbenzoylformamide (96) which gives P-lactam 97. In the photocyclization of plain 96 in the solid state, optically active P-lactam 97 of high optical purity was obtained in high chemical yield. Thus no optically active host compound is necessary for the enantioselective reaction 48>. 

In a related study, the same group investigated molybdenum-catalyzed alkylations in solution and on a solid phase [35], demonstrating that microwave irradiation could also be applied to highly enantioselective reactions (Scheme 7.15). For these examples, commercially available and stable molybdenum hexacarbonyl [Mo(CO)6] was used to generate the catalytic system in situ. The reactions in solution provided good yields (see Scheme 6.50). In contrast, the conversion rates for the solid-phase examples were rather poor. However, the enantioselectivity was excellent (>99% ee) for both the solution and solid-phase reactions. 

Toda et al. reported that the topotactic and enantioselective photodimerization of coumarin and thiocoumarin takes place in single crystals without significant molecular rearrangements [49]. Molecular motion needs to be called upon to explain the photochemically activated cycloaddition reaction of 2-benzyl-5-benzylidenecyclopentanone. The dimer molecules, once formed, move smoothly in the reactant crystal to form the product crystal [50]. Harris et al. investigated the reactivity of 10-hydroxy-10,9-boroxophenanthrene in the solid state and the mechanism of the solid-state reaction was characterized by both X-ray diffraction and thermal analysis [51]. It was demonstrated that the solution chemistry of 10-hydroxy-10,9-boroxophenanthrene is different from that in the solid state, where it undergoes dimerization and dehydration to form a monohydride derivative. 

Enantioselective Reactions in the Solid/Cas Reactor versus Liquid Systems... 

Solid enantioselective base catalysts have not been investigated systematically and at the moment only reactions 36 and 42 seem to be suitable for synthetic application. 

In a related study Hallberg el al. also investigated molybdenum-catalysed allylic alkylations in solution and on solid phase33 demonstrating that microwave irradiation could also be applied to highly enantioselective reactions (Scheme 7.13). 

Due to high efficiency and in some cases even enantioselectivity, solid state reactions have recently attracted considerable attention to various types of organic reactions [194-197]. The solid-state Michael reactions between 4-arylidene-3-methyl-l-phenyl-5-pyrazolones 267a-f and indole gave rea-... 

Until recently organic photochemistry has only partially focused on stereoselective synthesis, one of the major challenges and research areas in modern organic synthesis. This situation has dramatically changed in the last decade and highly chemo-, regio-, diastereo- as well as enantioselective reactions have been developed. Chemists all over the world became aware of the fascinating synthetic opportunities of electronically excited molecules and definitely this will lead to a new period of prosperity. Photochemical reactions can be performed at low temperatures, in the solid or liquid state or under gas-phase conditions, with spin-selective direct excitation or sensitization, and even multi-photon processes start to enter the synthetic scenery. 

Bromo-2-thioaryloxy-3-methylcyclohexen-l-one, 2a, is an achiral compound. Its conformation can be fixed in a chiral twisted form in the solid state, but it forms racemic crystals, and hence the solid-state reaction produces a racemic mixture of (—) and (+ )3a. A method for achieving an enantioselective reaction is to form an inclusion complex with a chiral host compound, (— )-(R,R)-( — )-fran.s-2,3-bis(hydroxy diphenyl methyl)-1,4-dioxa spiro-[4,4]nonane, ( — )-4. In a typical experiment, a benzene (5 mL) and hexane (5 mL) solution of (— )-4 and 2a left at room temperature for 24 h gave a 1 1 inclusion compound of (-)-2a and 4 as colorless crystals [38]. 

This new approach is valuable because strong molecular interactions often achieve chirally twisted molecular conformations and enantioselective reactions in the solid state, processes that may be relevant to the introduction of the homo-chiral biological world. Solid-state photochemistry and spectroscopy are promising research areas. 

The inclusion complex 26, shown in Scheme 11, has been used as a host by Toda and coworkers to carry out a number of enantioselective reactions [231]. For example, irradiation of a 1 1 host-guest assembly of a-tropolone methyl ether 27 and (S,S)-( — )-26, in the solid state gave (lS,5R)-( — )-28 of 100% ee. The authors state that the high stereoselectivity is a result of the steric hindrance to disrotatory ring closure from one direction due to the structure of the host. This leads to the formation of only one enantiomer of the product. More details on this topic are available in Chap. 13. 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

When the solid state reaction is carried out in an inclusion complex with an optically active host compound, an optically active reaction product is obtained by enantioselective reaction. This methodology is very effective for photoreactions. In some cases, a photoreaction which is inefficient in solution proceeds very efficiently as the inclusion complex. 

Only three enantioselective Wittig-Homer reactions using optically active reagents have been reported [17J. In comparison with these, the solid state reaction is much more simple and successful. 

Bromo-2-thioaryloxy-3-methylcyclohexen-l-one, 2a, is an achiral compound. Its conformation can be fixed in a chiral twisted form in the solid state, but it forms racemic crystals, and hence the solid-state reaction produces a racemic mixture of (—) and (+ )3a. A method for achieving an enantioselective reaction is to form an inclusion complex with a chiral host compound, (— — )-... 

Inserting the guest into the host can sometimes improve the selectivity of its reactions. The polymerization of 1,3-butadiene in urea crystals preferentially leads to the crystalline 1,4-trails polymer.55 Such solid-state reactions can improve the selectivity in many reactions.56 If performed with a chiral diol, the reaction can give products with high enantioselectivity (7.3). 

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