Chiral tropolone ether

There is also rapid development in the domain of standard silica-based zeolites. Their versatility can be extended by imprinting. For instance, Davis and Katz [15] recently successfully carried out imprinting and obtained a silica framework with pore walls anchoring three aminopropyl groups in cavities. Another achievement was reported by Ramamurthy, Schefer and coworkers [16]. The latter authors were able to obtain 90% diastereomeric excess of a product of the photochemical reaction in a commercially available zeolite containing chiral tropolone ether 433 in its pores. 

NaY zeolites modified with (— )-ephedrine or (— )-norephedrine showed even better performance in the photolysis of chiral tropolone ether 22c immobilized in the supercage, affording 23c in 90% de. In contrast, irradiation of 22c in solution or on a silica surface in the presence of enantiopure ephedrine or norephedrine gave 1 1 diastereomeric mixtures. 

Joy, A., Scheffer, J.R. and Ramamurthy, V. (2000) Chirally modified zeolites as readion media photochemistry of an achiral tropolone ether. Organic Letters, 2, 119-121. 

The ionic chiral auxiliary approach was also applied to the enantioselective photocylization of tropolone. Irradiation of salt crystals of tropolone ether carboxylic acid 29 with several chiral amines afforded the enantiomerically enriched secondary products 31 [52]. The best results were obtained with optically pure 1-phenylethylamine and l-amino-2-indanol, which gave optical yields in the 60-80% ee range depending on the extent of conversion. 

Tropolone ether 35 undergoes a disrotatory 4tt electrocyclic ring closure to yield the corresponding bicyclo[3.2.0] product 36 (Scheme 18) [284,285]. The chirality... 

With (+)-ephedrine as a modifier on NaY, an ee of 69 % for one of both enantiomers was obtained. With tropolone ethers already containing a chiral carbon atom, a diastereomeric excess of 90% was observed. 

Upon exposure to UV light, a-tropolone methyl ether (142), included within chirally modified Y zeolite, has been found to undergo 4 7r-electron disrotatory electrocyclic ring closure to afford " the bicyclic photo-isomer (143). 

In the above-discussed examples, a chiral inductor is used to induce chirality on the product of a reaction. In the absence of any specific interaction between a chiral inductor and a reactant, it is unable to force every reactant molecule close to the chiral agent. This is one of the main reasons for poor enantioselectivity. The 69% ee obtained in the case of tropolone phenylethyl ether/ephedrine/NaY (dry) despite this limitation is remarkable. In an effort to reduce this limitation and to maintain closeness between the chiral center and the reaction site, Ramamurthy et... 

Figure 45 Photocyclization of (S)-tropolone 2-methylbutyl ether within chirally modified NaY zeolites. The diastereomeric excess (%) and the isomer enhanced are shown on the HPLC traces. The first eluted isomer on the HPLC column is arbitrarily assigned 93.

Irradiation of (S )-tropolone 2-methyl butyl ether in solution yields a 4-electron electrocyclization product as a 1 1 diastereomeric mixture (Sch. 8) [106]. In solution the presence of the chiral auxiliary in proximity to the reactive center has no influence on the product stereochemistry. When irradiated within NaY zeolite, however, the same molecule affords the cyclized product in 53% diastereomeric excess. The restricted space of the zeolite supercage apparently forces communication between the chiral center and the reaction site. 

To examine the viability of CIM a number of photoreactions (electrocyclic reactions, Zimmerman (di-n) reaction, oxa-di-7i-methane rearrangement, Yang cyclization, geometric isomerization of 1,2-diphenyl-cyclopropane derivatives, and Schenk-ene reaction) which yield racemic products even in presence of chiral inductors in solution have been explored (Sch. 40) [187,189-200]. Highly encouraging enantiomeric excesses (ee) on two photoreactions within NaY have been obtained photocyclization of tropolone ethylphenyl ether (Eq. (1), Sch. 40) and Yang cyclization of phenyl benzonorbornyl ketone (Eq. (3), Sch. 40). The ability of zeolites to drive a photoreaction that gives racemic products in solution to ee >60% provides... 

Figure 1 An adsorption (top)-desorption (bottom) model for chiral induction on a zeolite surface, incorporating a reactant (tropolone alkyl ether, shown at the left), a chiral inductor (with four different substituents, at the right), and a cation (small ball on the surface). Tropolone s carbonyl and ether oxygens hydrogen-bond to chiral inductor, while its tt system interacts with zeolite s cation ion. ...

As briefly mentioned above, Takeshita et al. reported the first enantiodifferentiat-ing photoisomerization of tropolone derivatives to the optically active bicyclo[3,-2.0]heptadienones in 1980 [99], but the product ee and detailed chiral discrimination mechanism have not been determined until recently. Ramamurthy and coworkers reinvestigated the photobehavior of tropolone alkyl ethers in a-, (3-, and y-CDx cavities [102]. 

Irradiation of tropolone alkyl ether 22 (Scheme 14) led to a 4ir-disrotatory ring closure to yield bicyclo[3.2.0]heptadienone 23 with two chiral centers, while prolonged irradiations led to the formation of a secondary product 24 [76-78]. As the same photocyclization was performed in chirally modified zeolites, it is interesting to compare the asymmetric photochemical behavior of 22 in the distinctly different chiral confined media of zeolites and cyclodextrins. Even in the... 

Based on the observation that the best ee is obtained with bifunctional chiral agents (ephedrine, pseudoephedrine, norephedrine, and valinol see Scheme 43), we tentatively conclude that a multipoint interaction between the reactant molecule, the chiral inductor, and the zeolite interior is necessary to induce preferential adsorption of tropolone alkyl ether from a single enantiotopic face. The dependence of chiral induction (% ee) on the nature of cations (Scheme 45) suggests a crucial role of the cation present in the supercages in the chiral induction process. This is further strengthened by the results observed with wet and dry zeolites. The presence of water decreases chiral selectivity (Scheme 45). Water molecules... 

The most promising result was obtained when (S)-tropolone 2-methylbutyl ether (chiral ether) was irradiated within an ephedrine included NaY (Fig. 15) [295,306]. In the absence of ephedrine, diastereomer A is obtained in 53% diaste-reomeric excess. When (— )ephedrine was used as the chiral inductor, the same isomer was enhanced to the extent of 90%. The importance of this result becomes more apparent when one recognizes that irradiation in solution of the same com-... 

Figure 13 Adsorption of tropolone alkyl ether (TAE) on a surface. The chiral inductor may control the enantiotopic face by which TAE adsorbs. In the absence of a chiral inductor, TAE will show no preference for adsorption from either enantiotopic face. Note that the same chiral inductor interacts differently when the TAE adsorbs through different enantiotopic faces.

Figure 14 A cartoon representation of tropolone methyl ether and norephedrine included within a supercage under wet and dry conditions. The model helps to rationalize the difference in ee obtained under the two conditions. Dark circles represent the cations. Hydrogen bonding between the chiral inductor and interaction between the cation and TME are disturbed by water molecules.

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