Cyclodextrin, diastereoselectivity

Photodecarboxylation of NSAIDs Inside Cyclodextrin Diastereoselective Photodecarboxylation of 2-Phenylpropionic Acid in Zeolite Medium Photolysis of Ibuprofen and the Methyl Ester of Naproxen 64.5 Conclusion.65-11... 

In a search for more effective approaches to the problem of stereoselective dioxygenation, alternative methods have been developed. While the inclusion of alkenes and O2 within a chiral cyclodextrin cavity furnished hydroperoxides with modest ee values, neighboring stereocenters and chiral auxiliaries could induce highly stereoselective dioxygenation. In 1987 Kropf and Reichwaldt, and three years later Adam and coworkers reported on the photooxygenation of phenyl-substituted alkenes 36 producing allyUc hydroperoxides 37 and 38 with high diastereoselectivity (dr 80/20). In the best example... 

A remarkably high diastereoselective excess was obtained in the addition of the anion of (S)-(-)-methyl 1-naphthyl sulfoxide to n-alkyl phenyl ketones. The sulfoxide was prepared in optically pure form by oxidation of the complex of methyl 1-naphthyl sulfide and 13-cyclodextrin with peracetic acid followed by crystallization. Desulfurization of the adducts provided enantiomerically pure tertiary alcohols (393]. 

Cyclodextrins have been covalently modified for catalytic oxidation, such as compounds 57, 62-65 (Schemes 3.14 to 3.16) [44, 45]. Enantioselective epoxidation of styrene derivatives, and carene using 20-100 mol% of the CD-ketoester 57 has been achieved. The inclusion-complex formation was confirmed by aH NMR titration experiments, confirming the 1 1 substrate catalyst stoichiometry under the reaction conditions. In the oxidation of carene, NOE and ROESY experiments showed different behavior according to the size of the R group (Scheme 13.14). Evidence was found for the formation of inclusion complexes with compounds 58 and 59. On the other hand, compounds 60 and 61 proved to interact with the catalyst via a tail inclusion vide infra). The increased diastereoselectivity observed with compounds 58 and 59 might be explained by a closer proximity to the covalently linked dioxirane. 

Another method used in the diastereoselective synthesis of isoxazo-lines involved reactions of the iron complexed trienes (115) with nitrile oxides to give the cycloadducts (116) and (117) in a ratio of ca. 9 1 (Scheme 53) (89TL6517). There have been reports on the use of baker s yeast in the enantioselective synthesis of isoxazolines from 4-vinyIpyridine and arylnitrile oxides, and of the enhancement of that selectivity using jS-cyclodextrin (90TL3201 92PACI141). 

In other reports, /i-cyclodextrins have been used to induce asymmetry in borohydride reduction of ketones, a diastereoselective reduction has been controlled by a n-allyltricarbonyliron lactone tether , a phosphinamide has been combined with a dioxaborolidine unit as an activated, directed catalyst for ketone reduction, reductive amination using benzylamine-cyanoborohydride converts 3-hydroxy ketones into syn-1,3-amino alcohols, l-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propan-1 -one has been reduced diastereoselectively, and production of chiral alcohols via (i) Itsuno-Corey and Brown procedures and (ii) lithium aluminium hydride modified by chiral nucleophiles has been reviewed. 

With catalytical amounts of chiral hosts hopefully enantio- and diastereoselective syntheses can be carried out. Regioselective reactions using cavity-enclosed guests have been already achieved using the cyclodextrins. This can most certainly be mimicked by synthetic hosts which are tailor-shaped to meet the specific problem. 

Figure 3.3 Complementary diastereoselectivity in the acylation of ft-cyclodextrin with the acid chloride of Ibuprofen and in the hydrolysis of the corresponding cyclodextrin ester ...

Inoue et al, reported the intramolecular [4 + 4] photocycloaddition of 6A,6C-bis(2-anthracenecarboxylate) ester of a-cyclodextrin (a-CD) in water, which gave the antz-head-to-head cycloadduct (after base hydrolysis) in highly regio- and enantioselective manner in the presence of y-cyclo-dextrin (y-CD). " Diastereoselective photocyclodimers of ester of (249) tethered to cellulose were obtained. Saigo et al., found the diastereo- and enantio-selective photocyclodimerization of (249) and (250) by use of enantiopure amphiphilic amino alcohols as a matrix. The enantioselective photoreaction of (249) was also reported by Shinkai et al. (25Ia,b). 

Several transition metal-based Lewis acid catalysts such as FeCls, CrCls, SnCU, or A1(03S0Ci2H25 )s were shown to be highly effective for aza-type Michael additions of amines such as indoles and pyrroles to a,/ -unsaturated compounds in aqueous solution. Addition of thiols to a,/ -unsaturated ketones in water was also catalyzed by SDS or /3-cyclodextrin. There is also a single report on the stereoselectivity of base-catalyzed Michael additions of thiols to nitro-olefins, where moderate diastereoselectivities were obtained (Scheme 8.13). 

Unfortunately, the diastereoselectivity of this reaction was not very good ( =3/2). Two models were offered to explain the rate-accelerating effect of P-cyclodextrin on this Diels-Alder reaction. These two models illustrating possible binding of p-cyclodextrin to intramolecular cycloaddition substrate 6.4 are shown below ... 

Hoshino, T., Ishida, K., Irie, T., Hirayama, E, Uekama, K., and Yamasaki, M., Reduction of pho-tohemolytic activity of benoxaprofen by P-cyclodextrin complexation,/. Incl Phenom.,6,415,1988. Lalitha, A., Pitchumani, K., and Srinivasan, C., Induced diastereoselectivity in photodecarboxylation of 2-phenylpropionic acid in faujasite zeolites. Tetrahedron, 57, 4455, 2001. 

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