Modification of face selectivity by inclusion in cyclodextrins

Abstract

The photocycloadditions of 5-X-adamantan-2-011s (5-X-AD, where X = F, CI, Br, OH, Ph, and t-Bu) with fumaronitrile have been studied in acetonitrile and in aqueous solutions. When X is CI, Br, Ph, or t-Bu, irradiation of an aqueous solution containing P-cyclodextrin (b-CD) leads to a dramatic reversal in face selectivity compared to that found in acetonitrile and water; however, there is no significant change in product ratio compared to that found in aqueous solution in the presence of a- and r-CD. The effect observed with 8-CD is interpreted with the assumption that the carbonyl a face syn to the bulky 5-substituent is partially blocked by the torus of the host due to complexation of the AD and CD. IH NMR and concentration dependence studies provide support for this interpretation. Similar reversals of face selectivity upon complexation with P-CD are observed in the thermal reduction of these ketones by sodium borohydride. It is also noted that a much enhanced syn hydride delivery occurs in water as compared to organic solvents and that this enhancement vanishes upon cooling. Cyclodextrins (CDs) are cyclic oligosaccharides with internal cavities capable of forming complexes with hydrophobic organic and organometallic molecules in aqueous The inner diameters of the cavities are approximately 4.5 8, in a-CD, 7.0 A in @-CD, and 8.5 8, in y-CD.'v2 One of the most fascinating and far-reaching aspects of their chemistry is their ability to serve as enzyme models both in terms of substrate complexation and reactivity. Efforts have recently been made to modify CDs so as to enhance their catalytic power^.^-^ The physical chemistry of complexation by CDs has been extensively ~tudied.l-~ Recently the inclusion complexes of CDs were found to modify the intra- molecular photoreactions of guest molecules by imposing con- straints on the conformations and on the mobility of reactive intermediate~.~~ ~ However, their use in intermolecular thermal or photoreactions has been limited.9 Among the thermal bimolecular reactions studied1&13 in CDs, Diels-Alder reactions have received the most attention. Breslow and co-workers have found that Diels-Alder reactions are ac- celerated by 0-CD in aqueous solution.1° Their suggest a solvophobic congregation of the reactants in the cyclodextrin cavity. It has also been that the endo/exo ratios in several Diels-Alder reactions increase dramatically by the use of aqueous solutions and of added CDs. Sangwan's results included the first example of the significant influence of CDs on diastereo selectivities in Diels-Alder reactions. Ramamurthy, Eaton, and co-workers have exploited the use of CDs as host to examine photochemical and photophysical processes that occur in molecules complexed within them and to compare their behavior in aqueous solutions and in the solid state.'** Their studies dealt mostly with intramolecular events, with only a single molecule present in the CD cavity. We have previously reported that the photocycloadditions of 5-substituted adamantan-2-ones (5-X-ADs, Scheme I) with fu- maronitrile in acetonitrile, show anti/syn product ratios varying in the range of 53/47 to 60/40 (Table I).14 The anti-oxetanes, formed through syn-face attack of fumaronitrile, are the major products in all cases (Scheme 1). In an earlier paper one of us also rep~rtedl~ the general face selectivity in the addition of nucleophiles to 5-X-ADS. Since there is virtually no steric bias in the approach to the carbonyl group, this selectivity must be electronic in nature. It was furthermore noted that this selectivity is for the syn face when X is electron-withdrawing and for the anti face when it is a donor. This phenomenon was explained in terms of the hyperconjugation model of the transition state ad- vocated by Cieplak16 to explain the well-known preferred axial approach of nucleophiles toward the carbonyl group in cyclo- hexanones. According to this model, the energy of the activated ~~~~~~ ~~