Proximity Effects in Acid and Base‐Catalysed Ether Formation

Abstract

SummaryWhen heated with sodium ethoxide in ethanol 7-methylidenebicyclo [3.3.I]nonan-3-endo-01 (endo-1) is converted into 1 -methyl-2-oxa-adamantane (3). This reaction involves nucleophilic addition of a hydroxy group to an unactivated olefinic bond. Formation of the cyclic ether 3 also takes place when endo-1 is heated in aqueous ethanol. This electrophilic addition is strongly catalysed by weak acids and suppressed by weak bases. These unusual reactions proceed more slowly with 7-methylbicyclo [3.3.l]non-6-en-3-endo-o1 (endo-2) and can be ascribed to a proximity effect. This follows from the IR. and NMR. spectra of endo-1 and endo-2 which show strong intramolecular hydrogen (OH-n) bonding. The unsaturated endo-and exo-alcohols 1 and 2, respectively, undergo only em-complexation with silver ion.According to molecular models') the hydroxy groups in the endo-isomers of 7-methylidenebicyclo [3.3.1]nonan-3-01 (endo-1) and 7-methylbicyclo [3.3.l]non-6-en-3-01 (endo-2) are within van der Waals distance of the olefinic double bonds when the six-membered rings adopt the twin-chair 1 and chair-half chair conformation 22). Unusual interactions between these functional groups are therefore to be expected. In fact endo-1 undergoes facile cyclization to the cyclic ether l-methyl-2-oxa-adamantane (3) when treated with 25% sulfuric acid [3]3)4).In view of the anticipated strong intramolecular hydrogen bonds in endo-1 and endo-2 it was of interest to determine whether addition of a nucleophile would take place in the absence of an external acid. The n-bonded hydroxy group might serve as a sufficiently strong electrophilic catalyst for attack of external nucleophiles, such as water or an alcohol, leading to an addition product of type 4 and 5 ( S = H or alkyl).Furthermore, the presence of n-electrons in unactivated olefinic bonds renders them accessible to electrophilic attack, whereas strongly electron-withdrawing sub-') *) 3, 4,e.g. CPK Precision Molecular Models, Ealing Beck Ltd., Watford, England. Unsubstituted bicyclo[3.3. llnonane appears to prefer a distorted twin-chair conformation, 3-and 7-substituted derivatives a chair-boat conformation [ 11 [2]. Also when endo-1 is treated with CHzIz and the zinc-copper couple [4]. Numerous other intramolecular reactions of 3,7-substituted bicyclo[3.3.l]nonanes have been reported, e.g. [l-31 [5-91.