Regioselective Short Synthesis of Epiisoborneol Neopentyl Ether as Chiral Auxiliary: An Absolute Configuration Reset

Abstract

AbstractThe regio‐selective four step synthesis of (1S,2R,3S,4R)‐4,7,7‐trimethyl‐3‐(neopentyloxy)bicyclo[2.2.1]heptan‐2‐ol, as recognized efficient chiral auxiliary, is presented. The strategy based on opening of the key acetal 15 (=(2S,3aR,4S,7R,7aS)‐2‐tert‐butyl‐4,8,8‐trimethylhexahydro‐2H‐4,7‐methano‐1,3‐benzodioxole) thus circumvents the poor reactivity of the neopentyl electrophile under alkylation conditions. Following the same strategy, but using the unreported acetal 22 (=(2R,3aS,4S,7R,7aR)‐2‐tert‐butyl‐4,8,8‐trimethylhexahydro‐2H‐4,7‐methano‐1,3‐benzodioxole), the corresponding unreported bis‐endo alcohol 23 (=(1R,2R,3S,4S)‐3‐(2,2‐dimethylpropoxy)‐4,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐ol) could be isolated only in poor yield. An alternative regioselective synthesis, including an ultimate endo‐reduction remains to be found. Several erroneous chiroptical properties from the literature are corrected.