Synthesis of (1R,3R)-3-[2-(Aminoethyl)-2,2-dimethylcyclobutyl]methanol and (1S,3R)-(3-Amino-2,2-dimethylcyclobutyl)methanol from (+)-Nopinone

Abstract

The title amino alcohols 6 and 7, which are of interest as intermediates in the synthesis of carbocyclic analogs of nucleosides, were synthesized from (+)-nopinone (8). Ring opening of a-isonitrosonopinone leads to a cyanoester which can be directly reduced to 6. Alternatively, a longer route from the lactam 12, one of the Beckmann rearrangement products of 8, leads also to 6, in a higher overall yield. Besides this the isomeric lactam 13 was transformed, upon hydrolytic opening, oxidative degradation of the lateral chain and reduction, into 7.