Scaffold Editing of Cubanes into Homocubanes, Homocuneanes via Cuneanes

Abstract

The selective synthesis of cage‐type hydrocarbons through the editing of the highly symmetric molecule cubane can be anticipated as one of the efficient approaches. In this paper, we identify a catalyst that facilitates the efficient scaffold isomerization of cubanes into homocubanes. This approach, which involves the direct synthesis of homocubanol esters, is promising as a novel method for the synthesis of phenoxy bioisosteres. Additionally, we observed that the isomerization of 1,4‐bis(acyloxymethl)cubane results in the generation of both D2‐ and C2‐symmetrical bishomocubanes. The same catalyst was also applied to the isomerization of acyloxymethylcuneanes, producing homocuneanol esters.

How to Set the “Chirality” of Polyhedral Small Molecule Hydrocarbons: Decoration and Editing of Cubane Skeleton

“…Recently, we have discovered that the rearrangement to homocubane proceeds extremely efficiently when a catalytic amount of benzoyl triflate (available from silver triflate and benzoyl chloride in situ) was applied to acyloxymethyl cubane, which can be easily derived from cubane carboxylic acid ester. [27] The reaction showed good functional group tolerance, and it can be stated that a highly effective catalyst for this ringexpansion type of scaffold editing has been found (Scheme 10). However, it must be noted that the homocubanes generated from achiral 1,4-disubstituted cubanes are still achiral molecules.…”

“…As shown in Scheme 14, treatment of cuneane derivatives 28 were treated with a catalytic amount of benzoyl triflate gave the corresponding homocuneanes 29. [27] This method can be considered superior for utilizing acyloxysubstituted cage hydrocarbons as optically active substances.…”