Rhodium-Catalyzed Asymmetric Pauson-Khand Reaction To Synthesize Tricyclo[6.2.1.0^4,11] Undecanes

Chemists are committed to developing methods for preparing enantiomerically enriched compounds for the total synthesis of natural products or biologically active molecules.Chiral tricyclic[6.2.1.0^4,11]undecane scaffolds with multiple chiral centers are prevalent in a large number of sesquiterpenoids as key synthetic intermediates.Although the existence of various methods to synthesize these tricyclic skeletons,they often requires multiple steps.It is challenging to establish multiple chiral centers in these stepwise reactions.It will be a remarkable development to directly obtain this tricyclic fused rings in a way of completely enantio-controlled,diaster-control,step-economic and atomic economic.Recently,Diels-Alder reaction,Ni-catalyzed,Rh-catalyzed and Cu-catalyzed have been developed to enantioselectively synthesize tricyclic fused rings.However,these methods are limited to the 6-6-5 ring system,and the 6-5-5 ring system has rarely been developed.With the continuous increase of molecular diversity and complexity,novel transformations with excellent sterocontrol performance,different ring sizes and a wide range of applications are still in high demand.Pauson-Khand（PK）reaction is one of the most powerful tools for the preparation of cyclopentenone,which is structural units or key intermediates in the synthesis of complex molecules.Although several synthetic applications have demonstrated the high enantioselectivity of the reaction,the asymmetric PK reaction has been achieved only once in the total synthesis.This absence reflects the narrow substrate scope and difficult enantioselectivity control of the asymmetric PK reaction.The challenges for asymmetric PK reaction include the following:（i）the electronic properties of the ligands required for the olefin replacement metal-CO step and the oxidative cyclization step are opposite.（ii）the non-terminal alkene is reluctant to react.We envisioned that the asymmetric PK reaction of the alkynyl-tethered cyclohexadienone in the presence of CO will realize the one-step construction of a chiral tricyclic[6.2.1.0^4,11]undecane scaffolds.Here,we report a rhodium（I）-catalyzed enantioselective synthesis of tricyclo[6.2.1.0^4,11]undecanes with three contiguous chiral centers via desymmetrization Pauson-Khand-type reaction of alkynyl-cyclohexadienone.