Synthesis and Application of β-Substituted Pauson-Khand Adducts: Trifluoromethyl as a Removable Steering Group

摘要

The Pauson-Khand reaction (PKR) is a well-established methodology for the construction of cyclic and polycyclic structures containing five-membered rings. Since its discovery in 1973 this reaction has been widely used in organic synthesis. The intramolecular PKR has been extensively applied to build polycyclic compounds. In this case, both the stereo- and regioselectivity are controlled by the substrate. The intermolecular version of the reaction has been less exploited because of its smaller range of reactive alkenes, although it has the advantage that in many cases the stereochemistry can be controlled by the presence of either chiral auxiliaries (bound to the alkyne or the alkene) or chiral ligandsbound to the intermediate cobalt complex). However, one of the difficulties encountered with the intermolecular PKR is the control of the regiochemical outcome. While this control is achieved when dealing with terminal alkynes (in this case only the α-substituted cyclo-pentenone I is formed), with internal nonsymmetric alkynes the regiochemistry of the PK adducts depends on a combination of steric and electronic effects, which are difficult to predict (Scheme 1). In the absence of steric effects, electron-donating groups (EDGs) show preference for the α-position, whereas electron-withdrawing groups (EWGs) tend to displace to the β-position.However, recent studies have shown that the electronic effects are much less significant than previously described and can, therefore, be overcome by the steric effects.