Chiral Auxiliary Approach for Gold(I)-Catalyzed Cyclizations

Two different classes of stereoselective cyclizations have been developed using a chiral auxiliary approach with commercially available [JohnPhosAu(MeCN)SbF6] as catalyst. First, a stereoselective cascade cyclization of 1,5-enynes was achieved using the Oppolzer camphorsultam as chiral auxiliary. In this case, a one-pot cyclization-hydrolysis sequence was developed to directly afford enantioenriched spirocyclic ketones. Then, the stereoselective alkoxycyclization of 1,6-enynes was mediated by an Evans-type oxazolidinone. A reduction-hydrolysis sequence was selected to remove the auxiliary to give enantioenriched beta-tetralones. DFT studies confirmed that the steric clash between the chiral auxiliary and alkene accounts for the experimentally observed diastereoselective cyclization through the Si face. The stereoselective gold(I)-catalyzed cascade cyclization of 1,5-enynes and alkoxycyclization of 1,6-enynes with chiral auxiliaries has been developed, affording, after hydrolysis, synthetically challenging enantioenriched ketones. This chiral auxiliary approach is an alternative to the use of complex chiral catalysts in gold(I)-catalyzed asymmetric cyclizations.image

Automated summary

This study presents two classes of stereoselective cyclizations using a chiral auxiliary approach. The first class involves the stereoselective cascade cyclization of 1,5-enynes using Oppolzer camphorsultam as chiral auxiliary, leading to the synthesis of enantioenriched spirocyclic ketones. The second class focuses on the stereoselective alkoxycyclization of 1,6-enynes mediated by Evans-type oxazolidinone, resulting in the formation of enantioenriched beta-tetralones after removal of the auxiliary.