Enantioselective synthesis of highly oxygenated acyclic quaternary center-containing building blocks via palladium-catalyzed decarboxylative allylic alkylation of cyclic siloxyketones.

Aurapat Ngamnithiporn,Michael D Bartberger,Toshihiko Iwayama,Brian M Stoltz

doi:10.1039/d0sc04383d

Abstract

The development of a palladium-catalyzed enantioselective decarboxylative allylic alkylation of cyclic siloxyketones to produce enantioenriched silicon-tethered heterocycles is reported. The reaction proceeds smoothly to provide products bearing a quaternary stereocenter in excellent yields (up to 91% yield) with high levels of enantioselectivity (up to 94% ee). We further utilized the unique reactivity of the siloxy functionality to access chiral, highly oxygenated acyclic quaternary building blocks. In addition, we subsequently demonstrated the utility of these compounds through the synthesis of a lactone bearing vicinal quaternary-trisubstituted stereocenters.

Highlights

Silicon-containing hetereocycles are an important class of organic molecules o en used in the context of temporary functional groups in the synthesis of natural products and drug molecules.[1]
We believe that utilization of the silicon functionality in the alkylation products would allow for the synthesis of enantioenriched acyclic quaternary stereocenters, a motif that still poses a signi cant challenge in organic synthesis.[9]
With the substrates in hand, our studies continued with an investigation of the palladium-catalyzed decarboxylative allylic alkylation (Table 1)

Summary

Introduction

Silicon-containing hetereocycles are an important class of organic molecules o en used in the context of temporary functional groups in the synthesis of natural products and drug molecules.[1]. Scheme 1 Enantioselective synthesis of cyclic siloxanes. An enantioselective method to access cyclic siloxanes bearing all-carbon quaternary stereocenters has not been reported to date.

Results

Conclusion