Due to the synthetically importance of chiral cyclic ether skeleton, catalytic asymmetric heteroatom Diels-Alder (HDA) reactions have been intensively explored since Danishefsky et al reported the first HDA reaction with aldehydes catalyzed by ZnCl<sub>2</sub> in 1982. A variety of chiral metal complexes as catalysts have been developed for HDA reaction of Danishefsky's diene with aldehydes. With the successful application of VANOL-derived chiral mesoborate catalysts on asymmetric epoxidation of aldehydes, we attempted to extend these catalysts to HDA reactions with aldehydes. This mesoborate type of catalysts has one boron center with two molecules of VANOL-derived ligands, serving as a Brønsted acid-assisted chiral Lewis acid (BLA) catalyst. By mixing one equivalent of borane dimethylsulfide with two equivalents of VANOL derivatives followed by removal of volatiles generated the active mesoborate catalyst. After screening different ligands, dienes and other reaction conditions, the HDA reaction between Danishefsky's diene and 4-bromobenzaldehyde was successfully optimized with 96% yield and 91% <i>ee</i> under –40 °C in toluene for 1 hour with 10 mol% catalyst. The substrate scope was studied and both electron-rich and electron-poor aromatic aldehydes were tolerated with excellent yield and enantioselectivities. Further study includes expending the substrate scope to aliphatic aldehydes and all ketones.

Catalytic asymmetric heteroatom Diels–Alder reactions catalyzed by VANOL-derived chiral borate catalysts

2019 Fall National Meeting

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