Cis-Selective Double Spirocyclization via Dearomatization and Isomerization under Thermodynamic Control.

Spiro compounds have been considered key scaffolds for pharmaceutical applications. Although many synthetic methods exist for monospirocycles, fewer approaches are known for dispirocycles. Here, we report a highly cis-selective method for constructing a 5/6/5-dispirocyclic structure containing pyrrolidine and γ-lactam rings with various substituents from a series of N-arylpropiolamides. The high cis-selectivity would result from isomerization under thermodynamic control. Cis- and trans-diastereomers can be in equilibrium, favoring cis-adducts.

Rapid Access to Dispirocyclic Scaffolds Enabled by Diastereoselective Intramolecular Double Functionalization of Benzene Rings.

Here we describe the diastereoselective synthesis of (5r,8r)-1,9-diazadispiro[4.2.48 .25 ]tetradecatrienes via domino double spirocyclization of N-arylamide derivatives. This reaction can serve as a fast way to synthesize diazadispirocycles, which are found in the core structures of bioactive natural products. Product diversification via Suzuki-Miyaura cross coupling and application to the synthesis of 1-oxa-9-azadispiro[4.2.48 .25 ]tetradecatrienes were also conducted.