Lewis-Acid-Catalyzed Dearomative [4π + 2σ] Cycloaddition of Bicyclobutanes with Isoquinolinium Methylides for the Synthesis of Ring-Fused Azabicyclo[3.1.1]heptanes
Qin Jiang, Jianyang Dong, Xuechen Zhou, Huijuan Liao, Zhou Juan, Dong Xue
Abstract
Dearomative cycloadditions are valuable for efficiently generating three-dimensional molecular complexity. However, despite recent reports of cycloadditions of bicyclobutanes (BCBs) for the synthesis of aza-bicyclo[3.1.1]heptanes (aza-BCHeps), which are bioisosteres of meta -substituted aza-arenes, dearomative cycloaddition of BCBs with N -heteroarenes for the synthesis of ring-fused aza-BCHeps has yet to be achieved. Herein, we disclose a method for Lewis acid–catalyzed [4π + 2σ] cycloaddition of isoquinolinium methylides with BCBs, which furnished a diverse array of previously inaccessible ring-fused 3-aza-BCHeps. We demonstrated the synthetic utility of the method by carrying out scaled-up reactions and transforming the products.