[3+2] Cycloaddition of alkyl aldehydes and alkynes enabled by photoinduced hydrogen atom transfer

[3+2] Cycloaddition is a step- and atom-economic method for the synthesis of five-membered rings. Despite the great success of 1,3-dipolar cycloadditions, the radical [3+2] annulation of alkynes remains a formidable challenge. Herein, a photoinduced decatungstate-catalyzed [3+2] cycloaddition of various internal alkynes using abundant aliphatic aldehydes as a three-carbon synthon is developed, producing elaborate cyclopentanones in 100% atom economy with excellent site-, regio-, and diastereoselectivity under mild conditions. The catalytic cycle consists of hydrogen atom abstraction from aldehydes, radical addition, 1,5-hydrogen atom transfer, anti-Baldwin 5-endo-trig cyclization, and back hydrogen abstraction. The power of this method is showcased by the late-stage elaboration of medicinally relevant molecules and total or formal synthesis of (+/-)-beta-cuparenone, (+/-)-laurokamurene B, and (+/-)-cuparene. In contrast to the prevalence of 1,3-dipolar cycloadditions, radical [3+2] annulations of alkynes are underexplored. Here, the authors describe [3+2] cycloadditions of various internal alkynes with readily accessible aliphatic aldehydes via photoinduced decatungstate catalysis.

Automated summary

The authors developed an efficient [3+2] cycloaddition method using a photoinduced decatungstate catalyst. Abundant aliphatic aldehydes were used as the three-carbon synthon, allowing the synthesis of elaborate cyclopentanones under mild conditions.