Convergent Synthesis Of Bicyclo[4.1.0]Heptane Through Three-Component Coupling Of 1,6-Enynes,α-Diazo Sulfonium Triflate,and H₂O/D₂O

As a unique and important structure motif,the cyclopropane ring is widely prevelant in many biologically active natural products and pharmaceuticals.To this end,numerous efforts have been devoted to developing an efficient and economical synthesis of cycloprapane derivatives.Common strategies of preparing cyclopropane have suffered from the use of expensive transition metal catalysts,stoichiometric alkali metal or moisture and air sensitive organometallic reagents.For example,Freund reaction,Wurtz reaction,Kulinkovich reaction and Simmons-Smith reaction.It is of great mechanistic innovation and synthetic significance to develope a mild photoredox strategy to produce cyclopropane derivatives.On the other hand,D-labeling provides a powerful approach for further modification of activity based on known properties of the original structure,selective incorporation of deuterium atoms onto organic moieties for screening of drug candidates and isotope labeling purposes has received broad attention.However,traditional methods for the synthesis of deuterated compounds often require transition-metal catalysts,and expensive deuterium source.Furthermore,selective styrene deuteration method via radical pathway remains undeveloped.Therefore,we used cheap and readily available D₂O as the deuterium source to synthesize deuterated alkenes containing cyclopropane backbone based on radical process,which possess high application value.In summary,we developed a highly diastereoselective protocol for the convergent synthesis of azabicyclo[4.1.0]heptane through three-component coupling of enynes,α-diazo sulfonium triflate,and water.At the same time,we used D₂O as the deuterium source to synthesize deuterated alkenes containing cyclopropane motif with high deuteration rate.The reaction has the characteristics of simple operation and high atom economy.A total of 36 products were synthesized,including 5 deuterated products.The structures of the starting materials and products were characterized by NMR,IR,HRMS and X-ray.