Efficient synthesis of 2H & 13C labeled benzaldehydes via regio-selective formylation

Benzaldehydes are important building blocks in synthetic organic chemistry that have wide applications for the synthesis of natural products and pharmaceutical drugs. Herein we report a general synthetic methodology for the synthesis of highly functionalized 2H and 13C labeled benzaldehydes in transfer of isotopic purity >99% via regio-selective formylation. Regio-selective deprotonation of substituted benzene 1 with LDA/n-BuLi at −78 °C and treatment with DMF-d7 or EtO-13CHO led to the synthesis of 2-deutero-1,3-disubstituted benzaldehydes 2/4 in moderate to good yields. The synthetic methodology described represents a simple yet versatile route to functionalized formyl-deuterated, tritiated 13C and 14C labeled benzaldehydes.