Using 2-diazo-3,3,3-trifluoropropanoate as a nontraditional two-carbon reaction partner, a Rh(III)-catalyzed defluorinative [4 + 2] annulation for the synthesis of 1,3,4-functionalized isoquinolines was developed. The reaction proceeds by sequential C-H carbenoid insertion, dual C-F bond cleavage/annulation, and N- to O-sulfonyl migration. The resultant products were converted to diverse 1,3,4-trisubstituted isoquinolines based on the functionalization of the newly installed 1-sulfonate, 2-fluoro functional handles, and/or remaining ester motif.