Controlling the radical 5-exo-trig cyclization, and selective synthesis of seco-iso-cyclopropylfurano[e]indoline (seco-iso-CFI) and seco-cyclopropylthiophene[e]indoline (seco-CTI) DNA alkylating subunit of the duocarmycins

The free radical cyclization of benzofuran bromo-allylic chloride 6 in toluene produced an unpredicted mixture of 6-benzyloxy-N-t-Boc-3-(chloromethyl)furano[e]indoline (1) and 7-benzyloxy-N-Boc-3-(chloromethyl)furano[f]quinoline (2). DFT calculations indicated that the indoline radical (6B), formed from 5-exo-trig closure of intermediate 6A, was less polar than the corresponding quinoline radical (6C). Based on this result, we report herein that cyclization of chlorides 6–8 in a polar aromatic solvent consistently and exclusively produced the indoline product in good yield (74–83%).