Solvent-controlled regioselective C(5)-H/N(1)-H bond alkylations of indolines and C(6)-H bond alkylations of 1,2,3,4-tetrahydroquinolines with para -quinone methides.

Solvent-promoted and -controlled regioselective bond alkylation reactions of para -quinone methides ( p -QMs) with N -H free-indoline and 1,2,3,4-tetrahydroquinoline (THQ) under metal-free conditions have been developed. In the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as the solvent, 1,6-addition alkylation reactions of p -QMs with NH-free indolines and THQs efficiently gave C5-alkylated indolines and C6-alkylated THQs. Using catalytic amounts of HFIP in DCM, the reaction of indolines and p -QMs resulted in the alkylation of indolines at the N1-position. HFIP plays two roles in the reactions: converting the indoline and THQ into bidentate nucleophiles and activating the p -QMs to achieve the 1,6-addition alkylation via hydrogen bond clusters. The indoline and THQ act as a C-nucleophile due to the H-bond clusters between HFIP and the nitrogen atom, whereas upon using catalytic amounts of HFIP, the compounds act as an N -nucleophile. All alkylation products were transformed into the corresponding indoles and quinolines via oxidation in the presence of diethyl azodicarboxylate (DEAD). Furthermore, the synthetic utilities have been showcased with both the removal of the tert -butyl groups from the C5-alkylated indole products and submission to their Suzuki coupling reactions.