Science of Synthesis

Joule, J. A., Science of Synthesis, (2001) 10, 395.

Most indole syntheses which involve making the 1—2 and 2—3 bonds in the same pot depend on the generation of a nucleophilic benzylic carbon to react, in conjunction with a nucleophilic nitrogen, with an electrophile (the future α-carbon) to generate the heterocycle. The most obvious way in which to achieve this is via a N,C-dianion then reaction with an ester, or equivalent.

Meeeeeeeee ee ee eeeeeeeee eeeee eeeee eeee e eeeeeeeeee ‌888‌ eeeeeee eeeeee eeeeeeeeeeeee, ee eee eeeeeeeee M-eeeeeeee eee ee eee eeeeeeee eeeeee, ee eeeeeeee eeee eeee e eeeeeee ‌888‌, eeeeeee ‌888‌ eeeeeeeee eeee eee eeeeeeeeeee eeee ee eeeee (‌Meeeee 88‌).[‌888‌–‌888‌]

‌Meeeee 88‌ Meeeeee eeee M,M-Meeeeeeeeee e-Meeee-M-eeeeeeeeeeeee[‌888‌–‌888‌]

Meeeeeeee, M,M-eeeeeeeeeeee ee e-eeeee-M-eeee-(eeeeeeeeeeeeee)eeeeeeee ‌888‌[‌888‌] eeeeee eee eeeeeeeee ee 8-eeeeeeeeeeeee eeeeeee ‌888‌ eee eeeeeeee eeee eeeeeeeeeeeeeeeee (‌Meeeee 88‌). Meeeeeeee eeeeeeee ee eeeee eeeeeeee eeee Meeeeee eeeeee eeeee ee eee eeeeeeeee ee M-eeee-eeeeeeeeeeeeee-eeeeeeeee 8,8-eeeeeeeeeeeee eeeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeee eee Meeeeeeeeeee ee M-eeee-Meeeeeeeeeeeee-Meeeeeeee e-Meeeeeeeeeeeeee[‌888‌]

e-(Meeeeeeeeee)eeeeeeee ‌888‌ eee eeee ee eeeeee eeeeeeeee ee eeee eeeeeee eeeee ee eeeeeeee eeee eeeeee eeee eeeeeee ‌888‌ (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeee eee Meeeeeeeeeee ee e-(Meeeeeeeeee)eeeeeeee [‌888‌]

Me eeeeeee eeeeeee, eeeeeeee eeee eeeee eee eee eeee ee eee eeee eeee eeee eee eeee ee eee eeee eee: M,8-eeeeeeeeeeeeeee (‌888‌) ee eeeeeeeeeeee eeeeeee eeee eeeeeeeeee eeeee eeee eeeeee eeeeeee, eeee eeeeeeee eee M-eeeeeeee eee eeeeeeee eeeeeeeeee (→ ‌888‌) ee eee eeeeeeee eeeeeeee; eeeee eeeeeeeee ee eee eeeeeeee eeeeee, eeeee M-eeeeeeeeeeeeeee eeeee ‌888‌ ee eeeee eeeeeeee-ee-eeeeeeee eeee eeeeeee eeeee eeee eeeeeeeee ee eeee eee 8-eeeeee-8M-eeeeeee ‌888‌ (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ 8-Meeeee-8M-eeeeeee ee Meeeeeeeee ee eee eeeee-Meeeee Meeee ee Meeeeee M-Meeeee-M-(e-eeeee)eeeeeeeeee[‌888‌]

Me eeeeeeeeeee eeeee eee eee eeeeeeeeee ee 8-eeeeeeeeeeeeee ‌888‌ eeeeeeee eeee-eeeee eeeeeeeeeeee ee eeeee eee(eeeeeeeeeeeeee)eeeee-eeeeeeeee eeeeeeee ‌888‌ → ‌888‌, eeeeeeee ee eeeeeeeeee eeee eeeeeeeeeeeeee eeeeeeeeeeeee ‌888‌, eeeeeeeee eeeeeee ee eeee eeeeeee ee eeee eee eeee eeeeeee ‌888‌ (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeee eeee 8-(Meeeeeeeeee)-M,M-eee(eeeeeeeeeeeeee)eeeeeeeeee[‌888‌]

8-(Meeeeeeeeeeeeeeeeeee)eeeeeeee ‌888‌ eeeee eeee eeeeeeee eeeeeeeee ee eeee eeeeeee ‌888‌ eeeeeeee ee eeee eeeeeee ee M8; eee eeeeeeee eeeeeeeeeee ee eeeeeeeeee ee eeeeee eeeeeeeeeeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ 8-Meeeeeeeeee eeee 8-(Meeeeeeeeeeeeeeeeeee)eeeeeeee eee Meeeeeee Meeeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

8M-Meeeee-8-eeeeeeee; Meeeeee Meeeeeeee:[‌888‌]

8-Meeeee-M-(eeeeeeeeeeeeee)eeeeeee (888 ee, 8.88 eeee) ee eeeeeee (88 eM) eee eeeee ee 8.8 M MeMe ee eeeeeee (8.88 eM, 8.88 eeee) eee eee eeeeeee eeeeeeee eee 8 e. Meeee eeeeeee ee −88°M, eeeeeeeeeeee-8(8M)-eee (8.88 e, 8.88 eeee) eee eeeee ee MMM (8 eM) eeee. Mee eeeeeee eee eeeeeee ee ee, ee MeMe eeeee, eeee Me8M ee eeeeeee eee eeeeeee. Meeeee, eeeeeeeeeee, eee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee) eeee eee eeeeeee; eeeee: 888 ee (88%); ee 88.8–88.8°M.

8-(eeee-Meeeeeeeeeeeee)-8-eeeeeee-8M-eeeeee (‌888‌, M8 = M; M8 = 8-MMe); Meeeeee Meeeeeeee:[‌888‌]

M-(eeee-Meeeeeeeeeeeee)-8-eeeeeee-8-eeeeeeeeeeeee (88.8 e, 88 eeee) ee MMM (888 eM) eee eeeeeee eeee 8.8 M e-MeMe (88 eM) ee −88°M eee eeeee 88 eee eee eeeeeee eeeeeee ee −88°M eeeeee 8 e. Mee eeeeeee eee eeeeeeee ee −88°M, eeee MMM (8.8 eM, 88 eeee) eeeee. Meeee 8 eee, M8M (888 eM) eee eeeee eee eee eeeeeee eee eeeeeeeee eeeee MeMMe (8 × 888 eM). Mee eeeeeeee eeee eeeeee eeee M8M, eeeee eee eeeeeee eeeeeeeeee. Me eee eeeeeee, 88 M MMe (8 eM) eee MMM (888 eM) eeee eeeee eee eeee, eeeee 8 eee ee ee, Me8M (888 eM) eee eeee ee eeeeeee eeeeeee. Mee eeeeeeee eeeeeee eee eeeeee eeee M8M, eeee eeeee, eeeee (Me8MM8) eee eeeeeeeeee. Meeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee) eeee eee eeeeeee ee ee eee; eeeee: 8.8 e (88%).

8-Meeeee-8-(8-eeeee)-8M-eeeeee (‌888‌, M8 = 8-Me; M8 = 8-Mee); Meeeeee Meeeeeeee:[‌888‌]

MeMe (8 eeee) eee eeeee ee 8,8,8,8-eeeeeeeeeeeeeeeeeeeee (8.88 e, 8 eeee) ee MMM (8 eM) ee −88°M, eeee, eeeee 8 eee, eee eeeeeeeee eeeeee eeee eee eeeee ee M-eeeeee-8-eeeeee-8-(eeeeeeeeeeeeeeeeeeee)eeeeeee (8.88 e, 8.8 eeee) ee MMM (8 eM) ee −88°M. Meeeee 8-eeeeeeeeeeeeee (8.88 e, 8.8 eeee) ee MMM (8 eM) eee eeeee eee eee eeeeeee eeeeeee ee 8°M. Meeee 88 eee, ee MM8Me eee eeeee eee eee eeeeeee eeeeeeeee eeee MM8Me8, eee eeeeeee eeeee (Me8MM8) eee eeeeeeeeee, eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 8:8) eeee eee eeeeeee; eeeee: 8.88 e (88%); ee 888–888°M.

8-Meeeee-8-eeeeee-8M-eeeeee (‌888‌, M8 = Me); Meeeeee Meeeeeeee:[‌888‌]

Me M,8-eeeeeeeeeeeeeee (‌888‌; 8.8 e, 88 eeee) ee MMM (88 eM) eeeee eeeee eee ee −88°M eee eeeee 8.8 M MeMe ee eeeeee (8.8 eM, 88 eeee). Mee eeeeeee eee eeeee ee 8°M eeeee MM8 eee eeeeee eeeeeee eee eeee eee 8 eee. Mee eeeeeee eee eeeeeeeeee eeeee eeeeeee eeeeeeee, MMM (88 eM) eeeee eeeee eeeee eee eee eeeeeeeee eeee eeeee ee −88°M eee eeeeeee eeee 8.8 M MeMe ee eeeeee (8.8 eM, 88 eeee) eeeeeeee eee eeeeeee ee eeee ee −88°M eee 88 eee. Mee eeeeeee eee eeeeeeee ee −88°M eee eeeee eeeeeeee (8.88 e, 88 eeee) ee MMM (8 eM) eeeee. Mee eeeeeee eee eeeeeee ee eeee ee ee eee e eee eeeee. Meeeeeeeeee eee eee eeeeeeee ee 8 M ee MMe (88 eM) ee 8°M eeeeeeee ee eeeeeeeeeeeeee eeee MeMMM8 eee eeeeeeeeee eeee MM8Me8 eee eeeeeeeeeee eeee eee eeeeeee; eeeee: 8.88 e (88%); ee 88–888°M.

8-Meeeee-8M-eeeeee (‌888‌, M8 = M; M8 = Me); Meeeeee Meeeeeeee:[‌888‌]

e-Meeeeeeee (8.8 e, 88 eeee) ee MMM (88 eM) eee eeeee ee 8.8 M MeMe (88 eM, 88 eeee) ee 8°M. Mee eeeeeeeee eeeee eeeeeeeeee eee eeeeeee eee 8 e ee 8°M eeee MMMMe (88.8 e, 888 eeee) eee eeeee eee eee eeeeeee eeeeeee ee ee eee 8 e. Meeee eeeeeeeeee, eee eeee eee eeeeeeeeee eee eee eeeeeee eeeeeeeee (ee 888–888°M/88 Meee) ee eeee 8-eeeeee-M,M-eee(eeeeeeeeeeeeee)eeeeeee; eeeee: 8.88 e (88%); eeeeeeeee eee.

8-Meeeee-M,M-eee(eeeeeeeeeeeeee)eeeeeee (8.8 e, 8.88 eeee) eee MMM (8.88 e, 8.8 eeee) eeeeeeee eeee MMMM (88 ee) eeee eeeeee ee eeeeee ee MMe8 (88 eM). Mee eeeeeeeeeeee eeeeeeeeeee eee eeeeeeee eee eee eee eeeeeeee eeeeeeeeee ee eeee e eee eeeeeee eeeee eee eeeeeeeee (ee 88–88°M/8.88 Meee) ee eeee 8-(eeeeeeeeeee)-M,M-eee(eeeeeeeeeeeeee)eeeeeee ee e eeeee eeeeee eee; eeeee: 8.88 e (88%).

8-(Meeeeeeeeee)-M,M-eee(eeeeeeeeeeeeee)eeeeeee (8.8 e, 8.8 eeee) ee MMM (8 eM) eee eeeee eeeeee ee 8°M ee eeeeeee eee Me eeee (8.8 e, 8.8 eeee) eeeeeeeee eeee 8,8-eeeeeeeeeeeee. Meeee eeeeeeee eee 8 e, eee eeee eee eeeee ee e eeee (−88°M) eeeeee ee eee MeMe (8.88 e, 8 eeee) eee MeMM (8.88 e, 8.8 eeee) ee MMM (8 eM). Mee eeeeeee eee eeeeeee ee −88°M eee eeee eeeeeeee ee −88°M eeee MeMe (888 ee, 8.8 eeee) ee MMM (8.8 eM) eee eeeee eee eee eeeeeee eeeeeee ee, eeee eeeeeeeeee ee −88°M eee 88 e. Mee eeeeeee eee eeeeee eeee eee. ee MM8Me eee eeeeeee eeeeeeeee eeee MM8Me8, eeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/Me8M/MM8 8:8:eee eeeee) ee eeee eee eeeeeee; eeeee: 888 ee (88%); ee 888–888°M.

References