Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 116.

The simplest method for the ring closure of o-alkynylarylamines is their reaction with bases; 2-(phenylethynyl)aniline forms 2-phenyl-1H-indole simply by heating with sodium amide in dimethylformamide.[‌412‌] Coupling o-bromo- or o-iodoarylamines or urethane derivatives thereof ‌467‌ with (trimethylsilyl)acetylene gives intermediates ‌468‌ which can be cyclized to heterocyclic ring unsubstituted indoles, simply by extended treatment with hot sodium ethoxide in ethanol[‌415‌] or even better by using potassium tert-butoxide in tert-butyl alcohol (‌Scheme 154‌).[‌416‌] Similarly, ethyl {5-(trifluoromethyl)-2-[(trimethylsilyl)ethynyl]phenyl}carbamate, gives 6-(trifluoromethyl)-1H-indole using sodium ethoxide in refluxing ethanol.[‌417‌] That the extra acidity of N-hydrogen in these urethanes is not necessary for base-promoted closure is illustrated by the conversions of N-benzyl 2-alkynylanilines into N-benzyl-1H-indoles using potassium tert-butoxide at room temperature.[‌418‌]

Mee eeeeeee ee 8-eeeeeeeeeeeeeee ee M-eeeeeeee 8M-eeeeeee (e.e., ‌888‌), e.e. eeee ee eeeee ee eee eeeee ee eee, eee ee eeeeeeee eeee eeeeeeeee eeeeeee ee eeee eeeeeeeee eeee-eeeeeeee, M-eeeeeeeeeeeeeeee-8-eee eeeee eee eeeeeee ee eeee eeee;[‌888‌,‌888‌] ‌Meeeee 888‌[‌888‌] eeee eeeeeeeeeee eeee eeee ee eeeeeee eeee, eeeee e eeeee eeeeeeeeeee eeeeeee.

‌Meeeee 888‌ Meeeeee eeee M-Meeeeeeeeeeee Meeeeeee[‌888‌,‌888‌]

Meee eee eeeeeeee eee eeeeeee ee e eeee-eeeeeeeeeeeeeeeeeee eeeee ee eeeeee eeeeeeeeee eeeee, ee ee eeeeeeee ee eeeeeee e eeeeeeee ee eeeeeee 8-eeeeeeeeeee eeeeeee eeee ee 8-eeeee-8M-eeeeee (‌888‌) eee ‌888‌ (‌Meeeee 888‌).[‌888‌]

‌Meeeee 888‌ Meee-Meeeeeeee Meeeeeeee ee 8-Meeee-8M-eeeeee eeee ee e-Meeeeeeeeeeeeeee[‌888‌]

Meee eeeee ee eeeeeee eee ee eeee eeee eeeeeeeeeee; 8,8′-eeeeeeeee (‌888‌) ee eeeeeeee ee eeeeeeee M-(eeeeeeeeeeeeee)-8-eeeeeeeeeee eeee (eeeeeeeeeeeeee)eeeeeeeee ee eeee ‌888‌, eeeeeeeee eeeeeeeeeeee ee eee eeeeeeeeeeeee M-eeeeeeee eeeeeeeee eeeee ‌888‌ eeeee eeee eeeeeeeee eeeeee eeee-eeeeeeeee eeeeee eeee eeeeeeeee ee eeeeee eeeeeeeee ‌888‌ (‌Meeeee 888‌).[‌888‌]

‌Meeeee 888‌ Meeeeeee-Meeeeeee Meee Meeeeee ee M-(Meeeeeeeeeeeee)-e-eeeeeeeeeeeeeeeee[‌888‌,‌888‌,‌888‌]

Meeeeee 8-, 8-, eee 8-eeeeeeeeeeee ‌888‌ eee ee eeeeeeee eeeeeeee eeee eee eeeeeeee 8-eeeeeeeeeeee, ee eeeeeeeeee M-eeeeeeeeeeeee, eeeeeeeeee ee eee eeeeee eeee eee eeeeeeeee­eeee­eeeeeeeeeeee, eeeeeeee eeee ee eeeeee, eee eeee eeeeeee ee eee eeeeee ‌888‌ eeeee eeeeeeeee eeee-eeeeeeee (‌Meeeee 888‌).[‌888‌]

‌Meeeee 888‌ Meeee-8M-eeeeeee eeee Meeee-8-eeeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 888‌

Meeeeeee ee eee eeee eee ee eeeeeeee eeeeee ee eeeeeeeeeeeeeeeeee eeeeeeee[‌888‌] (‌Meeeee 888‌) ee eeeeeee-eeeeeeeee [(eeeeeeeeeeeeeeee)eeeeeeeeeeeeeeeee eeeeeeee].[‌888‌]

‌Meeeee 888‌ Meeeeee ee Meeeeee Meeee Meeeeeee ee Meee[‌888‌]

‌Meeeeeeeeee 888‌

e Meee 88% ee eee 8-(eeeeeeeeeeeeee)eeeeee.

Meeeeeeeeeee Meeeeeeee

8-Meeeee-8-(eeeeeeeeeeeee)-8-(eeeeeeeeeeeeeee)-8M-eeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeeee eeeeeee eeeeeee ee eeeeeeee ee eee eee ee eeeeeee eeee eeeeeeee eee ee eeeeee eeeeeeeeeee ee eee eeeeeee.

MM (88 ee, 8.88 eeee) eee eeeeeeeee eeeee eeeee ee MMM (8 eM). M eeee ee 8,8-eee(eeee­eeeeeeeee)-8-(eeeeeeeeeeeeeee)eeeeeee (888 ee, 8.88 eeee) ee MMM (8 eM) eee eeeee eeeeeeee eee eee eeeeeee eee eeeeeee ee ee eee 88 e. Mee eeeeeeee eee eeeeeeee eeee M8M, eee eeeeeee eee eeeeeeeee eeee Me8M, eee eee eeeeeee eee eeeee (MeMM8). Mee eeeee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/Me8M 8:8) ee eeeeee eee eeeeee ee e eeeeee eeeee; eeeee: 88 ee (88%); ee 888–888°M.

8-Meeee-8M-eeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeeee ee eeee-eeeeeeeeeeee eeeee eeeeeeeeeee eeee eeeee eee eee eeeeee ee eeeee eee.

M eeeeeee ee 8-eeeee-M-(eeee-eeeeeeeeeeeeee)eeeeeee (‌888‌; 8.8 e, 8.8 eeee), (eeeeeeeeeeeeee)eeeeeeeee (8.88 eM, 8.8 eeee), MeMe8(MMe8)8 (888 ee, 8.8 eeee), MeM (88 ee, 8.8 eeee), eee Me8M (88 eM) eeee eeeeeee eeeeeeee eee 88 eee. M8M (88 eM) eee Me8M (88 eM) eeee eeeee eee eee eeeeeee eee eeeeeeee eeeeeee Meeeee. Mee eeeeee eeee eeeeeeeee, Me8M eee eeee eee e eeeeeee eeeeeeeeee, eee eee eeeeeeee eeeeeeee eeeeee eeee eeeeee eeee eeeee, eeeee (MeMM8), eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeeee ee eeeeeeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee 8:88) ee eeee eeeeeeee, eeeee eee eeeeeeeee (888°M/8 Meee) ee eeee M-(eeee-eeeeeeeeeeeeee)-8-[(eeeeeeeeeeeeee)eeeeeee]eeeeeee (‌888‌) ee e eeee eeeeee eeeeee; eeeee: 8.88 e (88%).

8.88 M e-MeMe ee eeeeeee (8.8 eM, 8.8 eeee) eee eeeee ee e eeee ee M-(eeee-eeeeeeeeeeeeee)-8-[(eeeeeeeeeeeeee)eeeeeee]eeeeeee (‌888‌; 8.8 e, 8.8 eeee) ee Me8M (8 eM) ee -88°M eeeee eeeee. Meeee eeeeeeee eee 8 e, eee eeee eee eeeeee ee -888°M, 8,8-eeeeeeeeeeeee (8.88 eM, 8.8 eeee) eee eeeee, eee eee eeeeeee eee eeeeeee ee ee. Meeee (88 eM) eee eeeee eee eee eeeeeee eee eeeeeeeee eeee Me8M (8 × 88 eM). Mee eeeeeeee eeee eeeeee eeee eeeee (88 eM), eeeee (MeMM8), eee eeeeeeeeeeee ee eeee e eeeeeee, eeeee eee eeeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee 8:888) eeeeeeeee eeeeeeee eeeee eeee 8-eeeee-M-(eeee-eeeeeeeeeeeeee)-8-[(eeeeeeeeeeeeee)eeeeeee]eeeeeee (‌888‌) ee eeeeeeeeeeeeeee (eeeeee); eeeee: 8.88 e (88%); ee 88–88°M.

Meeeee eeeeeeeee eee eeeeeeee ee eeeeeee 8-eeeee-M-(eeee-eeeeeeeeeeeeee)-8-[(eee­eeee­eeeeeee)eeeeeee]eeeeeee (‌888‌; 8.88 e, 8.8 eeee) eeee e-MeMM (8.88 e, 8.8 eeee) ee e-MeMM (8 eM) eee 8 e. Mee eeeeeee eee eeeeeeeeee eeeee eeeeeee eeeeeeee, M8M (88 eM) eee eeeee, eee MM8Me8 (8 × 88 eM) eee eeee ee eeeeeee eee eeeeeee eeeeeeee, eeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee 8:8); eeeee: 88 ee (88%); ee 88–88°M.

8-Meeee-8M-eeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

Mee eeeeeeee ee 8-eeeee-M-(eeeeeeeeeeeeee)eeeeeee (8.88 e, 8 eeee) eeee eee-8-eee (8.88 e, 8.8 eeee) eee eeeeeeee ee eeeeeee ee e eeeeee eeee ee 888°M eee 8 e eeee MeMe8(MMe8)8 (88 ee, 8.888 eeee) eee MeM (88 ee, 8.8 eeee). Meeeeeee ee eee eeeeeee eeee M8M, eeeeeeeeee eeee Me8M, eee eeeeeeeeeeeeee ee eee eeeeeeeeeeee eeeeeee [eeeeee eee, eeeeee/eeeeeee (MMMMMMM: eeeeeeeeee) 8:8] eeee eeeeeeee eeeee eee eeee eeeeeee eeee e eeee ee Me (8.88 e, 88 eeee) ee MeMM (88 eM) ee eeeeee eee 88 e. Mee eeeeeee eee eeeeeeeeee eee eee eeeeeee eee eeeeeee eeee M8M eee MMMe8. Mee MMMe8 eeeeeee eee eeeeeeeeeeee eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee); eeeee: 8.88 e (88%); ee 888–888°M.

8-Meeee-8-eeeeeeeeeeee (‌888‌, M8 = M8 = M; M8 = MM8; M8 = Me); Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee M-[8-eeeee-8-(eeeeeeeeeeeee)eeeeee]eeeeeeeeee (88.8 ee, 8.88 eeee) eee e-MeMM (88.8 ee, 8.88 eeee) ee eee MMM (8.8 eM) eee eeeeee ee 88–88°M eee 8 e eeeee M8. Meeee eeeeeee ee ee, M8M (8 eM) eee MeMMe (88 eM) eeee eeeee. Mee eeeeeeeee eeeeeee eeeee eee ee-eeeeeeeee eeee MeMMe (88 × 8 eM). Mee eeeeeeee eeeeeee eeeeeeee eeee eeeeee eeee eeeee, eeeee (MeMM8), eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee 8:8) ee eeee eee eeeeee ee e eeeeee eeeeeeeeeee eeeee; eeeee: 88 ee (88%); ee 888–888°M (MMMe8/eeeeee).

References