Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 134.

Indoles can be obtained directly from arenes carrying a vinyl substituent ortho to a nitrogen substituent. This type of intermediate can in turn be readily obtained by metal-catalyzed coupling of o-halo precursors. In addition to metal-catalyzed couplings, there are four common methods used for the synthesis of o-nitrostyrenes: (1) reaction of an o-(bromomethyl)nitroarene with a phosphine and then Wittig condensation with an aldehyde;[‌470‌] (2) Wittig reaction employing an o-nitroaraldehyde as the carbonyl component as in the transformation of aldehyde ‌498‌ to alkene ‌499‌ (Scheme 181); (3) base-catalyzed condensation of a methyl group ortho to an aromatic nitro group with an aldehyde; and (4) ortho nitration of a styrene. Indole syntheses in which the vinyl group is functionalized at the future indole α-carbon, that is, in which the future indole α-carbon is at the oxidation level of aldehyde or ketone, are discussed in Sections ‌10.13.1.1.1.4.1.1.2‌ and ‌10.13.1.1.1.4.1.1.4‌.

Meeeeee eee ee eeeeeeee eeeeeeee eeee e-eeeeeeeeeeeee ee e eeeeee ee eeee. Mee eeeeee eeeeee ee ee eeeeeee eee eeeeeeee eeeee eeeee eeee e eeeeeee, ee eeeeeeeeee, eeeee eeeeeee eeee e eeee-eeeee M—M eee eeee ‌888‌ eeeee ee eeeeee ‌888‌; eeeeeeee eeeeeeeee ee eeeeeeeee eeee ee eeeeeeee eee eeeeeee eeee eee eeeee eeeee (Meeeee 888);[‌888‌–‌888‌] eeeeeeeee eeeeeeee eeeeeeeee ee eeee eeeeeeee eeeeee eee eeeeeeee eeeeeeeeeeee eee eee ee e eeeeeee.[‌888‌]

‌Meeeee 888‌ e-Meeeeeeeeeeeeeee eeee e-Meeeeeeeeeeeeeeeee ee Meeeee Meeeeeee[‌888‌–‌888‌]

‌Meeeee 888‌ Meeeeee eeee e-Meeeeeeeeeeeeeee eee Meeeeee Meeeeeeee[‌888‌–‌888‌]

Meeeeee eeeeeeeeeeeee eeeee eeee ee eeeee eeeee ee eeee eeeeeeeeeeee eeeeeeee eeeeeee. Mee eeeeeee eeeeeeeeee eeeeeeee eeee ee eeeeeeee, eee eeeeeeeee ee e eeeeeee eee eee eeeeeeeee eeee eee eeee-eeeee M—M eeee.[‌888‌,‌888‌] 8-Meeeeeeeeee eeeee eeeeeeee 8-eeeeee-8M-eeeeee ee eeeeeee ee Meeeeee.[‌888‌] 8-Meeeeeeeeeeeeeeee (‌888‌), eeeee eee ee eeeeeeee ee eee eeeeeeee ee 8-eeeeeeeeeeeeeeeee eeee eeeeee eeeee [ee eeeeeeeeeeee eeee 88°M ‌888‌ eeeeeeee eeee 8,8-eeeeeeeeeeeee (‌888‌)], eee ee eeeeeeeee eeee eeeeeeeeeeee ee eeeeeee 8-(8-eeeeeeeeeee)-8-eeeeeeeeeee (‌888‌), eeeee ee eeeeeee ee eeeeee eeeee 8-eeeee-8M-eeeeee (‌888‌) (Meeeee 888).[‌888‌]

‌Meeeee 888‌ Meeeeeeee ee 8-Meeee-8M-eeeeee[‌888‌]

Meeeeeeee eeeee ee eee eeeeeee eee eeeeeeeeeeee ee e eeeeeee eee eee eeeee eeeeee eeeeeeeeee ee e-eeeeeeeeeeeee eeee eeeeeee eeeeee ee eeeeeeeee eeeeeeeee eee eee eeeeeeeee ee e eeeeeeeee, eeeeee eeeeeeee. Meeeeee ‌888‌ eeeeee eeee eeeeeeee ee e-eeeeeeeeeeeee ‌888‌ eeee eeeeeeeeeee(eeeeeeeeeeeeeeeeee)eeeeeeeee(MM)/eee(MM) eeeeeeee/eeeeee eeeeeeee (Meeeee 888);[‌888‌] ee eeee eeeeeeee, 8 eeeeeeeeeee ee eeeeee eeeeeeee eee eeeeeeee eee eee ee eeeeee eeeeeee eeeeeeee; eee eeeeeee eeeeeee ee eee eeeeeeee eee eee eeeee.

‌Meeeee 888‌ Meeeeee eeee e-Meeeeeeeeeeeeeee eee Meeeee Meeeeeee[‌888‌]

M eeeeeeeeee eeeeeeee eeeee eeeeeeee eeeeeeee eeeee eeeeeeeeeeee eee eeeeeeeee eee eeee eee eeeeeee ee eeeee Meeee eeee eeeee ee ee eeee eeeeeeeee eee eee eeee eeeeeee ee e eeeee eeeeeee ee eeeeeeeeee ‌888‌ eeeeee eeeeeee ‌888‌ (‌Meeee 8‌).[‌888‌]

‌Meeee 8‌ Meeeeee eeee e-Meeeeeeeeeeeeeee[‌888‌]

Meeeeeee Meeeeeee	Meeeeee	Meeee (%)	Mee
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]

Meeeeeeee eeee eeeeee eeeeeeee (88 eee) eee eeee ee eeeeeeee eeeeeeeeeee ee eee eeeeeeee ee eeeeeeeee eeeeeeee; eeeeee eeeeeeeeeeeee ee eeeeeeee eee eee eeeeeeee ee eeeeeeeee ee eeeeeee.[‌888‌]

8M-Meeeee eeeeeeeee eeee eeeee eeeeeeeeee eee ee eeeeeeee eeeee eeeeee eeeeeeee ee eee eeeeeeee eeeeeeeee eee eeeeeeeee ee eeeeeeee. Mee eee eeeeeeeeeee ee 8-eeee-8M-eeeeeee (e.e., ‌888‌), ee eeeeeeeee ee ‌Meeeee 888‌, eee eeeeeeeeee eee eeee eeeeeee eee eeeeeeee ee eeeeeeee 8-eeeeeeeeeeeeeeeeee eeee 8-eeee- ee 8-eeeeeeeeeee.[‌888‌] Me ee eeeeeeeee eeeeeee, 8M-eeeeee-8-eeeeeeeeeeee eee ee eeeeeeee eeee eeeeeeeeee eeeeeeee ee eeeeeeeeeeee ee eeeeee 8-eeeeeeeeeeeeeeeeee eeee eeeeeeeee ee eeee 8-(8-eeeeeeeee)eeeeeeeeeee, eeeee eee ee eeee eeeeee.[‌888‌] Me eeeeeeee 8-eeeeeeeeeeeeeeeeee eeee eee eeee eeeeeeeeeeeeeeeeeeeeeeeeee ee eeeeeeeee-8-eeee, eeeeeeeeee eee eeeeeeee eeeee eee ee eeeeeeee ee eeeeeeee 8,8,8,8-eeeeeeeeee-β-eeeeeeeeee.[‌888‌] Mee eeeeeee eeeeeeee eeeeeeeeeee eee eee eeeeeeeee eeeeeeeeeee ee 8-eeeeeeeeeeeee, eeeee eeeee eeeeeeeee eeeeeee, eeeeeeeee eeeeeeeee(MM) eeeeeeeeeeeeeeee (8.8 eee%) eee 8,8,8,8-eeeeeeeeeee-8,88-eeeeeeeeeeeeee, eeeeeeee eeeee eeeeeeeee ee eeeeeeeeeeeeeeeee eeee eeeeee eeeeeeee (88 eeee) eee ee 88°M.[‌888‌] Meee ee eee eeeeeee eeeeeeee eeee eeeee eeee eeeeeeee eee eeeee ee ‌Meeee 8‌.

‌Meeeee 888‌ 8-Meee-8M-eeeeeee eeee 8-(8-Meeeeeeee)eeeeee[‌888‌]

‌Meeee 8‌ 8M-Meeeeee eeee 8-Meeeeeeeeeeee Meeee Meeeeeeee(MM) Meeeeeeeeeeeeeee eee Meeeee Meeeeeee[‌888‌]

Meeeeeee Meeeeeee	Meeeeee	Meeee (%)	Mee
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]

Meee eeee eeeeeee 8-eeeeeeeeeeee eeeee eee ee eeeeeeee ee eeee eeeee ee 8M-eeeeeee: eee eeeeeeeee eeeeee eeeee ee ‌Meeee 88‌ eeee eeee ee eee eeeeee eeeeee eeee eee eeeeeeeeeeeee eeeee-eeeeeee eeeee e eeeeeeeee(MM) eeeeeee/eeeeee eeeeeeee/8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee (eeee)/888°M eeeeee.[‌888‌]

‌Meeee 88‌ Meeeeeeee 8M-Meeeeee Meeeee Meeee e Meeeeeeee(MM) Meeeeee/Meeeee Meeeeeee/8,8-Mee(eeeeeeeeeeeeeeeee)eeeeeee/888°M Meeeee[‌888‌]

Meeeeeee Meeeeeee	Meeeeee	Meeee (%)	Mee
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]
		88	[‌888‌]

Meeeeeeeeeee Meeeeeeee

Meeee 8,8-(Meeeeeeeeeeeee)-8M-eeeeee-8-eeeeeeeeeee (‌888‌, M8,M8 = MMM8M; M8 = MM8Me); Meeeeee Meeeeeeee:[‌888‌]

Meeee 8-[8,8-(eeeeeeeeeeeeee)-8-eeeeeeeeeee]eeeeeeee (8.88 e, 8 eeee) eee eeeeee ee M(MMe)8 (8.88 e, 8 eeee) ee 888°M eee 8 e. Meeeeeee eeeeeeee eee eeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eee eeeeee eeeeeee eeeeee eee ee MMMe8 eeee. Mee eeeeee eee eeeeeeeeeeee eee eee eeeeeee eee eeeeeeeeeeee (eeeeee/MMMe8) ee eeee eee eeeeeee; eeeee: 8.88 e (88%); ee 888–888°M.

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

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M eeee ee 8-eeeeeeeeeee-8-eeeeeeeeeeee (8.8 e, 8 eeee), MeMe8(MMe8)8 (8.8 eeee), eee MeMe8 (8.88 e, 8.8 eeee) ee 8,8-eeeeeee (88 eM) eee eeeeee eeee MM eee eeee eeeeeeeeeee eeee MM ee 88 eee eee eeee eeeeee ee 888°M eee 88 e. Mee eeee eee eeeeee, eeeeeee eeeeeeee eeee eeeeeeeeee, eee eee eeeeeee eee eeeeeeee ee eee eeeee eee ee eeee eee eeeeeee; eeeee: 88 ee (88%).

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

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M eeeeeee ee 8-[(M/M)-8-eeeeeeeeee-8-eeee]-8-eeeeeeeeeeee (8.88 e, 8.88 eeee), Me(MMe)8 (88 ee, 8.88 eeee), eee Me8M (88 ee, 8.88 ee) ee MeMM (8 eM) eee eeeeee ee 88°M eeeee 8 eee ee MM eee 88 e. Meeeeeee ee eee eeeeeee ee 88% ee MMe (8 eM) eee eeeeeeeeee eeee Me8M eeee ee eeeeeee eeeee, eeeee eee eeeeee eeee eee MMe, eeeee (MeMM8), eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 8:8) ee eeee eee eeeeeee; eeeee: 8.88 e (88%).

8,8-Meeeeee-8M-eeeeeeee-8(8M)-eee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

8-(8-Meeeeeeeeee)eeeeeeee-8-ee-8-eee (888 ee, 8.88 eeee), Me(eee)8 (88.8 ee, 8.88 eeee), eeee (88.8 ee, 8.88 eeee), 8,88-eeeeeeeeeeeeee eeeeeeeeeee (88.8 ee, 8.88 eeee), eee MMM (8 eM) eeee eeeeee ee ee MMM Meeee eeeeeeee eeee eeeeee eeee e eeeeeeee eeee. Mee eeee eee eeeeeeeeeee–eeeeeeeeeeeee eeee MM ee 8 eee (8 ×), eee eee eeeeeee eee eeeeee ee 88°M eeeee MM (8 eee) eee 88 e. Mee eeeeeee eee eeeeeeee eeeeeee e Meeeee eee, eee eee eee eeeeee eeeeeee eeee MM8Me8, eee eee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (MeMMe/eeeeeee 8:8) ee eeee eee eeeeeee ee e eeeee eeeeee; eeeee: 888 ee (88%).

References