Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 46.

In an extraordinary, but nonetheless efficient and certainly practically simple process, ortho-substituted nitroarenes ‌161‌ react with 3 equivalents of vinylmagnesium bromide to give 7-substituted indoles ‌162‌ (‌Scheme 57‌); see also ‌Table 2‌.[‌196‌–‌198‌] Better yields are obtained from nitroarenes which have larger ortho substituents and virtually no indole is produced if there is no ortho substituent.[‌197‌,‌198‌] The use of prop-1-enyl-, allyl-, and 2-styrylmagnesium bromides produces the corresponding 3-methyl-, 2-methyl-, and 3-phenyl-1H-indoles.[‌199‌] The use of 6 molar equivalents of the Grignard reagent in a mixture of diglyme and dimethoxyethane has been advocated for more efficient Bartoli reaction.[‌200‌] The Bartoli 1H-indole synthesis has been conducted on solid support, by linking substituted nitrobenzoic acids through the carboxylic acid group to Merrifield resin; there is the usual pattern of poorer yields (for example making 7-fluoro-1H-indoles) from substrates with smaller substituents ortho to the nitro group.[‌201‌]

‌Meeeee 88‌ Meeeeee Meeeee Meeeeeeee[‌888‌–‌888‌]

Meeeeeee eee eeeeeee eeeeeee ee eee ee eee eeeee ee eee eeeeeeeee (‌Meeeee 88‌) eee eee eeeeeee eeeeeee, ee eee eeee eeeee eeee eeeeeee eeeeee ee ee eee eeeee eeeee eeeeee eeeeee ‌888‌, eeee eeeeeeeeee eeeeeeeeeee ee eeeeeeeee eeeeeee eeeee eee eeeee ee eeeeeee eee eeeeeee eeeeeeeeee ‌888‌ ee eee eeeeeeee. Me ee eeee eeeeeeee eeee eee eeeeee eeeeeeeeee ee eeeee Meeeeeee eeee, eeeee, ee eeeeee eeeeeeeeee ee eeeeeeeeeeee ‌888‌ eeeee eeeeeeeee e 8,8-eeeeeeeeeee eeeeeeeeeeeee (ee eeee ‌888‌) eee eeeeeeeeeeee eeee eeeeeee ee ‌888‌, eeee eee eeeee eeeeeeeeee ee Meeeeeee eeeeeee eeeeee ee e eeee ee eeeeee eee eeeeeeeeeeeee eee eeee eeeeeeeeeeeee ee eeeeeeeeeeee ‌888‌, eeeee eeee ee eee eeeeeeee ee Me(MM)Me eeee ‌888‌ eeeeee eee eeeeee ‌888‌.[‌888‌]

‌Meeeee 88‌ Meeeeeee Meeeeeeee ee Meeeeee Meeeeeeee[‌888‌]

‌Meeee 8‌ Meeeeee eeee Meeeeee Meeeeeeee[‌888‌–‌888‌]

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

Meeeeeeeeeee Meeeeeeee

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

M eeee ee eeeeeeeeeeeeee eeeeeee (8 eeee) ee MMM eee eeeee eeeeeee ee 8-eeeeeeeeeeee (8.88 e, 8 eeee) ee MMM (88 eM) ee -88°M eeeee M8. Meeee eeeeeeee eee 88 eee, eee eeeeeee eee eeeeee eeee eee. ee MM8Me, eee eeeeeeeee eeeeeee eee eeeeeeeee eeee Me8M, eee eee eeeeeee eee eeeee (Me8MM8) eee eeeeeeeeeeee. Meeeeeeeeeee ee eeeeeeeeeeeeee (eeeeee eee) eeee eee eeeeeee; eeeee: 88%; ee 88–88°M.

References