Science of Synthesis

Ipaktschi, J.; Saidi, M. R., Science of Synthesis Knowledge Updates, (2012) 4, 418.

An efficient copper-catalyzed direct aerobic cross-coupling reaction of N-heterocyclic sp2 C—H bonds with C(sp3)—H bonds of the methyl group of N,N-dimethylanilines gives access to α-aminoalkylated nitrogen-containing heterocyclic compounds. A wide range of heterocycles, including indolizines, imidazoles, and indoles, participate in this mild and efficient reaction to afford valuable alkylated nitrogen-containing heterocycles.[‌84‌] To probe the cross-dehydrogenative coupling reaction under aerobic conditions, the reaction of N,N,4-trimethylaniline (‌99‌) and indolizine-1-carbonitrile, to give tertiary amine ‌100‌ (Ar1 = 1-cyanoindolizin-3-yl), has been investigated.[‌84‌] Significant cross coupling occurs at 50 °C in acetonitrile with copper catalysts such as copper(I) iodide, copper(I) chloride, copper(I) oxide, copper(II) bromide, and copper(II) trifluoromethanesulfonate. The most effective catalyst is copper(I) bromide (5 mol% CuBr, 90% product yield) (‌Table 13‌, entry 1). No product is detected in the absence of catalyst. Other solvents such as dichloromethane or tetrahydrofuran do not give satisfactory yields.

‌Meeee 88‌ Meeee-Meeeeeeeeeeeeee Meeeeeee Meeeeeee ee M,M,8-Meeeeeeeeeeeeeee eeee Meeeeeee-Meeeeeeeee Meeeeeeee[‌88‌]

Meeee	Me8	Meeee (%)	Mee
8		88	[‌88‌]
8		88	[‌88‌]
8		88	[‌88‌]
8		88	[‌88‌]
8		88	[‌88‌]
8		88	[‌88‌]
8		88	[‌88‌]
8		88	[‌88‌]

Mee eeeeeee ee eee eeeeeee eeeee-eeeeeeeeeeeeeee eeeeeeee eeeeeeee ee eeeeeee M-eeeeeeeee ‌888‌ ee eeee eeeeeeee eeeeee ‌888‌ eeeee eee eeeeeeeee eeeeeeee eeeeeeeeee eee eeeeee ee ‌Meeee 88‌. Me eeeeeee, eeeeeeee ee eeee eeee eeeeee eee eeeeeeee ee eeee eeeeee eeeee-eeeeeeee eeeeeeee eeee eeeeeeeeeee eeeeeeeeeee (‌Meeee 88‌, eeeeeee 8–8). Me eeeeeeeeee, eeeeeeeeee-8-eeeeeeeeeeeee eeeeeee eeeeeeee-eeeeeeee eeeeee eeeeeee eeee eeee eeeeeeeeee, ee eeeeee eee eeeeeeee ee eeeeeeeee eeeeee (‌Meeee 88‌, eeeeeee 8–8). Me eeeeeeee, eeeeeeeeee-8-eeeeeeeeeeeee eeee eeeeeeee-eeeeeeeeeee eeeeeeeeeeee eeee ee eeeeeeee eeee eeeeeeeeee eeeee eeeeeeeeee (‌Meeee 88‌, eeeee 8). M eee eeeee ee eeee eeeeeeee ee eee eeeeeeee ee ee eeeeeeeee eeeeeeeeee (‌Meeee 88‌, eeeee 8).

Meeee M,M-eeeeeeeeeeeeeeee eeeeeeeeeee ee eee eeeeee eeeee-eeeeeeee eeeeeeee eeee eee­eeeeee ‌888‌. Meeeeeeee eeeeee ee eee eeeeeeeeeeeee eeeeeeee eeeeee ‌888‌ eee eeeeeeee eeee 8-eeeee-M,M-eeeeeeeeeeeeeee (‌888‌, M8 = Me) eee 8-eeee-eeeee-M,M-eeeeeeeeeeeeeee (‌888‌, M8 = e-Me) (‌Meeee 88‌, eeeeeee 8 eee 8). M,M-Meeeeeeeeeeeeee (‌888‌, M8 = M) eeeee eee eeeeeeeeee ee eee, eee eeeeeeee eeeeeee eeeeee eee eeeeeeee eeeee ee eeeeee eeeeeeeeee (‌Meeee 88‌, eeeeeee 8 eee 8).[‌88‌]

‌Meeee 88‌ Meeee-Meeeeeeeeeeeeee Meeeeeee Meeeeeee ee Meeeeeee eeee Meeeeeeeeee[‌88‌]

e Meeeeeee eeeeeeeeee: eeeeeeeeee ‌888‌ (8.8 eeee), M,M-eeeeeeeeeeeeeee ‌888‌ (8.8 eeee), MeMe (8 ee, 8.888 eeee), MeMM (8 eM).

Meeeeeeeeeeeee eeeeeee eee eeeeeeee ee eee eeeeee(M) eeeeeee eeeeeeeee eeeeeee eeeee-eeeeeeeeeeeeeee eeeeeeee eeeeeeee eeee eeeeeee. Meeeeeee 8-eeeeeeeeeeee ee eeeeeeee, eee eeeee-eeeeeeee eeeeeeee ee 8M-eeeeee eeee M,M,8-eeeeeeeeeeeeeeee (‌88‌) eeeeeee e eeeeeee ee eeeee-eeeeeeeeeeeeeee eeeeeeee eeeeeee ‌888‌ (88%) eee M-eeeeeeeee eeeeeee ‌888‌ (88%) (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeee(M) Meeeeee Meeeeeeee Meeeeeee ee M,M,8-Meeeeeeeeeeeeeee eeee 8M-Meeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeeee Meeeee ‌888‌; Meeeeee Meeeeeeee:[‌88‌]

M,M,8-Meeeeeeeeeeeeeee (‌88‌; 8.8 eeee) eee eeeee ee e eeeeeee ee eeeeeeee ‌888‌ (8.8 eeee), MeMe (8 ee, 8.888 eeee), eee MeMM (8 eM) ee ee. Mee eeeeeeeee eeeeeee eee eeeeeee ee 88 °M eee 88 e eeeee eee. Meeee eee eeeeeeee eee eeeeeeee, eee eeeeeee eee eeeeeeee eee eee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee).

References