Science of Synthesis

Shen, Q.; Guo, F.; Hartwig, J. F., Science of Synthesis: Cross Coupling and Heck-Type Reactions, (2013) 2, 184.

The reactions of hetaryl halides with secondary arylamines are more challenging and less studied than those with primary arylamines. Palladium complexes containing 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl as the ligand were the first catalysts reported for the palladium-mediated coupling of 2- or 3-bromopyridines and 3-bromoquinoline with N-methylaniline. The reactions require 2 mol% tris(dibenzylideneacetone)dipalladium(0) and 4 mol% 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, and the scope is rather limited.[‌12‌] Two more examples of such couplings were reported with 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl as the ligand: Heo described the coupling of N-methylaniline with 3-bromo-2-(benzyloxy)pyridine and 3-bromo-6-(benzyloxy)pyridine under microwave irradiation at 120 °C for 10 minutes.[‌22‌,‌26‌] With 1,3-bis(diphenylphosphino)propane as the ligand, the palladium-catalyzed aminations of 2-bromopyridine and 6-aryl-2,4-dichloropyridine also occur with N-methylaniline. In general, the third-generation catalysts containing electron-rich ligands are much more active for the reactions of secondary hetarylamines with hetaryl chlorides and bromides than catalysts containing bidentate arylphosphines.

Me 8888, Meeeeeee eeeeeeee eeee 8-eeeeee- eee 8-eeeeeeeeeeeeee eeeeee eeee M-eeeeeeeeeeeee ee eee eeeeeeee ee 8 eee% ee eeeeeeeee(MM) eeeeeee eee eeeeeeeeee MeeeMeee (‌8‌) ee 888 °M.[‌88‌] Meeeeee eeeeeee eeee eee eeee eeeee eeeeeeeeeeee eeee eee eeeeeeeeeee eeeeeeeee eeee eee eeee eeeeeeee MeMeee (‌88‌) eeeee ee e eeeeeeee eeee eeeeeeee eee eeeeeeee ee e eeee eeeee eeeeeee eee eeeee eeeeeeeeeeee. M eeeeee ee eeeeeee eeeeeeeee, eeee ee 8-eeeeee-8-eeeeeeeeeeeeeee, 8-eeeeee-8-eeeeeeeeeeeeeee, 8-eeeeeeeeeeeeeee, eee 8-eeeeeeeeeeeeee, eeeee eeee M-eeeeee- ee M-eeeeeeeeeeee ee 88 °M eeee 8.888–8.8 eee% eeeeeeeeeee ‌88‌ (‌Meeee 8‌).[‌88‌,‌88‌,‌88‌,‌88‌]

‌Meeee 8‌ Meeeeeee Meeeeeeee/Meeeeeeeʼe Meeeee Meeeeeeee Meeeeeee ee Meeeeee Meeeeee eeee Meeeeeeee Meeeeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌]

Meeee	Me8	M	M8	Me Meeeeee	Me (eee%)	Meeeee (eee%)	Meeee (%)	Mee
8	8-eeeeeee	Me	Me	Me(MMe)8	8	‌8‌ (8)	88	[‌88‌]
8	8-eeeeeee	Me	Me	Me(MMe)8	8	‌8‌ (8)	88e	[‌88‌]
8	eeeeeeeee-8-ee	Me	Me	Me8(eee)8	8	‌8‌ (8)	88	[‌88‌]
8		Me	Me	‌88‌	8	‌88‌ (8)	88	[‌88‌]
8		Me	Me	‌88‌	8.88	‌88‌ (8.88)	88	[‌88‌]
8	eeeeeee-8-ee	Me	Me	‌88‌	8.8	‌88‌ (8.8)	88	[‌88‌]
8		Me	Me	‌88‌	8.8	‌88‌ (8.8)	88	[‌88‌]

e Mee eeeeeeeeeeeee eeee ee eee 8-eeeeeeeeeeeeee eeeeeeeee eee eeee.

Meeeeee eeeee eeeeeee, eeee ee eeeeeee ‌88‌–‌88‌,[‌88‌–‌88‌] Meeeeeeʼe eeeeee (‌88‌),[‌88‌,‌88‌] 8-(ee-eeee-eeeeeeeeeeeeee)-8-eeeeeeeeeeee (‌88‌) (eeeeeeeee ee Meeeeeʼe eeeeeeeeee),[‌88‌] eee 8,8-eee(8,8-eeeeeeeeeeeeeeeee)eeeeeeee-8-eeeeeee (‌88‌; MMe), eeee eeee eeeeeeee ee eeeeeee eeeeeeee eeeeeeeee ee eeeeeeeeeeeee eeee eeeeeeeee eeeeeeeeee, eeeee eeeeeeeee eeeeeee 8.8–8 eee% eeeeeeee eeeeeee eee eeeeeeeeeeee ee 888–888 °M (‌Meeeee 8‌).

‌Meeeee 8‌ Meeeeee Meeeeee eee eee Meeeeeeee-Meeeeeeee Meeeeeee ee Meeeeeeeeeeee eeee Meeeeeeee Meeeeeeeee

M-Meeeeeeeeeee eeeeeeee (MMM) eeeeeee eeeeeeeeee eeeeeeeeee eeeee ee eeeee ee eee eeeeeeee-eeee eeeeeeeeee ee eee eeeee-eeeeeeeeee eeeeeeeee eee eee eeeeee ee eeeeeeeeee eeeeeeee M-eeeeeeeeeeee eeeeeee eeeeeee eeeeeeeee eeeeee eeeeeeeee eee eee eeeeeeee ee eeee eee eeeeeee eeeeeee eeee eeeeeeeee eeeeee. Meeee eeeeeeee eeee M-eeeeeeeeeeeee eeeeeee eeee 8-eeeeeeeeeeeeee, 8-eeeeeeeeeeeee eee 8-eeeeeeeeeeeeee ee eee eeeeeeee ee 8.8 eee% eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eee 8.8 eee% 8,8-eee(8,8-eeeeeeeeeeeeeeeee)eeeeeeee-8-eeeeeee eeeeeeeeeeeee (MMe•MMe), ee eeeeee eeeeeeeeeeee eeeeee ee 888 °M eeeee 8 e.[‌88‌] Meeeeeeee eeeeeeeee eeee e eeeeeeeeeee [Me(MMe)(eeee)Me] eeeee ee eeee eeeeee eeeee. Meeeeeeee ee 8-eeeeeeeeeeeeee eee 8-eeeeeeeeeeeeee eeee eee eeee eeeee eeeeeee ee 88 °M.[‌88‌] Meeeeee eeeeeee eeeeee eeee e eeeeeeeee eeeeeeee [Me(MMM)(eeeee)Me] ee eeee eeee eeeeeeee eee eeee eee eeeeeeee ee eeeeeee eeeeeee eeee eeeeeeeee eeeeeeeeee eeeeee ee e eeee eeeeee eeee, eeee ee eeee eeeeeeeeeee, eeee eeeeeeeee ee eeeee eeeeeeeeee eeeeeeeee ee eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eee eee M-eeeeeeeeeeee eeeeeee ee eeeee eee eeeeeeeeeeeeee eeeeeeeeeee [Me(MMe)(eeee)Me]. Mee eeeeeee, eeeeeeeee ee 8-eeeeeeeeeeeee, 8-eeeeeeeeeeeeee, eee 8-eeeeeeeeeeeeee eeee M-eeeeeeeeeeeee eeeee eeeeeeeeee eeeeee 88, 88, eee 88 eeeeeee, eeeeeeeeeeee. Mee eeee eeeeeeeeee ee eee eeeeeeee ee eeeeee eee ee eee eeeeee eee eeeeeeeee eeeeeeeee ee eee eeeeeeeeeeeee eeeeee eeeeeeeee eeeeeee [MeM] ee eeeeeeee.[‌88‌,‌88‌]

Mee(eee)eeeeeeeeee eeeeeeeeee e eeeeeee eeeee ee eee ee eee eeeeeeeeeeee eee ee eeeeeee eeeeeeee eee ee eeeee eeeeeeeee eeeeeeeeeeee ee eeeeeee eeeeeeeeeeeeeeeeee (MM) eeeeeee eeeeeee. Mee eeeeeeee eeeeee eeeeeeeeee ee e eeeeeeeee eeeeeeeee eee eee-eeee-eeeeeeeeeeeeee ee eeeeeeeeeeee eeeeee eee eee eeeeeeeee ee eeee eeeeee ee eeeeeeeee. Meeeeeee eeeeeeee eeee eeeeeeeeeeeeeeee eeeeeeeeeeeeeee eeeee eeee eeeeeeeeeeee eeee 8.88–8.8 eee% eeeeeeeee(MM) eeeeeee eee 8.88–8.8 eee% eee-eeee-eeeeeeeeeeeeee ee eeee eee eeeeeee eeeeeeeeeeee ee eeeeeeee eeeeee (‌Meeee 8‌, eeeee 8).[‌88‌] Meeeeeeeeeee, Meeeeee eee ee-eeeeeee eeeeeee eee eeeeeee ee eeeeeeeee eeeeeeeeeee ee eeeee- eee eeeeeeeeeeeeeeee eeeeeeeeeee eeeeeeeee eee eeeeeeeee eeee eee eeeeeeeee eeeeeeeeeee ee eee eeee-eeeeeeee eeee eee eee eeeeeeeee-eeeeeeeee eeeeeeeee ee eeeeeeeee eee eeeeeeeeeeeeee.[‌88‌] Meeeeee eeeeeee eeee eee eeee eeeee eeeeee eeee ee eee eeeeeeee ee 8 eee% ee eee(eeeeeeeeeeeeeeeeeeee)eeeeeeeee(8) eee eee-eeee-eeeeeeeeeeeeee ee e 8:8 eeeee, eeeeeeeee ee eeeeeeeeeee, eeeeeeeeeeeeeee, ee eeeeee-eeeeeeeeeee eeeeeeeeeeeeeee eeee M-eeeeeeeeeeeee eeeee ee eeee eeeeeeeeeee ee eeee ee eeeeeeeee eeeeee. Meeeeeeee ee eeeeeeeeeeeeeeee eee M-eeeeeeeeeeeee eeeeeee eeeeeeeeeeee ee 888 °M eee eeee eeeeeeeeee. Me eeeeeeee, eeeeeeeee ee eeeeeeeeeee eee eeeeeeeeeeeeeee eeee eeeeeeeeeeee eeeeeee ee 888 °M ee eeee eeee eeeeee ee eee eeeeeeee eeeeeeee eeeeeeee. Mee eeee ee eee eeeeeeeeee eee eeeeeeeeee eeeee, eee eeee eeeeeee eeeee eeeeeee eeeeeee, eeeeee 8- ee 8-eeeee-8-eeeeeeeeeeee, 8-eeeeeeeeeeeee, 8-eeeeeeeeeeeeeeeeeee, eee 8-eeeeee-8-eeeeeeeeeeeeeeeeeee (eeeee 88), eeeee eeee M-eeeeeeeeeeeee ee eeeeeeeeeeee ee eeee eeeeee, eeeeee ee eeeeeeee eeee eeeeeeee eeeeeee [e.e., 8 eee% Me(M8MMM8)8 eee e-Me8M] (‌Meeee 8‌).[‌88‌]

Meeeeeeee eeeeeeeee ee Meeeeeeeʼe MMeee (‌8‌) eee MeMeee (‌88‌) eeeeeee eee eeee eeeeee eeeeeeeee eee eee eeeeeeee ee eeeeeeeeeeeeeeee eeee M-eeeeeeeeeeeee, eeeeeeeee ee 888 °M, ee eeeeeeeee eeeee.[‌88‌] Meeee, eee eeeeeeeeeee eeeeeeeee eeee eee eeee eeeeeeee MeMeee eee eeeee ee ee eeeeee eeeeeeee, eee eee eeeeeeeee eeeee eeee e eeee eeeee ee eeeeeeeeee. Meee eeeeeee eeeeeeeeeeeeeeeeeeeeee ee eee eeee, eeeeeeeee eeeeeeeeee eeeeee eeee 8-eeeeeeeeeeeeee; 8-, 8-, 8-, eee 8-eeeeeeeeeeeeee; 8-eeeeeeeeeeeeeeeeee (‌Meeee 8‌, eeeee 88); eee 8-eeeeee- eee 8-eeeeeeeeeeee ee eee eeeeeeee ee 8–8.8 eee% ‌88‌ eee 8–8.8 eee% ‌88‌ ee 8 eee% ‌88‌ eee 8 eee% ‌88‌ (‌Meeee 8‌).[‌88‌,‌88‌]

‌Meeee 8‌ Meeeeeeee-Meeeeeeee Meeeeeee ee Meee-Meeeeeee Meeeeee Meeeeee eeee Meeeeeeee Meeeeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌]

Meeee	Me8	M	Me8	M8	Me Meeeeee	Me (eee%)	Meeeee (eee%)	Meeee (%)	Mee
8	8-eeeeeee	Me	Me	Me	Me(MMe)8	8.88	e-Me8M (8.88)	88	[‌88‌]
8	8-eeeeeee	Me	Me	Me	Me(eee)8	8	e-Me8M (8)	88	[‌88‌]
8	8-eeeeeee	Me	Me	Me	Me(eee)8	8	e-Me8M (8)	88	[‌88‌]
8	8-eeeeeee	Me	Me	Me	Me8(eee)8	8	‌8‌ (8)	88	[‌88‌]
8	8-eeeeeee	Me	Me	Me	Me(eee)8	8	e-Me8M (8)	88	[‌88‌]
8	8-eeeeeee	Me	Me	Me	Me(MMe)8	8	‌8‌ (8)	88	[‌88‌]
8	8-eeeee	Me	Me	Me	Me(eee)8	8	e-Me8M (8)	88	[‌88‌]
8	8-eeeee	Me	Me	Me	Me(eee)8	8	e-Me8M (8)	88	[‌88‌]
8	eeeeeee-8-ee	Me	Me	Me	Me(MMe)8	8	e-Me8MMe (8)	88	[‌88‌]
88		Me	Me	Me	Me(M8MMM8)8	8	e-Me8M (8)	88	[‌88‌]
88		Me	Me	Me	Me8(eee)8	8	‌8‌ (88)	88	[‌88‌]
88		Me	8-Mee	Me	‌88‌	8	‌88‌ (8)	88	[‌88‌]
88		Me	8-MMM8M8	Me	‌88‌	8	‌88‌ (8)	88	[‌88‌]
88		Me	Me	Me	‌88‌	8.8	‌88‌ (8.8)	88	[‌88‌]

Meeeeeeeeeee Meeeeeeee

M-Meeeee-M-(8-eeeeeee)eeeeeee (‌Meeee 8‌, Meeee 8):[‌88‌]

Me(MMe)8 (8.8 ee, 8.88 eeee, 8.8 eee%), eeeeeeee-8-eeeeeeeeeeeeeeeeeeeeeee (‌8‌; 8.8 ee, 8.88 eeee, 8.8 eee%), eee e-MeMMe (888.8 ee, 8.8 eeee) eeee eeeee ee ee eeeee-eeeeee eeeeeeeeee Meeeeee eeee (eeee-eeeee). Mee Meeeeee eeee eee eeeeeeeee eee eeeeeeee eeee eeeee eeeee eeeee eee eeee eeeeee eeee e eeeeee eeeeee. Meeeeee (8 eM), 8-eeeeeeeeeeeeee (888.8 ee, 8 eeee), eee M-eeeeeeeeeeeee (888.8 ee, 8.8 eeee) eeee eeeeeeeeeeee eeeee eeeeeee eee eeeeee eee eeeeeee. Mee eeeeee eee eeeeeeee eeee e Meeeee eeeee eee, eee eee eeeee eee eeeeee. Mee eeeeeee eee eeeeee ee 888 °M eee eeeeeee eee 88 e eeeee eee 8-eeeeeeeeeeeeee eee eeeeeeee (MM eeeeeeee). Meeee eeeeeee, eee eeeeeee eee eeeeeee eeee Me8M (88 eM), eeeeeeee eeeeeee e eeee ee Meeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee ee eeee eee eeee eeeeeee ee e eeee eeeeee eee; eeeee: 888 ee (88%).

M-Meeeee-M-eeeeeeeeeeeeee-8-eeeee (‌Meeee 8‌, Meeee 8):[‌88‌]

Me e eeeeee, e eeeee-eeeeee eeee eee eeeeeee eeee 8-eeeeeeeeeeeeee (888 ee, 888 µM, 8.8 eeee), M-eeeeeeeeeeeee (888 ee, 8.8 eeee), e-MeMMe (888 ee, 8.8 eeee), eeeeeee (8.8 eM) eee e eeeeeee eee. M eeeeeeeeee ee Me(eee)8 (8.88 eeee, 8 eee%) eeee e-Me8M (88.8 ee, 8.88 eeee, 8 eee%) ee eeeeeee (8.8 eM) eee eeee eeeee ee eee eeeeeeeee. Mee eeeeeeeee eeeeee eeeeeee eee eeeeeee eee 88 e ee ee. Mee eeeeeee eee eeee eeeeee eeee eeeeeee (88 eM), eee eee eeeeeeeee eeeeeee eee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeeee eeeeeee, Me8M/eeeeeee 8:88) ee eeee eee eeeeeee ee e eeeeeeeee eee; eeeee: 888 ee (88%).

References