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Please login to access the full content or check if you have access via Reactions of Secondary Arylamines with Hetaryl Electrophiles

DOI: 10.1055/sos-SD-208-00126

Shen, Q.; Guo, F.; Hartwig, J. F.Science of Synthesis: Cross Coupling and Heck-Type Reactions, (20132184.

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]
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8 eeeeeeeee-8-ee Me Me Me8(eee)8 8 8 (8) 88 [‌88‌]
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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]

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Meeeeee eeeee eeeeeee, eeee ee eeeeeee 8888,[‌88‌‌88‌] 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).

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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%).