Science of Synthesis

Hay, M. B.; Hicks, J. D., Science of Synthesis: Cross Coupling and Heck-Type Reactions, (2013) 2, 135.

Palladium catalysis is typically more effective than copper catalysis for the N-arylation of secondary aromatic amines with aryl bromides. In comparison to the catalysts used for primary aromatic amine arylations, smaller ligands are often employed for secondary aromatic amine arylations. This change is due to the increased steric demands of secondary aromatic amine nucleophiles. The major ligand classes employed for the coupling of secondary aromatic amines with aryl bromides include large-bite-angle bidentate ligands, bulky trialkylphosphines, dialkyl(biaryl)phosphines, N-heterocyclic carbenes, and azaphosphatrane ligands.

Meeee-eeee-eeeee eeeeeeeee eeeeeeeee eeeeeee eeeeeeee eee ee eee eeeee eeeeee eeeeeee ee ee eeeeeeeee eee eee M-eeeeeeeee ee eeeeeeeee eeeeeeee eeeeee eeee eeee eeeeeeee (‌Meeeee 88‌). Meeee eeeeeee eeee Meeeeee eee Meeeeeee eeeeeee ee eeeeeeee eeeeeee eeeeeee eeee [8,8′-eee(eeeeeeeeeeeeeeeee)eeeeeeeee]eeeeeeeeeeeeeeeee(MM) eee eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8)/MMMMM, eeeeeeeeeeee.[‌88‌,‌88‌,‌88‌] Mee eeeeeeeee/MMMMM eeeeeeee eeeeee eee eeee eeee eeeeeeeeeee eeeeeeee eee eeeeeeeeeee eeeeeee M-eeeeeeeeeeeee eeee eeeeeeeeeeeeee eeeeeee eeee eeeeeeee. eeeee-Meeeeeeeeee eee eeeeeeee-eeeeeeeee eeee eeeeeeee eee eeeeee eeeeeeeee eeeeeeee eeeeeeee, eee eeeee eeeeeeeeeeee ee eeee eeeeeeeeee eeeeeeee-eeeeeee eeee eeeeeeee eee eeee ee eeee. Mee eeee ee eee eeeee eeeeeeeeeee ee eeeeeeee eeeeeee, ee eeeeeeee eeeeeeeeeeee eeeeee eeee eeeeee ee eeeee eeeeeeeee eeeeee ee eee eeeeee eee ee eeeeeeeeeee eeeeeeeee ee eee eeee eeeeeee ee eee eeeeeeeeeeeee eeeee. M eeeeee eeee, eeee ee eeeeee eeee-eeeeeeee, ee e eeeeee eeeeeeeeeeee eeeeeee (eeeeeee ee MMM) ee eeeeeeeee eeeeeeee, eee eeee eeeeeeeee eeee eeeeeeee e eeee eeee ee eeee eeeeeeeee.

‌Meeeee 88‌ Meeeeeeee-Meeeeeeee Meeeeeeee ee Meeeeeeee Meeeeeee Meeeee eeee Meee Meeeeeee Meeee Meeeeeeee/Meeeeeeee Meeeee Meeeeeeee[‌88‌,‌88‌,‌88‌-‌88‌]

‌Meeeeeeeeee 88‌

Me8	M8	Me8	Meeeeeee	Meeeeeeeee	Meeee (%)	Mee
Me	Me	8-MeMM8M8	Me8(eee)8 (8.88 eee%), MMMMMe	MeMMe, eeeeeee, 888 °M	88	[‌88‌]
Me	Me	8-Me8MM8M8	Me8(eee)8 (8.8 eee%), MMMMMe	e-MeMMe, eeeeeee, 888 °M	88	[‌88‌]
Me	Me		Me(MMe)8 (8 eee%), 8e	e-MeMMe, eeeeeee, 88 °M	88	[‌88‌]
Me	Me	8,8-Me8M8M8	Me8(eee)8 (8.88 eee%), MMMMMe	e-MeMMe, eeee, 888 °M	88	[‌88‌]
Me	Me	8-MeM8M8	MeMe8(eeee) (8 eee%)	e-MeMMe, MMM, 888 °M	88	[‌88‌]
Me	Me	8-MMM8M8	Me(MMe)8 (8 eee%), 8e	e-MeMMe, eeeeeee, 88 °M	88	[‌88‌]
Me	Me	8-MeM8MM8M8	Me8(eee)8 (8.8 eee%), MMMMMe	Me8MM8, eeeeeee, 888 °M	88	[‌88‌]
Me	Me	8-MeM8MM8M8	MeMe8{M(8-Mee)8}8 (8.88 eee%), MMMMMe	Me8MM8, eeee, 888 °M	88	[‌88‌]

e Meeee (Me/eeeeee) 8:8.8.

e Meeee (Me/eeeeee) 8:8.

e Meeee (Me/eeeeee) 8:8.

Meeeeeeeeeeeeee eeeeeeeeeee eeeeeeeeeeeeeeeee eee eeee ee eeeeeeee ee eeeeeeee e eeeeeee eeeee eeee eee eeeeeeeee eeee eeeeeeee eeeee e eeeeeeeeee eeeeeee (‌Meeeee 88‌).[‌88‌] Meee eeeeeee eeeeeeee eeeeeeeee ee eee eeeeeee eeeee eeeeeeeee eeeee eeeeeeeee/MMMMM, eeeeeee ee eee eeeeeeee eee eeeeeeeee/eeeeeeeeee, eee eeeeeeeeee ee eee eeeeee eeeeeeeee eeeee e eeeeeeeee eeeeeeeee eeeeeeee. Meeeeeee (‌8‌) ee eeeeeeeee ee eeeeeeeee eeeeee eee eee eeeeeeee ee eeeeeeee-eeeeeeeee eeeeeeeee eeeeeeeeee eeee eeeeeeee-eeeeeeeee eeee eeeeeeee, eeeeeee MeeeMeee (‌8‌) eeeeeee eeeeeeee-eeee eeeeeeeeee eeee e eeeeeee ee eeee eeeeeeee. Meeee eeeeeeeee eee eeeeeeeee ee 88 °M ee eeeeeee eeeee eeeeee eeee-eeeeeeee ee e eeee.

‌Meeeee 88‌ Meeeeeeee-Meeeeeeee Meeeeeeee ee Meeeeeeeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

e Meeee (Me/eeeeee) 8:8.8.

Meeee eeeeeeeeeeeeeeeeee eee eeeeeeeeee eeee eee eee eeeeeeee ee eeeeeeeee eeeeeeee eeeeee eeee eeee eeeeeeee ee eeee eeeeeeee eeeeee ‌88‌. Meeeee eeeeeee eeeeeeee eeeeeee eee-eeee-eeeeeeeeeeeeee,[‌88‌,‌88‌,‌88‌] ee-eeee-eeeee(8-eeeeee-8,8-eeeeeeeeeeeeeeeeeee)eeeeeeeee (‌88‌),[‌88‌,‌88‌] eee ee-eeee-eeeee(eeeeeeeee)eeeeeeeee (‌Meeeee 88‌).[‌88‌] Mee eeeeeeee eeeeeeeee eeeee eee eee M-eeeeeeeee ee eeeeeeeee eeeeeeee eeeeee eeee eeee eeeeeeee eee eeee eeeeeeeeeeee eeee eeeeeeeee/eee-eeee-eeeeeeeeeeeeee. Mee eeeee ee eeeee eeeeeeeeeeee eeeeeeee eeeeeeeeeee eeeeeeeeee eeee ee eeeeeeeeee eeeeeeeee M-eeeee- eee M-eeee-eeeeeeeeeee eeeeeeee.[‌88‌,‌88‌,‌88‌] Mee eeee eeeeee eeeee eeeeeeee e eeeeeee ee eeeeeeeeeeeeee eeeeeee eeeee-, eeee-, eee eeee-eeeeeeeeeee eeee eeeeeeee. Meeeeeeee eeeeeeeee eee eeeeeeeee/eee-eeee-eeeeeeeeeeeeee eeeeeeee eeeeee eeeeeeeee eeeeeee e eeeeee eeeeeeeeeeee eeeeeee (MMM ee eeeeeee) ee eee eeeeeeee ee eeeeee eeee-eeeeeeee, eeeeeeee eeeeeeee eeeeeeeeee eeeeeeeee eeeeeee eeeeeeeee eeeeeeeee eeee eeee eeee eeeeeeeee.[‌88‌]

Mee eeeeeeeee/eeeeeeeeeeeeeeeeeeee ‌88‌ eeeeeeee eee ee eeee eee eee eeeeeeee ee eeee eeeeeeeeeeeee eee M-eeeeeeeeeeeee eeee eeee eeeeeeee.[‌88‌,‌88‌] Meee eeeeeeee eee ee eeee ee eeeeeeee eeeeeeeeeee eeee eeeeee eeee-eeeeeeee ee ee eeeeeee eeeeeee ee ee eeeeeee eeeeeeeeeee ee eeeeeee eeeeeeeee eeeeeeeee. Mee eeeeeee eeeeeeeeee eeeeee eee eeeeeeeeee ‌88‌ (MMM).[‌88‌] eeeeeeeee/ee-eeee-eeeee(eeeeeeeee)eeeeeeeee eee eeee eeeeeeeeeee eeeeeee eeeeeeeee eeeeeeee eeeeee ee eeee eeeeeeeeeee, ee eeeeeeeeeeee ee eee eeeeeeee ee M-eeeeeeeeeeeee eeee eeeeeeeeeeeeee eee eeeeeeeeee eeeeee eeee eeeeeeee (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeeeeee-Meeeeeeee Meeeeeeee ee Meeeeeeee Meeeeeee Meeeee eeee Meee Meeeeeee Meeee Meeeeeeee/Meeeeeeeeeeeeeeee Meeeeeeee[‌88‌,‌88‌,‌88‌,‌88‌-‌88‌]

‌Meeeeeeeeee 88‌

Me8	M8	Me8	Meeeeeee	Meeeeeeeee	Meeee (%)	Mee
Me	Me	8-Me8MM8M8	Me8(eee)8 (8.88 eee%), e-Me8MMM8e-Me•MMM8e	e-MeMMe, eeeeeee, ee	88	[‌88‌]
Me	Me	8-MeMM8M8	88 (8 eee%)	e-MeMMe, eeeeeee, ee	88	[‌88‌]
Me	Me	8-MeMM8M8	Me{M(e-Me)8}8 (8 eee%)	MMM, MMMM,e eeeeeee, M8M, 88 °M	88	[‌88‌]
Me	e-Me	8-MeMM8M8	Me(MMe)8 (8.8 eee%), e-Me8Me	e-MeMMe, eeeeeee, 888 °M	88	[‌88‌]
Me	Me		{Me(η8-M8M8)Me}8 (8.8 eee%), 88e	e-MeMMe, eeeeeee, 888 °M	88	[‌88‌]
Me	Me	8-Mee	{Me(η8-M8M8)Me}8 (8.8 eee%), 88e	MMM, 88, M8M, ee	88	[‌88‌]
Me	Me	8-Mee	{Me(η8-M8M8)Me}8 (8.8 eee%), 88e	MMM, 88, M8M, ee	88	[‌88‌]
Me	Me	8-Mee	Me8(eee)8 (8.88 eee%), e-Me8MMM8e-Me•MMM8e	e-MeMMe, eeeeeee, ee	88	[‌88‌]
Me	Me	8-e-MeM8M8	[MeMe{M(e-Me)8}]8 (8.8 eee%)	e-MeMMe, MMM, ee	88	[‌88‌]
8-Mee	8-Mee	8-Mee	Me(MMe)8 (8 eee%), e-Me8Me	e-MeMMe, eeeeeee, 888 °M	88	[‌88‌]
Me	Me	Me	Me(MMe)8 (8.8 eee%), e-Me8Me	e-MeMMe, eeeeeee, 888 °M	88	[‌88‌]
Me	Me	8-M8MM8M8	Me8(eee)8 (8.88 eee%), e-Me8MMM8e-Me•MMM8e	e-MeMMe, eeeeeee, ee	88	[‌88‌]
Me	Me	8-MMM8M8	Me8(eee)8 (8.8 eee%), e-Me8Me	e-MeMMe, eeeeeee, ee	88	[‌88‌]

e Meeee (Me/eeeeee) 8:8.

e MMMM = eeeeeeeeeeeeeeeeeeeeee eeeeeee.

e Meeee (Me/eeeeee) 8:8.

e Meeee (Me/eeeeee) 8:8.8.

Meeeeeeeeeeeeeee eeeeeeee ee eeeeeeeee eeeeee eeeee eee eee eeeeeeee ee M-eeeeeeeeeeeee eeee e eeeeeee ee eeee eeeeeeee ee eeee eeeeeeee eeeeee ‌88‌ (‌Meeeee 88‌), eeee MeeeMeee (‌88‌), MeMeeeMeee (‌88‌), eee MeeeMeee (‌8‌) eeeee eee eeee eeeeeeee eeee.[‌88‌,‌88‌,‌888‌,‌888‌] Meeeeeeee eee eeeeeeeee eeeeeeeee ee eeeeeeeeeeeeeee ee eeeeeee eeee e eeeeee eeee, eeee ee eeeeee eeee-eeeeeeee ee eeeeeeeee eeee-eeeeeeee; eeeeeee, eeeeeee eeeeeeeeeeeeeeeeeeeeee ee e eeeeee eeeeeeeeeee eee eeee eeeeeeeeee eeeeeeeeee eeeeee eeeeeeeeee eeeeee (eeeeeee, eeeee, ee ee eeeeeeeeee eeeeee).[‌88‌] Meeee eeeeeeeee eeeeeeeee eeeeeeeee/eeeeeee(eeeeee)eeeeeeeee eeeeeeeee eee eeeeeeeee eeeeeeeee ee eeeeeeee eeeeeeeeeeee (88–888 °M) ee eeeee eee eee eeeeeeee eeeeeeeee eeeee.

‌Meeeee 88‌ Meeeeeeee-Meeeeeeee Meeeeeeee ee Meeeeeeee Meeeeeee Meeeee eeee Meee Meeeeeee Meeee Meeeeeeee/Meeeeee(eeeeee)eeeeeeeee Meeeeeeee[‌88‌,‌88‌,‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

Me8	M8	Me8	Meeeeeee	Meeeeeeeee	Meeee (%)	Mee
Me	Me	8-MMM8M8	Me8(eee)8 (8.88 eee%), 88e	MeMMMM, MMM, 88 °M	88	[‌88‌]
Me	Me	8-MeMMM8M8	Me8(eee)8 (8.88 eee%), 8e	MeMMMM, MMM, 88 °M	88	[‌88‌]
Me	Me	8,8-Me8M8M8	MeMe8 (8.8 eee%), 88e	e-MeMMe, eeeeeee, 88 °M	88	[‌888‌]
Me	Me	8-MM(MM8)8M8M8	Me8(eee)8 (8.88 eee%), 88e	MeMMMM, MMM, 88 °M	88	[‌88‌]
Me	Me	8-e-MeM8M8	Me8(eee)8 (8 eee%), 88e	e-MeMM, eeeeeee, ee	88	[‌88‌]
Me	Me	8,8-Me8M8M8	Me8(eee)8 (8.8 eee%), 88e	e-MeMMe, eeeeeee, 88 °M	88	[‌88‌]
Me	Me		Me8(eee)8 (8 eee%), 88e	e-MeMMe, eeeeeee, 88 °M	88	[‌888‌]
Me	Me	8-MeM8MM8M8	Me8(eee)8 (8 eee%), 88e	M8MM8, MMM, 888 °M	88	[‌88‌]

e Meeee (Me/eeeeee) 8:8.

e Meeee (Me/eeeeee) 8:8.

e Meeee (Me/eeeeee) 8:8.

M-Meeeeeeeeeee eeeeeeee eee eeeeeeeee eeeeeee eee eee eeeeeeee ee eeeeeeeee eeeeeeee eeeeee eeee eeee eeeeeeee, eeeeeeee e eeeeeee eeeeee ee eeeeeeee eeee eeee eeeeeeee (‌Meeeee 88‌).[‌88‌,‌888‌] M-Meeeeeeeeeeee eee eeee eeeeeee eeee eeeeeeee-eeee, eeeeeeee-eeeeeee, eee eeeeeeee-eeee eeee eeeeeeee. Meeeeeeee eeeee eeeeeeeee/M-eeeeeeeeeeee eeeeeee eeeeeeeee eee eeeeeeeee eeeeeeeee ee eeee eeeeeeeeeee eeee e eeeeee eeee.

‌Meeeee 88‌ Meeeeeeee-Meeeeeeee Meeeeeeee ee Meeeeeeee Meeeeeee Meeeee eeee Meee Meeeeeee Meeee Meeeeeeee/M-Meeeeeeeeeee Meeeeee Meeeeeeee[‌88‌,‌888‌]

‌Meeeeeeeeee 88‌

e Meeee (Me/eeeeee) 8:8.

Meeeeeeeeeeeeeeeee eeeeeee ‌88‌ eee ‌88‌ eeee eeee eeeeeeeee eee eee eeeeeeeee-eeeeeeeee eeeeeeee ee eeeeeeeee eeeeeeeeee eeee eeee eeeeeeee (‌Meeeee 88‌).[‌88‌,‌888‌] Mee eeeeeeeeeeeeeeeeee eeeee ee eeeeee eeeeeee eeeeeeee eeeeeeee eeee eeeeeeee eeeeeeee eeeee eee eeeeee eeee eeee eee eeeeeeeeeee eeeeeeee eeeeee eeeeee e eeeee, eeeeeeee-eeee eeeeee. Meeeeee ‌88‌ eee ‌88‌ eeee eeee eeee eee eee eeeeeeee ee M-eeeeeeeeeeeee eeee e eeeeeee ee eeee eeeeeeee, eeeeeeeee eeeee eeeeeeeeee eeeeee eeeeeeeeeeeee, ee eeee eeeeeeee eeeeee. Meeeeee eeeeeeeeeeeeeeeeeeeeee ee eeeeeeeee eeeeeeee ee e eeee eee eeee eeeeeeee eeeeeeeeee eeeeeee eeeeee, eeeeee, ee eeeeeeeeee eeeeeee. Meee eeeeeeee eeeeeeeeee eeee eeeeeeeee eeeeeeeeee eeeeee eeeeee eeeeee eeee-eeeeeeee ee eeee ee eeeeeee.

‌Meeeee 88‌ Meeeeeeee-Meeeeeeee Meeeeeeee ee e Meeeeeeee Meeeeeee Meeee eeee Meee Meeeeeee eeeee Meeeeeeee/Meeeeeeeeeeeeee Meeeeeeee[‌88‌,‌888‌]

‌Meeeeeeeeee 88‌

e Meeee (Me/eeeeee) 8:8.

Meeeeeeeeeeeeeeee ‌88‌ ee ee eeeeeeeee eeeeee eee eee eeeeeeee ee eeeeeeeee eeeeeeee eeeeee eeee eeee eeeeeeee (‌Meeeee 88‌).[‌88‌] Meee M-eeeeeeeeeeeee eee eeeeeeeeeeeee eee eeeeeeeee eeeeeeee eeeeeeee eeee 8-eeeeeeeeeeee, 8-eeeeeeeeeeeeeeeee, ee 8-eeeeeeeeeeee eeeee eee eeeeeeeee/eeeeeeeeeeeeeeeee eeeeeeee. Meeeeeeee eee eeeeeeeee ee 88 °M eeee eeeeee eeee-eeeeeeee ee eeeeeee.

‌Meeeee 88‌ Meeeeeeee-Meeeeeeee Meeeeeeee ee Meeeeeeeeeeee eeee 8-Meeeeeeeeeee Meeee Meeeeeeee/Meeeeeeeeeeeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeeee Meeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

Me e eeeeee, e eeeee-eee eeee eeeeeeee eeee e eeeeeee eee eee eeeeeee eeee eee eeee eeeeeee (8.8 eeeee), eee eeeeeeeee eeeee (8 eeeee), Me(eee)8 ee Me(MMe)8 (8–8 eee%), e-Me8M (8.8–8.8 eee%), eee e-MeMMe (8.8 eeeee). Meeeeee (8 eM/eeee eeeee) eee eeeee ee eeeeeee e eeeeee eeeeeee. Mee eeee eee eeeeeee eeee eee eeeeee, eee eee eeeeeee eee eeeeeee ee ee eeeee eee eeeeeeee eeeeeeee eee eeeeeeee, ee eeeeee ee MM ee MMM eeeeeeee. Mee eeeeeeeee eeeee eeeee eeeeeeeeee eee eeeeeeee eeee eeeeee eee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee).

Meeeeeee Meeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

Me eeee-eeeee eeeeeeeeee Meeeeee eeeee eee eeeeeeeee eee eeeeeeeeee eeee eeeee. Mee eeeee eee eeeeeee eeee Me8(eee)8 (8 eee%), MeeeMeee (‌88‌; 8 eee%), eee e-MeMMe (8.8 eeeee). Mee eeeee eee eeeeeeeee eee eeeeeeeeee eeee eeeee eee eeee eeeeee eeee e eeeeee eeeeee. Meeeeee (8.8 eM/eeee eeee eeeeeee), eee eeee eeeeeee (8.8 eeeee), eee eeeeeeeee eeeee (8.8 eeeee), eee eeeeeeeeee eeeeeee (8.8 eM/eeee eeee eeeeeee) eeee eeeee eeeeeee eee eeeeee (eeee eeeeeee ee eeeeee eeee eee eeeeee ee ee eeee eeeee eeeeeeeee eee eeeeeeee ee e-MeMMe). Mee eeeeee eee eeeeeeee eeee e Meeeee eeeee eee, eee eeeee eee eeeeee, eee eee eeeeeee eee eeeeeee ee ee eeeee eee eeeeeeee eeee eeeeeee eee eeee eeeeeeeeee eeeeeeee, ee eeeeee ee MM eeeeeeee. Mee eeeeeeeee eeeeeee eee eeeeeee eeee Me8M, eeeeeeee eeeeeee Meeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee).

References