Science of Synthesis

Hay, M. B.; Hicks, J. D., Science of Synthesis: Cross Coupling and Heck-Type Reactions, (2013) 2, 107.

General Introduction

The N-arylation of aromatic and heteroaromatic amines has developed into a powerful method to construct aromatic amine subunits found in a variety of natural products, pharmaceutical compounds, and materials. The importance of this structural motif has led to the development of numerous robust methods that can effect the arylation of aromatic amines in high yield using a wide array of substrate combinations. Transition-metal-mediated reactions using palladium or copper have rapidly become the preferred method to effect these transformations due to the high tolerance of functional groups and high yields observed using these methods.

Meeeeeeee-Meeeeeeee M-Meeeeeeee: Mee eeeeeeeee eeee ee eeeeeeeeee eeeeeeeee eeeeeeeee-eeeeeeeee M-eeeeeeeee ee eeeeeeee eee eeeeeeeeeeeeee eeeeee eee eeeee eeee e eeee eeeee ee eeeeeeeeee eeeeeeeeeeee eeeeeeeeee eeee eeeeeeeeeeeeee.[‌8‌-‌8‌] Meeeeee eee eeeeeeeee eeeeee, eeeeee, eeee, eeeeeee, eee eeeeeeeeeee eee eee eeeeee eee M—M eeeee-eeeeeeee eeeeeeee. Meee eeeee eeeee ee eeeeeeeee eee eeeee eeee eeeeeee eeeeeeeee e eeeeeeee eeee. Meeeeeeeeee eeeeeeee eeee eee eeeeeeeee eeeeeeeee M—M eeeee eeeeeeee eee eeeeeee eeeeeeee ee eeeeeeeee eee eeeeeeeeeee eeeeeeee eee eeee eeeeeeeeeeeeee. Meeee eeeeeeeee eeee eeee eeeeeeee eee eeeeeeeeeeeeeee eee eeeeeeee ee eeeeeee eeeeeee eee eeeeeee eeeeeeeee eeeee eeeee ee ‌Meeeee 8‌.

‌Meeeee 8‌ Meeeeeee Meeeeeeee Meeee eee Meeeeeeee-Meeeeeeee Meeeeeeee Meeeeeeee[‌8‌]

Meeee ee eeeeeeee eee eeeeeeeee eeeee, ee ee eeeeeeeee ee eeeeee eeeeeeeee eeeeeeeee ee eee eeeeee eeeeeeeee(8) eeeeeeee eeee e eeeeeeeee eeeeeeeee. Mee eeeee ee eeeeeeeee eeeeeeeeee eee eeeeeeeee eeeeeeee: (8) eeeeeeeee(8) eeeeeeeee ee (8) eeeeeeeee(MM) eeeee. Meeeeeeee(8) eeeeeeeee [e.e., Me8(eee)8, Me(eee)8, ee Me(MMe8)8] eee eeeeeeeeeeee eeeeeee ee eeeee eeeeeee ee eeeeeeee eeee eee eeeeee eeeeeeee [Me(8)Me] eeee eeeeeeeeeee eeee e eeeeee.[‌8‌] Mee eeeeeeeeeeeee eee eeee eeee eeeeeeeeeee eeeeeee (e.e., eee) eee eeeeeee eeeeeeeee eee eeeeeee eeeeeeeee(8) eeeeeeeeee [e.e., Me(MMe8)8] eee eee eeeeeeeee.[‌8‌-‌8‌] Meeeeeeeee, eeeeeeeee(MM) eeeee eee eeee eeeeee ee eee eeee eeeee eeeeeeeee(8) eeeeeeeeeeee eee eeeeeee eeeeeeeee ee eeeeeeeee(8) eeeeee eeeeeeee eee eeeeeeeee eeeee. Meeeeee eeeee ee eeeeeeee eeeeeeeee(MM) ee eeeeeeeee(8) eeeeeee eeeeeeee ee eee eeeeeeeee(MM) eeee eeee eeeeeeeeeeeee eeee,[‌88‌] e eeeeeeee eeeeeeeee,[‌88‌] ee ee eeeee eeeeeeeee eeeeeeeeee β-eeeeeeeee[‌88‌] (‌Meeeee 8‌). Mee eeeeeee eeeeeeee eeeeee, eeeeeeeee eeeeeeeee eee β-eeeeeee eeeeeeeeeee ee eee eeeee eeeeeeeee ee eee eeeeeeee eeeeee e eeeeeeeeeee eeeee ee eeeee ee eee eeeeeeee.

‌Meeeee 8‌ Meeeee Meeeeeeee Meeeeeeee Meeeeee

Meeeee eeeeeeeeeeee eeee eee ee eee eee-eeeeee, eeeeee-eeeeeeeee eeeeeeeee(MM) eeeeeeeeeee eeeeeeee ‌8‌ (‌Meeeee 8‌), eeeee eeeeeeeee eeeeeeeee ee eee eeeeeeee ee eeee.[‌88‌] Meee eeeeeeeeeeeee, eeeee eeeeeeeeeeee eeeeeeee ee eeeeeeeeee ee eeeeeeee eee eee eeeeee eeeeeeee [Me(8)M8] eeeeeee eee eeee eee ee eeeeeeeeee eeeeeeeee. Meee eeee ee eeeeeeeee(MM) eeeeeeeeeee ee eeeeeeeeeeee eeeeeeeee eee eeee eeeeeee.

Meee eeeeeeeee ee eee eeeeee Me(8)Me eeeeeee, eee eeeeeeee eeeeee eee eeeeeeeee eeeee eee eeeeeeeee eeeeeeeee eeeeeeee ee eee eeee eeeeee, eeeeeeeee eee Me(MM)(Me8)MMe eeeeeee (‌Meeeee 8‌). Mee eeeeeee eeee eeeee eee eeeeeeeee eeeeeeee ee eeee eeeeeeeee < eeee eeeeeeee ~ eeee eeeeeeeeeeeeeeeeeeeeeeeeee < eeee eeeeeee eee eeeeeeeeee eeee eee eeeeeeee eeee eeeeeeeee ee eee M—M eeee.[‌88‌] Mee eeeeee ee eee eeeeee eeeeeee eeeeeeeeee eeeeeeeee ee eeee eeeee ee eee eeeeeeeee eeeee, ee eeeeeeeee eeeeeeee ee eeeeeeeee eeeeeeeeeee ee ee eeeeeeee-eeee eeeeee. Meeeeeee- ee eeeeeee(eeee)eeeeeeeeee eee eeeee eeeeeeee eee eeee eeeeeeee eeeeeeeeeeeee eeee ee eeee eeeeeeeee, eeeeeee eeee eeeeeee, eeeeeeee, ee eeeeeeeeeeeeeeeeeeeeeeeeee eeeeeee eeeeeeeee eeeeeeee eeee eeeeee.[‌88‌,‌88‌] Meeeeeeee eeeeeeeee e eeee eeeee ee eeeeeee, eeeeeeeee eeee eeeeeeee-eeee eeeeeeeeeeeeeeeee, eee eeeeeeeee eee eeeee eeeeeeeeee.

Mee Me(MM)(Me8)MMe eeeeeeeee eeeeeeee eeeeeee eeeeee eeee eee eeeeeeee eeeee eeeeeeeee eeeeeeee e eeeeeeeee eeeee. Mee eeeee eeeeeeeee eeeeeeeee eeeee eee eeeeeeeee(MM) eeeeeeeee eeeeeeee eeeeeee eee ee eeee eeeeeeeeeeee.[‌88‌] Mee eeeeeee eeeeeeee eee eeeeeeeeeeeeee eeeee eeeeeeeeeeee, eee eeeeeee eeeeeee ee eeeee eee eeee-eeeeeeee eeee ee eee eeeeeeeee eeeee.[‌88‌] Meeeeee ee eeeee eeee eeeeeeeeeeeeeee, eeeeeeee-eeee eeeeeeee eeeee eeeeeeeeee eee eeeeeeeee eeee eeeeeeeeee eee M—M eeeee eeeeeeee.[‌88‌] Meeeeeeeee, eeeeeeee-eeeeeeeee eeeeeee eeeeeeeeeee eee eeeeeeeee eeeeeeeeeee eeeeeeeeee eee ee eeeee eeeeeee eeeeeeeeeeeeeee eee eeeeee eeeeeee ee eeeeeeeeee ee eee Me(MM)(Me8)MMe eeeeeeeee eeeeeeee eeeeeee.[‌88‌,‌88‌] Mee eeeeeeeeeeeee eeeee ee eeeeeeeeeee ee eee eeeeeeeee eeeeeee ee eee eeeeeeeee M—M eeee eeee eeeeeee ee eee eeeeeeeee eeeeeeee eeeeeee.[‌88‌] Mee eeeeeeeee eeeeeee ee eeee eeee eeeeeee ee e eeeeeee ee eeeeee ee eeee eeeee eeeee eeee ee eeeeeeeeeee eeee eeeeeee.[‌88‌] Me e eeeeee, e eeee eeeee ee eeeee eeee eeee eeeeeeee ee eeeee eeeeeeeee, eeeeeeeee eeeeee eeeee eeee-eeeeeeeee, eeeeeee eeeeeeeeeeeeeeeeeeeeee, eeeeeeeee eeeeeeeee, eeeeeeeee eeeeeeeee, ee eeeeee eeeeeeeee. Meeeee eeeee eeeeeee eeeeeeeee eeeeeeeeeeeee eeeee, eee eee eee ee eeeeeeeeee eeee eeee-eeeeeeeee eeeeeeeeee eeeeee. Me eeeee eeeee, eeeeee eeeee eeee ee eeeeeeeee eeeeeeeee, eeeeeeeee eeeeeeeee, ee eeeeee eeeeeeeee eee ee eeeeeeee.

Mee eeeee eeee ee eee eeeeeeeee eeeee, M—M eeee-eeeeeee eeeeeeeee eeeeeeeeeee, ee eeeee eeeeeeeeeee ee eeeee, eeeeeeeeee eeeeeeeeee eeeeeeeeeee eeeeeee [e.e., eee-eeee-eeeeeeeeeeeeee ee eeeeeee(eeeeee)eeeeeeeeee] ee eeeee-eeee-eeeee eeeeeeeee eeeeeee [e.e., MMMMM, Meeeeeee, ee MeMM-eMe (eee ‌Meeeee 8‌)].[‌88‌] Me eeeeeeee ee eeeeeeeee eeeeeeee, eeeeeeeee eeeeeeeeee eeeeeeee-eeee eeeeeeeee eeeeeee eeeeeee M—M eeee-eeeeeee eeeeeeeee eeeeeeeeeee.[‌88‌]

Meeeeeeeeeee Meeeeeeeeeeeee eee Meeeeeeee-Meeeeeeee M-Meeeeeeee: Mee eeeeeeeeee eeeeeeeee ee eeeeeeeee-eeeeeeeee eeeeeeee eee eeeeeeeeeeeeee eeeee eeeeeeeee eeeeeeeee eeeeeeee eeeeeeeeeeeee ee eeeeeee eeeeeeeeeeee eeeeeeeee, eeeeeeeee eeeeee eeeeeeeee, eeeee eeeeeeeeeee, eee eeee eeeeeeee eeee.[‌88‌]

Mee ee eee eeee eeeeeeeeeee eeeeeeeee ee eeeeee eeeeeeeee, ee eeee eee eeeeee Me(8)Me eeeeeee eee eeee eeeeee eee eeeee ee eeeeeeeee. Meeeeeeee ee eee eeeeee eeeeeeeee(8) eeeeeeee eee eeee ee eeeeeeee eeeeeeee ee eeeeeee eeeeeeee eeee. Meeeeeeee eeeeeee eeeeeee eeeeeee eee eeeeeeeee. Mee eeeeeee, eeee eeeeeeeeeeeeeeeee eee ee eeeeee eeeee eeeeeee eeeeeeeeee eeee eeeeeee eeeeeeeee eeee, eeeeeee eeeeeeeeeeeeeeeeee eee eeeeeee eeee eeeeeee eeeee eeeeeee eeeeeeeeee. Me eeeeeeeeee eeeeeeee, eee-eeeeee eeeeeeeeeeeeeeeeeee eeeee eee eeeeeeeeeeee eeeeeeeee eee eeee eeeeeee eeeeeeeeeeeeeeeee eeeeeee.[‌88‌] Meeeeeee eeeeeee eee eee eeeeee Me(8)Me eeeeeee eee ee eeeee eeeeee eeeeeeeee, eeeeee eeeeeeeee eeeeeeeeee [e.e., Me(MMe)8, MeMe8(MMMe)8, eee Me8(eee)8] eee eeeeeeeee eee eee eeeeeeee eeeeee.

Meeeeee, eeeee eeeeeeeeeee ee eee ee eeeeeeeee eeeeeee eeee eeee eeeee ee M-eeeeeeeee eeeeeeeee ee eeee eee eeeee eeeeeee eee eeeee eeeeeeeeeeee eeeeeeeee eeeeeeee eeeeeee eeeeeee eeeeeeeeeeee. Me eeeeeeee eeeee, eeeeeee eeeeeeee eeeeee eeee eeeeeeee eee eee ee eeeee ee e eeeeeee ee eeeeeeeee eee e eeeeeee ee M—M eeeee-eeeeeeee eeeeeeeee.[‌88‌,‌88‌]

Meeeeee eeeeee ee eeeeeeee eeeeeeeeeeeee eeeee eeeeee eeee eeeeeeeee eeeeeeeee eeeeeeeee eeeeeeeee eeeee eeee ee eeeeeeeee eeeeeeeee, eeeeeeeee eeeeeeeee, ee eeeeee eeeeeeeee.[‌8‌] Mee eee eeeeeeeeee ee eeeee eeeee ee eeeeeee eeeeeeee eee eeee ee eeeeeee eeeeeeee eeeee eee eeeeeeeeee eeeeee. Meee eeeee eeeee eeeee, eeeeeeee eee eeee eeeee ee eee eee eeeeeee eeeeeee.

Meeeee-Meeeeeeee M-Meeeeeeee: Meeeeeeee eeeeeeeee ee eeeeeeeee eee eeeeeeeee eeeeee eee eeeeeeee eeeeeeeeee eeee eeee eee eeeeeee eeeeeeeeeeeee, eeeeeeee eeeeee-eeeeeeee eeeee eeeeeeee eee ee eeeeeeeeeeee ee eeeeeee eeeeeeeeee (‌Meeee 8‌).[‌88‌-‌88‌]

‌Meeee 8‌ Meeeeeeeee eee Meeeeeeeeee ee Meeeee-Meeeeeeee M-Meeeeeeee ee Meeeeeee Meeeee[‌88‌-‌88‌]

Mee eeeeeee eeeeeeee eeeeeeee ee eeeeee-eeeeeeee eeeeeeeeee eee eee eee eeeeeeee eee eeeeeee eeee ee eeeeee eeeeeeee ee eeeee eeeeeeeeee eeeeee. Meeee eeeeeeeeeeeeeee eeeeee eeeeee ee eeeeeeeeee eeeee eee eee ee eeeee-eeeee eee eeeeeeeeeeeeee eeeeeeeeeeee.[‌8‌] Meeeeeee, eeeeee-eeeeeeee eeeeeeeee eeeeeee eeeeeeee eeeeeeeeee eeee eeeeee ee eeeeeeeee eeeee eeeeeeee ee eeeeeeeee-eeeeeeeee. Meeeee-eeeeeeee M-eeeeeeeeee eee eeeee eeeeeeeeeee eeee eeeeee eeeeeeee eeeeeee eeeeeeee e eeeeeeeeeeee eeeee eeeee eeee ee e eeeeeeeeee eeee eeeeeeeeee. Me eeeeeeee, eeee eeeeeeeeeeee eeeeeee eee ee eeeeeeeeeee ee eeeeeeeee eeeeeeeee. Meeeee-eeeeeeee eeeeeeeee eeee eeeeeee eeee ee eee eeeeeeee ee eeeeee eeeeeeeeeeee eeeeeeeeeeeeee eeeeeeeeee, eeeee eee eeeee eeee eeeeeeeeee eee eeeeeeeee eeeeeeeee. Meeeee eee eeee eeee e eeeeeee eeeeeeeeee eeeee eeeeeeeee eeeeeeee ee eeeeeeeee eeeeeeeee.

Meeeeeee eeeeee-eeeeeeee eeeeeeeeee eeee eeee eeeeeeee, eeeee eeeeeeeee eeee eeeeeeeeeee eeee eeee ee eeeeeeeeeeee, eeeee eeeeeeeee eeeee eeee eee eeeeee eeeeeeeeee ee eeeeee eeeeee eeeeeeeee. Meeee eeeeeeeee eeeee eeeeeeee eeee eeeeeeee eeeeeee (>88 eee%) eee eeeeeeee eeeeeeee eeeeeeeeeeee (88–888 °M) eee eeeeeeeee ee eeeee eeeeeeeeee. Meeeeeeeee eeeeeeeee eeeeeeeeee eeeeeee eeeee-eeeeeeeee eeeeee eee eeeeeeeee eeeeeeeeeee eee eeeeee-eeeeeeee eeeeeeeeee. Meeeeee, eee eeeeeeeeeeee eeeee ee eeeeeee ee eeee eeeeeeee eee eeeeeee. Meee eeeeeeeee eee eeeeeeeeeeeee eee eeeee ee eeeee eeeeeeee eeeeeeeeee.

Meeeeeeeeeee Meeeeeeeeeeeee eee Meeeee-Meeeeeeee M-Meeeeeeee: Meeeee-eeeeeeeee eeeeeeeeee eeeeeee eeeeeee eeeeeeeeeeee eeeeeeeeeee ee eeeee eeeeeeeee eeeeeeeeeeee. Mee eeeeeee, eeeeee-eeeeeeeee eeeeeeeeee eee eeeeeeeee eee eeeee e eeeeeeee ee eeeee eeeeeeeeee ee eee eeeeeee ee eeeee. Me eeeeeeeeee, eeeeee-eeeeeeee eeeeeeeee eeee eeeeeeeee eeeeeeeeeee ee eeeee.[‌88‌] Meeeeeeeee eeeee eee eeeeee ee eeeeeeeeeeee eeeeeeeeee ee eee eeee eeeeee eeee eeeeee eee eeeeee eeeee eeee eeeeeeee.[‌88‌] Me eeeee eee eeeeeeeee-eeeeeeeee eeeeeeeeee, eee eee ee eeeeeeeee eeeeeeeee eeeee eee eeee ee eeeeeeee eeeeeeeeeee. Meeeeeeee, ee ee eeeeeeeeeee ee eeee eeeee eeeee eeeee ee eee ee eeeee ee eeeeee eeeeeeeeeeee eeeeeee.

Meeeee-Meeeeeee Meeeeeeee M—M Meeeeeee: Mee eeeeeeeee eeeeeeee ee eeeeee eeee eeeeeeeeeee eeeee eeeeeeeee ee Meee eee Mee eee eeeeee e eeeeeeeeeeeee eeeeeeeeeee ee eeeeeee M-eeeeeeeee eeeeeeeee eee eee eeeeeeeee ee eeeeeeee eeeeee.[‌88‌,‌88‌] Mee eeeeeeee eeeeeee eee eeeeeeeee M—M eeeeeeee eeeeeee eeeeeeeeeeeeee eeeeee, eee eeee eeeeee eeeeeeeeeeee eeee eeeeeeee eee eeeeeeee eeeeeeeee eeeeeee eee eee ee eeeeee ee e eeeeeeee eeeeeee.[‌88‌,‌88‌]

Meee–Mee–Meeee eeeeeeeee eeee eeee eeeeeeeeee eeee eeeeeeee eeee eeeeeeeeeee eeeeee- eee eeeeeeeee-eeeeeeee eeeee eeeeeeeee. Meeeee-eeeeeeee eeeeeeeee eeeeeeee eeeeeeeee eee eeeee eeeeeeee eeeee eeee eeeeeeee eeeeeeeeee (e.e., eeee eeeeeeeeeee eeee ee eeeee eeee), eeeee eee ee eeeeeeeee eee eeeeeeeee eeeeeeeeee. Meeeeeeeeeee, eeeee eeeeeeeee eee eeeee eeeeeeee ee e eeee eeeee ee eeeeeeeeeeee. Mee eeeeeeeeeee ee eeee eeeeee eee eeeeeee ee eeeee ee eeeeee-eeeeeeee eeeeeeeeee eeeee eeee eeeeeee. Mee eeeeeee, eeeee eeeeeeeee eee eeeeeeeee ee eeeeee eeeeeeeeeeeeee, ee eeeeeeeee eeeeeeee eeeeee eee 8-eeeeeeeeeee eeeeeeeeeee eeeee eee eeeee eeeeeeeeeee eeeeeeeee eeeeeeeeeeee.[‌88‌]

Meee ee eeeeeeeeeeee eeeeeeeeee, eeeeee-eeeeeeee eeeeeeeee eeeee eeeeeeeee eeee eeeeeee eeeeeeeeeee. Meeee eeeeeeeee eee eeeee eee eeeee ee eeeeeee eeeeeeeeee, ee eeeeee ee eeeeeeee eeee ee e eeeeeeee eeeeeee. Me eeee eeeee, eeeee eeeeeeeee eee ee eeeeeeee eeeeeeeee eee eeeeeeeee eeeeee eee eeeee ee eeeeeeee eeeee, eeeeeeeeee eeeeeeeee eeeeeeeeee ee eee eeeeeee eeee eeee eee eeeeeeeeeeeee eeeeee. Meeee, eeeeeeeee eeeeeeee eeeee eee eeeeeeee eeeeeeeeeeeeeee eee ee eeeeeeee eeeeeee eee eeeeeeee ee e eeeeee-eeeeeeeeeeee eeeee. Meee-eeeee eeeeeeeeee eeeee, eeee ee eeeeeeeeeeeee eeee (eeeeeeee eeee), eee eeeee eeeeeeee eee eeee eeeeeee.[‌88‌]

References