Science of Synthesis

Scholz, U.; Dong, W.; Feng, J.; Shi, W., Science of Synthesis: Cross Coupling and Heck-Type Reactions, (2013) 2, 93.

The amination of thiazoles or benzothiazoles has been demonstrated by two major copper-catalyzed approaches. A highly versatile protocol with very mild reaction conditions uses copper(I) iodide as the catalyst and potassium hydroxide as the base. No ligand is necessary; however, the reaction is run in a biphasic mixture of water and chloroform and uses a phase-transfer catalyst to allow for good conversions at 35–40 °C, giving aminothiazoles such as ‌73‌ [R1 = H; R2,R3 = (CH2)2O(CH2)2] (‌Scheme 51‌).[‌82‌] In the case of a bifunctional nucleophile such as piperazine, full conversion to the diarylated product is observed using the above conditions, probably due to the better solubility of the monoarylated intermediate in chloroform. However, when chloroform is replaced by a more polar solvent such as ethanol, a clear selectivity for the monoarylated species ‌73‌ [R1 = H; R2,R3 = (CH2)2NH(CH2)2] is observed. In the case of bromothiazoles, a standard approach using copper(I) iodide, proline as the ligand, and potassium carbonate as base in dimethyl sulfoxide also gives the respective products in good yields.[‌98‌] A variety of alkylamines can be used successfully following this protocol.

‌Meeeee 88‌ Meeeeeeee ee Meeeeeee Meeeeeeeeeeee[‌88‌,‌88‌]

‌Meeeeeeeeee 88‌

M	M8	M8	M8	Meeeeeeeee	Meeee (%)	Mee
Me	M	(MM8)8M(MM8)8		MMM, Me8MeM+Me−, M8M/MMMe8, 88–88 °M	88	[‌88‌]
Me	M	(MM8)8MM(MM8)8		MMM, Me8MeM+Me−, MeMM, 88–88 °M	88	[‌88‌]
Me	M(M)MM(MM8)8Me	M		eeeeeee, M8MM8, MMMM, eeeeeeeee, 888 °M,	88	[‌88‌]
Me	M(M)MM(MM8)8Me	M		eeeeeee, M8MM8, MMMM, eeeeeeeee, 888 °M	88	[‌88‌]
Me	M(M)MM(MM8)8Me			eeeeeee, M8MM8, MMMM, eeeeeeeee, 888 °M	88	[‌88‌]
Me	M(M)MM(MM8)8Me	(MM8)8M(MM8)8		eeeeeee, M8MM8, MMMM, 888 °M	88	[‌88‌]

Meeeeeeeeeee Meeeeeeee

8-Meeeeeeeeeeeeeeeee [‌88‌, M8 = M; M8,M8 = (MM8)8M(MM8)8]; Meeeeee Meeeeeeee:[‌88‌]

Me e eeeee-eeeeeeee eeeee, eeeeeeeeee (8.88 e, 8.888 eee) eee MeM (8.88 e, 8.888 eee) eeee eeeeeee eee 88 eee, eeeeeee e eeee eeee. Me eeee eeeeeee, MMM (8.88 e, 8.88 eee) eeeeeeeee ee M8M (8 eM) eee eeeee eee eeeeeeee eee eeeeeeeee eee 88 eee. Meee, Me8MeM+Me− (8.888 e, 8.888 eeee) eee eeeee eeeeeeee ee eee eeeeeeee ee 8-eeeeeeeeeeeeee (8.88 e, 8.88 eee) ee MMMe8 (88 eM). Mee eeeeeee eee eeeeeee eee 8 e ee 88–88 °M. Mee eeeeeee eeeee eee eeeeeeeee eee eee eeeeeee eeeee eee eeeeee eeee MMMe8 (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeee (Me8MM8) eee eee eeeeeeee eeee eeeeeeeeee ee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee; eeeee: 8.88 e (88%).

References