Science of Synthesis

Tomé, A. C., Science of Synthesis Knowledge Updates, (2015) 2, 63.

The ruthenium(II)-catalyzed azide–alkyne cycloaddition reaction was reported for the first time in 2005 by Fokin and Sharpless.[‌4‌] Using terminal alkynes, and depending on the ligand, these reactions afford exclusively the 1,5-disubstituted 1,2,3-triazoles or the 1,4-disubstituted 1,2,3-triazole regioisomers (see below). In their initial studies, these authors found that chloro(η5-pentamethylcyclopentadienyl)bis(triphenylphosphine)ruthenium(II) [Ru(Cp*)Cl(PPh3)2] is an efficient catalyst for ruthenium(II)-catalyzed azide–alkyne cycloaddition for terminal or internal alkynes.[‌4‌,‌126‌–‌128‌] Later, it was found that chlo­ro(η5-pentamethylcyclopentadienyl)ruthenium(II) tetramer [{Ru(Cp*)Cl}4] in dimethylformamide performs significantly better than chloro(η5-pentamethylcyclopentadienyl)bis(triphenylphosphine)ruthenium(II) (‌Scheme 5‌).[‌129‌] In addition, higher yields of tri­azoles ‌9‌ are obtained and shorter reaction times are required when the reactions are carried out under microwave irradiation.

‌Meeeee 8‌ Meeeeeeee Meeeeeeeeee ee 8,8-Meeeeeeeeeeee 8,8,8-Meeeeeeee eee Meeeeeeee(MM)-Meeeeeeee Meeee–Meeeee Meeeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 8‌

M8	M8	Meeee (%)	Mee
Me	Me	88	[‌888‌]
8-MM8M8	Me	88	[‌888‌]
8-MeMM8M8	Me	88	[‌888‌]
8-Mee	Me	88	[‌888‌]
8-Mee	Me	88	[‌888‌]
8-MeM8MM8M8	Me	88	[‌888‌]
Me	MM8MMe	88	[‌888‌]
Me	(MM8)8MM	88	[‌888‌]
Me		88	[‌888‌]
Me		88	[‌888‌]
Me	(MM8)8MMeee	88	[‌888‌]
Me	8-eeeeeee	88	[‌888‌]
Me	MM8MM(MM8Me)8	88	[‌888‌]

M eeeeeeeeee eeeeeee ee eee eeeeeeeee eeeeeeeee ee eeeee eeeeeee ee eeee eeeeee eeeeeeee eeeeeee ee eee eeeeeeeeeeeee eeee eeeeeee eeeeee, eeeeeeeee ee eee eeeeeeeee ee 8,8,8-eeeeeeeeeeeeee 8,8,8-eeeeeeeee.[‌8‌,‌888‌,‌888‌] Meee eeeeeeeeee eeeeeeee eeeeeee eee eeee, eee eeeeeeeeeeeeeeee ee eee eeeeeeeeeeeee ee eeeeeeeeee ee eeeeeee eeeeeee: (e) ee eee eeeeee eeeeeeee e eeeeeeee eeee eeeee eeeee (e.e., eeeeeeeeeee eeeeeeee eee eeeeee) eee eee eeee ee eeeeee eeeeee eeeeeee eee β-eeeeee ee eee eeeeee eee eee eeeeeeee eeeeeeee ee eee eeeee; (e) ee eee eeeeeee ee eeee eeeeeeeee eeeeee, eeeeeeeeeeeeeeee ee eeeeeeee eeeeeeeee ee eee eeeeeeeeee (eee eeeeeeee ee eeeeee) eeeeeeeeee ee eee eeeeee: eee eeee eeeeeeeeeeeeeee eeeeee ee eee eeeeee eeeeeee M8 ee eee eeeeeeee.[‌888‌] Mee eeeeeeeee ee eee eeeeeeeee(MM)-eeeeeeeee eeeee–eeeeee eeeeeeeeeeeee eeeeeeee eee eeee eeeeeee ee eeeeeee eeeeeeeeee eeeeeee.[‌888‌,‌888‌]

Mee eeeeeeeee eeeeeeee (eeeee eee eeeeeeeee) ee e eeeeee ee eeeeee(η8-eeeeeeeeeeeeeeeeeeeeeeeeeee)eeeeeeeee(MM) eeeeeeeee ee eeeee–eeeeee eeeeeeeeeeeeee eee eeeeeeeee eee eeeeee(η8-eeeeeeeeeeeeeeeeeeeeeeeeeee)eee(eeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [Me(Me*)Me(MMe8)8], eeeeee(eeeeeeeee-8,8-eeeee)(η8-eeeeeeeeeeeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [Me(Me*)Me(eee)], eee eeeeee(eeeeeeeeeeeee)(η8-eeeeeeeeeeeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [Me(Me*)Me(eee)] eeee eeeee ee ee eee eeee eeeeeeeee eeeeeeeee.[‌888‌] Mee eeeeeeeeeee ee eeeeeeeee eeeeeeeee eeee eee eeeeeee eeeeeee Me(Me*)M(M) (M = eeeeeeeee ee M-eeeeeeeeeeee eeeeeee eeeeee; M = Me ee MMM8MM8) eee eeee eeeeeeee ee eeeee–eeeeee eeeeeeeeeeeee eeeeeeeee. Mee eeeeeeeee eeeeeeeee eeeeee(η8-eeeeeeeeeeeeeeeeeeeeeee­eeee)(eeeeeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [Me(Me*)Me{M(eMe)8}] eee eeeeee(η8-eeeee­eeeeeeeeeeeeeeeeeeeeee)(eeeeeeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [Me(Me*)Me(MMe8)] eeeeeeeee eee eeee eeeeeeeee eeeeeeeeeee (eeeeeeeeeee ~88%) eee, ee eee eeeee, eee 8,8-eeeeeeeeeee eee eee eeee eeeeeee.[‌888‌] Mee eeeeeeeee eeee eeeeeee eee ee eeeeeeeeeeeeeee ee eeee eeeeeeeeeee eeee 8 eee% ee eeeeeeeee eeeeeeee. Mee eeeee-eeee eeeeeeeee (eeeeeee eeeeeeeee) eeeeeeeee eeeee eee eeee eeeeeeeeee eeee <8% eeeeeeeeee.

Mee eeeeeeeee(MM)-eeeeeeeee eeeee–eeeeee eeeeeeeeeeeee eeeeeeeee eee ee eeeeeeeeeeee eeeeeee ee eeeeeeeeeeeeeeee(MM) ee eeeeeeeeeeeeeee(MM) eeeeeeeee eeeee eee eeeeee(M)-eeeeeeeee eeeee–eeeeee eeeeeeeeeeeee eeeeeeee eeeee.[‌888‌] Mee eeeeeeeeeee eeeeeeeeeeee ee eeeeeeeee(MM)-eeeeeeeee eeeee–eeeeee eeeeeeeeeeeee eee, eee eeeeeee, eeee[‌888‌–‌888‌].

Mee eeeeee ee Mee eee Mee eeeeeeee e eeeeeeee eeeeee eeeeee ee eee eeeeeeeeeee ee eeeeeeeee(MM)-eeeeeeeee eeeee–eeeeee eeeeeeeeeeeee eeeeeeeee. Meeeeeeee(MM) eeeeeeeee eeeeeee eeeeeeeeeeeeeeee eeeeeee, eeee ee eeeeeeeeeeee(eeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [MeMe8(MMe8)8], eeeeeeee(eeeeee)eeeeeeeeeee(eeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [MeMeM(MM)(MMe8)8], eeeeeeeeeeeeeeeeeeeee(eeeeeeeeeeeeeeeeee)eeeeeeeee(MM) [MeM8(MM)(MMe8)8], eee eee(eeeeeeeeeeeeeeeeee)eeeeeeeee(MM) eeeeeee [Me(MMe8)8(MMe)8], eeeeeeee eee eeeeeeeeeeeee ee eeeeee eeeee eee eeeeeeeeeeeeeee ee eeee eeeeeeeeeee eee 8,8-eeeeeeeeeeeee 8,8,8-eeeeeeee eeeeeeeeeee.[‌888‌] Me eeee, eeee eeeeeeeeeeeeeeeeeeeee(eee­eeee­eeeeeeeeeee)eeeeeeeee(MM) ee eee eeeeeeee, eeeeeee eeeeee eeeeeee eeeee eeee e eeeee ee eeeeeeee eeeeeee ee eeeeeee 8,8-eeeeeeeeeeeee 8,8,8-eeeeeeeee ‌88‌ eeee 888% eeeeeeeeeee eee eeeeeeee ee eeeeeeeee eeeeee (88–88%; ‌Meeeee 8‌). Meeee eeeeeeeee(MM) eeeeeeeee, eeee ee MeM(η8-MM8)(MM)(MMe8)8, eee eeee eeeeeeeee eeeeeeeee eee eee eeeeeeeeeeeee ee eeeeeee eee eeeeeeeee eeeee eeeeee eeee e eeeee ee eeeeeeee eeeeeee, eeeeeeee 8,8-eeeeeeeeeeeee 8,8,8-eeeeeeeee eeeeeeeeeee.[‌888‌]

‌Meeeee 8‌ Meeeeeeee Meeeeeeeeee ee 8,8-Meeeeeeeeeeee 8,8,8-Meeeeeeee eee Meeeeeeee(MM)-Meeeeeeee Meeee–Meeeee Meeeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 8‌

Meeeeeeeeeee Meeeeeeee

8,8-Meeeeeee-8M-8,8,8-eeeeeeee (‌8‌, M8 = M8 = Me); Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meee eeeeee eee eeeeeeeee, eee eeeeeeeeeee eeeeeeeee ee eeeeeeee ee eeee, eeeee, eee eeeeeeee.

Me e eeee ee MeM8 (888 ee, 8.88 eeee) eee eeeeeeeeeeeeeee (888 ee, 8.8 eeee) ee MMM (8 eM) eee eeeee [{Me(Me*)Me}8] (88 ee, 8.8 eeee). Mee eeee eee eeeeeee eeee M8, eeeeee, eee eeeeee (eeeeeeeee) ee 888 °M eee 88 eee. Me eee eeeeeee eeee eeeee MeMMe (88 eM) eee M8M (88 eM). Mee eeeeee eeee eeeeeeeee eee eee eeeeeee eeeee eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee eeeee (8 × 88 eM), eeeee (MeMM8), eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Meeee eeeeeeeeeeeeee (MeMMe/eeeeee 8:8) eeeeeee eee eeeeeee ee e eeeee eeeee; eeeee: 88%; (ee 888–888 °M).

References