Product Class 13: 1,2,3-Triazoles

A solid-phase, regioselective, copper(I)-catalyzed, 1,3-dipolar cycloaddition of terminal alkynes
to azides has been used to prepare peptido-1,2,3-triazoles. [145] Copper(I) salts are
used as catalysts in the reaction of resin-bound terminal alkynes to primary, secondary,
and tertiary alkyl azides, aryl azides, and an azido sugar at 258C, affording selectively 1,4disubstituted
1H-1,2,3-triazoles with quantitative conversions and purities ranging from
75 to 99%. [145]
13.13.1.1.3.1.1.3.5 Variation 5:
Intramolecular 1,3-Dipolar Cycloadditions
The intramolecular 1,3-dipolar cycloaddition of an azido group onto a C”C bond gives
polycyclic triazoles. Azides 122 and 124, for example, give triazoles 123 (52%) and 125
(59%), respectively, when heated in refluxing toluene (Scheme 50). [146]
Scheme 50 Synthesis of 1,2,3-Triazoles via Intramolecular
1,3-Dipolar Cycloadditions [146]
N 3
122
OH
toluene, reflux, 36 h
52%
N
N
N
123
HO OTBDMS
HO
N 3
124
FOR PERSONAL USE ONLY
450 Science of Synthesis 13.13 1,2,3-Triazoles
toluene, reflux, 24 h
59%
OH
N
N
N
125
OTBDMS
Propargyl azides 127 undergo intramolecular cycloaddition reactions yielding N-unsubstituted
1H-1,2,3-triazoles 130 (Scheme 51). The reaction must be carried out in nucleophilic
solvents, such as methanol or ethanol, or in the presence of nucleophiles such as
azide ion, amines, or thiols, if not, then only polymeric triazole products are obtained.
The mechanism of this transformation involves the rearrangement of the propargyl azide
to allenyl azide 128 that gives by rapid ring closure the triazafulvene 129. This short-lived
intermediate is trapped by nucleophiles to give triazoles 130 in good yields. [147,148] Since
propargyl azides can be prepared from propargyl halides or propargyl tosylates 126
(X = halogen, OTs) and sodium azide, various substituted 1,2,3-triazoles can be synthesized
in good yields in one-pot procedure from these precursors without the necessity to
isolate the potentially hazardous propargyl azides. In the presence of sodium hydroxide
the propargyl azides 127 undergo base-catalyzed (prototropic) rearrangement to allenyl
azides 131. The immediate cyclization of this intermediate leads to the triazafulvene
132, which can be trapped by nucleophiles to give triazoles 133 in good yields (Scheme
51). [148]
A. C. TomØ, Section 13.13, Science of Synthesis, 2004 Georg Thieme Verlag KG