Direct synthesis of 1,5-disubstituted-4-magnesio-1,2,3-triazoles, revisited

Organic Letters

Volumn 6, Issue 8, 2004, Pages 1237-1240

  Krasiński, Antoni ^a   Fokin, Valery V ^a   Sharpless, K Barry ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3 TRIAZOLE DERIVATIVE; ACETIC ACID DERIVATIVE; ALKYNE DERIVATIVE; AZIDE; BROMINE DERIVATIVE; MAGNESIUM DERIVATIVE;

ADDITION REACTION; ARTICLE; DRUG SYNTHESIS; METHODOLOGY;

ACETYLENE; ALKYNES; AZIDES; BROMIDES; CHEMISTRY, PHARMACEUTICAL; MAGNESIUM; MOLECULAR STRUCTURE; TRIAZOLES;

EID: 2442698173     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0499203     Document Type: Article

References (24)

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19. 4Cl, the products are extracted using ethyl acetate or chloroform. Provided the azide-acetylide couple is reactive and there is no intention of in situ derivatization of the 4-magnesio-triazole, the reactions can even be performed on 2 mmol or larger scale with no special precautions concerning moisture or oxygen exclusion, in screw-capped vials. In the case of less reactive (electron-rich aromatic) azides and/or when further functionalization of the intermediate 4-halomagnesio triazoles is intended, maintaining complete dryness is crucial.
20. This particular compound was synthesized at the concentration of 2.0 M at room temperature in 4 h. The reaction times for less active azides (e.g., p-methoxyphenyl azide) can be shortened to about 1 h at 50°C.
21. Similar observations were made in the copper(I)-catalyzed reaction, described in ref 9.
22. Structures tentatively assigned by mass spectrometry.
23. However, it is important to note that labeling of the 4-position with the other isotopes of hydrogen, namely, deuterium (98% D incorporation, Table 2, entry 1) and tritium can be very useful for mechanistic and biological studies. Once attached to the carbon at the 4-position of the 1,5-disubstituted triazoles, the hydrogen atom is very difficult to remove (Begtrup, M., personal communication; ref 3b suggests that 5-lithiation of triazoles is strongly favored over 4-lithiation, even in the absence of a directing group at the 1-position).
24. Reactions between phenyl azide and chloromagnesium phenylacetylide were performed on 6 mmol scale at 50°C for 1 h, and then the electrophile (neat or as a concentrated THF solution) was added. For experimental procedure see ref 10.