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. 2016 Sep 16;18(18):4566-9.
doi: 10.1021/acs.orglett.6b02088. Epub 2016 Aug 29.

Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino, and Carboxyl Groups via the Nicholas Reaction

Sarah M Wells  1 , John C Widen  2 , Daniel A Harki  2 , Kay M Brummond  1
Affiliations

Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino, and Carboxyl Groups via the Nicholas Reaction

Sarah M Wells et al. Org Lett. .

Abstract

The Nicholas reaction has been applied to the installation of alkyne ligation handles. Acid-promoted propargylation of hydroxyl, sulfhydryl, amino, and carboxyl groups using dicobalt hexacarbonyl-stabilized propargylium ions is reported. This method is useful for introduction of propargyl groups into base-sensitive molecules, thereby expanding the toolbox of methods for the incorporation of alkynes for bio-orthogonal reactions. High-value molecules are used as the limiting reagent, and various propargylium ion precursors are compared.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Synthetic methods for alkyne incorporation.
Scheme 1
Scheme 1
Decomplexation of Co2(CO)6-alkyne 7.
Scheme 2
Scheme 2
Reaction of primary amine 9h with BF4− salt 12.
Scheme 3
Scheme 3
Synthesis of alkyne probes 15 and 17.
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