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

Sarah M. Wells; John C. Widen; Daniel A. Harki; Kay M. Brummond

doi:10.1021/acs.orglett.6b02088

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

Sarah M. Wells, John C. Widen, Daniel A. Harki, Kay M. Brummond

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4566-4569
Number of pages	4
Journal	Organic Letters
Volume	18
Issue number	18
DOIs	https://doi.org/10.1021/acs.orglett.6b02088
State	Published - Sep 16 2016

Bibliographical note

Funding Information:
We acknowledge the NIH (R21-CA194661 to D.A.H. and R01-GM054161 to K.M.B.) and the Department of Defense (PC141033 to D.A.H.) for funding. Mass spectrometry performed at the University of Minnesota was conducted at the Masonic Cancer Center Analytical Biochemistry Core Facility, which is supported by the National Institute of Health (P30-CA77598).

Publisher Copyright:
© 2016 American Chemical Society.

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10.1021/acs.orglett.6b02088

http://europepmc.org/articles/pmc5234733

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

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.",

author = "Wells, {Sarah M.} and Widen, {John C.} and Harki, {Daniel A.} and Brummond, {Kay M.}",

note = "Funding Information: We acknowledge the NIH (R21-CA194661 to D.A.H. and R01-GM054161 to K.M.B.) and the Department of Defense (PC141033 to D.A.H.) for funding. Mass spectrometry performed at the University of Minnesota was conducted at the Masonic Cancer Center Analytical Biochemistry Core Facility, which is supported by the National Institute of Health (P30-CA77598). Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

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doi = "10.1021/acs.orglett.6b02088",

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AU - Wells, Sarah M.

AU - Widen, John C.

AU - Harki, Daniel A.

AU - Brummond, Kay M.

N1 - Funding Information: We acknowledge the NIH (R21-CA194661 to D.A.H. and R01-GM054161 to K.M.B.) and the Department of Defense (PC141033 to D.A.H.) for funding. Mass spectrometry performed at the University of Minnesota was conducted at the Masonic Cancer Center Analytical Biochemistry Core Facility, which is supported by the National Institute of Health (P30-CA77598). Publisher Copyright: © 2016 American Chemical Society.

PY - 2016/9/16

Y1 - 2016/9/16

N2 - 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.

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

Abstract

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