Application of Glaser-Hay Diyne Coupling To Constrain Nα-Amino Acid Amides via a N-N Bridge

Sergii Okorochenkov; Viktor Krchňák

doi:10.1021/acscombsci.8b00179

Application of Glaser-Hay Diyne Coupling To Constrain N^α-Amino Acid Amides via a N-N Bridge

ACS Comb Sci. 2019 Apr 8;21(4):316-322. doi: 10.1021/acscombsci.8b00179. Epub 2019 Feb 11.

Authors

Sergii Okorochenkov¹, Viktor Krchňák^{1

2}

Affiliations

¹ Department of Organic Chemistry, Faculty of Science , Palacky University , 17. Listopadu 12 , 771 46 Olomouc , Czech Republic.
² Department of Chemistry and Biochemistry, 251 Nieuwland Science Center , University of Notre Dame , Notre Dame , Indiana 46556 , United States.

PMID: 30673274
DOI: 10.1021/acscombsci.8b00179

Abstract

We present the application of a Glaser-Hay diyne coupling for the synthesis of conformationally constrained N^α-amino acid amides with different diyne ring sizes. Twelve-membered rings were the smallest rings that could be prepared by this approach. We observed the formation of triethylammonium adducts in the cases of smaller (10- and 11-membered) rings. Calculation of the conformational barriers for the cyclization reactions of various ring sizes demonstrated that the formation of amino acid-derived smaller rings by this reaction is thermodynamically unfavorable.

Keywords: Amino acid constrain; Glaser−Hay diyne coupling; medium-sized ring; solid-phase synthesis; triethylammonium adduct.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkynes / chemistry
Amides / chemical synthesis*
Amines / chemistry
Amino Acids / chemistry*
Catalysis
Cyclization
Diynes / chemistry*
Models, Molecular
Molecular Conformation
Solid-Phase Synthesis Techniques / methods
Thermodynamics

Substances

Alkynes
Amides
Amines
Amino Acids
Diynes