Inverse-electron demand Diels Alder Reactions between glycals and tetrazines

Cecilia H Marzabadi; Stephen P Kelty; Alexandra Altamura

doi:10.1016/j.carres.2022.108623

Inverse-electron demand Diels Alder Reactions between glycals and tetrazines

Carbohydr Res. 2022 Sep:519:108623. doi: 10.1016/j.carres.2022.108623. Epub 2022 Jun 17.

Authors

Cecilia H Marzabadi¹, Stephen P Kelty², Alexandra Altamura³

Affiliations

¹ Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Ave., South Orange, NJ, 07079, USA. Electronic address: cecilia.marzabadi@shu.edu.
² Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Ave., South Orange, NJ, 07079, USA; Center for Computational Research, Seton Hall University, South Orange, NJ, 07079, USA.
³ Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Ave., South Orange, NJ, 07079, USA; Hackensack Meridian Medical School, 340 Kingsland St, Nutley, NJ, 07110, USA.

PMID: 35738050
DOI: 10.1016/j.carres.2022.108623

Abstract

The inverse-electron demand Diels Alder reaction (IEDDA) of substituted tetrazines with 2,3-unsaturated sugars (glycals) has been investigated to prepare novel carbohydrate-based heterocycles. The cycloaddition reactions occurred in moderate to good, isolated yields and gave acyclic, C-linked pyranose diazines as the major products (33-90%). The effects of variations in sugars, sugar protecting groups, and reaction solvents on the yields and products obtained in these reactions were studied. Lower yields of adducts were isolated for TBDMS-protected glucals and for 4,6-O-benzylidene protected glucals. When unprotected sugars were used, the reactions failed to give the desired cycloadducts. A range of substituted tetrazines were also evaluated in these reactions. For comparison, HOMO-[LUMO + 1] gaps for glycal-tetrazine pairs were calculated using Density Functional (DFT) calculations at the B3LYP/631G+ level.

Keywords: Glycal; HOMO-[LUMO + 1] gaps; IEDDA cycloaddition; Pyridazine; Tetrazine.

MeSH terms

Cycloaddition Reaction*
Electrons
Heterocyclic Compounds*
Sugars

Substances

Heterocyclic Compounds
Sugars