Synthesis of 7‐Azido‐3‐Formylcoumarin – A Key Precursor in Bioorthogonally Applicable Fluorogenic Dye Synthesis

Abstract

Coumarins represent an important group of natural products and a common part of various drugs and fluorescent dyestuffs. Herein, we present the synthesis of a coumarin that can serve as a key starting material in the design and synthesis of bioorthogonally applicable fluorogenic dyes. The synthesis of 7‐azido‐3‐formylcoumarin started from 7‐diallylaminocoumarin. This allyl protected aminocoumarin is otherwise hard to obtain by conventional methods but was conveniently accessed in good yields by a sequential, Wittig‐reaction–UV isomerization process. This sequential approach was studied in more details and applied for the synthesis of a series of substituted coumarins even in one‐pot.

Heptafluorobutyric Acid Catalyzed Cross-Dehydrogenative Coupling of 7-Aminocoumarins with 1,2,4-Triazines: A Straightforward Pathway to 3-Triazinyl-7-aminocoumarins

“…4-Unsubstituted 7-aminocoumarins 1a-d were prepared from the corresponding 4-aminosalicylic aldehydes and diethyl malonate according to the published procedure. 46 Spectroscopic data for compounds 1a-d were in agreement with the literature. 46 4-Methyl-, 4trifluoromethyl-and 4-hydroxy-7-diethylaminocoumarins (1g-i) were prepared from 3-(diethylamino)phenol and the corresponding ethyl acetoacetate or diphenyl malonate according to the published procedure.…”

“…46 Spectroscopic data for compounds 1a-d were in agreement with the literature. 46 4-Methyl-, 4trifluoromethyl-and 4-hydroxy-7-diethylaminocoumarins (1g-i) were prepared from 3-(diethylamino)phenol and the corresponding ethyl acetoacetate or diphenyl malonate according to the published procedure. 47,48 The spectroscopic data for compounds 1g-i were in agreement with the literature.…”

Recent Advances in Biologically Active Coumarins from Marine Sources: Synthesis and Evaluation

“…As a result of the importance of these scaffolds in organic and medical chemistry, many synthetic routes to obtain simple substituted coumarins have been explored over the years [ 38 , 39 ]. The most classical strategies involve Knoevenagel [ 40 ], Pechmann [ 41 ] and Perkin [ 42 ] condensations, intramolecular [ 43 , 44 ] and intermolecular Wittig reactions [ 45 ], ring-closing metathesis [ 46 ], as well as different reactions between the corresponding salicylaldehydes with ketene [ 47 ] or arylacetonitriles ( 18 ) [ 48 ] ( Scheme 1 ).…”