Beilstein J. Org. Chem.2018,14, 2689–2697, doi:10.3762/bjoc.14.246
was carried out for several salicylaldehydes and gave a clear improvement in the yield of the corresponding triazolochromenes and consequently showed to be a viable alternative for solid salicylaldehydes.
Keywords: ball milling; multicomponent reaction; 3-nitro-2H-chromene; one-pot synthesis; 1,2,3
prove the plausibility of the one-pot three-component reaction, we commenced our trials with the synthesis and isolation of 3-nitro-2H-chromene (3) as reported in the literature [15], followed by the 1,3-dipolar cycloaddition of the nitroalkene moiety with organic azides. We based the 1,3-dipolar
desired product 5a was obtained in 67% yield, together with an oxidized ring opened side product 6 in 20% yield. The overall yield of 5a after two steps was 48%, considering that the 3-nitro-2H-chromene (3) was obtained in a yield of 71%.
We continued our studies by verifying the obtained regiochemistry
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Graphical Abstract
Scheme 1:
Two-step reaction towards triazolochromene 5a and obtained oxidized side product 6.
Beilstein J. Org. Chem.2016,12, 462–495, doi:10.3762/bjoc.12.48
resulting enolate is directed to the upper face of the 3-nitro-2H-chromene due to hydrogen bonding of the enolate with the ammonium cation. The thiourea moiety, firstly activates the 3-nitro-2H-chromene through two hydrogen bonds, making it more electrophilic (LUMO lowering effect) and secondly it orients
(Scheme 42) [62]. The resulting (R)-3-nitro-2H-chromene was isolated in rather moderate optical purity.
In 2010, a domino Michael hemiacetalization reaction was reported between cyclic 1,3-dicarbonyl compounds 134 and β-unsaturated α-ketoesters 87 utilizing a novel tyrosine-derived thiourea 135 (Scheme 43
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Graphical Abstract
Scheme 1:
Activation of carbonyl compounds via enamine and iminium intermediates [2].