Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1 H-triazoles and regiospecific access to bromomethylcoumarins from Morita-Baylis-Hillman adducts

Abstract

The direct transformation of Morita-Baylis-Hillman (MBH) adducts into molecules of interest is a crucial process wherein allylic hydroxy-protected or halogenated MBH adducts are commonly preferred. Herein, we report an azidophosphonium salt (AzPS)-catalysed straight forward protocol for synthesising structurally demanding (E)/(Z)-cinnamyl-1H-1,2,3-triazoles and halomethylcoumarins from MBH adducts. The novel methodology, efficient catalyst, and direct utilization of MBH adducts under mild reaction conditions qualify the reported procedures as powerful synthetic tools.

Keywords: Morita–Baylis–Hillman adducts; halomethylcoumarin; organocatalyst; phosphonium salt; triazolation.

Scheme 1

Literature-reported cycloaddition reactions of MBH acetates involving azides and alkynes [–28].

Scheme 2

Synthetic methodologies for triazolations of MBH adducts. a) Literature-reported indirect triazolation of MBH adducts [–33]. b) This work: phosphonium salt-catalysed triazolation of MBH adducts.

Scheme 3

Scope of the one-pot cascade reaction of the unprotected Morita–Baylis–Hillman adducts 3a–q.

Figure 1

Proposed mechanism for the synthesis of 1,4-disubstituted triazoles.

Scheme 4

Comparative analysis of the sequential one-pot reaction.

Figure 2

Proposed mechanism for the synthesis of 3-(bromomethyl)coumarins.