Catalyst-Free [4+2] Cycloaddition of Ynamides with 2-Halomethyl Phenols To Construct 2-Amino-4H-Chromenes and α-Halo Enamides Simultaneously

Abstract

We report the development of a facile protocol for the [4+2] cycloaddition of ynamides and 2-halomethyl phenols to afford the corresponding 2-amino-4H-chromenes and α-halo enamides under catalyst-free conditions. The reaction proceeds under mild conditions and exhibits good tolerance toward various functional groups and generates high yields. The plausible mechanism involves the formation of an active intermediate keteniminium as well as o-methylene quinone.

Multicomponent Reactions (MCRs) with o‐Quinone Methides

“…The [4 + 2] cycloaddition of 2-halomethyl phenols 218 a-c with ynamide derivative 219 to construct 2-amino-4Hchromenes (220 a-c) and α-haloenamides (221 a-b) simultaneously under catalyst-free conditions was recently reported by Tang et al (Scheme 24a-b). [66] In the plausible mechanism, hydroxy-containing compounds 218 a-c can be deprotonated by ynamide 219, resulting in the formation of keteniminium 221 a and ortho-quinone methides 223 a-c. Subsequently, nucleophilic attack of bromide ion on the less hindered side of the compound 222 led to formation of (E)-α-bromoenamide 221 a.…”

“…Subsequently, nucleophilic attack of bromide ion on the less hindered side of the compound 222 led to formation of ( E )‐α‐bromoenamide 221 a . The 2‐amino‐4 H ‐chromenes 220 a – c were obtained in good yields from the parallel [4+2] cycloaddition of o ‐QMs 223 a – c with another equivalent of yanamide 221 a [66] …”

“…The 2-amino-4H-chromenes 220 a-c were obtained in good yields from the parallel [4 + 2] cycloaddition of o-QMs 223 a-c with another equivalent of yanamide 221 a. [66]…”

α-Haloenamides: Synthesis and Subsequent Transformations

“…This process that necessitates the use of 2 equivalents of ynamide provides a general way to construct 2-amino-4H-chromenes and α-bromo-or α-chloroenamides simultaneously in one step (Scheme 17). 22 Scheme 17 α-Haloenamides and 2-amino-4H-chromenes from ynamides and 2-halomethylphenols.…”

“…This process, which necessitates the use of 2 equivalents of ynamide, provides a general way to construct 2-amino-4Hchromenes and -bromo-or -chloroenamides simultaneously in one step (Scheme 17). 22…”