Microwave‐Assisted Organocatalyzed Rearrangement of Propargyl Vinyl Ethers to Salicylaldehyde Derivatives: An Experimental and Theoretical Study

Abstract

The microwave-assisted imidazole-catalyzed transformation of propargyl vinyl ethers (PVEs) into multisubstituted salicylaldehydes is described. The reaction is instrumentally simple, scalable, and tolerates a diverse degree of substitution at the propargylic position of the starting PVE. The generated salicylaldehyde motifs incorporate a broad range of topologies, spanning from simple aromatic monocycles to complex fused polycyclic systems. The reaction is highly regioselective and takes place under symmetry-breaking conditions. The preparative power of this reaction was demonstrated in the first total synthesis of morintrifolin B, a benzophenone metabolite isolated from the small tree Morinda citrifolia L. A DFT study of the reaction was performed with full agreement between calculated values and experimental results. The theoretically calculated values support a domino mechanism comprising a propargyl Claisen rearrangement, a [1,3]-H shift, a [1,7]-H shift (enolization), a 6π electrocyclization, and an aromatization reaction.

A Mild and Versatile Friedel–Crafts Methodology for the Diversity‐Oriented Synthesis of Redox‐Active 3‐Benzoylmenadiones with Tunable Redox Potentials

“…Most of the cited methodologies required dry conditions, high temperatures, or pre‐activation of the reagents. Nevertheless, noticeable progress has been made by using trifluoroacetic anhydride (TFAA) or trifluoroacetic acid/trifluoroacetic anhydride (TFA/TFAA), under mild heating conditions and air moisture, to allow the S E Ar of activated and non‐strong deactivated benzoic acids, depending on the nucleophilic strength of the aromatic compound.…”

A Domino Strategy for the Synthesis of 2H‐Pyrans from Propargyl Vinyl Ethers

“…These PVEs are easily accessible from ketones, through a two‐step procedure entailing: 1) generation of the tertiary propargylic alcohol, and 2) transformation of the alcohol into the corresponding β‐alkoxy‐acrylate derivative 6 . We have also shown that the microwave irradiation of these tertiary PVEs 6 in the presence of catalytic amounts of imidazole generates salicylaldehyde derivatives 8 through an all‐pericyclic domino process (Scheme c) . During these studies, we discovered that this process could be funneled toward the formation of trisubstituted 2HPCs 7 by a careful control of the temperature.…”

“…The propargyl vinyl ethers were prepared according to our previous experimental procedure (see below for a general procedure). Products 6a , 6e ,[18a] 6h , 6i 6j 6k ,[18b] 6l ,[18b] 6m , 6q ,[18b] 6r ,[18a] 6t ,[18a] 6u ,[18a] 7a , 7r ,[18a] and 18 have been described previously.…”

Recent Advances in the Synthesis of 2H-Pyrans

“…The protocol delivered 2HP structures endowed with different topologies, including monocycles ( 53 - mc ), 2,2-spiro-bicycles ( 53 - sbc ), and 2,2-spiro-macrobicycles ( 53 - smbc ). The main limitation arose from the presence of a t Bu substituent at the alkyne position (R 1 ): In this case, the reaction followed a different pathway through a sequential [1,7]- H shift/6π-electrocyclization/MeOH elimination set of reactions [54].…”