Preparation of Highly Functionalised Benzofurans from ortho‐Hydroxyphenones and Dichloroethylene: Applications and Mechanistic Investigations

Abstract

Highly functionalised benzofurans have been prepared from ortho-hydroxyphenones and 1,1-dichloroethylene. The key intermediate, a chloromethylene furan, smoothly rearranged into the corresponding benzofuran carbaldehyde under acidic conditions. Some mechanistic investigations have been performed and several biologically active benzofurans have been synthesised.

Highly Stereoselective Synthesis of Terminal Chloro-Substituted Propargylamines and Further Functionalization

“…However, reaction of commercially available 1,2-dihaloethenes with organolithium reagents efficiently generates lithiated haloacetylides in situ via E2 elimination and deprotonation as shown in Scheme . As lithiated haloacetylides generated in this manner have been shown to be effective nucleophiles with carbonyl electrophiles, we envisioned that this approach could be applied in the diastereoselective addition to chiral imines. Due to the good diastereoselectivities observed in the addition of lithium acetylides to Ellman N - t -BS imines (up to >99:1 dr) and the success of a similar strategy by Poisson and co-workers in the addition of lithiated ynol ethers (derived from dichloroenol ethers) to N - t -BS imines, we chose to explore the use of these chiral imines to access optically active terminal halo-substituted propargylamines.…”

Diastereoselective Synthesis of Terminal Bromo-Substituted Propargylamines via Generation of Lithium Bromoacetylide and Addition to Chiral N-tert-Butanesulfinyl Aldimines

“…We began by exploring the in situ generation of the bromoacetylide nucleophile and addition to phenyl N - t -BS aldimine 1a as shown in Table . Following a slight modification of Markó’s reaction conditions, a cis/trans mixture of 1,2-dibromoethene was treated with 2 equiv of LDA (2.0 M solution in THF/heptane/ethylbenzene) at −78 °C for 30 min to generate lithium bromoacetylide. Phenyl N - t -BS aldimine 1a was then added, and the reaction was placed in an ice bath and allowed to react for 1 h. This procedure (Table , entry 1) produced the desired terminal bromo-substituted propargylamine 2a in moderate yield (48%) and stereoselectivity (dr = 5:1).…”

“…In contrast to our unsuccessful attempts to generate and intercept lithium bromoacetylide with N - t -BS aldimines, Markó and co-workers demonstrated that lithium bromoacetylide could be generated from the reaction of 1,2-dibromoethene (commercially available as a mixture of cis/trans isomers) and LDA and subsequently added to a ketone electrophile as shown in Scheme b . Markó’s report, combined with the considerable precedent for the addition of lithium acetylides to Ellman N - t -BS imines, , led us to hypothesize that generation of lithium bromoacetylide and addition to N - t -BS aldimines should be possible and sparked further efforts in our laboratory toward that goal.…”

Synthesis and Application of [3.3.0]Furofuranone in Total Synthesis

“…Treatment of methyl propiolate with LDA followed by addition of 4‐hydroxy‐2‐butanone 84 gave rise to exo ‐methylene ester 85 through an allenyl enolate intermediate. Ester 85 underwent Michael addition of the methoxy group followed by a spontaneous lactonization to afford adduct 86 (Scheme ) …”