Tungsten-Promoted Intramolecular Annulation of Propargyl Bromides with Ketones and Aldehydes for Synthesis of Fused 2,5-Dihydrofurans

Abstract

Metal carbonyl salts CpW(CO) 3 Na, Re(CO) 5 Na, and CpFe(CO) 2 Na were used for intramolecular cyclization of 1-(3-bromo-1-propynyl)-2-(3-oxopropyl)benzene. Among these salts, CpW(CO) 3 Na was found to be the most effective in yielding a metalated fused η 1 -2,5-dihydro-3-furyl complex. To generalize this cyclization, a number of organic substrates containing propargyl bromide and tethered aldehyde or ketone were prepared. Cyclizations of these substrates by CpW(CO) 3 Na proceeded with moderate yields (50%-65%), producing fused tungsten-η 1 -2,5-dihydrofur-3-yl compounds of five-, six-, and seven-membered rings. Demetalations of these organometallic products by (NH 4 ) 2 Ce(NO 3 ) 6 in CH 3 OH/CH 2 Cl 2 under flowing CO provided fused 3-(methoxycarbonyl)-2,5dihydrofurans; the yields were 50-60% for most cases. Consecutive oxidations of the representative η 1 -2,5-dihydrofur-3-yl complex 15 to its fused η 1 -2-furyl and further to η 1 -butenolide derivative were accomplished in good yields. Demetalations of these two fused η 1 -heterocycles were successful for η 1 -butenolide but not for the η 1 -2-furyl derivative.

Tungsten-Mediated Syntheses of Fused α-Methylenebutyrolactones from Propargyl Bromides Containing Tethered Aldehydes and Ketones

“…The η 1 -propargyl compound 2 was readily prepared from the 1:1 stoichiometric reaction between CpW(CO) 3 Na and 3-[2-(3-bromoprop-1-ynyl)phenyl]propionaldehyde ( 1 ) . We previously reported that tungsten−η 1 -propargyl species underwent alkoxycarbonylation reaction 4a in the presence of Bronsted acid catalyst.…”

“…In this 1:1 stoichiometric reaction, CpW(CO) 3 Na showed kinetic differentation for the two functional groups; it reacted more rapidly with propargyl bromide to yield tungsten−propargyl species in high yields (>85%). In contrast, other metal anions such as CpFe(CO) 2 Na and Re(CO) 5 Na gave the corresponding propargyl species in low yields (0−30%) . One important feature of these tungsten−propargyl complexes is the lack of allenyl−propargyl equilibrium.…”

“…Previously, we have examined the reactions between metal carbonyl anions with propargyl bromides containing tethered aldehydes and ketones as depicted in Scheme (eq 3) . In this 1:1 stoichiometric reaction, CpW(CO) 3 Na showed kinetic differentation for the two functional groups; it reacted more rapidly with propargyl bromide to yield tungsten−propargyl species in high yields (>85%).…”

“…One important feature of these tungsten−propargyl complexes is the lack of allenyl−propargyl equilibrium. As shown in Scheme (eq 3), treatment of these tungsten−propargyl species with a suitable amount of Lewis acid delivered fused tungsten−2,5-dihydrofuryl compounds of five-, six-, and seven-membered carbocyclic rings, further providing bicyclic unsaturated ester after Ce(IV) oxidation …”

Carbonylation

“…This reaction has been used in a synthesis of avenaciolide 4.258 and isoavenaciolide (Scheme 4.89) 99. Related 1 -propargylic tungsten complexes 4.259 have been found to be sufficiently nucleophilic, with Lewis acid assistance, to attack aldehydes in an intramolecular fashion (Scheme 4.90) 100. The initial cyclisation products, believed to be 2 -allene complexes 4.260, cyclize to 1 -complexes 4.261, which can be oxidatively carbonylated to esters 4.262.…”