The Effect of the Carbon Ligand on the Reaction of Organozinc Reagents in the Synthesis of Substituted 2,5-Dihydrofurans: A Rare Example of An Uncatalysed Allylic-Substitution Reaction Involving Alkyl Zinc Halides

Abstract

Organozinc halides derived from Grignard reagents behave differently in their reaction with ethyl (±±)‐(2RS,3SR)‐tetrahydro‐4‐methylene‐2‐phenyl‐3‐(phenylsulfonyl)furan‐3‐carboxylate (3) according to the hybridisation of the carbon ligand. During the development of short multi‐component reactions for the synthesis of diverse functionalized ethyl 2,5‐dihydrofuran‐3‐carboxylates it was discovered that aryl and vinyl zinc halides undergo clean reaction with 3 in the presence of Pd(PPh3)4. In contrast, when alkyl zinc halides are reacted with 3 in the presence of Pd(PPh3)4, reductive desulfonation of 3 is observed. Remarkably, in the absence of a transition metal catalyst, the allylic substitution of 3 with alkyl zinc halides proceeds cleanly and in moderate to good yield.

Addition of Metal Enolate Derivatives to Unactivated Carbon−Carbon Multiple Bonds

“…Interestingly, this transformation could be achieved in situ in a multicomponent domino reaction. 307,308,317 The same strategy applied to nitroalkene as Michael acceptors 318 led to the formation of the corresponding pyrrolidine derivatives in moderate to good yields (46-68%, 3 examples). 308…”

“…306 A similar approach to dihydrofurans and pyrroline derivatives based upon a copper-catalyzed cyclization followed by an intramolecular Pd-catalyzed allylic substitution was disclosed shortly after by the same authors (see section 4.7.1). 307,308 Silyl enol ethers and silyl ketene aminals have been recently shown to undergo Pd(II)-catalyzed intramolecular addition onto alkynes. 309 In particular, the enantioselective cyclization of silyl enol ethers of aryl ketones was achieved at 0 °C or room temperature in the presence of 10 mol % of ((R)-DTBM-segphos)Pd(OTf) 2 in Et 2 O/AcOH (100:1).…”

“…Similarly, propargyl alcohol added onto ethyl 2-phenylsulfonylcinnamate 218 in the presence of catalytic amounts of NaH and a Cu(I) salt to give methylene tetrahydrofurans in good to high yields (Scheme 215). 307 The reaction could be carried out with CuI or with CuI(PPh 3 ) n (n ) 1-3) complexes, which are more soluble in organic solvents. The procedure was extended to solution-phase parallel synthesis of tetrahydrofurans.…”

Utilities of Some Carbon Nucleophiles in Heterocyclic Synthesis

“…Pb(OAc) 2 mate [76]. Upon treatment with Pd(0) and phenylvinyl zinc chloride, the methylene tetrahydrofuran 138 can be converted into a 2,3,4-trisubstituted-2,5-di-hydrofuran 139.…”

Addition of Tetrahydrofuran to [60]Fullerene through C−H Bond Activation Induced by Arylzinc Reagents

“…One possible pathway is shown in Scheme . We assume that the first step is a single-electron oxidation of the arylzinc reagent by fullerene that generates the corresponding aryl radical and a fullerene radical anion, and the second step is hydrogen atom abstraction from the 2-position of THF by the aryl radical. Coupling of the 2-tetrahydrofuranyl radical with the fullerene radical anion produces the mono(2-tetrahydrofuranyl) fullerene anion C 60 (C 4 H 7 O) - and ZnI + .…”