Pd^II‐Catalyzed Domino Heterocyclization/Cross‐Coupling of α‐Allenols and α‐Allenic Esters: Efficient Preparation of Functionalized Buta‐1,3‐dienyl Dihydrofurans

Abstract

A mild, palladium(II)-catalyzed reaction of alpha-allenols with alpha-allenic esters in a heterocyclization/cross-coupling sequence, applicable to a wide range of substitution patterns, has been developed for the preparation of 2,3,4-trifunctionalized 2,5-dihydrofurans. Our studies indicate high levels of chemo- and regiocontrol. The possibility of using optically active substrates as well as substrates of increased steric demand, such as tertiary alpha-allenols, makes this novel sequence of heterocyclization/cross-coupling an attractive method in organic synthesis. The current mechanistic hypothesis invokes a regiocontrolled palladium(II)-mediated intramolecular oxypalladation of the free allenol component, that then undergoes a cross-coupling reaction with the allenic ester partner, followed by a trans-beta-deacyloxypalladation with concomitant regeneration of the Pd(II) species.

Palladium‐Catalyzed Highly Chemoselective Cascade Coupling‐Cyclization of Allenol Derivatives and Aryl Halides for the Construction of Dihydrobenzofuranols or Chromanols and Indolinols

“…Alcaide and et al. have reported that two different α‐allenols can react in a heterocyclization/cross‐coupling sequence to produce buta‐1,3‐diene dihydrofuran . When they used the allenol 1 a as a substrate, which contains three functional groups, aliphatic hydroxy, allenyl, and phenylic hydroxy groups, the typical α‐allenol cyclization reaction occurred with the phenylic hydroxy group (γ‐allenol) untouched (Scheme ).…”

Cross‐Coupling/Cyclization Reactions of Two Different Allenic Moieties

“…This coupling sequence was also extrapolated to sterically more encumbered tertiary allenic alcohols. [9] All substrates reacted efficiently to afford high yields of the corresponding spiro adducts, such as the oxindole shown in Scheme 8, obtained in a 76 % isolated yield. As before, all products were obtained as single isomers, that is, with complete E selectivity with regard to the newly established C=C double bond.…”

Novel Aspects on the Preparation of Spirocyclic and Fused Unusual β-Lactams

“…Treatment of enantiopure α-allenols 41 with the appropriate coupling partner under optimized conditions, led to formation of the desired products 47-49 as single isomers (Scheme 16). Similarly, the heterocyclizative cross-coupling between 2azetidinone-tethered allenols and α-allenic acetates has resulted in the achievement of β-lactam-dihydrofuran hybrids in good yields [25]. acrylate, which leads to the final spirocycles 49a and 49b and Pd(0) in a β-hydride elimination [24].…”