Fully Substituted Pyranones via Quasi-Heterogeneous Genuinely Ligand-Free Migita–Stille Coupling of Iodoacrylates

Abstract

Migita-Stille coupling of (Z)-β-iodoacrylates with (E)-α-stannyl allylic alcohols to furnish 5-alkylidene-4-substituted-5,6-dihydro-2H-pyran-2-ones is efficiently catalyzed by 2% Pd black in DMF, while Pd(PPh3)4 is inactive. Heterogeneous Pd released in solution is most likely responsible for the catalysis. The reaction is applicable to other substrates, without having to resort to ligands, additives, and/or solid support for Pd. The resulting pyranones can be rearranged to fully functionalized pyranones in another single step.

A New Insight into the Stereoelectronic Control of the Pd0‐Catalyzed Allylic Substitution: Application for the Synthesis of Multisubstituted Pyran‐2‐ones via an Unusual 1,3‐Transposition

“…[d] Labeled with 13 C in the exo ‐methylene (see ref. ). [e] Carried out in DMF at 90 °C over 120 min; the 3b / 6b ratio was 31:65 (see ref.…”

“…[e] Carried out in DMF at 90 °C over 120 min; the 3b / 6b ratio was 31:65 (see ref. ). [f] Carried out on a gram scale.…”

“…The precipitate was filtered off and the organic phase was dried over anhydrous Na 2 SO 4 . Chromatography on silica gel (hexanes/EtOAc 7:3) furnished pyran‐2‐one 3d (1.460 g, 8 mmol, 68 %) as a yellow oil …”

“…[7] It is, therefore, of little surprise that the past decade has witnessed ac onsiderable effort aiming at the development of an efficient and modularc onstruction of the pyran-2-one core. [8,9] We have recently disclosed [10,11] anew methodf or rapid assembly of novel 4-substituted-5-alkylidene pyran-2-ones 3 through ac ross-coupling of 2-tributystannyl allyl alcohols 1 and b-iodo acrylates 2,c atalyzed by the ligand-free palladium black (Scheme 2). Notably,t his reaction did not proceed under ho-mogeneous conditions with PdL 4 ,p resumably due to the enhanced stability of the ligatedp roducts of the initial oxidative addition.…”

“…Notably,t his reaction did not proceed under ho-mogeneous conditions with PdL 4 ,p resumably due to the enhanced stability of the ligatedp roducts of the initial oxidative addition. [11] Palladium-catalyzed1 ,3-rearrangement of 5-alkylidene pyran-2-ones While screening the reaction conditions for the preparation of pyran-2-one 3a (R 1 = Pr,R 2 = Ph;s ee Table 2f or R 1 and R 2 ), an unexpected formation of the isomeric 4,6-disubstituted-5methylene pyran-2-one 6a as byproduct( 11 %) waso bserved (Scheme3)i nt hose cases when the Pd black catalystu sed, was generated from Pd(PPh 3 ) 4 through air oxidationo ft he phosphine ligand. [11] Subsequently,i somerization of 3b,l abeled at the 6-position with 13 C, was found to proceed under homogeneousc onditions with Pd(PPh 3 ) 4 (3 mol %) in DMF (dimethylformamide)a t1 20 8Cf or 60 min, which afforded 3b and 6b in 30 %a nd 64 %y ield, respectively.…”