Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

Abstract

SummaryThe study of Pd-catalysed cyclisation reactions of alkenols using different catalytic systems is reported. These transformations affect the stereoselective construction of mono- and/or bicyclic oxaheterocyclic derivatives depending on a starting alkenol. The substrate scope and proposed mechanism of Pd-catalysed cyclisation reactions are also discussed. Moreover, the diastereoselective Pd-catalysed cyclisation of appropriate alkenols to tetrahydrofurans and subsequent cyclisation provided properly substituted 2,5-dioxabicyclo[2.2.1]heptane and 2,6-dioxabicyclo[3.2.1]octane, respectively. Such bicyclic ring subunits are found in many natural products including ocellenynes and aurovertines.

Ready Access to Densely Substituted Furans Using Tsuji–Wacker-Type Cyclization

“…1-Phenylhex-5-ene-2,3-diol (7a). 22 Compound 7a was synthesized by following general procedure A and purified by silica gel column chromatography (70:30 petroleum ether/ethyl acetate): isolated yield of 0.128 g, 30%, white solid, as a diastereomeric mixture; IR υ max (film) 3410, 2921, 1639, 1437, 1273 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7. 2H),3H),1H),1H),1H),1H),1H),2.92 (ddd,J = 13.7,6.5,4.2 Hz,1H),1H),1H),1H),2.13 (dd,J = 29.2,4.3 Hz,1H), 2.06−1.90 (m, 1H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 138.…”

“…2-Benzyl-5-methylfuran (12). 22 Compound 12 was synthesized by following general procedure E and purified by silica gel column chromatography (99:1 petroleum ether/ethyl acetate): isolated yield of 0.049 g, 55% Colorless liquid; IR υ max (film) 3029,2922,2858,1567,1452,1218,1022, 712 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7. 32−7.28 (m, 2H), 7.24−7.18 (m, 3H), 5.86 (s, 2H), 3.92 (s, 2H), 2.25 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 152.…”

“…It is also worth mentioning that the intramolecular acetalization of a dihydroxy-substituted geminal alkene to provide fused perhydrofurans under Wacker-type conditions was reported by Alonso et al Even, the group of Runeberg and Gracza disclosed the remarkable synthesis of oxaheterocyclic core intermediates differently via Pd-catalyzed Tsuji–Wacker type cyclization, where they unexpectedly got disubstituted furan as a byproduct. Rao et al used I 2 and DBU to cyclize the diols with an olefin in the middle of their reaction sequence .…”