A Synthesis of Densely Functionalized 2,3-Dihydropyrans Using Ring-Closing Metathesis and Base-Induced Rearrangements of Dihydropyran Oxides

Abstract

The preparation of dihydropyran and dihydrofuran oxides and their rearrangement in the presence of lithium dialkylamides to functionalized 2,3‐dihydropyrans or 2,3‐dihydrofurans, respectively, is described. The regiochemical outcome of the reaction can be influenced by the relative configuration of the starting epoxides and the steric demand of the base. The 2,3‐dihydropyrans obtained were converted stereoselectively to difunctionalized 3,4‐dihydropyrans by the carbon‐Ferrier reaction, or to fused acetals by addition of dimedone, mediated by ceric ammonium nitrate. The stereochemical results are rationalized by mechanistic proposals.

Development of a Phase-Transfer-Catalyzed, [2,3]-Wittig Rearrangement

“…The 1 H NMR spectroscopic data was similar to the data reported for the corresponding methyl ester. 55 Preparation of 2-(Allyloxy)-2-phenyl-1-(pyrrolidin-1-yl)ethan-1-one (7). To a flame-dried, 20-mL Schlenk flask fitted with magnetic stir bar and septum was added washed sodium hydride (23.0 mg, 0.96 mmol, 1.1 equiv).…”

Olefin metathesis and isomerization: From undesired side reactions to useful synthetic methodology

“…Starting point and inspiration of our investigation on this field was the unexpected result described in Scheme 1. The ring closing metathesis of diallyl ethers (5, n = 0) and allyl homoallyl ethers (5, n = 1) to oxacycles 6 is normally an extraordinarily facile process where undesired olefin isomerization does not play a role [33]. If the alternative pathway, selective isomerization to 7 followed by Claisen-rearrangement to pent-4-enals 8, is desired, conditions are needed that will (1) suppress ring closing metathesis and (2) induce the in situ conversion of precatalyst A to an isomerization catalyst.…”

Stereoselective Syntheses of Enantiomerically Pure 2,5-disubstituted Dihydropyrans Based on Olefin Metathesis

“…After column chromatography, 26 (334 mg, 78%) was obtained as a colorless liquid. None of the bis-carboxylated dienediol could be detected: 1 Carbonic Acid tert-Butyl Ester 1-(Hydroxyoxiranylmethyl)-allyl Ester (27). An oven-dried Schlenk tube was charged under an argon atmosphere with dichloromethane (55 mL).…”

“…For the synthesis of 3-hydroxy-substituted dihydropyrans 4 we considered a two-step synthesis from R-hydroxy carbonyl compounds 25 6: first, a chelate controlled diastereoselective addition of a vinylmetal compound yields dienes 5, which are then subjected to RCM (Scheme 1). 26, 27 In this paper, we report an evaluation of different strategies for the regio-and stereoselective synthesis of enantiomerically pure 2,5-disubstituted dihydropyrans, based on the combination of ruthenium-catalyzed olefin metathesis with either Claisen-rearrangement chemistry or palladium-catalyzed allylic substitution.…”