Pyridinium chlorochromate chemistry. New insight into oxidation of tetrahydrofurans

Abstract

A thorough investigation of the minor oxidation products of two penta-tetrahydrofuran compounds with pyridinium chlorochromate has been carried out. Isolation of ring-B oxygenated spiroketal and degradation products, including polycyclic mono-and bis-lactone compounds, supports the previously postulated involvement of cyclic enolether intermediates in the oxidation of THF and poly-THF substances with PCC. Based on the collected evidence, a new mechanistic route for the PCC-mediated oxidative cleavage of -hydroxy-THF compounds to -lactones has been postulated. The proposed mechanism well agrees with the one reported for the oxidative cleavage of 8-hydroxy-neoisocedranol oxide by RuO4, a fact that further supports our previous observation on the similar oxidizing behaviour shown by PPC and RuO4 towards THFcontaining compounds.

A Novel PCC-Catalyzed Process Involving the Oxidative Cleavage of an α-Bromomethyl-tetrahydrofuran Bond. Synthesis of (2S,3R)-2-{(R)-Bromo[(2R,3R,5S,6R)-3,5-dibromo-6-ethyltetrahydro-2H-pyran-2-yl]methyl}-5-oxotetrahydrofuran-3-yl Benzoate

“…The mechanism of this new process is unknown, but the involvement of a cyclic chlorochromatoperiodate diester (4, Scheme 2) can be hypothesized in agreement with literature precedents [7,8,21] and recent results disclosed by our studies [9].…”

“…In particular, the α-bromomethyl-tetrahydrofuran bond in the benzoylated species 2 (Scheme 1) underwent a novel type of oxidative cleavage to give the γ-lactone ring present in the final product 3, with the elimination of the three-carbon (C1-C3), bromoalkyne fragment. This process is strongly reminiscent of the pyridinium chlorochromate-mediated oxidative cleavage of α-hydroxymethyl-tetrahydrofurans to γ-lactones previously studied in our group [9,22].…”

“…Pyridinium chlorochroamte (PCC) is a well known oxidizing reagent. Although it is mostly used in the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, it has also been employed in a number of other processes [5], and recently, we [6][7][8][9] and others [10][11][12][13][14] have disclosed its ability to catalyze new synthetically useful reactions. We were now interested in testing some oxidative methods previously developed in our laboratories [8, [15][16][17] on a number of structurally diverse molecular frameworks in order to access a selection of variously functionalized substances for structure-activity relationship studies [18].…”

(±)-((2S,5R)-5-(Acetoxymethyl)tetrahydrofuran-2-yl)methyl Benzoate

“…Some of them play an important role in industrial processes [5,6]. As part of our ongoing studies on oxidative processes catalysed by transition metal oxo-species [7][8][9][10], we recently developed a new chlorochromatoperiodate (CCP)-catalysed process that allows the synthesis of bis-αacyloxy-1,4-and -1,5-diketones (2, Scheme 1) through the oxidative opening of bis-acylated 2,5-dihydroxyalkyl-substituted tetrahydrofurans and tetrtahydropyrans (acylated THFand THP-diols, 1, Scheme 1), respectively [11]. CCP is a powerful reagent, generated by the condensation of pyridinium chlorochromate (PCC) and periodic acid [12], capable of oxidising THF-containing compounds of varying structural complexity [8,9].…”

“…As part of our ongoing studies on oxidative processes catalysed by transition metal oxo-species [7][8][9][10], we recently developed a new chlorochromatoperiodate (CCP)-catalysed process that allows the synthesis of bis-αacyloxy-1,4-and -1,5-diketones (2, Scheme 1) through the oxidative opening of bis-acylated 2,5-dihydroxyalkyl-substituted tetrahydrofurans and tetrtahydropyrans (acylated THFand THP-diols, 1, Scheme 1), respectively [11]. CCP is a powerful reagent, generated by the condensation of pyridinium chlorochromate (PCC) and periodic acid [12], capable of oxidising THF-containing compounds of varying structural complexity [8,9]. Considering that THF-and THP-diols can be synthesised through the ruthenium- [13][14][15][16][17] and osmium- [18,19] catalysed oxidative cyclization of 1,5-and 1,6-dienes (Scheme 1), respectively, our process allows the regioselective bis-ketoacyloxylation of the starting diene.…”