syn-Oxidative Polycyclizations of Hydroxypolyenes:  Highly Stereoselective and Potentially Biomimetic Syntheses ofall-trans-Polytetrahydrofurans

Abstract

Acylperrhenate reagents promote hydroxyl-directed syn-oxidative polycyclizations of primary and secondary hydroxypolyenes, forming bis- and tristetrahydrofuranyl alcohols with excellent trans-stereoselectivity for each tetrahydrofuran ring. The combination of dichloroacetylperrhenate/dichloroacetic anhydride affords stereoselective syn-oxidative bicyclization to bistetrahydrofuranyl alcohol products, whereas trifluoroacetylperrhenate/trifluoroacetic anhydride or trichloroacetylperrhenate/trichloroacetic anhydride are more suitable for stereoselective formation of tristetrahydrofuranyl alcohols from acyclic hydroxytrienes. In the tricyclization reaction chirality induction from a single stereogenic hydroxyl group affords diastereoselective formation of six additional stereocenters in a single step. However, we have found that the growing polytetrahydrofuran chain can exert chelation effects upon the alkoxyrhenium intermediate, thus diminishing the degree of product diastereoselectivity. These syn-oxidative cyclization synthesis strategies mimic a possible pathway for the biosynthesis of many polycyclic ether natural products, including the tristetrahydrofuran acetogenin goniocin (1).

Pyridinium chlorochromate chemistry. New insight into oxidation of tetrahydrofurans

“…This survey allowed the identification of novel pathways working in the oxidation of differently substituted tetrahydrofurans with PCC, or allowed to confirm previously formulated mechanistic hypotheses on some PCC-mediated processes. 22,23 In addition, based on the acquired evidence, we could formulate a new plausible mechanistic route on the PCC-mediated oxidative cleavage of THF rings bearing a  tertiary alcohol function, 14,17,[25][26][27][28][29][30][31][32][33] such as 1 and 2, to the corresponding -lactones, that well agrees with the mechanism proposed for the analogous process mediated by RuO 4.…”

“…The transformations highlighted in points a and b point out the similarity of the oxidizing behaviour of PCC with the one displayed by RuO4 which catalyzes similar processes by reaction with 1. 13 The PCC-mediated conversion of -hydroxy mono-and poly-THF compounds to -lactones (see for example conversion of 1 to 2-4 or 5 to 6 in Scheme 1) is a well-documented process 14,17,[25][26][27][28][29][30][31] although no definitive proof on the cleavage mechanism has been provided. On the other hand, spirocyclization leading to compounds 5-8 is a novel transformation which is attractive both from a mechanistic and applicative point of view.…”

“…Conversion of 1 to 2-4. The PCC-mediated oxidative cleavage of -hydroxy mono-and poly-THF compounds to -lactones (see for example conversion of 1 to 2-4 or 5 to 6 in Scheme 1) is a well-documented process [25][26][27][28][29] interesting both from a mechanistic and applicative point of view. No definitive evidence on the real path of this transformation has been provided to date although plausible speculative reasoning have been put forward.…”

“…No definitive evidence on the real path of this transformation has been provided to date although plausible speculative reasoning have been put forward. 17,[25][26][27][28][29] In the light of the above collected evidence a comment to this transformation, with reference to THF bearing-tertiary alcoholic moieties, seems appropriate. When reasoning for example for the transformation of 1 to 3 (Scheme 1), a summary of the reported routes, explaining the oxidative cleavage of the C2-C3 bond, is shown in Scheme 13.…”

“…13 On this ground it seems conceivable that this route could also work in the oxidative cleavage of related -hydroxy-THF substances studied by others. [25][26][27][28][29] Scheme 13. Oxidative cleavage of the -hydroxy-THF portion of 1 according to previously formulated mechanistic hypotheses.…”