Synthesis of substituted tetrahydropyrans using metal-catalyzed coupling reaction

The purpose of this research is to explore the use of cobalt- and iron-catalyzed cross coupling reactions of alkyl iodides containing beta-tetrahydropyran groups to develop a general method to synthesize substituted tetrahydropyrans. Substituted tetrahydropyrans can be used towards the total syntheses of biologically active natural products. The starting iodide compounds underwent sp3-sp3 and sp3-sp2 cobalt- and iron-catalyzed cross-coupling reactions with different Grignard reagents. It was expected that the formation of the coupled product would be faster than the formation of the side products (elimination and homocoupling) and thus yield the desired substituted tetrahydropyrans. The results of this study showed that cobalt-catalyzed reactions are best used for sp3-sp3 coupling though in low yields while the iron-catalyzed reactions produced better yields for the sp3-sp2 couplings. However, the reactions still resulted in the formation of undesired elimination and homocoupling side products. In the future, optimization will be made to minimize the formation of the side products and to increase yields of the substituted tetrahydropyrans which can then provide a further basis for the use of cobalt- and iron-catalyzed cross-coupling reactions in the synthesis of natural products

Enantioselective Prins cyclization: BINOL-derived phosphoric acid and CuCl synergistic catalysis.

International audienceThe first catalytic enantioselective Prins cyclization is disclosed. The reaction is catalyzed by the combination of a chiral BINOL-derived bis-phosphoric acid and CuCl. The process consists of a tandem Prins/Friedel-Crafts cyclization that affords the hexahydro-1H-benzo[f]isochromenes products with three new contiguous stereogenic centers in high yields, and good enantio- and excellent diastereoselectivities

Synthesis of polysubstituted tetrahydropyrans by stereoselective hydroalkoxylation of silyl alkenols: En route to tetrahydropyranyl marine analogues

Producción CientíficaTetrahydropyrans are abundantly found in marine natural products. The interesting biological properties of these compounds and their analogues make necessary the development of convenient procedures for their synthesis. In this paper, an atom economy access to tetrahydropyrans by intramolecular acid-mediated cyclization of silylated alkenols is described. p-TsOH has shown to be an efficient reagent to yield highly substituted tetrahydropyrans. Moreover, excellent diastereoselectivities are obtained both for unsubstituted and alkylsubstituted vinylsilyl alcohols. The methodology herein developed may potentially be applied to the synthesis of marine drugs derivatives.Junta de Castilla y León (GR170)European Social Fund and the Junta de Castilla y León (Grant Q4718001C

Alcohol Dehydrogenase Triggered Oxa‐Michael Reaction for the Asymmetric Synthesis of Disubstituted Tetrahydropyrans and Tetrahydrofurans

An alcohol dehydrogenase‐mediated asymmetric reduction and subsequent intramolecular oxa‐Michael reaction has been developed for the preparation of tetrahydropyrans (or oxanes) and tetrahydrofurans, in excellent conversion, yield and high enantiomeric and diastereomeric excess. To highlight the utility of the methodology, we report the synthesis of an analogue of the fungal antioxidant brocaketone A. Also described is the preparation of the (‐)‐(R,R)‐enantiomer of the natural product, (+)‐(S,S)‐(cis‐6‐methyltetrahydropyran‐2‐yl)acetic acid

A comparison of the benzylic and the allylic group as a donor in the formal [4+2] cycloaddition to tetrahydropyrans using donor-acceptor cyclobutanes

The allyl group was shown to be preferred over the benzyl group as a donor in the formal [4+2]-cycloaddition reaction between a donor-acceptor cyclobutane and various aldehydes to give tetrahydropyrans

Diversity-oriented synthesis of a library of substituted tetrahydropyrones using oxidative carbon-hydrogen bond activation and click chemistry

Eighteen (2RS,6RS)-2-(4-methoxyphenyl)-6-(substituted ethyl)dihydro- 2Hpyran-4(3H)ones were synthesized via a DDQ-mediated oxidative carbon-hydrogen bond activation reaction. Fourteen of these tetrahydropyrans were substituted with triazoles readily assembled via azide-alkyne click-chemistry reactions. Examples of a linked benzotriazole and pyrazole motif were also prepared. To complement the structural diversity, the alcohol substrates were obtained from stereoselective reductions of the tetrahydropyrone. This library provides rapid access to structurally diverse non-natural compounds to be screened against a variety of biological targets. © 2011 by the authors