Tetrahydropyrans, substitute

One recognizes an oxane ring (tetrahydropyran) substituted by three secondary alcohol functions in an equatorial orientation, a side chain carrying a primary alcohol function and finally a hemiacetal hydroxyl carried by carbon 1. This intramolecular hemiacetal is derived from the addition of the oxygen carried by C-5 to an aldehyde function. 

Booth H, Readshaw SA (1990) Experimental studies of the anomeric effect. Part IV. Conformational equilibria due to ring inversion in tetrahydropyrans substituted a position 2 by the groups ethoxy, 2 -fluoroethoxy, 2, 2 -difiuoroethoxy, and 2, 2, 2 -trifluoroethoxy. Tetrahedron 46 2097-2110... 

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

Tetrahydropyran- and tetrahydrofuran-substituted rings are common in many complex natural products, such as polyether antibiotics, displaying a wide range of biological properties [4]. An appropriate combination of OH-directed diastereose-lective epoxidation of y- and 8-alkenols [VO(acac)2/TBHP or MCPBA] [5] or ster-... 

There are two possible ways for the ring opening of 35 in the polymerization The C1—O7 bond cleavage leads to the formation of a substituted tetrahydropyran ring 36 in the polymer chain, while the C1—O2 bond cleavage produces a substituted tetrahydrofuran ring 37. Product analysis of the acid-catalyzed hydrolysis of the... 

In a series of papers culminating in the report of a total synthesis of hemibrevetoxin B, Nakata and co-workers utilised a zinc catalysed ring expansion of poly-substituted tetrahydropyrans, exemplified by the transformation of 34 to 35 (Scheme 7) <96TL213, 96TL217, 96TL6365>. 

Aubele et al. studied the aqueous Prins cyclization using cyclic unsaturated acetals as oxocarbenium ion progenitors and allylsilanes are used as nucleophiles. Cyclizations proceed efficiently inside Lewis acidic micelles (of cerium salt) in water. A variety of vinyl- and aryl-substituted tetrahydropyrans with excellent stereocontrol was obtained (Eq. 3.26).113... 

Scheme 2.68. Diastereoselective formation of substituted tetrahydropyran-4-ones.

The structure of the antibiotic, 9, which has been variously named lacto-quinomycin-A and medermycin, was first reported by Okabe and coworkers in 1985.58 In early 2002,59 a communication was published reporting that the original structure, 9, was incorrect based on synthesis and that the substituted tetrahydropyran ring was attached to the 6-position to give 10, rather than the 8-position as originally reported. The authors based their conclusion on the fact that a key intermediate was identified as 6-bromo-3-hydroxybenzaldehyde rather than the 4-bromo-3-hydroxy benzaldehyde as previously reported.60... 

Tetrahydropyran (THP), aldehyde etherification, 67-68 Tetralin compounds, 5-methoxytetralin reduction of substituted naphthalene, 132-133... 

Haworth methylation of methyl /3-D-glucopyranoside and its 4-benzyl and 4-(tetrahydropyran-2-yl) ethers was investigated in connection with partial-methylation studies on cellulose.267 For the unsubstituted glycoside, the ratios of relative rate-constants k2 k3 k4 k were estimated to be 8 2 1 8, and, for the 4-ethers, it was found that ke> k2> k3 best agreements between calculated and experimental yields were found with the assumption that the rate constant for reaction at HO-3 is doubled when HO-2 is substituted. Later methylation studies,268 performed to low degrees of substitution, with analysis by gas-liquid chromatography, gave k2> k4> k3 for the reactivity... 

On treatment with acrylonitrile in 2% aqueous sodium hydroxide at 0°, tetrahydropyran-2-yl /3-D-glucopyranoside gave the 2-, 3-, 4-, and 6-0-(2-cyanoethyl) ethers (together with some diethers) in yields that, on extrapolation to zero reaction, showed3 9 k2 k3 k4 k6 to be in the ratios of 3 1 2 8 these values represent equilibrium, not rate, constants. The tendency for substitution at 0-6 is a consequence of the greater stability of an ether derived from a primary (compared to a secondary) hydroxyl group, as a result of lower steric interactions in the former. 

The preparation in good yield of (3-mercaptoethylphosphines has been accomplished by the free radical-induced addition of primary and secondary phosphines across the olefinic linkage of 2-(vinylthio)tetrahydropyran.446 The target materials were isolated by hydrolysis of the intermediate substituted thiotetrahydropyran. 

Starting from substituted allyl bis-(2,4-dimethyl-3-pentyl)-L-tartrate boronic acid, synthesis of a,/l-disubstituted tetrahydrofurans (134, n = 1) or tetrahydropyrans (134, n = 2) can be accomplished with high enantioselectivity (Scheme 3-46).79... 

In a different study, a d-allenyl alcohol 81 containing a chiral substituent was oxidized by DMDO and then cyclized to afford the substituted tetrahydropyran 82 with good diastereoselectivity [19] (Scheme 17.24). Interestingly, when oxone was used instead of DMDO, the eight-membered cyclic ether 83 was formed via the allene oxide intermediate. 

The oxidation of enol ethers at a reticulated vitreous carbon anode [2, 3] (Scheme 1) in a mixture of methanol/THF containing tetraethylammonium tosylate as the electrolyte and 2,6-lutidine as the base leads to substituted tetrahydrofu-ran and tetrahydropyran rings in good yields (51-96%). The major product obtained had a trans-stereochemistry. The cyclization failed to make seven-membered ring products. In order to determine the... 

Employing this as a guide, the author and his coworkers were successful in conclusively demonstrating general acid catalysis in the hydrolysis of three different types of acetals and ketals, 2- p-substituted phenoxy) tetrahydropyrans having electron withdrawing... 

This article deals with the conformational analysis of substituted oxanes (tetrahydropyranes) and derivatives in which ring methylenes are replaced by further oxygen atoms (di-, tri-, tetroxanes, pentoxanes, and O ) or by carbonyl group(s) (oxanones, Meidrum s acid derivatives) and, if conforma-tionally of interest, systems incorporating these rings in polycyclic structures... 

Aiming at the pyranose form of sugars, normal type hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems (5-10) (see routes A - D in the general Scheme 1) which are also important targets in the "Chiron approach" to natural product syntheses (2.) Hetero-Diels-Alder reactions with inverse electron demand such as a, p-unsaturated carbonyl compounds (l-oxa-1,3-dienes) as heterodienes and enol ethers as hetero-dienophiles, are an attractive route for the synthesis of 3,4-dihydro-2H-pyrans (11). 

Tetrahydrofuran itself can be opened using either the stoichiometric or the catalytic version of arene-promoted lithiation, but both cases need the activation by boron trifluoride. The catalytic reaction was performed by treating the solvent THF 324 with the complex boron trifluoride-etherate and a catalytic amount (4%) of naphthalene. The intermediate 325 was formed. Further reaction with carbonyl compounds and flnal hydrolysis yielded the expected 1,5-diols 326 (Scheme 95), which could be easily cyclized to the corresponding substituted tetrahydropyrans under acidic conditions (concentrated FlCl). 

H. Booth, K. A. Khedhair, and S. A. Readshaw, Experimental studies of the anomeric effect Part I. 2-substituted tetrahydropyrans, Tetrahedron, 43 (1987) 4699-4723. 

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