Oxane 2-substituted

Die Reduktion von 9-Brom-ll/3-hydroxy-steroiden mit Chrom(II)-Salzen, insbeson-dere mit Chrom(II)-acetat fiihrt zu 11/3-Hydroxy-steroiden (s. S.515), A9 (11)-Ste-roiden (s. S.518) und 5,9-Cyclo-steroiden. Die Cyclopropan-Bildung wird durch Chrom(II)-acetat in Dimethylsulfoxid bzw. Dimethylformamid begiinstigt. So laufen beim 9a-Brom-l l/3-hydroxy-3-oxo-l 7/ -acetyl-ostren-(510) in waBr. Aceton, THF, 1,4-Di-oxan oder N-Methyl-pyrrolidon Substitution, Eliminierung und Cyclisierung nebeneinan-der ab, in Dimethylsulfoxid oder Dimethylformamid erhalt man fast ausschlieBlich ///3-Hydroxy-3-oxo-17 3-acetyl-5,9-cyclo-dstran5 ... 

Reaction of 3,4-bis(phenylsulfonyl)-l,2,5-oxadiazole oxide isomers with ethanol and ethanethiol in basic medium gave the expected alkoxy- and alkylthio-substituted (benzenesulfonyl)furoxans, respectively <1996JHC327, 1997FES405>. Nucleophilic substitution of the sulfonyl group of 3,4-bis-(benzenesulfonyl)furoxan 222 in the presence of aqueous NaOH in tetrahydrofuran (THF) furnished the corresponding 3 -0-(3-benzenesulfonylfur-oxan-4-yl) derivative 223 in 79-92% yield (Equation 44) <2004JME1840>. 

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... 

The chair conformation is the preferred conformer for the oxane ring and substituted derivatives. In the case of poly-substitution (e.g., 1,3-diaxial groups), twist conformers can also participate in the equilibrium. Substituents can adopt the axial and equatorial positions ring interconversion between the chair conformers is fast on the NMR timescale at ambient temperature but becomes slow at low temperature (AG = 10.3 kcal mol- ) (73JA4634). 

The conformational equilibria of the various substituted oxanes in Table I are strongly dependent on the solvent. The polarity of the solvent and the possibility to form inter- or intramolecular hydrogen bonds are of significant influence (69CJC4427 87CJC213). 

Conformational Energies (Free Energy Differences, AC7kcal moL ) of Substituted Oxanes... 

Alcudia et al. [88JCS(P2)1225], in the same way, studied the conformational equilibria of the cis/trans isomeric 2-OMe-5-SR-substituted oxanes... 

Barby et al. [82JCS(P2)249] investigated the conformational equilibria of 2-NR2-substituted oxanes. The cis/trans isomeric 2-NR2-4-Me-derivatives proved to adopt preferred conformations (cis isomers 2-eq-A-eq trans isomers 2-ax-A-eq, except for /ram-2-NHMe-4-Me-oxane preferring the 2-ax-A-eq conformer by only 0.4 kcal mol ) the 2-NR2 monosubstituted oxanes (see Table I) prefer the equatorial position and do not show notable anom-eric interaction with the ring oxygen atom [82JCS(P2)249]. The same is true for 2-NHCOMe-oxane, but not for N3 and NCO substituents, respectively, in the 2-position (70ZOR863) (see Table I). 

The conformations of spiro-compounds containing the oxane ring have been reported (Scheme 5) (81CJC1132). They exist only in conformation 9a at room temperature at lower temperature, no indication of a second conformer was found. The methyl-substituted derivatives 10a and similar tricyclic analogs occur in the same conformation 11a. 

The C chemical shifts of 29 alkyl (Me,Et) substituted oxanes (830MR94) were used to train a neural network to simulate the C NMR spectra. The neural network, thus trained, was employed to simulate the C NMR spectra of 2-Et, franj-3,5-di-Me-, and 2,2,6-tri-Me-oxanes, respectively, compounds that exist >95% in one preferred chair conformation. In one case, the deviation for one methyl substituent proved to be considerable and was related to other conformers participating in the conformational equilibrium (94ACA221). 

Many mechanisms had been proposed in the past to rationalize this selectivity (tri-oxanes, perepoxide, exciplex, dipolar or biradical intermediates) however, it is now generally accepted that the reaction proceeds through an intermediate exciplex which has the structural requirements of a perepoxide. This assumption is supported by (a) the lack of stereoselectivity in the reactions with chiral oxazolines and tiglic acid esters (b) the comparison of the diastereoselectivity of dialkyl substituted acrylic esters with structurally similar non-functionalized aUtenes (c) the intermolecular isotope effects in the photooxygenation of methyl tiglate and (d) the solvent effects on regioselectivity. ... 

Posner and coworkers concluded that the low activity of the stannyl-substituted tri-oxanes indicated that the killing species must be an intermediate somewhere along the route after the 1,5-H shift has generated a C4-centred radical. 

Different reactivities of some substituted oxan-4-ols on oxidation by pyridinium chlorochromate (PCC) are rationalized on the basis of their conformational features, including twist conformations.2 A rate-determining carbon-carbon bond cleavage step in a glycol-PCC complex is proposed in the oxidation of butane-2,3-diol to acetaldehyde.3 Steroidal 6/i-hydroxy-4-en-3-onc was isolated as an intermediate in the oxidation of steroidal 5-en-3/i-ol with PCC.4... 

Reaction of this compound, or the considerably more explosive 2,6-dinitrobenzofur-oxan, with nucleophiles (secondary and tertiary amines, sodium hydroxide) showed evidence of Meisenheimer type complexes being formed - zwitteionic in the case of tertiary amines. Some of these broke down by elimination of water to give substituted benzoxadiazoles. All complexes and other isolated products are described as explosive. 4,6-Dinitrobenzofurazan iV-oxide Nucleophilic reagents See other furazan n-oxides... 

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. 

Table 2.2 Conformational free energies of substituted oxanes (between 163-183 K in chlorinated solvents) (from Eliel et al. 1982) (reproduced with kind permission from the American Chemical Society).

When a pyranose is transformed into a 1,6-anhydropyranose, the axial hydroxyl groups become equatorial and vice versa. This is undoubtedly the most interesting property from a synthetic point of view because of the change in reactivity. But there are limits to the usefulness of the 1,6-anhydro the endo face between the oxolane and the oxane is not very accessible and nucleophiles cannot be easily introduced there, so much so that it can be difficult to substitute activated hydroxyl groups by the 8 2 reaction involving endo attack. Finally, it should be noted that the preparation of certain 1,4-anhydropyranoses is also known. 

The most frequently used measure of the anomeric effect is based on the comparison of the stabihty of 2-substituted oxane (tetrahydropyran THP) and cyclohexane. In general, conformational properties of the oxane ring are similar to those of cyclohexane, with dominance of a chair conformation. It is further presumed that steric interactions in oxane are the same as in cyclohexane, with preference for equatorial positions of bulky substituents. The Gibbs energy of the anomeric effect, AG(AEl), can be expressed as the... 

Fig. 5.—The Standard Equilibrium in (a) Substituted Oxanes and (b) Substituted Cyclohexanes Used in the Definition of the Anomeric Effect by Eq. I.

Axial Preferences and the Gibbs Energy of the Anomeric Effect AG(AE,) (in kJ.moC ) in the 2-Substituted Oxanes ... 

The extent to which this kind of calculation is able to predict the effect of the solvent on conformational properties of carbohydrates has been thoroughly tested on 2-substituted oxane derivatives, D-glucopyranose, and methyl a- and y -D-glucopyranoside. In the model applied, the cavity term in Eq. 7 is based on an expression taken from the Scaled Particle Theory, and the electrostatic term is calculated according to the reaction held theory. The dispersion term takes into account both attractive and repulsive nonbonding interactions by using a combination of Lx)ndon dispersion energy and Bom-type repulsion. ... 

PCILO Calculated Bond Lengths (pm) and Bond Angles (degrees) for 2-Substituted Oxane Derivatives, Compared with... 

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