1.3- Dioxanes, conformational analysis

Ab initio calculations at the MP2 level of theory of a collection of substituted 1,3-dioxanes, 1,3-oxathianes, and 1,3-dithianes have been employed to study both the position of the conformational equilibria and the validity of the Perlin effect <2005T7349>. The 7h,c coupling constant proved to be a valuable tool in conformational analysis both twist conformers, in addition to the chair and alternative chair forms, could be readily identified simply by comparing experimental Vh,c coupling constants to the corresponding calculated values in the particular forms. In addition, the Perlin and reversed-Perlin effects of the C2-H fragments, c in 1,3-dioxanes,... 

Eliel, E. L. Nader, F. W. Conformational analysis. XX. The stereochemistry of reaction of Grignard reagents with ortho esters. Synthesis of 1,3-dioxanes with axial substituents at C-2.]. Am. Chem. Soc. 1970, 92, 584-590. 

In contrast to a thoroughly performed conformational analysis of 1,4-dioxanes and 1,4-oxa-thianes, the data on the conformational behavior of 1,4-dithianes are quite limited. According to NMR ( H, C) spectroscopy and molecular mechanics calculations, 2-alkyl-substituted 1,4-dithianes exist preferentially in the conformation with equatorially oriented substituents. For 1,4-dithianes with substituents of tbe CHjX type (X = aeetoxy, halogen), the predominance of axial conformers is observed originating from an intramolecular electrostatic attraction <91T9455). 

An oxonium ion is formed (5 -> 6) in the rate-determining step after a reversible (9-protonation and O/C-2 fission. Its formation is also responsible for the epimerization of 5-substituted 1,3-dioxanes, and is brought about by the action of nonaqueous protic or Lewis acids. It is important for the conformational analysis of these systems (by equilibration of the conformers 7 and 8 which occupy an equatorial and axial position, respectively). 

A conformational analysis of substituted 1,3-dioxanes and 2,5-disubstituted 1,3,2-dioxaborinanes has been performed by Kuznetsov et al by the use of vicinal proton-proton couplings and quantum-chemical methods. 

Eliel EL, Giza CA (1968) Conformational analysis of some 2-aIkoxytetrahydropyrans and 2-aIkoxy-l,3-dioxanes. Anomeric effect. J Org Chem 33 3754—3758... 

In CDCI3 solution of the minor dioxane, NMR analysis showed that it existed as an equUibrium mixture of twisted boat conformers. Adding shift reagent, Eu(F0D)3, resulted in the MeO-axial chair conformer (Scheme 30). 

Lemieux, R. U., and S. Koto The Conformational Properties of Glycosidic Linkages. Tetrahedron 30, 1933 (1974) Bailey, W. F., and E. L. Eliel Conformational Analysis. XXIX. 2-Substituted and 2,2-Disubstituted 1,3-Dioxanes. The Generalized and Reverse Anomeric Effects. J. Amer. Chem. Soc. 96, 1798 (1974) Anet, F. A. L., and I. Yavari Generalized Anomeric Effect and Barrier to Internal Rotation about the Oxygen-Methylene Bond in Chloromethyl Ether. J. Amer. Chem. Soc. 99, 6752 (1977). 

The Acid-Catalyzed Anomerization of the o-Glucose Penta Acetates. A Kinetic Thermodynamic and Mechanistic Study." /. Am. Chem. Soc. 73,2659 (1951). Anderson, C. B., and Sepp, D. T. "Conformation and the Anomeric Effect in 2-Halotetrahydropyrans."/. Org. Chem. 32,607 (1967). Eliel, E. L., and Giza, C. A. "Conformational Analysis. XVll1.2-Alkoxy- and 2-Alkylthiotetrahydropyrans and 2-Alkoxy-l,3-Dioxanes. Anomeric Effect." /. Org. Chem. 33,3754 (1968). Bottom Another example of a strong conformational bias introduced by the anomeric effect. 

The structure of the bisacetal formed from glucitol and p-isobutylbenzaldehyde has been shown to be l,3 2,4-bis(( -p-isobutyIben lidene)glucitol, by oxidative cleavage then reduction of the latter into the corresponding xylitol derivative. A conformational analysis of die 1,3-dioxane rings was also performed. 

A number of l,3-dioxan-2-ylium ions have been studied with respect to the preferred conformation. From a detailed H and C NMR study (790MR616) and the X-ray crystal structural analysis (94CJC2084), it was concluded that the 1,3-dioxan-2-ylium ions adopt the envelope conformation with the C —O —C —O—moiety in one plane (due to mesomerism) and C —C —forming the flap (Scheme 16). Ring interconversion 19a 19b and a 1 1 conformational equilibrium was assumed. 

Pihlaja and Rossi [83ACSA(B)289] prepared l,3-dioxan-2-one and all of its methyl derivatives, recorded their C NMR spectra, and derived the methyl substituent shift parameters by a multiple linear regression analysis of the anancomeric and two equivalent chair conformers (Table X). With these values, the authors estimated the conformational equilibria for two unequally populated chair conformations (Nos. 2, 3, 9, 11, and 14 in Table X). A consistent picture of the predominance of the chair conformation and the corresponding chair chair equilibria in l,3-dioxan-2-ones was obtained in complete agreement with earlier H NMR results. 

For compound 22, X-ray analysis demonstrates that the dioxane ring adopts the chair conformation and that the imidoyl amino group prefers an axial conformation <2002T2621>. For (l,4-benzodioxin-2(3//)-yl)methyl sulfamic acid ester 21, the conformation of the dihydrodioxin ring is close to an ideal half-chair and for 1,2,4,6,7,9-hexafluoro-... 

Toward a screening program for RhuA stereoselectivity, structurally more simplified dioxane derivatives 25-27 comprising enantiomeric and diastereomeric 3-hydroxyaldehyde geometries in a conformationally defined environment could be prepared easily from carbohydrate precursors (Scheme 2.2.5.10). First results from product analysis provide further evidence for occasionally biased fixation of... 

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