Conformational analysis. XX. Stereochemistry of reaction of Grignard reagents with ortho esters. Synthesis of 1,3-dioxanes with axial substituents at C-2

Abstract

The cis and trans isomers of 2-methoxy-4-methyl-l,3-dioxane, 2-methoxy-r-4,c/s-6-dimethyl-l,3dioxane, and 2-methoxy-4,4,6-trimethyl-l,3-dioxane (I-III) have been synthesized and their configuration is assigned on the basis of nmr data, dipole measurements, and, in the case of the 4,4,6-trimethyl compound, Overhauser effect studies. One stereoisomer each (the one with axial methoxyl) of 2-methoxy-2,4-dimethyl-, 2-methoxy-2,r-313 251 194 67,66.5 82 trans-IV1 47-48 (15) 1.4182 1.79 c 192 66 trans-V' 49-50 (15) nd8 240.5/ 191 65.4 trans-VP 54-55 (15) nd8 245 190 79 cis-I6

Synthesis and stereochemistry of some multi methylsubstituted 1,3-dioxanes

“…It has already been shown that 1 attains the 1,4-twist form 2,3 and by comparing its chemical shifts with those of 3 it is easy to believe that also 3 is predominantly in the 1,4-twist form ( Fig. 2) since 2-Me, 6-Me and 5-Me attain there pseudo equatorial positions and both methyl groups at C-4 are isoclinal thus being able to avoid any major interactions.…”

“…1 These compounds attain the 1,4-twist form. 2 These values calculated for the 2e5e6a-Me 3 chair. 3 These values calculated for the 2a5a6e-Me 3 chair.…”

“…3 kJ mol −1 more stable than the 2,5-twist form [∆H(1,4-CT) 25.0 kJ mol −1 ; ∆H(2,5-CT) 28.7 kJ mol −1 ]. 3,5 By applying the method of Eliel and Nader 2 we prepared a few trans-2,6-methyl-substituted derivatives where one or the other of these substituents occupies an axial orientation (if being in a chair form) to get further insight into the chair-twist problem. …”

Theoretical density functional study of substituted dioxanes: trans 3,6-dimethoxy-1,2-dioxane

“…1 In the first isomer exists a conformational equilibrium between synclinal and antiperiplanar structures. We inform about the rotation barriers of the methoxyl group calculated by both methods and then we analyse the stabilization of a conformer over the other one in terms of interactions depending on the orientation of the free electron pairs belonging to the exocyclic oxygen atom with respect to the C-O endo bonds and antibonds.…”

“…The relevance of these substituents arises from the fact that stereoelectronic effects take place, which implies they are more stable than their equatorial-equatorial isomers. 1 X-Rays and Nuclear Magnetic Resonance (NMR) experimental data of some substituted 1,3-and 1,4-dioxanes show they adopt a chair conformation, and it is suggested that the most stable isomer is the trans one. [2][3][4][5] Some previous theoretical studies have shown that although cyclic sixmembered systems preferentially adopt the chair conformation, some of them can choose the twist conformation.…”