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

Kalevi Pihlaja,Jorma Mattinen

doi:10.3998/ark.5550190.0013.523

Abstract

Several multimethyl-substituted 1,3-dioxanes [ trans -2,4,4,6-tetramethyl ( 1), r-2,4,4, c-5, t-6pentamethyl- (2), r-2,4,4, t-5, t-6-pentamethyl ( 3) and trans -2,4,4,5,5,6-hexamethyl-1,3-dioxanes (4)] with 2,6-trans-disubstitution has been prepared via the Grignard reaction of the corresponding axial 2-methoxy-1,3-dioxanes. Inspect ion of their 13 C NMR chemical shifts in respect of different substituent effects showed tha t 1 and 3 attain exclusively the 1,4-twist form whereas 2 and 4 still favor clearly the chair form due to the very strong steric interaction caused by the pseudo axial methyl groups at position 5. We also manage to equilibrate 1 and its cisepimer ( 5) although less than 1% of 4 was present at equilibrium. Thus only −∆G o = 12.9±0.5 kJ mol −1 could be given and it compares well with some lite rature values. Since the conformational energy of 4-axial methyl group in 5 is 12.2 kJ mol −1 the ∆H(1,4-CT) is equal to 25 kJ mol −1

Highlights

A great number of methyl-substituted 1,3-dioxanes have been prepared earlier.[1]
We have been for a long time interested in the chair-twist equilibria of methylsubstituted 1,3-dioxanes.[3−5] It was concluded quite some time ago that if there is no pseudo axial substituent in the twist form, the 2,4-syn-diaxially substituted derivatives attain a 2,5- or 1,4twist form (Figure 1) depending on the location of the geminal substitution in position 2 or 4, respectively.[3,6]
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 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 being able to avoid any major interactions

Summary

Introduction

A great number of methyl-substituted 1,3-dioxanes have been prepared earlier.[1]. only after Eliel and Nader[2] developed their special method for preparing trans-2,4,4,6-tetramethyl1,3-dioxane it became possible to synthesize other trans-2,6-methyl-substituted 1,3dioxanes. The experimental 13C NMR chemical shifts for the compounds 1−4 are given in Table 1 together with those estimated for 2, 3 and 4 using the shift increments reported earlier by Pihlaja et al.[3,4,5]

Results

Conclusion