Stereochemistry of Seven-membered Heterocycles: XLIV. Spatial Structure of 4-R-3,5-Dioxabicyclo[5.1.0]octanes

Abstract

Abstract4-R-3,5-Dioxabicyclo[5.1.0]octanes were prepared in good yields by reduction of the corresponding 8,8-dichloro derivatives in a system Lit-BuOH. According to the data of dynamic 1 H and 13 C NMR spectroscopy involving experiments in the NOESY mode the formal (R = H) at 93°C in (CD 3 ) 2 CO exists in nearly equally occupied chair forms with endo-and exo-oriented three-membered ring. The like structure were found in the diastereomeric 4-Me(t-Bu)-analogs. The characteristic feature of 13 C NMR spectra consists in considerable difference in the chemical shifts of the C 8 atoms (Dd ~1617 ppm). The data on epimerization of diastereomers and calculations along AM1 procedure suggest for formal a three-component equilibrium including a twist-form.It was shown formerly that dihalo derivatives of 3,5-dioxabicyclo[5.1.0]octane I and II exist in an equilibrium of chair-like and flexible forms [1] (Scheme 1).For adducts of dichloro-and dibromocyclopropanation the position of conformational and epimerization equilibria is governed by the repulsive interactions involving halogens and oxigens of the acetal fragment and also the bulky R substituent attached to C 4 atom. As show 13 C NMR data and semiempirical AM1 calculations for formals Ia and IIa the most favorable conformation is exo-chair. The analogous situation is observed in the diastereomers of the exo-series whereas for the endo-diastereomers the chair-like structure is significantly strained, and the conformational equilibrium is virtually totally shifted to the flexible form In case of identical substitution at the C 4 atom the position of epimerization equilibrium is the same in dichlorides and dibromides, but with growing bulk of the substituent at the acetal carbon the equilibrium is displaced to the chair form.It seemed reasonable to perform the conformational analysis for bicyclic acetals III where the sterical contacts involving the cyclopropane moiety and oxygen atom are minimized.This class compounds were formerly obtained in two ways, either by condensation of cis-1,2-dimethylolcyclopropane with paraformaldehyde, isobutyraldehyde [2], and cyclohexanone [3], or by cyclopropanation of 1,3-dioxacyclohept-5-ene by SimmonsSmith reaction [4]. We applied to the synthesis of compounds III the known procedure of hydrogenolysis of dichloro derivatives I with lithium in the tert-butanol. The yields of reaction products III were no less than 85% and were higher than those mentioned in [24]. The possibility of stereospecific reduction of easily available con-; 2 5 2 + ; 2 2 + 5 H[R 2 2 + 5 ; ,