Epimers equatorial

Dezocine (30) represents a class of bridged aminotetralins possessing morphine-like analgesic properties. It appears to be roughly equivalent in potency and addiction potential to morphine. The molecule combines molecular features of precedent aminotetralins and benzomor-phans and its structure fits the classical Morphine Rule. The 1-enantiomer is the more active and the p-epimer (equatorial NHj) is the active diastereomer. 

In the absence of steric factors e.g. 5 ), the attack is antiparallel (A) (to the adjacent axial bond) and gives the axially substituted chair form (12). In the presence of steric hindrance to attack in the preferred fashion, approach is parallel (P), from the opposite side, and the true kinetic product is the axially substituted boat form (13). This normally undergoes an immediate conformational flip to the equatorial chair form (14) which is isolated as the kinetic product. The effect of such factors is exemplified in the behavior of 3-ketones. Thus, kinetically controlled bromination of 5a-cholestan-3-one (enol acetate) yields the 2a-epimer, (15), which is also the stable form. The presence of a 5a-substituent counteracts the steric effect of the 10-methyl group and results in the formation of the unstable 2l5-(axial)halo ketone... 

The facile and selective oxidation of both primary and secondary hydroxy groups with certain nucleotides led Pfitzner and Moffatt (48) to explore the scope of the carbodiimide-methyl sulfoxide reagent with steroid and alkaloid alcohols. Relatively minor differences were apparent in the rate of oxidation of epimeric pairs of 3- and 17- hydroxy steroids whereas the equatorial lLx-hydroxyl group in several steroids was readily oxidized under conditions where the axial epimer was unreactive [cf. chromic oxide oxidation (51)]. 

The rate-determining step in the formation of the x-lithio ethers is the formation of a carbon radical as a precursor to the anion. The intermediate radical in the tetrahydropyranyl system is expected to be nonplanar, to be capable of rapid equilibration between the quasiequatorial and quasiaxial epimers, and to exist largely or entirely in the axial configuration at — 78 °C. However, treatment of the a-phenylthio ether 4 with LDMAN at higher temperature in the presence of A, A, lV, ./V -tetramethylethylenediamine leads to the more stable equatorial epimer of the lithio ether 5 and, after addition to benzaldehyde, the axial- and equatorial-substituted products were obtained in a ratio of 13 87. 

Imine 214 (R = H) gave a 3 1 mixture of ot/(3 chloro epimers of 215 (R = H) when a mixture of Lewis acids, TiCl4, and Ti(OiPr)4 was used. The stereoselectivity of the formation of 215 is rationalized by a chair-like transition state 217 with equatorial attack of chloride ion <1998TL7239, 2000JOC655>. 

It has been concluded that some secondary chroman-4-oIs adopt a half-chair conformation in which a quasi-axial OH group, which absorbs at ca. 3618 cm-1, is predominant over a quasi-equatorial hydroxyl, which shows two peaks (3622 and 3600 cm-1) (74BCJ509). A study of more complex tertiary chromanols has indicated that the cis epimer (94) exhibits peaks at 3619 cm-1 (free OH group) and 3604 cm-1 (bonded OH). The trans epimer (95) shows only one band (3620 cm-1) which is also associated with a hydrogen bonded hydroxyl group, though now in a quasi-axial orientation (81JCS(P2)944). 

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