Gem-dimethyl groups

Gemeprost (73 16.16-dimethvl-trans-A -prostaglandin-E]) is dramatically more potent on a dosage basis as an abortifacient than prostaglandin E2 itself and has fewer side effects. The gem-dimethyl groups at C-16 protect the alcohol moiety at C-15 from rapid metabolic oxidation. 

For oxathiane 1, lone pair selectivity is controlled by steric interactions of the gem-dimethyl group and an anomeric effect, which renders the equatorial lone pair less nucleophilic than the axial lone pair. Of the resulting ylide conformations, 25a will be strongly preferred and will react on the more open Re face, since the Si face is blocked by the gem-dimethyl group (Scheme 1.9) [3, 15]. 

The steric effect generated by the gem-dimethyl group of the thietane ring on the adjacent sp2 carbon atom makes the cycloaddition in these cases more sluggish compared with those of the parent thietane dioxide (6b)190. These cycloadditions provide a convenient entry into the strained thiabicyclo [2.2.0] hexane system (e.g. 287, 288 equation 107). 

This general picture is similar to that observed in the ring-closing propensity of open chain alkanes, where a gem-dimethyl group greatly improves the yield of cycles as opposed to polymers (see 87, 88). This is known as the Thorpe-Ingold effect and has been examined in depth 1451. The steric bulk of the substituents diminishes the conformational space available for the open pre-... 

Still another way to characterize metal surface sites by a chemical reaction is with the unique molecules (+)— and (—)—apopinene (Fig. 1.5).25-28 The apopinenes are an enantiomeric pair of molecules with a double bond steri-cally hindered on one side by a gem-dimethyl group. During hydrogenation, each enantiomer may hydrogenate to the saturated symmetrical apopinane or isomerize to its enantiomer, which will have the same reactivity on a symmetrical surface (Scheme 1.1). 

The two articles in this current volume describe recent developments with small ring compounds which have not teen compiled in such a context before. T. Hirao discusses selective transformations initiated by transition derivatives in the construction of functionally substituted five-, six- and seven-membered rings as well as open-chair compounds. Cycloadditions onto methylene- and alkylidene-cyclopropane derivatives, described by A. Goti, F. M. Cordero and A. Brandi, not only yield products with spirocyclopropane moieties which can be desirable as such or as potential mimics of gem-dimethyl groupings, but also intermediates which can undergo further transformations with ring-opening of the cyclopropane units. 

Had the compound been less stable than we would predict the discrepancy would have been easier to explain. One could argue that the gem- dimethyl groups would have resulted in destabilization because of buttressing . It is tempting to argue that the triene was contaminated by polymer and/or peroxide, both of which have lower enthalpies of formation. But we have no documentation of this. 

Two distinct dynamic NMR effects occur in 1,3-dioxocane and its derivatives having a gem-dimethyl group at the 2- and/or 6-positions (chemical, not conformational numbering) (76JA2059). These molecules have unsymmetrical boat-chair conformations (e.g. 432) which minimize non-bonded and dipole-dipole repulsions... 

However, initial experiments with this reagent gave poor results, with the secondary amide undergoing reduction along with the tertiary amide. Compound 101 [and 107, Fig. (29)] is sufficiently twisted such that the gem-dimethyl groups effectively block the (j-face of the tertiary amide, leaving the a-face relatively unencumbered. However, a modification of the alane procedure [60], proved satisfactory for this transformation. The piperazinedione 101 was pretreated with AlEt3, with the expectation that this Lewis acid would form a complex with the more exposed secondary lactam [106, Fig.(29).] and leave the tertiary lactam accessible for reduction. 

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