Quasi axial substituent

We explain the selective formation of diastereomer 52 on the basis of conformational arguments. The two likely conformers of 50 should have an essentially planar allyl moiety, whereas the six-membered ring should exist in two quasi-chair conformers with either the isopropyl or the methoxy group in the quasi-axial position. The conformer with the (bulkier) isopropyl group in a quasi-equatorial position is preferred. While access to the terminal allylic carbon (which leads to 51) appears to be unhindered, the quasi-axial substituent at the chiral carbon will interfere with the attack on the internal allylic center, directing the attack to the face opposite to the quasi-axial methoxy function, (- 52). These considerations account for the preference of 51 over 52 as well as for the suppression of the diastereomer. 

The enamines derived from cyclohexanones are of particular interest. The pyrrolidine enamine is most frequently used for synthetic applications. The enamine mixture formed from pyrrolidine and 2-methylcyclohexanone is predominantly isomer 17.106 A steric effect is responsible for this preference. Conjugation between the nitrogen atom and the tt orbitals of the double bond favors coplanarity of the bonds that are darkened in the structures. In isomer 17 the methyl group adopts a quasi-axial conformation to avoid steric interaction with the amine substituents.107 A serious nonbonded repulsion (A1,3 strain) in 18 destabilizes this isomer. 

Entry 5 is an example of use of an a-trimethylsilylallyl group to prepare a vinylsilane. The stereochemistry is consistent with a cyclic TS having the trimethylsilyl substituent in a quasi-axial position to avoid interaction with the bridgehead hydrogen of the bicyclic ring. 

Dienes in quasi-s-fraws conformation are found only in cyclic structures where perfect planarity is hindered. The DR also holds valid for this kind of conformation, as demonstrated by the considerations of Section II.D.l.a and also confirmed by all the reported calculations. Indeed, contrary to what is sometimes found for cisoid systems, the rotational strength evaluated by many types of calculation is invariably found to follow the diene rule for transoid systems. However, very small skew angles are usually found in real molecules and this implies that the main contribution to the observed optical activity cannot come from the weak intrinsic distortion, but is more likely to stem from the dissymmetric perturbations, notably of the allylic axial substituents. 

An interesting stereochemical profile of this cyclization is that in the five-membered product structures, substituents PhS and OH groups are placed cis to each other, whereas in six-membered products the placement is trans (Table 6, entry 7). The cis selectivity in the five-membered ring systems is not affected by a and fi-substituents of the alkoxides (entries 2, 3 and 4), indicating that the steric effect is not the dominant factor. Instead, interaction between the oxido and carbene center composes a five- (or seven-) membered transition state 28, which allows the carbene to abstract the nearest quasi axial hydrogen as a hydride to produce a carbonyl intermediate 29, leading to the cyclization products 27 and 30 (Scheme 13, Eq. 1). Similarly, the stereoselective stepwise cyclization of cis- and rra s-2-(3,3-dithiopropyl)cyclohexanol to 2-phenylthio-... 

Variable temperature studies again show the ring inversion (76T2339). They also indicate that a 2-methyl group shows equal preference for the quasi-axial or quasi-equatorial positions, presumably because there are no other axial substituents to cause 1,3-diaxial interactions. 

The conformational effects arising from the endoanomeric effect are for furanoses much less profound and as a result relatively little research has been performed in this area. The puckering of the furanose ring of an a and a P anomer usually adjusts the anomeric substituent in a quasi-axial orientation and hence both anomers experience a similar stereoelectronic effect. On the other hand, the conformational preference of the exocyclic C—O bond is controlled by the exoanomeric effect in the usual way. 

There exist two simple rationales to explain the observed direction of the dia-stereoselective bond activation in 7/Fe+, i.e., more pronounced loss of H2 from 7a/Fe+ in comparison to 7b/Fe+. At first, one can safely assume that the reaction proceeds via insertion of the docked Fe+ in a terminal C-H bond to form a six-membered ring. Depending on the relative stereochemistry at C(3) and C(4), the eliminations of H2 and HD, respectively, therefore involve quasi-axial or quasi-equatorial orientations of the methyl substituents in the intermediates eq- and ax-lOa of course, similar considerations apply to the associated transition structures (TSs). By analogy to conventional arguments of conformational analysis, an equatorial position of the methyl group is assumed to be preferred, thereby accounting for the experimentally observed H2/HD ratios. Thus, for the stereoisomer shown in Scheme 8, both the KIE and the equatorial position of the methyl substituent favor loss of H2, whereas the SE favors loss of HD from 7b/Fe+. However, for the latter this path is impeded by the operation of a kinetic isotope effect that slows down activation of a C-D bond. Secondly, one arrives at... 

Diethyl phosphorocyanidate adds to a,/J-unsaturated aldehydes or ketones in the presence of lithium cyanide in a 1,2-fashion28. Boron trifluoride-diethyl ether complex catalyzed rearrangement of these allylic phosphates shows high E selectivity (>85 15) for the adducts derived from aldehydes and Z selectivity (>90 10) for ketone adducts. The selectivity of the rearrangement can be explained by assuming a chairlike transition state, in which the sterically more demanding x-substituent occupies the quasi-equatorial position. The steric requirement decreases in the order of R1 > CN > H. Thus, the cyano substituent occupies the quasi-equatorial position in the aldehyde-derived adduct (R1 = H), but the quasi-axial position in the ketone-derived adduct (R1 = CH3, C6H5). 

With two exceptions the 1/3-methyl substitution decreases anabolic activity and significantly decreases androgenic activity. A -Andros-tenes were the exceptions, for which distortion of ring A causes the normally equatorially oriented j8-substituent to assume a quasi-axial position. 

Dialkyl substitution in the 5a-dihydro series or A -series causes a considerable distortion and forces the a-substituent to orient itself in a quasi-axial conformation. Since we have already seen the importance of axial attachment at C-3 and will see the same at C-5, it is not surprising to find that the quasi-axial conformation at C-4 inteferes with the a-face attachment to the receptor at carbons 3 and 5 and hence abolishes activity. 

The 5,S conformation of glycopyranosyl oxacarbenium ions with 0-2 equatorial and the remaining substituents quasi-axial is important, especially for gluco, galacto, and related configurations. 

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