Axial position substituents

Compounds in which conformational, rather than configurational, equilibria are influenced by the anomeric effect are depicted in entries 4—6. Single-crystal X-ray dilfiaction studies have unambiguously established that all the chlorine atoms of trans, cis, ira j-2,3,5,6-tetrachloro-l,4-dioxane occupy axial sites in the crystal. Each chlorine in die molecule is bonded to an anomeric carbon and is subject to the anomeric effect. Equally striking is the observation that all the substituents of the tri-0-acetyl-/ -D-xylopyranosyl chloride shown in entry 5 are in the axial orientation in solution. Here, no special crystal packing forces can be invoked to rationalize the preferred conformation. The anomeric effect of a single chlorine is sufficient to drive the equilibrium in favor of the conformation that puts the three acetoxy groups in axial positions. 

Conversely, when A-alkyl tryptophan methyl esters were condensed with aldehydes, the trans diastereomers were observed as the major products." X-ray-crystal structures of 1,2,3-trisubstituted tetrahydro-P-carbolines revealed that the Cl substituent preferentially adopted a pseudo-axial position, forcing the C3 substituent into a pseudo-equatorial orientation to give the kinetically and thermodynamically preferred trans isomer." As the steric size of the Cl and N2 substituents increased, the selectivity for the trans isomer became greater. A-alkyl-L-tryptophan methyl ester 42 was condensed with various aliphatic aldehydes in the presence of trifluoroacetic acid to give predominantly the trans isomers. ... 

Another consequence of the chair conformation is that there are two kinds of positions for substituents on the cyclohexane ring axial positions and equatorial positions (f igure 4.8). The six axial positions are perpendicular to the ring, parallel to the ring axis, and the six equatorial positions are in the rough plane of the ring, around the ring equator. 

Even though cyclohexane rings rapidly flip between chair conformations at room temperature, the two conformations of a monosubstituted cyclohexane aren t equally stable. In methylcyclohexane, for instance, the equatorial conformation is more stable than the axial conformation by 7.6 kj/mol (1.8 kcal/mol). The same is true of other monosubstituted cyclohexanes a substituent is almost always more stable in an equatorial position than in an axial position. 

Chair cyclohexanes are conformationally mobile and can undergo a ring-flip, which interconverts axial and equatorial positions. Substituents on the ring are more stable in the equatorial position because axial substituents cause 1,3-diaxial interactions. The amount of 1,3-diaxial steric strain caused by an axial substituent depends on its hulk. 

The reactions of allylboronates 1 (R = H or CH3) may proceed either by way of transition state 3, in which the a-substituent X adopts an axial position, or 4 in which X occupies an equatorial position. These two pathways are easily distinguished since 3 provides 7 with a Z-olefin, whereas 4 provides 8 with an E-olefinic linkage. There is also a second fundamental stereochemical difference between these two transition states 7 and 8 are heterochirally related from reactions in which 1 is not racemic. That is, 7 and 8 arc enantiomers once the stereochemistry-associated with the double bond is destroyed. Thus, the selectivity for reaction by way of 3 in preference to 4, or via 6 in preference to 5 in reactions of a-subsliluted (Z)-2-butenylboronate 2, is an important factor that determines the suitability of these reagents for applications in enantioselective or acyclic diastereoselective synthesis. 

The diastereoselectivity of the reactions of (Z)-l-methyl-2-butenylboronate is greater than that of (Z)-l-chloro-2-butenylboronate, evidently because the smaller, more electronegative chlorine substituent has a greater preference to orient in the axial position of transition state 5 than the methyl group. Excellent diastereoselectivity has also been observed in reactions of 1-methyl-3,3-disubstituted 2-propenylboronates and aldehydes27,40. 

The stereoselectivity of these reactions has been interpreted in terms of chair-like six-membered ring transition states in which the substituents a to tin adopt an axial position, possibly because of steric and anomeric effects. The cc-substituted (Z)-isomers are less reactive because the axial preference of the a-substituent would lead to severe 1,3-diaxial interactions17. 

An intermediate allyltin trichloride, possibly stabilized by an oxygen-tin hypervalent interaction, which then reacts with the aldehyde via a chair-like six-membered ring transition state with the substituent a to tin in an axial position, may be involved94. On heating with aldehydes, the 4-benzyloxypentenylstannane shows only modest diastereofacial selectivity22. 

Steric hindrance also seems to provide information as to whether yn-aldolates or cmb-adducts predominate in the equilibrium. Considering the chair conformations of the syn- and owz -aldolates, the latter seems to be thermodynamically more stable since it avoids the axial position of the substituent Y which it occupies in the s> -isomer. Indeed, the azzb-diastereomcr is favored in most reversible aldol additions ... 

Alkylations of 6-methoxycarbonyl six-membered cyclic (V-acyliminium ions show a strong preference for the formation of m-products. This is explained by the A0-3 strain between the substituent and the (V-mcthoxycarbonyl group of the iminium ion, forcing the substituent into an axial position. Stereoelectronically preferred axial attack by the nucleophile then leads to the 2,6-d.v-disubstituted piperidine derivatives. 

The ESR spectrum of the thioxanthene S, S-dioxide radical anion itself shows that the two possible conformers coexist, since the two methylene protons are not equivalent. In the case of the 9-monoalkyl derivatives, the large coupling constant observed for the 9-proton leads to the conclusion that the 9-substituent is in the boat equatorial position as in II1 F Thus the radical anions and the neutral molecule display different conformations. The protons in the 9-position of the radical anions of cis-9-methylthioxanthene S-oxides (2, n — 1, R1 = H, R2 = CH3) have an appreciable coupling constant10 which suggests that these radical anions have the substituent in the pseudo-axial position. Furthermore, in the radical anions the S—O bond is pseudo-axial. These situations are exactly the opposite of that observed for the neutral compound. 

The cyclic dimer, tetramer, and hexamer can be crystallized in acetonitrile, and also in chloroform (the former two oligomers). X-ray analysis of the crystals of the cyclic dimer47 disclosed that it consisted of a pair of different enantiomers of 53 and that all of the four substituents attached to the two tetrahydropyran rings occupied the axial position as illustrated in Fig. 54s). Such a conformation is in... 

Similar behavior is found in the 1,3-dithianes, " and 2,3-disubstituted 1,4-dithianes have also been examined. With certain nonalkyl substituents (e.g., F, NO2, SOMe, NMe ) the axial position is actually preferred. ... 

Now, let s make sure you know how to draw the substituents. The rules are the same as before. All axial positions are drawn straight up and down, alternating ... 

N.m.r. spectroscopy has played an important part in determining the stereochemistry of the 1,3-dioxaphosphorinanes (52). The presence of the saturated six-membered ring means that there are usually conformational effects to be unravelled before configurational assignments can be made. The chair conformation is generally dominant. Phosphorus substituents which exhibit shielding effects show that in many P " phosphorinanes this substituent occupies an axial position and Sis( has been used to establish the equatorial conformation of a t-butyl substituent at C(5). Even in P" derivatives the isomer possessing the bulkiest P-substituent in an axial... 

As one would expect, the tri-substituted cis-trans-2,4-diaryl-3-dimethylaminothietanes (187c,d) were shown by NMR to have all three substituents in pseudoequatorial positions with the remaining hydrogens in axial positions . ... 

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. 

Fooking more closely at fluorocyclohexane systems, it has been observed that a fluorine substituent in the axial position is much more highly shielded than one in the equatorial position. Of course,... 

Conformational analysis of diastereomeric pyrido[ 1,2-/ ][ 1,3 oxazin-l -ones 91 and 92 revealed that 91 adopted an O-inside m-fused conformation, whereas 92 existed in a /ram-fused form <1996SL100>. Both isomers contained the C-8 substituent in an axial position to avoid A<1,3) strain, which would be present in alternative conformations. 

Structural investigations of individual stereoisomers and equilibrium mixtures revealed some general features (83M11). A phenyl group at phosphorus is predominantly in an axial position when there is no steric hindrance. The introduction of bulky substituents onto carbon atoms of the ring shifts the equilibrium toward an equatorial form, and one more twist conformer appears. The influence of equatorial substituents on the equilibrium position is clearly pronounced in the case of P(III) derivatives as well as for a P(IV) compound. The substitution of a phenyl group by a... 

Structural studies of the initial diazaphosphorinanes and their complexes revealed a close connection between the structure of the former and the number of coordinating borane molecules. When substituents of a diazaphosphorinane with R = Ph are equatorial, addition of three molecules of borane in the axial position is not energetically favorable. In the case of R = CH2Ph there is a form with one axial substituent hence the third molecule of borane may approach the equatorial nitrogen lone electron pair (89IZV1375). 

The structure catalyst prepared using this ligand is shown in Fig. 11 and suggests that the high molecular weights can be attributed to the bulky substituent blocking at least one of the axial positions on the palladium center. 

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