Pseudoequatorial

The stereochemical features of the Claisen rearrangement are very similar to those described for the Cope rearrangement, and reliable stereochemical predictions can be made on the basis of the preference for a chairlike transition state. The major product has the -configuration at the newly formed double bond because of the preference for placing the larger substituent in the pseudoequatorial position in the transition state. ... 

Similar to cyclohexanones, substituted cyclopentanones also adopt a conformation with the substituents in a sterically favorable position. In the case of 2-substituted cyclopentanones 1 the substituent occupies a pseudoequatorial position and the diastereoselectivity of nucleophilic addition reactions to 1 is determined by the relative importance of the interactions leading to predominant fra s(equatorial) or cw(axial) attack of the nucleophile. When the nucleophile approaches from the cis side, steric interaction with the substituent at C-2 is encountered. On the other hand, according to Felkin, significant torsional strain between the pseudoaxial C-2—H bond and the incipient bond occurs if the nucleophile approaches the carbonyl group from the trans side. 

With a-alkyl-substituted chiral carbonyl compounds bearing an alkoxy group in the -position, the diastereoselectivity of nucleophilic addition reactions is influenced not only by steric factors, which can be described by the models of Cram and Felkin (see Section 1.3.1.1.), but also by a possible coordination of the nucleophile counterion with the /J-oxygen atom. Thus, coordination of the metal cation with the carbonyl oxygen and the /J-alkoxy substituent leads to a chelated transition state 1 which implies attack of the nucleophile from the least hindered side, opposite to the pseudoequatorial substituent R1. Therefore, the anb-diastereomer 2 should be formed in excess. With respect to the stereogenic center in the a-position, the predominant formation of the anft-diastereomer means that anti-Cram selectivity has occurred. 

Ternay and coworkers examined the conformations of thioxanthene-10-oxide (186) and related compounds. They found that oxygen preferred the pseudoequatorial position, 186e, but that the amount of pseudoaxial conformer, 186a, increased when the oxygen was complexed with iodine monochloride or trifluoroacetic acid171. 

As one would expect, the tri-substituted eis-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 positions202. 

Cyclization of an organolithium tethered to a suitably positioned carbon-carbon jt-bond is a thermodynamically favorable process that proceeds in a totally regioselective exo-fashion with a high degree of stereocontrol via a transition state in which the lithium atom is intramolecularly coordinated with the remote rc-bond.9 The stereochemical outcome of the cyclization of a substituted 5-hexenyllithium follows from the preference of the substituent to occupy a pseudoequatorial position in the chair-like transition state depicted below.7... 

Compounds 225a-f showed interesting dynamic phenomena on the NMR time scale with broad lines at room temperature and appearance of two sets of sharp peaks at -50 °C corresponding to conformers 226 and 227 (Fig. 3). By contrast, 225 g-1 exist essentially as one conformer. These results show that the presence of a Me substituent adjacent to the 0 atom in ring B and syn to the ring junction hydrogen (see 225 g) prejudices the molecule in favor of conformer 226, thus placing the Me substituent pseudoequatorially (cf. 226, = Me). Sim-... 

Entries 3 to 6 are examples of ester enolate alkylations. These reactions show stereoselectivity consistent with cyclic TSs in which the hydrogen is eclipsed with the enolate and the larger substituent is pseudoequatorial. Entries 4 and 5 involve SN2 substitutions of allylic halides. The formation of the six- and five-membered rings, respectively, is the result of ring size preferences with 5 > 7 and 6 > 8. In Entry 4, reaction occurs through a chairlike TS with the tertiary C(5) substituent controlling the conformation. The cyclic TS results in a trans relationship between the ester and vinylic substituents. 

With the corresponding secondary alcohols, the preferred cyclization is via a conformation with a pseudoequatorial conformation. 

Entry 13 shows cyclization with concomitant loss of the benzyloxycarbonyl group. The TS for this reaction is 5-exo with conformation determined by the pseudoequatorial position of the methyl group. 

Internal nucleophilic capture of seleniranium ion is governed by general principles similar to those of other electrophilic cyclizations.96 The stereochemistry of cyclization can usually be predicted on the basis of a cyclic TS with favored pseudoequatorial orientation of the substituents. 

In Entry 13, the dioxinone ring undergoes thermal decomposition to an acyl ketene that is trapped by the solvent methanol. The resulting (3-keto-y,8-enoate ester then undergoes stereoselective cyclization. The stereoselectivity is controlled by the preference for pseudoequatorial conformations of the C(6) and C(9) substituents. 

This stereoselectivity can be explained by a five-membered TS for the sigmat-ropic rearrangement step. The observed A-stereochcmistry results if the larger alkyl substituent adopts a pseudoequatorial conformation. 

In contrast to these adducts in which the boratabenzene ring is bound ti to the main-group metal, reaction of [C5H5B-Me]Li with PbCl2 affords a bent-sandwich complex, Pbfi/ -CsI LBMeh.31 This report provided the first structural characterization of an r 6-bonding mode to a p-block metal. Reaction of Pb(Ti6-C5H5BMe)2 with a Lewis base such as bipyridine leads to a complex wherein the bipyridine is bound in the pseudoequatorial plane. 

The stereochemical outcome of the reaction of 1-43, formed from 1-40 by desily-lation, can be explained by assuming a pseudoequatorial orientation of the epoxide moiety in a pseudo-chair-chairlike transition state 1-44 which, after being attacked by the phenolic oxygen, furnishes the correct trans-fused stereoisomer 1-41 (Scheme 1.12). The conformation 1-45, which would lead to 1-46 seems to be disfavored. 

Conformational studies of cis-A, b-H- and /ra r-6,llb-/7-6-methyl-2,3,4,6,7,llb-hexahydro-l/7-pyrimido[6,l- ]-isoquinolin-2-ones 89 and 90 by means of the MM2 method as implemented in HyperChem 4.5 suggested that in the lowest-energy conformations the heterocyclic moiety adopted /ram-fused ring annelation in both cases, with a pseudoequatorial and axial methyl group, respectively <1997LA1165>. 

Quantum-chemical calculations for model isoxazolidines C and C demonstrated that the conformer C containing the pseudoequatorial nitrogen lone pair is thermodynamically highly favorable, whereas the conformer D with the equatorial... 

The conformation bearing the substituent at the asymmetric center in a pseudoequatorial position (R1) is more stable than that bearing the substituent... 

It is to be noted that in the allyl vinyl ether (where R, > R2) the newly formed double bond has the E configuration. This is because that in the chair-like transition state, there is preference for placing the larger group in the pseudoequatorial position. 

If the transition state has the chair conformation 9, groups in the terminal positions of each allyl moiety can occupy pseudoaxial or pseudoequatorial positions. We therefore calculated the structures with a single methyl subsituent the results are shown in Fig. 6. 

FIGURE 8. MM2-85 calculated lp—N—C—H rotational potential curve (C in the tricyclic ring system) for 68, with a pseudoequatorial piperazine ring. The conformations A (dashed line) and B (solid line) are defined in Scheme 6. Reproduced with permission from Reference 108... 

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