Pseudoequatorial groups

C Chemical shifts for a number of methylcyclopentanones have been examined the cyclopentanone ring was considered to exist as a half chair and data were interpreted on the basis that an axial a-methyl is less stable than equatorial p-methyl. The chemical shift for P-carbons in 3-methyl-, cis-2,4-dimethyl-, and 2,2,4-trimethyl-cyclopentanones is 20.4 + 0.1 p.p.m., whereas in 2-methyl-, trans-2,5-dimethyl-, and ds-2,4-dimethyl-cyclopentanones the a-methyl chemical shift was centred around 14.3 p.p.m. Taking these values as representative of equatorial and pseudoequatorial groups, it was concluded that in cyclopentanones the carbonyl group shields C-2 methyl carbons less than in cyclohexanones. This was attributed to the larger 0==C—... 

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. 

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. 

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. 

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>. 

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. 

One can attribute the selective formation of materials with the ester and allyl units trans to one another, to the preference for the allyl unit to occupy a pseudoequatorial rather than a pseudoaxial orientation in the product-determining transition state. Compare, for example, transition state formulation 68 with 69. This stereochemical outcome is fortunate, as later on in the sequence, it is necessary for the allyl unit (after functional group modification) to swing across the top face of the cyclopentyl ring system during the conversion of 62 to 63. Were the substituents cis to one another, this would not be possible. 

The NOESY spectrum of 41 was also in agreement with the presence of both conformations. In the case of 41 A, the interactions H-5/H-9, and H-2/H-6 were the most relevant the latter was consistent with a pseudoequatorial (P) disposition of the hydroxyl group at C-2. For 4IB, the most important NOESY interaction was observed between H-7 and H-5 and between H-6 and H-4. 

The greater stability of the anti isomer is attributed to the pseudoequatorial position of the methyl group in the chair-like chelate. With larger substituent groups, the thermodynamic preference for the anti isomer is still greater.10 11 Thermodynamic equilibration can be used to control product composition if one of the desired stereoisomers is significantly more stable than the other. 

To model the crucial step of covalent adduct formation, adducts resulting from quenching of lO-azaBaP-4,5-epoxide with cytosine via the exocyclic amino group were computed, and their geometrical features and relative energies were compared (Fig. 24). The most stable stereoisomer was the one with the cytosine moiety trans to the hydroxyl, with both groups in pseudoequatorial conformation. Two structures... 

Data on the apparent dipole moment and H NMR spectra of thianthrene-5-oxide 24 under different conditions of solvent and temperature support the rapid conformational equilibrium of 24, which flaps between two limit boat conformations with the sulfoxide group in a pseudoaxial or pseudoequatorial position, respectively. Variable-temperature... 

H NMR spectra have established the interconversion barrier of /ra r-thianthrene 5,10-dioxides and confirmed that the conformational equilibrium of rfr-thianthrene 5,10-dioxides is strongly displaced toward the conformation with both sulfinyl groups in the pseudoequatorial position <2005JCX13450>. 

Pummerer reactions of both isomers of sulfoxide 145 with an excess of Ac20-Ac0H in boiling benzene afforded the same mixture of as- and /ra r-acetoxyderivatives 146 the former is the major product (as-146 Jrafis-146 = 92 8), with the 2-aryl group being pseudoequatorial and the 3-acetoxy moiety pseudoaxial (Equation 23) <2004MI317>. 

Alkenyl nitrones, having the alkene connected to the nitrone nitrogen atom, have been used in another approach to intramolecular reactions (231-235). Holmes and co-workers have this method for the synthesis of the alkaloid (—)-indolizidine 209B 137 (210,231). The alkenyl nitrone 134, was obtained from the chiral hydroxylamine 133 and an aldehyde. In the intramolecular 1,3-dipolar cycloaddition, 135 was formed as the only isomer (Scheme 12.45). The diastereofacial selectivity was controlled by the favored conformation of the cyclohexane-like transition state in which the pentyl group was in a pseudoequatorial position, as indicated by 134. Further transformation of 135 led to the desired product 137. 

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