Pseudoaxial substituent

This is readily explained by torsional interactions, which force the encfo-substituent into a pseudoaxial position trans to the partially formed C-0 bond. The steric interaction of the substituent with the second pseudoaxial substituent, even with hydrogen, is then stronger than that of a pseudoequatorial substituent with the transferred oxygen. 

In cyclic systems, however, conformational constraints can override the inherent preference for chairlike transition states in Cope as well as Claisen rearrangements and lead to a partial involvement if not a dominance of boat-like TS structures. In the Ireland rearrangement of lactones of type (247), for example, chair-like transition state (249) is accessible only when the diaxial bridging methylene chain becomes sufficient in length (n = 7, Scheme 44). The preference of boat-like transition state (250) over (251) is due to a serious A - -type interaction between the endocyclic oxygen atom and pseudoaxial substituent R in (251). 

Cyclohexenes The conformational equilibria for monosubstituted cyclohexenes are known to be less biased against the axial conformer than is the case with the saturated analog. This may be attributed to the absence of one 1,3-diaxial hydrogen interaction for either an axial or a pseudoaxial substituent in the half-chair conformations ... 

The stereochemistry of nucleophilic 1,4-additions to enones (Michael-type additions) is controlled by stereoelectronic factors. In the absence of compelling steric effects, the nucleophile approaches the [3-carbon of the enone antipamllel to the neighboring (y) pseudoaxial substituent (circled H in the example below). 

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. 

When an additional methyl substituent is placed at C(3), there is a strong preference for alkylation anti to the 3-methyl group. This is attributed to the conformation of the enolate, which places the C(3) methyl in a pseudoaxial orientation because of allylic strain (see Part A, Section 2.2.1). The axial C(3) methyl then shields the lower face of the enolate.55... 

The anion of cyclohexanone /V,/V-dimclhyl hydrazone shows a strong preference for axial alkylation.122 2-Methylcyclohexanone N,N-dimethylhydrazonc is alkylated by methyl iodide to give d.v-2,6-dimclhylcyclohcxanone. The 2-methyl group in the hydrazone occupies a pseudoaxial orientation. Alkylation apparently occurs anti to the lithium cation, which is on the face opposite the 2-methyl substituent. 

C-Alkylations of l,4-dihydro-27/-pyrazino[2,l-A]quinazoline-3,6-diones at positions C-l and CM were studied in detail. Compounds of type 57 could be alkylated diastereoselectively at C-l, owing to the geometry of the piperazine ring, which is locked in a flat boat conformation with the R4 or R1 substituent in a pseudoaxial position to avoid steric interaction with the nearly coplanar C(6)-carbonyl group. Alkylation of 57 (R2 = Me, Bn, R4 = Me) in the presence of lithium hexamethyldisilazide (LHMDS) with benzyl and allyl halides resulted, under kinetic control, in the 1,4-trans-diastereomer 59 as the major product, with retention of the stereocenter at CM (Scheme 5). 

In this scheme, a highly puckered metallocycle was envisioned, possessing pseudoaxial and equatorial substituents, and reaction pathways were said to be favored which minimized the following effects (a) 1,3-diaxial interactions of substituents on the two a-carbons (b) axial substituent interactions with juxtaposed ring carbons and (c) 1,2-diequatorial interactions. This scheme predicts relatively nonstereospecific metathesis of rra/j.v-olefins but highly stereospecific metathesis of ra-olefins. For example, the following pathways for reactions of m-olefins were proposed ... 

Lewis-acid promoted C-allylations of furanose acetates 101 with allyl-(trimethyl)silane are a-selective and the selectivity is governed by the alkoxy group at C-3. The lowest energy conformers bear the 3-alkoxy group in a pseudoaxial orientation (Scheme 35). To a lesser extent, the 2-substituent... 

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. 

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

It is apparent from Table 1 that the cyclohexadiene ring in 1,2-dihydrocorannule-nes is significantly flatter than either 1,3-cyclohexadiene itself or 9,10-dihy-drophenanthrene due to the constriction imposed by the remainder of the bowl-shaped ring system. Nonetheless, the lack of planarity means that substituents at may adopt either pseudoaxial (pa) or pseudoequatorial (pe) positions. However, the surface of the corannulene system is curved, and, unlike 1,3-cyclohexadiene and 9,10-dihydrophenanthrene, neither the two pa positions nor the two pe positions are equivalent. Thus, substituents in 1 -/ -1,2-dihydrocorannulenes may be (1) endo-pseudoaxial (endo-pa), (2) e do-pseudoequatorial (e/ido-pe), (3) exo-pseudoaxial (exo-pa), and (4) exo-pseudoequatorial (exo-pe), where endo and exo are related to concave and convex orientations, respectively. 

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