Orientation pseudo-axial

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. ... 

As a consequence of the pericyclic reaction path, the addition of a-stereogenic allylmctals to carbonyl compounds is accompanied by an effective 1,3-chirality transfer in the allylic moiety combined with 1,4-chira induction at the prostereogenic carbonyl group3032. The scheme also demonstrates the importance of the orientation of the substituent X in the six-membered transition state. By changing from a pseudo-axial to a pseudo-equatorial position, the cation-induced sy/i-attack addresses opposite faces of both prostereogenic moieties, leading to a Z-and an -isomer, these being enantiomeric in respect to the chiral moiety. 

We were mesmerized by the X-ray structure of hydroxy ketone 56 with its AB-ring junction being both. -hybridized, revealing a very different conformation from that of 48. The structure showed near-perfect chairs for the m-fused l-a /-decalinic. With this conformational preference, the p-Me group is pseudo-equatorial with the a-Me group now being pseudo-axial position. We believe this new a-Me orientation is responsible for the fact that the C5a-carbonyl is not reduced by NaBFLt it is sterically inaccessible, even by a nucleophile as small as a hydride. 

The role of Ti(OPri)4 in this process is shown in Figure 2-7. The aldehyde is illustrated in two conformations, the solid lines indicating the more favorable orientation. The conformation represented by the dashed line is disfavored by a steric interaction with a pseudo-axial aryl group. Assuming that the attack of a nucleophile comes from the direction of the viewer, this hypothesis accounts for the Sf-face selectivity in all known Ti-TADDOLate-mediated nucleophilic additions to aldehydes. 

With the analogous reagent 125, however, the corresponding allylboronate intermediate 126 is thought to favor a transition structure 127 where the a-substituent is positioned in a pseudo-axial orientation in order to escape nonbonding interactions with the bulky tetraphenyl dioxaborolane (Eq. 99). This way, a Z-configured allylic alcohol unit of opposite configuration is obtained in diol product 128. This type of steric control with chiral a-substituted allylboronates... 

It has been shown that methyl thiocellotrioside (44d), tetraoside (44i) and pentaoside (44j) are potent inhibitors of endoglucanase I (EGI, family 7) and cellobiohydrolase II (CBHII, family 6) from Humicola insolens [41]. Furthermore, a crystal of EGI of Fusarium oxysporum was soaked in a solution of compound (44j), and a clear density for three sugar rings was seen in subsites -2, -1 and -hi. It has been found that the pyranose ring in subsite -1 adopts a boat conformation leading to a pseudo-axial orientation for the scissile bond (Fig. 2) [66]. 

Electrophilic heterocyclizations of 2-(pent-l-en-5-yl)-l,3-benzoxazin-4-ones (142) and their C-2 epimers afforded diastereomeric mixtures of 9-methyl-5a,6,7,8,9,ll-hexahydropyrido[2,l-h][l,3]benzoxazin-10-ones (143 and 144), and their C-5a epimers, respectively, containing the 9-methyl group in the pseudo-axial orientation (89TL7321 90TL6765). Diastere-omers 143 and 144 interconvert in response to acidic catalysis (89TL7321). 

The trans-dimethyl precursors (Rp CHj, R2= C=CH, or the opposite) are known to exist in conformation 45A where both secondary methyl groups are axially oriented. The cis-dimethyl precursors 48 take conformation 48A which has an equatorial methyl group at C-2 and a pseudo-axial one at C-l. 

This compound ((3R,3 i )-(P,P)-trans-1,1, 2,2, 3,3, 4,4 -octahydro-3,3 -dimcthyl-4,4 -biphenanthrylidene, (P,P)-trans-35) was prepared by McMurry coupling of (R)-3-methyl-4-keto-l,2,3,4-tetrahydrophenanthrene, which in turn was obtained through resolution or asymmetric alkylation methods.1671 X-ray analysis showed that (P,P)-trans-35 adopts a double helical structure, with the two methyl substituents in a pseudo-axial orientation. Calculations confirmed this preferred conformation for (P.P) -trans-35, and showed that (M,M)-trans-35, with both methyl groups in pseudo-equatorial orientations, was 8.6 kcal mol-1 less stable (Scheme 22). For the cis isomer, the same features were observed, with (M,M)-cis-35 (diequatorial Me-substitu-ents) less stable than (P,P)-cis-35 by 11.9 kcal mol-1. 

This different behavior is ascribed to the pseudo-axial orientation of the C—F bond. The [MH]+ ions are in fact more stable for the / -anomer of 117 and for the a-anomer of 118. The HF and AcOH losses are strongly dependent on the relative spatial arrangement of... 

The diastereoselectivity of the reduction depicted in Figure 14.46 is determined when the hydroxylated radical A is reduced to the hydroxylated organosodium compound B. For steric reasons, the OH group assumes a pseudo-equatorial position in the triva-lent and moderately pyramidalized C atom of the radical center of the cyclohexyl ring of intermediate A. Consequently, the unpaired electron at that C atom occupies a pseudo-axially oriented AO. This preferred geometry is fostered and settled once and for all with the second electron transfer. It gives rise to the organosodium compound B. B isomerizes immediately to afford the equatorial sodium alkoxide. 

The high trans diastereoselectivity often observed in cyclisations involving substrates bearing substituents at the C4 position, such as 74, can be rationalised by comparing the two possible chair-like transition structures (Scheme 5.49). Positioning the R group substituent in a pseudo-equatorial orientation relieves the A1,3 strain observed for the alternative conformer with the same substituent in a pseudo-axial position.81... 

While it is probably reasonable to draw general trends from this series, it should be kept in mind that most of the data came from different laboratories, as indeed there are four different reports for the simple pyrrolidine enamine that account for the range from 85 to 96%. Some of the factors that contribute to determining the regioisomeric composition of enamines are A -strain, which destabilizes the more substituted isomer, and A - -strain, which destabilizes the less substituted isomer (Scheme 6). The former effect was used by Johnson to effectively convert c/j-2,4-dimethylcyclohexanone to the trans isomer through formation of the less substituted pyrrolidine enamime, where a pseudo-axial orientation of the 2-methyl group reduces the level of A - -strain (equation... 

Treatment of lithium alkynides with aluminum trichloride leads to tri(ethynyl)aluminum intermediates, which on treatment with haloalkanes give the corresponding disubstituted acetylenes. " The reaction is successful with tertiary haloalkanes and a variety of alkynes have been prepared (Scheme 9). An interesting variation of this method has been reported by Trost and Ghadri who reacted a diethylethynylalumin-um with an allyl sulfone in the the presence of the Lewis acid aluminum trichloride. When the allyl sulfone was part of a six-membered ring, then the alkyne was introduced exclusively in a pseudo axial orientation (Scheme 10). 

In crystalline furanose 8.16, the chlorine atom adopts a pseudo-axial orientation and the nitrogen atom, a pseudo-equatorial one. The orientation of the N-O bond is given by the Newman projection along the C-l-N bond, 8.18. A compact model indicates that one face of the N=O bond is very hindered. It is probable that the same conformation exists in solution and that this is what imposes the endo approach as shown in 8.19 in which the cyclohexadiene tries to avoid the sugar support of the nitroso chloro derivative. 

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