Orientation pseudo-equatorial

This could explain the lack of activity observed by Cannon et al. for the octahydrobenzo[g]quinoline XV (27). If no N-substituent is attached, the electron pair could orient pseudo-equatorially, but directed nearly 180° from the orientation attainable by XVI or XVII. Addition of an n-propyl would force the electrons into the pseudoaxial conformation. 

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. 

In addition to the [4+2] cycloaddition, intramolecular [2+2] photocycloaddition was also successfully used as a main procedure in the synthesis of (i)-ginkgolide B <00JA8453>. The studies on the model reactions and molecular mechanics calculation show that the stereochemistry of the substituents at C6 and C8 should influence severely the reaction diastereoselectivity. When syn-diastereomer 41 is subjected to irradiation the reaction gives a single diastereomer 42 in a quantitative yield since two substituents at C6 and C8 would be in pseudo-equatorial orientation in the chair-like transition state. 

A change in the allyl hapticity (q3 to p1 slippage) leading to the less substituted titanium-carbon o bond accounts for the observed y-regioselectivity. The anti diastereoselectivity stems from a pseudo-equatorial orientation of the aldehyde group. The diastereoselectivity of the reaction can be reversed through the use of a more coordinating cosolvent such as HMPA (Scheme 13.7) [14]. This reversal of anti to syn diastereoselectivity can be rationalized in terms of an open transition state. 

This protocol is also effective for the cyclization of an allenylaldehyde, the synthetic utility of which has been demonstrated in the synthesis of (+)-testudinariol A (Scheme 16.89) [97]. Cyclization of an allenylaldehyde provides a ris-cyclopentanol bearing a 2-propenyl group at the C2 position. The reaction mechanism may be accounted for by coordination of Ni(0) with both the aldehyde and the proximal alle-nyl double bond in an eclipsed fashion with a pseudo-equatorial orientation of the side chain, oxidative cyclization to a metallacycle, followed by Me2Zn transmetalla-tion and reductive elimination. 

Yttrium-catalyzed enyne cyclization/hydrosilylation was proposed to occur via cr-bond metathesis of the Y-G bond of pre-catalyst Cp 2YMe(THF) with the Si-H bond of the silane to form the yttrium hydride complex Ig (Scheme 8). Hydrometallation of the C=G bond of the enyne coupled with complexation of the pendant G=G bond could form the alkenylyttrium alkyl complex Ilg. Subsequent / -migratory insertion of the alkene moiety into the Y-C bond of Ilg could form cyclopentylmethyl complex Illg. Silylation of the resulting Y-C bond via cr-bond metathesis could release the silylated cycloalkane and regenerate the active yttrium hydride catalyst. Predominant formation of the /ra //j--cyclopentane presumably results from preferential orientation of the allylic substituent in a pseudo-equatorial position in a chairlike transition state for intramolecular carbometallation (Ilg —IHg). 

These results indicate that the cyclization via a chair-like transition state having the iminium cation in a pseudo-equatorial orientation (cf 33) is more facile than that with an axial orientation (cf. 34). Note again the relative orientation of the iminium cation and the olefinic double-bond which is antiperiplanar in 33 and synclinal in 34. 

In the first step of the catalytic cycle a coordinatively unsaturated Pd(0) species - which is formed in situ from Pd(OAc)2 and PPh3 -inserts into the alkenyl-I bond of 8 to give 42 (syn addition). Next an insertion of the terminal olefin into the cr-alkenyl-C-Pd bond forms the six-membered ring in 43. The stereochemistry can be explained by 41 reaction of the si-face of the exomethylene group involves a nearly coplanar orientation of the Pd-C bond and the C-C-zrbond. The siloxy substituent is placed pseudo-equatorially. 

Figure 4. Conformations of l,10-diaza-18-crown-6 with either diaxial orientation of the N-lone pairs (a), or pseudo-equatorial orientation of the lone pairs (b) (conformation (a) has lower energy if substituent at N is R = H, but higher energy with R = Me, favoring then conformer (b) models after energy minimization in gas phase with MM2, Ph.D. Dissertation of V. Rudiger, Saarbrucken), Exp. observed (in MeOH) AG(complex) for R = H 10.0 kJ/mol for R = Me 29.5 kJ/mol.

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. 

The aldimine of Figure 13.34 is a chiral and enantiomerically pure aldehydrazone C. This hydrazone is obtained by condensation of the aldehyde to be alkylated, and an enantiomerically pure hydrazine A, the S-proline derivative iS-aminoprolinol methyl ether (SAMP). The hydrazone C derived from aldehyde A is called the SAMP hydrazone, and the entire reaction sequence of Figure 13.34 is the Enders SAMP alkylation. The reaction of the aldehydrazone C with LDA results in the chemoselective formation of an azaenolate D, as in the case of the analogous aldimine A of Figure 13.33. The C=C double bond of the azaenolate D is fraws-configured. This selectivity is reminiscent of the -preference in the deprotonation of sterically unhindered aliphatic ketones to ketone enolates and, in fact, the origin is the same both deprotonations occur via six-membered ring transition states with chair conformations. The transition state structure with the least steric interactions is preferred in both cases. It is the one that features the C atom in the /3-position of the C,H acid in the pseudo-equatorial orientation. 

Structure B corresponds to the most stable transition state of the Ireland-Claisen rearrangement of Figure 14.49. In this transition state, the substituent at the allylic stereocenter is in a pseudo-equatorial orientation with respect to the chair-shaped skeleton. This is the same preferred geometry as in the case of the most stable transition state B of the Claisen rearrangement of Figure 14.48. The reason for this preference is as before that is, an allylic substituent that is oriented in this way experiences the smallest possible interaction with the chair skeleton. The obvious similarity of the preferred transition state structures of the Ireland-Claisen rearrangements of Figures 14.49 and 14.48 causes the same trans-selectivity. 

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... 

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. 

---