Pseudo-equatorial group

Conformational studies of c/5-6,11/)-H- and /rnns-6,ll/)-H-6-methyl-2,3,4,6,7,1 l/)-hexahydro-l//-pyrimido[6,l-n]isoquinolin-2-ones (136 and 137) by means of the MM2 method implemented in the HyperChem 4.5 suggested, that in the lowest-energy conformations heterocyclic moiety adopted trans-fu ed ring annotation in both cases, with a pseudo-equatorial and -axial methyl group, respectively (97LA1165). 

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 first total synthesis of (T)-arteannuin M was accessed using a tandem oxy-Cope/ene reaction.87 Divinylcyclohexanol 138 was heated in toluene and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give compound 140 as a single diastereomer in 55-60% yield (Scheme 28). The diastereoselectivity is controlled by the pseudo-equatorial position of the alkyl group in the transition state 139. 

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. 

Cyclic Esters of Phosphorous Acid.—A large number of 2-substituted-4-methyl-l,3,2-dioxaphospholans (88) have been prepared and their stereochemistry and conformations investigated by 1H and 31P n.m.r.69 Unlike the corresponding 1,3-dioxans, the tra/w-isomer (88a) is favoured in all cases, and each isomer is best described in terms of two rapidly equilibrating half-chair conformers with the 4-alkyl group pseudo-axial or pseudo-equatorial. 

Ether was a better solvent in cases where the propargylic position was unsubstituted (methylene group) since, in THF, a competitive [1,2] -Wittig rearrangement took place and led to diminished yields. When applied to the secondary homoallylic propargyl ethers 388, the zinc-ene-allene cyclization afforded the c -2,3,5-trisubstituted tetrahydrofurans 389 with moderate to satisfactory levels of diastereoselectivity, which could be rationalized by the preferential pseudo-equatorial positioning of the homoallylic substituent in the cyclic... 

Only one of the two isomeric 1-hydroxy-3-oxoindolizidines (96) can be benzoylated with benzoyl chloride. This difference in reactivity is explained by the assumption that the hydroxy group in the reactive isomer occupies a more accessible pseudo equatorial position and that it occupies a pseudo axial position in the inactive isomer. 

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