Conformations, ring Conjugate addition

Synthetic chemists can now work with three-dimensional pictures of the conjugate addition available on a website [80]. In the absence of steric hindrance (5-methylcyclohexenone, for example), an axial attack through a half-chair conformation is favored, while in the cortisone synthesis an equatorial attack through a half-boat conformation is favored because of the constraint imposed by the bicyclic rings [83]. 

If a new chiral centre is formed on a saturated six-membered ring, conformational control is a possibility. We have already seen conformational effects in the reduction of ketone 48 and the same kind of arguments apply to attack on ketones by carbon nucleophiles. The alcohol 59, needed to make an analgesic 58, can obviously be made from the ketone 60 and that is the result of conjugate addition to cyclohexenone.12... 

In the case of absence of the saturated carbon atoms, the bending and 1,2-allylic strains cannot be considered as the reasons for a flat potential energy surface around minimum. Therefore, it was suggested [27, 28] that the deviation of characteristics of cyclic conjugated systems from their aromatic features is responsible for conformational flexibility of such dihydroaromatic rings. In addition, it was demonstrated... 

The stereoselectivity of conjugate addition reaction of 34 can be rationalized as follows. The conformation of 34 is restricted to A by the oxazolizinone ring, and the vinyl anion attacks from stereoelectronically preferred (3-axial direction to give rise to the adduct 35 exclusively. 

As you now know (p. 1134) aU esters and lartones prefer to be in the conformation shown for the first compound so that they can enjoy stabilization by the anomeric effect. The second ester would also prefer o be like this too (first diagram below) but in this conformation it cannot cyclize at all. Even in the less favourable conformation it uses for reaction, it prefers conjugate to dirert substitution as the latter would give a strained truns-cycloheptene. The first compound can enjoy both the anomeric effert and conjugate addition as a frans-alkene in a ten-membered ring is fine. It is better than fine in the heterocyclic product as the lactone also enjoys the anomeric effect... 

Anti stereochemistry in six-membered rings Conformational control from a chiral centre in the cyclohexenone Remote stereochemical control in five-membered rings prostaglandins Regio- and stereochemical control in open chain compounds Asymmetric induction by a chiral auxiliary on the enolate Tandem Michael-Michael Reactions One Conjugate Addition Follows Another Double Michael or Diels-Alder reaction ... 

We shah end this section on conformational control in six-membered rings with the preparation of a useful chiral molecule 8-phenylmenthol from the natural product (i )-(-i-)-pulegone. The first step is a conjugate addition to an exocyclic alkcne. A new stereogenic centre is formed by protonation of the enolate intermediate but with virtually no stereoselectivity. 

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