Enolates bridgehead

Catalytic reduction of bridgehead enol lactone over Pd/C indicates that, indeed, the syn addition from the exo face of the bridgehead double bound establishes the relative configuration of all substituents [264], Equilibration studies performed in EtONa/EtOH also established that the ratio of the epimers corresponds to an equilibrium mixture. Under mild basic conditions (NajCOj/ EtOH), the product isomerization occurs to a very small extent. The product distribution is best understood by rapid conformational relaxation to one of the two low-eneigy half-chair conformations. The stereochemistry is established at the subsequent protonation step. This takes place with a strong preference for axial protonation from the /I face at carbon 2 to produce the most stable chair conformation (Scheme 14.12). 

The cyclohexanone ring is locked in a boat form in 451, in a chair form in 453 while it is flexible in 454. As a result, the bridgehead C3 — H bond in 451 is appropriately aligned to overlap with the x orbital of the carbonyl group, whereas it is not in 453 and 454. On that basis, the facile bridgehead enolization of 451 by comparison with 453 and 454 is readily explained by the principle of stereoelectronic control. This is also supported by the... 

If bridgehead enolates are, however, generated in the presence of a strong, base-resistant electrophile, under optimized conditions no oligomers but the expected, bridgehead-derivatized products can sometimes be isolated (Scheme 5.16). In the examples in Scheme 5.16 interestingly no ortho-mctalation of the phenyl group is observed. 

Giblin, G. M. P. Kirk, D. T. Mitchell, L. Simpkins, N. S. Bridgehead enolates substitution and asymmetric desymmetrization of small bridged carbonyl compounds by lithium amide bases. Org. Lett. 2003, 5, 1673-1675. 

Simpkins and coworkers reported the use of chiral bases in the enantioselective generation of bridgehead enolates (Scheme 36)76. Initial studies revealed that external quench protocols were ineffective in trapping the carbanion. Addition of a mixture containing chiral base (R,R) 3 and LiCl to a solution of ketone 55 and TMSC1 at —105 °C gave mono (—)-a-silylated ketone 56 in 76% yield and >96% ee. 

Formation of the antiaromatic enolate 11 from the low acidity ketone 10 " is evidently unfavourable compared with its acyclic variant 17. Attempts at isolating a stable enol derivative of 10, such as its silyl enol ether, have proved unsuccessful ". Treatment of benzocyclobutanone (10) with LiTMP in THE at —78°C, followed by the addition of trimethylsilyl chloride (MesSiCl), gave the corresponding C-silylated benzocyclobutanone 18 (equation 3) ". The non-aromatic C-lithiated ketone 20 appears to be more preferred than its related 0-lithiated enolate 11. Unlike traditional lithium enolates, this particular lithium enolate reacts in situwilh its parent compound, benzocyclobutanone (10), to give the diketone 19 (equation 3). In comparison, bridgehead enolates have also been shown to be similarly reactive ... 

After some standard transformations the base induced double ringopening of 28 to A/B ring compound 29 was achieved in 85 % yield, including protection at Cl3. For the oxidation at C1 in 29 the proton was abstracted with potassium t-butoxide at the tertiary carbon and not at C9 to give once again the unusual bridgehead enolate, which was oxi-... 

Shea KJ, Fruscella WM, England WP. Dichlorocyclopropa-nation and ring cleavage of bridgehead enol lactones. A ster-eocontrolled ring expansion sequence. Tetrahedron Lett. 1987 28 5623-5626. 

---