Enones bridgehead—

In another example (Scheme 8), the intramolecular cycloaddition of an azido functionality onto an enone group afforded bicyclic derivatives with bridgehead iV atoms. The cyclopentenone derivative 28 afforded the indolizidinone 30 through the proposed compound 29 which might react through a diradical intermediate or through a betaine intermediate <2002TL5385>. 

Addition of RJCuLi to bridgehead enones.1 Ordinarily organocuprates do not react with a bridgehead halide. However, they can undergo conjugate addition to bridgehead enones generated in situ from p-bromo ketones with potassium t-butoxide or lithium 2,6-di-r-butyl-4-methylphenoxide (6,95). 

Even stronger polarizations of double bonds in alkenes are induced by electron withdrawing substituents, as present in enol ethers, enones, and enamines (Sections 4.6.2, 4.7, and 4.9.2). Deshielding of C-7 in norbornadiene (75.5 ppm, Table 4.12) is understood as arising from interaction of antibonding n orbitals at the olefinic carbon atoms with o orbitals of the bridgehead bonds [214, 216]. Spiroconjugation in spiro[4.4]nonatetraene is interpreted similarly [242]. 

Step 2 Formation of the cis-fused 5,6 ring is thermodynamically preferred. The acidic conditions lead to the equilibration (epimerization) of one of the bridgehead positions via enol-keto tautomerization due to the acidity of the y-hydrogen, activated by the enone and ester groups. 

Various convergent Pb(iv)-promoted coupling reactions between vinylstannanes and cyclic /3-keto esters were used to prepare tetrasubstituted a-alkyl-/3-ketoesters which underwent subsequently a tandem alkylation, anion-accelerated oxyCope rearrangement and a trans-annular Dieckmann cyclization to afford bridgehead enone-containing... 

The new ring is a six-membered ring and we have numbered it to convince you. It is, of course, a rather strained bridged compound, but the key point is that dehydration is impossible. No enolate can form at the bridgehead, because bridgehead carbons cannot be planar (see Chapter 19) and the enone product cannot exist for the same reason the carbons marked ( ) in the brown structure would all have to lie in the same plane. The aldol has a perfectly acceptable conformation but that elimination is impossible. The aldol product remains in equilibrium with the alternative aldol products, but only one elimination is possible—and that is irreversible, so eventually all the material ends up as the one enone. 

There is no stereochemical bias in the conjugate addition of nucleophiles to bridgehead enones. Nevertheless, it should be mentioned here that the /i-alkoxy ketones roc-29-31 were prepared by addition of alcohols to the corresponding unstable enones21,22. 

However, when the carboxy enone rac-5 was irradiated in methanol, both the cis- and transfused bicyclic methoxy ketones trans-6 and cis-6 were isolated24. Clearly, epimerization at the bridgehead carbon atom may occur due to Norrish type-I reactivity of the product ketones rac-2, rac-4 and rac-6. Therefore, subsequent photochemical equilibration may well account for the observed product distributions. 

Note that under basic conditions, dehydration of the bridged aldol product would place a double bond at the bridgehead, forming a highly strained enone. 

Hydride shift. An alkoxide-accelerated hydride shift establishes the [in,out] bridgehead configurations that are characteristic of ingenol. Thus, heating a dicarbocyclic dienol with KH/18-crown-6 in dioxane gives the desired enone in 64% yield. ... 

Conjugate addition of allylsilanes to a/8-enones is promoted by titanium(iv) chloride. Most significantly an allyl group can be transferred to the bridgehead position in a fused cyclic a/8-enone using this technique (Scheme 78). ... 

The bicyclo[5,3,l]undec-7-ene-ll-one-l-carboxylic acid derivative (77) represents a case close to the limit for the possible existence of a bridgehead double bond. Unusual chemical and spectroscopic properties had suggested incomplete conjugation of the a -enone system, and this is confirmed by the analysis of (77) which reveals that the C(8)-C(7)-C(l l)-0 torsion angle is 37.6°. This value is in good agreement with the angle of 40° which had been predicted from an empirical examination of the u.v. spectrum. 

Bicyclic bridgehead olefins with a carbonyl group in the largest bridge can be constructed by oxy-Cope rearrangement of 3-hydroxy-l,5-dienes of types (15) and (16). Considerable interest has been shown in the strained bicyclic enone (17) and several independent syntheses have been reported. ... 

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