Butyrolactone Annulation

Cyclobutanone annulation onto a carbonyl group translates into y-butyrolactone annulation because of the facility of the Baeyer-Villiger reaction (Eq. 68 a)8). Indeed, the reaction proceeds sufficiently rapidly that even basic hydrogen peroxide effects the oxidation whereas, with less reactive carbonyl partners, peracids must be used. 

Perbenzimidic acid also effects rearrangement35). Use of basic hydrogen peroxide permits the substrates to contain olefins with immunity as in Eq. 69. The high 

71 becomes an effective cyclopentenone fusion. Such a sequence has proven to be the preferred preparation of polyquinanes exemplified in Eq. 72 52). 

Beckmann like rearrangements have not been extensively explored but should translate this spiroannulation into a y-butyrolactam synthesis 108). 

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Homoenolates generated catalytically with NHCs can also be employed for C-C and C-N bond formation. Bode and Glorias have independently accomplished the diastereoselective synthesis of y-butyrolactones by annulation of enals and aldehydes [121, 122]. Bode and co-workers envisioned that increasing the steric bulk of the acyl anion equivalent would allow reactivity at the homoenolate position. While trying to suppress the competing benzoin and enal dimerization the authors comment on the steric importance of the catalyst. Thiazolium pre-catalyst 173 proved unsuccessful at inducing annulation. A-mesityl substituted imidazolium salt 200 was found to provide up to 87% yield and moderate diastereoselectivities (Scheme 34). 

The stereoselectivity of this reaction rises when more bulky nucleophiles are employed (compare entries 7, 3,1, and 5). This is most impressively demonstrated by comparison of the y-lactol reduction with its allylation leading to 205 or 206, respectively (Scheme 10). Formation of tetrahydrofuran derivative 208, dihydrofuran 209, or unsaturated a-methylen-y-butyrolactone 207 illustrate that various modes of straightforward work-up procedures provide two different five membered heterocycles 93 b-96). A second example without the geminal dialkyl substitution at C-3 of the siloxy-cyclopropane depicted in Eq. 86 making available the annulated tetrahydrofuran-3-carboxylate 210 underlines the generality of the C-C-bond forming hydroxyalkylation reaction via ester enolates. 

Sohn SS, Rosen EL, Bode JW (2004) N-Heterocyclic carbene-catalyzed generation of homoenolates y-butyrolactones by direct annulations of enals and aldehydes. J Am Chem Soc 126 14370-14371... 

A procedure which could be useful in the construction of annulated butyrolactones is outlined in Scheme 38.3< ° Vinyl lithium intermediates do not undergo cyclisation it is a pity that the introduction of the lactone carbonyl group into the initial product requires so many steps A rather neat application of the enolate... 

An annulation of a y-butyrolactone nn -ecome the carbonyl group and the subst iffective cocatalyst for this reaction, but apparently promotes the formation of. arbonylation. That phenols are unreacti e -tep under the conditions employed. 

An annulation of a y-butyrolactone ring to naphthols recruits CO and an aldehyde to become the carbonyl group and the substituted a-carbon. Trifluoroacetic acid is a highly effective cocatalyst for this reaction, but HO Ac, PhCOOH, and TsOH are not. The acid apparently promotes the formation of 2-(l-hydroxyalkyl)naphthols, which undergo carbonylation. That phenols are unreactive may be due to the difficulty in achieving this first step under the conditions employed. 

Bromoetherification of alkenes can be achieved using NBS in the desired alcohol as the solvent. The reaction of 1,3-dichloropro-pene with NBS in methanol yields an a-bromo dimethyl acetal in the first step in a convenient synthesis of cyclopropenone. Using propargyl alcohol the reaction depicted in eq 22 has been extended to an annulation method for the synthesis of a-methy-lene-y-butyrolactones. Intramolecular bromoetherification and bromoamination reactions are generally very facile (eq 23). In natural products synthesis, bromoetherification has been used for the synthesis of cyclic ethers (by subsequent debromination, see... 

NHC-catalysed umpolung of enals appears to be a useful tool for annulation reactions that generally induces molecular complexity from simple starting materials. Enals have thus been reported as appropriate reaction partners for asymmetric annulation reactions with isatins and benzodi(enone)s to yield spirocyclic oxindolo-y-butyrolactones (121), and polycyclic compounds (122), respectively. Both annulation processes have been catalysed by chiral NHCs and accomplished in good yields with high regio- and/or stereo-selectivities. In parallel, the mechanism of the NHC-catalysed annulation reaction of butenal with pentenone has been computationally explored at the B3LYP/6-31+G and M06-2X/6-31G levels of theory. This study has clearly emphasized the key role played by proton-transfer steps in both the rate and the course of the reaction. 

In addition, chiral 4,5,5-trisubstituted y-butyrolactones bearing two stereocentres including one quaternary carbon centre were synthesised by You et al. on the basis of chiral Al-heterocyclic carbene-catalysed annulations of enals and keto esters. The use of this type of chiral organocatalysts allowed tuning the... 

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