Cyclobutanone aldol reactions

Clark and coworkers have used a similar process for generation and aldol reactions of a cyclobutanone enolate one example of many is illustrated in equation (22). Direct formation of the enolate in this case gives aldols in low yield. 

In the 2010s, Aitken et al. demonstrated that a solvent-free organocata-lysed aldol reaction could be achieved by addition of 2-hydroigr-cyclobutanone 11 n = 1) to 4-nitrobenzaldehyde in the presence of L-threonine (Scheme 12.4). The temperature played an important role in the stereochemical outcome, as the -adduct 12 was obtained at low temperature, whereas the same reaction performed at 25 °C and/or in wet DMF led mainly to the a t/-adduct regardless of the amino acid structure. 

Small variations on this theme allow it to be extended to the formation of eight-membered rings a substrate containing a vinyl cyclobutanone 11.158 yields a cyclooctenone 11.159 (Scheme 11.53)7 while addition of CO can yield a cyclooctadione 11.161 that may undergo an intramolecular aldol reaction (Scheme 11.54). ... 

A desymmetrizing aldol reaction of 3-substituted cyclobutanones with aryl aldehydes in CH2CI2 has been promoted with dr up to 99 1 and ee < 99% stereodirected by N-phenylsulfonyl (5)-proline. Proline-based di- and tri-amides have also been used effectively to catalyse asymmetric aldol condensation and the importance of each chiral centre of the catalyst has been discussed. 

The cyclobutanone is the important aspect. We shall want to make it by ketene cycloaddition (the key reaction) (Chapter T 33) and this we can do after an aldol disconnection. 

These reactions lead to optically active products when an optically active phosphine is used in place of triphenylphosphine. Thus treatment of the enol of optically active 6 with pivaldehyde gives the aldol 7 in 98% isolated yield. The absolute configuration was confirmed by X-ray diffraction. Only one method is known at the present time for removal of the metal moiety. Thus oxidation of 7 with ferric chloride affords the optically pure cyclobutanone 8 in 70% yield. 

Aldol condensation of acetals spiroannelation.. lapanese chemists have reported a new method of annelation that involves as the first step aldol condensation of acetals or ketals with the bissilylated succinoin mediated with BF3 etherate or TiC U. The method is formulated in equation (I) for the reaction of the acetal of bcnzaldchydc. Owing to the ring strain of cyclobutanone, the aldol... 

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