Highly diastereoselective one-pot synthesis of spiro[cyclopenta[a]indene-2,2'-indene]diones from 1-indanones and aromatic aldehydes.
Treatment of 1-indanones with aromatic aldehydes and NaOEt in THF affords complex spiropolycyclic compounds through a four-component reaction in which two molecules of each starting compound are combined with formation of four new carbon-carbon bonds, leading to the elaboration of a new five-membered ring that bears five contiguous stereogenic centers with a well-defined relative configuration. Different amounts of a minor epimer of the main product are also formed. The presence of methoxy substituents in the indanone component and the use of aldehydes derived from pi-excedent heterocycles make the dimerization step a slower transformation. In these cases, better yields of spirodimers are obtained starting from the preformed enones. The reaction seems to take place by cross-aldol condensation, dehydration, and dimerization of the thus formed enones. The molecular mechanism of the dimerization reaction of enone 5g has been studied using DFT methods at the B3LYP/6-31G level. The dimerization takes place through a process involving a Michael addition of a carbanion, obtained by deprotonation of 5g at the 3-position, to a second molecule of 5g, followed by an intramolecular Michael addition in the corresponding intermediate. The final protonation of the resulting anion accounts for the formation of the cis-fused pentacyclic system.
Camps
Pelayo
P
Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal, 643, 08028-Barcelona, Spain. camps@ub.edu
Domingo
Luis R
LR
Formosa
Xavier
X
Galdeano
Carles
C
Gonzalez
Diana
D
Muñoz-Torrero
Diego
D
Segalés
Sílvia
S
Font-Bardia
Mercè
M
Solans
Xavier
X
D000447:Aldehydes / Q000737:chemistry; D019281:Dimerization; D007189:Indans / Q000737:chemistry; D007192:Indenes / Q000138:chemical synthesis*; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000447:Aldehydes; D007189:Indans; D007192:Indenes; D013141:Spiro Compounds; C013352:indacrinone