- THE ALDOL-TYPE CONDENSATION OF LITHIUM, BORON AND TITANIUM ENOLATES OF ISOCARANYL ACETATES WITH BENZALDEHYDE. THE METAL AND CHIRAL AUXILIARY EFFECTS
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A new approach to chiral enolates by using a chiral ester (isocaranyl acetates) and a chiral organometallic reagent (boranes and titanates) is reported.The effect of this double enantiodifferentiation and the effects of the isomerism of chiral auxiliary (2- and 4-isocaranyl) and that of the metal (Li, B, Ti) on the enantioselectivity of aldol condensation of 2- and 4-isocaranyl acetates with benzaldehyde are discussed.Lithium and boron enolates of isocaranyl acetates add preferentially to the si-face of benzaldehyde while the addition of analogous titanium enolates occurs preferably on the re-face of the aldehyde.The enolborinate which gives the highest ee value is that obtained by transmetallation reaction of the lithium enolate of (+)-2-isocaranyl acetate with (-)-di-4-isocaranylchloroborane.Obversely the enoltitanate prepared from (-)-4-isocaranyl acetate and the LDA-(+)-di-2-isocaranoxy(chloro)cyclopentadienyl titanate system is that which gives the highest enantiofacial discrimination.The chiral auxiliary effect has been used to plan the synthesis of (+)-4α-acetoxy-3β-trimethylsilyloxy-trans-carane, the titanium enolate of which gives (R)-(+)-β-hydroxy-β-phenylpropionic acid in high enantiomeric excess.
- Fringuelli, Francesco,Piermatti, Oriana,Pizzo, Ferdinando,Scappini, Anna Maria
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p. 195 - 200
(2007/10/02)
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- Acid-catalysed Terpenylations of Olivetol in the Synthesis of Cannabinoids
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Examination of the toluene-p-sulphonic acid-catalysed reaction of (1S,2S,3R,6R)-(+)-trans-car-2-ene epoxide with olivetol shows that, inconsistently with the accepted mechanism, (3R,4R)-(-)-o- and -p-cannabidiols are produced as well as (3R,4R)-(-)-Δ1- and Δ6-tetrahydrocannabinols.Evidence is now presented that, as in Petrzilka's reaction employing chiral p-mentha-2,8-dien-1-ols, the reacting species is the delocalised (4R)-p-mentha-2,8-dien-1-yl cation (9).Similar terpenylation using (1S,3S,4R,6R)-(+)-trans-car-3-ene epoxide shows that besides the reported (-)-Δ6-THC, o- and p-cannabidiols, Δ1-THC and Δ4,8-iso-THC can also be produced.The nature of the products, the chirality, and the characteristics of the reaction implicate again the delocalised cation (9).Its formation via Kropp-type rearrangement is excluded and a pathway leading to (4R)-p-mentha-2,6,8-triene, which on protonation gives (9), is proposed.Protonated on C-8, the triene can be trapped and isolated as (4R)-p-mentha-2,6-dien-8-ol.The latter, made in (+/-)-form from citral, proved to be an excellent terpenylating agent for producing cannabinoids.Terpenylation of olivetol by the pinanes (1S,4S,5S)-(-)-cis-verbenol and (1R,5S,7R)-(+)-cis-chrysanthenol is compared.A major drawback of the latter is partial racemisation which occurs in the verbenone-chrysanthenone isomerisation during its photochemical preparation.Whilst Δ1-THC cannot be directly obtained from verbenol, its tertiary allylic cation permits a much higher yielding terpenylation than the secondary cation from chrysanthenol.
- Crombie, Leslie,Crombie, W. Mary L.,Jamieson, Sally V.,Palmer, Christopher J.
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p. 1243 - 1250
(2007/10/02)
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