76833-22-2

Upstream product

• 4695-62-9 fenchone 
• 100-66-3 methoxybenzene 
• 578-57-4 2-bromoanisole 

Relevant academic research and scientific papers

Enantiopure Methyl- A nd Phenyllithium: Mixed (Carb-)Anionic Anisyl Fencholate-Aggregates

Methyl- A nd phenyllithium aggregates with enantiopure anisyl fencholate units form after reaction of organolithium reagent with (+)-anisyl fenchol in hydrocarbon and some ethereal solvents. These carbanionic aggregates are characterized by X-ray crystal analyses and exhibit both 3:1 stoichiometry and distorted cubic Li4O3C1 cores, in which three lithium ions coordinate the carbanion (i.e., methylide or phenylide). These three lithium ions define a Lewis acidic surface (Li3), binding the carbanion and expanding with the steric demand of the carbanion (i.e., from Me: 2.62 ?2, over n-Bu: 2.65 ?2 (previous work) to Ph: 2.79 ?2). Methylation and phenylation reactions of various prochiral aldehydes employing these methyllithium and phenyllithium aggregates yield alcohols with up to 44% ee. To rationalize the formation of the mixed (carb-)anionic aggregates, aggregate formation energies, describing co-condensations of RLi (R = Me, Ph, n-Bu) and lithium fencholates, are computed for the 3:1 and 2:2 stoichiometries. These computed aggregate formation energies point to preferences for 3:1 over 2:2 aggregates, as it is also apparent from experimental aggregate formations, confirmed by X-ray crystal analyses. In close analogy to the X-ray crystal structures, the computed Li3 surfaces increase with increasing steric demand of the carbanions. The chiral, mixed (carb-)anionic RLi-fencholate aggregates hence adapt to different carbanion sized and arise not only with small (Me) or primary carbanions (n-Bu) but even with the larger secondary phenyl anion.

Effect of Ortho Substituants on the Direction of 1,2-Migrations in the Rearrangement of 2-exo-Arylfenchyl Alcohols

A series of 2-exo-arylfenchyl alcohols (11a-k) was submitted to acid hydrolysis in EtOH/10 M HCl (2:1-1:1, v/v) or with trifluoromethanesulfonic acid (TfOH) (1 equiv) in CHCl3 under varying conditions. In all cases, initial formation of the cyclofenchene 12 took place, and after prolonged treatment with acid the reaction proceeded along one of two pathways depending on the nature of the aryl substituent. When the aryl substituent was o-NH2 11b or o-OH 11e, Wagner-Meerwein rearrangement took place to give a carbocationic intermediate 9 that was trapped by the N or O heteroatom to give (2R,4aR,9aR)-9-aza-2,4a-(10,10-dimethylmethano)-1,2,3,4,4a,9a-hexahydro-9a- methyl-9H-fluorene (3b) and (3R,4aR,9bR)-3,9b-(10,10-dimethylmethano)-1,2,3,4,4a,9b-hexahydro-4a- methyldibenzofuran (3c), respectively. In the case of 3c bearing an oxygen heteroatom, equilibration to give the thermodynamic product (1R,4S,4aR,9bR)-1,2,3,4,4a,9b-hexahydro-1,4-methano-1,4a,9b- trimethyldibenzofuran (4a), arising from Nametkin rearrangement, took place via the intermediate 2-fenchyl cation. In contrast, when the aryl substituent was o-OCH3 11f, direct conversion of the cyclofenchene to the Nametkin product 4a occurred with no detectable prior formation of the Wagner-Meerwein product. In the case of o-tolylfenchyl alcohol 11k, cyclofenchene formation was facile, but subsequent conversion to either the Wagner-Meerwein or Nametkin products was highly disfavored. The results indicate that ortho substitution disfavors Wagner-Meerwein rearrangement through adverse steric and electronic effects. However, when the ortho substituent is NH2 or OH it is proposed that anchimeric assistance provides an intermediate 15a that is stereoelectronically predisposed to Wagner-Meewein rearrangement.

Tandem Wagner-Meerwein rearrangement-carbocation trapping in the formation of chiral heterocyclic ring systems

Ortho lithiated protected anilines and phenols undergo exclusive addition to fenchone from the exo face. The corresponding adducts, under acidic conditions undergo cationic rearrangement followed by internal trapping of the new cation with amino, hydroxyl or methoxyl substituents to give enantiomerically pure chiral heterocyclic ring systems. The nature of the rearrangement is dependent on the donor group and ifs ability to stabilise a positive charge. With an amino donor group a product due to Wagner-Meerwein rearrangement is formed while with a methoxy donor group Nametkin rearrangement is the preferred pathway.