Studies in Stereochemistry. 47. Asymmetric Induction by Leaving Group in Nucleophilic Aromatic Substitution

Article abstract of DOI:10.1021/jo00199a036

We report here the first examples of transfer of asymmetry from a leaving group to a biaryl product in nucleophilic, aromatic substitution reactions.Chiral products 2-<2-(1,1'-binaphthylyl)>-4,4-dimethyl-Δ²-oxazoline (6), 2-<2-(2'-methoxy-1,1'-binaphthylyl)>-4,4-dimethyl-Δ²-oxazoline (8), and 2-<2-(3'-methoxy-1,2'-binaphthylyl)>-4,4-dimethyl-Δ²-oxazoline (11) were produced in high to medium optical yields by aryl-aryl coupling reactions in which 1-naphthyllithium, 3-methoxy-2-naphthyllithium, or 2-methoxy-1-naphthylmagnesium bromide was treated with 2-<2-(1-alkoxy naphthyl)>-4,4-dimethyl-Δ²-oxazolines 15-19.The alkoxy leaving groups of the naphthyloxazolines were derived from the naturally occuring alcohols l-menthol, quinine, quinidine, α-fenchol, and borneol.The oxazoline group activates the aromatic nucleus toward nucleophilic aromatic substitution by stabilizing the transition states leading to and from ?-complex intermediates.These reaction intermediates are diastereomeric and are therefore of unequal free energy.Thus one enantiomeric product is formed faster than the other.The configurations of starting materials and products (with the exception of 11) were established by converting them to compounds of established absolute configuration.The optical yields in the 14 reactions examined ranged from ca. >95percent to 8percent and the chemical yields from 88percent to 7percent.The l-menthoxy leaving group gave the highest chiral transfer efficiences (percent chemical yield x optical yield), which ranged from 65percent to 41percent.The more spherical, least dissymmetric α-fenchoxy and bornoxy groups gave the lowest optical yields (77-8percent ee) but rather good chemical yields (88-65percent).The quininoxy and quinidinoxy group produced the most consistently high optical yields (94-80percent ee) but the lowest chemical yields (7-27percent).These two leaving groups gave products of opposite configurations in the three systems examined.The highest value observed for the difference in free energy of the diastereomeric transition states was Δ(ΔG excit.)=2.4 kcal mol^-1 and involved 2-methoxy-1-naphthylmagnesium bromide as nucleophile, quininoxy as leaving group, and 8 as product.Unlike most covalently bound chiral auxilliary units used for asymmetric induction in organic synthesis, those of the current study are displaced during the reaction.The direction of the configurational biases is interpreted in terms of the superposition of steric effects on the tendency of the lithium and magnesium ions to be ligated internally in the ?-complex intermediates.