Enantioselective α‐Arylation of Cyclic Ketones Catalyzed by a Combination of an Unmodified Cinchona Alkaloid and a Palladium Complex

Abstract

A palladium/Cinchona alkaloid-catalyzed a-arylation between cyclic ketones and aryl halides under phosphine-free conditions is presented. The use of a simple, unmodified Cinchona alkaloid results in high levels of activity and selectivity with up to 93% ee. These enantioinduction levels are comparable or even higher than the ones reported using palladium/BINAP complexes. To the best of our knowledge, this represents the first use of unmodified Cinchona alkaloids as ligands/catalysts in asymmetric transition metal complex-catalyzed crosscoupling reactions.

N-Heterocyclic carbene complexes enabling the α-arylation of carbonyl compounds

“…In 2012, Glorius and co-workers explored the effects of a quinine additive in the asymmetric a-arylation of 2-methyl-1tetralone catalyzed by Pd(dba) 2 or [Pd(SIPr)(Z 3 -allyl)Cl] (1). 33 They showed that without any addition of quinine, the reaction proceeded quickly within 1.5 h (yield = 48%). In the presence of quinine full conversion was observed after 4 h. The slower reaction rate could be caused by the binding of quinine to Pd, therefore blocking or hindering access to active sites around the metal complex.…”

α-C(sp3)-H Arylation of Cyclic Carbonyl Compounds

“…However, ketone 17d gave the corresponding product with low ee value (78%) in this system [44]. Interestingly, nearly comparable yields and ee values were obtained by using quinine as the co-catalyst with Pd(dba) 2 [45].…”

“…However, ketone 17d gave the corresponding product with low ee value (78%) in this system [ 44 ]. Interestingly, nearly comparable yields and ee values were obtained by using quinine as the co-catalyst with Pd(dba) 2 [ 45 ].

Scheme 11 Enantioselective α -C(sp 3 )-H arylations of cyclic ketones reported by Buchwald et al

Scheme 12 Enantioselective α -C(sp 3 )-H arylations of cyclic ketones reported by Hartwig et al

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Quinine based ionic liquids: A tonic for base instability

“…Quinine salts are well known as phase transfer catalysts, most famously in the Sharpless asymmetric dihydroxylation [13]. Quinine halides are often used in the presence of strong bases such as KOH [14] and sodium tert-butoxide [15]. This indicates that the cation is relatively stable under basic conditions.…”