Enantioselective Synthesis of Tertiary and Quaternary Stereogenic Centers: Copper/Phosphoramidite‐Catalyzed Allylic Alkylation with Organolithium Reagents

Umpolung of Carbonyl Groups as Alkyl Organometallic Reagent Surrogates for Palladium‐Catalyzed Allylic Alkylation

“…[6] Tr aditional allylations of nonstabilized carbon nucleophiles typically involve alkyl organometallic reagents (Scheme 1A). [11] Since then, other alkyl organometallic reagents (such as organozinc, [6a,b,12] lithium, [13] aluminum, [14] or zirconium [15] reagents) and alkyl boron reagents [6d,e] have also been used for allylations.A lthough these alkyl organometallic reagents have numerous industrial applications,t here are still substantial drawbacks associated with them. [8] Later, Hoveyda, [9] Feringa, [10] and others made systematic investigations on the use of organomagnesium reagents for allylic substitutions.…”

Enantioselective Synthesis of All‐Carbon Quaternary Stereogenic Centers via Copper‐Catalyzed Asymmetric Allylic Alkylation of (Z)‐Allyl Bromides with Organolithium Reagents

“…Alternatively, the use of different chiral copper catalysts in combination with organozinc,4 organoaluminium,5 organomagnesium6 and organoboron7 reagents has been shown to be highly effective in the AAA of prochiral trisubstituted allyl compounds. Recently, we reported, for the first time, the use of organolithium reagents for the copper‐catalyzed allylic alkylation of E trisubstituted allyl bromides 8. 9 By using a catalyst comprising CuBr⋅SMe 2 and a chiral phosphoramidite as ligand, and by selecting a proper combination of dichloromethane and hexane as solvent and co‐solvent, we could tame the highly reactive alkyllithium reagents and use them for the regio‐ and enantioselective synthesis of a range of all‐carbon stereogenic centers, avoiding side reactions such as lithium–halogen exchange or homocoupling reactions (Scheme a).…”

“…In these cases the enantioselectivity of the process is controlled by the chiral catalyst and the product is obtained either as the antipode of the enantiomer product derived from the E isomer with lower enantioselectivity4d, 5a, 7d or as the same enantiomer with similar enantioselectivity,6b depending on the catalytic system used. As the olefin geometry of the allyl substrate is an important selectivity parameter, and lacking comprehensive information on the copper‐catalyzed AAA of Z trisubstituted allyl compounds,10 we decided to investigate this reaction using organolithium reagents as part of our research program based on the development of direct catalytic cross‐coupling reactions of these highly reactive compounds 8. 9, 11 Herein, we report a catalytic methodology that allows for the copper‐catalyzed AAA of Z trisubstituted allyl bromides (Scheme b).…”

Inter- and intramolecular enantioselective carbolithiation reactions

“…However, recently a general catalytic methodology for the enantioselective intermolecular addition of alkyllithiums has been reported, though it implies transmetalation to copper complexes. In this case, the use of a copper-base chiral catalytic system allows carbon–carbon bond formation by allylic alkylation with alkyllithiums, with high enantioselectivities and high functional-group tolerance [28–29]. This process may open new interesting applications in organolithium chemistry, though it is beyond the scope of this review.…”