Cinchona alkaloids allylic amination

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

The same group has reported the enantioselective electrophilic 7-amination of a,(3-unsaturated dinitriles and nitrile esters through allylic C-H activation with a cinchona alkaloid catalyst [56]. Thus (Scheme 11.15), the reaction of the corresponding unsaturated nitrile with diazo compound B0C2N2 in the presence of 10 mol% of catalyst 31 afforded the 7-aminated nitrile adducts in good yields (65-90%) and excellent enantioselectivity (86-99% ee). 

A Lewis base-assisted Brpnsted base catalysis strategy has been used for direct asymmetric vinylogous alkylation of allylic sulfones with Morita-Baylis-Hillman (MBH) carbonates, in which a strong Brpnsted base, f-butoxy anion, generated in situ from a tertiary amine catalyst and MBH carbonate, is crucial in activating unstabilized nucleophiles. The y-regio-selective alkylation products were obtained with good to excellent enantiomeric excess (up to 98% ee) values when catalysed by a modified cinchona alkaloid. 

Under a different manner of cinchona alkaloid activation, azodicarboxylates were utilized as substrates for enantioselective aUylic aminations. The electrophilic addition of nucleophiles to electron-withdrawing aUyUc C-H bonds (21) was feasible via activation by a chiral Bronsted base, DHQ(2PYR) (Scheme 13.6) [15]. This discovery, from Jorgensen s group, highUghts the first enantioselective, metal-free allylic amination using alkyUdene cyanoacetates with dialkyl azodicarboxylates. 

Cinchona alkaloids have also heen used to catalyse the asymmetric functionalisation of anions, such as amination with diimides. Such diimide amination reactions can he used to functionalise the a-position or the y-position of a stabilised anion to yield functionalised chiral amines (331) (Scheme 14.100). This is a metal-free alternative to palladium catalysed allylation chemistry. 

Scheme 14.100 Cinchona alkaloid catalysed allylic amination. ...

---