Asymmetric Cycloadditions Catalyzed by Quinuclidine Tertiary Amine

Asymmetric Cycloadditions Catalyzed by Quinuclidine Tertiary Amine 

Cinchona alkaloids possess a nucleophilic quinuclidine structure and can perform as versatile Lewis bases to react with ketenes generated in situ from acyl halides in the presence of an acid scavenger. The resulting ketene enolates can react with electrophilic C=0 or C=N bonds to deliver chiral [i-lactones [5] or [i-lactams [6], respectively, in a [2 + 2] cycloaddition manner, which is discussed in Chapter 5 in detail. Gaunt et al. also developed practical one pot cydopropanation processes mediated by the modified cinchona alkaloids via ammonium ylide intermediates [7]. Although the catalytic strategy has been well established, the utilization of ammonium enolate based [4 + 2] cycloaddition is rare probably because of the relative unreactivity of the 

Substrates for this type of cycloadditions are not limited to o-quinones and o-benzoquinone imides but can be extended to o-benzoquinone diimides also. In a preliminary study, it was found that some unidentified byproducts as well as the desired quinoxalinone were formed, which made the reaction sluggish and resulted 

With Zn(OTf)2 (10mol%) as the cocatalyst, the 3,4-dihydroquinoxalin-2-one products 4 were obtained in remarkably increased yields and with excellent en-antioselectivities ( 99% ee) in each case (Table 10.1, entries 1-12). It is worth to note that the opposite enantiomer was obtained with similarly high enantioselectivity and yield for the cycloaddition reaction when benzoylquinine (BQN, lb) was used instead of BQD la (entry 13). 

Lectka et al. reported a detailed synthetic and mechanistic study of unusual [4 + 2] cycloaddition of ketene enolates and o-quinones by the bifunctional catalysis of cinchona alkaloids BQD la (or BQN lb) and Lewis adds. The undertaken investigations based on the integration of experimental and calculated data itself demonstrated a surprising cooperative LA/LB interaction on a ketene enolate. It showed that the reaction of o-quinone undergoes a mechanistic switch in which the mode of activation changes from Lewis acid (LA) complexation of the quinone to metal complexation of the chiral ketene enolate. 

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Asymmetric Cycloadditions Catalyzed by Quinuclidine Tertiary Amine 299... 

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