Cycloaddition cinchona alkaloid catalyzed

Asymmetric Cycloadditions Catalyzed by QumucM me Tertiary Amim 303 Table 10.2 Cinchona alkaloid catalyzed ketene-N-thioacyl imine [4 + 2] cycloadditions ... 

Nelson and co-workers reported cinchona alkaloid-catalyzed [4-1-2] cycloaddition of ketenes and N-thioacyl imine, affording the 4,5-cw-disubstituted l,3-thiazin-6-one derivatives 146 with high enantioselectivities (>95% ee) and diastereoselectivities (>95 5 cis. trans). Scheme 3.47 [63], Ketene, in situ generated from acyl halide 143 and base, followed by addition to imine which was generated in situ via basic elimination of a-amido sulfone 144, providing the ketene-imine addition pathway toward the cycloadducts. 

Scheme 3.47 Cinchona alkaloid-catalyzed [4-1-2] cycloadditions of ketenes with a-amido...

Asymmetric Cycloadditions Catalyzed by Bifiinctional Cinchona Alkaloids... 

Asymmetric Cycloadditions Catalyzed by Bifunctional Cinchona Alkaloids 309... 

As discussed above, the vast synthetic potential of cinchona alkaloids and their derivatives in the asymmetric cycloadditions has been well demonstrated over the past few years. Cinchona-based organocatalysts possess diverse chiral skeletons and are multifunctional. There is no doubt that the further development of cinchona-based organocatalysts and their catalyzed cycloaddition reactions will continue to provide exciting results in the near future. 

Nelson and co-workers reported a cinchona alkaloid-Lewis acid-catalyzed acycl chloride aldehyde reaction, an extension of ketene-aldehyde cycloaddition, providing 3,4-cw-p-lactones 168 with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (>96% de), [69], The methodology was later applied by the group in the enantioselective total synthesis of (-)-pironetin (Scheme 3.53). 

Scheme 3.53 Cinchona alkaloid 145/LiC10,-catalyzed ketene-aldehyde cycloadditions...

Peters and Zajac reported the cinchona alkaloids, e.g. quinine, catalyzed formal [2+2] cycloadditions of sulfonylchlorides 177 and highly reactive non-nucleophiUc iminesl78, affording the P-sultams 180, Scheme 3.56 [72]. 

Stereoselective [4 + 2] cycloadditions ofketenes and thioacylimines 509, both created in situ are catalyzed by an optically pure cinchona alkaloid (TMSQ) in the presence of LiC104/i-Pr2NEt (9 1 CH2Cl2/Et20, 78 °C) via the quinine-derived enolate 510 to afford the enantio-enriched ds-4,5-disubstituted 1,3-thiazin-6-one 512 via sulfur addition to the acyl ammonium ion 511, with 95 to >98% ee and cis/trans 95 5 to >97 3 (Scheme 167) (2007JA11690). 

Within this area, cinchona alkaloids have also catalyzed cycloaddition reactions with 2-pyrones. For example, treatment of 3-hydroxy-2-pyrone 74 and trany-3-benzoylacrytic ester 75 with 5mol% of cinchona alkaloid 76 affords cycloadduct exo-11 in 93 7 dr and 91% In this reaction, related mechanistic studies suggest that 76 (and derivatives) might function as a bifunctional catalyst by simultaneously raising the energy of the HOMO of the diene and... 

A stereoselective [3+2] dipolar cycloaddition of azomethine imines 141 with ot,P-unsaturated aldehydes catalyzed by ot,a-diarylprolinol salts was also reported by Chen et al. [88]. More important, they extended the strategy to cyclic enones by employing a Cinchona alkaloid-derived bifunctional primary amine catalyst 142 (Scheme 1.52) [89]. The synergistic hydrogen-bonding interaction of the catalyst and 1,3-dipoles 141 plays a critical role in high enantiocontrol (dr >99 1, up to 95% ee). 

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