Cycloaddition cinchona-catalyzed

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

Asymmetric Cycloaddition Reactions Catalyzed by Cinchona-Based Primary Amines 313... 

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

Asymmetric Cycloadditions Catalyzed by Bifiinctional Cinchona Alkaloids... 

Asymmetric Cycloadditions Catalyzed by Bifunctional Cinchona Alkaloids 309... 

Asymmetric Cycloaddition Catalyzed by Cinchona-Based Phase-Transfer Catalysts... 

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. 

In a completely different context, a cascade Michael/intramolecular addition process involving nitroalkenes and isocyanoesters has been developed, which results in a formal [3 -I- 2] cycloaddition reaction and therefore consisting of a direct and very efficient methodology for the asymmetric synthesis of 2,3-dihydropyrroles (Scheme 7.70). ° The reaction was catalyzed by cinchona... 

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...

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... 

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