Stereoselectivity enantioselective organocatalytic

In 2005, Cordova and coworkers described the first example of the enantioselective organocatalytic aza-hetero-Diels-Alder reaction [60]. The one-pot three-component direct aza-hetero-Diels-Alder reaction under the catalysis of prohne afforded the desired cycloadducts 135 with excellent chemo-, regjo-, and stereoselectivity (Scheme 38.39). This reaction was considered to proceed via a plausible Mannich-Michael reaction pathway. Recently, Wang and coworkers developed a chiral ionic liquid catalyst for this reaction to afford up to >99% ee [61]. 

Vicario, et al. reported the first organocatalytic enantioselective [3 + 2] cycloaddition reaction between a,p-unsaturated aldehydes 28 and azomethine ylides, generated in situ from imines 201, Scheme 3.65 [82], Efficient shielding of the Si face of the iminiiim intamediate by the bulky group of catalyst 202 lead to a stereoselective fic-face and endo-type approach of the ( )-1,3-dipole, and provide pyrrolidine 203 with high diastereoselectivity and enantioselectivity. 

Combinations of enamine-iminium ion activations together with other organo-catalytic activations in asymmetric organocatalytic domino and multicomponent reactions have been developed to achieve the enantioselective consecutive formation of two or more bonds in a stereoselective fashion. 

Synthesis of eicosanoid 555 commenced with a stereoselective organocatalytic cyclopropanation achieved by reacting bromoacetate 559 with Michael acceptor 560 in the presence of dimeric catalyst 561. As the authors were not able to resolve product 562 using an enantioselective HPLC phase, the exact enantiomeric excess could not be determined oti this stage but was found to be satisfactory for the rest of the sequence. With respect to the synthesis of lactonealdehyde 556, the cyclopropanation was carried out by adding the Weinreb- m dt 563 to enone 564 to furnish the key intermediate 565, which was transferred further into 556 in a similar manner (474) (Scheme 118). 

It worth to mention that despite the importance of the Kabachnik-Fields reaction, stereoselective versions for the synthesis of enantioenriched a-aminophosphonates are scarce [212, 213], and only few enantioselective examples have been published to date (for reviews on enantioselective catalytic direct hydrophosphonylations of imines, see Refs. [162a-c]). Organocatalytic examples use well-known chiral binol-derived phosphoric acid organocatalysts (Fig. 12.6,80 and 81) [214], and regarding metal catalysis, chiral scandium(III)-A,A -dioxide and... 

L-Proline was also used by Zhong et aL to promote a highly stereoselective organocatalytic domino aminoxylation-aza-Michael reaction occurring between 2-(5-oxopentylidene) malonate derivatives and aromatic nitroso compounds. This process furnished chiral multifunctionalised tetrahydro-1,2-oxazines in good to high yields, an excellent enantioselectivity of 99% ee in general and exceptional levels of diastereoselectivity of >98% de, as summarised in Scheme 4.8. 

Although considerable improvements have been made for endo-selective cycloadditions of azomethine imines, methods for exo and enantioselective cycloaddition of azomethine imines were relatively scarce. By employing novel, multifunctional primary amine catalysts 145 derived from cinchona alkaloids in the presence of triisopropylbenzene sulfonic acid (TIPBA) 146 as cocatalyst, Chen and coworkers developed the first organocatalytic, highly exo-selective, and enantioselective 1,3-DC reaction of cyclic enones 142 and azomethine imines 143 in 2007 [53]. The additional and synergistic hydrogen-bonding interaction of catalyst and 1,3-dipole is essential for enantiocontrol, and excellent stereoselectivities were achieved for a broad scope of substrates (dr > 99 1, up to 95% ee) (Scheme 2.37). 

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