Catalysis dienamine

Scheme 2.18 Enantioselective Michael addition of enolizable ot,p-unsaturated aldehydes to nitroalkenes via dienamine catalysis.

Development of new methods in organic synthesis and their applications to the synthesis of biologically interesting natural products 12CPB1. Dienamine catalysis as an emerging technology in the synthesis of bioactive molecules and natural products 12EJ0865. 

Later, Melchiorre and coworkers accomplished a challenging direct vinylogous aldol reaction of 3-methyl-2-(yclohexen-l-one with a-keto esters utilising a bifunctional primary amine-thiourea. Catalyst 48 based on the (l/ ,2/ )Kiiphenylethylene-l,2-diamine backbone combined with benzoic acid as cocatalyst promoted the reaction by means of a concomitant activation of both reacting partners (see TS in Scheme 19.55), the ketone via dienamine catalysis and the ester via hydrogen-bonding interactions (Scheme 19.55). 

One year later, Vicario and coworkers developed an unprecedented [2-1-2] cycloaddition reaction of a,p-unsaturated aldehydes with a-hydro gr-methylnitroalkenes (Scheme 19.58). The addition of the achiral thiourea 8 proved to be essential for achieving high levels of efficiency and enantio-control, since it served to activate the electrophile through hydrogenbonding interactions, while prolinol ether 51 served to activate the nucleophile by means of dienamine catalysis. The [2 + 2] cycloaddition... 

S.4.4.5. -Substituted Cyclohexenone Derivatives. Inspired with the dien-amine catalysis developed by Jprgensen and co-workers [138], Melchiorre and coworkers [139] found that the chiral primary amine salts 142 could selectively activate the 7-position of ummodified cyclic a,(3-unsaturated ketones through dienamine catalysis (Scheme 5.70). The direct vinylogous Michael addition of p-substituted... 

Over the last few years the Christmann group has reported some interesting approaches towards the synthesis of mono- and bicyclic skeletons based on dienamine catalysis (172, 173). As an example, (Scheme 45) compound ( )-188, a pungent constituent of black cardamom (174), was synthesized in a single transformation starting from the acyclic tethered a,(3-unsaturated dialdehyde 189. The bicyclic product 188 could be obtained in reasonable yield and good enantios-electivity through a formal [4 -i- 2] cycloaddition catalyzed by 138 in the presence... 

Bertelsen S, Marigo M, Brandes S, Diner P, Jprgensen KA (2006) Dienamine Catalysis Organocatal5dic Asyrrunetric y-Amination of a,p—Unsaturated Aldehydes. J Am Chem Soc 128 12973... 

Albrecht, L., Dickmeiss, G., Acosta, F. C., Rodriguez-Escrich, C., Davis, R. L., Jorgensen, K. A. (2012). Asymmetric organocatalytic formal [2 -I- 2]-cycloadditions via brfunctional H-bond directing dienamine catalysis. Journal of the American Chemical Society, 134, 2543-2546. 

Parra, A., Reboredo, S., Aleman, J. (2012). Asymmetric Synthesis of Cyclobutanes by a Formal 2-1-2 Cycloaddition Controlled by Dienamine Catalysis. Angewandte Chemie -International Edition, 51, 9734-9736. 

Appayee, C., Fraboni, A. J., Brenner-Moyer, S. E. (2012). y-Amino alcohols via organocascade reactions involving dienamine catalysis. Journal of Organic Chemistry, 77, 8828-8834. 

Scheme 38.11 Dienamine catalysis of Diels-Alder reactions...

By employing the dienamine-catalysis strategy, Chen and coworkers accomplished an unprecedented and highly regio- and stereoselective inverse-electron-demand aza-hetero-Diels-Alder reaction of a,P-unsaturated imines 136 with a,P-unsaturated aldehydes 143 [66]. Various multifunctional piperidine derivatives 144 and 145 can be obtained, with excellent levels of enantioselectivity, that are potentially useful in the synthesis of natural products and medicinal chemistry (Scheme 38.43). 

Over the past decade, rapid growth has been achieved in organocatalytic asymmetric Diels-Alder and hetero-Diels-Alder reactions. Numerous organocatalysts such as chiral amines, guanidines, N-heterocyclic carbenes, Bronsted acids, and bifunctional catalysts have been successfully developed. The activation modes for these catalysts, such as imine-catalysis, enamine-catalysis, dienamine catalysis. 

The enantioselective organocatalytic functionaUzation of carbonyl compounds at the 7 position represents a highly challenging and persistent problem for asymmetric synthesis [33]. Recently, Melchiorre and coworkers [34] reported a chiral Bronsted acid-assisted dienamine catalysis for the direct asymmetric y-alkylation of a-substituted linear a,(l-unsaturated aldehydes (Scheme 43.22). In this reaction, the chiral phosphoric acid 106 can induce the formation of a chiral contact ion-pair from alcohol 103 [35], which may synergistically engage in a matched combination with the chiral covalent dienamine intermediate derived from chiral primary... 

Figure 44.3 Natural products synthesized via dienamine catalysis.

Inspired by dienamine catalysis in inverting the inherent reactivity of a,P-unsaturated aldehydes, which acted as nucleophiles for direct enantioselective y-amination with... 

SCHEME 1,26 Aza-Diels-Alder reaction with alehydes by dienamine catalysis. 

Although the diversity of asymmetric inverse-electron-demand hetero-Diels-Alder reactions has been weU established, examples of aU-carbon-based catalytic asymmetric versions have rarely been reported, and aU faU into the LUMO-lowering strategy. Based on previous applications of dienamine catalysis in asymmetric inverse-electron-demand hetero-Diels-Alder reactions, Li et al. extended this strategy to all-carbon-based asymmetric inverse-electron-demand Diels-Alder reactions (Scheme 1.28) [36]. The products of cyclohexene derivatives with substantial substitution diversity of electron-deficient dienes and crotonaldehyde were obtained with high diastereo- and enantioselectivities (up to 99% ee, dr up to 95 5). 

Based on the success of dienamine catalysis in inverse-electron-demand Diels-Alder reactions, Jia et al. explored the possibility of applying the HOMO-activation mode to poly-conjugated enals, such as 2,4-dienals, to form a reactive dienamine... 

SCHEME 1.28 Diels-Alder reaction by dienamine catalysis. 

Hong et al. s preparation of palitantin, a natural product with potential antibiotic and antifungal activity, is another application of dienamine catalysis to natural product synthesis (Scheme 11.28). L-Proline was able to self-condense two 107 units forming the six-member ring 108 containing... 

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