Cyclic enone systems amine catalysts

A particularly difficult situation arises when combining in the same reaction the use of these rather unreactive acceptors such as enones with the incorporation of ketones as Michael donors in which the formation of the intermediate enamine by condensation with the amine catalyst is much more difficult. For this reason, the organocatalytic Michael addition of ketones to enones still remains rather unexplored. An example has been outlined in Scheme 2.22, in which it has been shown that pyrrolidine-sulfonamide 3a could catalyze the Michael reaction between cyclic ketones and enones with remarkably good results, although the reaction scope was exclusively studied for the case of cyclic six-membered ring ketones as nucleophiles and 1,4-diaryl substituted enones as electrophiles. In this system the authors also pointed toward a mechanism involving exclusively enamine-type activation of the nucleophile, with no contribution of any intermediate iminium species which could eventually activate the electrophile. Surprisingly, the use of primary amines as catalysts in this transformation has not been already considered. 

Jensen et al. also displayed their efforts toward this direction by combining an Au(I) complex and a secondary amine catalyst. They first demonstrated an enone-involved Michael addition/cycloisomerization process by means of primary amine and An catalysis [51]. They then embarked on a similar reaction by replacing enone with enals, while the catalytic system comprised a secondary amine and a Cu or An catalyst [52], which yielded the cyclic chiral enal 176 with comparable results (Scheme 9.57). 

With the multifunctional primary amine-thiourea catalyst (which was prepared from (l/ ,2/ )-l, 2-diaminocyclo-hexane and 9-amino (9-deoxy) epiquinine) in the absence of additives, the asymmetric Michael addition of malonate to cyclic enone proceeded well to afford 1,4-adducts in excellent yields and enantioselectivities (Table 9.10). Particularly noteworthy is that all examined malonates afforded higher than 95% enantioselectivities. In general, the reaction could even complete within a short period of time (12-18 hours) to give >90% yields and high enantioselectivity (93-96% ee) when the reactions were carried out at an elevated reaction temperature. Moreover, the reaction of 2-cyclohepten-l-one also afforded more than 90% ee and 83% yield. Furthermore, the use of 4,4-dimethylcyclohex-2-enone resulted in 77% yield with 91% ee. Only 2-cyclo-penten-l-one furnished medium yield and enantioselectivity. In contrast to previous reports, this reaction system exhibits excellent catalytic activity in asymmetric Michael addition with a broad scope of both malonate and cyclic enone. 

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