Double Michael reaction, optimization

TABLE 2 Optimization of the Double Michael Reaction — Cont d... 

The results from four other reactions with catalyst 407 are summarized in Sch. 56. Induction ranged from 5 to 49 % ee, below the value obtained (74 % ee) from the reaction of enone 404 and malonate 405. The reaction of malonate 405 with the unsaturated carbonyl compounds 413, 392 and 414 all failed to produce product. The reaction of 405 with acrolein led to polymerization. The stoichiometry of catalyst formation is crucial for optimization of the Michael adduct. The reaction between enone 404 and nitroester 411 with catalyst 394 generated with 2.0 equiv. BINOL gave the double Michael adduct 416 as the major product. When the amount of BINOL is increased to 2.45 equiv. the Michael adduct 415 constitutes a minimum of 80 % of the product mixture. Larger amounts of BINOL resulted in an insoluble catalyst. 

With the development of the enantioselective allylic-allylic alkylation of a,a-dicyanoalkenes and MBH carbonates by dual organocatalysis of commercially available modified cinchona alkaloids and (5)-BINOL, Chen and co-workers have delivered an elegant construction of cyclohexene derivatives. The intramolecular Michael reaction of allylic allylic alkylation product 75a could be cyclized to give the desired cyclohexene 76 in the presence of DBU (Scheme 4.25). In the presence of nucleophile BnNH2, allylic compound 75b furnished an imexpected cyclic product 77 rather than the formal double Michael adduct. Interestingly, the reaction of a,a-dicyanoalkene 79 and MBH carbonate 80 under optimized catalytic conditions directly afforded cyclohexene derivatives 81a-c in... 

Knoevenagel CondensatiorL This method can be used to introduce electron-withdrawing groups into conducting polymers by the reaction of an aromatic aldel de with a ben Uc nitrile catalyzed by an amine or amine salt (Fig. 68). Careful optimization of the reaction conditions is needed to reduce unwanted side reactions such as hydrolysis of the nitrile group or Michael addition to the double bond [881-894]. 

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