Catalysts for Conjugate Addition

The first systematic investigation of Lewis acid-catalyzed additions of indole to enones used Yb(OTf)3. The enones examined included methyl vinyl ketone, pent-3-en-2-one, 4-phenylbut-3-en-2-one and cyclohexenone, all of which gave good yields. The p,p-disubstituted systems 4-methylpent-3-en-2-one and 3-methylcyclo-hex-2-enone gave lower yields [210]. 

A catalyst consisting of 20% ZnBr2 on Caio(P04)6F2, fluoroapatite, gave 90% yields with several p-unsubstituted enones, but p-aryl reacted more slowly, although good yields were obtained in most cases [221]. Dry montmorillonite K-10 clay gave good results when one equivalent of ethanol was added and the 

When carried out in the presence of excess indole, conjugate addition can be followed by b/s-indolylmethane formation at the remaining carbonyl group. This was observed, for example, with Zr(OTf)4 [224]. 

Products of this type can also be formed as unwanted by-products under other conditions. 

Another mechanism for catalysis of conjugate addition is via iminium salts. This reactivity has been exploited for several enantioselective catalysts (see Sect. 6.2). A simple example is provided by the use of pyrrolidine salts [225]. 

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Coumalic acid, 56, 51 Crotyl fluoride, 57,73 18-CROWN-6,57, 30 Curtius rearrangement, 59, 1 Cyanide ion, as catalyst for conjugate addition of aldehydes, 59, 56 p-Cyanobenzenesulfonyl cyanide, 57, 89 2-( 1 -Cyanocyclohexyljhydrazinecarboxylic acid methyl ester, 58,102 Cy a noferrocene, 56, 30 Cyanogen chloride, 57, 88... 

Thioazolium ions, as catalysts for conjugate addition of aldehydes, 59, 57 Thiobutyric acid, 55, 129, 131 Thioketals, conversion to vinyl sulfides,... 

The fluoride ion is an effective catalyst for conjugate additions involving relatively acidic carbon nucleophiles.292 The reactions can be done in the presence of excess... 

Several modifications have been made to organoaluminum-based catalysts. Methylaluminum bis(2,6-di-tert-butyl-4-alkylphenoxide) (MAD) shows high diastereofacial selectivity in carbonyl alkylation (Scheme 72).31 11 Aluminum tris(2,6-diphenylphenoxide) (ATPH) has been developed as a catalyst for conjugate addition reactions. Since a carbonyl group is stabilized by steric effect of ATPH, the 1,4-adduct is obtained selectively.312... 

The first organocatalyzed conjugate addition of a-substituted p-ketoester to a,P-unsaturated ketones was presented by Deng et al. [42] (Scheme 3). Although traditional Cinchona alkaloids were efficient catalysts for conjugate addition of carbon nucleophiles to nitroalkenes and sulfones, replacement of the C(9)-OH with an ester group (Q-7b) showed great improvement in stereoselectivity. The reaction is applicable to a variety of cyclic and acyclic enones (16,18). 

Green, J. Woodward, S. Selective monoacylation of 2,2 -binaphfhol as a route to new monothiobinaphthol-based Cu catalysts for conjugate addition. Synlett 1995, 155—156. 

However, neither Cul nor CuBr2 activated by ClSi(CH3)3 and HMPA is useful as a catalyst for conjugate addition of CH3MgBr to a,(5-unsaturated esters. Even the CH3Cu BF3 complex is not useful in this reaction. Surprisingly, the Cu(II) complex 1 is remarkably efficient (equation I). 

Several chiral catalysts for conjugate addition have been explored, including both protic and Lewis acids. 3,3 -hri-(4-Nitrophenyl)-BINOL-phosphoric acid gives 40-98% yields and 40-55% ee with p-aryl enones [243]. 

Catalyst for Conjugate Additions. The catalytic effect of copper(II) chloride on the 1,4-addition of /3-dicarbonyl compounds to (arylazo)alkenes and aminocarbonylazoalkenes has been studied in some detail. The reactions proceed at ambient temperature in THF and afford the corresponding pyrrole derivatives (eq 15). This mild method requires no other catalyst and succeeds with 8-diketones, /3-ketoesters, and /3-ketoamides. Copper(II) chloride also catalyzes the addition of water, alcohols, phenol, and aromatic amines to arylazoaUcenes (eq 16). ... 

On the other hand, ruthenium hydrides selectively promote monoaddition. The ruthenium hydrides (r] -C5H5)RuH(PPh3)2 56 and (r] -C5Me5)RuH(PPh3)2 57 are efficient catalysts for conjugate addition of various carbonyl compounds to activated alkenes to furnish the polycarbonyl compounds such as 58 and 59 (Scheme 24) [31]. 

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