Bifunctional catalysis ketone addition

Scheme 6.102 Bifunctional catalysis with primary amine thiourea 99 Proposed transition states to explain the onfi-diastereoselectivity (A) and the syn- diastereoselectivity (B) of the Michael addition of both acylic and cyclic ketones to frans-P-nitrostyrene.

A bifunctional catalysis involving urea/ketone hydrogen-bond interactions and ion-pair formation between the nucleophile and the quinucUdine nitrogen are postulate to explain the observed enantioselectivity. On the other hand, imininm catalysis is proposed for salt 204, where both the cation and the anion are chiral, which exhibits high reactivity and selectivity for the addition of alkylic nucleophiles to linear enones (Fig. 2.28) [384]. 

The availibility of three geometric isomers of our artificial enzyme lets us examine other reactions that can show bifunctional catalysis. Enolization of a ketone— and its addition to an aldehyde group in an aldol condensation—are two cases examined so far in which an isomer of our catalyst is preferred that is not the one that was best in the ribonuclease mimic. The geometric preference indicates something novel about the geometry of enolization reactions. 

Highly functionalized 3,4-disubstituted lactones have been prepared in good delee via Michael addition of aryl methyl ketones to 2-furanones, using bifunctional catalysis by a simple chiral diamine and tosic acid ESI-MS suggests that a catalytic monosalt 0 forms. 0... 

Trost s group reported direct catalytic enantioselective aldol reaction of unmodified ketones using dinuclear Zn complex 21 [Eq. (13.10)]. This reaction is noteworthy because products from linear aliphatic aldehydes were also obtained in reasonable chemical yields and enantioselectivity, in addition to secondary and tertiary alkyl-substituted aldehydes. Primary alkyl-substituted aldehydes are normally problematic substrates for direct aldol reaction because self-aldol condensation of the aldehydes complicates the reaction. Bifunctional Zn catalysis 22 was proposed, in which one Zn atom acts as a Lewis acid to activate an aldehyde and the other Zn-alkoxide acts as a Bronsted base to generate a Zn-enolate. The... 

The Tsogoeva group, in 2006, reported the introduction of newly designed bifunctional secondary amine-functionalized proline-based thioureas (95 and 96) and the primary amine-functionalized thioureas (97-99) for catalysis of the asymmetric addition of ketones to trans-P-nitrostyrenes (Figure 6.30) [260, 261]. Using... 

L-Prolinamides (71) with a pendant alcohol act as recoverable bifunctional catalysts of direct nitro-Michael addition of ketones to -nitrostyrenes, giving syn-de s up to 94% and ees up to 80%.204 The pyrrolidine provides enamine catalysis, and the side-chain donors can hydrogen-bond the nitro oxygens. 

Oxazole-containing molecules found several applications in catalysis and materials chemistry. Pyrrolidinyl-oxazole-carboxamide catalysts 140 were reported as new chiral bifunctional organocatalysts effective in the asymmetric Michael addition of ketones to nitroolefins (140BC8008). Compound 141 exhibits different spectral properties (both in absorption and emission) in response to external stimuli, such as pressure and protonation, and it is therefore promising for the realization of piezofluorochromic materials (14CC2569). 

A bifunctional iminiumyhydrogen-bonding catalysis has been very recently employed for the first enantioselective organocatalytic conjugate addition of a phosphorous nucleophile (diarylphosphane oxides) to a,ji-unsaturated ketones [370]. The process, which allows efficient additions to cyclic and linear enones as well as the generation of quaternary stereocenters, is catalyzed by quinine-derived thiourea... 

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