Aldimines aldol reaction

In general the reaction of an aldehyde with a ketone is synthetically useful. Even if both reactants can form an enol, the a-carbon of the ketone usually adds to the carbonyl group of the aldehyde. The opposite case—the addition of the a-carbon of an aldehyde to the carbonyl group of a ketone—can be achieved by the directed aldol reaction The general procedure is to convert one reactant into a preformed enol derivative or a related species, prior to the intended aldol reaction. For instance, an aldehyde may be converted into an aldimine 7, which can be deprotonated by lithium diisopropylamide (EDA) and then add to the carbonyl group of a ketone ... 

Their previous screening of catalysts for of aldol reactions and Robinson annu-lations suggested the possibility that chiral amines might also be able to catalyze the Mannich reaction [30, 31]. Thus, screening of catalysts for Mannich-type reactions between N-OMP-protected aldimines and acetone revealed that chiral diamine salt 10, L-proline 11, and 5,5-dimethylthiazolidine-4-carboxylic acid (DMTC) 12 are catalysts of Mannich-type reactions affording Mannich adducts in moderate yields with 60-88 % ee. To extend the Mannich-type reactions to aliphatic imines, the DMTC 12-catalyzed reactions are performed as one-pot three-component procedures. The o-anisidine component has to be exchanged with p-anisidine for the one-pot reactions to occur. The DMTC 12-catalyzed one-pot three-component direct asymmetric Mannich reactions provide Mannich adducts in moderate yield with 50-86 % ee. 

Ester-Mannich Additions. The E 0) enolate (7) reacts with A-allyl or A-benzyl aldimines to afford chiral p-amino esters (eq 11). As with the aldol reactions, best selectivities are achieved with imines derived from aromatic or unsaturated aldehydes. The... 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

Table 1 Directed Aldol Reactions of Metallated Aldimines with Carbonyl Compounds (Scheme 3)...

Alder s. Diene syntheses Aldimines s. Metallo aldimines Aldol condensation s. a. Retroaldol reaction —, intramolecnlar -, diazoketols, cyclic by - 26,938 Aldol-type condensation, intramolecnlar, to heterocycles 26,935 Aldonolactones... 

Ishihara developed a highly efficient Mukaiyama aldol reaction between ketones and trimethylsilyl enolates catalysed by sodium phenoxide-phosphine oxides (46) as simple homogeneous Lewis-base catalysts (0.5-10 mol%) (Scheme 2.29). For a variety of aromatic ketones and aldimines, aldol and Mannich-type products with an a-quaternary carbon centre were obtained in good to excellent yields. Remarkably, a retro-aldol reaction was not observed. On a scale of up to 100 mmol, benzophenone and trimethylsilyl enolate gave the product in 97% yield (34.8 g) using 0.5 mol% of catalyst. 

Chiral amines can react with so-called Mannich donors such as ketones or aldehydes. The resulting chiral enamines wiU then attack a Mannich acceptor, usually a prochiral aldimine, thereby introducing one or two chiral centers in the Mannich product. This usually is a P-aminoaldehyde or P-aminoketone, optionally substituted at the a-position. Inspired by their work on proline-catalyzed asymmetric aldol reactions [1], the List group envisioned that the related Mannich reactions might also be carried out with a catalytic amount of an enantiomerically pure chiral amine. This led in 2000 to the first direct catalytic asymmetric organocatalyzed Mannich reaction, catalyzed by L-proline (1, Scheme 5.1) [2],... 

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