Hydroformylation-Mannich reaction

Scheme 5.146 Hydroformylation-(Mannich reaction) tandem reaction.

Earlier, the same authors employed the same strategy to the synthesis of optically active amine compounds from alkenes through a three-component domino hydroformylation-Mannich reaction. The combination of rhodium catalyst hydroformylation with L-proline-catalysed asymmetric Mannich reaction worked well to afford the domino product in moderate yield and good enantioselectivity of 74% ee, as shown in Scheme 7.51. 

Scheme 7.51 Three-component domino hydroformylation-Mannich reaction catalysed by chiral amine catalysis and rhodium catalysis.

Indeed, this has been realised and BASF started a plant on a 5000ton/year scale in 1989 [81, 82]. The process is based on the hydroformylation of ethylene. Subsequently the propanal is converted via a Mannich reaction into methacro-lein, oxidation and esterification then leads to MM A (Scheme 5.45). 

Fig. 2.17 At the centerpiece of organic chemistry the making of new carbon-carbon bonds in stereoselective fashion using organometallic catalysis, (a) Aldol-Tishchenko reaction [81], (b) Pictet-Spengler reaction [82], (c) Mannich reaction [83], (d) hydroformylation [84],...

It is also worth mentioning that the multiphase approach has been used as a strategy to avoid undesired consecutive reactions [lla-c] or even to segregate two different and incompatible catalysts in one-pot or in tandem syntheses. In a typical example, Chaudhari et al. described the combination of a hydroformylation step -catalyzed by phosphine-modified rhodium complexes - with the Mannich reaction of the 0x0 aldehydes formed, catalyzed by tertiary amines. Thus the manufacture of methacrolein according to Figure 7 proceeds best in two different phases the organic phase for hydroformylation and the aqueous phase in which the Mannich reaction is achieved (Figure 8) [lid]. 

Chercheja et al. reported a metal-catalyzed hydroformylation combined with an organocatalyzed stereoselective Mannich reaction in one pot. L-Proline was used as the organocatalyst, and 69 was obtained in 52% yield and 71% ee. 

Instead of formyl groups, imino groups formed immediately after the hydroformy-lation by the reaction with amines can also be attacked by C-nucleophiles. Such a combination of metal catalysis and organocatalysis was realized in a tandem reaction covering hydroformylation and Mannich reaction by the Eilbracht group (Scheme 5.146) [36]. The reaction rate and stereoselectivity were strongly dependent on the temperature. At room temperature, almost no conversion of the olefin... 

Bidentate ligands were used by Alper and coworkers. The bis(diphenylphospino-methyl)amine ligands were prepared on primary amine-terminated PAMAM dendrons on silica as well as polyamido dendrons on polystyrene via the double Mannich-like reaction with formaldehyde and diphenylphosphine (Scheme 15.36a). " Subsequently, Alper and coworkers subjected the dendronized ligand-decorated supports to complexation with rhodium and palladium precursors in order to prepare active catalysts for a number of important chemical transformations (Scheme 15.36b). Initially, the dendronized rhodium catalysts were tested in the hydroformylation reaction and carbonylative ring expansion of... 

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