Domino hydroformylation- aldol

A similar, but intermolecular version of the domino hydroformylation-(aldol condensation)-hydrogenation reaction was presented by Seller and colleagues in 2014 (Scheme 5.133) [22]. NAPHOS was used as a ligand for rhodium in the hydroformylation and in the final hydrogenation step. PyrroUdine acted as the organocatalyst. A range of terminal olefins were thus converted either with acetone or aromatic ketones into saturated product ketones. 

Scheme 5.133 Domino hydroformylation-(aldol condensation)-hydrogenation reaction with a rhodium catalyst based on NAPHOS for both hydroformylation and hydrogenation.

Hydroformylation of olefins has been established as an important industrial tool for the production of aldehydes. In recent years, novel asymmetric tandem reactions have included a rhodium-catalysed enantioselective hydroformylation. In this context, in 2007 Abillard and Breit ° and Chercheja and Eilbracht independently reported a novel domino hydroformylation-aldol reaction catalysed by an achiral rhodium catalyst and L-proline catalyst (Scheme 7.49). Possibly owing to the fact that proline is hard but the rhodium catalyst is soft, the proline can be compatible with the rhodium catalyst to allow this domino reaction to be achieved. By fine adjustment of the hydroformylation rate to that of the L-proline-catalysed aldol addition, the undesired homodimerisation of the aldehyde could be avoided. As a result, by in situ hydroformylation reaction, the donor aldehyde of a... 

Later, Eilbracht et al. developed a related enantioselective domino hydroformylation-aldol reaction catalysed by a rhodium complex in combination with a chiral amine derived from L-proline. In this process, the reaction of acetone with vinylbenzene afforded the corresponding chiral p-hydrojgr ketone in 69% yield, a moderate diastereoselectivity of 74% de, and a high enantioselectivity of 93% ee, as shown in Scheme 7.50. ... 

Scheme 7.49 Domino hydroformylation-aldol reaction catalysed chiral amine catatysis and rhodium catalysis.

Scheme 5.129 Domino hydroformylation-cross aldol addition of acyclic olefins with aldehydes.

Scheme 5.131 Domino hydroformylation-cross aldol addition with a chiral rhodium catalyst and a chiral aldol condensation catalyst.

The synthesis of aldehydes from alkenes known as hydroformylation using CO and hydrogen and a homogeneous catalyst is a very important industrial process [204]. Today, over seven million tons of oxoproducts are formed each year using this procedure, with the majority of butanal and butanol from propene. To further increase the efficiency of this process it can be combined with other transformations in a domino fashion. Eilbracht and coworkers [205] used a Mukaiyama aldol reaction as a second step, as shown for the substrate 6/2-63 which, after 3 days led to 6/2-65 in 91% yield via the primarily formed adduct 6/2-64 (Scheme 6/2.13). However, employing a reaction time of 20 h gave 6/2-64 as the main product. 

---