Domino hydroformylation- -hydrogenation reaction

In a similar way, carbocycles having a quaternary center could be obtained from acyclic unsaturated 1,3-dicarbonyl compounds [206]. Other combinations are the domino hydroformylation/Wittig olefmation/hydrogenation described by Breit and coworkers [207]. The same group also developed the useful domino hydroformyla-tion/Knoevenagel/hydrogenation/decarboxylation process (Scheme 6/2.14) [208] a typical example is the reaction of 6/2-66 in the presence of a monoester of malonic acid to give 6/2-67 in 41 % yield in a syn anti-ratio of 96 4. Compounds 6/2-68 and 6/2-69 can be assumed as intermediates. 

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.

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. 

More recently, during research aimed at supporting the highly linear selective hydroformylation catalyst [Rh(H)(Xantphos)(CO)2] onto a silica support, the presence of a cationic rhodium precursor in equilibrium with the desired rhodium hydride hydroformylation catalyst was observed. The presence of this complex gave the resulting catalyst considerable hydrogenation activity such that high yields of linear nonanol could be obtained from oct-1-ene by domino hy-droformylation-reduction reaction [75]. 

Wittig yhdes have been shown to be compatible with hydroformylation conditions, and may thus be used in a domino reaction sequence such as from 16a to 38 (Scheme 5.15) [20]. When an a-unsubstituted ylide is employed, the resulting alkene undergoes in-situ rhodium-catalyzed hydrogenation in a triple tandem reaction to convert 10 a to 39. Several other examples were reported establishing the generality of this domino reaction sequence. 

Tandem or domino reactions using hydroformylation as the first step allow the immediate transformation of the formed aldehydes into other valuable chemical compounds (see Chapter 5) [41]. As discussed previously, the hydrogenation of olefinic substrates or product aldehydes is a commonly observed side reaction in the hydroformylation with Ru complexes. On the other hand, the reduction of the aldehydes can be desired. 

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