2,5-Dihydrofuran, asymmetric hydroformylation

Abstract This chapter presents the latest achievements reported in the asymmetric hydroformylation of olefins. It focuses on rhodium systems containing diphosphites and phosphine-phosphite ligands, because of their significance in the subject. Particular attention is paid to the mechanistic aspects and the characterization of intermediates in the hydroformylation of vinyl arenes because these are the most important breakthroughs in the area. The chapter also presents the application of this catalytic reaction to vinyl acetate, dihydrofurans and unsaturated nitriles because of its industrial relevance. 

The phosphine-phosphite BINAPHOS ligand was first used in the Rh-catalyzed asymmetric hydroformylation of heterocyclic olefins such as 2,5-dihydrofuran, 3-pyrroline derivatives, and 4,7-dihydro-1,3-dioxepin derivatives. It provided the optically active aldehydes as single products with enantioselectivity between 64-76% ee. In the hydroformylation of 2,5-di-... 

Table 3 Rh-catalyzed asymmetric hydroformylation of 2,5-dihydrofuran 46 with ligands 30, 4, 16-19a...

Good enantioselectivities and excellent regioselectivities have been attained in the Rh-catalysed asymmetric hydroformylation of 2,5- and 2,3-dihydrofuran using diphos- phite ligands, resulting in the formation of the 3-formyltetrahydrofuran in both... 

Scheme 2.148 Xanthene-based hybrid phosphine-phosphonite ligand for efficient asymmetric hydroformylation of 2,5-dihydrofuran.

Similar to the reaction with 2,3-dihydrofurans as a substrate, related 2,3-pyrrohns may also isomerize under hydroformylation conditions into the corresponding 2,5-isomers (Scheme 4.28). The latter, in turn, are transformed into pyrrolidin-3-carbaldehyde [44]. An example of the a-regioselective reaction was given by the Nozaki group in the framework of an asymmetric hydroformylation [21a]. The A-Boc protected substrate was reacted with syngas in the presence of a chiral Rh(BINAPHOS) catalyst to give the desired carbaldehyde with a moderate a/p-ratio. 

Ligand 18a was also successfully applied in the Rh-catalyzed asymmetric hydroformylation of 2,5-dihydrofuran and 2,3-dihydrofuran. Good enantioselectivities (up to 75% ee) and excellent regioselectivities (up to 99%) were achieved. Note that both enantiomers of tetrahydrofuran-3-carbaldehyde can be obtained using this ligand by simple substrate change from 2,5-dihydrofuran to 2,3-dihydrofuran [21]. 

Diphosphites derived from naturally occurring carbohydrates (Figure 14.4) have been applied to the asymmetric hydroformylation of a range of substrates (including ees as high as 91% in the asymmetric hydroformylation of vinyl arenes). However, they have a niche for dihydrofuran substrates for the reaction of 2,5-dihydrofuran, an excellent ee of 88% was reported, with no isomerism being observed. For the reaction of the isomeric 2,3-dihydrofuran,... 

Selective monosubstitution in the starting dibromide by PPh2 was realized at lowtemperatures [71]. Conversion of the second bromo substituent into the phosphorus diamide and final reaction with the diol produced the hybrid ligand. In the hydroformylation of 2,5-dihydrofuran, up to 91% ee with no isomerization was achieved, which is the best value reported to date. Noteworthy, the partially hydrogenated binaphthyl unit and the phenyl substituents in the 3,3 -positions are essential for the success of the asymmetric catalysis. Related ligands with a binaphthyl backbone, with or without Me-substituents in 3,3 -positions, resulted in poor conversions and stereoselectivities. 

There are only very few reports in the literature on the hydroformylation of partially unsaturated O- or N-containing six-membered ring heterocycles. Rather harsh conditions were applied (Co catalyst, 50-140atm, 130-150°C) [67]. Claver, Castillon, and Bayon [68] showed that tetrahydropyranes require, also with modified rhodium catalysts, much severe hydroformylation conditions than the corresponding dihydrofurans. Moreover, poor regioselectivity was noted. These features may be responsible for the fact that, up to now, no asymmetric version could be realized. A similar situation is faced with 1,2,3,4-tetrahydropyridin as substrate. It could not be converted with a Rh(Bisdiazaphos) catalyst at 70 °C and 140 psi (about 10 bar) pressure [43]. 

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