Enantioselective hydroformylation olefins

Neutral catalysts or catalyst precursors based on fluorinated ligand systems have been applied in compressed CO2 to a broad range of transformations such as Zn- and Cr-catalyzed copolymerization of epoxides and CO2 [53, 54], Mo-catalyzed olefin metathesis [9], Pd-catalyzed coupling reactions [43, 55, 56] and Pd-catalyzed hydrogen peroxide synthesis [57]. Rhodium complexes with perfluoroalkyl-substituted P ligands proved successful in hydroformylation of terminal alkenes [28, 42, 44, 58], enantioselective hydroformylation [18, 59, 60], hydrogenation [61], hydroboration [62], and polymerization of phenylacetylene... 

Because of their high solubility in supercritical carbon dioxide (scCOj), similar fluorous catalyst systems have also been successfully used for enantioselective hydroformylation of olefins in this environmentally benign reaction medium [19] (Scheme 3.4). 

Scheme 3.4 Synthesis ofthe chiral fluorous (R,S)-3-H F -Binaphos (16) ligand for the rhodium-catalyzed enantioselective hydroformylation of olefins in supercritical carbon dioxide (seCOj) [19] (Rf = (CH2)2(CF2)6F).

The enantioselective hydroformylation process confronts a series of challenges. First, the hydroformylation of alkenes tends to form linear over branched products. Thus, enantioselective hydroformylation of alkenes must be conducted with uns)rmmetrical "vinylidenic" olefins (2,2-disubstituted) that establish a stereocenter at the carbon p to the carbonyl group, or with mono-substituted olefins that form the branched product. As noted above, vinylarenes, vinyl acetates, and other olefins bearing electron-withdrawing groups, form branched products. Thus, reactions of these olefins have been the greatest focus of enantioselective hydroformylations. 

Both platinum and rhodium catalysts have been studied for enantioselective hydroformylation. The asymmetric hydroformylation of an itaconate derivative occurs with the highest selectivity in the presence of platinum catalysts (Equation 17.17). However, the chemical yields of branched aldehydes from reactions catalyzed by platinum catalysts are typically low. Therefore, enantioselective hydroformylation of mono-substituted olefins with platinum catalysts have generally been unsatisfactory, and most effort has been spent on developing rhodium catalysts for asymmetric hydroformylation. 

Table 17.1. Scope of the enantioselective hydroformylation of olefins catalyzed by rhodium and (S, fl)>BINAPHOS.i...

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... 

Nozaki K, Takaya H, Hiyama T. Enantioselective hydroformylation of olefins catalyzed by rhodium(I) complexes of chiral phosphine-phosphite ligands. Top. Catal. 1997 4 175-185. 

The first highly enantioselective asymmetric hydroformylation was the asymmetric hydroformylation of styrene.120 In 1991, Stille et al.121 reported the achievement of up to 96% ee using a chiral bisphosphine complex of PtCl2 as the catalyst in combination with SnCl2. However, the Pt(II)-catalyzed hydroformylation of arylethenes and some functionalized olefins has several disadvantages, such as low reaction rates, a tendency for the substrates to undergo hydrogenation, and poor branched-to-linear ratio. 

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-... 

The maximum enantioselectivity of 18 % achieved so far in aqueous hydroformylations may not seem very promising. However, the history of asymmetric hydrogenation of prochiral olefins and ketones demonstrates that such a situation may change fast if there is a strong drive behind the case. 

Asymmetric Hydroformylation of Other Olefins In contrast to vinylarenes, the asymmetric hydroformylation of aliphatic alkenes, especially 1-aIkenes, is still very challenging, although the Rh-BINAPHOS (5a) catalyst has made significant improvement in enantioselectivity as compared to that achieved by previous catalysts. Representative results are summarized in Scheme 4.5. The reaction of... 

Effects of GO and H2 partial pressures on the reaction rate and selectivity of asymmetric hydroformylation of 1-hexene and styrene are examined using (7 ,A)-BINAPHOS-Rh catalyst system. For both substrates, high GO partial pressure tends to retard the reaction the partial pressure of H2 hardly affects the reaction rate (Phz -5 MPa). In most cases, the regio- and enantioselectivities are independent of H2 and GO pressure. Deuterioformylation experiments clearly demonstrate the irreversibility of the olefin-insertion step at total pressures of 2-10MPa (D2/G0=I/I). This fact proves that the regio- and enantioselectivity of the present hydroformylation should be controlled by the olefin-insertion step. Herrmann reported the theoretical calculation of the olefin coordination step, explaining selectivity obtained with (i ,A)-BINAPHOS/Rh system for the hydroformylation of styrene. 

A number of papers on asymmetric hydroformylation of olefins using chiral bis-phosphite or bis-phosphine ligand were reported by 2000. Here, we focus on some examples that achieved high enantioselectivities. 

In spite of extensive studies on the asymmetric hydroformylation of olefins using chiral rhodium and platinum complexes as catalysts in early days, enantioselectivity had not exceeded 60% ee until the reaction of styrene catalyzed by PtCl2[DBP-DIOP (l)]/SnCl-> was reported to attain 95% ee in 1982 [8]. Although the value was corrected to 73% ee in 1983 [9], this result spurred further studies of the reaction in connection to possible commercial synthesis of antiinflammatory drugs such as (S)-ibuprofen and (S)-naproxen. The catalyst PtCl2[BPPM... 

Spectacular enantioselection has been observed in hydrogenation (cf. Section 2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], olefin epoxidation (cf Section 2.4.3) [5] and dihydroxylation (cf Section 3.3.2) [6], hydrovinylation (cf Section 3.3.3) [7], hydroformylation (cf Section 2.1.1) [4a, 8], carbene reactions [9] (cf Section 3.1.10), olefin isomerization (cf Section 3.2.14) [10], olefin oligomerization (cf Section 2.3.1.1) [11], organometallic addition to aldehydes [12], allylic alkylation [13], Grignard coupling reactions [14], aldol-type reactions [15], Diels-Alder reactions [12a, 16], and ene reactions [17], among others. This chapter presents several selected examples of practical significance. 

Polymer-supported chiral catalysts have likewise been prepared in order to obtain access to reusable systems (cf. Section 3.1.1, especially Section 3.1.1.3). For example, copolymerized functionalized BINAP [160, 161] could be applied in the enantioselective hydrogenation of olefinic substrates (up to 94 % ee). Similarly, the copolymerization of vinyl-BINAPHOS with styrene derivatives led to a heterogenized auxiliary which made it possible to hydroformylate styrene and vinyl acetate (Rh catalysis) with selectivities and enantioselectivities close to those provided by the parent homogeneous catalytic system [162]. 

---