Vinyl arenes, asymmetric hydroformylation

Rhodium-Catalyzed Asymmetric Hydroformylation of Vinyl Arenes. .. 41... 

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 first report to use diphosphite ligands in the asymmetric hydroformylation of vinyl arenes revealed no asymmetric induction [46]. An important breakthrough came in 1992 when Babin and Whiteker at Union Carbide patented the asymmetric hydroformylation of various alkenes with ee s up to 90%, using bulky diphosphites 2a-c derived from homochiral (2R, 4R)-pentane-2,4-diol (Scheme 4) [17]. Their early results showed that (a) bulky substituents are required at the ortho positions of the biphenyl moieties for good regio- and enantio-selectivity and (b) methoxy substituents in the para positions of the biphenyl moieties always produced better enantio-selectivities than those observed for the corresponding ferf-butyl-substituted analogues. 

Over the years, several authors have developed new diphosphite ligands with binaphthyl, spiro, pyranoside, and macrocyclic backbones for asymmetric hydroformylation of vinyl arenes with low-to moderate success (ee s from 36% to 76%) [48-58]. 

Perfluoroalkyl-substituted BINAPHOS ligand 29c was also developed for the asymmetric hydroformylation of vinyl arenes in SCCO2. With this ligand regio-and enantio-selectivity (ee s up to 93.6%) were high without the need for hazardous organic solvents [63,64],... 

The asymmetric hydroformylation of functionalized aliphatic alkenes is generally more difficult than the hydroformylation of vinyl arenes. The rhodium-catalyzed hydroformylation of vinyl acetate (36) yields 2- and 3-acetoxypropanals, 37 and 38, with high chemoselectivity. Ethyl acetate and acetic acid can also be found as by-products. One of the potential applications of vinyl acetate hydroformylation is the production of enantiopure propane 1,2-diol (Scheme 6). 

The asymmetric hydroformylation of vinyl arenes can provide a route to the preparation of the profen class of drugs. Naproxen and ibuprofen, two examples in the profen class, are NSAIDs on the market.50... 

In summary, both S- and J -enantiomers of the product can be obtained with excellent regio- and enantioselectivity. These results are among the best ever reported for the asymmetric hydroformylation of vinyl arenes [1]. 

A series of chiral phosphine-phosphite ligands afforded complexes RhH(L-L)(CO)2 like 25, which showed catalytic activity toward asymmetric hydroformylation. Chiral diphosphite ligands derived from D-(+)-glucose were also coordinated to Rh(l), affording complexes rhodium-hydrido-carbonyl-diphosphite species of the type RhH(PP)(CO)2 (PP = diphosphite), which also proved to be effective asymmetric catalysts for the hydroformylation of vinyl arenes. ... 

Asymmetric hydroformylation of vinylarenes allows access to the 2-aryl propionic acids, an important family of nonsteroidal anti-inflammatory agents, known as the profen drugs (Scheme 14.6). For the reactions of vinyl arenes, early platinum-based catalysts again provided higher enan-tioselectivities than the rhodium catalysts available up to the early 1990s. However, the platinum complexes suffered from poor chemo- and regioselectivities. 

SCHEME 14.6. Asymmetric hydroformylation of vinyl arenes allows access to profen dmgs such as naproxen and flurbiprofen. 

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,... 

Dieguez M, Pamies O, Ruiz A, Castillon S, Claver C. Chiral diphosphites derived from D-glucose new ligands for the asymmetric catalytic hydroformylation of vinyl arenes. Chem. Eur. J. 2001 7 3086-3094. 

---