Regioselective hydroformylation vinyl acetate

The influences of the ligand-to-metal ratio, reaction temperature and syngas pressure on the enantioselectivity and regioselectivity were also studied. A multi-substrate screening approach has recently been used by Dow Chemical Company to identify the best catalyst for the hydroformylation of vinyl acetate. Here, the chiral phosphite Kelliphite, 5 (Fig. 1) gave enantioselectivity up 88% ee and excellent regioselectivity for the branched isomer [24,25]. 

BINAPHOS (176a), developed by Takasago, has been used in the asymmetric hydroformylation of styrene and vinyl acetate with enantioselectivites of 94% ee and 90% ee, respectively. The regioselectivities (branch/normal ratios) ranged 88/12 to 85/15 in both transformations.225 226... 

Rhodium catalysts with Kelliphite (177) have been tested in the asymmetric hydroformylation of vinyl acetate. Enantioselectivities of 90% ee and regioselectivities of >99.5/0.5 (b/1) have been achieved in initial screening experiments.230... 

S,S-1). These turned out be excellent asymmetric hydroformylation catalysts for non-ste-rically hindered substrates such as vinyl esters (Scheme 6). Enantioselectivities of 85 % (ee 85 %) and regioselectivities of 80 % n/i ratio 4 1) have been achieved for vinyl acetate at 85 °C and 6.2 bars of CO/H2 (1 1), the turnover frequency being 476 cycles per hour. [14]... 

Conventionally, this reaction is conducted in the presence of a Lewis acid. We had to check that the catalyst used in the hydroformylation was still active in the presence of such an acidic additive. To this point, only catalytic amounts of PPTS (pyridinium p-toluenesulfonate) had been used in CHC reactions. This study was conducted on substrate 21, which was designed to allow only the hydroformylation/cyclization sequence (Scheme 9). It was synthesized by peptide coupling between 0-Me-phenylglycinol and vinyl acetic acid in a yield of 84%. Without an acidic additive, the hydroformylation reaction of this substrate proceeded in 93% yield and produced the linear aldehyde/branched aldehyde in a ratio of 92 8. We obtained the enamide after the CHC reaction in very good yields both in the presence of pTSA and Lewis acids (e.g., BF3-Et20, Zn (OTf)2). In addition, it should be noted that the regioselectivity of the hydroformylation reaction dictated by chelation of the BiPhePhos ligand is not disturbed by the presence of the acidic additive. 

Discovered more than 70 years ago, hydroformylation is nowadays one of the most important reactions in the chemical industry because aldehydes can be transformed to many other products. In the enantioselective version, rhodium/ diphosphorus ligand complexes are the most important catalytic precursors, although cobalt and platinum complexes have also been widely used. For these systems, the active species are pentacoordinated trigonal-bipyramidal rhodium hydride complexes, [HRh(P-P)(CO)2]. In those complexes, the coordination mode of the bidentate ligand (equatorial-equatorial or equatorial-apical) is an important parameter to explain the outcome of the process. The most common substrates of enantioselective hydroformylation are styrenes followed by vinyl acetate and allyl cyanide. With these substrates, mixtures of the branched (b, chiral) and linear (1, not chiral) aldehydes are usually obtained. In addition, some hydrogenation of the double bond is often observed. Therefore, chemo- and regioselectivity are prerequisites to enan-tioselectivity and all of them must be controlled. An additional eomplieation is that chiral aldehydes are prone to racemise in the presenee of rhodium spe-... 

The first example of catalytic hydroformylation of vinyl acetate was published in 1949 by Adkins and Krsek [26] [CojfCO), CO/H2 = 100-150 atm, 120-125°C] (Scheme 4.25). Rh as a catalytically active metal was tested first by Brown and Wilkinson in 1969 [27]. In general, Rh-catalyzed hydroformylation of vinyl acetate occurs with extremely high iso-regioselectivity with simple monodentate phosphines [28], phosphonites [20], phosphinites [29], and phosphites [30]. Also, with bidentate diphosphine or diphosphite ligands the a-product is predominantly formed [31]. Therefore, this substrate is frequently screened as a model... 

Scheme 4.26 Highly n-regioselective hydroformylation of vinyl acetate depending on the catalyst used and subsequent transformations.

Recent studies showed that the chiral phosphite kelliphite 21 (Figure 3.4) provided high enantioselectivities and excellent regioselectivity toward debranched isomer in vinyl acetate (ee s up to 88%) and allyl cyanide (ee s up to 78%) hydroformylation [22]. 

The bis-(diazaphospholidine) ESPHOS 44 provided high enantioselectivity (up to 89% ee) and regioselectivity (92-97% in the branched aldehyde) in the Rh-catalyzed hydroformylation of vinyl acetate (Figure 3.12) [38]. 

Si02-tethered rhodium complexes, derived from Rh(CO)2(acac) and 3-(mercapto) propyl- and 3-(l-thioureido)propyl-functionalized silica gel, were used as catalysts in the hydroformylation of various vinyl arenes and vinyl acetate. Conversions, che-moselectivity, and regioselectivity obtained with the Si02-tethered catalysts were comparable with those of the well-known homogeneous rhodium catalysts [85]. 

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