Regioselectivity in hydroformylation

Regioselectivity in hydroformylation is influenced by electronic and steric effects [4, 5]. Thus the formation of the C a-Rh bond is favored over that of the C P-Rh bond by the well known P-silicon effect (Fig. 3), which stabilizes a positive charge on the p-C atom. From the resulting intermediate la the /50-product should form predominantly. On the other hand, steric effects induced by bulky substituents on silicon or rhodium would favor the sterically less hindered normal alkyl rhodium complex with the C P Rh intermediate Ila as the precusor to the -aldehyde. The observed //so-ratios very close to 1 1 for the Rh-catalyzed hydroformylation of vinyltrimethylsilane indicate that the electronic P-effect obviously is canceled out by the steric demand of the MesSi-groups. Since addition of PPha will favor an active complex with a larger number of bulky phosphine ligands (L = PPhs in Fig. 2), the formation of the linear alkylrhodium complex intermediate Ila to lid is prefered [6]. 

The most valuable product of C4 hydroformylation is n-pentanal, whereas the isomers 2-methylbutyraldehyde and 3-methylbutyraldehyde are less in demand and lower in value. A catalyst with high selectivity should not catalyze the hydroformylation of 2-butene and should coonvert 1-butene predominantly to n-pentanal. Both requirements are fulfilled by the Rh/TPPTS system [19]. However, despite the high regioselectivity in hydroformylation, a side reaction occurs which diminishes the overall selectivity. Under reaction conditions, parallel to the hydroformylation reaction part of the n-l-butene is isomerized to n-2-butene, which is not hydroformylated in the presence of Rh/TPPTS under regular reaction conditions. 

Several hybrid QM/MM computational investigations of propene insertion into the Rh-H bond of HRh(L)2(CO)(CH2=CHCH3) were performed to address the issue of regioselectivity in hydroformylation catalysis and the kinetics involved. Cundari reported that for L = PPhj, the ea isomer is more stable than the ee isomer, and and the ea isomer is the one that produces the linear aldehyde while the more active ee isomer produces branched aldehyde. These findings are not in accord with the experimental studies on the bite angle effect. 

The chemo- and regioselectivities of hydroformylation reactions of open chain, conjugated dienes using the usual catalyst are, in most cases, rather low [36]. The rhodium/ mesitylene co-condensate (catalyst A), in the presence of bis(diphenylphosphino)ethane, DPPE, catalyses the hydroformylation of 1,3-butadiene, isoprene, and E,Z)-, 3-pentadiene to the corresponding p,y-unsaturated monoaldehydes, with unusually high chemo- and regioselectivities (Scheme 17). 

The major problem remains control of regioselectivity in favor of the branched regioisomer. While aryl alkenes as well as heteroatom-substituted alkenes favor the chiral branched isomer, for aliphatic alkenes such an intrinsic element of regiocontrol is not available. As a matter of fact branched-selective and asymmetric hydroformylation of aliphatic alkenes stands as an unsolved problem. In this respect regio- and enantioselective hydroformy-... 

Table 4 Turnover frequencies and regioselectivities (in parentheses) for a 5x2 ligand matrix of DA ligand (11,14-17)/AD ligand (12, 18) derived self-assembled bidentate ligands in the [Rh]-catalyzed hydroformylation of l-octenea... 

A catalyst used for the u-regioselective hydroformylation of internal olefins has to combine a set of properties, which include high olefin isomerization activity, see reaction b in Scheme 1 outlined for 4-octene. Thus the olefin migratory insertion step into the rhodium hydride bond must be highly reversible, a feature which is undesired in the hydroformylation of 1-alkenes. Additionally, p-hydride elimination should be favoured over migratory insertion of carbon monoxide of the secondary alkyl rhodium, otherwise Ao-aldehydes are formed (reactions a, c). Then, the fast regioselective terminal hydroformylation of the 1-olefin present in a low equilibrium concentration only, will lead to enhanced formation of n-aldehyde (reaction d) as result of a dynamic kinetic control. 

As demonstrated by Hoffmann and coworkers, hydroformylation can also be combined with an allylboration and a second hydroformylation, which allows the formation of carbocycles and also heterocycles [213]. A good regioselectivity in favor of the linear aldehyde was obtained by use of the biphephos ligand [214]. Reaction of the allylboronate 6/2-76 having an B-configuration with CO/H2 in the presence of catalytic amounts of Rh(CO)2(acac) and biphephos led to the lactol 6/2-80 via 6/2-77-79 (Scheme 6/2.17). In a separate operation, 6/2-80 was oxidized to give the lactone 6/2-81 using tetrabutyl ammonium perruthenate/N-methylmorpholine N-oxide. 

The new family of phospholes with 2,4,6-trialkylphenyl substituent on the phosphorus atom show, in many respects, a special reactivity. Due to the flattening of the P-pyramid, the arylphospholes exhibit aromaticity and hence underwent Friedel-Crafts reactions. The regioselective functionalization through reaction with phosphorus tribromide gave a variety of phospholes with an exocyclic P-moiety. Novel phosphole platinum and rhodium complexes were prepared and a part of them was tested in hydroformylation reactions. 

We applied the QM/MM IMOMM method [41] to Rh-diphosphine catalyzed hydroformylation, to provide a quantitative theoretical characterization of the origin of regioselectivity in Rh-diphosphine systems. We focused on the experimentally characterized xantphos ligands, for which variation in electronic properties is minimal. Using the IMOMM method, which only accounts for the steric properties of ligands, was fully justified. 

However, platinum catalysts have several disadvantages they have low reaction rates, they hydrogenate the substrate and their regioselectivity to the branched aldehyde is low. The selectivity of Pt-diphosphite/SnCl2 systems is also low. When the appropriate diphosphite is used, ee s can be as high as 90% [13]. In the early 90s, several reports were published which described the state of the art in hydroformylation with both rhodium and platinum systems [14-16]. 

---