Stefano Paganelli

Aqueous Biphasic Hydroformylation Catalysed by Protein‐Rhodium Complexes

The water-soluble complex derived from Rh(CO)2(acac) and human serum albumin (HSA) proved to be efficient in the hydroformylation of several olefin substrates. The chemoselectivity and regioselectivity were generally higher than those obtained by using the classic catalytic systems like TPPTS-Rh(I) (TPPTS=triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt). Styrene and 1-octene, for instance, were converted in almost quantitative yields into the corresponding oxo-aldehydes at 60 °C and 70 atm (CO/H2=1) even at very low Rh(CO)2(acac)/HSA catalyst concentrations. The possibility of easily recovering the Rh(I) compound makes the system environmentally friendly. The circular dichroism technique was useful for demonstrating the Rh(I) binding to the protein and to give information on the stability in solution of the catalytic system. Some other proteins have been used to replace HSA as complexing agent for Rh(I). The results were less impressive than those obtained using HSA and their complexes with Rh(I) were much less stable.

A protein–rhodium complex as an efficient catalyst for two-phase olefin hydroformylation

Abstract A highly efficient and chemoselective biphasic hydroformylation of olefins was accomplished using water soluble complexes formed by the interaction between Rh(CO) 2 (acac) and human serum albumin (HSA), a readily available water soluble protein. A new type of shape-selectivity was observed in the hydroformylation of sterically hindered olefins.

Asymmetric Michael additions catalysed by Ni(II) and Co(II) complexes with homochiral ligands

Abstract Two Michael-type addition reactions of nitromethane to chalcone, reaction (1a), and of methyl 1-oxo-2-indanecarboxylate to methyl vinyl ketone (reaction (1b)) have been tested for catalytic asymmetric induction when carried out in the presence of Ni(II) or Co(II) and homochiral ligands. Proline-derived ligands in conjunction with Ni(II) are found to be moderately effective asymmetric inductors in the former addition (up to 59% e.e.). For this addition the absolute configuration of the adduct ( 2 ) has been established via correlation with ( S )-(+)-1-(dimethylamino)-2,4-diphenylbutan-4-one ( 21 ). For reaction (1b), Co(II) complexes appear to be the more effective catalysts; the highest e.e. (38%) was obtained with a tetradentate ligand, a diaminodiol ( 16 ). Although the e.e.s so far obtained are not much better than those previously obtained, the method appears to allow further improvement.

Rhodium-catalyzed michael additions of activated nitriles to α,β - unsaturated esters

The Michael additions of activated nitriles to methyl acrylate (MA) and methyl vinyl ketone (MVK) proceeds with fair to high yields (46–92%) in the presence of catalytic amount of HRh(CO)(PPh3)3 1 under mild eaction conditions.

Synthesis of 2-chromanol by hydroformylation of 2-hydroxystyrene derivatives

Abstract 2-Benzyloxy- and 2-tosyloxystyrene were hydroformylated under different reaction conditions with the aim to obtain the corresponding linear aldehydes, valuable intermediates to 2-chromanol, a structural moiety present in several interesting therapeutically active molecules. The best results were obtained by using the catalytic precursor Pt(Xantphos)Cl 2 in toluene or the water-soluble catalytic system Rh(CO) 2 acac/Xantphos(SO 3 Na) 2 in the biphasic medium water/toluene. Rather good regioselectivities were also achieved employing the unmodified complex Rh 4 (CO) 12 at high temperature and low pressure for very short reaction times: unfortunately the chemoselectivity of the process was not satisfactory, due to the extensive formation of the substrate hydrogenation product.

Rhodium catalyzed hydroformylation of 1,1-bis(p-fluorophenyl)allyl or propargyl alcohol: a key step in the synthesis of Fluspirilen and Penfluridol

Abstract Fluspirilen (1) and Penfluridol (2), two neuroleptic agents, belong to a wide class of pharmaceuticals that contain in their molecules a 4,4-bis(p-fluorophenyl)butyl group bound to a nitrogen atom of a pyrrolidine, piperidine or piperazine moiety. A key intermediate for the synthesis of compounds 1 and 2, 4,4-bis(p-fluorophenyl)butylbromide (15), has been prepared starting from commercially available 4,4′-difluorobenzophenone (7) following a preparative route involving the rhodium catalyzed hydroformylation in toluene or in the biphasic system toluene/water or cyclohexane/water of 1,1-bis(p-fluorophenyl)-2-propenol (8) and/or 1,1-bis(p-fluorophenyl)-2-propynol (12). Fluspirilen and Penfluridol were obtained in 70–80% yield by reaction of bromide 15 with 1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one (16) and 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol (17), respectively. The overall yields of the two pharmaceuticals 1 and 2, based on starting ketone 7, were about 35–40%.

Hydroformylation of norbornene and 2,5-norbornadiene catalysed by platinum(0)-alkene complexes in the presence of methanesulfonic acid: determination of the stereochemistry of the reaction

Abstract The hydroformylation of norbornene catalysed by [Pt(C2H4)(dppb)]/CH3SO3H (dppb = 1,4-bis(diphenylphosphino)butane) occurs under standard oxo conditions giving the exo-norbornanecarboxaldehyde exclusively. The deuteroformylation of this olefin shows that the addition of H and CHO groups is cis. As for the chemoselectivity of the monohydroformylation of 2,5-norbornadiene, the catalytic system affords better results than the more common catalytic precursors of rhodium and platinum/tin complexes; the regioselectivity towards the exo-aldehyde is lower.

Hydroformylation of functionalized olefins catalyzed by water-soluble rhodium carbonyl complexes

Abstract The hydroformylation of 1,1-diarylethenes, 1,1-diarylallylalcohols, and aryl vinyl ethers was carried out in biphasic system water/toluene (cyclohexane) in the presence of rhodium carbonyl complexes with the water-soluble ligand, sulfonated triphenylphosphine P(C6H4-m-SO3−Na+)3 (TPPTS), under standard reaction conditions. The yields of the expected aldehydes are generally high without any addition of co-solvents, hydrophobic auxiliary ligands, or other agents able to improve the transport across the two phases.

Esters and N,N-dialkylamides of 2-(trifluoromethyl)acrylic acid (TFMAA) through Pd-catalysed carbonylation of fluorinated unsaturated substrates

Abstract Esters and amides of 2-(trifluoromethyl)acrylic acid (TFMAA) have been synthesised by two different routes involving CO-chemistry. The alkoxycarbonylation of 2-bromo-3,3,3-trifluoropropene was carried out in the presence of PdCl 2 (PPh 3 ) 2 . High substrate conversions were obtained, but the yield in acrylic esters was generally low because the desired unsaturated esters reacted further adding a molecule of alcohol to the C–C double bond. The carbonylation of 2-bromo-3,3,3-trifluoropropene in the presence of secondary amines produced the corresponding unsaturated amides in high yields; the addition of the amine to the C–C double bond also occurred, but this side reaction was minimised by using secondary cyclic amines such as morpholine or piperidine. Alternatively, the acrylic esters can be obtained by hydromethoxycarbonylation of 3,3,3-trifluoropropyne using the catalytic system Pd(OCOCH 3 ) 2 /2-pyridyldiphenylphosphine/CH 3 SO 3 H. In this process the most important side product is the isomeric crotonic ester. The regioselectivity of the reaction can be controlled to a great extent by a suitable choice of the solvent.

Aryloxypropanoic herbicides by asymmetric hydroformylation catalyzed by rhodium carbonyl complexes modified with phosphorus ligands

Abstract Three aryl vinyl ethers have been subjected to enantioselective Rh(I) catalyzed hydroformylation using diphosphites 10 and 11 described in the literature and diphosphites 12–16 synthesized in our laboratories as ligands. All these ligands afforded in most cases 80–90% yields 2-aryloxypropanals as valuable precursors of the very selective herbicides, 2-aryloxypropanoic acids. The same unsaturated substrates have been also hydroformylated in the presence of Rh complexes with commercially available ferrocenylphosphines 17–19: these catalytic complexes showed generally satisfactory reaction rates as well as regioselectivities, but in some cases, lower chemoselectivities than those containing diphosphites. The enantioselectivities obtained with all described ligands were rather low (up to 9%).