Mauro Marchetti

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.

Synthesis of homochiral pyridyl, bipyridyl and phosphino derivatives of 2,2-dimethyl-1,3-dioxolane: Use in asymmetric catalysis

Abstract Homochiral pyridyl, bipyridyl and phosphino derivatives of 2,2-dimethyl-1,3-dioxolane were prepared from L-(+)-tartrate. These compounds were assessed in metal catalyzed asymmetric addition of diethylzinc to benzaldehyde, hydroformylation of styrene, hydrocarboethoxylation of styrene and allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate.

Hydroformylation of some functionalized olefins catalyzed by rhodium(I) complexes with pydiphos and its P-oxide

Abstract The chiral optically active pyridylphosphines pydiphos ( 10 ) and its P -oxide ( 11 ) were tested as ligands in rhodium(I) complexes to form catalysts for the enantioselective hydroformylation of some functionalized olefins. These hydroformylation reactions provide in most cases good chemo- and regioselectivity, but unsatisfactory enantioselectivity. In the hydroformylation of styrene, vinyl acetate and phenyl vinyl ether, the Rh (I) complex containing the P -oxide 11 is remarkably more active than the catalyst formed with the pyridylphosphine analogue 10 .

Asymmetric hydrogenation, hydroformylation and hydrocarbalkoxylation of olefins by transition metal complexes with steroidal phosphines

Abstract Two new optically active phosphines, 3α-diphenylphosphino-5α-cholestane [(+)-DICOL] and 2,3-O-(5′α-cholestan-3′,3′-ylidene)-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane [(−)-DIOCOL] have been prepared and used as ligands in transition metal catalyzed asymmetric processes. In CO-insertion reactions, especially in the Pd promoted hydrocarbalkoxylation,(+)-DICOL-based complexes displayed a remarkable catalytic activity and a very high regioselectivity, but a poor stereoselectivity. Optical yields of up to 93% and up to 34%, respectively, were obtained in asymmetric hydrogenation and hydroformylation catalyzed by rhodium complexes with (−)-DIOCOL.

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%.

(-)-(4S,5R)-4-(2-"Pyridyl)-5-(diphenylphosphino)methyl-2,2-dimethyl-1,3-dioxolane a New Chiral Ligand for Enantioselective Catalysis

Abstract The title compound (PYDIPHOS) has been prepared by a ten reaction sequence from dimethyl L-(+)-tartrate and checked in the palladium-catalyzed asymmetric hydroesterification of styrene and in the nickel catalyzed asymmetric cross-coupling reaction of 1-phenylethyl magnesium bromide with vinylbromide.

Asymmetric synthesis by chiral ruthenium complexes: X. Enantioface discriminating isomerization of olefins☆

Abstract Prochiral 3-methyl-5-phenylpent-2-ene has been isomerized in the presence of H 4 Ru 4 (CO) 8 [(−)-DIOP] 2 , both in the presence and in the absence of hydrogen. ( S )-(+)-1-Phenyl-3-methylpent-1-ene was formed as the consequence of an enantioface differentiating process.

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.