C Botteghi

Asymmetrische katalysen: XLVI. Enantioselektive Hydrosilylierung von Ketonen mit [Rh(COD)Cl]2 und optisch aktiven Stickstoff-Liganden☆

The synthesis and characterisation of 16 optically active nitrogen ligands, namely, pyridinethiazolidones, pyridinethiazolines, pyridinimidazolines, Schiff bases and bipyridines, are described. These ligands are used as cocatalysts together with the procatalyst [Rh(COD)Cl]2 in the catalytic hydrosilylation of prochiral ketones with diphenylsilane. With these homogeneous in situ catalysts, optically active 1-phenylethanol is produced from acetophenone after hydrolysis of the silyl ether. The diastereomers of N-(1-phenylethyl)-2-(2-pyridinyl)-thiazolidine-4-one give opposite optical inductions. The best optical purity of 71.6% ee is obtained with a pinanyl-substituted bipyridine.

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.

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 .

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.

Synthesis of Optically Active Aliphatic Nitriles from Aldehydes and Acids

Abstract Optically active nitriles are very useful starting products for the preparation of chiral amines1, ketones2 and pyridines3. They are usually accessible from the corresponding acids via amide dehydration4, through nucleophilic substitution of suitable leaving groups by he CN− anion5 and by dehydration of aldomixes3. However, the preparation of optically active nitrils with the asymmetric center in the -a- position with respect to the functional group and with high optical purity presents some difficulties due to the possible racemization of the chiral center in the starting compound used for the its preaparation and in the reaction products themselves4,6

Optically Active Nitrogen Ligands. II. Synthesis of (-)-S-3-sec-Butyl- and (+)-S-5-sec-Butyl-2-(2′-Pyridyl)Pyridine

Abstract Syntheses of optically active (-)-S-3-sec-butyl- and (+)-S-5-secbutyl-2-(2′-pyridyl)pyridine are described. The value of the maximum rotatory power for both compounds is reported.