Structure and Photochemical Behavior of the Cyclodextrin Inclusion Complexes of the Benzoylthiophene‐Derived Drugs Tiaprofenic Acid (=5‐Benzoyl‐α‐methylthiophene‐2‐acetic Acid) and Suprofen (=α‐Methyl‐4‐(2‐thienylcarbonyl)benzeneacetic Acid)

The effect of β‐cyclodextrin (β‐CD) on the excited‐state reactivity of the two benzoylthiophene derivatives, tiaprofenic acid (TPA; 2 ) and suprofen (SPF; 3 ) in their carboxylate forms is studied. The presence of β‐cyclodextrin does not affect the nature of the photoproduced transients and the photoproducts, but increases the photodegradation quantum yields of both drugs. The efficiency of the photodecarboxylation process is enhanced. This effect is rationalized in the light of the inclusion of 2 and 3 in the β‐CD cavity, affecting the energy of the lowest excited states of the drugs. The structure of the complexes is determined by induced circular dichroism, and molecular‐mechanics and dynamic Monte Carlo calculations. The photoreactivity of the decarboxylated photoproduct 7 of tiaprofenic acid ( 2 ) in presence of β‐CD is also examined.     

Photoreaction between 2-benzoylthiophene and phenol or indole

Laser flash photolysis, density functional theory (DFT) calculations, and product studies have been performed to understand the mechanism of photoreduction of 2-benzoylthiophene (BT) in the presence of phenol or indole. Time-resolved experiments showed that BT ketyl (BTH) and phenoxy (PhO) or indolyl (In) radicals are generated with high rate constants and quantum yields close to 1. However, low conversions (specially in the case of indole) of the starting reagents are obtained upon prolonged lamp irradiation, indicating that recombination within the radical pairs must occur to a large extent, regenerating the starting materials. The solvent-dependence of the quenching rate constants, together with DFT theoretical studies, indicate fundamental differences between the mechanisms of the reaction of BT triplet with phenol and indole. Thus, data for phenol agree with the involvement of a hydrogen-bonded exciplex BT(.)HOPh, where concerted electron and proton transfer leads to the BTH(.)OPh radical pair. However, in the case of indole, electron transfer at the BT(.)HIn stage precedes proton transfer. Finally, C-C cross-coupling products have been isolated and characterized in the preparative irradiation of BT in the presence of phenol and indole. The structures of the products have been confirmed by alternative synthesis.     

Diastereoselective formation of chiral iridium hydrides containing the chiral P,N-chelate ligand (4S)-2-(2-(diphenylphosphino)phenyl)-4-isopropyl-1,3-oxazoline

The iridium complex [Ir(mu-Cl)(PN)(PPh3)]2 (1) reacts with H2 affording only the kinetic isomer OC-6-55-C of the dihydride [IrClH2(PN)(PPh3)] (2) and with methanol yielding, also exclusively, the thermodynamic isomer OC-6-53-C (2b) of the same dihydride; complex 2b has been characterised by X-ray diffractometric methods.     

Enantioselective 1,3-dipolar cycloaddition of nitrones to methacrolein catalyzed by (eta5-C5Me5)M{(R)-prophos} containing complexes (M = Rh, Ir; (R)-prophos = 1,2-bis(diphenylphosphino)propane): on the origin of the enantioselectivity

The rhodium and iridium Lewis-acid cations [(eta(5)-C(5)Me(5))M{(R)-Prophos}(H(2)O)](2+) ((R)-Prophos = 1,2-bis(diphenylphosphino)propane) efficiently catalyze the enantioselective 1,3-dipolar cycloaddition of nitrones to methacrolein. Reactions occur with perfect endo selectivity and with enantiomeric excesses up to 96%. Intermediates [(eta(5)-C(5)Me(5))M{(R)-Prophos}(methacrolein)](SbF(6))(2) (M = Rh (3), Ir (4)) have been spectroscopically and crystallographically characterized. The nitrone complexes [(eta(5)-C(5)Me(5))M{(R)-Prophos}(nitrone)](SbF(6))(2) (M = Rh, nitrone = 1-pyrrolidine N-oxide (5), 2,3,4,5,-tetrahydropyridine N-oxide (6), 3,4-dihydroisoquinoline N-oxide (7); M = Ir, nitrone = 1-pyrrolidine N-oxide (8)) have been isolated and characterized including the X-ray crystal structure of compounds 6 and 8. The equilibrium between methacrolein and nitrone complexes is also studied. [Ir]-adduct complexes are detected by (31)P NMR spectroscopy. A catalytic cycle involving [M]-methacrolein, [M]-nitrone, as well as [M]-adduct species is proposed, the first complex being the true catalyst. The absolute configuration of the adduct 4-methyl-2-N,3-diphenyl-isoxazolidine-4-carbaldehyde (9) was determined through its (S)-(-)-alpha-methylbenzylamine derivative diastereomer. Structural parameters strongly suggest that the disposition of the methacrolein in 3 and 4 is fixed by CH/pi attractive interactions between the pro-S phenyl ring of the Ph(2)PCH(CH(3)) moiety of the (R)-Prophos ligand and the CHO aldehyde proton. Proton NMR data indicate that this conformation is maintained in solution. From the structural data and the results of catalysis the origin of the enantioselectivity is discussed.     

Protonation reactions of dinuclear pyrazolato iridium(I) complexes

The complex [[Ir(mu-Pz)(CNBu(t))(2)](2)] (1) undergoes double protonation reactions with HCl and with HO(2)CCF(3) to give the neutral dihydride complexes [[Ir(mu-Pz)(H)(X)(CNBu(t))(2)](2)] (X = Cl, eta(1)-O(2)CCF(3)), in which the hydride ligands were located trans to the X groups and in the boat of the complexes, both in the solid state and in solution. The complex [[Ir(mu-Pz)(H)(Cl)(CNBu(t))(2)](2)] evolves in solution to the cationic complex [[Ir(mu-Pz)(H)(CNBu(t))(2)](2)(mu-Cl)]Cl. Removal of the anionic chloride by reaction with methyltriflate allows the isolation of the triflate salt [[Ir(mu-Pz)(H)(CNBu(t))(2)](2)(mu-Cl)]OTf. This complex undergoes a metathesis reaction of hydride by chloride in CDCl(3) under exposure to the direct sunlight to give the complex [[Ir(mu-Pz)(Cl)(CNBu(t))(2)](2)(mu-Cl)]OTf. Protonation of both metal centers in [[Ir(mu-Pz)(CO)(2)](2)] with HCl occurs at low temperature, but eventually the mononuclear compound [IrCl(HPz)(CO)(2)] is isolated. The related complex [[Ir(mu-Pz)(CO)(P[OPh](3))](2)] reacts with HCl and with HO(2)CCF(3) to give the neutral Ir(III)/Ir(III) complexes [[Ir(mu-Pz)(H)(X)(CO)(P[OPh](3))](2)], respectively. Both reactions were found to take place stepwise, allowing the isolation of the intermediate monohydrides. They are of different natures, i.e., the metal-metal-bonded Ir(II)/Ir(II) compound [(P[OPh](3))(CO)(Cl)Ir(mu-Pz)(2)Ir(H)(CO)(P[OPh](3))] and the mixed-valence Ir(I)/Ir(III) complex [(P[OPh](3))(CO)Ir(mu-Pz)(2)Ir(H)(eta(1)-O(2)CCF(3))(CO)(P[OPh](3))].     

Structural and dynamic studies on amido-bridged rhodium and iridium complexes

Treatment of [[M(mu-Cl)(diolefin)](2)] with the lithium salts of primary and secondary amines (LiNRR') in diethyl ether affords the complexes [[M(mu-NRR')(diolefin)](2)] (M=Rh, Ir; diolefin=1,5-cyclooctadiene (cod), tetrafluorobenzobarrelene (tfb); R'=H, R=tBu, Ph, 4-MeC(6)H(4); R=R'=Ph, 4-MeC(6)H(4)). Mixed-bridged chloro/amido complexes are intermediates in these syntheses, two of which, [[Rh(cod)](2)(mu-NHR)(mu-Cl)] (R=tBu, 4-MeC(6)H(4)), have been isolated. Replacement of the diolefin ligands by carbon monoxide or tert-butyl isocyanide in selected compounds takes place with retention of the binuclear structure to give the corresponding complexes [[M(mu-4-HNC(6)H(4)Me)(CO)(2)](2)], [[Rh(mu-4-HNC(6)H(4)Me)(CNtBu)(2)](2)] (12), and [[Rh(mu-NPh(2))(CNtBu)(2)](2)] (13). Single-crystal X-ray diffraction analyses of the complexes [[Rh(mu-NRR')(cod)](2)] (R'=H, R=4-MeC(6)H(4) (3); R=R'=4-MeC(6)H(4) (5)), 12, and 13 have shown that the conformation of the "RhN(2)Rh" four-membered metallacycle is planar in 5 and folded in 3, 12, and 13. The complexes with primary amides, 3 and 12, were found to exist as the syn,endo stereoisomers. The fluxionality of the complexes with secondary amides is due to rotation of the aromatic substituents about the N-C(ipso) bond and, in the case of 13, to the inversion of the "RhN(2)Rh" metallacycle as well. The complexes [[M(mu-NHR)(cod)](2)] (R=Ph, 4-MeC(6)H(4)) were found to exist as isomeric mixtures in solution, the syn/anti ratio being 2:3 for the rhodium derivatives and 1:1 for their iridium counterparts. Again, the motion detected was due to rotation of the aromatic substituents, and could be frozen only in the case of the syn isomers. The complex [[Rh(mu-NHtBu)(cod)](2)] with aliphatic amido ligands was found to be the anti folded isomer and proved to be nonfluxional. The most common conformation of the "RhN(2)Rh" metallacycle in these compounds is folded, and the preferred configuration varies from syn for the less encumbered compounds to anti on increasing the bulkiness of the bridging and ancillary ligands.     

Chiral pyridylamino-ruthenium(II) complexes: synthesis, structure and catalytic properties in Diels-Alder reactions

Half-sandwich complexes [(eta(6)-arene)RuCl(pyam)][SbF(6)] (pyam = L(n) = N-(2-pyridylmethyl)-(R)-1-phenylethylamine (L(1)), N-(2-pyridylmethyl)-(R)-1-naphthylethylamine (L(2)), N-(2-quinolylmethyl)-(R)-1-naphthylethylamine (L(3)), N-(2-pyridylmethyl)-(R)-1-cyclohexylethylamine (L(4)), N-(2-pyridylmethyl)-(1R,2S,4R)-1-bornylamine (L(5))) have been synthetised and characterised. Treatment of these compounds with AgSbF(6) generates dicationic complexes [(eta(6)-arene)Ru(pyam)(H(2)O)](2+) which act as enantioselective catalysts for the Diels-Alder reactions of methacrolein and cyclopentadiene. The catalytic reactions occur quickly at room temperature with good exo : endo selectivity (from 84 : 16 to 98 : 2) and moderate enantioselectivity (up to 74% ee). The molecular structures of the chloride complexes (R(Ru),S(N),R(C))-[(eta(6)-p-MeC(6)H(4)iPr)RuClL(1)][SbF(6)], (R(Ru),S(N),S(C2))-[(eta(6)-p-MeC(6)H(4)iPr)RuClL(5)][SbF(6)], and that of the aqua complex (R(Ru),S(N),S(C2))-[(eta(6)-p-MeC(6)H(4)iPr)RuL(5)(H(2)O)][SbF(6)](2), were determined by X-ray diffractometric methods. The distinctive variations observed in the molecular structures of these complexes only concern the puckering parameters of the metallacycle and the relative disposition of substituents within this ring. A clear trend to localise the most steric demanding substituents at equatorial positions is evident from the structural study.