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This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions. For each reaction, the catalytic data, as well as examples of their application to the synthesis of more complex molecules, are collected. Sections in which we discuss key mechanistic aspects for high selectivity and a comparison with other metals (with advantages and disadvantages) are also included. For Pd-catalyzed asymmetric allylic substitution, the catalytic data are grouped according to the type of nucleophile employed. Because of the prominent position of the use of stabilized carbon nucleophiles and heteronucleophiles, many chiral ligands have been developed. To better compare the results, they are presented grouped by ligand types. Pd-catalyzed asymmetric decarboxylative reactions are mainly promoted by PHOX or Trost ligands, which justifies organizing this section in chronological order. For asymmetric oxidative allylic substitution the results are grouped according to the type of nucleophile used.

The dinuclear iridium hydride complexes [IrH(CH3CN)(L1)(μ-H)]2(BArF)2 (7; L1 = (S)-2-(2-((diphenylphosphanyl)oxy)propan-2-yl)-4-isopropyl-4,5-dihydrooxazole, BArF = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate), [IrH(CH2Cl2)(L1)(μ-H)]2(BArF)2 (8), [IrH(L2)(μ-H)]2(BArF)2 (9a; L2 = (S)-1-[2-(2-adamantan-2-yl-4,5-dihydrooxazol-4-yl)-ethyl]-3-(2,6-diisopropylphenyl)-1,2-dihydroimidazol-2-ylidene), and [IrH(L3)(μ-H)]2(BArF)2 (9b; L3 = (S)-1-[2-(2-tert-butyl-4,5-dihydrooxazol-4-yl)-ethyl]-3-(2,6-diisopropylphenyl)-1,2-dihydroimidazol-2-ylidene) were prepared from the corresponding mononuclear [Ir(COD)(L)]BArF precursors by treatment with H2 and characterized by 2D NMR spectroscopy and X-ray diffraction. Conversion to a trinuclear iridium hydride complex, which is usually observed for N,P iridium hydride complexes, is inhibited by addition of 0.5 equiv of [H(OEt2)2]BArF or acetonitrile. Reactions with acetonitrile or 6,6′-bi-2-picoline afforded the mononuclear iridium dihydride complexes [Ir(H)2(CH3CN)2(L1)]BA...

A novel, highly stereocontrolled, and very flexible synthetic access to biologically relevant trideoxypropionate building blocks in optically pure form has been developed. On the basis of a three-step sequence comprising a thermal oxy-Cope rearrangement, an iridium-catalyzed hydrogenation, and an auxiliary-controlled enolate methylation, trideoxypropionates with easily adjustable relative configuration were synthesized in excellent yields. In addition, the functionalized end groups allow for chemoselective manipulations and further elongation of the chain. The underlying strategy constitutes the first noniterative process for the assembly of polydeoxypropionates and has further been applied in total syntheses of the pheromones (+)-vittatalactone and (+)-norvittatalactone, which had been isolated from the striped cucumber beetle Acalymma vittatum.

Aryl−iridium(III) hydride complexes with a P-coordinated phosphinate were formed from [Ir(cod)Cl]2 and secondary phosphine oxide−oxazoline ligands under basic conditions. The structure of these complexes, whose formation involved C−P cleavage, was assigned by X-ray analysis and NMR spectroscopy.

The first synthesis of the natural product (+)-mutisianthol was accomplished in 11 steps and in 21% overall yield from 2-methylanisole. The synthesis of its enantiomer was also performed in a similar overall yield. The absolute configuration of the sesquiterpene (+)-mutisianthol was assigned as (1S,3R). Key steps in the route are the asymmetric hydrogenation of a nonfunctionalized olefin using chiral iridium catalysts and the ring contraction of 1,2-dihydronaphthalenes using thallium(III) or iodine(III). The target molecules show moderate activity against the human tumor cell lines SF-295, HCT-8, and MDA-MB-435.

Two cationic rhodium(I)−tetrasilylene complexes, (4; BArF = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) and (5), were prepared from [Rh(cod)2]BArF and 1,3-di-tert-butyl-2,3-dihydro-1H-1,3,2-diazasilol-2-ylidene (1) or its saturated analogue 2, respectively (Figure 1). The two complexes were characterized by X-ray analysis and NMR spectroscopy. The crystal structures revealed a square-planar coordination geometry for both complexes. Only tetrakis(silylene) complexes were formed, even in the presence of less than 4 equiv of silylene.

[reaction: see text] New Ir-SimplePHOX complexes Ir-6-Ir-9 catalyze the quantitative, highly enantioselective hydrogenation of a range of unfunctionalized and functionalized olefins. Synthesis, catalytic results, and X-ray crystal structures are presented here.

Two trinuclear iridium hydride clusters of the type [Ir3(μ3-H)(H)6(PHOX)3]X1X2 (X1 = PF6, X2 = OTf; X1 = X2 = PF6; X1 = X2 = OTf; PHOX = (S)-4-tert-butyl-2-[2-(di-o-tolylphosphinyl)phenyl]-4,5-dihydrooxazole, (S)-2-[2-(diphenylphosphinyl)phenyl]-4-isopropyl-4,5-dihydrooxazole) have been prepared and characterized by X-ray diffraction and multidimensional NMR. They contain a single bridging hydride in pseudo-trans position to the P-donors. The complexed PHOX ligands reveal a chiral pocket involving one pseudoequatorial P-aryl substituent and one pseudoaxial (proximate to the oxazoline substituent) P-aryl group. These trinuclear complexes are shown to be inactive as hydrogenation catalysts.

Experimental kinetic studies of the coupling of p-bromobenzaldehyde (1) with butyl acrylate (2) using the dimeric palladacycles complex (4) with chelating nitrogen ligands were carried out together with kinetic modeling using a reaction rate expression based on the mechanism shown in Scheme 2. The oxidative addition product of 1 was found to be the resting state within the catalytic cycle. The formation of dimeric Pd species external to the catalytic cycle helped to rationalize a non-first-order rate dependence on catalyst concentration. Theoretical modeling showed how the relative concentrations of the different intermediate species within the catalystic cycle can influence the observed rate dependence on Pd concentration. It was shown how conventional kinetic studies may give reaction orders in substrates which differ from those which would be observed under practical synthetic conditions. Comparison between phosphine- and nonphosphine-based palladacycles suggests that they follow the same reaction mechanism. The role of water in accelerating the initial formation of the active catalyst species is noted.

A series of new Ru(II) complexes containing two chelating P,N ligands of the type (2-oxazolin-2-ylmethyl)diphenylphosphine (PCH2-oxazoline I), (2-oxazolin-4,4-dimethyl-2-ylmethyl)diphenylphosphine (PCH2-oxazoline-Me2 II), and (2-oxazolin-4-(S)-isopropyl-ylmethyl)diphenylphosphine (PCH2-oxazoline-iPr III) have been prepared and characterized by IR, 1H, 13C{1H}, and 31P{1H} NMR spectroscopy and by X-ray diffraction studies in the cases of cis,cis,cis-[RuCl2(PCH2-oxazoline)2] (1) and cis,cis,trans-[RuCl2(PCH2-oxazoline-Me2)2] (3). Four different types of octahedral coordination geometries are found for these complexes depending on the ligand. With I, cis,cis,cis and trans,trans,trans geometries were characterized in complexes 1 and 2, respectively, whereas with ligand II only the cis,cis,trans isomer 3 was formed. Reaction of the enantiomerically pure ligand III with [RuCl2(COD)]n afforded a mixture of isomers, and complex trans,cis,cis-[RuCl2(PCH2-oxazoline-iPr)2] 4 was fully characterized. This complex was...

We compare the coordination behavior of the new chiral ligand (S,S)-bis[1-(4-isopropyl-4,5-dihydrooxazol-2-yl)-1-methylethyl] phenylphosphonite (V), abreviated NOPONiPr and referred to as bis(oxazolinyl) phenylphosphonite, toward Ru(II) with that of NOPONMe2 (IV). Although the similarity between IV and V led to the expectation that they would coordinate in a similar manner, considerable differences were observed. Whereas reaction of [RuCl2(η6-p-cymene)]2 with IV afforded the pentacoordinated complex [RuCl2(NOPONMe2)] 1, the chiral ligand V led instead to the dinuclear, chloride-bridged complex [Ru(μ-Cl)Cl(NOPONiPr)]2 (3). The crystal structures of 1 and 3 have been determined by X-ray diffraction. The mer arrangement of the NOPONMe2 ligand in 1 results from the presence of the four methyl groups, two of which would point toward each other and lead to a steric clash if a fac geometry were adopted. Preliminary theoretical calculations on 1 at the EHT level indicated that coordination of ethylene parallel to...

The protocol based on reaction calorimetry which is described in this paper offers a multidimensional kinetic and stability profile of a catalyst candidate in liquid and multiphase reactions. The scale-transparent picture of catalyst properties provided by this method should make it generally useful for rapid screening of candidates for catalytic process steps as well as for fundamental kinetic and mechanistic studies of organic reactions. In the example described here, new Pd complexes with nitrogen-based ligands were found to be more active than phosphapalladacycles in the Heck coupling of aryl halides with olefins.

Supercritical carbon dioxide (scCO2) was shown to be a reaction medium with unique properties for highly efficient iridium-catalyzed enantioselective hydrogenation of prochiral imines. Cationic iridium(I) complexes with chiral phosphinodihydrooxazoles, modified with perfluoroalkyl groups in the ligand or in the anion, were synthesized and tested in the hydrogenation of N-(1-phenylethylidene)aniline. Both the side chains and the lipophilic anions increased the solubility, but the choice of the anion also had a dramatic effect on the enantioselectivity with tetrakis-3,5-bis(trifluoromethyl)phenylborate (BARF) leading to the highest asymmetric induction. (R)-N-phenyl-1-phenylethylamine was formed quantitativley within 1 h in scCO2 [d(CO2) = 0.75 g mL-1] at 40 °C and a H2 pressure of 30 bar with enantiomeric excesses of up to 81% using 0.078 mol % catalyst. The use of scCO2 instead of conventional solvents such as CH2Cl2 allowed the catalyst loading to be lowered significantly owing to a change in the rate pr...

A series of chiral C2-symmetric bisoxazolines with trans-1,2-diaminocyclohexane backbones was synthesized. In view of the promising results obtained by Trost with analogous bispyridine ligands, we tested our new ligands in the enantioselective molybdenum-catalyzed allylic alkylation of 1- and 3-monosubstituted allylic substrates. Enantiomeric excesses of up to 98% and branched/linear ratios of up to 11:1 were obtained with (E)-3-(n-alkyl)allyl carbonates. (E)-3-Phenoxyallyl acetate gave a branched/linear ratio of >20:1 and an ee of 98%.