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H-bond to deliver fluoride Simple fluoride salts are theoretically convenient reagents for carbon-fluorine bond formation. In practice, they are often insoluble in the solvents that dissolve their reaction partners. Pupo et al. developed urea-based catalysts that make fluoride soluble through hydrogen bonding. Moreover, their chiral substituents bias the reaction toward one of two mirror image products of C–F bond formation. This strategy should be applicable to the asymmetric addition of other salts, too. Science , this issue p. 638

C-H activation plays a central role in organometallic catalysis. Concerted metallation-deprotonation (CMD) has been dominant as the pathway for C-H bond cleavage. In the course of studying the mechanism of C-H activation of arylamides and arylureas with Pd complexes as part of catalytic oxidative Heck reactions, DFT calculations were carried out. The turnover-limiting C-H activation is acid-catalysed and can occur readily in the absence of acetate or other coordinating bases. The calculations simulated experiment, so that ligated sulfonate and water, both previously observed by X-ray characterization, were incorporated in the model. A Wheland-type complex between acetanilide and Pd was readily located, but the reactive C-H and the coordinated sulfonate were poorly placed for intramolecular proton transfer. Involvement of a water molecule coordinated to sulfonate provides a low-energy pathway to the palladacycle. The relative reactivity of substituted acetanilides and arylureas according to this model fits well with existing literature. General-base catalysis as described here has broader potential.

Hydrogen-bonding with fluoride is a key interaction encountered when analyzing the mode of action of 5'-fluoro-5'-deoxyadenosine synthase, the only known enzyme capable of catalyzing the formation of a C-F bond from F-. Further understanding of the effect of hydrogen-bonding on the structure and reactivity of complexed fluoride is therefore important for catalysis and numerous other applications, such as anion supramolecular chemistry. Herein we disclose a detailed study examining the structure of 18 novel urea-fluoride complexes in the solid state, by X-ray and neutron diffraction, and in solution phase and explore the reactivity of these complexes as a fluoride source in SN2 chemistry. Experimental data show that the structure, coordination strength and reactivity of the urea-fluoride complexes are tunable by modifying substituents on the urea receptor. Hammett analysis of aryl groups on the urea indicates that fluoride bind-ing is dependent on [sigma]p and [sigma]m parameters with stronger binding being observed for electron-deficient urea ligands. For the first time, defined urea-fluoride complexes are used as fluoride-binding reagents for the nucleophilic substitution of a model alkyl bromide. The reaction is slower in comparison with known alcohol-fluoride complexes, but SN2 is largely favored over E2, at a ratio surpassing all hydrogen-bonded complexes documented in the literature for the model alkyl bromide employed. Increased second-order rate constants at higher dilution support the hypothesis that the reactive species is a 1:1 urea-fluoride complex of type [UF]- (U = urea) resulting from partial dissociation of the parent compound [U2F]- . The dissociation processes can be quantified through a combination of UV and NMR assays, including DOSY and HOESY analyses that illuminate the complexation state and H-bonding in solution.

The field of asymmetric hydrogenation grew rapidly after the early 1970s. What had begun as a demonstration of enantioselectivity in catalysis by purely chemical means became an important tool both for academic research and for industry. Right from the beginning, a question was posed as to how relatively simple catalysts were able to generate such unprecedented levels of stereoselectivity. This article provides an account of Oxford-based contributions to the field of rhodium complex catalyzed asymmetric hydrogenation from 1978 onward, when the initial realization of this practical catalytic method for synthesis of single enantiomers had already been achieved. NMR-based experiments that help to elucidate the structures of reactive intermediates in catalysis are strongly emphasized here and linked to the present understanding of the mechanism of a reaction that has sustained interest over the intervening years.

A synthesis of the title phosphinamine (PHENAP) is described, following previously established methodology, Resolution via the C,N-palladocycle derived from ( R )-N,N-dimethyl-α-methyl-1-naphthylamine led to two crystallographically defined complexes with the ( R , S )-form posessing a chelated ligand and the ( R , R )-form open with only the phosphine coordinated. Palladium allyl complexes of the ligand were strikingly different from those of the corresponding isoquinoline ligand QUINAP, and the differences could be rationalised by recourse to molecular models, with the additional fused arene ring of PHENAP playing a critical part in defining the coordination sphere through its steric pressure. A brief appraisal of Pd-catalysed allylic alkylation reactions was performed with the new ligand.

Allyl fluorides are reactive toward Pt-catalyzed alkylation with malonate and likewise toward N- and O-nucleophiles under mild conditions. The reactivity of fluoride as a leaving group equals or exceeds that of the esters and carbonates commonly employed in allylic alkylation. The order of leaving-group ability with Pt catalysts was found to be F ≥ OCO 2Me ≫ OBz ≥ OAc. This discouraged the application of platinum catalysts for the reverse reaction, fluorination of allylic substrates. Fluoride displacement involves predominant or complete retention of configuration in all the observed cases, and this was confirmed as a general feature of Pt catalysis, the stereochemical integrity being as high or higher as in Pd catalysis for the examples chosen. © 2012 American Chemical Society.

Reactive intermediates in the asymmetric Heck reaction between aryl electrophiles and 2,3-dihydrofuran have been identified by NMR and mass spectrometry, with BINAP or the achiral diphosphanes dppp and dppf as ligands. The major cationic species observed is an alkylpalladium produced by addition of PdAr to the alkene followed by two further PdH-mediated isomerisation steps. This last species has been characterised at - 60° by 1H-, 13C-, and 31P-NMR, including HMQC techniques. The regiochemistry of PdAr and PdH addition to the reactant are opposite as defined by the reaction with (2-2H1)-2,3-dihydrofuran. DFT Calculations on the reaction pathway between [CH2(PH2)]PdPh+ and 2,3-dihydrofuran reveal several structurally interesting intermediates involving agostic β-H-atom, ipso-Ph or reactant O-atom bonded to the Pd-atom, and elucidate the isomerisation pathway.

A method for the preparation of diphosphineruthenium complexes from a range of diphosphine precursors is described. The stable products, of general formula P2Ru(allyl)acac (P = phosphine ligand), do not catalyse the hydrogenation of alkenes but can easily be converted into catalytically active species by reaction with trimethylsilyl trifluoromethanesulfonate. The chemistry involved in this transformation is discussed. Catalysis of the hydrogenation of a range of alkenes, and direct comparison with related rhodium reductions, is described. Some mechanistic insights are gained through additions of D2 to alkenes and parallel hydrogenations on deuterated solvent, supporting the intervention of conventional dihydride and alkyl hydride intermediates which undergo exchange with solvent at both stages.

The conformations of two classes of 7-ring diphosphine metal chelate have been analysed, based on DIOP- or BINAP-type structures. A combination of X-ray analysis, DFT calculations, data analysis based on the CDS structure database and solution NMR studies has been employed. The conformational flexibility of DIOP-type structures has been endorsed, and the scope of BINAP complex flexibility defined. BINAP complexes possess an intrinsic conformational mobility. Analysis of the metal-adjacent torsion angles C-P-M-P′ and C′-P′-M-P provides a useful probe for the ligand-metal environment, and may be more generally useful. © 2010 Elsevier Ltd. All rights reserved.

Palladium(II) complexes catalyse the amide-directed displacement of an aryl-Si group and its replacement by an electrophilic alkene at ambient temperature, analogous to an oxidative Heck reaction. A palladacyclic intermediate is involved, and the reaction enables substitution to occur specifically in the electron-poor ring of benzanilides. The procedure described provides a formal link between directed lithiation and the Heck reaction.

It's a rate thing: Crucial conceptual advances have allowed for the development of a Pd-mediated pathway to Caryl-F by using either electrophilic (right) or nucleophilic (left) fluorinating reagents. Of significance is the recognition that PdIV intermediates reduce the barrier to C-F reductive elimination and the use of an ancillary bulky ligand to force reductive elimination from a 14-electron PdII complex. © 2009 Wiley-VCH Verlag GmbH and. Co. KGaA.

The stereochemical course of rhodium-catalysed addition of hydrogen and catecholborane to bicyclo[2.2.1]heptadiene, and of hydrogen to a range of cyclic dienes has been analysed. For hydroboration, the overall catalytic reaction possesses exo-selectivity, but the initial step is endo-selective. For hydrogenation (deuteration), the first step may occur with either exo- or endo- selectivity, depending on the structure of the diene. This enables a distinction to be made between pathways involving prior dissociation of the diene, and direct addition to the complexed diene without full dissociation. The relative ease of hydrogenation of the first and second double bonds varies markedly with reactant structure, and also depends on the choice of catalyst ligands. For dicyclopentadiene, hydrogenation of the cyclopentene double bond is accompanied by rapid alkene isomerisation, as revealed by deuterium addition. The asymmetric hydrogenation of acyclic skipped meso-dienes is reported, demonstrating control of relative rates of the two sequential steps, with ees of up to 53% after the first reduction.

Enantiomerically enriched ( S , S )-bicyclo[3.3.1]nona-2,6-diene has been synthesised from the readily available diketone ( S , S )-bicyclo[3.3.1]nonane-2,6-dione. The stereochemical purity is maintained on complexation to rhodium. There is a very strong preference for the formation of the homochiral over the heterochiral (alkene) 2 Rh + OTf − complex; the self-recognition involved can be rationalised by analysis of DFT calculations.

The synthesis of a new paracyclophane phosphine is described. This ligand was highly efficient in the ruthenium-catalyzed asymmetric hydrogenation of various aromatic and heteroaromatic ketones.

In 1954 Schlesinger and co-workers observed the direct reaction of diboron tetrachloride with simple organic compounds under mild conditions, the 1,2 addition product being formed with either ethylene or acetylene. In the following 25 years a series of addition reactions to simple alkenes, alkynes and dienes was demonstrated. B2F4 was shown to react in similar manner, albeit under more forcing conditions. Crucially, it was demonstrated that the addition to (E)- or (Z)-but-2-ene occurred with cis-stereospecificity. Only sporadic interest was shown in this field thereafter until catalysed addition reactions of diboron reagents were realized. Encouraged by this revival of interest through the discovery of transition-metal and nucleophilic catalysis of diboryl additions, DFT analysis of uncatalysed additions of B2X4 has been carried out and interpreted. This includes the relative reactivity of several B–B reagents with ethene, and that of B2Cl4vs. B2F4 additions, including benzene, naphthalene and C60 as reactants. This allows the analysis of relative reactivity vis-a-vis substitution on boron, and also direct comparison with hydroboration by HBCl2. [4 + 2] Addition of diboron reagents to dienes with B–B cleavage competes with direct [2 + 2] addition, favourably so for B2F4. The computational results demonstrate that the stereospecific addition to isomeric but-2-enes is a rare concerted [2σs + 2πs] process.

Ruthenium-arene complexes can act as efficient catalysts for the coupling of areneboronic acids with electrophilic alkenes. The chemoselectivity is completely different from palladium coupling, with full tolerance for halogen in the arene. NMR and ES-MS studies have been carried out to elucidate the reaction pathway.

A practical synthesis of the atropisomerically chiral ligand QUINAP is described, followed by its efficient resolution into enantiomers by employing a deficiency of the chloropalladium complex derived from 1‘-(R)-1‘-(dimethylamino)-1-ethylnaphthalene. The X-ray structure of the ligand, which crystallises as a conglomerate, is reported.

The orthometalated complex [{Pd(μ-Cl){κ2-P,C-P(OC6H2-2,4-tBu2)(OC6H3-2,4-tBu2)2}}2] reacts with phenylboronic acid hydrate and K2CO3 in dimethylacetamide to give [Pd{κ2-P,C-μ2-O-P(O)(C6H2-2,4-tBu2)(C6H3-2,4-tBu2)(DMAc)}]. When the reaction is repeated in dimethylformamide 3,3‘,5,5‘-tetra-tert-butyl-2,2‘-biphenol is isolated. Both compounds have been characterized crystallographically. The reaction of palladium dichloride with PiPr2(OC6H4-4-Et) in 2-methoxyethanol followed by recrystallization in the presence of ethanol leads to the formation of trans-[PdCl2{PiPr2(OEt)}2], which was also characterized by crystallography. To determine whether related solvolytic processes have a bearing on catalytic activity, the performance of a range of catalysts with “hydrolyzed” and “nonhydrolyzed” ligands was assessed in the Suzuki coupling of aryl bromides. In some cases it was evident that hydrolysis plays a significant role on the catalytic activity; however, this depends not only on the ligand, but also on the combi...

The cis-specific hydrofluorination proceeds through sequential H- and F+ addition and is distinct from known hydrofluorinations involving radical intermediates.

This paper describes the hydrofluorination of alkenes through sequential H(-) and F(+) addition under palladium catalysis. The reaction is cis specific, thus providing access to benzylic fluorides. The mechanism of this reaction involves an ionic pathway and is distinct from known hydrofluorinations involving radical intermediates. The first catalytic enantioselective hydrofluorination is also disclosed.

Using a combination of electrochemical and NMR techniques, the oxidative addition of PhX to three closely related bis-diphosphine P2Pd(0) complexes, where the steric bulk of just one substituent was varied, has been analysed quantitatively. For the complex derived from MetBu2P, a rapid reaction ensued with PhI following an associative mechanism, and data was also obtained by cyclic voltammetry for PhOTs, PhBr and PhCl, revealing distinct relative reactivities from the related (PCx3)2Pd complex (Cx = cyclohexyl) previously studied. The corresponding EttBu2P complex reacted more slowly with PhI and was studied by NMR spectroscopy. The reaction course indicated a mixture of pathways, with contribution from a component that was [PhI] independent. For the CxtBu2P complex, reaction was again monitored by NMR spectroscopy, and was even slower. At high PhI concentrations reaction was predominantly linear in [PhI], but at lower concentrations the [PhI] independent pathway was again observed, and an accelerating influence of the reaction product was observed over the concentration range. The NMR spectra of the EttBu2P and CxtBu2P complexes conducted in C6D6 shows some line broadening that was augmented on addition of PhI. NMR experiments carried out in parallel show that there is rapid ligand exchange between free phosphine and the Pd2Pd complex and also a slow ligand crossover between different P2Pd complexes. DFT calculations were carried out to further test the feasibility of C6D6 involvement in the oxidative addition process, and located Van der Waals complexes for association of the P2Pd(0) complexes with either PhI or benzene. PhI or solvent-assisted pathways for ligand loss are both lower in energy than direct ligand dissociation. Taken all together, these results provide a consistent explanation for the surprising complexity of an apparently simple reaction step. The clear dividing line between reactions that give a di- or monophosphine palladium complex after oxidative addition clarifies the participation of the ligand in coupling catalysis.

Synthetic procedures for the preparation of two types of functional resin are described, both based on 2% cross-linked polystyrene with a high density (>60%) of side-chains and terminated by a primary alcohol. In the first case the C11 side-chain is linked to the polymer through a sulfide, and in the second an ether linkage is employed to incorporate a (CH2CH2O)4 unit. In both cases the resins have 13C NMR spectra that are informative in the chain terminus region without special operating conditions. Model intermolecular metathesis reactions were carried out on allylcarbamic acid tert-butyl ester and various alkenes with Grubbs' catalyst. On the basis of these experiments, gel-phase metathesis was successfully demonstrated between a polymer-bound allyl ether and simple symmetrical disubstituted alkenes, monitoring the extent of reaction by 13C NMR. These reactions did not go to completion even with recycling and some evidence for competing interchain metathesis is presented, based on the increased broadening and reduced mobility of the ensuing polymer.Key words: alkene metathesis, ruthenium, gel-phase, 13C NMR.

An analysis has been made of deviations from ideal centrosymmetric bonding of alkenes to transition metals in square-planar complexes. Three separate approaches have been employed. Firstly, the geometries obtained for a series of X-ray crystal structures of monosubstituted rhodium-alkene complexes have been obtained. Secondly, DFT computations on closely related rhodium-alkene complexes are reported. Thirdly, the data have been augmented by recourse to the crystal structure serach and retrieval file (CSSR) database to retrieve the X-ray data for square-planar ethene and monosubstituted alkene complexes. The results obtained from these analyses provide a consistent picture. Two distortions from ideality are important: twisting of the alkene about the axis between the metal (M) and the alkene centroid and rolling of the alkene around a cylinder enclosing the metal, such that the two C−M bonds remain equal in length. The presence of both of these is verified through both X-ray structure determinations and DFT calculations. For the rolling distortion, there is a relationship between the electronic character of the substituent on the alkene and the direction of roll. The net effect of this is to place the more nucleophilic carbon of the alkene closer to the square plane. The significance of this for the regiochemistry of the Heck reaction is briefly discussed.

The asymmetric synthesis of ( R )-2-isopropyl-5-methylhex-5-enal in 98% ee is described. It was discovered that the key alkylation step employing an Evans chiral auxiliary and 3-methylbut-3-en-1-yl trifluoromethanesulphonate as the alkylating agent led to significant competing O -alkylation, a phenomenon not previously reported. Type II carbonyl ene cyclisation of the aldehyde with a range of Lewis acids led to either the ( R , R )- or ( R , S )-5-methylidenecyclohexanols without concurrent racemisation of the alpha stereogenic centre of the aldehyde. Conditions for effecting the easy racemisation of a model enantiomerically pure aldehyde, ( S )-2-methylbutanal, were developed. In an effort to secure a dynamic kinetic resolution procedure, these conditions were applied to ( R )-2-isopropyl-5-methylhex-5-enal. However, a competing and dominant Prins cyclisation occurred instead leading to a mixture of all possible cycloadducts, all of which were obtained in 98% ee. Any unreacted aldehyde was found to be enantiomerically pure.

Catecholboronate esters formed by asymmetric hydroboration of arylalkenes are not directly converted to amines by reaction with hydroxylamine-O-sulfonic acid. Prior conversion to a trialkylborane by reaction with ZnEt2 or MeMgCl permits a subsequent amination reaction to occur with essentially complete retention of configuration, leading to a range of primary alpha-arylalkylamines in up to 97% enantiomeric excess (ee). Secondary, but not tertiary amines may be formed by a related pathway when in situ generated alkylchloramines are employed as the aminating agent. The catalytic asymmetric hydroboration, beta-alkylation and amination steps may be combined in a single stage. Overall, this provides a practical procedure for the synthesis of enantiomerically enriched arylamines, exemplified inter alia by the synthesis of (S)-1,2,3,4-tetrahydro-1-naphthylamine in 95-97% ee and of (R)-N-(cyclohexyl)-1'-(4-methoxyphenyl)ethylamine in 93% ee.

Nonlinearity in the diastereoselectivity of epoxidation of allylic alcohols with mixtures of titanium isopropoxide, tertbutyl hydroperoxide, and diethyl tartrate was observed. Racemic and enantiomerically pure alcohols E-2-methyl-4-hexen-3-ol and E-1-methoxy-5-(O-tertbutyldimethylsilyloxy)-2-penten-4-ol were prepared. Epoxidation reactions were carried out with Ti(OPri)4 and ButOOH accompanied by diethyl tartrate of varying enantiomeric purity. The simplest explanation of these results is that a dimeric epoxidation reagent is involved, with significantly different reactivity for the homochiral and racemic forms. Chirality 12:496–504, 2000. © 2000 Wiley-Liss, Inc.

A full range of catalytic asymmetric hydroborations (see diagram) of aryalkenes may be carried out with a single family of ligands.

In palladium-catalysed cross-coupling reactions, the outcome of competition between aryl bromides and aryl triflates depends on the nucleophilic partner; Suzuki couplings with R-B generally follow a different pattern from other R-M species.

Different cyclization products are formed with different Lewis acids in the ene cyclization of 5-hexenals (see scheme on the right; a: methylaluminum bisphenoxide, b: Me2 AlCl, c: Sc(OSO2 CF3 )3 ). This is not surprising, but it is gratifying that these result can be rationalized with an internally consistent model.

A series of phosphinamines in which the aryl substituents are varied has been prepared from the known triflate 1 by palladium catalysed reaction with the appropriate secondary phosphine oxide followed by reduction with trichlorosilane. In four of the six cases attempted, resolution was successfully completed by fractional crystallisation of the diastereomeric cationic complexes formed with di-μ-chloro-bis[(R)-dimethyl(1-phenethyl)aminato-C2,N]dipalladium, as previously described. The order of crystallisation was not predictable and in one case the specific rotation of the derived phosphine was anomalous, although the CD spectrum in the 220–350 nm region was as expected by comparison with the parent compound.

(S)-(4-Methoxyphenyl)-ethyl-1,3,2-benzodioxaborole, (S)-1-(4-chlorophenyl)ethyl-1,3,2-benzodioxaborole and (S)-1-indanyl-1,3,2-benzodioxaborole, intermediates in the catalytic asymmetric hydroboration of 4-chloro- and 4-methoxystyrene, were isolated as pure oils in 75%, 84% and 49% yield respectively. For the first example, amination with N-chloromagnesio-N-methyl-O-trimethylsilylhydroxylamine gave a mixture of (S)-1-(4-methoxyphenyl)-N-methylethylamine in 33% yield, 88% e.e. and (S)-1-(4-methoxyphenyl) ethanol in 31% yield, 86% e.e.. Related results were obtained in the other cases, and the steps of catalytic hydroboration and amination could be combined in a single sequence without isolation of the intermediate. Numerous variants were carried out in the amination procedure with only marginal improvements in chemoselectivity. An investigation of the mechanism was carried out using low temperature heteronuclear NMR on 13C-1-(S)-1-(4-chlorophenyl)ethyl-1,3,2-benzodioxaborole. The dual pathway is a result of an irreversible and unselective initial step.

Several closely related palladium-catalysed reactions involve the addition of Pd–C across an alkene, and subsequent β-elimination of Pd–H to give a more substituted alkene. The Pd–C precursor, normally possessing an sp2 carbon bound to palladium, can be formed in several different ways, leading to sub-classes of reaction based on a common principle and convergent outcomes. The reaction pathway can vary from simple to highly subtle depending on the nature of the reactants and the ligation of the catalyst. Mechanistic analysis provides results that elucidate the pathway and link the different reaction types. The identification of reactive intermediates by NMR, ES-MS and other spectroscopic techniques, or by less direct methods, is an integral part of the process. This Feature Article covers ligand-free palladium catalysis, including the contributions of the authors, and separates catalysis where ligands are involved into cationic and neutral pathways.

Several closely related palladium-catalysed reactions involve the addition of Pd-C across an alkene, and subsequent β-elimination of Pd-H to give a more substituted alkene. The Pd-C precursor, normally possessing an sp(2) carbon bound to palladium, can be formed in several different ways, leading to sub-classes of reaction based on a common principle and convergent outcomes. The reaction pathway can vary from simple to highly subtle depending on the nature of the reactants and the ligation of the catalyst. Mechanistic analysis provides results that elucidate the pathway and link the different reaction types. The identification of reactive intermediates by NMR, ES-MS and other spectroscopic techniques, or by less direct methods, is an integral part of the process. This Feature Article covers ligand-free palladium catalysis, including the contributions of the authors, and separates catalysis where ligands are involved into cationic and neutral pathways.

The reaction products are isolated with very high degrees of regioselectivity (

This paper describes a new catalytic method for the regio- and stereocontrolled fluorination of allylic carbonates. This transformation uses TBAF·4tBuOH as the fluoride source and [Ir(COD)Cl]2 as the catalyst; the most commonly used [Ir(COD)Cl]2/phosphoramidite system is ineffective. Synthetically, this reaction is characterized by a high degree of structural conservation in going from substrates to the products. The fluorination of (E)-allylic carbonates leading to linear (E)-allylic fluorides (l : b > 20 : 1, E : Z > 20 : 1) is unprecedented and a unique feature of fluoride as the nucleophile. The first examples of transition metal catalyzed fluorination affording (Z)-allyl fluorides (Z : E ratio >20 : 1) are disclosed along with the successful fluorination of branched, linear (E)- and (Z)-allyl carbonates with [18F] fluoride in the presence of [Ir(COD)Cl]2. 18O-Labeling of the reactant reveals internal return during the allylic ionization step, and pathways for effective intra- and intermolecular isotope exchange. © 2013 The Royal Society of Chemistry.

A synthesis of the title ligand is described in which the key step is the dilithiation of 1,1'- bis (dimethylaminomethyl)-3,3'-biindolyl and electrophilic trapping with ClPPh 2 . Concomitant N-deprotection and resolution with bis [(R)-dimethyl(1-(1-naphthyl) ethylaminato-C 2 ,N)palladium chloride] led to selective recovery of the S-enantiomer. The N-dimethylaminomethyl-substituted biindolyl, but not the parent compound, showed strongly second-order behaviour for 13 C NMR peaks in the region of the phosphorus atom due to a desymmetrising 13 C-induced isotope shift of the 31 P resonance.

The rhodium complexes 1 and 3 catalyse asymmetric hydroboration with differing selectivity originating in the disparate steric environments of the catalysts.

Stereoisomeric benzylidinemalonates have been synthesised. In the case of N-(2-ethoxycarbonyl-3-phenylpropenoyl)-2-oxazolidinone, both E- and Z-isomers could be obtained, but the Z-isomer isomerised (>95%) to the E-isomer in the presence of catalytic amounts of Rh(I) complex catalysts. For ethyl tertbutylamidobenzalmalonate, the Z-isomer initially predominates under Knoevenagel conditions, but is very readily converted into the more stable E-isomer, which is here isolated stereoisomerically pure and is the only product of other synthetic routes. The configuration of benzylidinemalonates was established in two cases by X-ray crystallography, and the relative stability of the isomeric forms correctly simulated by MM2 calculations. In both the amide and oxazolidinone series, asymmetric hydrogenation catalysed by cationic Rh complexes gave a configurationally stable product cleanly but in low e.e.

A variety of benzyl fluorides is applied in the reactions using carbon, nitrogen, oxygen or sulfur nucleophiles.

Calculations help: Recent work from Schoenebeck's group has demonstrated beyond reasonable doubt that the dimeric LPd(I) Br catalysts that are widely used in coupling chemistry operate through prior formal reduction to an LPd(0) species. Conversely, L(2)Pd(0) catalysts can be activated by oxidation. In other cases a binuclear species can persist through the catalytic cycle.

Benzylic fluorides are suitable substrates for Pd(0)-catalyzed Tsuji-Trost substitution using carbon, nitrogen, oxygen, and sulfur nucleophiles and for cross-coupling with phenylboronic acid. For the bifunctional substrate 4-chlorobenzyl fluoride, fine-tuning of the reaction conditions allows for the regioselective displacement of either the chlorine or fluorine substituent. The leaving group ability of fluoride vs other groups displaced in substitution is CF(3)CO(2) ≈ p-NO(2)C(6)H(4)CO(2) ≈ OCO(2)CH(3) > F > CH(3)CO(2), a ranking similar to allylic fluorides under Pd catalysis.

A synthesis of the title diphosphine is described, in which the key step is a Michael addition of lithium diphenylphosphide to a vinylphosphineborane 9, itself formed by stereospecific ring opening of the ephedrine-derived oxazaphospholidine borane by reaction with vinyl lithium. The resulting phosphinamide 11 can be further elaborated to the desired product R-5 in 96% e.e., superior to that obtained in a parallel synthesis involving the vinylphosphine oxide 1 In the latter case enantiomerically pure S-product can be obtained by recrystallisation of palladium complex 7 and recovery of the diphosphine by displacement with KCN.

The X-ray crystal structure of N,N,-Bis-[2-((4S)-(methyl)-1,3-oxazolinyl)]methane-bis(η 2 -ethene)ihodium(1) has been determined, and demonstrates a specific distortion from ideal bonding geometry of the alkenes which maintains C 2 symmetry. This distorted structure is shown to be maintained in solution for this complex and the (4S)-(1-methylethyl) analogue by 1 H NMR studies particularly nOe, Extended Huckel calculations have been carried out on a simple model, and demonstrate the relative ease of some (RhCC) bending modes in which C 2 symmetry is maintained.

Attempted catalytic hydroboration of (4-methoxyphenyl)ethene 1 with R,R-3-isopropyl-4-methyl-5-phenyl-1,3,2-oxazaborolidine 6 proceeded extremely slowly relative to the 3-methyl analog 2 derived from φ-ephedrine when diphosphinerhodium complexes were employed. With phosphine-free rhodium catalysts, especially the 4-methoxyphenylethene complex 7, the reaction proceeded rapidly and quantitatively to give only the corresponding (E)-vinylborane 9 and 4-methoxyethylbenzene 8 in equimolar amounts

The use of p-nitrobenzoate as the leaving group is essential for the success of the process.