Free Ylide Research Articles

A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N−H Bonds

AbstractFree carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high‐pKa Brønsted acid catalysts that enable free carbene insertion into N−H bonds of amines to prepare chiral α‐amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high‐energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high‐pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton‐transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.

A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N-H Bonds.

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pKa Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.

Melding of Experiment and Theory Illuminates Mechanisms of Metal-Catalyzed Rearrangements: Computational Approaches and Caveats

AbstractThis review summarizes approaches and caveats in computational modeling of transition-metal-catalyzed sigmatropic rearrangements involving carbene transfer. We highlight contemporary examples of combined synthetic and theoretical investigations that showcase the synergy achievable by integrating experiment and theory.1 Introduction2 Mechanistic Models3 Theoretical Approaches and Caveats3.1 Recommended Computational Tools3.2 Choice of Functional and Basis Set3.3 Conformations and Ligand-Binding Modes3.4 Solvation4 Synergy of Experiment and Theory – Case Studies4.1 Metal-Bound or Free Ylides?4.2 Conformations and Ligand-Binding Modes of Paddlewheel Complexes4.3 No Metal, Just Light4.4 How To ‘Cope’ with Nonstatistical Dynamic Effects5 Outlook

Metal Bound or Free Ylides as Reaction Intermediates in Metal-Catalyzed [2,3]-Sigmatropic Rearrangements? It Depends

Density functional theory calculations were applied to study four previously published metal-catalyzed [2,3]-rearrangements from onium ylide intermediates, in pursuit of generalizations about when,...

Phosphine-phosphonium ylides as ligands in palladium-catalysed C2-H arylation of benzoxazoles

As balanced electron-rich P,C-chelating ligands, phosphine-phosphonium-ylides are considered for their ability to in situ promote palladium-catalysed direct C(sp2)H arylation. Using methyl phosphonium salts of 2,2'-bis(diphenylphosphino)-1,1'-binaphtyl ("methyl-BINAPIUM") as ylide precursors under optimized reaction conditions, arylation of benzoxazole was found to proceed in moderate to high yield to give functional 2-aryl benzoxazoles. A strong anion effect of the non-salt free ylide was evidenced (TfO− > I− > PF6− ≈ salt-free). This first example of phosphonium ylides as ligands in catalytic C–H activation extends the prospect of their general implementation in homogeneous transition metal catalysis.

Mechanistic insights into the chemoselectivity of PtCln (n = 2, 4)-catalyzed O[sbnd]H insertion and cyclopropanation compared to Rh- and Cu-catalyzed reactions

Allyl alcohol could provide an interesting model for chemocontrol in transition metal-catalyzed insertion of carbenoid into OH bond and olefin cyclopropanation. The chemoselectivity of PtCl2- and PtCl4-catalyzed (compared to Rh and Cu) reactions between methyl α-diazophenylacetate and unsaturated allyl alcohol has been carried out by DFT calculations. The potential energy profiles confirm that the intermediate free enol formed by intramolecular proton transfer is more favorable compared to the formation of the free ylide and cyclopropanation. The [1,3]-proton shift of the enol readily provides the final OH insertion product, which has a barrier of 4.5 and 6.9 kcal/mol using metal-assisted two-allyl-alcohol clusters as a proton shuttle. Calculations provide a good explanation for the OH insertion vs cyclopropanation of platinum, copper and rhodium catalysts have been used in these reactions. This study is expected to improve the understanding of platinum-catalyzed reactions for the CX bond construction and provide guidance for the future design of new catalysts and new reactions.

Mechanistic investigations on asymmetric N-H insertion of amines catalyzed by palladium-chiral guanidine complex

The mechanism and stereoselectivity of the asymmetric N-H insertion reactions between α-diazocarbonyl compounds and amines mediated by palladium-chiral guanidine complexes were investigated at the BP86-D3(BJ)/def2TZVP (SMD, CH2Cl2)//BP86-D3(BJ)/def2SVP (SMD, CH2Cl2) level at 303 K. The non-catalytic reaction occurred through a stepwise mechanism, with a high activation barrier of 56.4 kcal mol−1. Good linear correlations between the global nucleophilicity index (N) of amine, Hammett substituent constants (σP), and the activation energy barriers (ΔG≠) were found. The Pd(0)-guanidine-catalyzed reaction consisted of three continuous steps, including: (i) generation of Pd-carbene intermediate by dinitrogen loss from α-diazoesters substrate, (ii) formation of CN bond, and (iii) 1,2-H transfer by metal-associated ylide, accompanying with the regeneration of catalyst. A water molecule accelerated the final H-transfer by constructing hydrogen bonding network. The cyclohexyl group in ligand provided sufficient steric shielding around Pd-carbene intermediate from the re-face attack by amines. The combination of the hydrogen bonding orientation of amide moiety of guanidine ligand, as well as the steric repulsion between the ester group of α-diazoester substrate and bulky CH(Ph)2 group in ligand played an important role in controlling the stereoselectivity, affording the predominant S-configuration product observed in experiment. Introducing one aromatic ring to chiral backbone of the guanidine ligand enhanced the enantiodifferentiation of products by increasing the difference of strain energy (ΔΔEstrain) of Pd-carbene moiety along two competing pathways. Different from Pd(0)-catalyst, the Pd(II)-chiral guanidine complex accelerated N-H insertion reaction via Lewis acid catalysis. In this process, the formation of free ylide in the reaction led to low ee. These results were in good agreement with experimental observations.

Enantioselective [2,3]-Sigmatropic Rearrangements: Metal-Bound or Free Ylides as Reaction Intermediates?

Out of bounds: Enantioselective rearrangement reactions are a long-standing challenge in organic synthesis. Recent advances are highlighted that led to the development of the first enantioselective Doyle-Kirmse reaction and enantioselective rearrangement reactions of iodonium ylides.

Synthesis, Thermochemistry, Bonding, and13C NMR Chemical Shift Analysis of a Phosphorano-Stabilized Carbene of Thorium

Reaction of the Th(IV) metallacycle [Th(CH2SiMe2NSiMe3)(NR2)2] (1; R = SiMe3), with Ph3P═CH2 affords the Th(IV) carbene [Th(CHPPh3)(NR2)3] (2) in good yield. In solution, complex 2 exists in equilibrium with complex 1 and free ylide, Ph3P═CH2. The thermodynamic parameters of this equilibrium were probed using variable-temperature NMR spectroscopy, and these results are compared to those collected for the isostructural U(IV) complex [U(CHPPh3)(NR2)3]. X-ray diffraction studies, together with NMR spectroscopic data and DFT calculations, provide clear evidence for actinide–carbon multiple bonding in the title complex 2, which features the shortest Th–C distance measured thus far. This interaction is best characterized as a strongly polarized σ(Th–C) bond augmented by a three-center two-electron π(Th–C–P)-type interaction. In addition, 13C NMR chemical shifts of carbon atoms bonded to the thorium center were identified as quantitative measures of the An–C bond covalency for a series of structurally related Th...

Regioselective and Stereospecific Copper-Catalyzed Deoxygenation of Epoxides to Alkenes.

Two copper salts (Cu(CF3CO2)2 and IMesCuCl) were identified as earth-abundant, inexpensive, but effective metal catalysts together with diazo malonate for chemo-/regioselective and stereospecific deoxygenation of various epoxides with tolerance of common functional groups (alkene, ketone, ester, p-methoxybenzyl, benzyl, tert-butyldimethylsilyl, and triisopropylsilyl). In particular, the unprecedented regioselectivity allowed for the first time monodeoxygenation of diepoxides to alkenyl epoxides. Density functional theory mechanistic studies showed that the deoxygenation occurred by collapsing the free ylide, unfavoring the possible intuitive pathway via cycloreversion of possible oxetane.

Intramolecular Reactions of Metal Carbenoids with Allylic Ethers: Is a Free Ylide Involved in Every Case?

Rhodium-, copper- and iridium-catalyzed reactions of the (13)C-labelled diazo carbonyl substrates 18* and 19* were performed. Results obtained from copper- and iridium-catalyzed reactions of the (13)C-labelled α-diazo β-keto ester 19* indicate that either or both of these reactions do not proceed via a free oxonium ylide but instead follow a competing non-ylide route that delivers apparent [2,3]-sigmatropic rearrangement products. In the case of the iridium-catalyzed reaction of α-diazo β-keto ester 19*, results obtained from crossover experiments indicate that the initially formed metal-bound ylide dissociates to give an iridium enolate and an allyl cation, which recombine to form the -C bond.

Studies on the Reactivity of Migrating Group in [2,3]-Sigmatropic Rearrangement of Sulfur Ylides

The [2,3]-sigmatropic rearrangement of sulfur ylides is unique and useful reaction in organic synthesis. In this study, the reactivity of sulfides containing three different migrating groups (propargyl, allyl, and allenyl) in [2,3]-sigmatropic rearrangement of sulfur ylides has been compared. The competition reactions of phenylethyldiazoacetate with sulfides through sulfonium ylide [2,3]-sigmatropic rearrangement are designed under Rh(II)- or Cu(I)-catalyzed reaction conditions. Both intra- and intermolecular competitions of sulfides bearing two different migrating groups have been carried out. The ratio of products has been determined by H-1 NMR in order to compare the reactivity of different sulfides bearing allyl, propargyl or allenyl groups. Obvious disparity of the reactivity of these sulfides in [2,3]-sigmatropic rearrangement has been observed. Experimental data indicate that the tendency of preferential [2,3]-sigmatropic rearrangement has the following order: propargyl sulfide>allyl sulfide>allenyl sulfide. Catalysts such as Rh-2(OAc)(4), Rh-7(O2CCF3)(4), and Cu(CH3CN)(4)PF6 ligated with a series of diimine ligands have been investigated for these reactions. Rh(II) complexes are found more efficient than Cu(I) complexes, and Rh-2(O2CCF3)(4) is more efficient than Rh-2(OAc)(4). The efficiency of different catalytic system has been explained based on the proposed reaction mechanism. The reaction catalyzed by Rh(II) complexes is suggested to be different from that catalyzed by Cu(I) complexes. In the case of Cu(I)-catalyzed reaction, Cu(I)-bonded sulfur ylide is considered as the predominant intermediate, while the [2,3]-sigmatropic rearrangement is suggested to proceed through free ylide. Both steric hindrance and electronic properties of ligands influence the ratio and selectivity in Cu(I)-catalyzed reactions. This study provides useful information for further investigation of [2,3]-sigmatropic rearrangement of sulfur ylides.

Mercury(II) complexes of stabilized phosphine–phosphonium ylide derived from bis(diphenylphosphino)methane: Synthesis, spectra and crystal structures

The reaction of a mixed phosphine–phosphonium ylide, PPh2CH2PPh2C(H)C(O)Ph with mercury(II) halides in methanol under mild conditions yielded the P, C-chelated complexes, [HgX2(PPh2CH2PPh2C(H)C(O)Ph)] where X = Cl (2), Br (3), I (4). Single crystal X-ray diffraction studies reveal the presence of mononuclear complexes containing Hg atom in a distorted tetrahedral environment and long Hg–Cylide bond. The five-membered chelate rings in the two independent molecules present in the asymmetric unit of 4 adopt ‘envelope’ and ‘twist’ conformations. Spectroscopic studies also indicate the weaker Hg–C bonding. Additionally, the molecular structure of the free ylide (1) is also discussed.

One-Pot Synthesis of Stable Phosphorus Ylides by Three-Component Reaction between Dimethyl Acetylenedicarboxylate, Semicarbazones, and Triphenylphosphine

Protonation of the reactive 1:1 intermediate, produced in the reaction between dimethyl acetylenedicarboxylate and triphenylphosphine, by aromatic aldehyde semicarbazones leads to vinylphosphonium salts, which undergo Michael addition with the conjugate base of the NH-acid to produce highly functionalized, salt free phosphorus ylides in excellent yields.

New Complexes of Methyldiphenylphosphonium Cyclopentadienylide, Representative of a Class of Ligands Heretofore Much Neglected

Methyldiphenylphosphonium cyclopentadienylide, C5H4PMePh2 (II), has been synthesized and characterized spectroscopically and crystallographically and has been found to exhibit properties consistent with the zwitterionic structure IIb. The new group 6 coordination complexes (η5-C5H4PMePh2)M(CO)3 have been synthesized via substitution reactions of II with M(CO)6 (M = Cr, Mo) or W(CO)3(MeCN)3. Comparisons of ν(CO) values of these complexes with those of the isoelectronic (η6-C6H6)M(CO)3 and [(η5-C5H5)M(CO)3]- suggest that the electron-donating ability of the ylide is less than that of the cyclopentadienyl anion but much greater than that of benzene. Thermal and photochemical substitutions of the CO ligands of (η5-C5H4PMePh2)M(CO)3 (M = Cr, Mo) by equimolar amounts of PMe3 and PPh3 were not observed, but the ylide is displaced photochemically from (η5-C5H4PMePh2)Mo(CO)3 by excess PMe3 to form fac-Mo(CO)3(PMe3)3, while (η5-C5H4PMePh2)Mo(CO)3 reacts with I2 to form [(η5-C5H4PMePh2)Mo(CO)3I]I. The crystal structures of the free ylide and all four of its coordination complexes show that in each case one of the ylide phenyl rings not only eclipses the C5H4 ring but also is oriented toward it in an edge-on fashion. The intramolecular edge−face orientations involve interactions of an aromatic hydrogen atom with the C5H4 aromatic π systems and are rationalized in terms of electrostatic attractive forces between the slightly positive phenyl hydrogen atom and the negatively charged C5H4 ring. The electronic structures of II and of (η5-C5H4PMePh2)Cr(CO)3 have been investigated using ab initio methodologies; it is found that the near-degenerate HOMO and HOMO-1 orbitals of the free ylide exhibit symmetries very similar to those of the corresponding, doubly degenerate HOMO of the cyclopentadienyl anion (E1 symmetry) and that a lower energy, almost fully symmetric orbital corresponds to the fully symmetric bonding A1 MO of the cyclopentadienyl anion. In none of these three orbitals does there appear to be significant π involvement of an orbital on the phosphorus atom, consistent with the low P−C bond order implicit in the zwitterionic structure IIb. The primary ylide−metal interactions in (η5-C5H4PMePh2)Cr(CO)3 involve donation of the HOMO and HOMO-1 orbitals into the dxz and dyz orbitals of the chromium, while the calculated ylide−Cr(CO)3 bond dissociation energy is about 30% higher than the analogous ring−metal bond dissociation energy of (η6-C6H6)Cr(CO)3.

The preparation and structural elucidation of uranium (VI) complexes and salts of the phosphorus ylides Ph 3PCHCOPh, Ph 3PC(COMe)(COPh) and Ph 3PCHCOOCH 2CH 3

The reaction in methanol of the phosphorus ylides Ph 3PCHCOPh, benzoylmethylenetriphenylphosphorane (BPPY), and Ph 3PC(COMe)(COPh), α-acetyl-α-benzoylmethylenetriphenylphosphorane (ABPPY) with UO 2(NO 3) 2 · 6H 2O at 273 K leads to the formation of O-coordinated bis(ylide)-uranium (VI) complexes of the type [UO 2(ylide) 2(NO 3) 2], whereas the reaction of BPPY and UO 2(NO 3) 2 · 6H 2O under reflux in benzene yields the salt [ H - BPPY ] 2 + [ U 2 O 4 ( NO 3 ) 4 ( OH ) 2 ] 2 - . The reaction of Ph 3PCHCOOCH 2CH 3, carbethoxymethylenetriphenylphosphorane (EPPY) with UO 2(CH 3COO) 2 · 2H 2O produces the salt [H-EPPY] +[UO 2(CH 3COO) 3] −. The structures of the free ylides ABPPY and EPPY are also discussed.

4-Chloro-N-(trimethylammonio)benzamide chloride monohydrate.

The structure of the cation in the ylide hydrochloride [Me(3)NNHC(O)C(6)H(4)-Cl-p]Cl.H(2)O, or C(10)H(14)ClN(2)O(+).Cl(-).H(2)O, is compared with that of the free ylide. Protonation lengthens the N-C(O) bond but shortens the C=O and N-N bonds by approximately 0.03 A and increases the dihedral angle between the phenyl and ylide planes.

Stereoselective Synthesis of Tetrahydropyran‐3‐ones by Rearrangement of Oxonium Ylides Generated from Metal Carbenoids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective synthesis of tetrahydropyran-3-ones by rearrangement of oxonium ylides generated from metal carbenoids

The synthesis of tetrahydropyran-3-ones by copper-catalysed reactions of diazo ketone tethered allylic ethers has been explored. Product distribution can be explained by the intermediacy of a free ylide or direct rearrangement of a metal-bound ylide equivalent.

金属カルベン中間体を経るイリド形成を機軸とする不斉触媒反応

The tandem ylide generation and rearrangement or cycloaddition sequence triggered by copper (I) or dirhodium (II) complex-catalyzed decomposition of α-diazo carbonyl compounds has recently found numerous applications in organic synthesis. While exceptionally high levels of enantiocontrol in C-H insertions and cyclopropanations have already been achieved using welldesigned chiral metal catalysts, the development of an enantioselective version of this process has not been so straightforward as it was believed until several years ago that the reactions of ylides would occur from the free ylide detached from the catalyst rather than from the metal complexassociated ylide. The rapid recent developments in this area reviewed here have shown that high levels of asymmetric induction are possible with rearrangements of oxonium ylides and with 1, 3-dipolar cycloadditions of carbonyl ylides where the chiral metal catalyst can remain bound to the ylides in the product-forming step.