Cyclophosphazene-based multi-site coordination ligands

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The goal of the project was to prepare new catalyst systems, which would perform chemical reactions in an enantioselective manner so as to produce only one of the possible optical isomers of the product molecule. We have investigated the use of lanthanide metals bearing both diolate and Schiff-base ligands as catalysts for the enantioselective reduction of prochiral ketones to secondary alcohols. The ligands were prepared from cheap, readily available starting materials, and their synthesis was performed in a “modular” manner such that tailoring of specific groups within the ligand could be carried out without repeating the entire synthetic procedure. In addition. Tve have developed a new ligand system for Group IV and lanthanide-based olefin polymerization catalysts. The ligand system is easily prepared from readily available starting materials and offers the opportunity to rapidly prepare a wide range of closely related ligands that differ only in their substitution patterns at an aromatic ring. When attached to a metal center, the ligand system has the potential to carry out polymerization reactions in a stereocontrolled manner. Background and Research Objectives The modern pharmaceuticals and fine chemical industries are heavily reliant upon the ability to produce biologically active organic compounds (antibiotics, flavorings, pesticides, anesthetics, sweeteners etc.) of high optical (enantiomeric) purity. At one time, many drugs were supplied as racemic mixtures (containing equal quantities of both enantiomers) with the assumption that one enantiomer would perform the desired therapeutic function while the other would be harmlessly excreted. However, the catastrophic effects of the drug Thalidomide, sold in the 1960s as a racemic mixture, were traced to the supposedly benign (S)-isomer of the drug and since then the enantiomeric purity of many pharmaceutical products has been controlled by federal regulations. accomplished in one of two ways: (a) preparation of a racemic mixture followed by The preparation of a single enantiomer of a chiral organic molecule can generally be mechanical or chemical separation of the two enantiomers or (b) enantioselective synthesis in which only the target isomer is produced. The majority of pharmaceuticals are currently produced using the first of these methods, with the enantiomers often being separated by *Principal Investigator, email: jwatkin@lanl.gov

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Asymmetric catalysis in organic synthesis

Reaction of RCH2N(CH2CH2NHSO2Tol)2 (R = 2-NC5H4 (8, H2Lpy) or MeOCH2 (9, H2LOMe)) with Ti(NMe2)4 at room temperature afforded Ti(Lpy)(NMe2)2 (10) or Ti(LOMe)(NMe2)2 (11), respectively, which contain tetradentate bis(sulfonamide)amine ligands. The corresponding reactions with Ti(OiPr)4 or Zr(OiPr)4·HOiPr required more forcing conditions to form the homologous bis(isopropoxide) analogues, M(LR)(OiPr)2 (M = Ti, R = py (12) or OMe (14); M = Zr, R = py (13) or OMe (15)). Reaction of Ti(NMe2)2(OiPr)2 with H2LR formed 12 or 14 under milder conditions. The X-ray structures of 10−15 have been determined revealing Cs symmetric, 6-coordinate complexes except for 13 which is 7-coordinate with one κ2(N,O) bound sulfonamide donor. Compounds 10− 15 are all catalysts for the ring-opening polymerization (ROP) of e-caprolactone, with the isopropoxide compounds being the fastest and best controlled, especially in the case of zirconium. In addition, Zr(LOMe)(OiPr) 2 (15) was an efficient catalyst for the well-controlled ROP ...

Sulfonamide-Supported Group 4 Catalysts for the Ring-Opening Polymerization of ε-Caprolactone and rac-Lactide

Î·1-Indenyl derivatives of transition metal and main group elements: synthesis, characterization and molecular dynamics

Application of hybrid ONIOM, QM/QM and QM/MM theoretical methods to study catalytic reactions involving molecular, nano-sized and supported transition metal catalysts are reviewed. The best strategies for theoretical studies of full size chemical systems (without simplifying structural approximations and avoiding the usage of unreliable small size models) are highlighted. The influence of the steric and electronic effects of ligands, reactants and molecular environment on reactivity of transition metal catalysts is discussed.

Real size of ligands, reactants and catalysts: Studies of structure, reactivity and selectivity by ONIOM and other hybrid computational approaches ☆

Ruthenium complexes that incorporate a chiro-inositol derived diphosphinite ligand as catalysts for asymmetric hydrogenation reactions

Dichlorophenylphosphine reacts with indenyllithium in tetrahydrofuran followed by sulfur to yield di(1H-inden-3-yl)phenylphosphine sulfide (2). The same reaction sequence in toluene yields di(1H-inden-1-yl)phenylphosphine sulfide (3) as a mixture of (±) and two meso isomers. The structures of (2) and (±)-(3) were determined [(2): C24H19PS, Mr 370·42, monoclinic, P21/n, a 14·329(4), b 7·0936(10), c 19·405(5) A, β 99·18(2)°, Z 4, R 0·060 for 2422 observed reflections; (3): C24H19PS, Mr 370·42, monoclinic, P21/n, a 9·521(5), b 16·223(8), c 12·930(6) A, β 107·41(3)°, Z 4, R 0·105 for 923 reflections].

Synthesis and structure of two isomers of di(indenyl) phenylphosphine sulfide

Treatment of [RuCl2(COD)] n with the chiral diphosphinite ligand (1S,2S)-1,2-trans-bis-(O-diphenylphosphino)cyclohexane [(1S,2S)-14] and triethylamine gives the bis(diphosphinite) complex RuHCl[(1S,2S)-14]2 (15) in good yield. If (rac)-1,2-trans-bis-(O-diphenylphosphino)cyclohexane [(rac)-14] is used in place of (1S,2S)-14 in this reaction, a racemic mixture of RuHCl[(1S,2S)-14]2 and RuHCl[(1R,2R)-14]2 [(rac)-16] is formed. The X-ray crystal structure of (rac)-16·(2.5CH2Cl2) has been determined. Treatment of (rac)-16 with hydrogen in iso-propanol leads to the formation of a racemic mixture of RuH2[(1S,2S)-14]2 and RuH2[(1R,2R)-14]2 [(rac)-17]. The structure of (rac)-17 was confirmed by the X-ray analysis of a racemic crystal. Ruthenium mono(diphosphinite), diamine complexes of the general formula RuCl2(NN)(PP) are formed by the treatment of RuCl2(PPh3)3 with the appropriate diphosphinite (PP) and diamine (NN) ligands. In this way, the following complexes have been synthesized: RuCl2[(+)-DPEN][(1S,2S)-14] ...

Ruthenium complexes of chiral diphosphinite ligands with cyclohexane or chiro -inositol backbones as catalysts for asymmetric hydrogenation reactions

The title compound, [Ti(C15H17NO2S)Cl2], has a Ti atom bound to the N and O atoms of a p-toluene­sulfon­amide ligand, which is tethered by a three-carbon chain to a η5-cyclo­penta­dienyl group. The distorted square-pyramidal geometry is completed by two Cl atoms. The Ti—N bond length of 2.0375 (13) A is longer than that in related compounds, the N atom having asymmetric trigonal–planar geometry. Conformational strain relief is noted when compared with ethyl-tethered compounds.

Dichloro{N-[3-(η5-cyclopentadienyl)-propyl]-4-toluenesulfonamido-κ2N, O}-titanium (IV)

The monophosphinite ligands, 1D-1,2;5,6-di-O-cyclopentylidene-3-O-methyl-4-O-diphenylphosphino-chiro-inositol (D-P1), 1D-1,2;5,6-di-O-isopropylidene-3-O-methyl-4-O-diphenylphosphino-chiro-inositol (D-P2), 1D-1,2;5,6-di-O-cyclohexylidene-3-O-methyl-4-O-diphenylphosphino-chiro-inositol (D-P3), and 1D-1,2;5,6-di-O-cyclopentylidene-3-O-ethyl-4-O-diphenylphosphino-chiro-inositol (D-P4), can be conveniently prepared from the chiral natural products 1D-pinitol or 1D-chiro-inositol. On treatment of toluene solutions of RuCl2(PPh3)3 with two mole equivalents of the ligands D-PY (Y = 1–4) the complexes RuCl2(D-P1)2 (1), RuCl2(D-P2)2 (4), RuCl2(D-P3)2 (5), or RuCl2(D-P4)2 (6), respectively, are formed. Similarly, treatment of OsCl2(PPh3)3 with D-P1 gives OsCl2(D-P1)2 (7). The single crystal X-ray structure determination of 1 reveals that each D-P1 ligand coordinates to ruthenium through phosphorus and the oxygen atom of the methoxyl group. Treatment of 1 with excess LiBr or LiI results in metathesis of the chloride ligands and RuBr2(D-P1)2 (2) or RuI2(D-P1)2 (3), respectively, are formed. Exposure of a solution of 1 to carbon monoxide results in the very rapid formation of RuCl2(CO)2(D-P1)2 (8), thereby demonstrating the ease with which the oxygen donors are displaced from the metal and hence the hemilabile nature of the two bidentate D-P1 ligands in 1. Preliminary studies indicate that 1–7 act as catalysts for the asymmetric hydrogenation reactions of acetophenone and 3-quinuclidinone to give the corresponding alcohols in generally high conversions but low enantiomeric excesses.

Ruthenium and osmium complexes of hemilabile chiral monophosphinite ligands derived from 1D-pinitol or 1D-chiro-inositol as catalysts for asymmetric hydrogenation reactions

Cornelis Lensink

Papers

Ruthenium complexes that incorporate a chiro-inositol derived diphosphinite ligand as catalysts for asymmetric hydrogenation reactions

Synthesis and structure of two isomers of di(indenyl) phenylphosphine sulfide

Ruthenium complexes of chiral diphosphinite ligands with cyclohexane or chiro -inositol backbones as catalysts for asymmetric hydrogenation reactions

Dichloro{N-[3-(η5-cyclopentadienyl)-propyl]-4-toluenesulfonamido-κ2N, O}-titanium (IV)

Ruthenium and osmium complexes of hemilabile chiral monophosphinite ligands derived from 1D-pinitol or 1D-chiro-inositol as catalysts for asymmetric hydrogenation reactions