Jul 08, 2014 in 2012 our group reported the synthesis of a novel class of chiral p,n ligands g elaborated on the ubiquitous binepine scaffold h one of the few examples of chiral monodentate trialkyl phosphine ligand. Asymmetric catalysis using a man made chiral catalyst. Professor xumu zhang, chemfiles volume 5 article 4 professor xumu zhang at penn state has made remarkable advances by creating a toolbox of chiral phosphines which can be used on a variety of substrates, some of which have been historically resistant to facile hydrogenation. Using phosphine aldehydes to generate new metal complexes and the synthesis of chiral nhcamino ligands. Chiral phosphinate esters can serve as the entry point for the chemoenzymatic preparation of pchiral phosphines and phosphine oxides. Chiral allenecontaining phosphines in asymmetric catalysis feng cai, xiaotao pu, xiangbing qi, vincent lynch, akella radha, and joseph m. The new process is demonstrated on a wide range of substrates and leads to products that are wellestablished p chiral catalysts and ligands. The epic ligand survey continues with tertiary phosphines, pr3. Furthermore, an additional benefit in some reductions is.
Chiral monodentate phosphine ligands for the enantioselective. Design and synthesis of phosphine coupling reactions by. The chiral phosphines in scheme 14 produced low to moderate yields of pyrrolines with minimal asymmetric induction. Enantioselective cucatalyzed arylation of secondary. The synthesis and design of new phosphines is a continuing area of interest. School of physical and mathematical sciences a thesis submitted to the nanyang technological university in fulfillment of the requirement for the degree of. Chiral phosphines play significant roles in asymmetric catalysis. By utilizing naturally occurring amino acid lhydroxyproline as the starting material, prof.
Notice how the phosphites have smaller cone angles than their corresponding phosphines because the oxygen atoms act as spacers. Supportingsupporting information information for catalytic enantioselective synthesis of quaternary 3,3. Chiral phosphines that possess a stereogenic phosphorous center, while useful, have been challenging to prepare and difficult to handle owing to their susceptibility to aerobic oxidation. Preparation of phosphines through cp bond formation. They were synthesized with excellent enantioselectivity via asymmetric ortholithiation using secbutyllithium and sparteine.
Synthesis and resolution of a new pchiral hydroxy phosphine. The literature describing their synthetic and coordination chemistry, as well as their metalmediated applications in the field of catalysis, is extremely rich and varied. Tiglic acid, 2methylbutyric acid in pure sform as well as a racemic mixture, and smethyl mandelate were purchased from sigmaaldrich. Indolyloxindoles by combination of rh ii complex and chiral phosphines dianfeng chen,a chenlong zhang,a yue hu,a zhiyong hana and liuzhu gong a,b a hefei national laboratory for physical sciences at microscale and department of chemistry, university of. Synthesis using biocatalysts enzymes, cell cultures and antibody 6 4. Deboranation of the air stable borane adduct s4 to obtain 5, was achieved by treatment with nmethylpyrroli dine. Synthesis of new chiral phosphine ligands and their. Dinuclear pincerpalladiumii complexes and their use as. An axially chiral phosphine ligand based on restricted. Synthesis and applications of pchirogenic and axially chiral p,n phosphines as ligands and organocatalysts. Bidentante chiral phosphines were obtained from commercial sources including aldrich, strem, solvias, takasago, and chiral quest. Phosphorus nmr is a technique that just works thanks, nature.
State key laboratory for oxo synthesis and selective oxidation, lanzhou institute of chemical. Herein, we present a direct pdxiaophoscatalyzed crosscoupling reaction of easily accessible secondary phosphine oxides and aryl bromides, which provides rapid access to p chiral phosphine oxides. The bonding in phosphine ligands, like that of carbonyls can be thought of as having two important components. Thus, protection of the phosphorus atom during the ligand synthesis is a common practice. Synthesis of chiral p,nligands and their applications in asymmetric. The chiral organic ligand is an essential part of these compact molecular catalysts in differentiating enantiotopic atoms, groups, and faces of a variety of achiral and some enantiomeric molecules. Only a minor part of the chiral phosphines are chiral at the phosphorus atom pstereogenic. Contact your local sigmaaldrich office see back cover, by chiral ligands, chiralquest phosphines, chiral phosphines, chiral diols, chiral amines, chiral pyrrolidines and hkr epoxides abstract. Asymmetric synthesis of chiral phosphines and arsines promoted by organometallic complexes liu fengli b. Nucleophilic phosphine catalysis often involves the formation of lewis adducts, namely phosphonium dienolate zwitterions, as reaction intermediates 1,3,6,17. Enantioselective synthesis of pchiral tertiary phosphine. Ready, department of biochemistry, university of texas southwestern medical center, 5323 harry hines. Synthesis from a chiral pool and synthesis using a chiral auxiliary 5 3.
University of groningen application of monodentate secondary. The reaction proceeds efficiently with a wide array of. The synthesis of novel 3 and 17diphenylphosphinoandrostane derivatives via homogeneous catalytic pc coupling is described. Oh oh tf 2o, pyridine dcm,0ocrt 10% pdoac,15% dppb h py 2iea rbr or ri, k2co3 acetone, reflux hsicl3, tea toluene,110 oc l2 r me l3 r ipr l4 r bn l5 r ch21naph l6 r ch22naph 2. End use markets pharmaceuticals, and agrochemicals. We demonstrate that allenes, chiral 1,2dienes, appended with basic functionality can serve as ligands for transition metals.
Enantioselective synthesis of chiral phosphines 10 with ephedrine as a chiral auxiliary. The products were characterized by 1h and 31p nmr measurements. A new family of chiral phosphines based on planarchiral 1,ndioxanparacyclophane scaffold was created. Supporting by combination of rhii complex and chiral phosphines. In designing new phosphines there are a number of design features that need be considered. Solution and solidstate structural analysis reveals that one olefin of the allene can. Chiral phosphines are interesting ligands for the preparation of transition metal complex catalysts for asymmetric synthesis 5,6. Fe h pp 2 h pp 2 oh fe h pp 2 h pp 2 e om oc fe h pp 2 me co o h pp 2 fe h pp 2 h pp 2 n fe h pp 2 n h pp 2 fe pph 2 n squinaps12 diphenylphosphino 1 naphthylisoquinoline c 31h 22 np fw439.
Chiral tetrahydroquinolines, chiral pyridines, chiral nitrogen heterocycles, krohnke annulation introduction during our study on the synthesis of chiral p,nligands with pyridine ndonors,1,2 we needed a set of chiral substituted 2methylpyridines bearing a stereogenic centre on the carbon bonded to the 6position of the heterocycle. Supporting by combination of rhii complex and chiral. C hiral phosphines are essential ligands for enantioselective metal. The primary component is sigma donation of the phosphine lone pair. Acros organics, alfa aesar or aldrich and used as received. These chiral ligands are typically divided into three design archetypes. These intermediates are formed through nucleophilic attack of the phosphine catalysts at electronpoor nuclei normally carbon atoms and then proceed through several steps to form new. Pdf phosphinecatalyzed asymmetric intermolecular cross. Kwon chiral phosphines chiral catalysts, ligands, and. In many cases, the syntheses of appropriate phosphines are complicated by their sensitivity to air exposure.
Ready, department of biochemistry, university of texas southwestern medical center, 5323 harry hines boulevard, dallas, texas 753989038, united states. We have prepared a range of monodentate spos 17 by reaction of r2mgbr with r1pcl 2 reversed addition followed by hydrolysis scheme 2. Sampling and analytical methods phosphine in workplace. Phosphine is a colorless, flammable, and explosive gas at ambient temperature that has the odor of garlic or decaying fish. Catalytic asymmetric staudingerazawittig reaction for the synthesis of. Interconversions between p chiral molecules horner, tet.
Synthesis and applications of pchirogenic and axially. Phosphine ligands have the general formula pr 3 where r alkyl, aryl, h, halide etc. They are a subset of chiral phosphines, a broader class of compounds where the stereogenic center can reside at sites other than phosphorus. This general trend is true for all other substrates listed in table 2 entries 17 with only one exception the result in. Synthesis of chiral hydroxyl phospholanes from dmannitol and. Chiral phosphines are interesting ligands for the preparation of transition metal complex catalysts for asymmetric synthesis. Chiral phosphinate esters can serve as the entry point for the chemoenzymatic preparation of p chiral phosphines and phosphine oxides. Nov 21, 2005 the chiral phosphines were enantiomerically pure samples that were purchased from strem chemicals duphos and diop and from larodan fine chemicals ab nmdpp and dipamp. Pchirality exploits the high barrier for inversion of phosphines, which ensures that enantiomers of prrr do not racemize readily.
The synthesis of the functionalized p chiral phosphine bzphpchohphand its resolution by palladium metallacycles is reported. Andersson department of chemical and biological engineering organic chemistry chalmers university of technology abstract this thesis deals with the enantioselective synthesis of chiral mixed phosphorousnitrogen. Chiral quest phosphine ligands one of the most efficient methods for constructing chiral compounds is asymmetric hydrogenation. Synthesis of chiral 2methyl5,6,7,8tetrahydroquinolines. The asymmetric catalytic synthesis of chiral phosphines has only recently emerged and is under full development. Ohyun kwons laboratory prepared twelve different p chiral. Novel synthesis of chiral 1,2aminophosphine ligands and their. Synthesis and applications of pchirogenic and axially chiral. The ability of the carbon bead to capture phosphine may be dependent on the pitch used to produce the bead and should be tested on a lotbylot basis. Methyl and phenyl substituents were attached directly to the phosphorus center, while the.
The chiral phosphines were enantiomerically pure samples that were purchased from strem chemicals duphos and diop and from larodan fine chemicals ab nmdpp and dipamp. Tiglic acid, 2methylbutyric acid in pure sform as well as a racemic mixture, and smethyl mandelate were purchased from sigma aldrich. Sigmaaldrich is pleased to announce an agreement with chiralquest to distribute research quantities of a series of zhangs chiral phosphines for catalytic. A new family of chiral phosphines based on planar chiral 1,ndioxanparacyclophane scaffold was created. For palladium catalyzed coupling reactions, sterically demanding and electron releasing ligands are generally most effective in promoting the reaction. Pchiral phosphines are organophosphorus compounds of the formula prr. Described is the preparation, resolution, and absolute configuration of a new axially chiral monodentate phosphine ligand. Chiralquest phosphine ligands aldrich chemfiles 2006, 6. Triaryl phosphines p rofessor barry trost and coworkers at stanford university have recently reported progress in the area of enantioselective allylic substitutions.
Furthermore, because the energy barrier to umbrella flipping of phosphines is quite high, chiralatphosphorus ligands can be isolated in enantioenriched form and introduced to metal centers, bringing asymmetry just about as close to the metal as it can get in chiral complexes. The synthesis of the functionalized pchiral phosphine bzphpchohphand its resolution by palladium metallacycles is reported. Phosphines are most notable for their remarkable electronic and steric tunability and their innocencethey tend to avoid participating directly in organometallic reactions, but have the ability to profoundly modulate the electronic properties of the metal center to which theyre bound. Synthesis of chiral hydroxyl phospholanes from dmannitol and their use in asymmetric catalytic reactions wenge li, zhaoguo zhang, dengming xiao, and xumu zhang. Organophosphines are important in catalysts where they complex to various metal ions. Working with hazardous chemicals organic syntheses. Like nr 3, phosphines have a lone pair on the central atom that can be donated to a metal. In chemistry, a molecule or ion is called chiral k a. Chiral ferrocenyl phosphino ligands are certainly one of the most developed and successful classes of chiral ligands used in asymmetric catalysis.
Synthesis of chiral hydroxyl phospholanes from dmannitol and their use in asymmetric catalytic reactions wenge li, zhaoguo zhang, dengming xiao, and xumu zhang department of chemistry, the pennsylvania state university, university park, pennsylvania 16802 received january 18, 2000. Closely related are phosphite ligands which have the general formula por 3. Preparation of phosphines through c p bond formation. Chiral phosphine oxide binapo as a catalyst for enantioselective allylation of aldehydes with allyltrichlorosilanes. Both phosphines and phosphites are neutral two electron donors that bind to transition metals through their lone pairs. Finally, the ability of the new axially chiral phosphine ligand is demonstrated in a pd. Pdf chiral multifunctional thioureaphosphine catalyzed. Asymmetric synthesis of chiral phosphines and arsines.
Contact your local sigma aldrich office see back cover, by chiral ligands, chiralquest phosphines, chiral phosphines, chiral diols, chiral amines, chiral pyrrolidines and hkr epoxides abstract. Certain lots or grades of carbon bead after treatment have shown losses of up to 50% when sampling phosphine. Chiral allenecontaining phosphines in asymmetric catalysis. Among this variety of methods, asymmetric catalysis has proved to be an ideal method.
Catalytic asymmetric hydrogenations are among the most widely used industrial catalytic processes, due to their high turnover rates, efficiency and atom economy, and inexpensive material costs. Professor xumu zhang at penn state has made remarkable advances by creating a toolbox of chiral phosphines which can be used on a variety of substrates, some of which have been historically resistant to hydrogenation. Precursor for diphenylphosphino containing chiral ligands. The cyclopalladated compound containing the primary amine 11naphthylethylamine has been shown to be a better resolving agent for this phosphine than the corresponding metallacycle containing the tertiary amine n,ndimethyl11naphthylethylamine. Jan 20, 2012 the epic ligand survey continues with tertiary phosphines, pr3. Phosphine is used in semiconductor and plastics industries, in the production of a flame retardant, and as a pesticide. University of groningen application of monodentate. Sep 04, 2014 in this context, inspired by polyfunctional chiral smallmolecule catalysts, particularly amino acid and thioureabased systems 32, multifunctional chiral phosphines were constructed by installing a nucleophilic phosphine and a hydrogen bonding moiety on a molecular chiral backbone.
Only a minor part of the chiral phosphines are chiral at the phosphorus atom pstereogenic 79. The development of transitionmetalcatalyzed methods for the synthesis of p chiral phosphine derivatives poses a considerable challenge. We describe an allenecontaining bisphosphine that, when coordinated to rhi, promotes the asymmetric addition of arylboronic acids to. Synthesis of chiral hydroxyl phospholanes from dmannitol. Safer routes to industriallysignificant chiral catalysts bebhinn tullypenon, james t. Small amounts occur naturally from the break down of organic matter. According to the nmr investigation of the ptcl2p2type complexes, the steroidal phosphines are transcoordinated with respect to the ptcentre exclusively. Phosphineborane complexes are regarded as a convenient alternative to free phosphines 2124. With a palladium source, a chiral pocket forms about the metal center, leading to. Interconversions between pchiral molecules horner, tet. Using phosphine aldehydes to generate new transition metal. Enantioselective synthesis of planarchiral phosphines with 1. Welldesigned chiral catalysts rival natural enzymes in creating chiral environments for stereoselective synthesis. Enantioselective synthesis of planarchiral phosphines.
In collaboration with professor ohyun kwon, aldrich chemistry now offers a collection of rigid, chiral 2. A chiral amidephosphine bifunctional catalyst was developed and successfully applied to the asymmetric intermolecular crossvinylogous rauhutcurrier of alkyl vinyl ketones with paraquinone. Enantioselective synthesis of p chiral tertiary phosphine oxides with an ethynyl group via cuicatalyzed azidealkyne cycloaddition renyi zhu,a long chen,a xiaosi hu,a feng zhou ab and jian zhou abc we report the highly enantioselective synthesis of p chiral tertiary phosphine oxides featuring an ethynyl. Phosphines are also a group of organophosphorus compounds with the formula r 3 p r organic derivative. Pstereogenic compounds brandon rosen 29 march 2014.
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