Chiral Diphosphine Research Articles

Enantioselective synthesis of 2-methyl indolines by palladium catalysed asymmetric C(sp3)–H activation/cyclisation

The first example of the enantioselective methyl C-H activation by an intramolecular ArPdX species and subsequent cyclisation was developed. Palladium catalysts using commercially available chiral diphosphines yield good ee's (up to 93% ee) in the synthesis of 2-methyl indolines from 2-halo N-isopropyl anilides. This approach was also employed for the synthesis of enantioenriched cyclohexyl fused indolines with moderate enantioselectivities.

Self-assembled polymers of silver(i) with a chiral diphosphine ligand

Silver(I) salts, AgX, form self-assembled polymers with the chiral diphosphine ligand R,R-trans-C(6)H(10)(NHCO-2-C(6)H(4)PPh(2))(2), 1, of formula {Ag(2)X(2)(μ-1)}(n) and ring-opening polymerization of the trans chelate complex [Ag(1)]X has given the helical polymer [{Ag(μ-1)}(n)]X(n), when X = CF(3)SO(3).

Asymmetric Synthesis of Axially Chiral Biaryl Diphosphine Ligands by Rhodium-Catalyzed Enantioselective Intramolecular Double [2 + 2 + 2] Cycloaddition

The concise synthesis of axially chiral biaryl diphosphine ligands by the rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition of hexayne diphosphine oxides has been achieved. These new chiral diphosphine ligands could be employed as a ligand for the rhodium-catalyzed asymmetric catalyses.

ChemInform Abstract: Cobalt‐Catalyzed Asymmetric Hydrovinylation

AbstractReview: 15 refs.

Catalytic Enantioselective Synthesis of 4-Vinyl-2-trichloromethyloxazoline: An Access to Enantioenriched Vinylglycinol Surrogate

Cationic Pd(II) catalysts generated from chiral biphenyl diphosphine complexes or from COP-Cl promote enantioselective cyclization of E- and Z-configured allylic bis-trichloroacetimidates to highly enantioenriched 2-trichloromethyl-4-vinyloxazoline. This represents an exclusive example for olefin amination in high yield and enantioselectivity with trichloroacetimidate as the N-nucleophile by using a cationic palladium(II) complex as a catalyst providing an easy-to-deprotect enantioenriched vinylglycinol derivative.

ChemInform Abstract: Chemo‐ and Stereoselective Iron‐Catalyzed Hydrosilylation of Ketones.

AbstractThe ketones are enantioselectively reduced to the corresponding alcohols employing Fe(OAc)2 and a chiral diphosphine as catalyst, and either diethoxy(methyl)silane or PMHS as reducing agent.

Gold(I)-Catalyzed Asymmetric Synthesis of Planar Chiral Arene Chromium Complexes

Gold(I)-catalyzed asymmetric cyclization of 1,3-dihydroxymethyl-2-alkynylbenzene chromium complexes gave planar chiral isochromene chromium complexes with high enantioselectivity. Enantiomeric excess of the cyclization products was largely affected by a combination of axially chiral diphosphine(AuCl)(2) precatalysts and silver salts. A system of segphos(AuCl)(2) with AgBF(4) resulted in the formation of the corresponding antipode.

Iridium‐Catalyzed Asymmetric Hydrogenation of Quinoline Derivatives with C3*‐TunePhos

AbstractA series of C3*‐TunePhos chiral diphosphine ligands has been successfully applied in the iridium‐catalyzed enantioselective hydrogenation of quinolines, and this methodology provided an efficient access to a variety of optically active tetrahydroquinolines with up to 93% ee. Furthermore, attempts on the asymmetric hydrogenation of quinoline N‐oxide are also discussed.

Probing the stereo‐electronic properties of cationic rhodium complexes bearing chiral diphosphine ligands by 103Rh NMR

(103)Rh NMR represents a powerful tool to assess the global electronic and steric contribution of diphosphine ligands on [Rh(COD)(diphosphine)](+) complexes. In the case of DIOP, BINAP and MeDUPHOS, this approach proved to be more informative than classical CO-stretching frequency measurements. After validation, this method has been extended to a set of seven diphosphines. (103)Rh NMR measurements on [Rh(COD)(diphosphine)]PF(6) lead to the following order of donor properties: dppe > MeBPE > MeDUPHOS > dppb > DIOP > BINAP > Tol-BINAP. This trend has been validated by DFT in the case of DIOP, BINAP and MeDUPHOS. In conjunction, (31)P NMR chemical shift has been shown to reflect the ring constraints of the Rh-diphosphine scaffold. This contribution is a step towards a mechanistic investigation of the catalytic hydrogenation of unsaturated substrates by (103)Rh NMR and DFT.

Cobalt‐Catalyzed Asymmetric Hydrovinylation

Back to the first row: A surprisingly simple protocol involving chiral diphosphine complexes of cobalt(II) salts allows the highly enantioselective hydrovinylation of 1,3-dienes in extremely high selectivities and yields.

Isomerization of the diphosphine ligand 3,4-bis(diphenylphosphino)-5-methoxy-2(5H)-furanone (bmf) at a triosmium cluster and P–C bond cleavage in the unsaturated cluster 1,1-Os 3(CO) 9(bmf): Synthesis and X-ray diffraction structures of the isomeric Os 3(CO) 10(bmf) clusters and HOs 3(CO) 8(μ-C 6H 4)[μ-PhPC [dbnd]C(Ph 2P)CH(OMe)OC(O)

The labile cluster 1,2-Os 3(CO) 10(MeCN) 2 ( 1) reacts with the chiral diphosphine ligand 3,4-bis(diphenylphosphino)-5-methoxy-2(5H)-furanone (bmf) to furnish 1,2-Os 3(CO) 10(bmf) ( 2a) in high yield. Heating cluster 2a over the temperature range 358–383 K under CO leads to isomerization of the bmf ligand and formation of the diphosphine-chelated cluster 1,1-Os 3(CO) 10(bmf) ( 2b) and an equilibrium mixture consisting of 2a and 2b in a 15:85 ratio. Extended thermolysis of an equilibrium mixture of Os 3(CO) 10(bmf) is accompanied by CO loss and ortho-metalation of an aryl ring to afford an inseparable mixture of three diastereomeric hydride clusters HOs 3(CO) 9(C 29H 23O 3P 2) ( 3a– c). Thermolysis of HOs 3(CO) 9(C 29H 23O 3P 2) ( 3a– c) in refluxing toluene leads to P–C bond cleavage and formation of the benzyne-substituted clusters HOs 3(CO) 8(μ-C 6H 4)(μ-C 23H 19O 3P 2) ( 4a,b) as a 4:1 mixture of diastereomers. The unequivocal identity of the major benzyne-substituted cluster has been determined by X-ray diffraction analysis, where the activation of one of the phenyl groups situated α to the furanone carbonyl group in the bmf ligand has been established. The isomerization and activation of the bmf ligand are contrasted with other Os 3(CO) 10(diphosphine) derivatives prepared by our groups.

ChemInform Abstract: Practical Synthesis of (S)-2-(4-Fluorophenyl)-3-methylbutanoic Acid, Key Building Block for the Calcium Antagonist Mibefradil.

Abstract A short, technically feasible route was developed for the synthesis of (S)2-(4-fluorophenyl)-3-methylbutanoic acid (S)- 2 with an overall yield of 80% starting from 4-fluorophenylacetic acid. Asymmetric hydrogenation of the easily accessible unsaturated acid 3 in the presence of ruthenium(II) carboxylato complexes containing chiral atropisomeric diphosphines afforded (S)- 2 in up to 94% ee. The ee of (S)- 2 was upgraded to 98% by crystallization of its sodium salt. The same protocol was also applied to the synthesis of (S)-2-(4-chlorophenyl)-3-methylbutanoic acid.

ChemInform Abstract: Design and Synthesis of Optically Active Trans-Chelating Diphosphine Ligands. Application for Catalytic Asymmetric Synthesis

New chiral diphosphines 2,2“-bis[1-(disubstituted phosphino)ethyl]-1,1”-biferrocene, having both central and planar elements of chirality, was designed for a trans-chelating chiral diphosphine ligand (TRAP) for transition metals and synthesized form optically active N,N-dimethyl-1-ferrocenyl ethylamine. Some transition-metal complexes with the TRAP ligands were prepared and utilized as a chiral catalyst for asymmetric synthetic reactions.

ChemInform Abstract: Catalytic Asymmetric Hydrogenation of 1-Aza-2-cycloalkene-2-carboxylates Catalyzed by a trans-Chelating Chiral Diphosphine PhTRAP-Rhodium Complex.

Abstract A rhodium complex coordinated with a trans -chelating chiral diphosphine (S,S)-(R,R) -PhTRAP was an effective catalyst for asymmetric hydrogenation of N -acyl-1-aza-2-cycloalkene-2-carboxylates, which gave the corresponding protected cyclic α-amino acids with 73–97% ee.

Palladium(II) Complexes of C2‐Bridged Chiral Diphosphines: Application to Enantioselective Carbonyl‐Ene Reactions

Abstract(11bR,11′bR)‐4,4′‐(1,2‐Phenylene)bis[4,5‐dihydro‐3H‐dinaphtho[2,1‐c:1′,2′‐e]phosphepin] [abbreviated as (R)‐BINAPHANE], (3R,3′R,4S,4′S,11bS,11′bS)‐4,4′‐bis(1,1‐dimethylethyl)‐4,4′,5,5′‐tetrahydro‐3,3′‐bi‐3H‐dinaphtho[2,1‐c:1′,2′‐e]phosphepin [(S)‐BINAPINE], (1S,1′S,2R,2′R)‐1,1′‐bis(1,1‐dimethylethyl)‐2,2′‐biphospholane [(S,S,R,R)‐TANGPHOS] and (2R,2′R,5R,5′R)‐1,1′‐(1,2‐phenylene)bis[2,5‐bis(1‐methylethyl)phospholane] [(R,R)‐i‐Pr‐DUPHOS] are C2‐bridged chiral diphosphines that form stable complexes with palladium(II) and platinum(II) containing a five‐membered chelate ring. The Pd(II)‐BINAPHANE catalyst displayed good to excellent enantioselectivities with ee values as high as 99.0% albeit in low yields for the carbonyl‐ene reaction between phenylglyoxal and alkenes. Its Pt(II) counterpart afforded improved yields while retaining satisfactory enantioselectivity. For the carbonyl‐ene reaction between ethyl trifluoropyruvate and alkenes, the Pd(II)‐BINAPHANE catalyst afforded both good yields and extremely high enantioselectivities with ees as high as 99.6%. A comparative study on the Pd(II) catalysts of the four C2‐bridged chiral diphosphines revealed that Pd(II)‐BINAPHANE afforded the best enantioselectivity. The ee values derived from Pd(II)‐BINAPHANE are much higher than those derived from the other three Pd(II) catalysts. A comparison of the catalyst structures shows that the Pd(II)‐BINAPHANE catalyst is the only one that has two bulky (R)‐binaphthyl groups close to the reaction site. Hence it creates a deep chiral space that can efficiently control the reaction behavior in the carbonyl‐ene reactions resulting in excellent enantioselectivity.

Chiral diphosphines and diphosphinites derived from 2,2-biphosphole: Stereodynamic ligands for asymmetric catalysis

Abstract In this account, the recent advances on chiral stereochemically dynamic 2,2’-biphosphole ligands for applications in asymmetric catalysis are reported. In the first part, the synthesis of stereodynamic diphosphines and diphosphinites derived from 2,2’-biphosphole is presented. The second part describes the kinetic dynamic resolution to give diastereo- and enantiopure complexes. Applications in asymmetric allylic substitution, hydroformylation and hydrogenation are presented in the last part.

Bis((2-methoxymethyl)pyrrolidine)phosphine as effective chiral auxiliary for the stereoselective synthesis of chiral ferrocenyl diphosphines

The bis(2-methoxymethyl pyrrolidine)phosphine moiety is shown to be a very effective chiral auxiliary for the ortho- and diastereoselective lithiation of ferrocene, thereby allowing the highly selective attachment of various electrophiles to the cyclopentadienyl ring of ferrocene. The potential of the methodology is demonstrated by the synthesis of Kephos, a new family of ferrocenyl diphosphines and of OH-Taniaphos derivatives.

Electrophilic Trifluoromethylation of Primary Phosphines: Synthesis of a P-Bis(trifluoromethyl) Derivative of BINAP

The new chiral diphosphine ligand (R)-(2′-(bis(trifluoromethyl)phosphino)-1,1′-binaphthyl-2-yl)diphenylphosphine (2), which contains a bis(trifluoromethyl)phosphine group, was prepared in five steps from (R)-BINOL (5). As a key transformation, the unprecedented electrophilic double trifluoromethylation of the primary phosphine 8 was achieved using the hypervalent iodine trifluoromethylation reagent 1-trifluoromethyl-1,2-benziodoxol-3-(1H)-one (1), derived from o-iodobenzoic acid. The palladium dichloride complex of this ligand (10) shows the P(CF3)2 group with a high degree of pyramidalization at the P atom and a relatively short Pd−P bond (2.2230(4) Å), both features being indicative of the strong s-character of the phosphorus lone pair.

ChemInform Abstract: Axial Chirality Control by 2,4‐Pentanediol for the Alternative Synthesis of C3*‐TunePhos Chiral Diphosphine Ligands and Their Applications in Highly Enantioselective Ruthenium‐Catalyzed Hydrogenation of β‐Keto Esters.

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Synthesis of C3*-TunePhos Chiral Ligands and Their Application in Hydrogenation

C 2-Symmetric binaphthyl- or biphenyl-bridged diphosphine ligands BINAP, MeO-­BIPHEP, SEGPHOS, P-Phos and their analogues are well known as highly efficient chiral ligands for a variety of transition-metal-catalyzed asymmetric transformations. The authors report a diastereoselective synthesis of a series of C3*-TunePhos chiral diphosphine ligands. The synthetic utility of these ligands was explored for the ruthenium-­catalyzed asymmetric hydrogenation of β-keto ­esters and excellent ee values were achieved.