Chiral Phospholane Research Articles

Organocatalytic Stereoisomerization versus Alkene Isomerization: Catalytic Asymmetric Synthesis of 1-Hydroxy-trans-2,5-diphenylphospholane 1-Oxide

The potential for an organocatalytic asymmetric stereoisomerization or alkene isomerization as atom-economic reaction with minimal structural change was investigated. The McCormack cycloaddition of 1,4-diarylbuta-1,3-dienes with (dialkylamino)dichlorophosphane and aluminum trichloride gives <i>meso</i>-2,5-diaryl-1-(dialkylamino)-1-oxo-2,5-dihydro-1<i>H</i>-phospholes, which were identified as suitable substrates for asymmetric isomerization to (1<i>R</i>,5<i>R</i>)-2,5-diaryl-1-(dialkylamino)-1-oxo-4,5-dihydro-1<i>H</i>-phospholes in the presence of bifunctional organocatalysts (cinchona alkaloids, Takemoto catalyst) in up to 91% ee and quantitative yield. The substrate range and the mechanism of the catalysis were studied. The reaction involves proton abstraction by the base, but a primary deuterium KIE is absent. Enriched (1<i>R</i>,5<i>R</i>)-1-(diethylamino)-1-oxo-2,5-diphenyl-4,5-dihydro-1<i>H</i>-phosphole was hydrolyzed to (5<i>R</i>)-1-hydroxy-1-oxo-2,5-diphenyl-4,5-dihydro-1<i>H</i>-phosphole, which was hydrogenated diastereoselectively under dissolving metal conditions to give (2<i>R</i>,5<i>R</i>)-1-hydroxy-1-oxo-2,5-diphenylphospholane (Fiaud’s acid) in preference to <i>meso</i>-1-hydroxy-1-oxo-2,5-diphenylphospholane. An asymmetric catalytic total synthesis of Fiaud’s acid, which is a building block for chiral phospholane synthesis, has been realized in five steps from thiophene, using nickel-catalyzed Wenkert arylation, McCormack cycloaddition, asymmetric dihydro-1<i>H</i>-phosphole isomerization, hydrolysis, and diastereo­selective hydrogenation.

Synthesis of Binol-based diphosphinites bearing chiral phospholane units and their application in asymmetric catalysis

New diphosphinite ligands based on atropoisomeric diol backbones and (R,R)-2,5-dimethylphospholane moieties have been prepared and fully characterised. For each ligand structure, both diastereomers have been synthesised. These ligands are available through a straightforward procedure in good yields. The solid state structures of two diastereomeric ligands are reported. These ligands have been applied to Rh-catalysed asymmetric hydrogenations and hydroformylations of CC bonds as well as in Ir-catalysed asymmetric hydrogenations of CN bonds. Turnover frequencies in the range of 10,000h−1 and enantioselectivities of up to 98% ee have been achieved. The different chirality elements within the ligands led to marked cooperative effect in catalysis. Interestingly, there is no general privileged diastereomeric structure but rather a matched diastereomer for each application.

Probing the Importance of the Hemilabile Site of Bis(phosphine) Monoxide Ligands in the Copper-Catalyzed Addition of Diethylzinc toN-Phosphinoylimines: Discovery of New Effective Chiral Ligands

The hemilabile ligand Me-DuPHOS(O) 2 has proven to be a successful ligand for the copper-catalyzed addition of diethylzinc to N-phosphinoylimines. The corresponding alpha-chiral amines were obtained in high yields (80-98%) and enantiomeric ratios (19.0:1 to 99.0:1 er). Furthermore, this Cu* 2 catalytic system has been shown to be effective in the addition of diethylzinc to nitroalkenes and in the reduction of beta,beta-disubstituted vinyl phenyl sulfones. This paper describes a general structure/selectivity study in which the three ligand subunits (chiral phospholane-linker-labile coordinating group (Z)) are systematically modified and tested in the copper-catalyzed addition of diethylzinc to the N-phosphinoylimine 1 derived from benzaldehyde. This study led to the discovery of a new class of effective chiral ligands that combine a chiral phospholane unit and an achiral phosphine oxide.

Enantioselective Pd-catalyzed allylic amination with self-assembling and non-assembling monodentate phosphine ligands

New chiral phospholanes were prepared by coupling of bromo-substituted heterocycles with the enantiopure, building block (2 R,5 R)-2,5-dimethyl-1-chlorophospholane. Some of the new phosphine ligands have the potential for self-assembling via hydrogen bondings in a metal complex. By application of these and related ligands in the palladium catalyzed allylic amination reaction, high enantioselectivities (up to 99%) were achieved. The influence of the construction of the cyclic phosphine ligands on the enantioselectivity is analyzed.

Enantioselective Hydrogenation with Self‐Assembling Rhodium Phosphane Catalysts: Influence of Ligand Structure and Solvent

Three sets of new and related chiral phospholane and phosphepine ligands have been prepared for Rh-catalyzed enantioselective hydrogenation. The size and substitution pattern of the cyclic monophosphanes were varied. More importantly, the ligands differ in the nature of the heterocyclic group linked to the trivalent phosphorus atom: 2-pyridone or 2-alkoxypyridine. In the corresponding Rh complexes, the pyridone units of two monodentate P ligands can assemble by hydrogen bonding and form chelates. In contrast, synthetic precursors bearing alkoxypyridine appendages are not able to aggregate via intramolecular hydrogen bonds. The nature of self-assembly is dependent on the nature of the P ligand and the solvent used for the hydrogenation (CH2Cl2 vs. MeOH). These features affect the rate of the reaction as well as the enantioselectivity, which varied in the range of 0-99 % ee Complexation studies and DFT calculations were performed to explain these differences.

Syntheses and Applications of 2-Phosphino-2‘-alkoxy-1,1‘-binaphthyl Ligands. Development of a Working Model for Asymmetric Induction in Hydrovinylation Reactions

Among the handful of monophosphine ligands that effect asymmetric hydrovinylation of vinylarenes, 2-diphenylphosphino-2'-methoxy-1,1'-binaphthyl (MOP) is among the most accessible. Addition of a methyl group at the 3'-position of this ligand significantly improves the enantioselectivity of hydrovinylation of prototypical alkenes. Introduction of a chiral phospholane at the C2 position of this scaffolding has no effect on the enantioselectivity. These results are consistent with a model proposed for the asymmetric induction for this exacting reaction.

Enantioselective Synthesis of P-Stereogenic Benzophospholanes via Palladium-Catalyzed Intramolecular Cyclization

Enantioselective or diastereoselective intramolecular cyclization of functionalized secondary phosphines or their borane adducts catalyzed by chiral Pd(diphosphine) complexes gave P-stereogenic benzophospholanes in up to 70% ee. These results provide a new method for the synthesis of chiral phospholanes, which are valuable ligands in asymmetric catalysis. [reaction: see text]

New chiral monodentate phospholane ligands by highly stereoselective hydrophosphination

New chiral phospholanes 6 were prepared in both enantiomeric forms starting from l- and d-tartaric acid. The key step in the synthetic sequence is the double hydrophosphination of unsaturated chiral bis(lactone) 9 by NaPhPH(BH 3). This method was used for the first time in the formation of chiral phospholanes. The structure of phospholane 6a was confirmed by X-ray crystallography. σ-Donor properties of the phospholanes were estimated by measurement of 1 J( 31P– 77Se) coupling constants in the corresponding phosphine selenides. The new phospholanes were tested as ligands in the Rh-catalyzed enantioselective hydrogenation of functionalized standard olefins (65–92% ee).

Recent Developments in Chiral Phospholane Chemistry

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective Synthesis and Catalytic Behavior of Rhodium(II) Compounds with Metalated Chiral Phospholanes as Ligands

The reaction of Rh 2 (O 2 CR) 4 (R = CH 3 , CF 3 ) with the chiral phosphine (2R,5R)-2,5-dimethyl-1-phenylphospholane (1) results in the formation of the mono-metalated compounds Rh 2 (O 2 -CR) 3 [PC*] (PC*H = (2R,5R)-2,5-dimethyl-1-phenylphospholane; R = CH 3 (2), CF 3 (3)) in high yield. The diastereoisomers Rh 2 (O 2 CR) 2 [PC*] 2 ((P)-4 and (M)-6) are formed in a 3:1 ratio by thermal reaction of 2 with phosphine 1. However, the photochemical reaction of 2 with phosphine 1 in the presence of trifluoroacetic acid afforded compounds (P)-5 and (M)-7 in a 1:9 ratio. All these compounds, isolated as solvates with two molecules of RCO 2 H, were tested in the catalytic transformation of a-diazo compounds, with 3 and (M)-7 showing the highest selectivity.

Mono‐ and Dinuclear Rhodium and Iridium Complexes with Chiral Phospholanes as Ligands

AbstractThe dinuclear complexes [RhCl(L)2]2 (1, 2) with L = 1‐isopropyl‐(2S,5S)‐2,5‐dimethylphospholane (Isophos) and (2S,5S)‐2,5‐dimethyl‐1‐phenylphospholane (Phephos), respectively, prepared from [RhCl(C8H14)2]2 and four equivalents of L, react with Lewis bases such as L, CO, ethene and diphenylacetylene by cleavage of the chloride bridges. Mononuclear compounds of the general composition [RhCl(L)3] (3, 4) and trans‐[RhCl(L′)(L)2] (5−9; L′ = CO, C2H4, C2Ph2) were obtained, of which 4 (L = Phephos) and 8 (L′ = C2H4; L = Phephos) are in equilibrium with the precursors. Oxidative addition of H2 to 1 (L = Isophos) and [RhCl(PiPr2Ph)2]2 (10) affords the mononuclear dihydrido complexes [RhH2Cl(L)2] (13) and [RhH2Cl(PiPr2Ph)2] (14), respectively, via the unsymmetrical compounds [RhH2(L)2(μ‐Cl)2Rh(L)2] (11) and [RhH2(PiPr2Ph)2(μ‐Cl)2Rh(PiPr2Ph)2] (12) as intermediates. These intermediates can be isolated by treatment of 13 and 14 with one half equivalent of 1 or 10, respectively. The hydrogenation of the η3‐allyl and η3‐benzyl complexes [(η3‐2‐RC3H4)Rh(L)2] (16−18) and [(η3‐CH2Ph)Rh(L)2] (19, 20), which were prepared from 1 or 2 and the corresponding Grignard reagent, leads to the dinuclear RhIIIRhI products [RhH2(L)2(μ‐H)2Rh(L)2] (21, 22), which are structurally related to the dichloro(dihydrido) derivatives 11 and 12. Compound 21 (L = Isophos) reacts with CO to give trans‐[RhH(CO)(L)2] (23). While treatment of 1 with phenylacetylene yields the vinylidene complex trans‐[RhCl(=C=CHPh)(Isophos)2] (26), via η2‐alkyne and alkynyl(hydrido) intermediates, the reaction of 2 with PhC≡CH affords the labile enyne compound trans‐[RhCl{η2‐(E)‐PhC≡CCH=CHPh}(Phephos)2] (27). Reaction of 27 with CO gives 6 and the free enyne. The carbene complexes trans‐[RhCl(=CPh2)(L)2] (30, 31), obtained from trans‐[RhCl(=CPh2)(SbiPr3)2] (29) and L, react with ethene not by olefin metathesis but by formation of the isomeric olefins Ph2C=CHCH3 (32) and CH2=CHCHPh2 (33) in different ratios. With iridium as the metal center, carbonyl, dihydrido, and dihydrido(carbonyl) compounds with [IrCl(Isophos)2] as the building block have been prepared. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)

Synthesis and Application of Chiral Phospholane Ligands Bearing a Sterically and Electrically Adjustable Moiety.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient enantiodiscrimination of chiral monophosphine oxides and boranes by phosphorus coupled 13C NMR spectroscopy in the presence of chiral ordering agents

The synthesis of new chiral phospholanes via the corresponding oxides or boranes is reported and the analytical potential of 13C-{ 1H} NMR spectroscopy in weakly ordering polypeptide liquid crystalline phases in view to differentiate between enantiomers of these chiral phosphines precursors is explored. In particular results involving organic solutions of poly-γ-benzyl- l-glutamate (PBLG) and poly-ε-carbobenzyloxy- l-lysine (PCBLL) are described. This NMR approach allows determination of the enantiomeric composition, and provides therefore a new efficient alternative to classical methods usually used to analyze this class of compounds. A description of various spectral enantiodifferentiation patterns expected to be observed using 13C-{ 1H} NMR of enantiomers having a spin-1/2 heteroatomic nucleus, embedded in a chiral liquid crystal is presented.

Synthesis and Application of Chiral Phospholane Ligands Bearing a Sterically and Electrically Adjustable Moiety

AbstractA series of C1‐symmetric phosphine‐phospholane ligands, 1‐(disubstituted phosphino)‐2‐(phospholano)benzenes (5), which are called UCAPs, with an achiral phosphino group and a chiral phospholane which can be sterically and electrically adjustable, has been designed and synthesized. In the asymmetric hydrogenation of (Z)‐N‐benzoyl‐1‐phenylpropenamine (3), the stereorecognition abilities of the 5d−e–Rh catalysts which have a bulkier aryl substituent on the achiral phosphorus are superior to that observed with the DuPHOS‐Rh catalyst. The effects of varying substituents on the achiral phosphorus atom are discussed.

Enantioselective synthesis of phospholanes using chiral lithium amide desymmetrisation

The enantioselective deprotonation of 1,2,5-triphenylphospholane oxide with a chiral base, followed by electrophilic quenching, gives a range of chiral products in good yield and in ca. 85% ee. The absolute and relative configuration of two of the products was determined by X-ray crystallography. A number of the chiral phospholane oxides were subjected to further transformations, in particular reduction to give enantiomerically pure phospholanes.

ChemInform Abstract: Synthesis and X‐Ray Structure of Metalated Rhodium(II) Catalysts with a Chiral Phospholane.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis and X-ray Structure of Metalated Rhodium(II) Catalysts with a Chiral Phospholane

Synthesis and X-ray Structure of Metalated Rhodium(II) Catalysts with a Chiral Phospholane

Synthesis and X-ray Structure of Metalated Rhodium(II) Catalysts with a Chiral Phospholane

The reaction of Rh2(O2CR)4 (R = CH3, CF3) with the chiral phosphane (2S,5S)-2,5-dimethyl-1-phenylphospholane (PC*H), results in the formation of two diastereoisomers of Rh2(O2CCR)2(PC*)2, with (P) and (M) configuration. These can easily be isolated by chromatographic methods to obtain enantiomerically pure RhII compounds. Preliminary catalytic studies have shown that they induce moderate asymmetry in the cyclization of 5-aryl-1-diazo-2-pentanones and 1-diazo-5-hexen-2-one. X-ray analysis of the (M) diastereoisomer with formula Rh2(O2CCCH3)2(PC*)2 is reported. The crystallographic parameters are as follows: space group P21212 (orthorhombic) with a = 12.1347(11) A, b = 14.5870(13) A, c = 9.8171(9) A.

ChemInform Abstract: Synthesis of Chiral Hydroxyl Phospholanes from D-Mannitol and Their Use in Asymmetric Catalytic Reactions.

Chiral hydroxyl monophosphane 3 [(2S,3S,4S,5S)-3,4-dihydroxy-2,5-dimethyl-1-phenylphospholane] and bisphospholanes 5a [1,2-bis[(2S,3S,4S,5S)-3,4-dihydroxy-2,5-dimethylphospholanyl]benzene] and 5b [1,2-bis[(2S,3S,4S,5S)-2,5-diethyl-3,4-dihydroxyphospholanyl]benzene] were synthesized from readily available d-mannitol in high yields. Strategies for protection and deprotection of OH-groups in the presence of phosphines have been explored. Rate acceleration in the Baylis−Hillman reaction was observed when a hydroxyl phosphine was used as the catalyst. Rhodium complexes with chiral bisphospholanes are highly enantioselective catalysts for the asymmetric hydrogenation of various kinds of functionalized olefins such as dehydroamino acid derivatives, itaconic acid derivatives, and enamides. An interesting feature of the hydroxyl phospholane system is that hydrogenation of some substrates can be carried out in water with >99% ee and 100% conversion (e.g., itaconic acid).

ChemInform Abstract: Asymmetric Reactions Catalyzed by Chiral Metal Complexes. Part 85. Synthesis of New Atropisomeric Bisphosphine Ligands Bearing Chiral Phospholane and Their Use in Asymmetric Hydrogenation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.