Platinum-catalyzed enantioselective tandem alkylation/arylation of primary phosphines. Asymmetric synthesis of P-stereogenic 1-phosphaacenaphthenes

Enantioselective tandem alkylation/arylation of primary phosphines with 1-bromo-8-chloromethylnaphthalene catalyzed by Pt(DuPhos) complexes gave P-stereogenic 1-phosphaacenaphthenes (AcePhos) in up to 74% ee. Diastereoselective formation of four P-C bonds in one pot with bis(primary) phosphines gave C2-symmetric diphosphines, including the o-phenylene derivative DuAcePhos, for which the rac isomer was formed with high enantioselectivity. These reactions, which appear to proceed via an unusual metal-mediated nucleophilic aromatic substitution pathway, yield a new class of heterocycles with potential applications in asymmetric catalysis.     

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]     

Asymmetric synthesis of all-carbon quaternary spirocycles via a catalytic enantioselective allylic alkylation strategy

Rapid access to enantioenriched spirocycles possessing a 1,4-dicarbonyl moiety spanning an all-carbon quaternary stereogenic spirocenter was achieved using a masked bromomethyl vinyl ketone reagent. The developed protocol entails an enantioselective palladium-catalyzed allylic alkylation reaction followed by a one-pot unmasking/RCM sequence that provides access to the spirocyclic compounds in good yields and selectivities.     

Asymmetric synthesis of P-stereogenic o-hydroxyaryl-phosphine (borane) and phosphine-phosphinite ligands

The first asymmetric synthesis of P-stereogenic 2-hydroxyarylphosphine ligands is described, using borane complexation methodology. This synthesis is based on the highly stereoselective preparation of bromoarylphosphinite boranes, leading to the 2-hydroxyarylphosphine derivatives, by an intramolecular ortho Fries-like rearrangement mediated in basic conditions. The o-anisyl-2-hydroxynaphthylphenylphosphine borane has been decomplexed in EtOH, affording the P(III)-stereogenic hydroxyarylphosphine ligand with 84% yield. The interest of the hydroxyarylphosphine borane is also demonstrated by the preparation of a new class of phosphine-phosphinite ligands, by trapping the rearrangement products first with chlorodiphenylphosphine, Ph₂PCl, then with borane. The corresponding phosphine-phosphinites are obtained and purified as diborane complexes, with the decomplexation of these borane complexes being achieved by heating with dabco, to afford the free hybrid ligands with retention of the configuration at the P-atom (isolated yield up to 53%).     

Asymmetric synthesis of 2-chloroaziridines via a diastereoselective nucleophilic dichloromethylation and N-alkylation in one pot

A diastereoselective nucleophilic dichloromethylation between the N-tert-butanesulfinyl imines and dichloromethyllithium was developed. A series of 2-chloroaziridines with excellent yields and dr values were obtained via this nucleophilic addition and N-alkylation in one pot. On the basis of X-ray crystallography experiment, the predicting model for this diastereoselective transformation was provided.     

One-ligand catalytic asymmetric deprotonation of a phosphine borane: synthesis of P-stereogenic bisphosphine ligands

A new protocol for the catalytic asymmetric deprotonation of a phosphine borane using s-BuLi and substoichiometric quantities of chiral diamines is reported. The method involves three sequential additions of s-BuLi, and use of (-)-sparteine or the (+)-sparteine surrogate facilitates access to P-stereogenic phosphines with opposite configuration. The method is exemplified by the catalytic asymmetric synthesis of each enantiomer of precursors to QuinoxP*, trichickenfootphos, and Mini-PHOS.     

Selective homo- and heterodehydrocouplings of phosphines catalyzed by rhodium phosphido complexes

Reactions of the rhodium complex (dippe)Rh(eta3-CH2Ph) (1, dippe = iPr2PCH2CH2PiPr2) with ArPH2 (Ar = Ph, Mes) proceed via P-H oxidative additions to the phosphido complexes (dippe)Rh(mu-PHAr)2Rh(dippe) (3a, Ar = Ph; 3b, Ar = Mes). The corresponding reaction of Ph2PH occurs similarly, via the intermediate (dippe)Rh(PPh2)PHPh2 (4), to (dippe)Rh(mu-PPh2)2Rh(dippe) (3c). Complexes 3a-c and 4 are catalysts for the catalytic dehydrodimerizations of the corresponding phosphines to diphosphanes. Complex 1 is a more active dehydrocoupling catalyst, and substituent effects suggest that the active catalyst is mononuclear. Efficient dehydrocouplings of 2-EtC6H4PH2, 2-iPrC6H4PH2, and 2,4,6-iPr3C6H2PH2 were also observed. Complex 1 also catalyzes the heterocoupling of Ph2PH with PhSH (to Ph2P-SPh), and stoichiometric reactions in this system allowed isolation of (dippe)Rh(mu-SPh)2Rh(dippe) (6) and (dippe)Rh(SPh)PHR2 (7a, R2PH = MesPH2; 7b, R2PH = Ph2PH).     

Asymmetric total synthesis of (+)-virosine A via sequential nucleophilic cyclizations onto an activated formamide

The first synthesis of tetracyclic alkaloid virosine A is reported. The natural alkaloid was prepared in only 13 steps, in an enantioenriched form. The azabicyclo[2.2.2]octane core was efficiently assembled using a key Vilsmeier-Haack and Mannich cyclizations sequence performed in one pot.     

Asymmetric synthesis of α,β-epoxysulfones via phase-transfer catalytic Darzens reaction

Described is the asymmetric synthesis of α,β-epoxysulfones by the catalytic phase-transfer Darzens reaction of chloromethyl phenyl sulfone with various aromatic aldehydes in the presence of the cinchona alkaloid-derived chiral phase-transfer catalysts bearing N-2,3,4-trifluorobenzyl moiety. The trans-(αR,βR)-epoxysulfones were obtained in good chemical yields (81-95%) with high enantioselectivities (up to 97% ee) in the presence of N-(2,3,4-trifluorobenzyl)quinidinium bromide.     

Neutral p-cymene ruthenium complexes with P-stereogenic monophosphines. New catalytic precursors in enantioselective transfer hydrogenation and cyclopropanation

A family of eight neutral, pseudotetrahedral piano-stool ruthenium complexes C, of the type [RuCl₂(p-cymene)(PArPhR)] (Ar = 1-naphthyl, 9-phenanthryl and 2-biphenylyl; R = Me, i-Pr, OMe, –CH₂SiMe₃ and –CH₂SiPh₃) have been prepared and characterised, including the X-ray crystal structure for C6 (Ar = 2-biphenylyl; R = i-Pr). These complexes catalyse the asymmetric hydrogen transfer reaction of acetophenone in refluxing 2-propanol in the presence of potassium tert-butoxyde, reaching full conversions and up to 45% ee after 24 h towards the S enantiomer of 1-phenylethanol. Cationic complexes formed upon treatment of C with one equivalent of AgSbF₆ or (Et₃O)PF₆ are active in the cyclopropanation reaction of styrene and α-methylstyrene by ethyl diazoacetate. Low to moderate conversions (up to 58%), diastereoselectivities (up to 40% de), and moderate enantioselectivities (up to 69% ee) have been found. For both reactions, bulky complexes and C6 in particular lead to the best results.     

Neutral p-cymene ruthenium complexes with P-stereogenic monophosphines. New catalytic precursors in enantioselective transfer hydrogenation and cyclopropanation

A family of eight neutral, pseudotetrahedral piano-stool ruthenium complexes C, of the type [RuCl₂(p-cymene)(PArPhR)] (Ar = 1-naphthyl, 9-phenanthryl and 2-biphenylyl; R = Me, i-Pr, OMe, –CH₂SiMe₃ and –CH₂SiPh₃) have been prepared and characterised, including the X-ray crystal structure for C6 (Ar = 2-biphenylyl; R = i-Pr). These complexes catalyse the asymmetric hydrogen transfer reaction of acetophenone in refluxing 2-propanol in the presence of potassium tert-butoxyde, reaching full conversions and up to 45% ee after 24 h towards the S enantiomer of 1-phenylethanol. Cationic complexes formed upon treatment of C with one equivalent of AgSbF₆ or (Et₃O)PF₆ are active in the cyclopropanation reaction of styrene and α-methylstyrene by ethyl diazoacetate. Low to moderate conversions (up to 58%), diastereoselectivities (up to 40% de), and moderate enantioselectivities (up to 69% ee) have been found. For both reactions, bulky complexes and C6 in particular lead to the best results.     

Stereoselective synthesis of highly functionalised P-stereogenic nucleosides via palladium-catalysed P-C cross-coupling reactions

We have shown that the configuration at the P-stereogenic centre in a range of H-phosphonates can be assigned using a combination of chromatographic mobility, ¹H and ³¹P NMR data. We have also shown that the individual P-stereoisomers can be cross-coupled with vinyl and aryl halides, in the presence of a palladium(0) catalyst, to afford the corresponding vinyl- and arylphosphonates in a stereocontrolled manner.     

Asymmetric synthesis of a chiral hetero-bidentate As–P ligand containing both As and P-stereogenic centres

The organopalladium complex containing ortho-metalated (S)-[1-(dimethylamino)ethyl]naphthalene as the chiral auxiliary has been used as the chiral template to promote the asymmetric cycloaddition reaction between phenyldivinylphosphine and 3,4-dimethyl-1-phenylarsole. The reaction was completed in 1 h at room temperature, with the formation of two isomeric cycloadducts in the ratio 1:3. The major phenylvinylphosphino-substituted asymmetrical hetero-bidentate arsanorbornene ligand with chirality residing on both As and P centers was obtained stereoselectively on the chiral palladium template in moderate yield. The chiral heterobidentate ligand was isolated in its enantiomerically pure form by removal of the chiral auxiliary using concentrated hydrochloric acid and subsequent cleavage from the neutral complex [(As–P)PdCl₂] by using potassium cyanide. Similar to the earlier reported analogous diphenylphosphino-substituted asymmetrical heterobidentate arsanorbornene (As–P) ligand, an arsenic elimination process was also found in the dichloro and dibromo palladium complex whereas the diiodo species did not show similar reactivity, but the corresponding η² diiodo complex could be obtained from the η² dibromo complex by treatment with sodium iodide.     

Asymmetric synthesis of naproxen via a pinacol-type reaction

An asymmetric pinacol-type rearrangement was used in the synthesis of (S)-naproxen. The pinacol-type reaction of a vicinal diol provided an -aryl ketone which was oxidized with sodium hypochlorite in the presence of methanol to the methyl ester of naproxen.     

Asymmetric synthesis of amino acids via the catalytic reduction of substituted acylaminoacrylic acid azlactones

The kinetics of aminolysis and racemization of 2-methyl-4-benzyloxazolin-5-one upon reaction with S-phenylalanine methyl ester have been studied in dimethoxyethane solvent. The rates of aminolysis and racemization are comparable. Addition of an achiral component, namely Et₃N, to the reaction mixture, however, dramatically increases the rate of racemization. The presence of Et₃N also increases the ratio of rate constants for the formation of RS- and SS-diastereomers, which determines the reaction stereoselectivity.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 823–828, April, 1990.     

Asymmetric synthesis of amino acids via the catalytic reduction of acylaminoacrylic acid azlactone derivatives

Reductive aminolysis of 2-methyl-4-benzylidene-²-oxazolin-5-one upon treatment with a PdCl₂-S-phenylalanine ester (dimethylamide) catalytic system leads to the formation of the corresponding acylated dipeptide derivatives, with the R,S-configuration (diastereomer) predominating (DE 9–27%). The reaction stereoselectivity in dimethoxyethane increases sharply in the presence of triethylamine additive, and in the case of S-phenylalanine methyl ester reaches 47%. The stepwise mechanism for this process has been studied.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 811–818, April, 1990.     

Asymmetric synthesis of multifunctionalized pyrrolines by a ruthenium porphyrin-catalyzed three-component coupling reaction

[reaction: see text] Chiral multifunctionalized pyrrolines have been synthesized by a ruthenium porphyrin catalyzed three-component coupling reaction. In a one-pot reaction, ruthenium porphyrins catalyzed in situ generation of chiral azomethine ylides from chiral diazo esters and imines. Asymmetric 1,3-dipolar cycloaddition reactions of the chiral azomethine ylides with dipolarophiles afforded the corresponding pyrrolines in good yields and high diastereoselectivity (up to 92% de).     

Asymmetric catalytic anhydride openings via carbon-based nucleophiles

The asymmetric desymmetrization of cyclic anhydrides via the addition of carbon-based nucleophiles has been the focus of considerable levels of interest because it leads to optically active products. Over the past 20 years, a variety of different catalytic asymmetric alkylation reactions have been developed for the desymmetrization of cyclic anhydrides using different metal reagents as nucleophiles and using chiral ligands. The purpose of this review is to provide an overview of significant developments in this field. ~ 2013 Fen-Er Chen. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Asymmetric 1,3-dipolar cycloaddition with a P-stereogenic dipolarophile: an efficient approach to novel P-stereogenic 1,2-diphosphine systems

The asymmetric 1,3-dipolar cycloaddition of the P-stereogenic dipolarophile (S(p),S(p))-6 to C,N-diphenylnitrone (7) led to previously unknown P-stereogenic isoxazolinyl diphosphine dioxides (R(p),S(p))-8 in enantio- and diastereomerically pure form; their stereospecific reduction with Ti(OiPr)(4)/PMHS proceeds in high yield with retention of configuration at the phosphorus atoms to give enantio- and diastereomerically pure diphosphines, which are conveniently purified via the corresponding diphosphine-diboranes.