Enantioselective synthesis of cyclic sulfamidates via Pd-catalyzed hydrogenation

Using Pd(CF3CO2) 2/(S,S)-f-binaphane as the catalyst, an efficient enantioselective synthesis of cyclic sulfamidates was developed via asymmetric hydrogenation of the corresponding cyclic imines in 2,2,2-trifluoroethanol at room temperature with high enantioselectivities (up to 99% ee).     

Asymmetric hydrogenation of aromatic ketones using new chiral-bridged diphosphine/diamine-Ru(Ⅱ) complexes

<正>A series of chiral secondary alcohols were easily prepared by means of asymmetric hydrogenation of prochiral aromatic ketones using a new((R_(ax))-BuP)/(R,R)-DPEN-Ru(Ⅱ) complex catalyst system.The hydrogenation of 2-methylacetophenone in n-butanol (t-BuOK/Ru =45.6/1,S/C = 500,20 atm.of H_2,20℃,48 h) afforded(S)-1-(2'-methylphenyl)ethanol in 92%ee and99% conversion.     

Enantioselective diene Cyclization/Hydrosilylation catalyzed by optically active palladium bisoxazoline and pyridine-oxazoline complexes

A 1:1 mixture of (N-N)Pd(Me)Cl ?N-N = (S,S)-4,4'-dibenzyl-4,5,4', 5'-tetrahydro-2,2'-bisoxazoline (S,S-4a) and NaBAr(4) ?Ar = 3, 5-C(6)H(3)(CF(3))(2) (5 mol %) catalyzed the asymmetric cyclization/hydrosilylation of dimethyl diallylmalonate (2) and triethylsilane at -30 degrees C for 48 h to form an 8.1:1 mixture of the silylated carbocycle (S,S)-trans-1, 1-dicarbomethoxy-4-methyl-3-?(triethylsilyl)methylcyclop ent ane (S, S-3) (95% de, 72% ee) and dimethyl 3,4-dimethylcyclopentane-1, 1-dicarboxylate (S,S-6) in 64% combined yield. In comparison, a 1:1 mixture of the palladium pyridine-oxazoline complex (N-N)Pd(Me)Cl ?N-N = (R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline (R-5b) and NaBAr(4) (5 mol %) catalyzed the asymmetric cyclization/hydrosilylation of 2 and triethylsilane at -32 degrees C for 24 h to form carbocycle S,S-3 in 82% yield (>95% de, 87% ee) as the exclusive product. Asymmetric diene cyclization catalyzed by complex R-5b was compatible with a range of functional groups and produced carbocycles with up to 91% ee. The procedure also tolerated substitution at a terminal olefinic position and at the allylic position of the diene.     

The hydrogenation/transfer hydrogenation network: asymmetric hydrogenation of ketones with chiral eta6-arene/N-Tosylethylenediamine-ruthenium(II) catalysts

Chiral eta6-arene/N-tosylethylenediamine-Ru(II) complexes, known as excellent catalysts for asymmetric transfer hydrogenation of aromatic ketones in basic 2-propanol, can be used for asymmetric hydrogenation using H2 gas. Active catalysts are generated from RuCl[(S,S)-TsNCH(C6H5)CH(C6H5)NH2](eta6-p-cymene) in methanol, but not 2-propanol, or by combination of Ru[(S,S)-TsNCH(C6H5)CH(C6H5)NH](eta6-p-cymene) and CF3SO3H or other non-nucleophilic acids. This method allows, for the first time, asymmetric hydrogenation of simple ketones under acidic conditions. Hydrogenation of base-sensitive 4-chromanone and its derivatives with the S,S catalyst proceeds in methanol with a substrate-to-catalyst molar ratio of 1000-3000 (10 atm) to 7000 (100 atm), giving (S)-4-chromanols with 97% ee quantitatively. The reaction can be achieved even on a 2.4 kg scale. The mechanistic rationale for the catalytic efficiency is presented.     

Role of the NH2 functionality and solvent in terdentate CNN alkoxide ruthenium complexes for the fast transfer hydrogenation of ketones in 2-propanol

The reaction of [RuCl(CNN)(dppb)] (1; HCNN=6-(4-methylphenyl)-2-pyridylmethylamine) with NaOiPr in 2-propanol/C6D6 affords the alcohol adduct alkoxide [Ru(OiPr)(CNN)(dppb)].n iPrOH (5), containing the Ru-NH2 linkage. The alkoxide [Ru(OiPr)(CNN)(dppb)] (4) is formed by treatment of the hydride [Ru(H)(CNN)(dppb)] (2) with acetone in C6D6. Complex 5 in 2-propanol/C6D6 equilibrates quickly with hydride 2 and acetone with an exchange rate of (5.4+/-0.2) s(-1) at 25 degrees C, higher than that found between 4 and 2 ((2.9+/-0.4) s(-1)). This fast process, involving a beta-hydrogen elimination versus ketone insertion into the Ru-H bond, occurs within a hydrogen-bonding network favored by the Ru-NH2 motif. The cationic alcohol complex [Ru(CNN)(dppb)(iPrOH)](BAr(f)4) (6; Ar(f)=3,5-C6H3(CF3)2), obtained from 1, Na[BAr(f)4], and 2-propanol, reacts with NaOiPr to afford 5. Complex 5 reacts with either 4,4'-difluorobenzophenone through hydride 2 or with 4,4'-difluorobenzhydrol through protonation, affording the alkoxide [Ru(OCH(4-C6H4F)2)(CNN)(dppb)] (7) in 90 and 85 % yield of the isolated product. The chiral CNN-ruthenium compound [RuCl(CNN)((S,S)-Skewphos)] (8), obtained by the reaction of [RuCl2(PPh3)3] with (S,S)-Skewphos and orthometalation of HCNN in the presence of NEt3, is a highly active catalyst for the enantioselective transfer hydrogenation of methylaryl ketones (turnover frequencies (TOFs) of up to 1.4 x 10(6) h(-1) at reflux were obtained) with up to 89% ee. Also the ketone CF3CO(4-C6H4F), containing the strong electron-withdrawing CF3 group, is reduced to the R alcohol with 64% ee and a TOF of 1.5 x 10(4) h(-1). The chiral alkoxide [Ru(OiPr)(CNN)((S,S)-Skewphos)]n iPrOH (9), obtained from 8 and NaOiPr in the presence of 2-propanol, reacts with CF3CO(4-C6H4F) to afford a mixture of the diastereomer alkoxides [Ru(OCH(CF3)(4-C6H4F))(CNN)((S,S)-Skewphos)] (10/11; 74% yield) with 67% de. This value is very close to the enantiomeric excess of the alcohol (R)-CF3CH(OH)(4-C6H4F) formed in catalysis, thus suggesting that diastereoisomeric alkoxides with the Ru-NH2 linkage are key species in the catalytic asymmetric transfer hydrogenation reaction.     

Enantioselective Pd-catalyzed hydrogenation of fluorinated imines: facile access to chiral fluorinated amines

An enantioselective hydrogenation of simple fluorinated imines has been developed using Pd(OCOCF(3))(2)/(R)-Cl-MeO-BIPHEP as a catalyst, and up to 94% ee was achieved. This method provides an efficient route to enantioenriched fluorinated amines.     

Sonochemical asymmetric hydrogenation of isophorone on proline modified Pd/Al2O3 catalysts

The sonochemical asymmetric hydrogenation of isophorone (3,3,5-trimethyl-2-cyclohexenone) by proline-modified Pd/Al2O3 catalysts is described; presonication of a commercial Pd/Al2O3-proline catalytic system resulted in highly enhanced enantioselectivities (up to 85% ee).     

Catalytic asymmetric hydrogenation of 2,3,5-trisubstituted pyrroles

Catalytic asymmetric hydrogenation of N-Boc-protected pyrroles proceeded with high enantioselectivity by using a ruthenium catalyst modified with a trans-chelating chiral bisphosphine PhTRAP. The ruthenium catalyst prepared from Ru(eta3-methallyl)2(cod) and (S,S)-(R,R)-PhTRAP in the presence of triethylamine was the most enantioselective for the asymmetric hydrogenation of methyl pyrrole-2-carboxylate, giving the desired (S)-proline derivative with 79% ee in 92% yield. Moreover, 2,3,5-trisubstituted pyrroles bearing a large substituent at the 5-position were hydrogenated with 93-99.7% ee. The asymmetric reduction of 4,5-dimethylpyrrole-2-carboxylate gave only all-cis isomer and created three chiral centers with high degree of stereocontrol in a single process. This is the first highly enantioselective reduction of pyrroles.     

Highly enantioselective sequential hydrogenation of ethyl 2-oxo-4-arylbut-3-enoate to ethyl 2-hydroxy-4-arylbutyrate

The hydrogenation of (E)-ethyl 2-oxo-4-arylbut-3-enoate with [NH2Me2](+)[{RuCl [(S)-SunPhos]}2(mu-Cl3)] gave ethyl 2-hydroxy-4-arylbutyrate with 94-96% ee. Further investigation has proved that the hydrogenation proceeded via a sequential hydrogenation of CO and CC bonds, which is sensitive to the reaction temperature. Hydrolysis of ethyl 2-hydroxy-4-phenylbutyrate (ee 93%) provided the 2-hydroxy-4-phenylbutyric acid with 81% yield at 99% ee after a single recrystallization from 1,2-dichloroethylene.     

Carbonization of alumina-based catalysts in propionitrile ammonolysis

Summary The asymmetric hydrogenation of ethyl 2-acetoxyacrylate (EtA) by cinchonidine modified Pd/Al2O3 and Pt/Al2O3 catalyst is described (ee up to 60 &percnt;). This is the first example of asymmetric hydrogenation of an enol esters in heterogenized conditions.     

Ru-Catalyzed asymmetric hydrogenation of alpha-ketoesters with CeCl3.7H2O as additive

[reaction: see text] An efficient asymmetric hydrogenation of alpha-ketoesters is reported with use of a catalyst prepared from [Ru((S)-3)(benzene)Cl]Cl and CeCl(3).7H(2)O. Alpha-hydroxy esters are obtained in up to 96% ee. The addition of CeCl(3).7H(2)O not only improves the enantioselectivity, but also enhances the stability of the catalyst. As a result, the hydrogenation of methyl benzoylformate affords the product with 92% ee with a substrate/catalyst ratio of 10 000. Hydrolysis of 2 provides the final compound with 83% yield at 99% ee after a single recrystallization from 1,2-dichloroethylene.     

Efficient synthesis of an imidazole-substituted delta-amino acid by the integration of chiral technologies

Two methods to produce (2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)-pentanoic acid were investigated. Diastereoisomeric salt resolution, using the quinidine salt, gave the desired intermediate in 98% ee and 33% yield. Asymmetric hydrogenation of various substrates gave high conversions, with up to 83% ee. Integration of these two approaches via asymmetric hydrogenation of a quinidine salt substrate followed by crystallization provided the desired intermediate in 94% ee and 76% yield.     

A novel synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by sharpless asymmetric epoxidation method

Synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by the Sharpless asymmetric epoxidation reaction has been achieved. 2,4,5-Trifluorobenzaldehyde with methyl 2-(triphenyl-λ⁵-phosphanylidene)acetate gave methyl (E)-3-(2,4,5-trifluorophenyl)acrylate in 83% yield. The reduction of ester group with DibalH followed by Sharpless asymmetric epoxidation gave ((2R,3R)-3-(2,4,5-trifluorophenyl)oxiran-2-yl)methanol. Pd/C-catalyzed hydrogenation of epoxy alcohol furnished (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol with >90% ee and 71% yield.     

Synthesis of (S)-7-amino-5-azaspiro[2.4]heptane via highly enantioselective hydrogenation of protected ethyl 1-(2-aminoaceto)cyclopropanecarboxylates

Highly effective asymmetric hydrogenation of protected ethyl 1-(2-aminoaceto)cyclopropane carboxylates in the presence of [RuCl(benzene)(S)-SunPhos]Cl was realized, and high enantioselectivities (up to 98.7% ee) were obtained. This asymmetric hydrogenation provides a key intermediate for the enantioselective synthesis of (S)-7-amino-5-azaspiro[2.4]heptane moiety of quinolone antibacterial agents.     

铱催化 3-羟甲基-2H-苯并吡喃类化合物的不对称氢化

从(1R,2S)-环己烷吡啶醇出发,合成了具有不同轴手性的反式环己烷骨架铱络合物,并将其应用于3-羟甲基-2H-苯并吡喃的不对称氢化中.结果表明,当以Ir-8为催化剂,二氯甲烷为溶剂,氢气压力5MPa,室温反应16h时,可以取得极好的反应活性,产物最高对映选择性可达94%.     

Highly efficient chiral metal cluster systems derived from Ru3(CO)12 and chiral diiminodiphosphines for the asymmetric transfer hydrogenation of ketones

The chiral Ru cluster-based catalyst systems generated in situ from Ru3(CO)12 and chiral diiminodiphosphine tetradentate ligands effected asymmetric transfer hydrogenation of propiophenone in 2-propanol, leading to 1-phenyl-1-propanol in 94% yield and with 96% ee.     

Synthesis and enantioselective hydrogenation of seven-membered cyclic imines: substituted dibenzo[b,f][1,4]oxazepines

Highly enantioselective hydrogenation of seven-membered cyclic imines, substituted dibenzo[b,f][1,4]oxazepines, was achieved, with up to 94% ee, by using the [Ir(COD)Cl](2)/(S)-Xyl-C(3)*-TunePhos complex as the catalyst in the presence of morpholine-HCl.     

POLYKETONE FROM CO AND STYRENE: A USEFUL COPOLYMER CATALYZED BY A HIGHLY ACTIVE AND STABLE PALLADIUM CATALYST WITH 5-NITRO-1,10-PHENANTHROLINE LIGAND

A novel coordinated complex [(5-nitrophen)Pd(CF3CO2)2] (5-nitrophen = 5-nitro-l,10-phenanthroline) was first synthesized. By using XPS, IR, and 1H-NMR, its coordination unit was studied in comparison with those of complexes [(N- N)Pd(CH3CO2)2] and [(N - N)Pd(CF3CO2)2]. The H2,9 proton signals of 1H-NMR spectra of the complexes are excellent probes to monitor the evolution of the environment of the palladium atom. The state of anionic coordination was confirmed by the presence of IR absorption peaks of COO in complexes ([(N N)Pd(CH3CO2)2] and [(NN)Pd(CF3CO2)2]). Bonding energies of N1s and Pd3d5 obtained from XPS data testified to the strength of the N-Pd coordinating bond. The conclusion can be drawn by analyzing these data from IR, XPS and 1H-NMR that it is the unsymmetrical substitution of the 1,10-phenanthroline (phen) that makes the [(5-nitrophen)Pd(CF3CO2)2] more active.Experimental results showed that [(5-nitrophen)Pd(CF3CO2)2] exhibits much higher activity than [(bipy)Pd(CF3CO2)2] (1, l‘-bipyridine = bipy) and [(phen)Pd(CF3CO2)2] under the same conditions.     

Palladium-catalyzed enantioselective 1,3-rearrangement of racemic allylic sulfinates: asymmetric synthesis of allylic sulfones and kinetic resolution of an allylic sulfinate

Described is an asymmetric synthesis of cyclic and acyclic allylic S-aryl and S-alkyl sulfones through a highly selective palladium(0)-catalyzed 1,3-rearrangement of racemic allylic sulfinates. Treatment of racemic cyclic and acyclic allylic S-tolyl- and S-tert-butylsulfinates with Pd(2)(dba)(3).CHCl(3) as precatalyst and N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphosphino)benzamide] as ligand for the palladium atom afforded the corresponding isomeric allylic S-tolyl and S-tert-butyl sulfones of 93-99% ee in 82-96% yield. The rearrangement of the allylic sulfinates most likely proceeds in an intermolecular fashion via formation of a cationic pi-allylpalladium complex and the sulfinate ion. The racemic allylic sulfinates were obtained from the corresponding racemic alcohols and racemic tolylsulfinyl chloride and racemic tert-butylsulfinyl chloride, respectively, in high yields. Rearrangement of the racemic tert-butylsulfinic acid 2-cyclooct-1-enyl ester with Pd(2)(dba)(3).CHCl(3) and the bisphosphane was accompanied by a highly selective kinetic resolution of the substrate and gave at 50% conversion the (R)-configured sulfinate as mixture of the S(S) and R(S) diastereomers of 92% ee and 85% ee and the (S)-configured 3-tert-butylsulfonyl cyclooctene sulfone 15a with 98% ee in almost quantitative yields.     

An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation

A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)-3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.