Enantioselective Hydrogenation of Aromatic Ketones Catalyzed by a Mesoporous Silica‐Supported Iridium Catalyst

A mesoporous, silica‐supported, chiral iridium catalyst with a highly ordered dimensional‐hexagonal mesostructure was prepared by postgrafting the organometallic complex (1‐diphenylphosphino‐2‐triethylsilylethane)[(R,R)‐1,2‐diphenylethylenediamine]iridium chloride {IrCl[PPh₂(CH₂)₂Si(OEt)₃]₂[(R,R)‐DPEN] (DPEN=1,2‐diphenylethylenediamine)} on SBA‐15 silica. During the asymmetric hydrogenation of various aromatic ketones under 40 atm of hydrogen, the mesoporous, silica‐supported, chiral iridium catalyst exhibited high catalytic activity (more than 95% conversions) and excellent enantioselectivity (up to more than 99% ee). The catalyst could be recovered easily and used repetitively seven times without significantly affecting the catalytic activity and the enantioselectivity.     

An Ion‐Pair Immobilization Strategy in Rhodium‐Catalyzed Asymmetric Transfer Hydrogenation of Aromatic Ketones

A chiral diamine‐based homogeneous cationic rhodium catalyst was developed and two heterogeneous cationic rhodium catalysts were obtained via the encapsulation of the homogeneous cationic rhodium catalyst within Me‐SBA‐15 and Me‐SBA‐16. All these catalysts presented excellent catalytic activities and high enantioselectivities in ultrasound‐promoted asymmetric transfer hydrogenation of aromatic ketones and represent a successful use of the ion‐pair immobilization strategy. More importantly, the encapsulation of the cationic rhodium functionality within Me‐SBA‐16 had an obvious high recyclability, in which the recycled catalyst could be reused nine times without significantly affecting its enantioselectivity, showing good potential in industrial application.     

A Modular Furanoside Thioether‐Phosphite/Phosphinite/ Phosphine Ligand Library for Asymmetric Iridium‐Catalyzed Hydrogenation of Minimally Functionalized Olefins: Scope and Limitations

A highly modular furanoside thioether‐phosphite/phosphinite/phosphine ligand library has been synthesized for the iridium‐catalyzed asymmetric hydrogenation of minimally functionalized olefins. These ligands can be prepared efficiently from easily accessible D ‐(+)‐xylose. We found that their effectiveness at transferring the chiral information in the product can be tuned by correctly choosing the ligand components. Enantioselectivities were therefore excellent (ees up to 99%) in a wide range of E‐ and Z‐trisubstituted alkenes using 5‐deoxyribofuranoside thioether‐phosphite ligands. It should be pointed out that these catalysts are also very tolerant to the presence of a neighbouring polar group. For 1,1‐disubstituted substrates, both enantiomers of the hydrogenation product can be obtained in high enantioselectivities simply by changing the configuration of the biaryl phosphite moiety. The asymmetric hydrogenation was also performed using propylene carbonate as solvent, which allowed the iridium catalysts to be reused while maintaining the excellent enantioselectivities.     

Chiral Bis(N‐sulfonylamino)phosphine‐ and TADDOL‐Phosphite‐Oxazoline Ligands: Synthesis and Application in Asymmetric Catalysis

A series of N,P‐ligands has been prepared, containing a chiral oxazoline ring and as a second chiral unit a bis(N‐sulfonylamino)phosphine group embedded in a diazaphospholidine ring or a cyclic phosphite group derived from TADDOL. These modular ligands are readily synthesized from chiral amino alcohols and chiral 1,2‐diamines or TADDOLs. Palladium and iridium complexes derived from these ligands were found to be efficient catalysts for enantioselective allylic alkylation and olefin hydrogenation, respectively.     

Enantioselective Synthesis of Chiral Tetrahydroisoquinolines by Iridium‐Catalyzed Asymmetric Hydrogenation of Enamines

Chiral iridium complexes based on spiro phosphoramidite ligands are demonstrated to be highly efficient catalysts for the asymmetric hydrogenation of unfunctionalized enamines with an exocyclic double bond. In combination with excess iodine or potassium iodide and under hydrogen pressure, the complex Ir/(S_a,R,R)‐ 3a provides chiral N‐alkyltetrahydroisoquinolines in high yields with up to 98% ee. The L/Ir ratio of 2:1 is crucial for obtaining a high reaction rate and enantioselectivity. A deuterium labeling experiment showed that an inverse isotope effect exists in this reaction. A possible catalytic cycle including an iridium(III) species bearing two monophosphoramidite ligands is also proposed.     

Enantioselective Synthesis of Optically Active Alkanephos‐ phonates via Rhodium‐Catalyzed Asymmetric Hydrogenation of β‐Substituted α,β‐Unsaturated Phosphonates with Ferrocene‐Based Monophosphoramidite Ligands

A series of chiral β‐substituted alkanephosphonates was synthesized in high enantioselectivities via the first rhodium‐catalyzed asymmetric hydrogenation of the corresponding β‐substituted‐α,β‐unsaturated phosphonates using a ferrocene‐derived monophosphoramidite ligand, with which up to 99.5% ee have been achieved for the hydrogenation of (E)‐substrates and 98.0% ee for (Z)‐substrates.     

Chiral NCN Pincer Rhodium(III) Complexes with Bis(imidazolinyl)phenyl Ligands: Synthesis and Enantioselective Catalytic Alkynylation of Trifluoropyruvates with Terminal Alkynes

A series of new chiral C₂‐symmetrical NCN pincer rhodium(III) complexes with bis(imidazolinyl)phenyl ligands have been conveniently synthesized from easily available materials. The complexes were subsequently applied in the enantioselective addition of terminal alkynes to trifluoropyruvates. With catalyst loading of 1.5–3.0 mol%, the alkynylation of ethyl or methyl trifluoropyruvate with a variety of electronically and structurally diverse terminal alkynes gave the optically active trifluoromethyl‐substituted tertiary propargylic alcohols with enantioselectivities of up to >99% ee and high yields. Although good to excellent enantioselectivities (85–98% ee) could be achieved only for some of the aliphatic terminal alkynes under the optimized conditions, the enantioselectivities were consistently excellent (94% to >99% ee) in the case of aromatic as well as heteroaromatic alkynes and enynes.     

Enantioselective Rhodium‐Catalyzed Addition of Arylboronic Acids to Trifluoromethyl Ketones

A new C₂‐symmetrical, chiral bisphosphorus ligand proved to be efficient for the rhodium‐catalyzed nucleophilic addition of arylboronic acids to trifluoromethyl ketones, providing a series of chiral trifluoromethyl‐substituted tertiary alcohols in high yields (up to 93%) and excellent enantioselectivities (>99%).     

Regio‐ and Enantioselective Catalytic Hydrophosphorylation of Vinylarenes

Regioselective and stereoselective hydrophosphorylation of vinylarenes 1 with pinacol H‐phosphonate 2 can be achieved with transition metal catalysts. The use of rhodium catalysts such as the Wilkinson complex leads to the anti‐Markovnikov adducts 3 as the only observable reaction products. In contrast, palladium catalysts give high selectivities for the Markovnikov adducts 4 . In the presence of (R,S)‐BINAPHOS as a chiral ligand, significant enantioselectivities have been obtained for the first time in hydrophosphorylation reactions.     

N,N′‐Dioxide‐Magnesium Ditriflate Complex‐Catalyzed Asymmetric α‐Hydroxylation of β‐Keto Esters and β‐Keto Amides

The highly catalytic asymmetric α‐hydroxylation of 1‐tetralone‐derived β‐keto esters and β‐keto amides using tert‐butyl hydroperoxide (TBHP) as the oxidant was realized by a chiral N,N′‐dioxide‐magnesium ditriflate [Mg(OTf)₂] complex. A series of corresponding chiral α‐hydroxy dicarbonyl compounds was obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee). The products were easily transformed into useful building blocks and the precursor of daunomycin was achieved in an asymmetric catalytic way for the first time.     

Polyethylene Glycol as an Environmentally Friendly and Recyclable Reaction Medium for Enantioselective Hydrogenation

Polyethylene glycol (PEG) was found to be an inexpensive, non‐toxic and recyclable reaction medium for ruthenium‐ and rhodium‐catalyzed asymmetric hydrogenation of 2‐arylacrylic acids (Ru‐catalyzed CC bond reduction), enamides (Rh‐catalyzed CC bond reduction), β‐keto esters and simple aromatic ketones (Ru‐catalyzed CO bond reduction). In all cases, high catalytic activities and enantioselectivities have been achieved, which are comparable to those obtained in conventional organic solvent systems. The Ru and Rh catalysts prepared with commercially available chiral diphosphine ligands could be readily recycled by simple extraction, as in the case of ionic liquids, and reused up to nine times without obvious loss of catalytic activity and enantioselectivity. The reduced products were obtained from the extracts in high isolated yields. These results indicate that PEGs as new reaction media are attractive alternatives to room temperature ionic liquids.     

Synthesis of polymeric salen complexes and application in the enantioselective hydrolytic kinetic resolution of epoxides as catalysts

The polymeric (salen) Co(III) catalysts containing various counter anions have been synthesized, and the asymmetric catalytic activities of these newly synthesized polymer-type salen complexes were investigated in the HKR of terminal epoxides. The polymeric chiral salen Co(III) complexes catalyze the hydrolysis of epichlorohydrine, 1,2-epoxybutane, 1,2-epoxyhexane and epoxystyrene with very high enantioselectivities under mild conditions. The catalysts could be recovered and reused several times without further treatment after reaction, showing no loss of activity and enantioselectivity.     

Micellar Effects in Olefin Hydroformylation Catalysed by Neutral,Calix[4]arene‐Diphosphite Rhodium Complexes

The combination of calixarene‐derived surfactants and neutral rhodium complexes containing a hemispherical “1,3‐calix‐diphosphite” ligand led to efficient catalysts for the hydroformylation of octene and other olefins in water. While the surfactants allowed the formation of micelles that dissolve both the catalyst and the alkene, thereby resulting in high olefin:rhodium ratios, the diphosphite provided a tight envelope about the catalytic centre able to drive the reaction towards the linear aldehydes. Best results in the hydroformylation of 1‐octene were obtained when using [tetra(p‐sulfonato)]‐(tetra‐n‐butoxy)‐calix[4]arene as surfactant. With this additive remarkable linear to branched aldehyde ratios of up to 62 were obtained, the corresponding activities being higher than those observed when operating in an organic solvent [turnover frequencies (TOFs) up to 630 mol(converted 1‐octene)⋅ mol(Rh)⁻¹⋅h⁻¹].     

Direct Catalytic Asymmetric Aldol Reactions Assisted by Zinc Complex in the Presence of Water

A combination of zinc triflate and chiral C₂‐symmetrical prolinamide ligand leads to high enantioselectivities in direct aldol reactions essentially assisted by water. The presence of 5 mol % of the catalyst affords an asymmetric intermolecular aldol reaction between unmodified ketones and aldehydes to give anti‐products with excellent enantioselectivities ranging from 86–98 % ee. The same bis(prolinamide) ligand is found to catalyze the direct aldol reactions in the presence of water (or in water) with excellent stereocontrol and furnish the corresponding aldols in up to 99 % ee. For the demonstrated catalytic systems organic solvent‐free conditions are applied.     

Highly Efficient and Enantioselective Iridium‐Catalyzed Asymmetric Hydrogenation of N‐Arylimines

A catalytic method employing the cationic iridium‐(S_c,R_p)‐DuanPhos [(1R,1′R,2S,2′S)‐2,2′‐di‐tert‐butyl‐2,2′,3,3′‐tetrahydro‐1H,1′H‐1,1′‐biisophosphindole] complex and BARF {tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate} counterion effectively catalyzes the enantioselective hydrogenation of acyclic N‐arylimines with high turnover numbers (up to 10,000 TON) and excellent enantioselectivities (up to 98% ee), achieving the practical synthesis of chiral secondary amines.     

The Synthesis of Spirobitetraline Phosphoramidite Ligands and their Application in Rhodium‐Catalyzed Asymmetric Hydrogenation

A racemic 1,1′ ‐ spirobitetralin‐8,8′‐diol (SBITOL) was conveniently synthesized from 3‐methoxybenzaldehyde in 26 % yield over 9 steps and resolved via its bis‐(S)‐camphorsulfonates. The corresponding chiral spirobitetraline monophosphoramidite ligands have been prepared and their rhodium complexes were applied in the asymmetric hydrogenation of dehydroamino esters with good to excellent enantioselectivities (up to 99.3 % ee).     

Reusable Chiral Dicationic Chromium(III) Salen Catalysts for Aminolytic Kinetic Resolution of trans‐Epoxides

A series of new recyclable chiral dicationic chromium(III) salen complexes 1 – 10 bearing different substituents, viz., hydrogen, methyl, tert‐butyl, triphenylphosphinomethyl, triethylaminomethyl, methylimidazolium, methylpyridinium, methyl‐N,N‐dimethylpyridinium at the 3,3′‐ and 5,5′‐ positions of the salen unit with (1S,2S)‐(+)‐1,2‐diaminocyclohexane, (1S,2S)‐(−)‐1,2‐diphenyl‐1,2‐diaminoethane, and (S)‐(−)‐1,1′‐binaphthyl‐2,2′‐diamine collars have been synthesized and characterized by various physico‐chemical methods. These complexes were used as catalysts for the highly enantioselective aminolytic kinetic resolution of racemic trans‐epoxides with different anilines as nucleophiles at room temperature. With the use of catalyst 3 , anti‐β‐amino alcohols were obtained in excellent yields (>99% with respect to the nucleophile) and enantioselectivities (ee>99%) with the concomitant recovery of corresponding epoxides in high optical purity (ee up to >99%) and quantitative yields in 12 h. The catalyst 3 is recyclable in the aminolytic kinetic resolution process and worked well up to six cycles with retention of enantioselectivity.     

Chiral Bis(N‐arylamino)phosphine‐oxazolines: Synthesis and Application in Asymmetric Catalysis

N‐Arylation or N‐alkylation of chiral 1,2‐diamines followed by ring closure with phosphorus trichloride (PCl₃) and subsequent coupling with an oxazoline alcohol resulted in a new class of N,P ligands. The corresponding iridium tetrakis[3,5‐bis(trifluormethyl)phenyl]borate (BAr_F) complexes were found to be efficient catalysts for the enantioselective hydrogenation of unfunctionalized olefins and α,β‐unsaturated carboxylic esters.     

A Bifunctional Cinchona Alkaloid‐Squaramide Catalyst for the Highly Enantioselective Conjugate Addition of Thiols to trans‐Chalcones

A chiral squaramide catalysts‐promoted asymmetric sulfa‐Michael conjugated addition of thiols to trans‐chalcones is presented. Moderate to excellent yields and high enantioselectivities (up to 99% ee) were achieved under mild conditions.     

Highly Efficient Asymmetric Three‐Component Vinylogous Mannich Reaction Catalyzed by a Chiral Scandium(III)‐ N,N′‐Dioxide Complex

The asymmetric three‐component vinylogous Mannich reaction of an acyclic silyl dienol ester, an aldehyde and 2‐aminophenol was accomplished using a chiral N,N′‐dioxide‐scandium(III) complex as the catalyst. A variety of aldehydes were found to be suitable substrates for the reaction and the desired δ‐amino‐α,β‐unsaturated esters were obtained in 90–99% yields with good to excellent enantioselectivities (up to >99% ee) and complete regioselectivities. Moreover, the simple experimental procedures were air‐tolerant and convenient. The present catalytic process provides the potential for large‐scale syntheses of the chiral δ‐amino‐α,β‐unsaturated esters.