1,1′-Binaphthylazepine-based ligands for asymmetric catalysis. Part 2: New aminoalcohols as chiral ligands in the enantioselective addition of ZnEt2 to aromatic aldehydes

The new enantiopure 1,2-aminoalcohols 1b–1h having 1,1′-binaphthylazepine skeleton have been tested as catalytic precursors in the enantioselective addition of ZnEt₂ to benzaldehyde. The best results were seen with ligand 1d, which owes its chirality only to the atropisomerism of the binaphthyl nucleus and does not have any stereogenic carbon atom. In the presence of 1d benzaldehyde was quickly and cleanly transformed to (S)-1-phenylpropanol in 99% yield and 87% e.e. The same ligand was also used in the asymmetric ZnEt₂ addition to other aryl aldehydes giving rise to (S)-1-arylpropanols in almost quantitative yields and e.e.s up to 90%.     

Polymer-supported bis-cinchona alkaloid ligands for asymmetric dihydroxylation of alkenes—a cautionary tale

Careful work-up and purification of purported copolymers formed by free radical copolymerisation of a bis-cinchona alkaloid with methyl methacrylate shows that the level of incorporation of the bis-alkaloid into the polymer skeleton is below the detection limit of a routine nitrogen microanalytical protocol. This reluctance of the CC bonds in the bis-alkaloid to undergo copolymerisation with a methacrylate monomer is totally consistent with the well-known and extensively documented poor copolymerizability of allylic monomers. Direct free radical copolymerisation of allyl groups containing alkaloids and other allyl substituted optically active ligands is not therefore a general and simple option for the production of polymer-supported asymmetric catalysts.     

Highly enantioselective synthesis of β-hydroxysulfonamides by asymmetric transfer hydrogenation

A series of optically active β-hydroxy sulfonamides were synthesized for the first time by asymmetric transfer hydrogenation of the corresponding β-ketosulfonamides using the Ru-TsDPEN-HCOOH-Et₃N catalytic system, in excellent yields (up to 95%) with excellent diastereo- (up to > 99:1 dr) and enantioselectivities (up to >99% ee).     

Use of diamines containing the α-phenylethyl group as chiral ligands in the asymmetric hydrosilylation of prochiral ketones

Chiral diamines 1-7 were used in the enantioselective hydrosilylation of prochiral aromatic and aliphatic ketones. Some of these ligands combine chiral backbones and chiral N,N′-α-phenylethyl substituents that give rise to synergistic effects between these two groups and lead to catalysts that exhibit high enantioselectivity.     

Monohaloboryls (BHX-) as bridging ligands: observable dinuclear σ-(halo)boranyl intermediates in the synthesis of metalloborylenes

Upon treating transition-metal-dihaloboryl complexes of the form [L(n)MBX(2)] with K[(η(5)-C(5)H(5))MnH(CO)(2)], salt elimination occurs along with a migration of the Mn-bound hydride ligand onto the boron atom, thereby forming dinuclear σ-(halo)boranyl complexes of the form [L(n)M(μ-BHX)Mn(CO)(2)(η(5)-C(5)H(5))]. Most of these complexes react further at room temperature to lose HX and provide metalloborylene complexes [L(n)M-B = Mn(CO)(2)(η(5)-C(5)H(5))]; however, when ML(n) = Re(CO)(5) the σ-(halo)boranyl complex decomposes into unidentifiable products. We found through DFT calculations that two electronically and structurally distinct forms of the intermediate σ-(halo)boranyl complexes exist, one of which easily loses HX and one that does not.     

Studies on the asymmetric synthesis of huperzine A. Part 2: Highly enantioselective palladium-catalyzed bicycloannulation of the β-keto-ester using new chiral ferrocenylphosphine ligands

New chiral ferrocenylphosphine ligands were designed and tested in the enantioselective bicycloannulation of β-keto-ester 2 with bifunctional allylic agent 4. A range of e.e. values from 80 to 90% of the bicyclic intermediate 6 was achieved. Subsequently, enantiopure (−)-huperzine A was prepared in ca. 40% yield from β-keto-ester 2.     

Preparation of new chiral pyrrolidinebisphosphines as highly effective ligands for catalytic asymmetric synthesis of R-(−)-pantolactone

New chiral pyrrolidinebisphosphines, MSCPM, PCPM and BCPM, were prepared. Among them, BCPM was found to be the most effective ligand for catalytic asymmetric synthesis of R-(−)-pantolactone.     

Chiral pyrophosphites—synthesis and application as ligands in Rh(I)-catalyzed asymmetric hydrogenation

Enantiopure pyrophosphites have been prepared for the first time based upon two independent synthetic pathways. The new ligands based on binaphthols, which are remarkably stable towards oxidation, were tested in the Rh(I)-catalyzed asymmetric hydrogenation of functionalized olefins, where up to 70% ee could be achieved.     

Resolution of sclareolide as a key intermediate for the synthesis of Ambrox®

Sclareolide was efficiently resolved by a diastereomeric salt formation method using homochiral erythro-2-amino-1,2-diphenylethanol (ADPE) as a resolving agent.     

Camphor-based oxazaphospholanes as chiral templates for the enantioselective synthesis of α-chlorophosphonic acids

Constrained camphor-derived oxazaphospholanes have provided an efficient entry for the preparation of enantiomerically enriched α-chlorophosphonic acids.     

The synthesis of key intermediates in cembranolides

Two key intermediates of cembranolides- (2E,6E,10E)-3,7,11,15-tetramethyl-9-phenylsulfonyl-2,6,10,14-tetraen-1-hexadecanol (1) and (2E,6E,10E,14E)-2,6,10,14-tetramethyl-8-phenylsulfonyl-2,6,10,14-tetraen-1,16-hexadecanediol (2) were synthesized starting from geraniol and linalool and some improved synthetic methods were used.     

Reaction of catalytic enantioselective reductive aminolysis of δ2-oxazolin-5-ones as a method of asymmetric synthesis of α-amino acids

This investigation is devoted to the interaction of Δ²-oxazolin-5-ones, S(—)-α-phenylethy lamine and H₂ in the presence of PdCl₂ which yields α-phenylethylamides of acylamino acids of the S,S configuration, hydrolysis of the latter compounds resulting in the formation of optically pure amino acids and providing for chiral amine recycling. In DME, double bond saturation and ring opening in Δ²-oxazolin-5-one occur within the catalytic complex sphere without the intermediate formation of saturated oxazolinones or unsaturated amides. In t-BuOH, saturated oxazolinones are formed as intermediates. The catalyst formed in situ was shown to be a zero-valent Pd complex with S(—)-α-phenylethylamine stabilized by substrate coordination. The stereochemical pathway of the reactions has been traced. Reductive aminolysis involves cis-addition of H₂, while in reductive methanolysis H₂ trarns-addition occurs. The suggested process mechanism accounts for the ratio of aminolysis and racemization rates for saturated oxazolinones and the ratio of diastereomers of α-phenylethylamides of acylamino acids obtained by reacting unsaturated Δ²oxazolin-5-ones with S(—)-α-phenyl-ethylamine. In agreement with the postulated mechanism, the catalyst enantioselectivity is observed at the steps of substrate addition to the catalyst and proton transfer to the α-C-center, provided the process is carried out in DME. In the case of t-BuOH, the enantiodifferentiating action of the catalyst vanishes as a result of racemization, and process stereo selectivity appears at the step of saturated oxazolinone aminolysis with a chiral amine.     

Pd(II)/Brønsted acid catalyzed enantioselective allylic C-H activation for the synthesis of spirocyclic rings

A Pd(II)/Br?nsted acid catalyzed migratory ring expansion for the synthesis of indene derivatives possessing a stereogenic spirocyclic carbon center was developed. This transformation is believed to mechanistically proceed via enantioselective allylic C-H activation with concomitant semipinacol ring expansion to the nascent π-allylpalladium species. Enantioselectivities as high as 98% ee were attainable.     

Transformation of white phosphorus in the coordination sphere of nickel complexes with σ-donating ligands

Oxidation of white phosphorus in the coordination sphere of the nickel(ii) complex with 1,1,1-tris(diphenylphosphinomethyl)ethane and 1,1",5,5"-bis[methylenedi(p-phenylene)]di(3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane) was shown to be possible and accompanied by the transformation of P₄ into the -P₃ ligand. The change in the nickel state was monitored by cyclic voltammetry, ³¹P NMR spectroscopy, ESR, and IR spectroscopy.     

Cascade enantioselective synthesis of γ-aryl-γ-butyrolactones with a delayed stereoselective step

Enantioselective synthesis of γ-aryl-γ-butyrolactones is achieved using (S)-1-phenylethylamine as a chiral auxiliary. The synthesis involves cascade formation-destruction-formation of the chiral centre with a delayed stereoselective step. The actual stereoselective step has been found to be intramolecular nucleophilic attack on a diastereotopic carbocation formed, thereby resulting in the formation of non-racemic γ-aryl-γ-butyrolactones.     

BINOL-based azacrown ether catalyzed enantioselective Michael addition: asymmetric synthesis of α-aminophosphonates

Several novel 1,1′-bi-2-naphthyl-appended azacrown ethers with donor side-arms were synthesized and applied for the first time as chiral catalysts in the asymmetric Michael addition of an N-protected aminomethylenephosphonate onto acrylonitriles, resulting in high diastereoselectivity and enantioselectivity. The absolute configuration of the adduct was determined from its experimental and calculated CD spectra.     

Achiral β-amino alcohols as efficient ligands for the ruthenium-catalysed asymmetric transfer hydrogenation of sulfinylimines

Some achiral β-amino alcohols have been shown as efficient ligands for the ruthenium-catalysed asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropanol. The ruthenium complex prepared from [RuCl₂(p-cymene)]₂ (2.5 mol %) and 2-amino-2-methyl-1-propanol (5 mol %) leads to α-branched chiral primary amines with very high optical purities (up to 98% ee) by the diastereoselective reduction of the imines followed by removal of the sulfinyl group under mild acidic conditions. Short reaction times (2-3 h) were needed to complete the reduction reactions when they were performed at 50 °C.     

α-Pinene-type chiral Schiff bases as tridentate ligands in asymmetric addition reactions

A group of tridentate Schiff bases derived from (+)-α-pinene were synthesized. The steric effects in the transition state, the importance of π-π stacking interactions as well as the electronic effects of aryl aldehydes according to Hammett constant values in the enantioselective addition of Et₂Zn to aldehydes with the use of Schiff bases as chiral ligands are described. Also, a variety of aldehydes were cyanated using a catalyst prepared in situ from titanium tetraisopropoxide and chiral Schiff bases. The influence of a conjugated double-bond in the cyanation substrates on enantioselectivity was observed. The chemical structures of the chiral Schiff base-titanium alkoxide complexes are discussed based on their ¹H and ¹³C NMR spectra. 3D models of the Zn₂-complex catalyst and Ti-complex catalyst containing α-pinane-type Schiff bases based on X-ray diffraction experiments are postulated. The models presented were consistent with the reported chirality of the addition product and observed ee.