Asymmetric enamide hydrogenation using planar-chiral cyrhetrenes

The catalytic asymmetric hydrogenation of α-arylenamides using catalysts prepared in situ from [Rh(cod)₂]BF₄ and cyrhetrenyldiphosphines was effective with a range of enamides. The corresponding acetamides were obtained with up to 93% ee.     

Asymmetric hydrogenation using chiral phosphinite rhodium complexes

The Cu(I) complex of (1R,3R)-bis(diphenylphosphinoxy)-1,3-diphenylpropane (BDPODP) has been prepared and used for the transfer of the ligand to Rh(I). The Rh(I) complexes of this new phosphinite obtained by this method act as efficient asymmetric homogeneous hydrogenation catalysts for (Z)-α-(acylamino)-cinnamic acids.     

Highly enantioselective synthesis of α-(perfluoroalkyl)amines via hydrogenation of enamide precursors in the presence of chiraphos-rhodium catalyst

Highly (up to 99% ee) enantio-enriched perfluoroalkyl amines can be synthesized by the perfluoroalkylation of nitriles with Lewis acidic perfluoroalkyl titanate reagents and catalytic asymmetric hydrogenation with the chiraphos-Rh catalyst of the resultant perfluoroalkyl enamides via base-mediated tautomerization.     

Asymmetric enamide hydrogenation in the synthesis of N-acetylcolchinol: a key intermediate for ZD6126

A synthesis of N-acetylcolchinol, a key intermediate in the synthesis of ZD6126, was developed. The enantiodifferentiating step required the catalytic asymmetric hydrogenation of an enamide. After screening a range of metal and ligand combinations it was found that (S,S)-ⁱPr-FerroTANE Ru(methallyl)₂ and [(S,S)-^tBuFerroTANE Rh(COD)]BF₄ gave both high enantioselectivity (>90% ee) and high catalyst utility (molar S/C = 1000).     

Transfer hydrogenation of unfunctionalised alkenes using N-heterocyclic carbene ruthenium catalyst precursors

Transfer hydrogenation of unfunctionalised and aliphatic alkenes in iPrOH/KOH is efficiently catalysed by an olefin-tethered N-heterocyclic carbene ruthenium complex, which also catalyses double bond migration as a competitive and considerably faster process.     

Cycloruthenated primary and secondary amines as efficient catalyst precursors for asymmetric transfer hydrogenation

[reaction: see text] Ruthenacycles obtained by cyclometalation of enantiopure aromatic primary or secondary amines with [(eta6-benzene)RuCl2]2 or with [(eta6-p-cymene)RuCl2]2 are efficient catalysts for asymmetric transfer hydrogenation (TOF up to 190 h(-1) at room temperature). Enantioselectivities in the transfer hydrogenation of acetophenone ranged from 38% to 89%. It is possible to prepare the catalysts in situ, which allows the use of high throughput experimentation.     

Asymmetric hydrogenation of tryptophan precursors catalyzed by rhodium-DIOP complexes

Z-2-benzamido(acetamido)-3-(3-indolyl)-2-propenoic acids were hydrogenated with neutral and cationic rhodium(I) complexes containing the chiral diphosphine (–) or (+)–2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)-butane [(–) or (+)–DIOP].

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Z-2- ()-3-(3-)-2- () (I), (–) (+)-2,3--2,3--1,4- ()-.

     

Asymmetric hydrogenation of aromatic ketones using polymeric catalyst prepared from polymer-supported 1,2-diamine

tert-Butyloxycarbonyl (Boc) protected chiral 1,2-diamine monomers 3 were copolymerized with achiral vinyl monomers such as styrene, methacrylates, acrylates, methacrylamide, and acrylamide to give crosslinked polymers P2 containing chiral 1,2-diamine moieties. Deprotection of the Boc groups in the polymer afforded the crosslinked chiral 1,2-diamine polymer P3. The diamine polymer was allowed to react with RuCl₂/BINAP in DMF to form polymeric complex. Asymmetric hydrogenation of aromatic ketones smoothly proceeded using the polymeric complex to give the corresponding secondary alcohol in quantitative yield with high level of enantioselectivity up to 98% ee in a mixed solvent of DMF and 2-propanol. The polymeric catalyst can be recycled several times without loss of the activity.     

Asymmetric hydrogenation of imines and olefins using phosphine-oxazoline iridium complexes as catalysts

Herein we describe the synthesis of a new class of chiral phosphine-oxazolines and their application as ligands in iridium-catalyzed hydrogenations. Mechanistic aspects of olefin hydrogenation with this class of iridium catalysts are discussed and a selectivity model to help rationalize the results obtained is also presented.     

Asymmetric hydrogenation of dehydroamino acid derivatives catalyzed by a new aminophosphine phosphinite ligand derived from ketopinic acid

A new chiral aminophosphine phosphinite N,O-bis(diphenylphosphino)-(1S,2R)-1-(N-methylamino) methyl-2-hydroxyl-7,7-dimethylbicyclo[2.2.1]heptane was synthesized from ketopinic acid and its application to the asymmetric hydrogenation of dehydroamino acid derivatives examined.     

Asymmetric hydrogenation of quinolines with recyclable and air-stable iridium catalyst systems

The iridium complex-catalyzed asymmetric hydrogenation of quinolines in a DMPEG/hexane biphasic system was studied. Catalysts with C₂-symmetric ligands such as Xyl-P-Phos, Cl–MeO–BIPHEP, SYNPHOS, and DifluorPhos are highly effective for this type of reaction. Most of the catalysts tested can be retained in DMPEG (M_n = 500), and the asymmetric hydrogenation of various quinoline substrates can be carried out in DMPEG/hexane biphasic system with up to 92% ee. The catalysts and the products can be separated via simple phase separation, and the reactivity/stereoselectivity of the catalysts can be retained for at least three reaction cycles.     

Asymmetric hydrogenation of aryl ketones mediated by a copper catalyst

[reaction: see text] A novel asymmetric hydrogenation protocol using a copper catalyst is reported. A Cu(I) complex in the presence of nonracemic BDPP hydrogenates aryl ketones with moderate to high enantioselectivity.     

Asymmetric hydrogenation of quinolines with high substrate/catalyst ratio

The chiral diphosphinite ligand derived from (R)-1,1'-spirobiindane-7,7'-diol has been found to be highly effective in the Ir-catalyzed asymmetric hydrogenation of quinolines with high substrate/catalyst ratio (up to 5000) and high enantioselectivity (up to 94% ee).     

Asymmetric metal-free synthesis of fluoroquinolones by organocatalytic hydrogenation

A highly enantioselective organocatalytic transfer hydrogenation enabling the synthesis of both 6-fluoro-2-methyltetrahydroquinoline and 7,8-difluoro-3-methyl-benzoxazine has been developed. These key building blocks can for the first time be synthesized using the same methodology allowing fast and efficient, metal-free access to the antibiotic fluoroquinolones flumequine and levofloxacine.     

Divergent synthesis of L-sugars and L-iminosugars from D-sugars

An efficient divergent synthesis of L-sugars and L-iminosugars from D-sugars is described. The important intermediate, delta-hydroxyalkoxamate, prepared from D-glucono-/galactono-1,5-lactone, was cyclized under Mitsunobu conditions to give the O-cyclized oxime compound and the N-cyclized lactam compound as mixtures. A more detailed investigation revealed that the appropriate protecting groups and solvents controlled the specificity for the O-/N-cyclization of the delta-hydroxyalkoxamate. Suitable protection at the 6-position of delta-hydroxyalkoxamate, derived from D-glucono-1,5-lactone, afforded the corresponding O-alkylation product alone. Thus we succeeded in applying this to the total synthesis of L-iduronic acid. In contrast, with both TBDMS as the protecting group and RCN as the solvent the efficient conversion of D-glucono/galactono-1,5-lactone into the corresponding L-iminosugars (L-idonolactam and L-altronolactam) was achieved.     

Asymmetric hydrogenation of isobutyrophenone using a [(Diphosphine) RuCl2 (1,4-diamine)] catalyst

[reaction: see text] The use of three chiral 1,4-diamines in the [(diphosphine) RuCl(2) (diamine)] catalyst system is demonstrated in the hydrogenation of acetophenone. The use of a 1,4-diamine offers unique properties that allow tuning of the catalyst system. These include the first example of the use of a racemic diamine in combination with a chiral phosphine, which gives 95% ee in the hydrogenation of isobutyrophenone.     

Asymmetric hydrogenation of ketones using a ruthenium(II) catalyst containing BINOL-derived monodonor phosphorus-donor ligands

[structure: see text] A series of ruthenium(II) complexes containing BINOL-based monodonor phosphorus ligands have been prepared and applied to the asymmetric catalysis of the hydrogenation of aryl/alkyl ketones. The best ligands for this application are those which contain an aromatic groups with either a methoxide or bromide on the ortho position. Using these ligands, alcohols with ee's of up to 99% are formed.     

A heterogeneous Pd-Bi/C catalyst in the synthesis of L-lyxose and L-ribose from naturally occurring D-sugars

A critical step in the synthesis of the rare sugars, L-lyxose and L-ribose, from the corresponding D-sugars is the oxidation to the lactone. Instead of conventional oxidizing agents like bromine or pyridinium dichromate, it was found that a heterogeneous catalyst, Pd-Bi/C, could be used for the direct oxidation with molecular oxygen. The composition of the catalyst was optimized and the best results were obtained with 5 : 1 atomic ratio of Pd : Bi. The overall yields of the five-step procedure to L-ribose and L-lyxose were 47% and 50%, respectively. The synthetic procedure is advantageous from the viewpoint of overall yield, reduced number of steps, and mild reaction conditions. Furthermore, the heterogeneous oxidation catalyst can be easily separated from the reaction mixture and reused with no loss of activity.