The use of a new carboranylamidophosphite ligand in the asymmetric Rh-catalyzed hydrogenation of α- and β-dehydroamino acid derivatives

New chiral carboranylamidophosphite ligand was synthesized and tested in the Rh-catalyzed asymmetric hydrogenation of α- and β-dehydroamino acid derivatives (up to 93% ee). The catalytic performance is affected greatly by temperature and the nature of solvents. Importantly, we have shown that in the hydrogenation of the β-dehydroamino acid derivatives the use of acidic 1,1,1,3,3,3-hexafluoro-2-propanol led to a significant increase in the enantioselectivity, compared to isopropyl alcohol.     

Studies on the rhodium- and ruthenium-catalyzed asymmetric hydrogenation of α-dehydroamino acids using a family of chiral dipyridylphosphine ligand (P-Phos)

The applications of the chiral dipyridylphosphine ligand P-Phos and its derivatives Tol-P-Phos and Xyl-P-Phos in Ru- and Rh-catalyzed hydrogenations of the methyl esters of a variety of (Z)-2-acetamido-3-arylacrylic acids have been studied systematically. The results show that the electronic and steric properties of these ligands have significant influences on the enantioselectivity of the reduction. Rh and Ru complexes of the same dipyridylphosphine ligand family exhibit different trends in enantioselectivity toward the same substrate.     

Dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation

The dynamic kinetic resolution of β-aryl α-keto esters has been accomplished using a newly designed (arene)RuCl(monosulfonamide) transfer hydrogenation catalyst. This dynamic process generates three contiguous stereocenters with remarkable diastereoselectivity through a reduction/lactonization sequence. The resulting enantioenriched, densely functionalized γ-butyrolactones are of high synthetic utility, as highlighted by several secondary derivatizations.     

Synthesis of α,β-diamino acid derivatives via asymmetric Mannich reactions of glycine imino esters catalyzed by a chiral phosphoramidite·silver complex

AgOTf·phosphoramidite complexes efficiently catalyze the enantioselective Mannich-type reaction between benzophenone-imine glycine methyl ester and N-tosyl aldimines in the absence of a base. The corresponding syn-adducts, which are the direct precursors of α,β-diamino acids, are obtained with moderate to good syn-diastereoselectivities (up to 9:1) and high enantioselectivities (up to 99% ee).     

Rhodium-catalyzed and zinc(II)-triflate-promoted asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones

The asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones has been accomplished using an in situ formed rhodium-Josiphos catalyst. The reaction is enhanced by addition of catalytic zinc(II) triflate, which significantly improves turnover frequency while suppressing epimerization of the products.     

Diastereoselective photodeconjugation of chiral α,β-unsaturated esters

Chiral alcohols available in both enantiomeric forms have been tested for the diastereoselective photochemical deconjugation of 2,4-dimethylpentenoic acid esters. (R)-Pantolactone afforded selectively the (2R)-β,γ-unsaturated ester in good yield and high d.e. (89%), while analogous use of (S)-pantolactone gave the (2S)-stereoisomer with similar selectivity.     

Cu(I)-catalyzed asymmetric α-hydroxylation of β-keto esters in the presence of chiral phosphine-Schiff base-type ligands

Chiral phosphine-Schiff base-type ligand L1 prepared from (R)-(?)-2-(diphenylphosphino)-1,1′-binaphthyl-2′-amine was found to be a fairly effective ligand for Cu(I)-promoted enantioselective α-hydroxylation of β-keto esters using oxaziridine 2a as the oxidant to give the corresponding products in high yields along with moderate enantioselectivities.     

New one pot synthesis of a chiral α-hydroxy-γ-butyrolactone via sequential asymmetric hydrogenation of an α,γ-diketoester

The hydrogenation of ethyl 2,4-dioxovalerate in the presence of chiral rhodium or ruthenium catalysts provides direct access to 2-hydroxy-4-methyltetrahydrofuran-2-one 4 with syn:anti ratios of up to 84:16 and with up to 98% and 94% e.e. in the syn and anti form, respectively.     

Novel and practical asymmetric synthesis of β2,3-amino esters using asymmetric Michael addition of chiral amine

A practical method for the synthesis of chiral β^2,3-amino esters having various substituents was developed, which is characterized by an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted (E)-α,β-unsaturated esters. We found that a highly face-selective protonation occurred by the quick addition of water to the enolate intermediate derived from the Michael addition reaction to afford N-protected β^2,3-amino esters in moderate to excellent yields. This finding was made possible by the facile preparation of geometrically pure trisubstituted (E)-α,β-unsaturated esters, which was established recently by our group. The subsequent deprotection of the amino group in the Michael adduct by using N-iodosuccinimide (NIS) efficiently provided β^2,3-amino esters having various substituents.     

A novel and effective chiral phosphoramide catalyst for the borane-mediated asymmetric reduction of prochiral α-halo ketones

The novel chiral phosphoramide, 1,4-bis[(5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo(3.3.0)octan-2-yl]piperazine, was synthesised and successfully employed as a catalyst in the borane-mediated asymmetric reductions of prochiral α-halo ketones, providing the corresponding α-halo alcohols in 90–95% enantiomeric purities.     

Axially chiral C2-symmetric N-heterocyclic carbene (NHC) palladium complex-catalyzed asymmetric α-hydroxylation of β-keto esters

Axially chiral C₂-symmetric N-heterocyclic carbene (NHC) palladium diaquo complexes 1a and 1b, derived from (R)-BINAM, are effective catalysts for the enantioselective α-hydroxylation of β-keto esters using oxaziridine 2a as the oxidant to give the corresponding products in high yields along with moderate enantioselectivities.     

Use of rhodium complexes with amphiphilic and nonamphiphilic ligands for the preparation of chiral α-aminophosphonic acid esters by hydrogenation in micellar media

Several kinds of micelle forming amphiphiles were tested in the asymmetric hydrogenation of the prochiral dialkyl 1-benzamido-2-phenyl-ethenephosphonates in aqueous media. The chiral catalytic system [Rh(cod)₂]BF₄/BPPM or amphiphilized PPM proved to be suitable for the hydrogenation reaction affording enantiomeric excesses up to 99%. A chiral induction is possible to a certain extent (up to 11% ee) by selected chiral amphiphiles in the presence of achiral rhodium catalysts.     

Stereochemistry of transition metal catalyzed asymmetric intramolecular allyl transfer in chiral α-sulfinyl allylic esters

The stereochemistry of palladium or nickel catalyzed asymmetric intramolecular allyl transfer in chiral α-sulfinyl allylic esters was determined. The participation of the catalyst and the chiral sulfinyl functionality in these transformations, presumably by the coordination of the sulfinyl group to the catalyst, is discussed, and a novel mechanism is proposed for the rationalization of the results obtained.     

Highly efficient catalysts derived from planar chiral ferrocenes for asymmetric transfer hydrogenation of ketones

Planar chiral ferrocenes 1 and its diastereoisomer 2 were found to be good lig-ands for the ruthenium catalyzed asymmetric transfer hydrogenation of ketones with i-PrOH as hydrogen source under refluxing in the presence of sodium hydroxide. The results showed that the absolute configuration of alcohol seemed to be governed by the central chirality in the oxazoline ring instead of the planar chirality. At a ratio of 1:2 for Ru:ligand, 3000:1 S/C and >100,000/h-1 TOF were observed for acetophenone. For propiophenone 99% yield and 85% e.e. were obtained     

A robust Ru-PNNP catalyst system for the asymmetric hydrogenation of α,β-unsaturated ketones to allylic alcohol

A robust and stable Ru-Biphosphinobioxazoline catalyst system is discovered for the highly enantioselective hydrogenation of enones to allylic alcohols. A series of acyclic α,β-unsaturated ketones react well affording the desired products in high yields (up to 98%) and enantioselectivities (up to 98% ee). Simple manipulation process and tolerance of water and air make this catalysis more practical and appealing.     

Dynamic kinetic resolution of α-chloro β-keto esters and phosphonates: hemisynthesis of Taxotere® through Ru-DIFLUORPHOS asymmetric hydrogenation

The dynamic kinetic resolution (DKR) of racemic α-chloro β-ketoesters and α-chloro β-ketophosphonates through ruthenium-mediated asymmetric hydrogenation is reported. The corresponding α-chloro β-hydroxyesters and α-chloro β-hydroxyphosphonates were obtained in good to high enantio- and diastereomeric excesses using, in particular, the atropisomeric ligand DIFLUORPHOS. This methodology allowed an efficient preparation of the anti phenylisoserine side chain of Taxotere® which has been used for the hemisynthesis of the cancer therapeutic agent itself. In addition, ¹³C NMR in chiral oriented solvents was used to investigate the DKR effect.     

A facile synthesis of chiral ω-allyl- and ω-n-propyllactones via asymmetric allylboration of formyl esters with B-allyldiisopinocampheylborane

Asymmetric allylboration of aldehydes containing an adjacent ester group with B-allyldiisopinocampheylborane, followed by hydrolysis and cyclization, provides the corresponding allyl substituted lactones in high yields and ≥92% enantiomeric excess. Hydrogenation of these lactones provides the corresponding propyl substituted lactones without any loss of optical purity.     

Catalytic asymmetric chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones

Highly efficient catalytic chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones has been developed via a chloronium-based mechanism to deliver anti-regioselective vicinal chloroamines instead of the aziridinium intermediates delivered aminochlorides. The combination of TsNCl(2) and TsNH(2) as reagents made the transformation highly efficient, delivering the γ-carbonyl-β-chloro-α-amino acid derivatives and α-chloro-β-amino-ketone derivatives in nearly quantitative yields with up to 99% ee and 99:1 dr under 0.05-0.5 mol % catalyst loading. TsNHCl was demonstrated to act as the key reactive species to form a bridged chloronium ion intermediate in the presence of a chiral scandium complex. The method might provide useful information for further realization of other haloamination reactions.