C2-Symmetric 4,4′,5,5′-Tetrahydrobi(oxazoles) and 4,4′,5,5′-Tetrahydro-2,2′-methylenebis[oxazoles] as Chiral Ligands for Enantioselective Catalysis Preliminary Communication

The synthesis of a series of enantiomerically pure, C₂-symmetric 4,4′,5,5′-tetrahydro-2,2′-methylenebis[oxazoles] and 4,4′,5,5′-tetrahydro-2,2′-bi(oxazoles) is reported. Copper complexes with anionic tetrahydromethylenebis[oxazole] ligands are efficient catalysts for the enantioselective cyclopropane formation from olefins and diazo compounds (up to 96% ee in the reaction of styrene with menthyl diazoacetate). Tetrahydrobi(oxazole)iridium(I) complexes were found to catalyze transfer hydrogenations of aryl alkyl ketones with i-PrOH (up to 91% ee). Tetrahydrobi(oxazole)palladium complexes can be used as enantioselective catalysts for allylic nucleophilic substitution (up to 77% ee in the reaction of PhCH?CHCH(OAc)Ph with NaHC(COOMe)₂).     

Synthesis of new C1-symmetric bis(oxazoline) ligands with a chelating sidearm for stereoselective Mukaiyama aldol condensations

Novel C₁-symmetric bis(oxazoline) ligands with a secondary binding sidearm were prepared in enantiomerically pure form in good yields, in only four steps starting from commercially available reagents. These new chiral ligands were tested in the enantioselective Mukaiyama aldol condensation between the trimethylsilyl keteneacetal of methyl isobutyrate and a non-chelating substrate such as benzaldehyde to afford the product in up to 55% ee.     

C2-Symmetric hemiaminal ethers and diamines: new ligands for copper-catalyzed desymmetrization of meso-1,2-diols and asymmetric Henry reactions

The synthesis of novel, enantiomerically pure C₂-symmetrical hemiaminal ethers and diamines containing piperazine core is presented. The key steps of the synthesis involve the dimerization of an in situ generated α-amino aldehyde into the corresponding cyclic bis-hemiaminal, followed by dehydration in the presence of a base to give a 7-oxa-2,5-diaza-bicyclo[2.2.1]heptane derivative, which can be regarded as a bicyclic bis-hemiaminal inner ether. These compounds represent a new class of molecule, with a structure unambiguously established for the first time. Finally, sodium triacetoxy-borohydride reduction gave the corresponding diamines. Both classes of compounds, new diamines and hemiaminal ethers, were shown to be good ligands for the copper(II)-catalyzed desymmetrization of meso-diols (up to 87% ee) and Henry reactions (up to 84% ee).     

Reduction of substituted 1,10-phenanthrolines as a route to rigid chiral benzimidazolylidenes

Variously substituted 1,10-phenanthrolines are reduced to octahydrophenanthrolines in moderate to good yields with NaBH₃CN in acetic acid/methanol. The exact solvent composition is important to avoid the formation of tetrahydrophenanthrolines and N-alkylated byproducts, and to optimize the formation of octahydrophenanthrolines. Resolution of a racemic reduction product gives an enantiomerically pure C₂-symmetric diamine from which the corresponding rigid benzimidazolylidene is prepared, whereas reduction of chiral phenanthrolines derived from bicyclic ketones affords diastereomerically pure diamines, which may also be converted to benzimidazolylidenes.     

Efficient synthesis of chiral C2-symmetric diamines via allylboration of bis-N,N′-metallodiimines

An enantioselective synthesis of C₂-symmetric bis-homoallylic aromatic and heteroaromatic diamines in 54-89% yields, in 73-94% de and ?98% ee has been achieved via the allylboration of the corresponding N,N′-bis(trimethylsilyl)dialdimines and N,N′-bis(diisobutylalumino)dialdimines with B-allyldiisopinocampheylborane in the presence of methanol, followed by alkaline hydrogen peroxide workup. One-pot synthesis of stable N,N′-bis(benzaldimine-triethylborane) complexes and subsequent allylboration to afford benzene diamines is also described.     

Chiral N-heterocyclic carbenes as asymmetric acylation catalysts

Chiral N-heterocyclic carbenes are generated from C₂-symmetric 1,3-bis(1-arylethyl)imidazolium salts and potassium tert-butoxide. These C₂-symmetric imidazolidenyl carbenes catalyze enantioselective acylation of racemic secondary alcohols. The asymmetric acylation of 1-(1-naphthyl)ethanol was achieved in up to 68% ee of the acylated product, using (R,R)-1,3-bis[(1-naphthyl)ethyl]imidazolium tetrafluoroborate as a precursor of the chiral N-heterocyclic carbene and vinyl propionate as the acyl donor.     

Enantioselective copper-catalyzed cyclopropanation of styrene by means of chiral bispidine ligands

Enantiopure C₁- and C₂-symmetric bispidine ligands have been synthesized and screened in the asymmetric copper-catalyzed cyclopropanation of styrene. In order to improve the enantiomeric excesses (ee) of the cyclopropane derivatives, the best performing C₁-symmetric diamine ligand was selected for studies on the reaction conditions. The optimized procedure allowed us to obtain up to 91% ee for the cis-cyclopropane derivative and up to 79% ee for the trans one.     

Efficient synthesis of enantiomerically pure trans-2,5-bis(arylethynyl)pyrrolidines. A new entry into C2-symmetric chiral secondary amines

A new class of C₂-symmetric pyrrolidine derivatives bearing arylethynyl groups at the 2,5-positions has been synthesized in enantiomerically pure form from 1,7-octadiyne-3,6-diol in five steps. Some notable features of the synthesis are: (i) the formation of a separable diastereomeric mixture of pyrrolidine carbamates using a newly prepared chiral chloroformate; and (ii) the development of a new method for the deprotection of the carbamate via a novel SmI₂-promoted electron transfer process.     

One-step synthesis of paclitaxel side-chain precursor: benzamide-based asymmetric aminohydroxylation of isopropyl trans-cinnamate

A highly enantioselective (up to 97% ee) one-step synthesis of paclitaxel side chain precursor, (2R,3S)-isopropyl 3-benzamido-2-hydroxy-3-phenylpropionate, has been achieved by osmium-catalyzed asymmetric aminohydroxylation of isopropyl trans-cinnamate with N-bromobenzamide as an oxidant/nitrogen source in the presence of (DHQ)₂PHAL as a chiral ligand. Simple recrystallization of crude product (containing regioisomer and diol) from ethyl acetate gave the enantiomerically pure product.     

Novel C2-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands: synthesis and application in asymmetric diethylzinc addition to aldehydes

First synthesis of C₂-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands is described. The Mukaiyama–Michael reaction was applied as an important reaction for the synthesis of 2,2-bipyridylpropane 9. Among the ligands synthesized, ligand 11 exhibits excellent chiral induction (up to 97% ee) in diethylzinc addition to various aldehydes. The use of additional Lewis acid such as Ti(OⁱPr)₄ in diethylzinc addition reaction is not required for the present catalytic system.     

Asymmetric cyanosilylation of ketones catalyzed by novel chiral N,N′-dioxide titanium complexes

A novel C₂-symmetric chiral N,N′-dioxide titanium complex was described, which could efficiently catalyze the asymmetric cyanosilylation of ketones in high yields with up to 92% ee under mild conditions. In addition, the catalyst system was simple and the ligands could be easily prepared from commercially available chiral amino acid.     

Stereoselective reductions with macrocyclic NADH models

Macrocyclic NADH models with two (C₂ symmetry) or four (D₂ symmetry) nicotinamide units comprised in a ring have been prepared and found to reduce activated carbonyl compounds in good yields and high enantiomeric excess. The roles of magnesium ions as a cocatalyst and the temperature have also been investigated. The smaller, C₂-symmetric macrocycle gave 96% ee upon reduction of ethyl benzoylformate whereas the best result with the larger D₂-symmetric model was 81% ee for the reduction of methyl benzoylformate.     

Development of a new class of C1-symmetric bisphosphine ligands for rhodium-catalyzed asymmetric hydrogenation

A new class of C₁-symmetric bisphosphine ligands with three hindered quadrants have been obtained through facile synthesis from chiral BINOL derivatives. Their rhodium complexes have exhibited high enantioselectivities (up to 98% ee) in the asymmetric hydrogenation of various unsaturated prochiral olefins, providing an efficient catalytic system for the enantioselective synthesis of chiral amino acids and amines.     

A new chiral sulfinyl-NH-pyridine ligand for Ir-catalyzed asymmetric transfer hydrogenation reaction

A new flexible C₁-symmetric tridentate ligand (S)-N-(2-(tert-butylsulfinyl)benzyl)-1-(pyridin-2-yl)methanamine sulfoxide (L1) was successfully prepared and utilized as a chiral ligand for Ir(I)-catalyzed ATH (asymmetric transfer hydrogenation) reactions. Without any cooperation of other chiral center, encouraging ee and conversion values have been achieved, which provide us a better understanding on these types of ligands and a new strategy to develop new high-efficiency chiral catalysts for asymmetric reaction.     

Photocatalytic deoxygenation of N–O bonds with rhenium complexes: from the reduction of nitrous oxide to pyridine N-oxides

The accumulation of nitrogen oxides in the environment calls for new pathways to interconvert the various oxidation states of nitrogen, and especially their reduction. However, the large spectrum of reduction potentials covered by nitrogen oxides makes it difficult to find general systems capable of efficiently reducing various N-oxides. Here, photocatalysis unlocks high energy species able both to circumvent the inherent low reactivity of the greenhouse gas and oxidant N₂O (E⁰(N₂O/N₂) = +1.77 V vs. SHE), and to reduce pyridine N-oxides (E_1/2(pyridine N-oxide/pyridine) = −1.04 V vs. SHE). The rhenium complex [Re(4,4′-tBu-bpy)(CO)₃Cl] proved to be efficient in performing both reactions under ambient conditions, enabling the deoxygenation of N₂O as well as synthetically relevant and functionalized pyridine N-oxides.

A rhenium-based photocatalyst enables the deoxygenation of several compounds containing N–O bonds, such as N₂O and pyridine N-oxides.     

Catalytic asymmetric addition of arylboronic acids to N-Boc imines generated in situ using C2-symmetric cationic N-heterocyclic carbenes (NHCs) Pd diaquo complexes

The catalytic asymmetric addition of arylboronic acids to N-Boc imines generated in situ from stable and easily prepared α-carbamoyl sulfones was realized by using chiral cationic C₂-symmetric N-heterocyclic carbene (NHC) Pd²⁺ diaquo complexes 1a-c as the catalysts, producing the corresponding adducts in good to high yields (up to 89%) and good to high enantioselectivities (up to 90% ee).     

Enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by C2-symmetric chiral diols

Optically pure C₂-symmetric diols have been synthesized with moderate yields in a straightforward manner, and are used as catalysts in the enantioselective alkylation of aromatic aldehydes with diethylzinc. The addition of diethylzinc to benzaldehyde and sterically hindered 1-naphthaldehyde was achieved with excellent enantioselectivities (97–99% ee) under catalysis with (1R,2R)-1,2-bis(3,5-dibromophenyl)-ethane-1,2-diol and (1R,2R)-1,2-bis(3,5-diphenylphenyl)-ethane-1,2-diol.     

SPANamine derivatives in the catalytic asymmetric α-fluorination of β-keto esters

The use of C₂-symmetric enantiopure nitrogen ligands in the asymmetric catalytic α-fluorination of β-ketoesters is described. SPANamine 1 in the presence of nickel salts gives up to 63% ee in the fluorination of tert-butyl 2-oxocyclopentanecarboxylate with N-fluorosuccinimide (NFSI). The same enantioselectivity is obtained when SPANamine 1 is used as an organocatalyst, although the reaction is much slower.     

Copper powder-catalyzed N-arylation of imidazoles in water using 2-(hydrazinecarbonyl)pyridine N-oxides as the new ligands

2-(2-Hydrazinecarbonyl)pyridine N-oxides, which were derived from pyrrole-2-carbohydrazides and pyridine N-oxides, were synthesized and utilized as the ligands for copper powder-catalyzed N-arylation of imidazoles with aryl halides in water. Imidazoles could be arylated smoothly with various aryl halides to provide the title products in preferable yields without the need of an inert atmosphere.     

A novel C2-symmetric bisphosphane ligand with a chiral cyclopropane backbone: synthesis and application in the Rh(I)-catalyzed asymmetric 1,4-addition of arylboronic acids

The synthesis of a novel C₂-symmetric bisphosphane ligand was accomplished starting from trans-(2R,3R)-bis(3′,5′-diphenylphenyl)cyclopropane-1,1-dimethanol as a key intermediate. This ligand was tested in the asymmetric rhodium(I)-catalyzed 1,4-addition to cyclic enones. We also compared the new ligand with a similar phosphane ligand with a less bulky cyclopropane backbone. Good yields (up to 99%) and enantioselectivities (up to 89% ee) were observed. We demonstrated that the presence of a more bulky cyclopropane backbone resulted in a less effective ligand.