A novel and efficient synthesis of chiral C2-symmetric 1,4-diamines

A novel and efficient method for synthesis of (R,R)- and (S,S)-C₂-symmetric 1,4-diamines was established. The key steps are a combination of Pinacol Coupling and Corey-Winter olefination.     

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.     

Stereodivergent synthesis of novel chiral C2-symmetric bis-trifluoromethyl-2-oxazolidinones

A simplified effective synthetic process is described for the diastereoselective synthesis of the chiral C₂-symmetric CF₃-ureas (R,R)-15 and (S,S)-15 from (S)-α-phenylethylamine, glyoxal and CF₃I.     

Studies in symmetry-driven synthesis of ryanodol: application of nucleophilic alkynylation for regio- and stereoselective desymmetrization

We developed a simple and novel desymmetrization strategy toward the total synthesis of ryanodol. The advanced intermediate 1 with six contiguous tetrasubstituted carbons was synthesized from the previously reported 3 by employing two key nucleophilic reactions. The first nucleophilic reaction to C₂-symmetric tetraketone 2 installed the C6-tetrasubstituted carbon in a regio- and stereoselective fashion, leading to desymmetrized mono-alkynylated 8 without forming C₂-symmetric bis-alkynylated 9. The second addition to triketone 8 also proceeded regio- and stereoselectively to construct the C2-tetrasubstituted stereocenter of 10.     

Synthesis of cis bis-β-lactams via Staudinger cycloaddition reaction using C2-symmetric 1,2-diamines

An efficient stereoselective synthesis of bis-β-lactams via cycloaddition reaction (Staudinger reaction) of ketenes with bisimines derived from C₂-symmetric 1, 2-diamines is described. The reaction provided diastereomeric mixture of meso and C₂-symmetric cis-bis-β-lactams with higher selectivity for meso-bis-β-lactams.     

Regioselective synthesis and antioxidant activity of a novel class of mono and C2-symmetric bis-1,2,3-triazole and acridinedione grafted macromolecules

An expedient regioselectivesynthesis of novel mono, C₂-symmetric bis-triazole and acridinedione bridged macromolecules has been achieved in good yields employing intermolecular Cu(I) catalyzed azide and alkyne click reaction. Synthesis of O-propargyl acridinedione was achieved in three good yielding steps starting from dimedone, while the symmetrical aliphatic and aryl bis-azides were derived from appropriate dibromides in the presence of sodium azide in dry DMF. The synthesized mono and C₂-symmetric bis-macromolecules have been elucidated by ¹H, ¹³C, elemental and mass spectroscopic analysis. The antioxidant activity of synthesized compounds has also been investigated.     

A novel and efficient total synthesis of shikonin

A novel and efficient synthesis of shikonin was accomplished with excellent enantiomeric excess (99.3% ee) and high overall yield (47%) in only six steps. The synthetic strategy involved an efficient Ru(II)-catalyzed asymmetric hydrogenation employing C₂-symmetric planar chiral ruthenocene phosphinooxazoline ligand (L-3), followed by the subsequent removal of the methyl protecting groups. Meanwhile, it could be preliminarily confirmed that the chiral side chain of shikonin was difficult to be constructed in one step with both stereoselectivity and α-regioselectivity.     

Enantiospecific synthesis of (−)-muricatacin from l-(+)-tartaric acid

Enantiospecific synthesis of (−)-muricatacin, a bio-active lactone comprising of a 5-hydroxyalkylbutan-4-olide structural component has been achieved from l-(+)-tartaric acid. The key step involves a disteroselective reduction of a C₂-symmetric 1,4-diketone derived from tartaric acid followed by a selective Grignard reagent addition.     

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.     

The design and synthesis of a new potentially C3-symmetric ferrocenylphosphine

A new potentially C₃-symmetric phosphine ligand ‘manphos’ has been obtained and fully characterized. The ligand which is a tri-ferrocenyl-tetra-phosphine is obtained in a simple and effective two step synthesis starting from 1,1′-dibromoferrocene via the intermediate compound tris-(1′-bromoferrocenyl)phosphine or alternatively via 1'-bromo-1-diphenylphosphinoferrocene. The iso-propylphosphino-analogue of manphos, tris-(1'-diisopropylphosphinoferrocenenyl)phosphine, has also been obtained, in addition to several functionalised derivatives of triferrocenylphosphine where the ferrocene rings have been substituted in the 1′-position.     

One-pot synthesis of a novel C1-symmetric diphosphine from 1,3-cyclic sulfate. Asymmetric hydroformylation of styrene

Preparation of a novel homochiral diphosphine with C₁-symmetry from the cyclic sulfate of (2R,4R)-2,4-pentanediol is reported. Reaction of a lithium phosphide salt with the cyclic sulfate affords a γ-phospholylsulfate which can be converted to a diphosphine ligand on treatment with a second equivalent of lithium phosphide. Using this ligand in the platinum-catalyzed asymmetric hydroformylation of styrene, outstanding levels of regio- and enantiocontrol were obtained (89/11 iso/n isomeric ratio and 89% e.e.). The results are compared with those obtained with the analogous ligands (bdpp and bdbpp) having C₂-symmetry. The novel unsymmetric ligand possessed the advantageous catalytic features of the C₂-symmetric parent ligands.     

Simultaneous 2-O-deacetylation and 4-amination of peracetylated Neu5Ac: application to the synthesis of (4→4)-piperazine derivatives linked sialic acid dimers

A simultaneous stereoselective 2-O-deacetylation and 4-amination reaction of peracetylated Neu5Ac 1 has been established with cyclic secondary amines, such as 1-N-Boc-piperazine. Four C₂-symmetric and two asymmetric sialic acid dimers with (4→4)-piperazine derivatives linked were synthesized. They may serve as precursors of unnatural polysialic acids.     

Synthesis of C2-symmetric 1,4-diketones from tartaric acid dichloride

Cross-coupling reactions of tartaric acid dichloride with organocopper reagents, derived from Grignard reagents, cuprous bromide and lithium bromide, provide a simple and straightforward method for the synthesis of C₂-symmetric 1,4-diketones.     

Atropo-enantioselective synthesis of a C3-symmetric tripodal ligand with three axially chiral biaryl subunits

In contrast to the numerous successful applications of C₂-symmetric biaryls as powerful tools for asymmetric synthesis, there have so far been only few reports on combinations of C₃-symmetry with axial chirality. We present here the first enantioselective synthesis of a novel family of tripodal ligands containing three axially chiral biaryl subunits in an (M,M,M)- or, optionally, (P,P,P)-configured form. The incorporation of a PCl₂- and a TiCl-fragment into the central cavity was achieved.     

The synthesis of novel C2-symmetric P,N-chelation ruthenocene ligands and their application in palladium-catalyzed asymmetric allylic substitution

Novel air-stable C₂-symmetric tetrasubstituted ruthenocene-based ligands were readily synthesized and used for palladium-catalyzed asymmetric allylic substitution showing excellent enantioselectivity and high catalytic activity.     

Comparing propene polymerization with 1-butene polymerization catalyzed by MAO-activated C2- and C1-symmetric zirconocenes: An experimental and computational study on the influence of olefin size on stereoselectivity

Polypropene and poly(1-butene) have been synthesized under very similar experimental conditions with a series of MAO-activated C₂-symmetric and C₁-symmetric ansa-zirconocenes. The C₁-symmetric zirconocenes bearing the bilaterally symmetric fluorenyl or bis(2-methylthieno)cyclopentadienyl ligand connected through a dimethylsilyl bridge to substituted indenyl ligands produce isotactic polybutene of similar or higher molecular mass and with noticeably higher isotacticity, compared to isotactic polypropene prepared with the same catalysts under comparable conditions. Structural and mechanistic reasons for such behavior are discussed on the basis of QM/MM calculations.     

A novel optically active bisphosphine ligand CDP,derived from an anti head-to-head coumarin dimer: synthesis and application to the rhodium-catalyzed asymmetric hydrogenation of arylenamides

A novel optically active bisphosphine ligand CDP containing a C₂-symmetric cyclobutane ring was prepared from an enantiopure anti head-to-head coumarin dimer. CDP was successfully applied to the rhodium-catalyzed asymmetric hydrogenation of arylenamides, affording the corresponding amides up to 93% e.e.     

A short approach to the synthesis of the ritonavir and lopinavir core and its C-3 epimer via cross metathesis

A short synthesis of hydroxyethylene dipeptide isostere, a core unit of the HIV-protease inhibitors ritonavir and lopinavir, its C-3 epimer and C₂ symmetric diamino diol is described. The crucial aspects of the synthesis are self-cross metathesis and exploitation of C₂-symmetric of the metathesis product 8 to obtain the required skeleton.     

Nanopatterns of molecular spoked wheels as giant homologues of benzene tricarboxylic acids

Molecular spoked wheels with D_3h and C_s symmetry are synthesized by Vollhardt trimerization of C_2v-symmetric dumbbell structures with central acetylene units and subsequent intramolecular ring closure. Scanning tunneling microscopy of the D_3h-symmetric species at the solid/liquid interface on graphite reveals triporous chiral honeycomb nanopatterns in which the alkoxy side chains dominate the packing over the carboxylic acid groups, which remain unpaired. In contrast, C_s-symmetric isomers partially allow for pairing of the carboxylic acids, which therefore act as a probe for the reduced alkoxy chain nanopattern stabilization. This observation also reflects the adsorbate substrate symmetry mismatch, which leads to an increase of nanopattern complexity and unexpected templating of alkoxy side chains along the graphite armchair directions. State-of-the-art GFN-FF calculations confirm the overall structure of this packing and attribute the unusual side-chain orientation to a steric constraint in a confined environment. These calculations go far beyond conventional simple space-filling models and are therefore particularly suitable for this special case of molecular packing.

Scanning tunneling microscopy investigations of phenylene-based molecular spoked wheels with D_3h and C_s symmetries on graphite show the competitive or complementary effects of carboxylic acid groups and alkoxy chains on the nanopattern formation.     

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.