Tris-chelate complexes with chiral ligands: In search of diastereoisomeric selectivity with remote stereogenic centres

The chiral ligands, 4,4′-bis{(1S,2R,4S)-(−)-bornyloxy}-2,2′-bipyridine, (1S,2R,4S)-1, and 4,4′-bis{(1R,2S,4R)-(+)-bornyloxy}-2,2′-bipyridine, (1R,2S,4R)-1, have been prepared and characterized by spectroscopic techniques and, for (1S,2R,4S)-1, by single crystal X-ray diffraction. Despite the use of enantiomerically pure ligands, the formation of the complexes [Fe((1S,2R,4S)-1)₃]²⁺, [Ru((1S,2R,4S)-1)₃]²⁺, [Ru((1S,2R,4S)-1)(bpy)₂]²⁺ and [Ru((1R,2S,4R)-1)(bpy)₂]²⁺ proceeds without preference for either the Δ or Λ-diastereoisomers.     

A chiral cyclohexanone linked to polystyrene for solid-phase synthesis of chiral alpha-carbonyls

Two chiral cyclohexanones were linked to polystyrene resin. The polymer-bound auxiliaries were subjected to a sequence of four reactions, the last of which cleaves the desired alpha-chiral carbonyl compound off the resin, concurrently regenerating the resin-bound auxiliary in its original form. The resin can then be reused.     

A facile synthesis of novel chiral phosphonoacetates bearing a stereogenic phosphorus atom

Novel chiral phosphonoacetates bearing a stereogenic phosphorus atom were successfully synthesized by enzyme-catalyzed kinetic resolution of racemic phosphonoacetates.     

Novel chiral bisoxazoline ligands with a bipyridinyl backbone: preparation and interesting complexation behavior

Novel C₂-symmetric chiral bisoxazoline ligands with a bipyridinyl backbone were prepared with ease from 3,3′-dicarbomethoxy-2,2′-bipyridine and enantiomerically pure 2-amino alcohols via a corresponding amide as intermediate. Interestingly, when these ligands were coordinated with Pd(II) and Cu(I), different complexation behaviors were found.     

Efficient solid-phase synthesis of quinazoline-2,4-diones with various substituents on aromatic rings

We have developed a method for the solid-phase synthesis of quinazoline-2,4-diones with various substituents on the aromatic ring. Although there have been numerous reports of the solid-phase synthesis of quinazoline-2,4-diones, they were not applicable to the synthesis of the quinazoline-2,4-diones with electron-withdrawing substituents on the aromatic ring. Considering the poor nucleophilicity of the amino group of anthranilic acids, coupling of anthranilic acids to solid-supported amines was investigated without protecting the amino group. Various anthranilamides were prepared using anthranilic acids with electron-withdrawing substituents because a wide range of anthranilic acids are commercially available. These anthranilamides were successfully cyclized with carbonyldiimidazole to give quinazoline-2,4-diones with high purity.     

Phosphoramidate-mediated conversion of carbonyl ligands into isocyanide ligands: a new approach to chiral isocyanide ligands

Metal isocyanides have been used and studied by organometallic chemists for many years and, as a result, they have a rich and interesting chemistry. The nature of metal-free isocyanides and the methods of making isocyanide complexes, however, has resulted in the vast majority of studies to date being performed with structurally simple isocyanides. We report here a new approach to the synthesis of isocyanide ligands that involves the reaction of a metal carbonyl ligand with the anion of a phosphoramidate. As phosphoramidates can be synthesised in one step from amines, our method means that the structural diversity of readily available amines, particularly chiral amines, can now be incorporated into isocyanide ligands.     

Steric and electronic tuning of chiral bis(oxazoline) ligands with 3,3'-bithiophene backbone

[structure: see text] The role played by the electronic properties and the steric features of bis(oxazoline) ligands in the Cu(I)-catalyzed cyclopropanation of styrene effected with ethyl diazoacetate was investigated. Two pairs of new bis(oxazolines) displaying flexible and atropisomeric 3,3'-bithiophene backbones were synthesized and structurally and electronically characterized. For the first time, the electrochemical oxidative potential was used as a reliable index of the electronic density on the nitrogen atom of the chelating groups of new and, for comparative purposes, of already known bis(oxazolines). The Cu(I) complexes of the new ligands were prepared, and their enantioselection ability and catalytic efficiency were tested. This investigation suggests that steric factors and catalyst geometrical features are clearly more important than any consideration of the electronic properties of the chiral ligands.     

General approach for the synthesis of chiral perylenequinones via catalytic enantioselective oxidative biaryl coupling

By using oxygen as the terminal oxidant, copper complexes derived from chiral 1,5-diaza-cis-decalin catalyze the enantioselective oxidative biaryl coupling of highly functionalized naphthols to provide octa- and decasubstituted binaphthalenes with high selectivity (86-90% ee). Products containing very electron-rich naphthalenes were prone to epimerization under the reaction conditions. This epimerization could be suppressed by employing naphthol starting materials with phenol protecting groups that attenuated the electron-rich nature of the naphthalenes. Direct oxidation of the resultant chiral 1,1'-binaphthol framework completed the first asymmetric synthesis of a perylenequinone containing only an axial chirality element.     

Two dialkoxynaphthalene aldehydes as backbone amide linkers for solid-phase synthesis

Two new solid-phase handles for backbone amide anchoring based on regioisomeric dialkoxynaphthalene aldehydes (NALdehydes) were synthesized in five convenient steps from the corresponding commercially available dihydroxynaphthalenes. The two NALdehydes were coupled to an aminomethyl polystyrene support, the first monomer attached by efficient reductive amination, and the secondary amine acylated to form naphthalene amide linker (NAL-1 and NAL-2) anchoring. After on-resin synthesis, release of peptides was effected with TFA/H(2)O (95:5), TFA/DCM (50:50), or low TFA concentrations. The properties of the NAL handles were evaluated in the solid-phase synthesis of a series of peptides, in which NAL-2 showed the best cleavage properties.     

Template-directed approach to solid-phase combinatorial synthesis of furan-based libraries

A novel furan based scaffold 5-hydroxymethylfurfural has been identified for the generation of combinatorial libraries using template directed approach on solid phase. This scaffold has been utilized to afford furan-based bi-heterocyclic structures with extensive chemical diversity using cycloaddition, multicomponent and cyclization reactions.     

Dynamic behaviour attributed to chiral carbohydrate substituents of N-heterocyclic carbene ligands in square planar nickel complexes

Nickel complexes having acetylated glucopyranosyl group incorporated N-heterocyclic carbene (NHC) ligands with methyl or benzyl groups as an N-substituent exhibit two kinds of dynamic behaviours in solution (1)H NMR spectroscopy. One of the dynamic behaviours is attributed to the anti- and syn-rotamers, which occur by the rotation of the unsymmetrical NHC ligands around the axes of the Ni-C bonds. The other is attributed to the diastereomers of the syn-rotamers, which occur by opposite rotation of the imidazolylidene rings and the chiral carbohydrate group incorporated into the NHC ligands. Crystallographic analysis of the nickel complex having the NHC ligand with acetylated glucopyranosyl and benzyl groups as N-substituents showed CH-π interaction between the glucopyranosyl unit of each NHC ligand and the phenyl ring of the other NHC ligand in the complex in the solid state.     

A novel approach to the synthesis of benzoic and cinnamic acid derivatives with nor-isoprenoid substituents

A novel strategy for the synthesis of 4-(nor-polyprenyl)-substituted benzoic acids and their esters of the general formula1 as well as their vinylogs of the type2, based on the use of terephthalic aldehyde (3) and its tetramethyl acetal (13), is elaborated. The carbonyl groups in dialdehydes3 and12 can be selectively involved in the reaction sequences leading to the introduction of both aliphatic and functional substituents in positions 1 and 4 of the benzene ring.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 910–913, May, 1993.     

Atropisomeric amides as chiral ligands: using (-)-sparteine-directed enantioselective silylation to control the conformation of a stereogenic axis

An enantiomerically pure (1-trimethylsilyl)ethyl group, constructed by a (-)-sparteine-directed enantioselective quench of a laterally lithiated tertiary aromatic amide, exerts powerful thermodynamic control over the conformation of the adjacent tertiary amide substituent. Ortholithiation and functionalization of the amide in the 6-position allows the single amide conformer to be trapped as an enantiomerically and diastereoisomerically pure amide atropisomer. Protodesilylation of the amide gives functionalized atropisomeric amides with a stereogenic axis of single absolute configuration, whose barriers to racemization have been determined by polarimetry. Enantiomerically pure amides bearing phosphine substituents are effective ligands in a Pd-catalyzed allylic substitution reaction-the first use of a nonbiaryl atropisomer as a chiral ligand-and give products with 90% ee. The rate of racemization of the phosphine-substituted amide is powerfully influenced by the presence of palladium.     

Synthesis of novel norephedrine-based chiral ligands with multiple stereogenic centers and their application in enantioselective addition of diethylzinc to aldehyde and chalcone

Novel norephedrine-based chiral ligands with multiple stereogenic centers were conveniently prepared from norephedrine and N-substituted pyrrole. These novel chiral ligands were used to catalyze the enantioselective addition of diethylzinc to aldehydes and to chalcone in high yields and with good to high enantioselectivities. The absolute configuration of products was found to be affected by the stereogenic centers on the norephedrine part of the novel chiral ligands.     

A new approach to the synthesis of ‘chiral’ glycine

The stereospecific coordination of N-benzylglycinate ion in ΔR-(N-benzylglycinato)bis(ethylene-diamine) cobalt(III) chloride has been determined by X-ray crystallographic analysis, rotatory dispersion and ¹H NMR spectroscopy. The chiral glycinato-N and Co centres influence the relative rates of exchange of the diastereotopic glycine methylene protons in basic solution (pH 10·5 with Na₃PO₄inD₂O) and a synthesis supposedly of S-(N-benzyl)- 2-²H glycinate ion ≈ 80% optical purity) has been achieved.     

A facile approach to the synthesis of chiral 2-substituted benzofurans

An effective route to chiral optically active 2-substituted benzofurans directly from carboxylic acids is reported. This procedure, which allows the preparation of alpha-alkyl-2-benzofuranmethanamines from N-protected alpha-amino acids without sensible racemization phenomena, proceeds in good yields under mild conditions with the help of microwave irradiation.     

Microwave-assisted, solid-phase synthesis of a chiral 1,2,3,4-tetrahydro-quinoline library

The synergy of a solution-phase preparation of scaffolds with a solid-phase combinatorial synthesis let to develop an efficient route to a small library of chiral, highly functionalized tetrahydroisoquinolines. Both loading on the Merrifield resin and the key acid-catalyzed Pictet-Spengler condensation were efficiently promoted by microwave irradiation. The library was designed such that up to five points of diversity would be potentially introduced, making the strategy in principle suitable for generation of a large number of compounds.