P. P. Righetti

Copper (II) in organic synthesis. XI. Evaluation of the ligand architecture on the efficiency of a copper (II) catalyst for enantioselective Michael reactions

Abstract Several bis-copper (II) complexes with chiral ligands derived from 2-substituted 2-(salicylideneamino) ethanols have been tested as catalysts of enantioselective Michael reactions. The degree of enantioselection is strongly affected by the architecture of the ligand. The best result (75% e.e.) was obtained for a ligand having a substituent potentially suitable to induce the formation of a bis-tetradentate copper (II) complex with a square pyramidal coordination.

CHIRAL AMPLIFICATION IN DIELS-ALDER AND 1,3-DIPOLAR CYCLOADDITIONS CATALYZED BY BIS(OXAZOLINE)-ZN(II)-BASED CHIRAL COMPLEXES

Abstract A Zn(II)-bis(oxazoline) chiral complex catalyzes the cycloaddition reactions of alkenoyl-oxazolidinones with both cyclopentadiene and diphenyl nitrone. The 1,3-dipolar cycloaddition becomes exo selective with an ee of up to 86%. While the Mg(II)-based catalysts give a linear relationship between the ligands optical purity and the ee of the reaction product, a remarkable positive nonlinear effect was observed in both cycloadditions by using Zn(II) as the cationic core of the catalyst. The result may be rationalized by the formation of a stable, insoluble, and catalytically inactive heterochiral complex.

Copper(II) in organic synthesis. VIII enantioselective michael reactions with chiral copper(II) complexes as catalysts

Abstract - Using copper(II) chiral complexes as catalysts, enantioselective Michael reactions were performed. The degree of enantioselectivity depended on the design of the catalyst and the best results (70% e.e.) were obtained with tetradentate ligands.

Can a chiral catalyst containing the same ligand/metal components promote the formation of both enantiomers enantioselectively? The bis(oxazoline)-magnesium perchlorate-catalyzed asymmetric Diels-Alder reaction

Abstract The Diels-Alder (DA) reaction between cyclopentadiene (1) and 3-acryloyl-1,3-oxazolidin-2-one (2), to give the endo adduct 5 as the main product, has been found to occur enantiosectively in the presence of catalytic amounts of magnesium perchlorate (MP) and 2,2-bis{2-[(4R)-phenyl-, [(4R,5S)- and [(4R,5R)-diphenyl-1,3-oxazolinyl]}propanes (3a-c respectively). The intermedia are the tetrahedral complexes 4a-c, with 2 and 3 coordinated around Mg(II), and their structures were investigated by NMR. Whereas 3a and 3b gave ee of (S)- 5 in the range 28–73%, 3c was an excellent ligand and 97% ee of (S)- 5 was obtained. When two equivalents of hydroxylic ligands (water or alcohols) are added, all these complexes can expand the coordination number of Mg(II) from 4 to 6. The octahedral complexes 6a-c are again good catalysts of the DA reaction but, with 3a and 3b, the enantioselectivity is reversed and (R)- 5 is obtained with ee up to 89%. For the first time, achiral auxiliary ligands can be used to invert the enantioselectivity induced by a chiral bis(oxazoline), so that both enantiomers can be synthetized with the same metal cation and chiral ligand. The catalytic enantioselective processes are discussed and a rationalization of the experimental results is proposed.

Solvent effect in pericyclic reactions. IX: The ene reaction

The solvent effect on the ene reactions of diethylazodicarboxylate and triazolindione was determined in 18 and 16 solvents respectively. The first enophile gives a solvent effect that depends on solvent acidity (type a solvent effect), while in the second reaction the significant solvent effect is the result of the nucleophilic character of the solvent (type b solvent effect). These are the same solvent behaviours observed in the analogous Diels-Alder cycloadditions, and evidence of the close parallel between these two pericyclic reactions was produced by determining the effect of inorganic perchlorates on their rates.

1,3-Dipolar cycloadditions catalyzed by bis(oxazoline)-magnesium-based chiral complexes. The importance of a Mg(II) counterion

Abstract The 1,3-dipolar cycloaddition between N -acryloyl-oxazolidinone and diphenyl nitrone is catalyzed by chiral catalysts derived from bis(oxazoline) (R) - 7 and Mg(II) perchlorate or triflate. In addition to complete regioselectivity, the endo cycloadduct can be obtained with up to 86% ee . The stereochemical results are due either to the specific counterion or to the presence of molecular sieves (as well as to the relative reagent concentrations). As a consequence, the enantioselecvity is opposite to that induced by the catalyst derived from Mg(II) iodide with the same chiral ligand.

Solvent effect as the result of frontier molecular orbital interaction. V. Diels-Alder with heterodienophiles: a unified approach to the solvent effect of the Diels-Alder reactions☆

Abstract The solvent effect of Diels-Alder (D.A.) reactions with heterodienophiles was measured in several solvents. The rate of the reaction between 2,3-dimethylbutadiene (DMB) and diethylazodicarboxylate increases with the increases in the Acceptor Number of the solvent which behaves as an electrophile. The rate of the reaction between DMB and p. bromonitrosobenzene shows a small solvent effect which correlates with the cohesive pressure (δH2) of the solvent. The rate of the reactions between DMB and tetrachloro- or tetrabromo-o.benzoquinones give an inverse linear relationship with Dπ basicity parameters, thus rate decreases with increases in the nucleophilic character of the solvent..p]These monoparametric correlations (alternatively obtained with electrophilic, nucleophilic or cohesive pressure parameters of the solvent) rationalize the solvent effect of D.A. reactions reported in the literature, which fit one of the above reported three classes. The same result is obtained if the Kamlet-Taft multiparametric equation is applied to the same set of reactions. The main contribution remains that outlined with the monoparametric approach and some secondary effects or some borderline cases are usefully focussed

Chiral Lewis acid controlled Diels-Alder reaction: Factors affecting the stereoselective formation of both enantiomers in the bis(oxazoline)-magnesium catalyzed process

Abstract The chiral Lewis acid controlled Diels-Alder (CLAC-DA) reaction between cyclopentadiene and 3-acryloyl- or (E)-3-crotonyl-1,3-oxazolidin-2-ones (2a,b), to give the endo adducts 3a,b has been studied. The use of magnesium perchlorate (MP) or magnesium triflate (MT), and three chiral bis(oxazolines) (5–7) and, eventually, 2 equiv of achiral auxiliary ligands X [water or tetramethylurea (TMU)], induces a strong change of the enantioface selectivity. The intermediates are either tetrahedral or octahedral. The MP-based intermediates can be either tetrahedral, giving rise to the endo (S) adducts enantioselectively, or, by addition of 2 equiv X, octahedral giving rise to the endo (R) adducts. The MT-based intermediates always have an octahedral configuration in the presence of two triflate ligands, and the endo (R) adducts are obtained enantioselectively. The controlled use of the different reagents to assemble the catalysts gives either (S)- 3 a in 94% ee from a tetrahedral complex, or (R)- 3 a in 93% ee from an octahedral one, whereas (R)- 3 b can be prepared with ee up to 95%.

4-Naphthyl-substituted bis(oxazoline): A new, easily recoverable and efficient chiral ligand in asymmetric catalysis of the Diels-Alder reaction

Abstract 2, 2-Bis{2-[(4R)-(2′-naphthyl)-1, 3-oxazolinyl]}propane and its (4S) enantiomer were prepared starting from 2-vinylnaphthalene, following the Sharpless protocol, and were found to be optically pure (ee ≥ 99.5%) by hplc analysis. These new bis(oxazolines) are efficient chiral ligands in the asymmetric catalysis of the Diels-Alder reaction ofN-alkenoyl-oxazolidin-2-one derivatives since endo cycloadducts are obtained with up to 94% ee. Different Lewis acids were tested, the best one being the Mg(II) cation derived from the corresponding triflate. A remarkable feature of such new chiral ligands is the low solubility in polar solvents, so that the chiral ligand can be easily recovered by a simple filtration. The recovered ligand can be directly reused in other asymmetric syntheses, without any further purification and, overall, without any drop in the induced enantioselectivities. New chiral bis(oxazolines) were prepared starting from 2-vinylnaphthalene, and were shown to be efficient chiral ligands in the asymmetric catalysis of the Diels-Alder reaction of N-alkenoyl-oxazolidin-2-one derivatives: complexes built on magnesium triflate the endo cycloadducts to be obtained with up to 94% ee. A remarkable feature of such new chiral ligands is the low solubility in polar solvents allowing an easy recovery of the bis(oxazoline) in 75% yield by a simple filtration Download : Download full-size image .

Lithium perchlorate catalysis of the hetero Diels-Alder reaction: a specific lithium cation effect.

Abstract The lithium perchlorate catalysis of the hetero Diels-Alder reaction between 1-phenyl-4-benzylidene-5-pyrazolone and ethyl vinyl ether was kinetically investigated in five solvents. The rate increases as the salt concentration increases and a linear relationship between the relative rate and the molar fraction of the salt can be obtained. All correlations converge on a single value and this strongly supports the presence of a catalysis promoted by the lithium cation acting as a Lewis acid. The nature of the interaction between the catalyst and the solvent was also investigated.