Oreste Piccolo

Asymmetric nickel-catalyzed cross-coupling reaction of allylic substrates with grignard reagents

Two possible routes for the synthesis of optically active olefinic compounds through cross-coupling reaction between allylic electrophiles and Grignard reagents catalyzed by nickel complexes containing chiral diphosphine ligands were investigated: i) the reaction of chiral racemic (or prochiral) allylic compounds with achiral Grignard reagents and ii) the reaction of chiral Grignard reagents with allyl electrophiles. Optical yields higher than 90% were obtained for the first reaction route (compound 11) and up to 58% (compound 34) were obtained for the second route, using a C2 chiral ligand, namely (S,S)-1,2-dimethyl-1,2-ethanediylbis(diphenylphosphine).

Synthesis of (R)- and (S)-isopropylidene glycerol ☆

Abstract The preparation of (R)- and (S)-isopropylidene glycerol 1 of high enantiomeric excess (> 98%) was accomplished through salt formation between their hydrogen phthalates with (S)- and (R)-1-methylbenzylamine [MBA] respectively, selective crystallization of these salts and subsequent regeneration of optically active compounds 1 by saponification. The progress of resolution was followed by HPLC analysis on Chiralcel OJ, after converting the hydrogen phthalates into the corresponding mono methyl esters by diazomethane.

Asymmetric nickel catalysis in the cross-coupling reaction of aryl halides with Grignard reagents. A study of the factors influencing asymmetric induction

Abstract The synthesis of optically active 2-phenylbutane starting from phenyl halides and sec-butyl magnesium halides using nickel dichloro complexes of chiral homologues of 1,2-ethanediylbis[diphenylphosphine] has been investigated as a model cross-coupling reaction. Optical purities of up to 50% were obtained with little influence of the substituent(s) on the chiral ligand. By contrast the nature of the halide present in both the organic and the organometallic species is very important, leading to different optical purities and reversal of chiral discrimination. The nature of the ether solvent also modifies the optical yield; this influence, however, is not related to the basicity of the solvent. When the substrate is a substituted phenyl halide, the asymmetric induction seems to be strongly influenced by steric factors, but only slightly by electronic factors. The results suggest that there is a very complex mechanistic pathway for the catalyzed cross-coupling reaction and that the most important factor for the stereochemical course of the reaction is the structure of the alkylating organomagnesium species. Furthermore, the extent of the formation of isomeric alkylation products seems to be related to the stability of the metal containing chelate ring in the catalytic species.

RESOLUTION OF AMINES WITH ISOPROPYLIDENE GLYCEROL HYDROGEN PHTHALATE

Abstract The hydrogen phthalate of isopropylidene glycerol has been recently described as an efficient resolving agent of 1-arylethylamines. In order to gain more information on its versatility and to develop a rationale which accounts for its effectiveness, further 1-arylethylamines and other racemic amines were subjected to the same resolution process. A preliminary qualitative analysis of the results reported herein allows to identify some structural features of the aminic substrates conditioning the feasibility of the resolution.

Isopropylidene glycerol hydrogen phthalate: a new resolving agent. Application to the resolution of 1-arylethylamines

Abstract Hydrogen phthalates of ( R )- and ( S )-isopropylidene glycerol, obtainable from racemic isopropylidene glycerol by reaction with phthalic anhydride and successive resolution with ( S )- and ( R )-1-phenylethylamine or, alternatively, from ( R )-and ( S )-isopropylidene glycerol, were regarded as potential new resolving agents. A range of important 1-arylethylamines was selected to test their resolving capability. In particular, trial resolutions were carried out using equivalent amounts of racemic and hydrogen phthalate of ( R )-isopropylidene glycerol. The salts of the S isomers selectively crystallized from methanol or 2-propanol allowing to recover the ( S )-1-arylethylamines in high chemical and optical yields.

Isopropylidene glycerol hydrogen phthalate as a resolving agent: a study of its diastereomeric salts with (S)- and (R)-1-phenylethylamine

Abstract An insight into the mechanism of the highly efficient resolution of 1-phenylethylamine with enantiomerically pure isopropylideneglycerol hydrogen phthalate is provided by comparison of physicochemical and X-ray crystallographic data of the two diastereomeric salts formed by the amine with the S acid. In the nearly identical structures of these salts, the different disposition of the isopropylidene glycerol moiety stands out drawing attention to the critical role played by the chiral part of the acid in the discrimination between the amine enantiomers.

Boron trichloride catalyzed ortho carbonylation of phenols: : Synthesis of 2-hydroxy-aryl-carboxyamides and -ketones.

In the presence of equimolar quantity of BCl3, phenols 1 react with isocyanates and acyl chlorides to give, usually with good-excellent yields, 2-hydroxy-aryl-carboxy-amides 2 and 2-hydroxy-aryl-ketones 3 respectively. A distinctive behaviour of BCl3 in comparison with other Lewis acids is observed.

Nickel(II), palladium(II) and platinum(II) dichloro complexes containing optically active diphosphines

Abstract The preparation of new square-planar nickel(II), palladium(II) and platinum(II) dichloro complexes containing (R)-1,2-bis(diphenylphosphino) propane (R-prophos) (2S,3S)2,3-bis(diphenylphosphino)butane (S,S-chiraphos) and (R)-1,2-bis(diphenylphosphino)-1-phenylethane (R-phephos) is reported. The complexes have been characterized by elemental analysis, electronic, CD, infrared and 1 H- and 31 P-NMR spectral measurements.

Resolution of β-unsaturated amines with isopropylidene glycerol hydrogen phthalate

Abstract 1-Phenyl-2-propenylamine 2 , 1-phenyl-2-propinylamine 3 , 1-(1-cyclohexenyl)ethylamine 4 , ( E )-2-ethylidenecyclohexylamine 5 and α-methylallylamine hydrochloride 6 were selected as candidates for resolution with isopropylidene glycerol hydrogen phthalate 1 , previously described as an efficient resolving agent of 1-arylalkylamines. With only the exception of 5 , all these substrates were resolved by ( S )- 1 . In particular both the enantiomers of 2 and 3 were obtained in excellent yields and with very high enantiomeric excesses. The absolute configurations of non-racemic forms of 2 , 3 and 4 , not prepared before except those of 3 , were established by correlation with the respective hydrogenation products. The enantiomeric excesses of all the resolved substrates were accurately determined by chiral HPLC analysis. The fact that 1 resolves 4 and 6 but not their saturated analogues and shows higher efficiency in resolving 2 and 3 than 1-phenylpropylamine indicates the positive influence of the presence of β-unsaturation on the resolvability of aminic substrates with such an acid.

Nickel catalyzed asymmetric cross-coupling reaction between C6H5X and s-BuMgX. The influence of the nature of the halogens of the two reagents

Abstract The asymmetric cross-coupling reaction between phenyl halides and sec-butyl-magnesium halides has been carried out in the presence of [(+)( R -1,2-bis(diphenylphosphino)propane]nickel(II) chloride. The optical purity and the absolute configuration of the 2-phenylbutane were dependent on which halogen was present in the organic and the organometallic moieties.