ASYMMETRIC SYNTHESIS OF DIPHOSPHINE LIGANDS CONTAINING STEREOGENIC PHOSPHORUS CENTRES

Abstract

The mechanistic aspects of the reported [4 + 2] Diels-Alder reaction between vinylphosphines [ie (a) diphenylvinylphosphine, (b) diphenyl-1-propenyl-(E)-phosphine and (c) diphenyl-1-propenyl-(Z)-phosphine] and 3,4-dimethyl-1-phenylphosphole (DMPP) with the organo-palladium complex containing the ortha-metallated (S)-[1 (dimethylamino)ethyl] naphthalene (S)-74, acting as the chiral promoter were investigated. Optimum reaction conditions were obtained when non-coordinating solvent (dichloromethane) was used. The reaction time was very much reduced compared to the cycloaddition carried out in coordinating solvent (acetonitrile). Spectroscopic evidence was also obtained for the intermediate formed during the cycloaddition reaction where the diene and the dienophile are coordinated simultaneously to the palladium metal in two possible orientations. The relatively new 2-D 1H-ROESY NMR technique was successfully applied to determine the absolute configuration or the diphosphines cycloadducts. The absolute stereochemistry of the chiral ligands were ascertained using the unique and predictable absolute chirality of the ortho-metallated naphthylamine moiety as an internal reference. These information could not he obtained by X-ray structural analysis since suitable crystals of the palladium template complex containing the chiral naphthylamine auxiliary and the rigid diphosphine ligand (Sc,Rp)-84a-c, could not he obtained. It was also established that the naphthyl palladium complex (S)-74 exerted absolute enantiocontrol over the cycloaddition reaction to generate enantiomerically pure diphosphine ligands (Sp)-76a-c. The absolute stereochemistry of the optically active dichloro complex (Rp)-81c (obtained by refluxing the Diels-Alder product (Sc,Rp)-84c with concentrated hydrochloric acid), when examined by single-crystal X-ray analysis was found to be in total agreement with that established by the 2-D 1H-ROESY NMR for the corresponding cycloadduct (Sc,Rp)-84c, proving the reliability or this spectroscopic technique. In an effort to determine the prowess of the relatively cheaper bis(µ- chloro) bis[(R)-1-[1-(dimethylamino)ethyl]-2-phenyl-C,N]dipalladium (II) dichloro- methane solvate (R)-63 as a chiral inductor, the above mentioned Diels-Alder reactions were repeated in the presence of (R)-63. The cycloadducts (Rc,Sp)-96a-c were isolated and analogues a and b were characterised by X-ray crystallography. A close inspection of the crude product of the Diels-Alder reaction revealed that small amounts of the unfavourable isomers (Rc,Rp)-96a-c were also formed. Enantiomerically pure diphosphine ligands carrying two phosphorus and up to four carbon stereogenic centres were generated from the Diels-Alder reaction between divinylphosphines [ ie (a) divinylphenylphosphine, (b) di-1-propenyl-(E)-phenyl- phosphine and (c) di-1-propenyl-(Z)-phenylphosphine] and DMPP, with (S)-74 as the chiral inductor. For the cycloaddition reactions involving divinylphenylphosphine and di-1-propenyl-(E)-phenylphosphine, enantiomerically pure (Sc,Rp,Sp)-104a-b were formed. Due to the inability of the cycloadducts to crystallise, they were converted to the corresponding dichloro complexes (Rp,Sp)-101a-b and characterised by X-ray crystallographic analysis. In both the complexes, the vinylic group on the 5-phosphino phosphorus was below the PP'CN square planar, and the phenyl group above the plane. The cycloaddition reaction between di-1-propenyl-(Z)-phenylphosphine and DMPP resulted in the formation or two diastereomers in unequal amounts. The major isomer (Sc,Rp,Rp)-104c was isolated and characterised by 2-D 1H-ROESY NMR and X-ray analysis, which revealed the configuration at the 5-phosphino phosphorus to be opposite that or the other two analogues, (Sc,Rp,Sp)-104a-b. In this complex, the substituted vinylic group is above the plane while the phenyl group resides below the plane. Steric repulsion prohibites the vinylic group from occupying the position below the plane. The benzyl dimer (S)-63 failed to promote these sterically demanding Diels- Alder reactions. The cycloaddition reaction between DMPP and methyl acrylate was carried out. When coordinated DMPP in chloro-(R)-[1-[ 1-(dimethylamino )cthyl]-2-naphthalenyl- C,N][3,4-dimethyl-1-phenylphosphole]palladium (II) (Rc)-87 was treated directly with methyl acrylate, two diastereomeric cycloadducts with the functionalised phosphine in syn-endo stereochemistry (Rc,Rp)-122 and (Rc,Sp)-122, were obtained via an intermolecular mechanism. The cycloadducts bind as monodentate ligands to the palladium(II) metal template via the phosphorus atom only. The treatment of the chloro palladium complex (Rc)-87 with silver perchlorate resulted in the fomation of [1-[1-( dimethylamino )ethyl]-2-naphthalenyl-C,N] [3 ,4- dimethyl-1-phenylphosphole] (perchlorato-0) palladium (II) (Rc)-88. This perchlorato complex was then treated with methyl acrylate to yield the rigid monophosphine (Rc,Sp)-123 in syn-exo stereochemistry via an intramolecular cycloaddition process. Only one isomer was formed. However, the cycloadduct formed in this Diels-Alder reaction could not be induced to crystallise.