Synthesis and Stereoselective Interconversion of Chiral 1‐Aza‐3,6‐diphosphacycloheptanes

Abstract

AbstractCyclic seven‐membered bisphosphanes, namely 1‐aza‐3,6‐diphosphacycloheptanes 3–5 (3: 3,6‐diphenyl‐1‐(1‐phenylethyl)‐1‐aza‐3,6‐diphosphacycloheptane; 4: 1‐[(1R)‐1‐(4′‐methoxyphenyl)ethyl]‐3,6‐diphenyl‐1‐aza‐3,6‐diphosphacycloheptane; 5: 3,6‐diphenyl‐1‐[(1R)‐1‐phenylpropyl]‐1‐aza‐3,6‐diphosphacycloheptane), with chiral exocyclic substituents at the nitrogen positions have been synthesized, with the prevailing formation of meso stereoisomers (PRPS) as kinetically controlled products, by stereoselective condensation of 1,2‐bis(phenylphosphanyl)ethane, formaldehyde and primary optically pure amines, namely (S)‐(–)‐1‐phenylethylamine, (R)‐(+)‐1‐phenylethylamine, (R)‐(+)‐1‐phenylpropylamine, (R)‐(+)‐1‐(4′‐methoxyphenyl)ethylamine. The meso stereoisomers of bisphosphanes 3RSS, 3–5RSR readily form neutral and cationic P,P‐chelate complexes 6–9 with platinum(II) (6: cis‐dichloro‐(3R,6S)‐3,6‐diphenyl‐1‐[(1S)‐1‐phenylethyl]‐1‐aza‐3,6‐diphosphacycloheptaneplatinum(II); 7: cis‐dichloro‐(3R,6S)‐1‐[(1R)‐1‐(4′‐methoxyphenyl)ethyl]‐3,6‐diphenyl‐1‐aza‐3,6‐diphosphacycloheptaneplatinum(II); 8:bis{(3R,6S)‐[(1R)‐3,6‐diphenyl‐1‐(1‐phenylethyl)‐1‐aza‐3,6‐diphosphacycloheptane]}platinum(II) dichloride; 9: bis{(3R,6S)‐3,6‐diphenyl‐1‐[(1R)‐1‐phenylpropyl]‐1‐aza‐3,6‐diphosphacycloheptane}platinum(II) dichloride). The fast and selective formation of the cationic complex (9) of the meso isomer 5RSR allowed for the separation of the 5RRR and 5SSR isomers of the bisphosphane 5. In solution, selective stereoconversion of the pure 3RSS, 3RSR and 4RSR isomers into a mixture containing 3RRS, 3SSR and 4SSR stereoisomers as the predominant products was observed. As a result, the stereoconversion is accompanied by a change in not only the value but also in the sign of the specific rotation, [α]D20. The ratio of the stereoisomers in an equilibrium mixture of 3C(S) (3RSS/3RRS/3SSS in a 24:48:28 ratio) is in accord with their relative energies that were calculated with the B3LYP/6‐31G* basis. Kinetic studies of the stereoconversion of bisphosphane 3C(S) have been performed. The rate constants that were determined are indicative of a bimolecular interconversion mechanism, which is supposedly the reason for the relatively low activation energies for inversion at phosphorus. Molecular structures were obtained, by X‐ray crystal structure analysis, for the meso 3RSS and 3RRS stereoisomers of the N‐(S)‐1‐phenylethyl‐substituted bisphosphanes and for 4RSR.