Synthesis and unique reversible splitting of 14-membered cyclic aminomethylphosphines on to 7-membered heterocycles

Abstract

A novel type of 14-membered cyclic polyphosphine, namely 1,8-diaza-3,6,10,13-tetraphosphacyclotetradecanes 2a–4ahas been synthesized by the condensation of 1,2-bis(phenylphosphino)ethane, formaldehyde and alkylamines (isopropylamine, ethylamine and cyclohexylamine) as a RRRR/SSSS-stereoisomer. The structure of macrocycle 2a was investigated by NMR-spectroscopy and X-ray crystal structure analysis. The unique reversible processes of macrocycles 2a–4a splitting onto the corresponding rac- (2b–4b) and meso- (2c–4c) stereoisomers of 1-aza-3,6-diphosphacycloheptanes were discovered.

Self‐Assembly of Chiral 1,8‐Diaza‐3,6,10,13‐tetraphosphacyclotetradecanes via Dynamic Transformation of 7‐ and 14‐Membered Aminomethylphosphines

“…In the 31 P{ 1 H} NMR spectrum of the crude product isolated from the reaction with ( S )‐(+)‐ sec ‐butylamine, two singlets of different intensity (1:0.07) at –31.6 ppm ( 1a* ) and –31.9 ppm ( 1b * ) are observed (Figure a). The chemical shift values of 1a* and 1b* are very close to those observed for the S P S P S P S P /R P R P R P R P isomers of 14‐membered tetrakis‐phosphines and differ from the chemical shifts of the 1+1 condensation products, the 7‐membered heterocycles . Thus, these signals presumably belong to 14‐membered macrocycles.…”

“…Nevertheless, 14‐membered P 4 N 2 macrocycles were successfully obtained with various alkylamines as kinetically controlled products . These macrocycles underwent reversible proton‐induced transformation into 7‐membered 1‐aza‐3,6‐diphosphacycloheptanes without stereoisomerisation . This work continues the systematic study of P 4 N 2 macrocycles including the synthesis of chiral 14‐membered macrocycles with optically pure and racemic sec ‐butylamine and their behaviour in solution, which could lead to stereoisomerisation, transformation into 7‐membered cycles as well as exchange of endocyclic amino groups bearing the chiral carbon centre.…”

“…Interestingly, in the case of 16‐membered macrocycles, optically pure amines led to only one isomer, 16‐P 4 RSSR C SS , because the meso form of the macrocycle is preferred . Taking into account that the S P S P S P S P / R P R P R P R P stereoisomers (14‐P 4 RRRR /14‐P 4 SSSS ) are preferred for 14‐membered tetrakis‐phosphines, resolution of the enantiomeric pair by employing optically pure amines should be possible, resulting in two different isomers, 14‐P 4 SSSS C 2 SS ( 1a* ) and 14‐P 4 RRRR C 2 SS ( 1b* ). A variety of NMR correlation experiments ( 1 H‐ 1 H COSY, 1 H‐ 13 C HSQC, 1 H‐ 13 C/ 31 P HMBC, 2D 1 H DOSY, 1D NOESY, Figures S3–S35, Supporting Information) were used to elucidate the absolute configuration of the phosphorus atoms.…”

“…Kinetic experiments together with DFT calculations indicated the thermodynamic preference of the isomer 7‐P 2 RR/SS in all cases , . Nevertheless, 14‐membered P 4 N 2 macrocycles were successfully obtained with various alkylamines as kinetically controlled products . These macrocycles underwent reversible proton‐induced transformation into 7‐membered 1‐aza‐3,6‐diphosphacycloheptanes without stereoisomerisation .…”

“…However, chiral macrocycles with P,N donors have rarely been employed in asymmetric reactions, due to the difficult synthesis of phosphorus‐based macrocycles and the formation of diastereomeric mixtures when two or more phosphorus atoms are present . A synthetic strategy based on the dynamic covalent chemistry of macrocyclic aminomethylphosphines was developed for numerous 14‐, 16‐, 18‐ and 20‐membered P 4 N 2 macrocycles . The reaction between various secondary α,ω‐bis(phosphino)alkanes, formaldehyde and primary amines results in at least seven different products – two isomers of cyclic P 2 N bis‐phosphines and five stereoisomers of P 4 N 2 macrocycles.…”