Palladacycle mediated synthesis of cyano-functionalized chiral 1,2-diphosphine and subsequent functional group transformations

Cyano-functionalized allylic phosphine substrates containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary were synthesized from bromoacetaldehyde dimethylacetal via a one-pot process. The diastereoselective hydrophosphination reactions of the cis- and trans-allylic phosphine substrates gave the cyano-functionalized chiral 1,2-bis(diphenylphosphino)ethane products with high yield and stereoselectivity. The subsequent organic transformation reactions of the cyano-substituted products chemoselectively afforded the formyl- and hydroxyl-functionalized chiral 1,2-diphosphine complexes with retention of stereochemistry. The coordination properties and absolute configurations of the novel 1,2-diphosphine complexes were established by single crystal X-ray crystallography. The optically pure 1,2-bis(diphenylphosphino)ethane ligands with cyano-, formyl- and hydroxyl-functionalities could be liberated in high yields from the corresponding dihalo palladium complexes by treatment with aqueous potassium cyanide.

Graphical abstractCyano-functionalized allylic monophosphine substrates were synthesized from bromoacetaldehyde dimethylacetal via a one-pot process. Subsequent hydrophosphination and the functional group transformation reactions generated the cyano-, formyl- and hydroxyl-functionalized chiral 1,2-diphosphine products in high yields and stereoselectivity.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► One-pot synthesis of Cyano-functionalized allylic monophosphine. ► Asymmetric hydrophosphination of the allylic monophosphine substrates. ► Novel functional group transformations of cyano-functionalized 1,2-diphosphines. ► Access to a range of enantiomerically pure functionalized 1,2-diphopshine ligands.