Converging and Diverging Synthetic Strategies to Tetradentate (N,N′)-Diaminomethyl,(P,P′)-Ferrocenyl Ligands: Influence of tert-Butyl Groups on Ferrocene Backbone Conformation

Abstract

Hexasubstituted hybrid tetradentate (N,N′,P,P′)-ferrocenes bearing phosphino and aminomethyl groups, plus hindering tert-butyl moieties, were synthesized by using two different strategies: a "diverging" synthesis involving successive functionalization of preformed di-tert-butylated ferrocene and a "converging" assembly of the species from appropriately substituted cyclopentadienyl rings. While the new cyclopentadienyl salts formed are of interest, their assembly with iron dichloride used as a "converging" way to produce tetradentate ferrocene ligands presented several drawbacks. Conversely, the synthesis of new tert-butylated (aminomethyl)ferrocene derivatives was found convenient to further form (N,N′)-aminomethyl,(P,P′)-tert-butylated-ferrocenyl diphosphines by N-directed ortho-metalation. The novel N 2didentate and N 2 P 2 -tetradentate tert-butylated ferrocene compounds were all synthesized in good to high yields (48−96%) and tolerated aryl, alkyl, and heteroaryl phosphino groups as substituents on nitrogen and phosphorus atoms. They were characterized by X-ray diffraction and multinuclear NMR ( 1 H, 13 C, 31 P, 15 N). We observed the conformation control provided to rac-(N,N′)-diaminomethyl-(P,P′)-tert-butylated-ferrocenyldiphosphines with in particular the systematic near-eclipsed conformation of aminomethyl groups. This conformation is at the origin of the unexpected formation at RT of a zwitterionic cyclopalladate from an (aminomethyl)ferrocene derivative, arising from intramolecular Cp-proton transfer to the proximate free amino group by simple C−H activation reaction in the presence of palladium dichloride.

Highly Functionalized Ferrocenes

“…We first explored a converging way by cyclopentadienyl assembly, but the stereoselectivity control and the mixture of diastereoisomers formed needed too long separation procedure and limited the yield. We consequently explored a diverging way to obtain these ferrocenes with a high diastereoselectivity . This approach was initiated with the formation of aminomethyl and iminomethyl ferrocene derivatives.…”

“…These ferrocene derivatives were synthetized by reductive amination from the diformylferrocene 68 , obtained in two steps from 43a with a full diastereoselectivity confirmed by XRD (Figure ). After lithiation and formylation of 43a , the resulting compound 68 was treated with primary or secondary amines and reduced using NaHB(OAc) 3 , which allowed the selective formation of diamines 63–66 in very good to high yields (74–96 %) . As for the synthesis of diphosphinoferrocenes presented before, this functionalization way offers a high diastereoselectivity with the exclusive formation of rac stereoisomers.…”

“…The synthesis of secondary aminomethylferrocene 62 is similar to 63–66 however, with the use of 3:1 ratio of amine/aldehyde (Figure ). LiAlH 4 was used for reducing the iminomethyl ferrocene 67 , leading to the secondary amine 62 with a high yield of 95 % …”

“…A direct consequence of the introduction of t‐ Bu groups on the ferrocene platform was observed by the coordination chemistry of 63 to [PdCl 2 (PhCN) 2 ] (Figure ) . The spontaneous formation of a zwitterionic cyclopalladate 69 from C–H activation and nitrogen attack to form ammonium was obtained that does not occur with non‐ tert‐ butylated diaminoferrocene analogues.…”

“…Initially, the assembly of adequately substituted Cp salts was investigated for the formation of alkylated ferrocene (P,N)‐ligands (Figure ) . Dimethylaminomethylation of (diphenylphosphino)‐3‐ tert ‐butylcyclopentadienyllithium L was achieved in a 86 % yield using an iminium salt.…”