Asymmetric synthesis of hetero-1,2,3,4,5-pentasubstituted ferrocenes

Abstract

A four-step approach toward the first hetero-1,2,3,4,5-pentasubstituted ferrocene derivatives was successfully explored. Starting from Ugi's amine, enantioenriched compounds were made through the first asymmetric halogen ‘dance’ reaction reported.

Trapping of Transient Organolithium Compounds

“…In 2019, Erb and Roisnel reported the asymmetric synthesis of 1,2,3,4,5-pentasubstituted ferrocenes using the halogen dance (Scheme 25). [58] They obtained optically active (R,S p )-145 from a commercially available chiral ferrocene in three steps. Deprotolithiation with LiTMP generated the corresponding organolithium (R,S p )-146, and subsequent halogen dance gave lithiated ferrocene (R,S p )-147, which was stabilized by the vicinal fluoro group.…”

“…In 2019, Erb and Roisnel reported the asymmetric synthesis of 1,2,3,4,5‐pentasubstituted ferrocenes using the halogen dance (Scheme ) . They obtained optically active ( R,S p )‐ 145 from a commercially available chiral ferrocene in three steps.…”

Evidence for “Halogen‐Dance” and Ring‐Exchange Reactions in Chloro‐methylthio‐ferrocenes

“…[ 8 ] Quite astonishing there are only very few reports on halogen dance reactions of haloferrocenes, [ 9 ] but the high synthetic potential of this reaction could be shown very recently by the successful asymmetric synthesis of the first hetero‐1,2,3,4,5‐pentasubstituted ferrocenes. [ 10 ] In all studies it was stated that generally in chloroaromatics the chloro substituent would not undergo the halogen dance reactions.…”

Functionalization of 3‐Iodo‐N,N‐Diisopropylferrocene‐Carboxamide, a Pivotal Substrate to Open the Chemical Space to 1,3‐Disubstituted Ferrocenes

“…reaction in the ferrocene series. [9] However, due to very strong CÀ F bond, fluorine can hardly be converted into other functional groups. The chemistry of carboxamides being more developed, compound 1 was selected as a potential common precursor toward various 1,3-disubstituted ferrocenes.…”

“…Synthesis of the fluorinated ferrocene 22 by using N ‐fluorobenzenesulfonimide (NFSI) proved to be tricky concerning both the reaction and the purification process. Indeed, fluorination of substituted ferrocenes currently remains an unmet challenge . Furthermore, due to similar polarities between 1 and 22 , an efficient purification was hard to achieve.…”