Cobalt‐Catalyzed ortho‐Methylation of Ferrocenes Bearing ortho‐Directing Groups by Catalytic Directed C–H Bond Activation

Abstract

Transition‐metal‐catalyzed C–H functionalization is an emerging powerful alternative to ortho‐lithiation protocols. For ferrocene systems almost exclusively noble‐metal catalysts have so far been used. Herein we present the first examples of cobalt‐catalyzed ortho‐methylations by C–H activation at ferrocenes bearing various ortho‐directing groups (ODGs). The cobalt‐catalyzed ortho‐methylation results in the formation of racemic 1,2‐disubstituted ferrocenes in 21–89 % yield. In some cases symmetric 2,5‐dimethylated ferrocenes prevailed or even were the only isolated products.

Directed C–H Alkenylation of Aryl Imines with Alkenyl Phosphates Promoted by a Cobalt–N‐Heterocyclic Carbene Catalyst

“…of 2a furnished the dialkenylation product 10b in good yield (Scheme b). This observation is notable because Ackermann's catalytic system promoted exclusive mono‐alkenylation of the same ferrocene substrate ,…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…A catalytic system using Co(acac) 2 for alkylation of ferrocene derivatives was also studied, but only one example using an 8-aminoquinoline-derived amide as DG was reported, with 28% yield. 408 …”

“…The same group further investigated the potential of the bidentate DG in Fe-catalysed C–H allylation and alkylation of amides ( Scheme 97B ). 585 Using allyl chloride, the functionalisation of a broad range of substrates was possible including arenes, ferrocenes, 408 heteroarenes and alkenes (47–92% yield). When substituted allyl chlorides were reacted, allylated benzamides were obtained with moderate to good regioselectivity (from 2 : 1 to 5.7 : 1) in favour of the branched products.…”

Installing the “magic methyl” – C–H methylation in synthesis

“…In 2017, Butenschön documented the Co-catalysed ortho methylation of metallocenes, constituting a welcome addition to the expanding field of Co-catalysed methylation strategies (Scheme 20). 73 The reaction was amenable to ferrocenes bearing a variety of nitrogen-based DGs such as oxazolines, 8-AQ and triazolyldimethyl (TAM) carboxamides. Both mono-and di-methylated products were isolated, but only the di-methylated product was observed for substrates bearing an 8-AQ DG.…”