Zinc catalysed electrophilic C-H borylation of heteroarenes.

Matthew E Grundy,Michael J Ingleson,Gary S Nichol,Kang Yuan

doi:10.1039/d1sc01883c

Matthew E Grundy, Michael J Ingleson + Show 2 more

Open Access

https://doi.org/10.1039/d1sc01883c

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Abstract

Cationic zinc Lewis acids catalyse the C–H borylation of heteroarenes using pinacol borane (HBPin) or catechol borane (HBCat). An electrophile derived from [IDippZnEt][B(C6F5)4] (IDipp = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) combined with N,N-dimethyl-p-toluidine (DMT) proved the most active in terms of C–H borylation scope and yield. Using this combination weakly activated heteroarenes, such as thiophene, were amenable to catalytic C–H borylation using HBCat. Competition reactions show these IDipp–zinc cations are highly oxophilic but less hydridophilic (relative to B(C6F5)3), and that borylation proceeds via activation of the hydroborane (and not the heteroarene) by a zinc electrophile. Based on DFT calculations this activation is proposed to proceed by coordination of a hydroborane oxygen to the zinc centre to generate a boron electrophile that effects C–H borylation. Thus, Lewis acid binding to oxygen sites of hydroboranes represents an under-developed route to access reactive borenium-type electrophiles for C–H borylation.

Highlights

As it enables rapid construction of complex molecules, C–H functionalisation has become increasingly important.[1,2] Among the most useful moieties made via C–H functionalisation are C–B containing units, owing in part to the power of the Suzuki– Miyaura reaction.[3,4] This has made organoboranes ubiquitous nucleophiles and provides continued incentive to develop new routes to organoboranes,[5] via C–H borylation.[6]
The last decade has seen some notable progress in this area, including in Fe catalysed arene C–H borylation,[17,18,19,20,21] and in catalytic C–H borylation using boron based frustrated Lewis pairs (FLPs) and/or borenium cations.[22,23,24,25,26]
The stoichiometric reaction of 1-H31 with 2a and H borylation with pinacolborane (HBPin) led to C–H borylation

Summary

Introduction

As it enables rapid construction of complex molecules, C–H functionalisation has become increasingly important.[1,2] Among the most useful moieties made via C–H functionalisation are C–B containing units, owing in part to the power of the Suzuki– Miyaura reaction.[3,4] This has made organoboranes ubiquitous nucleophiles and provides continued incentive to develop new routes to organoboranes,[5] via C–H borylation.[6]. Borylation mechanism may be more relevant for substrates less acidic than alkynes, with no (hetero)arene deprotonation by a zinc-hydride reported to date to the best of our knowledge.[32] One alternative mechanism involves activation of a hydroborane by a zinc Lewis acid This would enhance electrophilicity at boron and form a functional equivalent of a borenium cation, species well documented to borylate p systems.[33] Such a mechanism was outlined in zinc catalysed alkyne borylation with HBDan (HBDan 1⁄4 1,8-naphthalenediaminatoborane), with zinc proposed to interact with the B–H unit (Fig. 1B), with pyridine enabling C–H deprotonation.[30] This can be viewed as a frustrated Lewis pair (FLP) borylation mechanism.[23] It should be noted that related intermediates When combined with the optimal base this leads to a catalytic C–H borylation methodology applicable to less activated heteroarenes (e.g. thiophenes) than normally observed using main group (redox inactive) catalysts

Results and discussion

80 PhCl 10

Conclusions

24 For early work see