Access to the meta position of arenes through transition metal catalysed C–H bond functionalisation: a focus on metals other than palladium

Abstract

The elaboration of simple arenes in order to access more complex substitution patterns is a crucial endeavor for synthetic chemists, given the central role that aromatic rings play in all manner of important molecules. Classical methods are now routinely used alongside stoichiometric organometallic approaches and, most recently, transition metal catalysis in the range of methodologies that are available to elaborate arene C-H bonds. Regioselectivity is an important consideration when selecting a method and, of all those available, it is arguably those that target the meta position that are fewest in number. The rapid development of transition metal-catalysed C-H bond functionalisation over the last few decades has opened new possibilities for meta-selective C-H functionalisation through the diverse reactivity of transition metals and their compatibility with a wide range of directing groups. The pace of discovery of such processes has grown rapidly in the last five years in particular and it is the purpose of this review to examine these but in doing so to place the focus on metals other than palladium, the specific contributions of which have been very recently reviewed elsewhere. It is hoped this will serve to highlight to the reader the breadth of current strategies and mechanisms that have been used to tackle this challenge, which may inspire further progress in the field.

Remote C−H Activation of Various N‐Heterocycles Using a Single Template

“…[3] Severald ifferenta pproaches have recently been employed successfully in remote CÀHa ctivation. [4][5][6][7][8] Ourg roup has developed at emplate-based methodology for meta-selective CÀHa ctivation,i nw hich the site selectivity is achieved by the precise recognitiono ft he distance andg eometry between the directing atom and the CÀHb onds. [5] Considering that this approachu ses distance and geometry as the key differentiation parameters, it is not surprising that one particular template designed for ac lass of substrates may not be adaptable to others.…”

“…Ahalf-gram scale reactiono f8m showedt he scalability of the present protocol. Similarly,3 ,4-dihydro-2H-benzo[b] [1,4]oxazine substrate 8n can also be olefinated at the C6 position in good yield with high site-selectivity.F inally,o lefination of a2 -phenylpyrrolidines ubstrate gave the meta-coupled product 9o with good selectivitya nd modesty ield. Considering the diverse structures of the aforementioned N-heterocycles, these results demonstrate the generality of using distance to predict selectivity in template-directed remote CÀHa ctivation.The indoline substrate 8e was chosen for investigating the olefin scope of the remote selective CÀHa ctivation( Ta ble 4).…”

One-Pot Iridium Catalyzed C–H Borylation/Sonogashira Cross-Coupling: Access to Borylated Aryl Alkynes

“…3-(Phenylethynyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-benzotrifluoride (12) From Sonogashira coupling of borylated aryl bromide: the general procedure A was applied to the borylated version of 3-bromobenzotrifluoride (9, 351 mg, 1.0 mmol, 1 equiv) with phenyl acetylene (121 µL, 112 mg, 1.10 mmol, 1.1 equiv) as the coupling partner for 10 h. The crude mixture was concentrated and passed through a plug of silica gel (CH 2 Cl 2 as eluent) to furnish the desired product as orange yellow oil, which solidified on standing (280 mg, 75% yield, mp 74-75 • C).…”

“…3-(Phenylethynyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-benzotrifluoride (12) From Sonogashira coupling of borylated aryl bromide: the general procedure A was ap the borylated version of 3-bromobenzotrifluoride (9, 351 mg, 1.0 mmol, 1 equiv) with acetylene (121 μL, 112 mg, 1.10 mmol, 1.1 equiv) as the coupling partner for 10 h. The crude was concentrated and passed through a plug of silica gel (CH2Cl2 as eluent) to furnish the product as orange yellow oil, which solidified on standing (280 mg, 75% yield, mp 74-75 °C From one-pot CHB/Sonogashira coupling: the general procedure B was applie bromobenzotrifluoride (279 μL, 450 mg, 2.0 mmol, 1 equiv). The borylation step was carried HBpin (436 μL, 384 mg, 3.00 mmol, 1.50 equiv) for 3 h. The Sonogashira coupling step was out with phenyl acetylene (242 μL, 225 mg, 2.20 mmol, 1.1 equiv) for 5 h. Gradient chromatography (pentane:dichloromethane 4:1 → pentane:dichloromethane 1:1) furnis desired product as orange yellow oil, which solidified on standing (473 mg, 64% yield, mp 74 3-(Trimethylsilylethynyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-toluene (13).…”

“…The regiochemistry of iridium-catalyzed CHB of arenes is traditionally governed by sterics [3,7,8]; often complementing regiochemical outcomes of electrophilic aromatic substitution and directed ortho metalation. Since its discovery [9], methods to expand regiocontrol (ortho, meta, and para) [10][11][12], sp 3 borylation protocols [13][14][15][16][17][18][19][20][21] and one-pot reactions [22][23][24][25][26][27] have been developed.…”