The use of coordinating moieties as directing groups for the functionalization of aromatic CH bonds has become an established tool to enhance reactivity and induce regioselectivity. Nevertheless, with regard to the synthetic applicability of CH activation, there is a growing interest in transformations in which the directing group can be fully abandoned, thus allowing the direct functionalization of simple benzene derivatives. However, this approach requires the disclosure of new strategies to achieve reactivity and to control selectivity. In this review, recent advances in the emerging field of non-chelate-assisted CH activation are discussed, highlighting some of the most intriguing and inspiring examples of induction of reactivity and selectivity.

Beyond directing groups: transition-metal-catalyzed C-H activation of simple arenes.

Transition metal-catalyzed direct functionalization of C–H bonds is one of the key emerging strategies that is currently attracting tremendous attention with the aim to provide alternative environmentally friendly and efficient ways for the construction of C–C and C–hetero bonds. In particular, the strategy involving regioselective C–H activation assisted by various functional groups shows high potential, and significant achievements have been made in both the development of novel reactions and the mechanistic study. In this review, we attempt to give an overview of the development of utilizing the functionalities as directing groups. The discussion is directed towards the use of different functional groups as directing groups for the construction of C–C and C–hetero bonds via C–H activation using various transition metal catalysts. The synthetic applications and mechanistic features of these transformations will be discussed, and the review is organized on the basis of the type of directing groups and the type of bond being formed or the catalyst.

Transition metal-catalyzed C–H bond functionalizations by the use of diverse directing groups

Oxidative Coupling between Two Hydrocarbons: An Update of Recent C–H Functionalizations

Recent advances in organocatalytic asymmetric Morita-Baylis-Hillman/aza-Morita-Baylis-Hillman reactions.

The use of coordinating moieties as directing groups for the functionalisation of aromatic carbon–hydrogen (C–H) bonds has become an efficient strategy for the selective construction of new carbon–carbon (C–C) and carbon–heteroatom (C–X) bonds in arenes. However many directing groups cannot be easily removed/modified from the products after C–H functionalisation, thus limiting the structural diversity of the products. This limitation can be overcome by employing removable/modifiable or traceless directing groups which can be easily attached to the starting materials and detached from the products. In this tutorial review, we give an overview of recent advances in this emerging field which have dramatically increased the synthetic applicability of C–H functionalisation processes.

Arene C–H functionalisation using a removable/modifiable or a traceless directing group strategy

Diverse opportunities: A Rhodium(III)-catalyzed ortho-selective olefination of arenes using a novel triazene as a directing group is reported. This method exhibits substantial post-functionalization synthetic versatility, overcoming a vital limitation in C sp 2-H activation/functionalization products: restricted structural diversity.

Rhodium(III)-catalyzed C-H activation of arenes using a versatile and removable triazene directing group.

Direct asymmetric allylic alkylation of butenolides with Morita-Baylis-Hillman carbonates.

Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species-carbocations, carbanions, radicals and carbenes-that is fundamental to our understanding of chemical reactivity. In contrast, the carbyne-a monovalent carbon with three non-bonded electrons-is a relatively unexplored reactive intermediate; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an 'assembly point' disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon-hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon-hydrogen bonds, while complementing current translational late-stage functionalization processes. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.

Generating carbyne equivalents with photoredox catalysis

We describe a direct synthesis of various ynones from readily available aldehydes and hypervalent alkynyl iodides. In this method, a gold catalyst and a secondary amine work synergistically to produce the trisubstituted allenyl aldehyde, which can be converted to the desired ynone through an in situ C–C bond oxidative cleavage using molecular oxygen.

https://web.pkusz.edu.cn/huang/files/2013/04/A-General-Synthesis-of-Ynones-from-Aldehydes-via-Oxidative-C–C-bond-Cleavage-under-Aerobic-Conditions.pdf

Zhaofeng Wang

Papers

Rhodium(III)-catalyzed C-H activation of arenes using a versatile and removable triazene directing group.

Direct asymmetric allylic alkylation of butenolides with Morita-Baylis-Hillman carbonates.

Generating carbyne equivalents with photoredox catalysis

A general synthesis of ynones from aldehydes via oxidative C-C bond cleavage under aerobic conditions.

Gold-catalyzed rearrangement of allylic oxonium ylides: efficient synthesis of highly functionalized dihydrofuran-3-ones.