CH Activation: A Complementary Tool in the Total Synthesis of Complex Natural Products

Abstract

The recent advent of transition-metal mediated C-H activation is revolutionizing the synthetic field and gradually infusing a "C-H activation mind-set" in both students and practitioners of organic synthesis. As a powerful testament of this emerging synthetic tool, applications of C-H activation in the context of total synthesis of complex natural products are beginning to blossom. Herein, recently completed total syntheses showcasing creative and ingenious incorporation of C-H activation as a strategic manoeuver are compared with their "non-C-H activation" counterparts, illuminating a new paradigm in strategic synthetic design.

Ruthenium‐Catalyzed Hydroarylation and One‐Pot Twofold Unsymmetrical C−H Functionalization of Arenes

“…[1][2][3] Despite the growth and success of CÀHa ctivation, synthetically useful DG-promoted multiple functionalizations of arene C À Hb onds are less explored, yet exceedingly attractive.Ingeneral, the steric/electronic/coordinating effect of the ortho-monofunctionalized product, obtained from the DG-coupled arene,h ampers the efficient introduction of other functional groups to the second ortho CÀHbond on the arene.C onsequently,e ffective twofold CÀHb ond functionalization of arenes remains challenging. [1][2][3] Despite the growth and success of CÀHa ctivation, synthetically useful DG-promoted multiple functionalizations of arene C À Hb onds are less explored, yet exceedingly attractive.Ingeneral, the steric/electronic/coordinating effect of the ortho-monofunctionalized product, obtained from the DG-coupled arene,h ampers the efficient introduction of other functional groups to the second ortho CÀHbond on the arene.C onsequently,e ffective twofold CÀHb ond functionalization of arenes remains challenging.…”

Recent Accomplishments in the Total Synthesis of Natural Products Through C–H Functionalization Strategies

“…From those times to the present era, C-H functionalization has been increasingly exploited in the synthesis of natural products and reviewed recently [3,26,27], so the aim of this chapter is to highlight the most recent achievements in this field. A number of molecules have been selected to illustrate the diversification that has taken place in terms of the range of natural products (their biosynthetic origin) and the C-H functionalization strategies executed in their construction.…”

Palladium-Catalyzed Direct Arylation of Selenophene

“…1 Such couplings are very attractive to replace classical palladium catalyzed type couplings, once they do not require the preliminary synthesis of one or two organometallic derivatives. 2 Therefore, these reactions are atom-economical and produce less waste. Up to now, to promote a cross-coupling reaction with the selenophene ring (1), a previous activation, either as a halide or as an organometallic (B, Mg, Sn and Zn) is required.…”