Palladium‐Catalysed, Directed CH Coupling with Organometallics

Abstract

Transition metal (TM)-catalysed C À H coupling using organometallic reagents is developing into a distinct transformation area for the construction of carbon-carbon (C À C) bonds. Among different TMs (Ru, Rh, Pd, Co, Fe), complexes of palladium(II) are emerging as the most effective and versatile catalysts and have already asserted a proven track-record for the catalytic activation and coupling of unactivated sp 2 and sp 3 C À H bonds with sp 2 and sp 3 organometallic reagents. A majority of these TMcatalysed C À H coupling reactions utilise a hetero-A C H T U N G T R E N N U N G atom contained in substrates as a directing group. In the last decade, both traditional as well as non-traditional but synthetically useful functional groups have been extensively exploited as directing groups. Novel directing groups based on mechanistic understanding have also been designed to enhance the reactivity of Pd(II) catalysts towards C À H bonds. In addition, the unprecedented application of exogenous ligands to Pd(II)-catalysed C À H coupling is also on the rise, and this approach has already demonstrated an extraordinary level of success not only in breaking unactivated C À H bonds enantioselectively, but also in improving reactivity of catalysts towards these C À H bonds.

2‐Methyltetrahydrofuran: A Green Solvent for Iron‐Catalyzed Cross‐Coupling Reactions

“…Furthermore, large-scale cross-coupling, cross-coupling of heteroaromatics ubstrates, and cross-coupling of challenging aryl tosylatesa nd carbamates mediated by Fe-N-heterocyclic carbene catalytic systems in eco-friendly 2-MeTHF were also carried out.T he developed methodw as applied to the key crosscoupling in the synthesis of af ibrinolysis inhibitor,f urther highlighting the potential of 2-MeTHF as ag eneral solvent for sustainable iron-catalyzed cross-coupling reactions. [1][2][3][4][5] Herein, we report that the iron-catalyzed cross-coupling of aryl chlorides and tosylates with challenging organometallic reagentsp ossessing b-hydrogens [12] proceeds in good to excellent yields with the green, sustainable, ande co-friendly 2methyltetrahydrofuran as as olvent ( Figure 1). [1][2][3][4][5] Selectivem ethods for cross-coupling reactions in green, renewables olvents are essentialt or educe environmental damage.…”

“…[10,11] The major challenge to maintain full sustainability of the process is the identification of green and renewable solvents that can be harnessed to replace the conventional solvents in this highly attractive cross-coupling manifold. [1][2][3][4][5] Herein, we report that the iron-catalyzed cross-coupling of aryl chlorides and tosylates with challenging organometallic reagentsp ossessing b-hydrogens [12] proceeds in good to excellent yields with the green, sustainable, ande co-friendly 2methyltetrahydrofuran as as olvent( Figure 1). Considering the importance of renewable solvents, the methodc onstitutes a valuablea ddition to the growing arsenal of iron-catalyzed cross-couplings for sustainable chemical synthesis.…”

Nickel‐Catalyzed C(sp2)−C(sp3) Kumada Cross‐Coupling of Aryl Tosylates with Alkyl Grignard Reagents

“…The practical utility has been additionally demonstrated in the synthesis of liquid crystals and pharmaceutical intermediates. (5) We demonstrate that the method operates with TON reaching 2000, which is one of the highest turnovers observed to date in Nicatalyzed cross-couplings.…”

“…[1][2][3] While high level of sophistication has been achieved in methods that lead to the synthesis of biaryls, [4] the cross-coupling using alkyl organometallics has been much less developed. [5] The key challenges presented by alkyl-organometallic reagents involve facile decomposition by β-hydride elimination and/or protodemetallation and slow transmetallation, which effectively limit the practicality of this transformation. [6] Simultaneously, the engagement of CÀ O electrophiles provides a powerful alternative to aryl halides in cross-coupling reactions.…”

Development of Direct Aromatic Coupling Reactions by Transition-Metal Catalysis

“…It is worth citing that coordination-assisted and palladiumcatalyzed aromatic CH arylations of functionalized arenes involving amides with aryl iodides 4n and arylmetal reagents 22 in the presence of an oxidant such as Ag(I) or Ag(I)/Cu(II) have been reported. The former reactions with aryl iodides are thought to proceed through a Pd(II)Pd(IV) cycle and those with arylmetals are oxidative direct arylations that correspond to Scheme 1C.…”