Transition-Metal-Catalyzed C–C Bond Formation from C–C Activation

Abstract

Ni-catalyzed cross coupling of aryl nitriles with arylboronic esters through C−CN cleavage. Encouraged by these results, we are interested in transition-metal-catalyzed C−C bond activation. Due to their broad availability, we then turned our attention to C−C cleavage of carboxylic acids. Rhodiumcatalyzed decarbonylative coupling of carboxylic acids with (hetero)arenes was then achieved through oxidative addition of in situ formed, more reactive mixed anhydrides to Rh(I) without the need for oxidants that are commonly required for the decarboxylative coupling of carboxylic acids. Subsequently, the decarbonylation of more challenging unstrained aryl ketones was realized under Rh catalysis assisted by N-containing directing groups. Following this work, a group exchange of aryl ketones with carboxylic acids was achieved through 2-fold C−C bond cleavage. By employing the chelation strategy, Rh-catalyzed C−C bond activation of secondary benzyl alcohols was also accomplished through β-carbon elimination of the rhodium alcoholate intermediates. The competing oxidation of secondary alcohols to ketones via β-hydrogen elimination of the same intermediates was suppressed as thermodynamically favorable five-membered rhodacycles are formed after β-carbon elimination. Different types of transformations of alcohols, including the Heck-type reaction with alkenes, cross coupling with arylsilanes, and Grignard-type addition with aldehydes or imines, have been achieved, showing the great potential of secondary alcohols in the formation of C−C bonds. These C−C bond-forming reactions are complementary to traditional cross couplings of aryl halides with organometallic reagents. However, these transformations produce small molecules as byproducts. To improve the atom economy, we then investigated C−C bond transformations of strained-ring cyclic compounds. Ni-catalyzed intermolecular cyclization of benzocyclobutenones with alkynes was recently achieved via the uncommon cleavage of the C1−C8 bond by employing a removable blocking strategy. Rhcatalyzed intramolecular annulation of benzocyclobutenols with alkynes was also achieved. In summary, our developments demonstrate the great potential of transition-metal-catalyzed C−C bond activation for the formation of new C−C bonds. To further expand the synthetic utility of C−C bond activation, more efforts are required to expand the substrate scope and to achieve earthabundant metal-catalyzed transformations.

Catalytic [4+n]-cycloaddition using furan-fused cyclobutanone as a privileged C4 synthon

“…On the basis of above results and previous studies [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] , a plausible reaction pathway has been proposed in Fig. 5.…”

“…Recently, the transition metal (TM) catalyzed carbon-carbon (C-C) bond activation of benzocyclobutenones (BCBs), followed by intramolecular insertion of an unsaturated unit, has emerged as an attractive and atom-economical approach for the direct construction of fused-, spirocyclic-, and bridged-frameworks through [4 + n]-cycloaddition (Fig. 1b) [43][44][45][46][47] . However, challenges remain in this area, including: (1) derivatization of BCBs to those that are heteroarene-fused remains elusive; (2) these transformations are mainly limited to the intramolecular versions due to the high reactivity of in situ formed metallacycle species; (3) the unsaturated units for [4 + 2]-cycloaddition have been primarily restricted to alkenes 48-51 , alkynes [52][53][54][55] , carbonyls 56 , oximes 57 , allenes/1,3-dienes 58 , and heteroarenes 59 , but imines and other readily available nucleophilic reagents are still unexploited; (4) only few catalytic asymmetric methods have been reported, and the asymmetric synthesis of chiral (hetero)arene fused heterocycles represents a signi cant challenge [60][61][62][63][64][65] .…”

Deacylative arylation and alkynylation of unstrained ketones

“…Among the traditional organic transformations of ketones, there are only a few reactions involving the fragmentation of α-C─C bonds, such as the Baeyer-Villiger oxidation, the Beckmann rearrangement, and the Schmidt reaction (9)(10)(11). Over the past decade, transition metal-catalyzed C─C activation reactions have substantially contributed to the functionalization of ketone substrates, offering an efficient and straightforward approach to accessing drug-like molecules and complex natural products (12)(13)(14)(15)(16)(17).…”

Assessing the activity and stereoselectivity of heterobimetallic Zr/Co complexes catalyzed terminal alkyne dimerization: A DFT study

“…The formation of carbon–carbon bonds and carbon‐heteroatom bonds is a crucial aspect of organic synthetic chemistry due to its flexibility and diversity, but it is difficult to perform under mild conditions. The introducing of transition metal catalysts has greatly facilitated the advancement of organic synthesis 1–4 . These catalysts offer broad applicability, mild reaction conditions, and efficient product separation, making them valuable for the synthesis of drug molecules 5,6 and natural products 7–9 via C‐X (X= C, N, O, S, halogen) coupling reactions.…”