Transient Directing Groups in Metal−Organic Cooperative Catalysis

Abstract

The direct functionalization of CÀ H bonds is among the most fundamental chemical transformations in organic synthesis. However, when the innate reactivity of the substrate cannot be utilized for the functionalization of a given single CÀ H bond, this selective CÀ H bond functionalization mostly relies on the use of directing groups that allow bringing the catalyst in close proximity to the CÀ H bond to be activated and these directing groups need to be installed before and cleaved after the transformation, which involves two additional undesired synthetic operations. These additional steps dramatically reduce the overall impact and the attractiveness of CÀ H bond functionalization techniques since classical approaches based on substrate pre-functionalization are sometimes still more straightforward and appealing. During the past decade, a different approach involving both the in situ installation and removal of the directing group, which can then often be used in a catalytic manner, has emerged: the transient directing group strategy. In addition to its innovative character, this strategy has brought CÀ H bond functionalization to an unprecedented level of usefulness and has enabled the development of remarkably efficient processes for the direct and selective introduction of functional groups onto both aromatic and aliphatic substrates. The processes unlocked by the development of these transient directing groups will be comprehensively overviewed in this review article.

The transient-chelating-group-controlled stereoselective Rh(i)-catalyzed silylative aminocarbonylation of 2-alkynylanilines: access to (Z)-3-(silylmethylene)indolin-2-ones

“…A plausible mechanism for the silylative aminocarbonylation protocol was proposed (Scheme 4). 5–12 Oxidative addition of the active Rh I species to silane 2a forms the H–Rh III –Si complex intermediate A. 12 Subsequently, coordination of the Rh III complex intermediate A with the N -(2-ethynylphenyl)acrylamide intermediate B, which is in situ generated from the reaction of 2-alkynylaniline 1 with acryloyl chloride and K 2 CO 3 , affords the intermediate C. Therein, intermediate C containing an acryl transient chelating group can strongly coordinate with the Rh III species, thus resulting in cis -silylrhodation across the CC bond to form the cis -silyl vinyl-Rh III intermediate D. 11,12 Intermediate D may undergo two pathways for the insertion of CO: 5 c – f ,8,12 One is the direct insertion of CO into the vinyl–Rh bond with the simultaneous formation of a N–Rh bond via the reductive loss of the acryl group with the aid of the base (K 2 CO 3 ) 12 j , k to generate the carbonyl-Rh III –N six-membered ring intermediate F; the other involves the formation of the vinyl-Rh III –N five-membered ring intermediate E through the reductive decomposition of the acryl C(sp 2 )–N bond with the aid of the base, 12 j , k followed by the insertion of CO to generate the intermediate F. The reductive elimination of intermediate F results in the desired product ( Z )-4 and regenerates the active Rh I species.…”

“…Using cinnamoyl chloride 3b as the transient chelating group may afford the alkyne cis -addition intermediate D′ and the alkyne trans -addition intermediate D′′ due to steric hindrance and electron effects from the cinnamoyl group. 11,12 The alkyne cis -addition intermediate D′ undergoes CO insertion, C–N bond cleavage, and N–Rh bond formation to afford the intermediate F, whereas the alkyne classic trans -addition intermediate D′′ may undergo hydroformylation with CO to form ( E )- 5eab . This is because the in situ generated cinnamyl C–N bond in the intermediate D′′ involving conjugative effects is more stable than the acryl C–N bond, leading to no cleavage of the cinnamyl C–N bond.…”

“…On that basis, we envisioned that if a transient chelating group 11 was present to coordinate with transition-metal catalysts, it may be possible to carefully control the corresponding stereoselectivity. Herein, we report a new method involving the acryl-transient-chelating-group-controlled stereoselective [Rh I (cod)Cl] 2 -catalyzed silylative aminocarbonylation of 2-alkynylanilines with CO and silanes, 12 enabling the synthesis of ( Z )-3-(silylmethylene)indolin-2-ones in moderate to good yields and with >99 : 1 Z / E stereoselectivity ( Scheme 1b ).…”

Palladium-Catalyzed C(sp3)–H Biarylation of 8-Methyl Quinolines with Cyclic Diaryliodonium Salts to Access Functionalized Biaryls and Fluorene Derivatives

“…The directing group (DG)-assisted proximal C–H bond activation is an efficient and powerful tool for site-selective functionalizations under transition-metal (TM) catalysis . However, inherent challenges to removing DG in the targeted molecules led to the discovery of easily removable DGs, transient DGs, traceless DGs, and modifiable DGs, which can reduce the synthetic manipulations . In this context, the development of intrinsic DGs is on the rise recently where the DG is a common functionality present in the substrate or complex molecule and the product.…”

Native Amine-Directed ortho-C–H Halogenation and Acetoxylation /Condensation of Benzylamines

“…A few reports have been published on ortho-C-H halogenation of protected benzylamines, with conversion of the free amine group into a better, static DG (Scheme 1a). 9 Notably this requires a pre-installation and removal step to access the free benzylamine products, while these reports are also limited to α-primary benzylamines. Meanwhile, halogenation of free amines has been limited, to the best of our knowledge, 10 to a recent transient DGmediated Pd-catalyzed γ-fluorination of aliphatic amines disclosed by Yu, 11 and reactions of 3° benzylamine-Pd complexes by Lewis.…”