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Constructing highly proficient C–X (X = O, N, S, etc.) and C–C bonds by leveraging TMs (transition metals) (Fe, Cu, Pd, Rh, Au, etc.) and enzymes to catalyze carbene insertion into X–H/C(sp2)–H is a highly versatile strategy. This is primarily achieved through the in situ generation of metal carbenes from the interaction of TMs with diazo compounds. Over the last few decades, significant advancements have been made, encompassing a wide array of X–H bond insertions using various TMs. These reactions typically favor a stepwise ionic pathway where the nucleophilic attack on the metal carbene leads to the generation of a metal ylide species. This intermediate marks a critical juncture in the reaction cascade, presenting multiple avenues for proton transfer to yield the X–H inserted product. The mechanism of C(sp2)–H insertion reactions closely resembles those of X–H insertion reactions and thus have been included here. A major development in carbene insertion reactions has been the use of engineered enzymes as catalysts. Since the seminal report of a non-natural "carbene transferase" by Arnold in 2013, "P411", several heme-based enzymes have been reported in the literature to catalyze various abiological carbene insertion reactions into C(sp2)–H, N–H and S–H bonds. These enzymes possess an extraordinary ability to regulate the orientation and conformations of reactive intermediates, facilitating stereoselective carbene transfers. However, the absence of a suitable stereochemical model has impeded the development of asymmetric reactions employing a lone chiral catalyst, including enzymes. There is a pressing need to investigate alternative mechanisms and models to enhance our comprehension of stereoselectivity in these processes, which will be crucial for advancing the fields of asymmetric synthesis and biocatalysis. The current review aims to provide details on the mechanistic aspects of the asymmetric X–H and C(sp2)–H insertion reactions catalyzed by Fe, Cu, Pd, Rh, Au, and enzymes, focusing on the detailed mechanism and stereochemical model. The review is divided into sections focusing on a specific X–H/C(sp2)–H bond type catalyzed by different TMs and enzymes. [ABSTRACT FROM AUTHOR]

Fe-based catalysts as well as enzymes typically yield low stereoselectivity for carbene insertion into X–H bonds. Here, we have utilized DFT methods to understand the mechanism and unusually high enantioselectivity in an Fe-spiroBox catalyzed carbene insertion reaction into the O–H bond of aliphatic alcohols. Our transition state model shows a unique binding of the reaction intermediates to the chiral catalyst enabled by weak non covalent interactions that is absent in other X–H insertion reactions. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases. [ABSTRACT FROM AUTHOR]

Multicomponent reactions provide an excellent approach toward quaternary carbon centres utilizing convergent chemical reactions in a highly selective manner under one‐pot conditions. The reactivity of substrates and metal catalysts is carefully controlled, precluding the formation of side‐products. In this context, transition metal catalyzed reactions of onium ylides generated via diazo precursors and nucleophiles with a third component (an electrophile) have garnered significant attention. Using an allylic precursor as the electrophilic partner provides opportunities to construct all‐carbon quaternary centres. Furthermore, the presence of an allyl fragment in the multicomponent product serves as a pivotal handle for carrying out subsequent modifications. Several recent studies have employed Rh, Pd, and dual Rh/Pd catalytic systems in multicomponent reactions involving allylic alkylation that proceed via a synergistic or relay pathway. Although not significantly successful, in a few cases, asymmetric induction is achieved through chiral phosphoric acids or chiral phosphine ligands. Limited substrate and catalyst scope and the underlying mechanistic complexities have posed formidable challenges, slowing the advancement of asymmetric reactions. This review provides details of multicomponent reactions using readily available substrates like diazo compounds, allylic carbonates, and nucleophiles (R‐OH, R‐NH2,,etc.) forming complex organic compounds. Our primary objective is to discuss the mechanistic issues that may facilitate the progress in asymmetric reactions in this field. [ABSTRACT FROM AUTHOR]

Heterobiaryls serve as relevant structural motifs in many fields of high applicative importance such as drugs, agrochemicals, organic functional materials etc. Cross‐dehydrogenative coupling involving direct oxidation of two C−H bonds to construct a C−C bond is actively being pursued as a more benign and 'greener' alternative for synthesizing heterobiaryls. Herein, we report a Cu(I)‐catalyzed cross‐dehydrogenative coupling of indoles and furans, two of the most important aromatic heterocycles using air as the terminal oxidant. The reaction proceeds with regio‐ and chemoselectivity to give the cross‐coupled products in good to excellent yields generally. A broad substrate scope with respect to both the coupling partners has been demonstrated to prove the generality of this reaction. This represents the hitherto unexplored cross‐dehydrogenative coupling methodology to obtain an indole‐furan biaryl motif. [ABSTRACT FROM AUTHOR]

The diverse reactivity of N‐heterocyclic carbenes (NHCs) in organocatalysis is due to the possibility of different modes of action. Although NHC‐bound enolates and dienolates are known, the related NHC‐bound cross‐conjugated aza‐trienolates remain elusive. Herein, we demonstrate the NHC‐catalyzed formal [6+2] annulation of nitrogen‐containing heterocyclic aldehydes with α,α,α‐trifluoroacetophenones leading to the formation of versatile pyrrolooxazolones (29 examples). The catalytically generated cross‐conjugated aza‐trienolates (aza‐fulvene type) underwent smooth [6+2] annulation with electrophilic ketones to afford the product in moderate to good yields under mild conditions. Preliminary DFT studies on the mechanism are also provided. [ABSTRACT FROM AUTHOR]