1062136-70-2

Upstream product

• 603-76-9 1-methylindole 
• 1179348-58-3 methyl 2-(dimethyl(oxo)-λ⁶-sulfaneylidene)-2-phenylacetate 
• 15206-55-0 methyl 2-oxo-2-phenylacetate 
• 71-43-2 benzene 
• 67-56-1 methanol 
• 22979-35-7 Methyl phenyldiazoacetate 
• 101-41-7 benzeneacetic acid methyl ester 
• 120-72-9 indole 
• 158953-96-9 1-methyl-3-deuterio-1H-indole 
• 4870-65-9 2-bromophenylacetic acid 
• 37167-62-7 bromo-phenyl-acetic acid methyl ester 

Downstream Products

• 1627153-22-3 4-[(1-methyl-1H-indol-3-yl)(phenyl)methyl]hepta-1,6-dien-4-ol 
• 1627153-02-9 diethyl (2E,7E)-5-hydroxy-5-[(1-methyl-1H-indol-3-yl)-(phenyl)methyl]nona-2,7-dienedioate 
• 1627153-26-7 1-[(1-methyl-1H-indol-3-yl)(phenyl)methyl]cyclopent-3-enol 

Relevant academic research and scientific papers

Enantioselective Indole Insertion Reactions of α-Carbonyl Sulfoxonium Ylides

The first example of organocatalytic enantioselective C–H insertion reactions of indoles and sulfoxonium ylides is reported. Under the influence of phosphoric acid catalysis, levels of enantiocontrol in the range of 20–93% ee and moderate yields (up to 50

Stoichiometric Photochemical Carbene Transfer by Bamford–Stevens Reaction

The photolysis of diazoalkanes is a timely strategy to conduct carbene-transfer reactions under mild and metal-free reaction conditions, and has developed as an important alternative to conventional metal-catalyzed carbene-transfer reactions. One of the major limitations lies within the rapidly occurring side reaction of the carbene intermediate with remaining diazoalkane molecules that result in the use of an excess of the reaction partner and thus impacts on the reaction efficiency. Herein, we describe a protocol that takes advantage of the in situ generation of donor–acceptor diazoalkanes by Bamford–Stevens reaction. Following this strategy, the concentration of the diazoalkane reaction partner can be minimized to reduce unwanted side reactions and to now conduct photochemical carbene transfer reactions under stoichiometric reaction conditions. We have explored this approach in the C?H and N?H functionalization and cyclopropanation reaction of N-heterocycles and could demonstrate the applicability of this method in 51 examples.

Borane-Catalyzed Stereoselective C–H Insertion, Cyclopropanation, and Ring-Opening Reactions

Lewis acidic boranes have been shown to be effective metal-free catalysts for highly selective reactions of donor-acceptor diazo compounds to a range of substrates. The reactions of α-aryl α-diazoesters with nitrogen heterocycles indole or pyrrole selectively generate C3 and C2 C–H insertion products, respectively, in good to excellent yields even when using unprotected indoles. Alternatively, benzofuran, indene, and alkene substrates give exclusively cyclopropanated products with α-aryl α-diazoesters, whereas the reactions with furans lead to ring-opening. Comprehensive theoretical calculations have been used to explain the differing reactivities and high selectivities of these reactions. Overall, this work demonstrates the selective metal-free catalytic reactions of α-aryl α-diazoesters with (hetero)cycles and alkenes. This simple, mild reaction protocol represents an alternative to the commonly used precious metal systems and may provide future applications in the generation of biologically active compounds. Efficient and facile routes to heterocyclic compounds are highly desirable because of their remarkable biological importance and applications in drugs approved by the Food and Drug Administration. Current synthetic routes frequently use precious metal-catalyzed reactions. The problems associated with the limited resources of precious metals as well as their toxicities can be avoided through metal-free approaches. Our investigations on the reactivities of diazoesters toward the (hetero)arenes reveal that by using Lewis acidic triarylboranes as a catalyst, we can selectively effect C–H insertion, cyclopropanation, or ring-opening in good to excellent yields. Main group, or metal-free, catalysis has become a burgeoning field; yet, this flourishing field is still in its nascent stage. The work described herein represents a step toward improving the applicability of main group catalysis by employing metal-free approaches in the functionalization of organic compounds. This work demonstrates the highly selective metal-free catalytic reactions of α-aryl α-diazoesters with a range of (hetero)cycles and olefins using Lewis acidic boranes. The simple, mild reaction protocol employed represents an alternative to the commonly used precious metal systems and may provide future applications in the generation of biologically active compounds.

Tridentate Nickel(II)-Catalyzed Chemodivergent C-H Functionalization and Cyclopropanation: Regioselective and Diastereoselective Access to Substituted Aromatic Heterocycles

A Schiff-base nickel(II)-phosphene-catalyzed chemodivergent C-H functionalization and cyclopropanation of aromatic heterocycles is reported in moderate to excellent yields and very good regioselectivity and diastereoselectivity. The weak, noncovalent interaction between the phosphene ligand and Ni center facilitates the ligand dissociation, generating the electronically and coordinatively unsaturated active catalyst. The proposed mechanisms for the reported reactions are in good accord with the experimental results and theoretical calculations, providing a suitable model of stereocontrol for the cyclopropanation reaction.

Photocatalytic Alkylation of Pyrroles and Indoles with α-Diazo Esters

This article describes the photoalkylation of electron-rich aromatic compounds with diazo esters. C-2-alkylated indoles and pyrroles are obtained with good yields even though the photocatalyst loading is as low as 0.075 mol %. For EWG-substituted substrates, the addition of a catalytic amount of N,N-dimethyl-4-methoxyaniline is required. Both EWG-EWG- and EWG-EDG-substituted diazo esters are suitable as alkylating agents. The reaction selectivity and mechanistic experiments suggest that carbenes/carbenoid intermediates are not involved in the reaction pathway.

Cp*Co(iii)-catalysed selective alkylation of C-H bonds of arenes and heteroarenes with α-diazocarbonyl compounds

Cp*Co(iii)-catalysed selective alkylation of directed C-H bonds of arenes and heteroarenes has been accomplished employing donor-acceptor carbenes, derived from α-diazocarbonyl compounds. The developed method allows ready access to various substituted α-(hetero)aryl-α-arylacetic acid derivatives in good to excellent yields. Synthetic utility was also shown through the synthesis of a substituted indole derivative, an anticancer agent.

Blue light-promoted photolysis of aryldiazoacetates

Aryldiazoacetates can undergo photolysis under blue light irradiation (460-490 nm) at room temperature and under air in the presence of numerous trapping agents, such as styrene, carboxylic acids, amines, alkanes and arenes, thus providing a straighforward and general platform for their mild functionalization.

Diastereotopic group selection in hydroxy-directed intramolecular C-H alkenylation of indole under oxidative palladium(II) catalysis

Group-selective palladium(II)-catalyzed ring closures involving C-H bond alkenylation are reported. The cyclization precursors contain a prochiral bis(homoallylic) alcohol unit tethered to either an arene or an indole. The homobenzylic hydroxy group in these substrates is positioned to act as a directing group in the ortho-selective C-H bond activation prior to the cyclization event. Arene-derived precursors reacted poorly, even when applying a protocol that had proven effective in intermolecular hydroxy-directed C-H bond alkenylations. No asymmetric induction was obtained with chiral ligands, mono-N-protected amino acids (MPAAs) in particular. Conversely, the cyclization of indole-derived precursors was substantially more efficient, and installation of a substituent in the benzylic position rendered these intramolecular C-H bond alkenylations diastereoselective. The diastereotopic group selection is high with diastereomeric ratios ranging from dr=91:9 to 94:6.

Amide-Functionalized Naphthyridines on a RhII-RhII Platform: Effect of Steric Crowding, Hemilability, and Hydrogen-Bonding Interactions on the Structural Diversity and Catalytic Activity of Dirhodium(II) Complexes

Ferrocene-amide-functionalized 1,8-naphthyridine (NP) based ligands {[(5,7-dimethyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L1H) and {[(3-phenyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L2H) have been synthesized. Room-temperature treatment of both the ligands with Rh2(CH3COO)4 produced [Rh2(CH3COO)3(L1)] (1) and [Rh2(CH3COO)3(L2)] (2) as neutral complexes in which the ligands were deprotonated and bound in a tridentate fashion. The steric effect of the ortho-methyl group in L1H and the inertness of the bridging carboxylate groups prevented the incorporation of the second ligand on the {RhII-RhII} unit. The use of the more labile Rh2(CF3COO)4 salt with L1H produced a cis bis-adduct [Rh2(CF3COO)4(L1H)2] (3), whereas L2H resulted in a trans bis-adduct [Rh2(CF3COO)3(L2)(L2H)] (4). Ligand L1H exhibits chelate binding in 3 and L2H forms a bridge-chelate mode in 4. Hydrogen-bonding interactions between the amide hydrogen and carboxylate oxygen atoms play an important role in the formation of these complexes. In the absence of this hydrogen-bonding interaction, both ligands bind axially as evident from the X-ray structure of [Rh2(CH3COO)2(CH3CN)4(L2H)2](BF4)2 (6). However, the axial ligands reorganize at reflux into a bridge-chelate coordination mode and produce [Rh2(CH3COO)2(CH3CN)2(L1H)](BF4)2 (5) and [Rh2(CH3COO)2(L2H)2](BF4)2 (7). Judicious selection of the dirhodium(II) precursors, choice of ligand, and adaptation of the correct reaction conditions affords 7, which features hemilabile amide side arms that occupy sites trans to the Rh-Rh bond. Consequently, this compound exhibits higher catalytic activity for carbene insertion to the C-H bond of substituted indoles by using appropriate diazo compounds, whereas other compounds are far less reactive. Thus, this work demonstrates the utility of steric crowding, hemilability, and hydrogen-bonding functionalities to govern the structure and catalytic efficacyof dirhodium(II,II) compounds.

CuO/SiO2 as a simple, effective and recoverable catalyst for alkylation of indole derivatives with diazo compounds

The purely inorganic copper oxide on silica catalyzes the reaction of methyl phenyldiazoacetate with N-methyl indole under mild reaction conditions, giving the alkylation (formally a C-H insertion) in position 3, and the catalyst can be recovered and reused at least in 5 consecutive runs with only minor loss in activity. The scope of the reaction includes various diazo compounds and indole or pyrrole derivatives leading to alkylation or cyclopropanation depending on the heterocycle structure. An alternative mechanism, without reduction of Cu(ii) to Cu(i), is proposed on the basis of the obtained results. The Royal Society of Chemistry 2013.