Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald–Hartwig (B–H) or Chan–Lam (C–L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)6 as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and

• ; carbonylative cyclization; Chan–Lam; nitrogen heterocycle; one-pot; Introduction Dibenzodiazepine units are without doubt highly privileged structures, endowed with numerous medicinally relevant properties, and notably include anti-anxiolytic and antidepressant activities. These scaffolds have received much

• review in 2018 focused on a variety of routes to these compounds [8]. The well-known Buchwald–Hartwig (B–H) and Chan–Lam (C–L) reactions have proven to be highly useful procedures that allow the step-economical synthesis of diverse biologically relevant heterocycles through C–N bond formation [9]. These

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• bond formation. However, these methods suffer from limitations such as moisture sensitivity, the requirement of specific ligands, and the use of expensive palladium catalysts [17]. Also, Chan Lam, Evans, and other research groups have developed copper-catalyzed C–N bond formation reactions by careful

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• seco-acid 36. Using this approach, the authors were able to achieve the formal synthesis of 2 reaching a key intermediate in 34% overall yield after 9 steps (Scheme 16). Cousin and co-workers [50] innovated by using the Chan–Lam coupling [23][24][25] for the diaryl ether formation and applying an

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• direct analogy to the RGD-peptide experiment shown above. In this case, a Cu(II)-mediated Chan–Lam coupling reaction was used to place each molecule on a arylborate ester coating the array (Scheme 2) [23]. The Cu(II) needed for the transformation was generated at the selected electrodes by the oxidation

• surface and a 1:1 R6A/cysteine methyl ester surface. Calibrating the array-based signaling experiment for monitoring small molecule G-protein interactions. A Cu(I)-catalyzed cross-coupling reaction on an array. An array-based Chan–Lam coupling reaction. A new method for decreasing the concentration of R6A

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• , which leads to formyl products from formal oxidative cleavage of a C=C bond. Our interest in vinylogous analogues of 2-nitroaryl photoreactive groups stems from studies into alkenylboronic acid reagents for Chan–Lam-type modification of peptide backbone N–H bonds, directed by a proximal histidine

• noting that N-formyl products are themselves acylating reagents, and thus could find use in photochemical generation of selective acyl donors. Uncaging of peptide backbone N–H bonds from Chan–Lam-type modification. Photocleavage of compounds 1 and 6 under basic conditions. Yield of products was

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• mechanisms, i.e., a Chan–Lam coupling and an Ullmann coupling. The Chan–Lam coupling involved a C–N bond formation (intermediate I, 84) which then entered into the Ullmann coupling to undergo intramolecular cyclization to form final product 78 and release Cu(III) to Cu(I) by reductive elimination. In this

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• C–C coupling reactions, is to consider the ability of organocatalysed photoredox reactions to perform reactions which create C–X (X = N, O, S) bonds, in reactions analogous to Buchwald or Chan–Lam couplings. An example of the creation of C–S bonds is given by Wang and co-workers, who have reported

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• . Presently, the most popular approaches in constructing a C(sp2)–S bond are the transition-metal-catalyzed Ullmann C–S coupling reaction [4][5][6][7][8], Chan–Lam cross-coupling reaction [9][10][11][12] as well as the transition-metal-catalyzed C–H bond activation [13][14][15]. Recently, as a new trend, the

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• Abstract A flow system to perform Chan–Lam coupling reactions of various amines and arylboronic acids has been realised employing molecular oxygen as an oxidant for the re-oxidation of the copper catalyst enabling a catalytic process. A tube-in-tube gas reactor has been used to simplify the delivery of the

• oxygen accelerating the optimisation phase and allowing easy access to elevated pressures. A small exemplification library of heteroaromatic products has been prepared and the process has been shown to be robust over extended reaction times. Keywords: Chan–Lam coupling; flow chemistry; gases in flow

• with a large number of nucleophiles and tolerated a variety of substrates, making the process one of the most efficient ways for C–N/O coupling [11]. Several modifications of the Chan–Lam reaction have been reported, expanding its scope and it has since been used to synthesise several biologically

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• loading. Based on our accrued experience [52], in a first attempt, we employed Cu(OTf)2 (10 mol %) in refluxing 1,2-dichlorethane (DCE) to effect C–C coupling, but the reaction provided (phenoxymethylene)dibenzene (12) as the only product formed through the C–O coupling (Chan–Lam–Evans coupling product

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• Dimitra Kontokosta Daniel S. Mueller Dong-Liang Mo Wiktoria H. Pace Rachel A. Simpson Laura L. Anderson Department of Chemistry, University of Illinois at Chicago, 845 W. Taylor St., Chicago, IL 60607, U.S.A 10.3762/bjoc.11.226 Abstract A Chan–Lam reaction has been used to prepare N-alkenyl-α,β

• . Keywords: Chan–Lam; copper; nitrone; oxygen transfer; pyridine; Introduction While most applications of the Chan–Lam reaction are focused on the synthesis of aryl ethers and aryl amines, our group has been interested in the use of the Chan–Lam reaction for the synthesis of O-alkenyl oximes and

• products [6][7][8][9][10][11][12][13]. Specifically, we reported that N-arylnitrones 3 can be prepared by a Chan–Lam coupling of 1 and 2 and that these compounds undergo a copper-catalyzed rearrangement to α,β-epoxyimines such as 4 [8]. Reduction of these products in the presence of a Lewis acid gave

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• arylboronic acids and substituted C-nitroazole coupling, applying the conditions described for the Chan–Lam reaction. This involves the use of chlorinated solvents, pyridine as base, and prolonged reaction times to obtain high yields of the product [28][29]. No detailed investigation on the influence of the

• acid. Most reports on the Chan–Lam coupling reaction underline the demand of air introduction into the reaction mixture to provide high yields of the products [22][24][36][37]. The plausible mechanism of this catalytic reaction was proposed by Evans [38] and described for N-nucleophiles by Collman [39

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N

• )TMEDA]2Cl2, omitting the base and working at room temperature [13][14]. Besides palladium and copper, nickel catalysis also allows the arylation of primary and secondary amines [15][16]. However, the three methods (Ullmann–Goldberg, Buchwald–Hartwig and Chan–Lam) have become standard procedures for N

• , published at the same time, was synthesized by the coupling of L-aspartic acid (83) to aryl bromide 82 in 55% yield and 90% ee (Scheme 20). Under these reaction conditions, CuI was found to be the copper source that caused the least amount of racemization [72]. Chan–Lam arylation in the synthesis of