A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• -step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions. Keywords: annulation; carbene; gold

• contrast to the most widely used ‘umbrella-like’ NHCs (Figure 1) [2][3]. An extended π-system influences the donor and acceptor properties of the carbene whilst substitution on the polycycle can position groups adjacent to the active centre. The imidazo[1,5-a]pyridin-3-ylidene motif (ImPy), independently

• fused imidazolium core (Scheme 2). No reaction was observed between 6a and [Ir(cod)Cl]2 in the presence of NEt3. A solution of the free carbene was prepared from 6 and reacted with [Ir(cod)Cl]2 and then CO to afford the AImOxIr(CO)Cl complex 15. A minor side-product with a strong red colour was formed

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• alcohols, followed by base-promoted cyclization to afford the target spirocyclic compounds in good to high yields. Keywords: diazoarylidene succinimides; intramolecular cyclization; rhodium(II) carbene O–H insertion; spirocycles; Introduction Spirocyclic motifs have emerged as auspicious frameworks for

• this protocol for spirocyclization and spiroheterocycle formation. The first step of the synthesis, the insertion of rhodium carbene into the O–H bond of 3-bromopropanol, was carried out under standard conditions in the presence of 0.05 mol % Rh2(esp)2 in dry DCM. 1H NMR spectroscopy was used to

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• carbene (NHC)-catalyzed radical relay, and (iv) mechanisms under electrochemical activation. By discussing selected literature examples, we illustrate how the activation mode of NHPI esters, and the reactivity of the resulting radical species, can vary depending upon the choice of catalytic or

• , accompanied by the formation of cyano-B(pin) 142. Importantly, in the absence of ZnCl2, intermediate 140 could be detected by HRMS and 11B NMR, highlighting the pivotal role of ZnCl2 in promoting rearomatization. N-Heterocyclic carbene (NHC) catalysis In 2019, Nagao and Ohmiya reported the decarboxylative

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• organic synthesis, as they can be used as diazo intermediates or carbene precursors for the rapid construction of complex molecules along with the introduction of fluoroalkyl groups [14][15][16]. Although the reaction of trifluorodiazoethane [17][18][19][20][21][22][23][24][25][26][27] as well as α-diazo

• reacts with the copper catalyst generating the Cu-carbene intermediate B, which undergoes nucleophilic attack by acetonitrile to form the intermediate C. Subsequently, nucleophilic addition of benzoic acid to intermediate C affords the acetimidic anhydride D with the release of CuI catalyst for the next

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• ][19]. These mesoionic carbenes (MICs), together with their pyrazolin-4-ylidene [20] and 1,2-isoxazol-4-ylidene cousins [21], are the strongest donors among the various types of carbene ligands known thus far [22]. A distinct class of mesoionic or abnormal carbenes based on the 1,2,3-triazole ring

• report described the preparation of a CAAC·CS2 zwitterion. Thus, in 2009 Bertrand et al. obtained the betaine 2 by reacting the free carbene 1 with a slight excess of CS2 in THF at room temperature (Scheme 1) [62]. The starting material that featured a bulky and rigid spirocyclic alkyl group derived from

• free carbene [39][41][42][58]. Hence, we decided to probe the feasibility of this approach for the synthesis of CAAC·CS2 and MIC·CS2 betaines from readily available aldiminium or 1,2,3-triazolium salts. Synthesis of CAAC·CS2 zwitterions To begin our study, we investigated the synthesis of CAAC·CS2

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• acknowledged to be effective in introducing substituents to the nitrogen atoms of NH-heterocycles by means of carbene insertion into the N–H bond upon catalytic or photolytic decomposition of diazo compounds [25]. Furthermore, the reaction of N-heterocycles containing multiple non-equivalent nitrogen atoms

• will be reported in the following works. Conclusion In summary, a new diazo reagent for the convenient incorporation of heterocyclic substituents at the alpha-position of glutarimide by Rh(II)-catalyzed insertion of carbene into the N–H bond of nitrogen heterocycles has been proposed. The method allows

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• molecule which catalyzes the macrocyclization reaction around the axle (Figure 1b). Results and Discussion In order to access the target [2]rotaxanes we made use of the CuAAC reaction, performed in the presence of a copper(I) N-heterocyclic carbene, a very stable and efficient class of catalysts used in

• active-metal template and clipping methods to yield the target interlocked molecules via [1 + 1] or intramolecular macrocyclizations, realized through CuAAC reactions catalyzed by axle-copper(I) N-heterocyclic carbene complexes. The [2]rotaxane obtained by [1 + 1] clipping (R1) could be only observed by

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• traditional heating methods. In the meanwhile, Qiu and Xu et al. reported the coupling reaction between diazo compounds 163 and N-sulfenylsuccinimides 1 under catalyst-, base-, and additive-free conditions (Scheme 71) [101]. The reaction proceeded via a radical pathway, in which a free carbene was generated

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• Nosheen Beig Varsha Goyal Raj K. Bansal Department of Chemistry, The IIS (deemed to be University), Jaipur, 302 020, India 10.3762/bjoc.19.102 Abstract N-Heterocyclic carbenes (NHCs) are a special type of carbenes in which the carbene carbon atom is part of the nitrogen heterocyclic ring. Due to

• addition; [3 + 2] cycloaddition reaction; hydrosilylation reaction; N-heterocyclic carbenes; NHC–Cu complexes; NHC–Cu complexes as catalyst; Introduction N-Heterocyclic carbenes (NHCs) are a neutral species having the carbene carbon atom as a part of the nitrogen heterocyclic ring. The transient

• ) reported by Arduengo et al. [3], turned out to be a watershed in this regard as it initiated intense research activity in this field. Compound 6 is stable in the absence of oxygen and air. The first air-stable carbene, namely 1,3-dimesityl-4,5-dichloroimidazol-2-ylidene (7b) [4] was obtained from the

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

•  1. Benzoguanidine has an extended π-conjugation compared with carbazole and is more nitrogen-rich (three N-atoms vs one in carbazole). Thompson et al. recently reported a series of carbene–metal–amide (CMA) (metal = Cu, Ag, Au) emitters employing a benzoguanidine ligand [10]. The extended π

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ]. However, numerous inconsistencies have been observed when comparing the outcomes of diazo- and iodonium ylide-based metallocarbene reactions, especially during metal-free control experiments, which led researchers to propose alternative, carbene-free reaction pathways for iodonium ylides. This was first

• , where the byproducts typically associated with free carbene formation (e.g., dimerization or rearrangement) were not observed (Scheme 2). In 1988, Hadjiarapoglou was investigating transition metal- and photocatalyzed intermolecular cyclopropanations between ylide 8 and norbornene, and found indane 9 was

• produced in 74% yield after six days at room temperature in the absence of catalyst (Scheme 2a) [107]. At that time, the authors did not articulate any theory as to how the reaction might initiate under such mild conditions, though they recognized that the decomposition of 8 into a free carbene would not

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

• generation of carbene as a reactive intermediate [36][37]. Also, spirocyclic iodonium ylides have been used for radiolabeling techniques [38]. In 2013, Shibata’s research group reported a novel trifluoromethanesulfonyl iodonium ylide for trifluoromethylthiolation of enamines, indoles, and ketoesters

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• significantly affect the C–H alkylation reaction and the reaction also proceeded well with hydrazones 13 obtained from aliphatic aldehydes or ketones. Based on mechanistic experiments and DFT calculations, the reaction presumably proceeds via a Cu–carbene migratory insertion (Scheme 4b). In the presence of CuI

• and the base the initial direct C–H activation of the ylide 12 gives the copper pyridinium ylide 15. The latter reacts with the diazo compound formed through reaction of hydrazone 13 with the base to give the copper–carbene species 16. Then, the intermediate 16 undergoes a Cu–carbene migratory

• with a bulky N-heterocyclic carbene ligand and (2,6-t-Bu2-4-Me-C6H2O)2AlMe (MAD) as the Lewis acid which allowed the direct C-4 alkylation of pyridines 1 (Scheme 12a). With the optimized reaction conditions in hand the group also screened the alkene and pyridine substrate scope which resulted C4

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• to the PBTA scaffold is an annulation of benzothiazoles with a pyrrole moiety (Scheme 1). It includes intramolecular cyclizations of benzothiazoles bearing a 3'-chloro substituent at C2 position (Scheme 1, entries 1 and 2) [5][6][7], intramolecular catalytic carbene cascade reactions of propargyl 1,3

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• ring, while flavylium triflate and 2,4,6-triphenylpyrylium tetrafluoroborate were not compatible with our reaction conditions. Heterodonor ferrocenyl phosphane–carbene ligands efficiently promote the conjugate addition of Grignard reagents to α,β-unsaturated lactones [58]. Building on this knowledge

• the trapping of metal enolates by Michael reactions with nitroalkenes 122 and disulfonyl ethylenes 124 (Scheme 31) [67]. The conjugate additions of dialkylzinc, Grignard, and trialkylaluminum reagents to cyclic enones 121 were realized using previously established chiral phosphoramidite, carbene or

• , which begins with a Cu-catalyzed enantioselective conjugate addition/enolate alkylation tandem reaction sequence utilizing the N-heterocyclic carbene ligand L40 [112]. Ketone 232 was isolated in 61% yield and 81% ee. Hereafter, the authors were able to synthesize the complex tetracyclic structure within

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• -Innovation Center of Efficient Processing and Utilization of Forest Resources College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China 10.3762/bjoc.19.39 Abstract A synthetic route to the bench-stable fluorinated masked carbene reagent diethyl 2-diazo-1,1,3,3,3

• fluorinated diazo compounds might be rationalized by their low accessibility and high volatility [44]. As a part of our continuing investigations in fluorinated carbene chemistry [45][46][47][48][49], we hypothesized that the synthesis of cyclopropanes with geminal trifluoromethyl and

• difluoromethylphosphonate groups at the ring might be possible by using our newly developed bench-stable diazo reagent CF3C(N2)CF2P(O)(OEt)2. Therefore, we report herein our preliminary results toward this goal via copper iodide-catalyzed cyclopropanation reaction of an acceptor carbene precursor with selected terminal

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• would afford the [2 + 2] adduct. Hydroruthenation of the allene produces 103 which can either undergo reductive elimination to afford the cyclopropanated bicyclic alkene or undergo a [2 + 2] cycloreversion to generate the Ru–carbene 104. The Ru–carbene 104 can rearrange to 100 through a 1,3-migration of

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• , Germany 10.3762/bjoc.19.34 Abstract A protocol for the mechanochemical synthesis of copper(I)/N-heterocyclic carbene complexes using cheap and readily available K3PO4 as base has been developed. This method employing a ball mill is amenable to typical simple copper(I)/NHC complexes but also to a

• sophisticated copper(I)/N-heterocyclic carbene complex bearing a guanidine moiety. In this way, the present approach circumvents commonly employed silver(I) complexes which are associated with significant and undesired waste formation and the excessive use of solvents. The resulting bifunctional catalyst has

• focus has seldomly been on the preparative methods to access the required catalysts themselves. As case in point, we decided to re-investigate the synthesis of copper(I)/N-heterocyclic carbene (NHC) complexes, which are broadly applicable catalysts for a wide variety of transformations [4][5][6]. While

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• triazoloporphyrins 32a–c and triazole-bridged bisporphyrins 34 in good yields. The “click reaction” of azidoporphyrin 30 with the terminal alkynes 31a–c and 33 in a THF/water (3:1) mixture was investigated by using different catalytic systems. Among these, copper carbene (SIMes)CuBr proved to be a better catalyst

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• /B‒H exchange [114]. Hevia reported a combination of a tris(alkyl)gallium species and bulky N-heterocyclic carbene acted as an FLP for B‒H insertion, and was used subsequently as a catalyst in the hydroboration of ketones, aldehydes, esters, and imines with HBpin [115]. Using an ONO-pincer-supported

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• Langemann reported an efficient and short total synthesis of the natural product dactylol (72) (Scheme 12) [37]. The main originality of this work was the use of the Schrock molybdenum carbene catalyst 73 for the ring-closing metathesis reaction. The metathesis precursor 70 was obtained in 4 steps from

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• expected allyl cation (3 + 2) cycloaddition reactivity is not operating under gold(I) catalysis, but instead it behaved as a reliable and quite stereoselective vinylgold carbenoid species, affording exclusively cyclopropanation products with a wide range of olefin substrates (Scheme 18c). The carbene-type

• formation of the cis-vinylcyclopropanes (Scheme 18c and 18d). Desulfurization of the adducts again yields the product of a formal cyclopropanation with a ‘naked’ vinyl carbene species, as demonstrated by the stereoselective synthesis of the protected cis-2-vinylcyclopropan-1-amine 123 (Scheme 18d). 7

• of dithiin-fused allyl alcohols and similar non-cyclic sulfur-substituted allyl alcohols. Applications of dihydrodithiins in the rapid assembly of polycyclic terpenoid scaffolds [108][109]. Dihydrodithiin-mediated allyl cation and vinyl carbene cycloadditions via a gold(I)-catalyzed 1,2-sulfur

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• ]. Compared with highly sensitive diazo compounds, iodonium ylides are known to show ready availability and good stability [29][30]. Our group has recently demonstrated that iodonium ylides can be used as carbene precursors in the Rh-catalyzed [4 + 2] cyclization of pyrazolidinones [31]. During the

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• pyrrole-fused heterocyclic tricycles [33]. The involvement of Nazarov and in particular aza-Nazarov reactions in the cyclization of alkynes that go through metal carbene intermediates has recently been reviewed by Gao and co-workers [34]. In 2019, we reported a highly effective aza-Nazarov cyclization for

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• calculation methods, as were the remarkably downfield shifts for the novel di- and trications 21 and 22, for which even drawing suitable resonance structures is a challenge. Two phosphinidenes (23, 24), i.e., carbene analogues with potentially anionic phosphorus atoms, have remarkably upfield chemical shifts