Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• pinacol esters [43]. The reaction took place in the presence of Ni(OTf)2, dtbbpy, Zn(0), and TMSCl (trimethylsilyl chloride) in DMF at 130 °C (Scheme 22). The Ni(OTf)2 catalyzed the transmetallation reaction with Ar-Bpin and subsequent insertion of CO. The reduction of the nitro group is catalyzed by Zn(0

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

• transmetallation of the organometallic coupling partner 120 to the TM catalyst (Scheme 23B). The resulting organometallic intermediate 121 can act as a reducing agent, transferring an electron to RAE 10 to form radical anion 11 and the corresponding oxidized metal complex 122. Following fragmentation, the ensuing

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• precursor for coordination compounds. The following transmetallation with cobalt(II) produced an intriguing Pacman-like coordination compound 16-Co(II) (Scheme 6) [66]. The spontaneous oxidation of cobalt(II) to cobalt(III) resulted in modifying the cobalt cation coordination sphere from a distorted-square

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

• complex was obtained through transmetallation as will be described later. In 2013, Cazin and co-workers [25] reported the synthesis of [NHC–CuCl] complexes similar to those reported earlier by Diez-González et al. [15], but using K2CO3 in place of alkali alkoxides under milder conditions. In contrast to

• DMSO. However, the Cu(I) complex 54 was obtained in trace amounts only (Scheme 18) [31]. This complex could be obtained in good yield through transmetallation of the corresponding Ag complex as discussed later in Scheme 24. Douthwaite and co-workers reported the synthesis of Cu(I) bromide complexes 56a

• N,N’-disubstituted salts, e.g., dicyclohexyl-substituted salt (ICy, SICy), to form the Cu complexes seemed somehow to be impeded [33]. Some of these complexes were used as NHC transfer reagents to obtain Au(I) and Pd(II) complexes through transmetallation [34]. In another interesting paper, Bertrand

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• the reaction temperature led to improved reaction outcomes (Supporting Information File 1, Table S1, entries 2 and 11). We have continued the evaluation of reaction conditions for improving the diastereoselectivity of the reaction. We have tested transmetallation of the in situ-generated zinc enolate

• to the ammonium enolate by treatment with n-tetrabutylammonium chloride (Table 1, entry 7). For this purpose, the enolate was added to a solution of n-Bu4NCl in THF, and then the reaction mixture was stirred for 30 min before the addition of tropylium NTf2. Prolonging the transmetallation reaction

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

• “built-in base” route relies on the use of Cu2O which can be directly reacted with a suitable NHC precursor 1 (Scheme 1c) [28]. In any case, the most common approach hinges upon the use of the preliminary preparation of an intermediate silver(I)/NHC complex followed by facile transmetallation to copper(I

• ) (Scheme 1d). In some cases, this transmetallation step is carried out in situ [14][15][29][30][31][32]. Notably, these generally successful synthetic routes produce a considerable amount of transition metal waste (next to the inherent use of solvents) and are therefore in misalignment with the principles

• of green chemistry. Syntheses via mechanochemical methods offer elegant and atom-economic alternatives to liquid state synthesis approaches [33][34][35][36][37][38][39][40][41][42][43]. In accordance with the in situ transmetallation route in liquid state synthesis, a one-pot two-step procedure in a

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• transmetallation step, and not in the coordination of the iron-containing intermediates [36][37]. The use of magnesium alkoxide salts, either as an ω-functionalization of the nucleophilic partner (Scheme 4) or as an external molecular additive such as EtOMgCl (Scheme 5), also likely proceeds similarly to the NMP

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• iodides showed good to excellent yields when coupled with phenylacetylene. The proposed mechanism is similar to the standard palladium-catalyzed Sonogashira reaction with the steps involving oxidative addition of the aryl/vinyl halide followed by transmetallation, and reductive elimination. The mechanism

• -phenanthroline as ligand resulted in a shorter reaction time and better yield in comparison with the other ligands tested. Mechanistically, the iron is oxidized from Fe(II) to Fe(III) in the reaction step by the addition of 2-iodophenol which is further followed by transmetallation and reductive elimination

• (Scheme 15). The precatalyst FeCl2 is activated under the reaction conditions which is denoted as complex A. The reaction begins with the oxidative addition of aryl/vinyl halide forming complex B. Iron acetylide on reaction with this complex in a transmetallation step yields complex C. The resulting

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• oxidative addition, transmetallation, and reductive elimination processes. On the other hand, iron may act as a Lewis acid, activating carbon–carbon multiple bonds via π-binding or heteroatoms via σ-complexes. This can either generate the organoiron complex after nucleophilic attack or produce a carbocation

• produce the pyrrolidinyl methyl radical 10 which may add to the iron center to form the Fe(III) complex 11. Reductive elimination would give rise to the final product, and transmetallation with a Grignard reagent regenerates the active Fe species. Alternatively, release of the aryl radical via ipso-attack

• species is stable enough to be selectively trapped by the less sterically demanding 2° alkyl radical 29. Reductive elimination would form the difunctionalized product and transmetallation with an aryl Grignard reagent regenerates the active Fe species 26, restarting the catalytic cycle. As driving Giese

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• previously reported procedure [20][45] was modified to improve the yield of inthomycin A ((rac)-1) by replacing the Stille coupling partners. The required (Z)-3-(tributylstannyl)propenal (57) was easily accomplished by LiAlH4 reduction of propargyl alcohol (14) and then transmetallation with Bu3SnCl followed

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and ⁶Li/¹³C NMR spectroscopic data

• Jürgen Vollhardt,
• Hans Jörg Lindner and
• Hans-Joachim Gais

Beilstein J. Org. Chem. 2020, 16, 2057–2063, doi:10.3762/bjoc.16.172

• from sulfonyl lithio methanides 1 [9] through α-deprotonation [1][2][4], and from arylsulfonyl dilithio methanides 3 [10][11] though ortho,α-transmetallation [10][11][12][13] (Scheme 1). We had found that the α-deprotonation of the lithio methanide 1a with n-butyllithium (n-BuLi) gave the stable silyl

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• with Suginome’s PhMe2Si-BPin [35] as a silicon pro-nucleophile (Scheme 11A) [36]. The mechanism followed the expected pathway involving transmetallation from boron to copper to form the corresponding Cu–Si species III. This intermediate then adds to the imine 45 to give intermediate IV, which after

• , Ohmiya and co-workers envisioned inverting the polarity of an aldehyde 81 via conversion into the corresponding α-alkoxyalkyl Cu(I) anion 78. Utilizing 78, which undergoes transmetallation to an initially formed Pd(II) intermediate (from oxidative addition) led to cross couplings affording benzhydryl

• -position on the ring could be accessed. A dual catalytic cycle was proposed, where the Cu–Si species formed in situ undergoes transmetallation to the Pd(II) species resulting from the attack of Pd(0) on the aziridine ring, ultimately affording the silylated product with silicon at the benzylic site (Scheme

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• copper catalysis (Scheme 15, conditions I) [39]. Mechanistically, the authors proposed the formation of a silver(I)–SeCF3 adduct, followed by a transmetallation step, yielding the active CuSeCF3 species. Good to very good yields were obtained on a broad scope, including amide-, ester-, and heterocycle

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• ) species B. The 1,2-addition of silylcopper(I) B to the aromatic aldehyde 1 [15][16][17][18][19] and the subsequent [1,2]-Brook rearrangement from the obtained α-silyl-substituted copper(I) alkoxide C forms the key intermediate, an α-silyloxybenzylcopper(I) species D. The transmetallation between D and an

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

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• that possesses higher thermal stability than the corresponding organolithium or -magnesium species due to the almost covalent C–Zn bond [29][30]. Moreover, organozinc reagents can be easily transformed to the “reactive” species, through a transmetallation process with a transition metal (e.g., Pd or Cu

• presence of 10 mol % of CuI in DMF at 50 °C for 24 h resulted in limited formation (11% yield) of the cross-coupling product 4a (Table 2, entry 1). The Cu(I)-catalyzed cross-coupling reaction with 3a was proposed to take place via the following three key reaction steps [36]: (i) transmetallation from 2-Zn

• to the corresponding Cu(I) species, (ii) oxidative addition of a CAr–I bond to the Cu(I) atomic center to generate Cu(III) species, and (iii) reductive elimination of the product 4a along with the regeneration of the Cu(I) salt. When the initial transmetallation from 2-Zn to the reactive Cu(I

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• undergoes oxidative addition with arylpyridine to generate I1. Then, elimination of neopentane (R–H) by reductive elimination gives cobaltacycle I2. Nucleophilic addition of I2 to imines, followed by transmetallation with a Grignard reagent and protonation provide the desired hydroarylation product 57. In

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• cyanotrifluoromethylation reaction. The mechanistic study of the oxy-trifluoromethylation of phenylacetylene has then led to demonstrate that the reaction is accelerated in the presence of additives such as B2pin2 [35]. A mechanism involving an initial step of transmetallation of B2pin2 with the Cu(I) catalyst was proposed

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• is subsequently desilylated with TBAF in the presence of CuCl and DABCO to obtain the alkynylcopper species D. In the meantime oxidative addition of the previously released iodoarene 2 to the Pd(0) species occurs and the resulting palladium(II) complex E then undergoes transmetallation with the

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• congruence with the reductive iodonio-Claisen rearrangement (RICR) to show that there may be an underlying mechanism which expands the reasoning behind the previously known C–C bond-forming reaction. By rationalizing the hypervalent iodine’s metal-like properties it was concluded that a transmetallation

• -guided electrophilic substitution (HIGES). Keywords: electrophilic aromatic substitution; hypernucleofugality; hypervalent iodine; iodonio-Claisen; transmetallation; Introduction Hypervalent iodine compounds have been known for over a hundred years, but it was not until their renaissance in the 1990’s

• transmetallation with an appropriate metalloid substrate. This concept is counter to previous mechanisms in which the electrophilic hypervalent iodine reagent is attacked by unsaturated C–C bonds [18][19][20][21][22]. To show evidence for this transmetallation event, benzyl metalloid groups were used under the

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• A, transmetallation of the boronic acid with the active Cu(II) species 73 gave the arylcopper(II) complex 74, which reacted with CF3• to afford the arylcopper(III) complex 75. Next, a reductive elimination gave the trifluoromethylated product with release of the Cu(I) complex 76 that was re-oxidised

• to the active copper(II) catalyst 73 to close the cycle. In path B, the copper(II) complex 73 reacted with CF3• to form the copper(III) complex 77, which after transmetallation with the boronicacid gave the same intermediate 75. Trifluoromethylation of potassium organotrifluoroborates: In 2013

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

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

• favourable thermodynamics with an increase in the electropositive nature of boron, which in turn increases the rate of the transmetallation step. Changing the group at the 4-position of the phenylboronic acid gave good yields for both electron-rich (19, 79% yield) and electron-poor (33, 76% yield

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• , whereupon it reacts with another equivalent of arylurea (Scheme 17) [231]. Similarly, BQ’s role in C–H coupling of boronic acids would likely be to oxidize Pd(0) to Pd(II) after the product forming step (Scheme 18). Transmetallation between the palladacycle and arylboronic acid followed by reductive

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• product derived from treating N-Boc-protected piperazines with sec-BuLi at –78 °C (Figure 3, conditions A) while the other converts the α-lithiation product to an α-Cu intermediate via transmetallation followed by electrophilic trapping (conditions B). As shown in Figure 3, conditions A generally work