Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• methylcobalamin and adenosylcobalamin (coenzyme B12) that serve as organometallic cofactors in B12-dependent enzymes. The photolysis (thermolysis) of alkylcob(III)alamins leads to the formation of the corresponding alkyl radical and cob(II)alamin with homolytic Co(III)–C bond cleavage (Figure 1b). This high

• (II) species and an alkyl radical intermediate A [54]. The prolonged lifetime of the radical intermediate A could be provided by the channel of MOF, enabling conversion to the acetyl-migrated radical B. The radicals A and B may abstract hydrogen radicals to form the reduced product and the acetyl

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

• Xiaoshen Ma and
• Seth B. Herzon

Beilstein J. Org. Chem. 2018, 14, 2259–2265, doi:10.3762/bjoc.14.201

• transfer (HAT) to the alkene substrate, followed by interception of the resulting alkyl radical intermediate with a SOMOphile. In addition, we report the first reductive couplings of unactivated alkenes and aryldiazonium salts by an HAT pathway. The simplicity and generality of the Co(acac)2–TBHP–Et3SiH

• synthesis [6][39][40][41][42][43][44][45][46][47]. Although mechanistically-complex [28] the outcome of these reactions can be rationalized as initiating by HAT to the alkene, to form the kinetically- and thermodynamically-favored alkyl radical intermediate, which may be in equilibrium with the

• ]. Mechanistic studies showed that Et3SiH participates in the formation of a cobalt hydride intermediate that delivers a hydrogen atom to the less-substituted position of the alkene. The resulting alkyl radical is believed to abstract a second hydrogen atom from DHB to generate the reduced product [2]. This

Investigations of alkynylbenziodoxole derivatives for radical alkynylations in photoredox catalysis

• Yue Pan,
• Kunfang Jia,
• Yali Chen and
• Yiyun Chen

Beilstein J. Org. Chem. 2018, 14, 1215–1221, doi:10.3762/bjoc.14.103

• investigate their reactivity toward alkyl radical and acyl radical additions in photoredox catalysis. The mechanistic investigations were carried out to study the derivatization of BI-alkynes in radical acceptor and oxidative quencher reactivity, and the electron-rich benziodoxole derivatives demonstrated

• tested the reactivity of tolylacetylenic benziodoxole derivatives 3a–f for deboronative alkynylation under photoredox catalysis conditions (Scheme 3) [20][34]. Using the tertiary alkyl trifluoroborate 4a as the alkyl radical precursor under literature conditions, the unsubstituted BI-alkyne 3c only

• ’-alkyne 3f gave the optimal 70% and 82% yields of alkynes 5d and 5e, which observed ≈10% yield improvement comparing to the unsubstituted BI-alkyne 3c. We then tested if the propensity of BI-alkyne derivatives toward alkyl radical additions was general and could extend to other alkyl radical precursors

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• . The reaction was found to be suitable for a series of steric and electronic different styrenes. However, aliphatic alkenes did not give the desired product. The author’s explain this observation by a lower stability of the free carbon-centred alkyl radical intermediate, compared to benzylic substrates

• heterocycles. However, aliphatic alkenes could not be applied probably due to the lower radical stability of the carbon-centred alkyl radical intermediate. Nevertheless, the method showed good functional group tolerance to electron-donating and withdrawing groups and also for heterocyclic structures like

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• was then added onto the substrate, furnishing radical intermediate 16, which was trapped by compounds 14 or 15 to form the radical copper species 17. From this intermediate, two plausible pathways were considered. First, the alkyl radical can be trapped by copper phosphate to provide the copper(III

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

• in a sealed tube at 110 °C. Mechanistic studies by electron spin resonance were carried out in which both the CF3• and the β-CF3 alkyl radical intermediate were observed by using 2-methyl-2-nitrosopropane as a radical spin trap. A single-electron oxidative free-radical process was clearly ascertained

• . For the iodination step, the authors proposed that the β-CF3 alkyl radical was intercepted by I2, which was formed by a multistep redox process from I2O5. In continuation of this work, the same research group described the bromotrifluoromethylation of alkenes under similar reaction conditions but

• -products. The mechanism was similar to previous examples to generate the β-CF3 alkyl radical intermediate 44, which was trapped by halogen atom transfer from the halogenating agent. The nitrogen-centered radical 45 oxidised Mes-Acr* by a single-electron-transfer process to restart the catalytic cycle

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• formyl and hydroxy groups. Preliminary mechanistic studies reveal that a secondary trifluoromethylated alkyl radical is involved in the reaction. Keywords: alkenes; cross-coupling; Heck-type reaction; palladium; secondary trifluoromethylated alkyl bromides; Introduction With the increasing number of

• substrate scope and high efficiency. The reaction can also extend to secondary difluoroalkylated alkyl iodide. Preliminary mechanistic studies reveal that a secondary alkyl radical via a SET pathway is involved in the reaction. Results and Discussion We began this study by choosing styrene (1a) and 2-bromo

• with para-methoxystyrene and para-fluorostyrene (4l and 4m). To probe whether a secondary trifluoromethylated alkyl radical is involved in the current reaction, radical inhibition experiments were performed (Table 2). When a reaction of 1a with 2a was carried out in the presence of PdCl2(PPh3)2 (5 mol

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• visible light (Scheme 4) [27]. Although the mechanism continues to be studied, it is hypothesized that irradiation of the copper–carbazole complex leads to an excited-state adduct that is capable of generating achiral tertiary alkyl radical intermediates through electron transfer with a racemic alkyl

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• nitroalkanes using palladium catalysis were known, prior to our work, no general catalytic methods for the alkylation of nitroalkanes existed. We envisioned that the catalytic generation of an alkyl radical under copper catalysis in the presence of a nitronate anion could lead to C-alkylated products. In

• such as TEMPO. Radical clock experiments provided ring-opened products, suggesting the presence of intermediate radicals. We propose that this reaction proceeds via a thermal redox process. We hypothesize that the alkyl radical is formed by transfer of a bromine atom from the alkyl halide to the copper

• catalyst. The resultant stabilized alkyl radical then undergoes coupling with a nitronate anion, forging the C–C bond. Single electron transfer from the resultant radical anion to the Cu(II) halide results in the observed product while simultaneously reducing the metal center to regenerate the catalyst. In

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• intriguing is the double role of the photocatalyst [fac-Ir(ppy)3], consisting of photo-induced generation of alkyl radical II and oxidation of radical IV to cationic intermediate V, the latter process also regenerated the catalyst. Finally, the deprotonation assisted by base resulted in various 6-alkylated

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• oxidation of the potassium salt of 16. Rapid cyclization gives 18, which recombines with the alkyl radical R4• under formation of product 19. A synthetic challenge is represented by the competing recombination of intermediate 17 with R4•, resulting in an open structure which was also isolated in some cases

Novel indolin-2-one-substituted methanofullerenes bearing long n-alkyl chains: synthesis and application in bulk-heterojunction solar cells

• Irina P. Romanova,
• Andrei V. Bogdanov,
• Inessa A. Izdelieva,
• Vasily A. Trukhanov,
• Gulnara R. Shaikhutdinova,
• Dmitry G. Yakhvarov,
• Shamil K. Latypov,
• Vladimir F. Mironov,
• Vladimir A. Dyakov,
• Ilya V. Golovnin,
• Dmitry Yu. Paraschuk and
• Oleg G. Sinyashin

Beilstein J. Org. Chem. 2014, 10, 1121–1128, doi:10.3762/bjoc.10.111

• nine different n-alkyl substituents. Their optical absorption and the first electrochemical reduction potential are close to those of PCBM. The lengthening of the n-alkyl radical at the nitrogen atom results in a gradual increase in the AIM solubility. The photovoltaic properties of PSCs based on the

Aerobic radical multifunctionalization of alkenes using tert-butyl nitrite and water

• Daisuke Hirose and
• Tsuyoshi Taniguchi

Beilstein J. Org. Chem. 2013, 9, 1713–1717, doi:10.3762/bjoc.9.196

• molecular oxygen, an alkoxy radical 26 is formed from the peroxynitrite intermediate (ROONO) generated by the reaction of the peroxy radical (ROO•) intermediate with t-BuONO. The alkoxy radical causes an 1,5-hydrogen shift to give the corresponding alkyl radical 27 followed by formation of another alkoxy

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• ][7][8] proceeding via catalysis in single electron steps (for experimental results see Scheme 1) [9][10]. The C–C bond forming step of the catalytic cycle is an intramolecular alkyl radical addition to substituted anilines. Even though only rarely used, reaction sequences employing such steps in an

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• ][7][8] and no reports on radical addition. We have already investigated diastereoselective alkyl radical additions to α-methylene-γ-phenyl- γ-lactam and reported that the N-unsubstituted lactam yields cis-α,γ-disubstituted lactams using (Me3Si)3SiH under UV irradiation, whereas the reactions of N

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

• Eietsu Hasegawa,
• Minami Tateyama,
• Ryosuke Nagumo,
• Eiji Tayama and
• Hajime Iwamoto

Beilstein J. Org. Chem. 2013, 9, 1397–1406, doi:10.3762/bjoc.9.156

• initially to produce Lewis base–acid complex 7, followed by inner-sphere ET involving elimination of CuOAc and AcOH, which gives cyclopropoxy radical 8. Either external or internal bond cleavage of 8 generates the respective primary alkyl radical 9 or tertiary alkyl radical 10. An equilibrium

• produces spirocyclic primary alkyl radical 11. Hydrogen-atom abstraction by 11 then leads to formation of spirocyclic ketone product 2, while trapping of 11 by CuOAc followed by β-H elimination (either hydride elimination or deprotonation) [39] of the resulting organocopper intermediate 12 generates the

• radicals [39]. As described, 1.1 equiv of Cu(OAc)2 leads to nearly complete reaction of 1b (see entry 1 and entry 2 in Table 1). Thus, CuOAc which is generated after initial ET between Cu(OAc)2 and 1b may capture the primary alkyl radical 11. In addition, although not predominant, oxidation of 10 by Cu(OAc

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• radical A gives an alkyl radical B, which adds to CO to give an acyl radical C. Finally, the 5-exo addition of acyl radical C onto an azide group takes place with the liberation of dinitrogen to give a cyclized amidyl radical D [29][30], which abstracts hydrogen from TTMSS, affording the 4,4-spirocyclic

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• phosphorylation of carboxylic thiohydroxamic mixed anhydrides (Scheme 13) [41]. Radical addition of a phenylsulfanyl radical to the thiocarbonyl generates the corresponding alkyl radical R•, which undergoes homolytic substitution at the phosphorus of P(SPh)3 to furnish (PhS)2P–R as the initial product (Scheme 14

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• efficiently furnish its bicyclo[5.4.0]undecane system, which is shown in bold in Figure 1. Subsequent to this observation, we performed model studies that demonstrated the viability of highly stereoselective 7-exo-trig acyl radical–6-exo-trig alkyl radical cyclizations as a means of preparing bicyclo[5.4.0

Electron and hydrogen self-exchange of free radicals of sterically hindered tertiary aliphatic amines investigated by photo-CIDNP

• Martin Goez,
• Isabell Frisch and
• Ingo Sartorius

Beilstein J. Org. Chem. 2013, 9, 437–446, doi:10.3762/bjoc.9.46

• • denote the sensitizer ketyl radical and the α-amino alkyl radical. The reason why some sensitizers yield polarizations that stem from the radical ion pair, even though the precursor to the products must be the neutral radical D•, is the existence of two deprotonation pathways of DH•+: The proton can be

• magnetic parameters of the α-amino alkyl radical of DABCO are not known precisely: A negative hyperfine coupling constant of about −14 G is to be expected for the single proton attached to its radical center, a noticeably larger positive one of about +19 G for the two protons at the adjacent carbon, and a

• account for the absorptive polarization, the g value of the α-amino alkyl radical must thus be larger than that of the sensitizer ketyl radical, which is corroborated by the polarizations of the regenerated sensitizer. Whereas these are undetectably small in the case of AQ and BP, XA exhibits weak

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• in synthesis. Pivotal to the processes disclosed so far using alkylzinc derivatives is zinc atom radical transfer [4]. In general terms, the reaction involves a radical chain process initiated by the formation of an alkyl radical from the organozinc derivative in the presence of oxygen [5][6][7][8][9

• ][10][11][12][13][14]. The newly formed radical then undergoes one or more radical transformations before being reduced by the alkylzinc reagent through homolytic substitution at zinc, producing a new organozinc derivative along with an alkyl radical that sustains a radical chain. Overall, the in situ

Photoreactions of cyclic sulfite esters: Evidence for diradical intermediates

• Rick C. White,
• Benny E. Arney Jr. and
• Heiko Ihmels

Beilstein J. Org. Chem. 2012, 8, 1208–1212, doi:10.3762/bjoc.8.134

• decarbonylation results in an alkyl radical. The latter reaction yields bibenzyl (4) and toluene (7) in the photoreaction of 8. It should be noted that the diradical BR2 may be formed also upon photoinduced ring-opening reaction of an intermediate oxirane 2a, which is not detectable in the reaction mixture

Convergent syntheses of Le^X analogues

• An Wang,
• Jenifer Hendel and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2010, 6, No. 17, doi:10.3762/bjoc.6.17

• the carbon sulfur bond giving a thioacetate salt and an alkyl radical. The alkyl radical is then converted to the corresponding anion by a second electron transfer and the resulting anion is protonated by ammonia giving trisaccharide 1. In contrast to the thioacetate 31, treatment of the 6

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• studies on similar substrates by TTF [5][8][16][17] and TMTTF [16] had shown competitive trapping of the intermediate alkyl radical 46 by TTF+• or TMTTF+•. Preparation of indoles Following the successful implementation of the methodology on the synthesis of indolines, we next sought to harness the aryl

• )]. We expected that the aryl radical 53a generated by the reduction of arenediazonium salt 49a by TDAE would undergo 5-exo-trig radical cyclization onto the vinyl bromide to afford the alkyl radical intermediate 54a, from which Br• would be eliminated to afford the exocyclic alkene 50a (Scheme 6). Such

Part 2. Mechanistic aspects of the reduction of S-alkyl- thionocarbonates in the presence of triethylborane and air

• Florent Allais,
• Jean Boivin and
• Van Tai Nguyen

Beilstein J. Org. Chem. 2007, 3, No. 46, doi:10.1186/1860-5397-3-46

• , Newcomb,[14] following Wood's and Renaud's reports, carried out kinetic estimations of the rate of hydrogen abstraction by an alkyl radical from the complex between Et3B and water using the routine radical clock method. This author also came to the conclusion that hydrogen abstraction from the α position