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

• arylborylation of α-alkylstyrenes 387 has been investigated, delivering 1,1-adducts 389, 390 in the presence of palladacycle PCy3Pd G3, while 1,2-adducts 391–393 result using APhosPd G3. The former reaction proceeds through a second-stage β-hydride elimination/re-insertion pathway, although for the latter set of

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• double bonds into the corresponding (Z)-monohalogenated derivatives using palladium(II) acetate, triphenylphosphine and tributyltin hydride. Following this procedure, we were able to obtain (Z)-bromide 4 in four steps and an overall yield of 39% [21][22][23][24]. Cross coupling of fragments 3 and 4 The

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• environmentally friendly than other frequently used hydrogen sources like hydrosilanes [17], tributyltin hydride (Bu3SnH) (often used in natural product syntheses) [18][19][20] and hydroboranes [21][22][23], since the only byproduct is water. The production, storage and use of H2 received much attention and

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• 19 instead. This compound was obtained from both aldehyde 15 and its precursor ethyl thioester methyl ester 14, respectively (Scheme 3). Both substrates 14 and 15 were reduced to the corresponding diol 17 with lithium aluminum hydride with 73% or 83% yield, respectively. Next, the selective

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• work of Stryker and co-workers on triphenylphosphine-stabilized copper hydride complexes [1][2], copper hydrides have been widely used for conjugate reductions of α,β-unsaturated carbonyl compounds [3]. Especially a chiral copper catalyst combined with a stoichiometric amount of a silane reagent, which

• generated copper hydride in situ, has successfully been utilized for enantioselective reactions with β,β-disubstituted α,β-unsaturated carbonyl compounds [4][5][6][7][8][9][10][11]. The pioneering work of Buchwald and co-workers on the enantioselective conjugate reduction of α,β-unsaturated esters using a

• plays crucial roles in both the catalytic activity and stereoselectivity [19][20][21]. Notably, these catalyst systems were also applicable for three-component coupling reactions using hydrosilanes as hydride reagents [17]. Based on this knowledge, we decided to investigate the effects of the phenol–NHC

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• oxidized copper complex oxidized the glycine ester, regenerating the catalyst, furnishing the N-centered radical cation. Then, the latter underwent a 1,2-hydride shift in the presence of the base (or the phthalimide anion) to form the α-amino radical that recombined with the alkyl radical formed in the

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• ] were the phosphine boranes were prepared by reacting phosphines with sodium borohydride. Alternatively, the reduction of phosphine oxide byproducts with lithium tetrahydridoaluminate, calcium aluminum hydride, and hydrosilanes can also be used to regenerate the phosphine ligands. Hydrosilane reagents

• -(diphenylphosphine)ethyl)-4,5-diazafluorene ligand 47 which includes a cyclopropylated intermediate (45, Scheme 8). The ligand was prepared by an initial cyclopropanation of diazafluorene 44. For this, 44 was treated with a dibromomethane solution in THF in the presence of sodium hydride under reflux for four hours

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• 22 upon coordination with the carbonyl oxygen atom of the amide group. The complex 22 then coordinated to the acrylate product 23, which rearranged to 24, and the β-hydride elimination of 24 yielded the desired olefinated product 21. C–H olefination of phenolic ethers: Based on Ackermann and co

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• hydride-mediated reaction of arylmethyl isocyanides with xanthate esters in DMF is reported. The products thus obtained were compared with the carbamothioates obtained by the sodium hydride-mediated condensation of the corresponding benzylamines and xanthate esters in DMF. To account for these unexpected

• reactions, a mechanism is proposed in which the key steps are supported by quantum chemical calculations. Keywords: benzylamines; carbamothioates; density functional theory; intrinsic reaction coordinate analysis; isocyanides; sodium hydride; xanthate esters; Introduction Carbamothioates (thiocarbamates

• reported the synthesis of thiazoles from xanthate esters [31]. In continuation of this ongoing work, we planned to synthesize 5-alkoxy-4-arylthiazoles 3 by the sodium hydride/DMF-mediated reaction of arylmethyl isocyanides 2 with S-alkyl xanthate esters 1 or O-aryl/O-alkyl dithiocarbonates. Unexpectedly

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• ones [54][70]. With respect to C–H activation reactions, the presence of surface oxides on our RuNC probably governed its ability to catalyse the C–H alkenylation reaction, in contrast to the role of reduced Ru(0) nanoparticles with hydride/deuteride species on their surface, reported by Pieters et al

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• electrophilic cyclizations to generate intermediate A. Intermediate A undergoes a 1,5-hydride shift, forming intermediate B. A subsequent cyclization forms intermediate C. Intermediate C generates intermediate E via one of two possible pathways: either a direct 1,3-hydride shift or an indirect pathway involving

• two 1,2-hydride shifts. Theoretical investigations by Hong and Tantillo suggested that the indirect transformation from intermediate C to E is energetically favored and might be biosynthetically relevant [38]. This finding is in agreement with the report by Sato and co-workers [39], who performed

• isotope labeling experiments combined with QM calculations. Intermediate G forms via a 1,5-hydride shift from C6 to C10 to generate a homoallylic cation, and the formation of intermediate H occurs due to cyclization to yield a cyclopropyl ring. Intermediate I forms due to isomeric formation of a

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• -arabinopyranoside (1), available in multigram amounts, was benzylated in 79% yield using benzyl bromide and sodium hydride in DMF, followed by hydrolysis of the anomeric aglycon of 2 with 5 M HCl and SrCl2 in acetic acid, which afforded the hemiacetal 3 as a 2:3 α/β anomeric mixture in 60% yield (Scheme 1

Terpenes

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 2966–2967, doi:10.3762/bjoc.15.292

• generate a highly reactive cationic intermediate that can be subject to a cascade reaction through typical carbocation chemistry, including cyclisation reactions, hydride migrations and Wagner–Meerwein rearrangements [1][2]. The cascade is usually terminated by deprotonation or attack of water. The

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• acid, catalyzed by in situ-generated copper hydride with diethoxymethylsilane as a reductive agent gave the γ,δ-unsaturated acid with good to excellent diastereoselectivities [27]. Various asymmetric organocatalyzed rearrangements are known [28]. However, the catalysis of sigmatropic rearrangements is

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• electrostatic interactions [54]. Moreover, TCs also assist intramolecular atom transfer and rearrangements including hydride or proton transfer and carbon shifts [10]. Eventually, the carbocation is quenched by deprotonation (E1-like) or nucleophilic attack (SN1-like) of water [45]. In contrast to

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• . Commercially available reagents and solvents were used as received unless otherwise stated. THF and diethyl ether were distilled over sodium/benzophenone. Acetonitrile and dichloromethane were distilled over calcium hydride immediately before use. Compounds 1a and 2 were synthesized according to literature

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• formation of (S)-63 over (R)-63. Hence, (S)-63 would be converted to ketone 62 via hydride transfer, whereas (R)-63 might be predominantly retained. Very recently, Wirth’s group demonstrated the use of chiral iodoarene 67 as a redox mediator for the electrochemical lactonization of diketo acid derivatives

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• in hydride abstraction with the formation of carbocation 9 and subsequent cyclization to the bicyclic alkoxyamine 10. The resulting isoxazolidine ring is then opened with m-CPBA in the usual way, retaining the configuration of the asymmetric center at 3aC-OH [13] (Scheme 4). The steric strain in

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• pirouette rearrangement of the reduced ring through a spirocyclic intermediate and then re-oxidation to phenanthrene. These reactions involve a complex series of proton and hydride transfers. Results and Discussion Beyond terphenyls, acid-catalyzed rearrangements pose limitations in the synthesis of

• difference between ipso cations and their non-ipso counterpart which might be formed rapidly by secondary 1,2-hydride shifts. In principle, the equilibrium product in these complex reactions might correlate with relative energies of the neutral quaterphenyl isomers. Reliable heats of formation for

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• result of heterolytic cleavage of the pyrophosphate–hydrocarbon bond or protonation of a double bond, (2) propagation of the carbocation along the forming terpene skeleton as a result of ring formations, hydride and/or methyl shifts, de- and reprotonation of intermediates, the creation of a terminal

• lead to different migration of the double bound and different hydroxylation pattern (Table 2 and Scheme 1). An exchange to leucine drastically changes the product to cembrane A (7) and 3,7,18-dolabellatriene 12 (Table 2 and Scheme 1) [36]. The cation migrates via a 1,5 hydride shift, as shown by

• Figure 7). F107 has been targeted by site-directed mutagenesis as well (Table 2 and Scheme 1) [30], leading to compounds R-cembrene A (7) and cyclooctat-1,7-diene (8). Now the cationic intermediate has two possibilities to react to G, either by a 1,3- and 1,5-hydride shift or by two 1,2-hydride shifts

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• methyltransferase, followed by 1,2-hydride shift and deprotonation, and a subsequent reduction of the exo-methylene intermediate gives rise to a methyl group (Scheme 2) [18]. The presence of the exo-methylene intermediate was experimentally proved but the enzyme responsible for the double bond reduction has not

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• closure to form the bisabolyl cation (6). A [1,3]-hydride shift to form carbocation 7 and 1,10-ring closure yield the amorphyl cation (8). Finally, deprotonation generates amorpha-4,11-diene (3) [8][9]. Several sesquiterpene synthases including ADS accept FDP analogues containing a variety of heteroatoms

• bisabolyl cation and the amorphane skeleton. Rather the active site conformations of 11 and cation 22 appear to enable a 1,11-cyclisation to 23. A subsequent [1,3]-hydride shift to cation 24 and deprotonation from C15 lead to 8-methoxy-γ-humulene (20, Scheme 3A). Alternatively, the nucleophilic 8-methoxy

• group could react at C10 to induce a fast 1,11-cyclisation, forming cation 25, which effectively competes with the isomerization of 11 to 8-methoxy-NDP. A subsequent [1,3]-hydride shift leads to 24 (Scheme 3A). Direct deprotonation of 22 at C15 forms the minor reaction product (E)-8-methoxy-β-farnesene

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• [5][32]. In 1999 Schmidt et al. were able to show that the enantiomers of germacrene D are formed via two different H-transfer pathways in Solidago canadensis. (S)-(−)-Germacrene D is generated by a cyclization reaction, that includes a 1,3-hydride shift as opposed to the cyclization reaction of (R

• )-(+)-germacrene D, that includes two consecutive 1,2-hydride shifts [33]. In all terpenes in Scheme 3, TOF–EIMS measurements showed that a deuterium atom is located in the isopropyl group. This can be explained by the assumption that in Vitis vinifera L. all sesquiterpenes are formed via the (S)-germacradienyl

• cyclization takes place only from (S)-(−)-germacrene D, from which the absolute configuration of these substances can be derived. While the detected labeling patterns in our feeding experiments are in full agreement with the 1,3-hydride shift pathway, the cloning and functional characterization of the

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• which alkali metal complexes are known, including those of Li [15], Na [16], K [17][18], and Cs [18]. These have been formed via traditional solvent-based routes, by deprotonation of the substituted propene precursor with a metal alkyl or hydride (Equation 2) or with the metal itself (Equation 3) [18

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• presence of sodium hydride. Helic[6]arene derivative H5 was synthesized by treatment of H1 with methyl bromoacetate followed by reduction with lithium aluminium hydride (Scheme 1). The guests G1–3 were prepared according to previously reported procedures [37][38][39]. Guest G4 was synthesized through