Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• could also activate the leaving group. After testing several kinds of phosphoramidite ligands with copper salts, the catalyst system L17/CuTc was selected for further studies. The solvent was found to play a crucial role in this reaction, with MTBE as the solvent of choice. Various organoaluminium

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

• )- and (E)-alkenes 311 afforded the (E)-alkene 312 as the major product. The targeted γ-borylated compounds (relative to the leaving group) were formed, each with high enantioselectivity, which can be used for further stereoselective C–C and C–X (X = heteroatom) bond formation. Catalytic Cu(NHC)-mediated

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• , a convertible isonitrile promoted the cyclization, but restricted the scope of structural diversity. For this reason, it is desirable to replace the amide with a better leaving group, an ester group, which will undergo the Dieckmann reaction more effectively to form a five-membered ring. It is worth

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

• most suitable Rh salt for the conversion. In addition, in spite of low yields, Rh species with valence states of 0, +1, +2 or +3 all promoted the reaction at least to some extent. It is worth noting that as a good leaving group, I− tends to leave in an alkaline environment, and dehalogenation and

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• a yield of 86%, the pyrazolo derivative 10p could only be obtained in a moderate yield of 38%. This might be explained by the tendency of the pyrazolo moiety to act as a leaving group and a following addition–elimination reaction with methanol can take place (the corresponding 2-methoxy-substituted

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• –86%) and yield (44–63%) remained decent. The efficiency of TolBINAP (L3)/CuI was also demonstrated in the ECA of Grignard reagents to the 4-chloro-α,β-unsaturated thioester 22 [31]. Interestingly, the presence of the internal chloro leaving group allowed a powerful tandem conjugate addition–enolate

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

• , Hong and Tantillo [38] and Sato and co-workers [39] investigated the CotB2 mechanism using QM tools. According to Meguro and co-workers [41], the cyclization process commences with the dissociation of the pyrophosphate leaving group of GGPP, forming an allylic carbocation, and two subsequent

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

• ) Terpene biosynthesis. LG: leaving group, black ball: acyl carrier protein. Abundance and distribution of bacterial terpene biosynthetic gene clusters as determined by genome mining (black) compared to experimentally characterized bacterial terpene BGCs (red). Terpenoid biosynthesis. Terpenoid biosynthesis

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• promise for further development of the reaction. The iodo group is an excellent leaving group and therefore, the generation of α-substituted hydration products through the addition of suitable nucleophiles to the reaction mixture is a strong possibility. Having proven the existence of the α-iodo

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• should be noted that the initial 3-aminoesters 1 are known compounds and can be obtained by the Fiesselmann thiophene synthesis from aryl-substituted acrylonitriles bearing a good leaving group at the C-3 position [22][23][24]. Methyl 3-chlorothiophene-2-carboxylates 2a–k were further involved in the

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• broad O–H absorption bands in their IR spectra (≈3400–3500 cm−1) and the presence of hydrogen-bonded water molecules in the crystal structure of E-3e (vide infra) indicate. The formation of betaines 3 includes the elimination of the N-phenyltriflamide anion, which is known as an excellent leaving group

• phosphonium betaines, which can formally be named 1,5-phosphonium-carbabetaines, but because of the extended delocalization of the negative charge are better described as 1-phosphonium-5-oxabetaines. The excellent leaving group character of the N-phenyltriflylamide anion ([N(Ph)SO2CF3]−) is a key factor in

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• hydroxy group more acidic and thus a better leaving group in the reaction. Next, the quaternary 11α-hydroxy group was acylated by freshly prepared 5-azidopentanoic anhydride in the presence of 4-DMAP at room temperature. Finally, the azidopentanoate 4 was successively introduced into a click reaction with

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• ). These cations 11 capture solvent molecules to give exclusively products 12 with net retention of configuration, a characteristic of carbocations that are stabilized by this type of rear lobe interaction. A series of cyclopropylcarbinyl substrates 13 and 14 (Figure 2), where X is a leaving group and R is

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• synthesis of adefovir dipivoxil (2) exploiting phosphonate 33. Impact of the leaving group on in situ conversion of 4 to 6. Impact of base, solvent and temperature on reaction performance and regioselectivity. Supporting Information Supporting Information File 506: Experimental part and NMR spectra.

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• general structure M–O–LG, with a metal and a leaving group connected to an oxygen atom, have been shown to be an excellent electrophilic oxygen source for nucleophilic organometallic species [72]. Since the original discovery of Müller and Töpel of lithiated peroxides [73], several studies have been

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• directly reflected by the observed hydrolysis rate, whereas the changes in polarity of the leaving alcohol do not give marked changes on the rate. The latter is due to the fact that the kinetic effects on the protonation step and the leaving group ability largely cancel each other. In our study, the

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• be the optimum leaving group by thorough investigations on the elimination of sulfide, sulfinyl, and sulfonyl groups at the 2-position of benzothiopyranone. Most 2-aminobenzothiopyranones were obtained in good to excellent yields under refluxing in isopropanol within 36 h. This method is base-free

• -imidazolylbenzothiopyranones [10]. It is well known that the sulfide, sulfinyl and sulfonyl groups are generally used as the leaving group for the synthesis of 2-substituted 4H-chromen-4-ones [11][12][13][14][15][16][17][18][19][20][21][22]. Due to the higher electronegativity of the oxygen atom compared to the sulfur atom

• provided a much higher product yield (Table 2, entries 1, 3 and 5 vs entries 2, 4 and 6, respectively) and sometimes required a shorter reaction time (Table 2, entry 3 vs entry 4) than the corresponding substrate 3a. To further verify the advantage of the sulfinyl group as the optimal leaving group, the

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• riboside. The stereochemical outcomes of the synthesis (anomeric ratio) depends on the nature and the stereochemistry of the leaving group X in sugar B (α- or β-anomer), on the nature of the substituents at the amide nitrogen atom in Nam, and on the conditions of glycosylation, such as solvent and

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• Nucleophilic substitution at silicon is already discussed with SN2 mechanism, following a backside attack opposite of the leaving group, as well as a front side attack near the leaving group [62][63][64][65][66][67][68]. A backside attack at the silicon in dichlorosilane 7 and monochlorosilanol 8 is blocked by

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• (Scheme 1) shows that, in addition to tubugi-1 itself, only the readily accessible building block 4 is required to construct the activated compound tubugi-1-SSPy (3) as a universal precursor for peptide–toxin conjugate syntheses [57]. The pyridyl disulfide is a leaving group which can be substituted by

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• and faster access to these biologically abundant and relevant α-D-GalpNAc-(1-3)-D-GalpNAc motifs. Undesired migration followed by benzylation of the 3-O-Bz GalN3 using several different benzylation procedures (LG: leaving group). Simple synthesis of two acceptors and two donors from the same common

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• amount of the formylated product 3 (Table 2, entry 4). A possible explanation for the increased yield of 3 when using TBAB could be due to slower displacement of leaving group by the “bulkier” source of bromide. In attempting to extend the residence time, the flow rate of the reaction mixture was

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• , we used an aprotic polar solvent like DMF, which weakly solvates the enolates. However, treatment of compound 10 with benzyl bromide and K2CO3 in DMF gave exclusively the C-3 alkylated derivative. Thus, we considered that a hard leaving group such as a sulfonate should play a key role in favouring O

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• versatile leaving group for further transformations. The involvement of the iodine in the radical reactions of styrenes is complicated by the fact that unsaturated compounds readily undergo electrophilic iodination with the addition of an external nucleophile [61][62]. The oxidants used for the preparation

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• different substitution pattern at positions 3, 4 and 5. PG: protective group, X: leaving group. Activation of 7 to oxocarbenium ion 9 in the Ritter reaction. Zemplén deacetylation of 10i. Benzylation of 10j to give 10b. Plausible mechanism of the Ritter reaction. For better clarity C-2 is not shown in