Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• ). However, an iodonium ion 6 was formed as a key intermediate in I2-mediated aza-annulations. Subsequently, the iodonium ion 6 proceeds through a 6-endo-dig cyclization to form the 5-iodopyridine 3. On the other side, the iodonium ion 6 may undergo 5-exo-dig cyclization to yield the 2-acylpyrrole 4

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• -metalation followed by a regioselective mercuri-cyclization reaction (Scheme 60). During the total syntheses of (±)-fastigilin C and (–)-fastigilin C (201), 2 equiv of Hg(TFA)2 were used to synthesize key intermediate tricyclic furan compounds 199, 200, and 203. Hg(TFA)2 helped in the desired ring-formation

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• serve as the nucleophile as displayed in the key intermediate shown in Scheme 10b. As a result, yields up to 70% and excellent enantioselectivities up to 94% ee could be achieved at room temperature. On the other hand, the secondary amine group in Takemoto’s catalyst 44 acts as a base, abstracting the

• proton of the enolizable β-ketoester 49 and thus activating the nucleophilic species. This enolate then adds to the cationic substrate from in situ upon halide abstraction of α-chloro amino acid derivatives 48 by the thiourea moiety of the bifunctional catalyst (Scheme 10c, key intermediate), leading to

• HCl co-catalyzed oxa-Pictet–Spengler reaction employing bisthiourea catalyst 72 bearing two aliphatic groups at one of the nitrogen atoms of one thiourea (Scheme 15) [51]. The key intermediate in this reaction system is the contact ion pair of the thiourea catalyst with the in situ-generated

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• can be formed from I and the Cr(III) salt to start the cycle, thereby providing intermediate VI. The latter then undergoes a ligand exchange with I to give the product and the key intermediate II. It is noteworthy that the secondary amide works both as the substrate and the ligand for the metal center

• compounds in excellent yields and short reaction times (Scheme 21B and C). The robustness of the manganese-catalyzed photo-flow reaction was demonstrated by a gram-scale preparation of the key intermediate in the synthesis of the pharmaceutical compound dantrolene (60) in high yields (Scheme 21D). The azide

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• key intermediate. The treatment of 9 with benzoyl chloride under suitable conditions to selectively protect the 3-NH group of the uracil moiety afforded N3-benzoyluridine (10). The reaction of TIPDS-protected hydroxynucleoside 9 with N3-benzoylthymine under Mitsunobu reaction conditions, followed by

• protection of 16 followed by introduction of an azide group in the C-2′ position of the molecule to afford nucleoside 22. The treatment of azide 22 with pyrrolidine in acetonitrile followed by hydrogenation afforded aminonucleoside 23, which was used as a key intermediate for the synthesis of the double

• anhydro nucleoside 26 and its transformation into the aminonucleoside 27. The key intermediate nucleoside 27 was then treated with 3-ethoxypropenoyl isocyanate or 3-methoxy-2-methylpropenoyl isocyanate in a mixture of benzene and DMF, followed by acidification with sulfuric acid affording the nucleosides

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• enantiomerically pure compound 54 after column chromatographic purification. Selective desulfinylation of 54 was carried out by using 1.0 M HCl in EtOAc, and further removal of the Tr group by the employment of TFA in dichloromethane afforded the 2-oxoindolinyl amino ester derivative 55, the key intermediate for

• key intermediate in the biomimetic synthesis of natural alkaloids. Interestingly, amino allylation of 5-bromopentanal (114) with (R)-tert-butanesulfinamide and allyl bromide (113, R = H) in the presence of indium metal gave homoallylamine derivative 115. In this transformation, imine (RS)-109 is a

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• . Results and Discussion Synthesis of regioisomeric oxazolidinones from (1S)-(−)-α-pinene (6) and (1R)-myrtenol (10) The synthesis of isopinocarveol (7), the key intermediate allylic alcohol, was performed according to a literature procedure in good yield [35]. The first step was the stereoselective

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• dibromide 3, produced by radical bromination of key intermediate 4. The principal challenge entailed in the envisaged synthesis was the construction of the bis(aryloxy)fluoromethane moiety of 4. The simplicity of this structure belies the paucity with which it is encountered in the literature, particularly

• undesired isomer were produced, recovery of unreacted 6 was simple and the quantity of 8 (<5%) was reduced compared to all previous attempts. Chromatographic separation permitted the removal of 8 and the isolation of a pure sample of compound 4. Synthesis of compound 1 Having produced the key intermediate 4

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• –elimination product 6b in good yield. These results provided crucial evidence for the mechanism of the reaction which suggested that β-sulfonyloxyenone could be the key intermediate in the formation of β-triazolylenone 3. Based on the above control experiments, the following mechanism is proposed. Initially

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• ]pyridine and 2-amino-1,6-dimethylimidazo[4,5-b]pyridine) [23], and imidazo[4,5-c]quinoline (imiquimod) [24] based on the electrocyclization of 2-azahexatriene involving an isocyanate moiety as the key intermediate. In addition, we recently reported the total syntheses of marinoquinolines A (3a), B (3b

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• is described elsewhere [18]. Conversion of the cyano compound 7 into the corresponding amidine compound 1, the key intermediate, proved cumbersome. Several experiments and reagents [29] were tried before finding trimethylaluminum (Al(Me)3) and NH4Cl [30] as the reagents of choice for this conversion

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• of further C(7a)-hydroxylated bacterial pyrrolizidines and related molecules. Pyrrolizidine 14 (Scheme 1), the key intermediate in Snider’s improved route to jenamidine A and Bode’s preparation of pyrrolizixenamides A (9) and D (12), is formed by N-cyclization onto the nitrile group in cyano-β

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• (Scheme 23). The aldehyde (Z)-(+)-143a was the common intermediate for the synthesis of (E)- or (Z)-selective vinyl boronates or vinyl halides (+)-145 to accomplish total syntheses of all inthomycins A–C ((+)-1, (+)-2 and (–)-3, see Scheme 25 and Scheme 26). With the key intermediate (Z)-(+)-143a in hand

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• determine whether diethyl fluorophosphonate is a key intermediate in the reaction with aromatic alkynes. Based on a method by Gupta et al. [29], we obtained diethyl fluorophosphonate. Subsequently, the diethyl fluorophosphonate did not react with an aromatic alkyne in the desired phosphonofluorination so

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• ] cycloaddition produces tricycle 36 in the preparation of (±)-hirsutene (14) [24]. (A) An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with allenyl diazo compound 38 as a key intermediate to give angular-fused triquinane 41 [29]. (B) Synthesis of (−)-crinipellin A (15) [30]. (C) Synthesis of

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• desired pyrroles 4c–e in moderate to good yield. Notably, methyl 2-methyl-1-phenyl-1H-pyrrole-3-carboxylate (4c) is a key intermediate in the synthesis of a TRPM8 antagonist [43]. The substrate scope of the aromatic amine component was then examined, and the remarkable efficiency of our pyrrole synthesis

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• % yield (Scheme 1). Alkylation of 5 with 1,2-dibromoethane provided key intermediate azido-bromide 6 in 60% yield. This two-step route to 6 is efficient, but the 16% overall yield was lower than desired. An alternate route began by converting diol 4 to bis(2-hydroxyethoxy)naphthalene 7 in 92% yield by

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• undergoes an addition reaction with a suitable nucleophile (Scheme 1). Importantly, the electrophilic mediated formation of this key intermediate 2 have been the cornerstone for allenamide chemistry over the past 15 years. Therefore, given the importance of the allenamide building block we sought a new

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• formed. The latter was indeed isolated as the main product (68% yield, Scheme 3). A plausible mechanism for the formation of the 2-aroylimidazoles 3/3' is depicted in Scheme 4. A key intermediate may be the in situ generated α-imino ketone 5. The latter is known to undergo dimerization to give 6 followed

• undergo a base-promoted loss of nitrogen to form α-imino ketones upon protonation [38]. A plausible mechanism for the formation of pyrimidine derivative 7a from 2a, in competition with imidazoles 3a/3a', is depicted in Scheme 5. The key intermediate 5a, formed by elimination of nitrogen from the enol

• very good yields (67–98%) when phenacyl azides are soluble in the eutectic mixture and is applicable to a range of substrates. Phenacyl azides, in turn, can also be competitively converted into 2,4-diaroyl-6-arylpyrimidines (45–88% yield) via an unprecedented cyclotrimerization reaction the key

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• photoredox catalysis. This interception leads to a new metallic key intermediate 3 by single-electron transfer (SET). The desired coupling product 4 is then obtained after a reductive elimination (Figure 19). Applying such an approach paved the way towards unprecedented couplings benefiting from a SET

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• ], a bicyclic sesquiterpene that belongs to the cuparene family isolated from Thuja orientalis [76]. More specifically, the authors designed a simple route to enone 67, a key intermediate in several previous total syntheses [77][78]. Its synthesis was achieved in two steps, namely a nickel-catalyzed

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• irradiation, gives the intermediate species 39. The abstraction of a thiyl radical from the intermediate 39 yields the key intermediate dioxetane 40 and regenerates the disulfide. Finally, the reaction between the enol 33 and the dioxetane 40 affords benzaldehyde (41) and the product 42. In 2008, Tsuboi and

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• starting material was converted into bis(hydroxymethyl)quinolizidinone 56. After mesylation and the double displacement with sodium sulfide, spirothietane-quinolizidine 57 was obtained as a key intermediate. It was further applied in the total synthesis of four different natural products of Nuphar

• series of thietanose nucleosides 118 [53]. Similarly, enatiomeric thietanose nucleosides 123 were prepared from L-xylose [53] (Scheme 24). In 2010, Takahata and co-workers designed and synthesized thietane-fused nucleosides. They first prepared a key intermediate spiro acetal 125, which was converted

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• the protected ᴅ,ʟ-N-Boc-2-bromophenylalanine (89) using a Stille coupling reaction to give the o-vinyl derivative 90 as key intermediate. A hydroboration reaction of compound 90 afforded the primary alcohol 91, which was directly fluorinated and deprotected to give the free amino acids 93 (ᴅ and ʟ