Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• authors prepared a wide scope of axially chiral products 186 in high yields with excellent enantiomeric purity. The reaction allows lowering of the catalyst loading to 2 mol %. Deprotection of the amino group enabled subsequent transformations, such as a reaction with isocyanate from which a new potential

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• carbanion to the isocyanate group forming intermediate B which undergoes protonation yielding the product. The authors attempted to perform different reductions of the products without any success. However, they performed a gram scale version of the transformation obtaining the product in comparable yields

• 35 bearing two adjacent stereocenters could be obtained in moderate to high yields (47–97%), moderate diastereoselectivities (1:1–3.1:1 dr) and excellent enantioselectivities (94–99% ee). It is worth noting that the steric effect of the isocyanate substituents had an important effect on the reaction

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• produce simple structured rotaxane species (Scheme 3) [46][47][48]. In this method, dodecanediamine and α-CD are mixed in water to form a pseudo[3]rotaxane (1), and the subsequent one-pot end-capping reaction driven by the amino group on the axle ends and substituted phenyl isocyanate produced [3]rotaxane

• structure analysis, and is purified by simple precipitation without requiring chromatography; (3) various end-capping agents are available, and well-optimized conditions can ensure a high yield (e.g., 2-methoxyphenyl isocyanate obtains an 85% yield after 3 h of reaction [49]). Owing to such a high-yield

• the coverage-ratio regulation achieved by controlling the feed ratio of β-CD-based pseudo[2]rotaxane and the spacer comonomer through copolymerization (Scheme 4C) [66]. Similarly, we reported the synthesis of poly[3]rotaxane via the polyaddition reaction of pseudo[3]rotaxane diamine and di-isocyanate

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• ]. The set of tert-butoxy A and tert-butylperoxy B radicals are formed from TBHP during the Cu(I)/Cu(II) redox cycle. The Cu(II)/TBHP system also provides oxidation of benzyl alcohol 80 to the corresponding aldehyde C. The reaction of isocyanate 81 with aldehyde C generates oxazoline D, HAT from D by the

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• Scheme 2 but is open to debate. Thus, formamide adds to the [D1]-aldehyde A to form hemiaminal B which eliminates D2O to give imine D. Deprotonation of formamide D forms the resonance and zwitterrion-stabilized isocyanate E [22]. We then hypothesize that zwitterion E rearranges with loss of CO2 to form

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• trifluoroacetonitrile imine, are highly versatile in that they react with olefins, acetylenes, dimethyl fumarate, dimethyl maleate, β-diketones, β-keto esters, bicyclic olefins, and potassium isothiocyanate and isocyanate affording the corresponding trifluoromethyl-containing compounds, generally with good yields [51

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• -dehydrative reaction of aldehydes with isocyanate analogs ([3] and references therein) (Scheme 1b) and an oxidative reaction of primary benzylic alcohols with sulfonamides or chloramine-T ([3] and references therein), and although they are elegant, they use substrates that are not readily accessible or toxic

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• final product, and previously reported Rh-catalyzed ARO reactions, the authors hypothesized the reaction begins with the oxidative addition of the Rh(I) catalyst into the bridgehead C–O bond of the oxabenzonorbornadiene producing 148 which is considered the enantiodetermining step. The isocyanate anion

• then nucleophillically attacks the alkene in an SN2’ fashion producing the trans-isocyanate 149. Subsequently, insertion of the Rh–O bond into the isocyanate results in 150. Finally, protonolysis produces the oxazolidinone product 147e as well as regenerates the active Rh(I) catalyst. In 2013, the

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• kind of reaction engaging the azido group in the CD chemistry is the phosphine imide reaction [30][31]. This transformation involves triphenylphosphine and carbon dioxide to convert azide into isocyanate [31], allowing coupling with amines or other nucleophile groups. It is interesting to note that the

• same conditions lead to a different product in CD chemistry [30]. In the absence of strong nucleophiles such as amines, the CD gives a dimer with a urea bridge instead of providing the isocyanate. The compound 5 was synthesized from 3 according to the standard procedure [30]. The synthesis of dimers

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling, and 2) immobilization on a solid support via reduction and reaction of the aniline with an electrophile such as polystyrene isocyanate. DOPO scaffold We previously reported the syntheses of both enantiomers of 8-phenyl DOPO 3 [38]. The syntheses proceed in only three steps (including the

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• for carboxylic acids, the carbon source is the carboxyl group. When carboxylic acids were used, the carboxyl moiety was first converted to an isocyanate via Curtius rearrangement [82][83][84][85], then reacted with imidazole to form the carbonylimidazole, and eventually reduced to the methyl moiety

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -workers [46]. They reacted the amine axle 11 with the axially chiral macrocycle (rac)-12 in a mixture of dichloromethane and trifluoroacetic acid in order to generate the pseudorotaxane (rac)-13. Then, an isocyanate stopper was added for the formation of the [2]rotaxane (rac)-14 in a yield of 42%. The X

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• the cavitand, which enhanced the selectivity of the monoester product 45. Similarly, the monohydrolysis of α,ω-diisocyanate 46 was achieved using the water-soluble cavitand D (Figure 13b) [77]. The residual isocyanate group was buried deep in the cavity of D and protected from further hydrolysis. The

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• . Compound 4a was then allowed to react with triphenylphosphine in CH2Cl2 at room temperature for 2 h to produce the iminophosphorane 5a by Staudinger reaction. Aza-Wittig reaction of 5a with phenyl isocyanate generated carbodiimide 6a, which was then treated with diethylamine to form the guanidine

• ). In cases when aliphatic isocyanates (compounds 8o–q, R3 = n-Bu, cyclohexyl and PhCH2) were used, 65–74% yields of the products were obtained. Even as the steric tert-butyl isocyanate was applied, the 3,4-dihydroquinazoline 8r was obtained in 42% yield, but when diphenylamine was used, no product was

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• . Results and Discussion Initially, we focused on the synthesis of β-lactam 2, which was prepared by the cycloaddition of chlorosulfonyl isocyanate (CSI) to cis,cis-1,3-cyclooctadiene, as described in the literature [26]. β-Lactam 2 was transformed into cis-amino ester 3 by cleavage of the lactam ring with

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• procedure. However, this method gave product 3a in only 44% yield. Therefore, we decided to prepare isothiocyanate 3a using thiophosgene in dry THF with Et3N. This procedure afforded the corresponding isothiocyanate 3a in 86% yield (Scheme 1). Isocyanate 3b was also synthesized from amine 2. The reaction

• nitroalkene 9 using catalyst (S,R)-C2. Synthesis of isothiocyanate 3a and isocyanate 3b. Synthesis of sulfinylthioureas C1 and ureas C2. Synthesis of adducts 8a,d,f in solution. Michael additions of aldehydes 6b–d with nitroalkene 9. Michael addition of 3-phenylpropanal (6c) to nitroalkene 11. Optimization of

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

• 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

• and treatment with pyrrolidine in acetonitrile to afford the C-3’-aminonucleoside 58. The reaction of this key intermediate with 3-ethoxypropenoyl isocyanate or 3-methoxy-2-methylpropenoyl isocyanate in a solvent mixture of benzene and DMF, followed by acidification with sulfuric acid produced the

• , followed by reduction of the corresponding nucleoside with tin chloride produced nucleoside 62 which was treated as a key intermediate for the production of the double-headed nucleosides 63 and 64. Reaction of nucleoside 62 with 3-ethoxypropenoyl isocyanate or 3-methoxy-2-methylpropenoyl isocyanate in 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

• epoxidation of (−)-α-pinene (6), carried out with meta-chloroperoxybenzoic acid (MCPBA), followed by a base-catalyzed allylic rearrangement mediated by aluminium isopropoxide (Al(OiPr)3). The resulting allylic alcohol 7 was reacted with trichloroacetyl isocyanate, followed by alkaline treatment, delivering

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

• ), and E (3e) comprising the pyrrolo[2,3-c]quinoline skeleton [25]. As demonstrated in Scheme 1, Curtius rearrangement of carboxylic acid 4 resulted in the formation of isocyanate 5, which, upon electrocyclization furnished pyrrolo[2,3-c]quinoline 6. Intermediate 6 was subsequently transformed into

• , affording aniline 15 in 65% yield. Treatment of 15 with phenyl isocyanate in CH2Cl2 gave urea 16a in 54% yield. To obtain carbodiimide 17a, 16a was treated with carbon tetrabromide (CBr4), PPh3, and Et3N in CH2Cl2. The reaction was monitored by TLC, which confirmed the complete consumption of the starting

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• with inversed configuration of the double bond. Several synthetic strategies starting from isocyanate [22][23] or oxindole [4][12] precursors work well only with protected nitrogen(s) in the starting compounds whose preparation and protection/deprotection also lengthens the total synthesis and

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• ) as the azide donor to facilitate the generation and immediate use of the intermediate acyl azide that would rearrange to an isocyanate upon heating. Toluene was chosen as a suitable solvent providing good solubility of the acid substrates (1 M) in the presence of triethylamine (1.0 equiv

• indicated that a slight excess of 1.8 equiv was needed to ensure the full and rapid conversion of the isocyanate intermediate into the desired Cbz-carbamate product 3. A Vapourtec E-series flow platform was used to operate this continuous process as depicted in Scheme 1. In order to rapidly create a small

• products (10–20%) was observed in several cases indicating the competitive attack of the isocyanate by adventitious water followed by the reaction of the resulting amine with a second isocyanate molecule. Consistent with the expectations, substituted phenylacetic acids such as ibuprofen showed an increased

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• the intermediate isocyanate, Scheme 29) [74]. Such transformations proceed with the conservation of the difluorocyclopropane unit and complement the methods for the cyclopropyl-ring synthesis discussed in the previous sections. Generation of fluorinated methylenecyclopropanes: Fluorinated

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• , oxazole 45 was prepared in good yield (86%) by treating ethyl glyoxylate with tosyl methyl isocyanate (TosMIC) in the presence of K2CO3 at 80 °C [44]. The reduction of the ethyl ester of 45 followed by NBS treatment gave unstable bromide 46 [45], which was immediately coupled to (E)-1,2-bis(tri-n

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• accomplished, followed by the reductive workup of the resulting selenoxide and an increase in its temperature, eliminating selenoxide to generate carboxylic acid (−)-83 in 90% yield. This acid was subjected to Curtius rearrangement [55] in the presence of DPPA as a source of azide, providing isocyanate (−)-84

• in 65% yield and complete stereochemistry retention. When isocyanate (−)-84 was treated with copper chloride in water and THF, the (+)-euphococcinine (2) was obtained in 63% yield. A similar sequence was used to synthesize natural (−)-adaline (1, Scheme 10). In this case, vinyl iodide 86 was obtained