Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• , homogenous iron catalysis they bear the chance to enable coupling reactions that rival that of noble-metal-catalysis. This review provides an overview of iron-catalyzed domino coupling reactions of π-systems. The classifications and reactivity paradigms examined should assist readers and provide guidance for

• species. However, the CDC reaction is not without its challenges, mainly due to the poor reactivity of C–H bonds; thus, chemists have devised protocols to activate different types of C–H bonds for the formation of C–C and C–X bonds. We classified the different CDC cascade reactions into two different

• observed similar trends in reactivity and came to the same mechanistic conclusions. Mechanistically, sequential and nonsequential CDC reactions are nearly identical. Typically, a CDC reaction is initiated through iron-mediated oxidation processes. In the case of a sp3 C–H species, an alkyl radical can be

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• . Therefore, there is great need to develop a more effective and rapid method for preparing diaryl methyl sulfones. p-Toluenesulfonylmethyl isocyanide (TosMIC), a versatile synthon in organic chemistry, has been widely used to synthesize a myriad of valuable chemicals due to its high reactivity shown by the

• important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33][34], and insertion

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• on the reactivity, but little on the enantiocontrol. In general, biaryl-2-amines with electron-donating groups showed higher reactivity than those with electron-withdrawing groups (Scheme 6). CPA 5 activates the reaction by creating a rigid and narrow chiral pocket, thus leading to better noncovalent

• elimination as opposed to styrenyl selectivity. In addition, the methacrylates were used as allyl surrogates to overcome the reactivity problem caused by steric hindrance of 1,1,-disubstituted alkenes, and the electron-withdrawing esters enhance the migratory insertion to form palladacycle I-2. The CPA

• electronic properties of the substituents on the aromatic rings of the indole have limited influence on the reactivity and remarkable effects on the enantioselectivity. For example, in the case of indole 20b, the enantioselectivity was drastically reduced due to steric hindrance present at the 2-position of

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• cytosine or 5-fluorocytosine. Further, hydrolysis of the 5'-O-acetyl group was evaluated with respect to reactivity and enantioselectivity utilizing several enzymes. They found that the butyrate ester derivative was hydrolyzed with a higher rate than the 5'-O-acetate derivative during the synthesis of ʟ

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• through inductive effects, and on amides, which should be more prone to engage in the cyclization owing to the high reactivity of expected N-acyliminium ions 4a (R1 = alkyl, R2 = acyl) in SEAr reactions. In the second screening round, we determined the isolated yields of the promising reactions identified

• also less desirable as reaction intermediates, owing to the difference in their respective reactivity. The results for the route going through N-methyl-2-(aminomethyl)biphenyls 9 are summarized in Scheme 4. We found that substrates bearing electron-donating groups at the aminomethyl carrying arene (9b

• , imidazole, DMF, 50 °C, 18 h; f) LAH, AlCl3, THF, rt, 12 h; g) TBHPaq, DCE, 100 °C, 18 h; h) pyridine, HF·pyridine, EtOAc, rt, 14 h. Proposed mechanism for the oxidative cyclization of amines 2a and 2b to fluorenone (3). Reactivity of different functional groups towards TBHP-mediated cyclization to give

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• –C≡N) are versatile building blocks in organic synthesis for the preparation of a plethora of functionalized compounds and heterocycles. The presence of conjugated acetylene and nitrile bonds in these compounds leads to an enhancement of reactivity of both functional groups. Thus, propynenitriles

• ; ArCH=CHCN) (see our work [17]) and 3-arylpropynenitriles 1 (this work) under electrophilic activation reveals unambiguously that the electrophilic intermediates generated from acetylene nitriles 1 possess higher reactivity. Thus, the hydroarylation of 3-arylpropynenitriles 1 promoted by AlBr3 proceeds

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• [1][2]. Their multifacial reactivity has been explored in asymmetric alkylations [3], hydroalkynylations [4], trifluoromethylcyanations [5], heterocycle synthesis [6], asymmetric acylations [7], hydroborations [8], hydrogenations [9], etc. They are also important pharmacophores, which display a range

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• experiments reveal that the presence of a β-silyl group in the enones is crucial for high reactivity under the optimized reaction conditions. Keywords: β-silyl α,β-unsaturated carbonyl compounds; β-silyl nitroalkanes; chiral organosilanes; organocatalysis; solvent-free synthesis; Introduction

• catalyst VIII led to ent-4 in 25% yield and 95% ee (Scheme 4). This observation confirmed that the presence of the β-silyl group in the enones played a key role in the high reactivity under the optimized reaction conditions. The stereochemistry of the silicon-substituted chiral center in compound ent-3k

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• significant improvement in the yield. In all cases where TMSN3 was used as an azide source, the lactam byproduct was not detected. Of special interest for us was the synthesis of conjugated tetrazoles from enones. Since the oxygen atom in the enone form has a lower affinity towards Lewis acid, the reactivity

• reported Lewis acid-mediated enone reactions with alkyl azides yielding enaminones [48]. Similarly, as with ketone, reactivity of the enone derivative 4 with HN3 in the presence of BF3⋅OEt2 (Table 2, entry 1) was examined. It was shown that a longer time is needed to achieve conversion, and the yield was

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• carbonyl group. This appears to be a rare example of a change in reaction conditions swinging the outcome from one mode of enaminone reactivity to the other. Following this optimized method, we undertook the synthesis of a range of enaminones 15 bearing a variety of aroyl and heteroaroyl substituents as

• the six-membered analogues, which readily lose the exocyclic double bond to give the iminium system 27 upon essentially irreversible protonation. Is this perhaps another example of the lower reactivity and greater relative stability of double bonds exo- to five-membered rings when compared with their

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• , several acids have been prepared in satisfactory yields. An unprecedented chemical behavior of a Petasis reaction product in diluted HCl solution leading to the formation of a phenylglycine derivative has been observed and the mechanism explaining such reactivity has been proposed. Keywords: amino acids

• contrast to the chemical behavior of amino acid 6a in the same conditions (see Scheme 7), no reaction was observed. The cyclization reaction of 12 carried out in 20% HCl led, as expected, to the double-cyclized derivative 14 (Scheme 9). To explain the difference in the reactivity between 6a and 12 we

• compound 16; the next step involves the formation of the iminium ion 17, which is then hydrolyzed to compound 8 and hydroxyacetaldehyde in the last step. Thus, the unexpected reactivity of 6a with diluted HCl may be explained by the electron-withdrawing effect exerted by the adjacent COOH group which

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

• reactivity, with a higher yield and a shorter reaction time. In addition, substrates 1 with aliphatic groups (such as R = n-propyl, n-pentyl, and n-hexyl) were also tolerated under standard conditions, with an excellent yield. The previous literature and control experiments showed that this aminative aza

• ) were used as selenyl and sulfenyl sources, respectively. The method was performed under open atmosphere to provide the target products in good to excellent yield. In comparison, the selenoamination of (E)-2-en-4-ynyl azides 1 showed higher reactivity and could be carried out at 0 °C in 1 h to give the

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• as the optimal catalyst. With the optimized reaction conditions in our hands, we continued investigating the scope of the reaction. First, we focused on the reactivity of anthranilamide (1a) with various aldehydes 2a–j (Scheme 1). Generally, aliphatic aldehydes delivered the cyclic aminals 3a–d in

• derivatives were successfully tested in the aminalization reaction. However, a decrease in reactivity and enantioselectivity was observed when compared to aliphatic aldehydes. The corresponding products 3e–j were isolated in lower yields (58–83%) with enantiomeric purities ranging from 20 to 70% ee. For

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• (Scheme 1). The eliminative cross-coupling of carbenoids can provide a way to unsymmetrical alkenes, provided the differential reactivity of the two carbenoids is suitably matched [2]. In the current letter, we report preliminary results on the latter strategy to form alkenes which possess an allylic

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

• periodic table [32]. Hg(II) salts have already manifested some unique reactivity and therefore attracted increasing interest from chemists [33]. Many examples involving Hg(II) salts with unsaturated bonds in presence of various nucleophiles giving rise to various types of products are abound in the

• the total synthesis of important natural products. Different Hg(II) salts were used stoichiometrically or catalytically depending upon the nature of functional groups and reactants. However, the reactivity of different unsaturated bonds involved in the cyclization primarily depends on the nucleophile

• toxicity concerns, Hg(II) salts are cheap, stable, and versatile in terms of reactivity, making them a viable option to similar transition metal catalysts. Schematic representation of Hg(II)-mediated addition to an unsaturated bond. First report of Hg(II)-mediated synthesis of 2,5-dioxane derivatives from

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• having a methoxy substituent as the leaving group for the formation of phenanthridines. Structure–reactivity relationship studies also indicated that an ortho- or para-methoxy group must be present to stabilize the incipient radical or radical cation intermediate. We propose that the reaction is

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• motif allowed to access the corresponding product 3l in a higher yield. Notably, phosphate 2a with no substitution on the aromatic ring and on the nitrogen atom showed a good reactivity, furnishing the corresponding product 3a in the highest yield, possibly owing to not having steric hindrance. It

• appeared that the position of the residue R1 on the aryl ring exerted a pronounced effect on the reactivity. For instance, 4-bromo-, 4-chloro-, 4,6-difluoro-, 7-fluoro-, and 7-chloro-substituted phosphates afforded the corresponding products 3h, 3i, and 3l–n in a higher yield than the 5-fluoro-, 5-bromo

• phenyl ring of the (2-oxoindolin-3-yl) phosphate had an obvious effect on the reactivity. For example, (2-oxoindolin-3-yl) phosphates bearing a bromo or fluoro substituent in the 6-position all gave the corresponding products in a higher yield than the analogous precursors substituted in the 5-position

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• investigate the transferability of this concept to our system, the light source was changed to blue LEDs. This change seemed to increase reactivity, observed by significantly more vigorous nitrogen release, resulting in shortening of the reaction time to 2 h. The reaction yield on the other hand was slightly

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• good indication for the reaction efficiency between the hydroxy residue of the RAFT-end group and the carboxylic group of the TPP molecule. It was assumed that the particle systems show similar reactivity profiles and resulted in high TPP attachment as depicted in Scheme 1. However, that still slightly

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• other hand, such electron-withdrawing groups, α to the reactive centre, dramatically changes the acidity of the substrate (and thus the reactivity of the enolate conjugate base) and as consequence its reactivity which can drastically impact the enantioselectivity in SN2 alkylation processes. In this

• process. In preliminary studies, we observed that a substituent at the catalyst C-2' position was enhancing the enantioselectivity of the reaction. Initial attention was therefore focused on the influence the other catalyst subunits (i.e., catalysts 7–9, Table 1) exerted over both reactivity and

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

• -transfer step. This provides low amounts of reactive, nucleophilic fluoride in the nonpolar solution, circumventing thereby selectivity and reactivity issues owing to the high basicity of alkali metal fluorides [58][59][60][61][62]. By modifying the reaction conditions, the same group was also able to

• enantioselective polycylization reaction of 51 (Scheme 11) [69]. Modification of the aromatic ring system on the chiral side of the thiourea catalyst proved to be crucial, as both the reactivity and the enantioselectivity were significantly influenced by the stabilization of the cationic substrate and not by

• crucial, while the urea analog of the catalysts proved less efficient and led to diminished reactivity and stereoselectivity. Further mechanistic studies corroborated this hypothesis as more electron-rich allylsilane derivatives were consumed slower despite being inherently more nucleophilic. Another

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• developed due to lower reactivity, poor regioselectivities and the need of noble metal catalysts [50][102][103][104][105][106]. Recently, Yu and co-workers conveniently achieved the direct alkenylation of α-amino C(sp3)–H bonds of amines 1 with alkenyl tosylates 58. The combination of the Ru(bpy)3Cl2·6H2O

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• strategy for the enanantioselective conjugate addition of amino acid derivatives for this reaction remains an unmet goal. Our group previously described a chiral cyclopropenimine catalyst that displayed outstanding reactivity for addition reactions of glycine imines [40][41]. We hypothesized that this

• reactivity might be sufficient to overcome the reactivity limitations of pronucleophiles derived from other α-amino esters [42]. In this paper, we describe the use of cyclopropenimine catalysis for the enantioselective catalytic Michael reaction of α-substituted amino ester imines. Results and Discussion To

• Michael adduct to cycloaddition product (Table 1, entry 2). Interestingly, the larger ring-containing catalyst 6 improved this ratio somewhat to 6:1 while retaining the enantiomeric ratio, albeit at the expense of reactivity (Table 1, entry 3). Incorporation of additional unsaturation (catalyst 7

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• governing the formation of initiating radicals. The slightly lower reactivity of NPG vs DABA can probably be ascribed to a lower production of initiating radicals in this case, rendering the associated PIS slightly less efficient to overcome the oxygen inhibition. This behavior has already been observed in

• other works when other NIR dyes were used in three-component PISs comprising an oxidant agent and an amine [8]. In all cases, NIR dyes proposed showed excellent reactivity using different amines and an iodonium salt. This suggests that an NIR approach is an elegant way for fast curing processes upon

• agreement with the proposed mechanism [4]. More particularly, it is interesting to compare the new proposed dye with IR 813, used as a benchmark structure. Under the same conditions, many dyes show a reactivity similar to IR 813. We noticed that IR 813 shows an excellent reactivity in NIR

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• general model suitable for the prediction of product selectivity and olefin bond chemodifferentiation in cross metathesis. In general, regarding the reactivity of the olefin bond in CM, alkenes can be categorized by the relative ability to undergo homodimerization via CM and the possibility of the