CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• indenes 39a–c from the α-(trifluoromethyl)allyl-substituted benzyl alcohols 38a–c in strong acids has been reported (Scheme 9) [59]. The significant rate retardation observed upon the addition of further CF3 groups, illustrated by the need for harsh reaction conditions, strongly supports the formation of

• delocalized α-(trifluoromethyl)carbenium ions 40a–c. Vasilyev et al. also investigated this Nazarov electrocyclization for the synthesis of indene derivatives. Thus, a variety of indenes 42 could be readily obtained from α-(trifluoromethyl)allyl-substituted benzyl alcohols 41a or the corresponding silyl

• allylic carbenium ions could exist in solution. The solvolysis of CF3-substituted allyl sulfonates was thus thoroughly examined by Gassmann and Harrington [76]. The solvolysis of doubly CF3-deactivated 90 in trifluoroethanol (TFE) required the presence of 2,6-lutidine, leading to ketone 91 and triflate 92

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

• major advantages of 17 over 12 are that the bromo derivative 17 is stable at room temperature and requires a lower temperature than 12 to decompose to difluorocarbene. By the use of BrCF2COONa in diglyme at 150 °C, various alkyl- and aryl-substituted alkenes, allyl alcohol esters, α,β-unsaturated esters

• good yields and with high (Z)-selectivity. The proposed mechanism involved the oxidative addition of the distal C–C bond to palladium, followed by a nucleophilic attack at the less hindered carbon atom of a 2-fluorinated palladium–π-allyl complex. Other examples of Pd-catalyzed ring-oрening reactions

• -valent transition metals such as Pd(0) also have a valuable catalytic role, particularly because of their ability to participate in oxidative addition reactions and to form π-allyl complexes. In the absence of nucleophiles, homolysis of the distal C–C bond takes place under the effect of high temperature

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• , Table 2, entries 11–18). This protocol enabled the synthesis of various α-benzylthio esters 3k–r bearing alkyl, allyl, and benzyl groups directly bonded to the oxygen atom of the ester group. It can be noted that these products were obtained in moderate to good yields. When methyl, octyl, and cyclohexyl

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• ] cycloaddition reaction of an aldehyde and a ketene followed by their isomerization-free Stille coupling with (E)-5-(3-(tributylstannyl)allyl)oxazole (Schemes 8–10) [22]. In this synthesis, the enantiopure β-lactone (+)-79a was synthezised from (Z)-aldehyde 78 and propionyl chloride according to Nelson’s method

• vinylogous Mukaiyama aldol reaction to produce the desired aldehyde (rac)-118 in 81% yield. Meanwhile, the TIPS protection of oxazole 119 and then subsequent lithiation at the C-5 position and quenching in situ with allyl bromide furnished oxazole derivative 121 in 90% yield (Scheme 16). An attempted cross

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

• in a 9:1 ratio. After chromatographic separation, alcohol (−)-77a, isolated in 67% yield and >99% de was subjected to a Claisen rearrangement, leading to aldehyde (−)-78 in 79% yield (96% de determined by 1H NMR). (−)-78 was treated with vinylmagnesium bromide to give a mixture of allyl alcohols

• acids as catalysts for C-allylation of unprotected oximes with allyl boronates [58]. After screening to find the best reaction conditions, oxime 103 was converted to α-tertiary acetal-protected hydroxylamine (±)-104 in the presence of 3,5-difluorophenylboronic acid and diisopropyl allyl boronate (108

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• the initiator would avoid the need to manipulate an oxygen-sensitive and pyrophoric reagent. Results and Discussion Table 1 and Table 2 show the selected optimization results for the use of amine–borane complexes in the SF5Cl radical addition on alkenes. We chose allyl benzyl ether (1) as the model

• allyl benzyl ether (1) (Table 2). In this case, increasing the reaction temperature generally led to higher yields. When the reaction was performed in hexane, the yields went from 1–2% to 72% when heating the reaction at 50 °C, compared to 30 °C and 40 °C, while a low yield of 32% was obtained with the

• MTBE and at 50 °C and 60 °C (Table 5). Unfortunately, the reaction yields did not increase, and these reaction conditions proved to be less efficient for the SF5Cl addition on allyl benzyl ether than the ones previously discussed. The only case where the yield was promoted by a decreased amount of the

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• and the 2-substitued analogue VII and found a significant difference between the two (Figure 4). Indeed, the total allyl charge on the 3-substituted intermediate III results to be almost neutral or even slightly negative (−0.056 e), confirming that the lone pair of the nitrogen atom can stabilize the

• positive charge of the allyl system by conjugation, affecting the following cyclization reaction. Meanwhile, the 2-substitued analogue VII does not present a conjugated system, and the total allyl charge cannot be stabilized, maintaining a positive value (+0.115). As a result, VII seems to be much more

• VIII compared to the analogue IV (−16.7 vs −0.9 kcal⋅mol−1). The π-donating ability of the nitrogen atom might have a clear stabilizing effect in VIII, while the nitrogen and the cationic allyl system are disconnected in IV. This effect is reflected in the corresponding transition states, with TS3

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

• transformation of 149 to phyllocladanol (21) was accomplished in four steps. In 2016, Winne and co-workers reported that (5,6-dihydro-1,4-dithiin-2-yl)methanol (151) can be served as a allyl-cation equivalent for the [3 + 2] cycloaddition and was applied in the synthesis of (±)-cuparene (13) [69] (Scheme 12B

• on 160 to the enone and produces 161. The newly formed 161 was subjected to 5-exo radical addition to the allyl sulfane and subsequent loss of a thiyl radical produces 162. A successive hydrolysis/decarboxylation upon heating and cleavage of acetal on 162 afforded aldehyde 163 in 90% yield. Coupling

• mechanism. (C) The completion of total synthesis of kopsanone (19). (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] cross-cycloaddition of cyclopropane 1,1-diesters with alkenes [68]. (B) (5,6-Dihydro-1,4-dithiin-2-yl)methanol 151 used as a versatile allyl

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• groups on the lower rim. Indeed, one week of stirring 3 with allyl bromide in the presence of Cs2CO3 provided the expected 1,3-alternate conformer 4a in 40% yield accompanied by a small amount of the partial cone conformer 4b (10%). The unequivocal proof of the structure of the isomer 4a was provided by

• synthetic intermediate as the presence of the allyl groups immobilizes the required conformation and at the same time enables the potential incorporation of the macrocycle into a polymeric matrix. Consequently, the subsequent reduction step was carried out in two alternative ways: (i) exclusive reduction of

• the nitro groups or (ii) concomitant reduction of the nitro groups and the allyl moieties. Thus, the reaction of 4a with SnCl2∙2H2O in ethanol gave the corresponding amine 5 in 57% yield after column chromatography on alumina. On the other hand, the four-day stirring of 4a with Pd/C under a H2

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• group C23 results in j1+ (Scheme 1E). The fragmentation of the C25–3–4 portion can be explained starting from 1•+ by a hydrogen rearrangement to k1•+ and α-cleavage to l1•+ (Scheme 1F). Another hydrogen rearrangement combined with an α-fragmentation then leads to the allyl cation m1•+ which may undergo

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• explained by the different stabilization of the respective ions (Figure 3). The abundance of m/z 68 is higher in isoprenyl esters due to the more stable allyl radical cation (Figure 3A). In contrast, prenyl ester fragmentation produces a stabilized allyl cation m/z 69 (Figure 3B), while isoprenyl esters

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• yields. On the other hand, methylene-lactone-fused spirolactams could be delivered from the allyl adducts in high yields through a sequential N-Boc protection/desulfinative lactonization. Keywords: bifurcated synthesis; electrophilic amide allylation; α-methylene-γ-butyrolactam; α-methylene-γ

• key reaction (Scheme 1b) [10][11]. More recently, an amide-functionalized allyl boronate was developed as an alternative reagent for the allylstannane [12][13][14][15][16], which led to the syntheses of not only cytotoxic methylene-lactones spiro-fused to a lactam ring (B) but also their analogous

• show excellent nucleophilicity arising from the oxindole–hydroxyindole tautomerization [18][19], this synthetic approach is undoubtedly attractive because it could complement our previous one using nucleophilic amido-functionalized allyl boronates in terms of the structural diversity as well as

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• diynols 4 with allyl bromide, NaH, and a catalytic amount of tetraethylammonium iodide. The analogous synthesis of selected methallylated oxaenediynes 9 required longer reaction times and a higher excess of methallyl chloride (3 equiv). Unreacted diynols 4 could be recovered by column chromatography

• the catalyst loading to 10% gave the product in quantitative yield (Table 1). Due to economy and unified conditions, we hence decided to perform all reactions at 5% loading of the precatalyst. We started our study with substrates 2, bearing an unsubstituted allyl chain (Scheme 12). The results of the

• the substitution of the triple bonds in the starting oxaenediynes, the modifications of the allyl group resulted in critical loss of reactivity. Thus, the oxaenediynes 9 bearing a methallyl group did not undergo RCEYM under G-I catalysis at all, regardless of the atmosphere (ethene or argon) chosen

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• allyl-anionic-type 1,3-dipoles [13][14]. Moreover, most researches focused on stable azomethine imines [3][4]. The most accessible and widely studied precursors for unstable azomethine imines are diaziridines, i.e., three-membered rings containing two nitrogen atoms [15]. Thus, the unstable N,N'-cyclic

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• products and subsequent cyclization into fused-ring cyclopropanes. Two new fluoroselenation protocols using PhSeBr/Deoxo-Fluor® and PhSeBr/Et3N⋅3HF, respectively, have been described, but the substrate scope of this reaction was more limited. The transformation of the obtained fluoroselenides into allyl

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• the trideuteriosumanene 33 in a stereoselective manner from the same trianion 31 just by trapping it with CD3OD/CH3OD (Scheme 5). In the same paper, they have also reported the hexaallylated sumanene 34 as well as hexa-p-methoxybenzylsumanene 35 by reacting sumanene (2) with allyl bromide and 4

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• metathesis using Grubbs’ 2nd generation catalyst (G-II, Scheme 3) [13]. Replacing the N-Boc protecting group with an N-tosyl group and allylic oxidation gave 30. The introduction of the allyl group at C-11 made use of the Kishi protocol [22] of the allyl-Grignard addition, followed by an ionic reduction. The

• amination of the tetrahydropyranone 50 to generate the (all-cis)-tetrahydropyran fragment. This group reported multiple different routes to 50. In an abortive route, the addition of allyl-Grignard to 5-methylfurfural, followed by the resolution of the racemic homoallylic alcohol with Amano lipase gave

• [38][39] (Scheme 16). After a protecting group manipulation, the C-1 allyl group was truncated via ozonolysis, and the C-3 hydroxy group was transformed into an exocyclic methylene group to give 99. The conversion of the C-6 alcohol moiety to a vinyl group by oxidation and Wittig methenylation to give

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

• subsequently formed radical (Scheme 3) [41]. The thought process behind this approach is based on three observations; (i) Akita and co-workers disclosure on the photoredox-catalyzed oxytrifluoromethylation of allenes 6 to give 2-trifluoromethylated allyl acetates 7 [42][43][44]; (ii) that intramolecular

• explored oxygen nucleophiles in their photoredox-catalyzed addition to enamides [48]. Consequently, the use of excess methanol provided the addition product 38, resulting from α-addition, in a modest isolated yield. The stability of product 38 was marginal, but an improved stability of the N,O’-allyl

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• structural motifs found in numerous natural products and pharmaceuticals with extraordinary biological and pharmaceutical activities [34][35]. However, no desired product (3ka) was obtained when there was a nitro group in the substrate (1k). Then, N-allyl-N-(2-formylphenyl)-4-methylbenzenesulfonamide (1l

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• reaction in more detail. In our previous studies, we investigated the reactions of CSI with various substrates such as carboxylic acids, alkenes and allyl or benzyl alcohols [43][44][45][46]. As a continuation of these studies, we performed one-pot syntheses of the title compounds by optimizing the

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

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• via a two-step process of triflation and azide substitution to produce the desired trisaccharide 24 [29]. Removal of the allyl group using iridium-catalyzed isomerization and subsequent treatment with iodine in the presence of water yielded trisaccharide acceptor 25 for the late stage [2 + 3

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

• -propargyl-N-[2-(trifluoromethyl)allyl]amides 24 were treated with dicobalt octacarbonyl to afford the cobalt alkyne complex, which was then heated in CH3CN. Under these conditions, trifluoromethylated cyclopentenone 25a was obtained in high yield (81%) and diastereoselectivity (anti/syn = 94:6) (Scheme 11

• ). The cyclization of internal alkyne substrate 24b yielded pyrrolidine ring-fused cyclopentenone 25b in similar yield but lower diastereoselectivity. Finally, N-propargyl-N-[2-(trifluoromethyl)allyl] ether 24d, containing an ether linkage instead of the aforementioned sulfonamide linkage, gave furan

• allyl ether 32a afforded the corresponding cis bicyclic product 33a in moderate yield and high diastereoselectivity (dr > 20:1). Other fluorinated allyl propargyl ethers 32b–d afforded the corresponding bicyclic PK-adducts 33 in moderate chemical yields but with high cis-selectivity. On the other hand

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• -lactams [6], quinolin-5-ones [7], spirobisglutarimides [8], indolizines [9], and spiro carbocyclic frameworks [10]. However, most of the reported synthetic transformations utilize either allylic hydroxy-protected or allyl halide-substituted MBH adducts [11][12][13][14][15][16][17][18][19][20][21][22][23

• transformations for complex molecules [29][30][31]. Two individual research groups have reported the multistep pathway to access the cinnamyl-1H-1,2,3-triazole derivatives IX from acetates of MBH adducts (Scheme 2) [32][33]. The other preferable moiety for triazole transformations is the allyl halide of MBH