Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• -unsaturated acetals 164 in the presence of electron-rich olefins using Ce(NO3)3 and SDS in water [74]. The mechanism of the reaction is shown in Scheme 39, which plausibly proceeded through trapping of oxocarbenium ion 166 in a chair-like transition state. The stability of the acetal under these reaction

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

• , fluoromethylene acetals. In the course of preparing synthetic samples of trace impurities in the herbicide pyroxasulfone, we were confronted with the problem of generating a bis(aryloxy)fluoromethane. Our intended route to structure 1 (Scheme 1) required the oxidation of bis-thioether 2, derived in turn from

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

• nitriles, amides, amide acetals, and imidoesters [1][2][3][5][11][14] or from their independently prepared 3-chloromethylidene- [4][9][15][16][17], 3-hydroxymethylidene- or 3-(alkoxymethylidene)oxindoles [2][5][6][18][19][20] and the appropriate amines. Recently, original methods involving the construction

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• )indole (10c) with 3 afforded the corresponding acetals 11a–c with 3-phenylbenzoheterole structures in 92%, 80%, and 93% yields, respectively. Acetals 11a–c successfully underwent TfOH-catalyzed cycloaromatization in HFIP to afford oxa-, thia-, and aza[4]helicenes 9a–c in 96%, 88%, and 93% yields

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

• -difluorocyclopropyl acetals 110 to form 2-aryl-3-fluorofurans 112 (Scheme 50) [99]. The reaction could proceed either via the intermediacy of the gem-difluorocyclopropyl ketone 111 (path a) or by the direct rearrangement of the protonated acetal (path b). Recently, the group of Amii has reported the conversion of 1

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• ], trifluoroacetaldehyde hemiaminals [16][17][18], N,O-acetals [19] and N,N-acetals [20], 2-(trifluoromethyl)-1,3-oxazolidines [21], and N-(tert-butylsulfinyl)trifluoroacetaldimine [11][22]. Other synthetic approaches to α-CF3-substituted amines include nucleophilic trifluoromethylation strategies [17], such as the

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• [4]. They are also essential for orthogonal protection of glucosamine, allowing the specific deprotection in subsequent steps (for example, the arylidene acetals at O4 and O6 could be regioselectively opened and transformed into Nap ethers) [19]. The C-3 hydroxy group in compound 14 was then acylated

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

• -acetals [39], which branded them as promising motifs. The above reports and the Lewis acid character of quaternary phosphonium salts (QPS) [40][41][42][43][44][45][46][47][48] qualifies them as reliable catalysts for the proposed methodology. The most elaborate process in the proposed methodology is the

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• ester [9], which is cleaved in the second step, upon solvolysis, forming the final product (Scheme 1). Bromotrimethylsilane (BTMS) is the main reagent in this reaction and is also known for its ability to cleave lactones, epoxides, acetals, and ethers [10]. BTMS also acted as a brominating agent and

Recent synthesis of thietanes

• Jiaxi Xu

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

• ) with alkenes worked as well [73]. In 1987, Ooms and Hartmann showed the photochemical [2 + 2] cycloaddition of diaryl thione 184b with ketene acetals 247 [74] (Scheme 48). In the same year, Nishio studied the photocycloadditions of nitrogen-containing cyclic thiones 249 and 250 with 2

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• ), ethers (2e), halogens (2i and 2l) [48][49][50], the medicinally important CF3 group (2m), and acetals (2p) were tolerated under these mild reaction conditions. The substitution pattern of the aryl groups, such as ortho (2c, 2e, and 2k), meta (2m and 2p), and para substitution (2b–2d, 2g, 2i, 2l, 2o, and

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

• carbonates to deliver the targeted products (Scheme 51) [94]. In addition to allylic carbonates, allylic acetals (319) were also used for C–B bond formation that, in the presence of CuCl/(R,R)-BenzP* and stoichiometric amounts of KO-t-Bu, provide access to α-chiral linear or carbocyclic (γ-alkoxyallylic

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• ) hydrogenolysis of benzyl ethers and benzylidene acetals over Pearlman’s catalyst [36] to furnish the desired pentasaccharide 1 in 49% overall yield (Scheme 4). The structure of compound 1 was unambiguously characterized by its NMR spectral analysis [signals at δ 5.37 (d, J = 2.0 Hz, H-1A), 5.29 (d, J = 3.5 Hz, H

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• and mixed acetals [21][22]. Either by benzoylation or benzylation of 9α or 9β and subsequent deisopropylidenation, glycosyl acceptors 1α/β and 2α/β were efficiently obtained (Scheme 1). Compounds 1α and 1β were previously prepared, but in lower yield [23][24], and compound 2α was obtained as a

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• Bratislava, Mlynská dolina, Ilkovičova 6, 84215 Bratislava, Slovakia 10.3762/bjoc.15.290 Abstract A range of chiral hydrogen-bond-donating organocatalysts was tested in the Ireland–Claisen rearrangement of silyl ketene acetals. None of these organocatalysts was able to impart any enantioselectivity on the

• hydrogen-donating organocatalysts and kinetic experiments suggest that the catalysts bind stronger to the starting silyl ketene acetals than to transition structures thus leading to inefficient rearrangement reactions. Keywords: DFT calculations; green solvents; H-bonding catalysts; Ireland–Claisen

• rearrangement; silyl ketene acetals; Introduction The Ireland–Claisen rearrangement is a reaction converting allyl esters to γ,δ-unsaturated carboxylic acids. Its key step is a [3,3]-sigmatropic rearrangement of a silyl ketene acetal, which is generated in situ by deprotonation of an allyl ester using a strong

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

• ; Introduction Acetals form one of the most common types of protecting groups for hydroxy functions. They are easily introduced by a rapid acid-catalyzed reaction and they are also readily cleaved under mild acidic hydrolytic conditions. These properties make the acetal structures usable even in other

• applications, where easily cleavable linkers are needed [1]. The stability and properties of acetals/ketals widely varies depending on their structure, which widens the scope of their applicability. The acid lability is increased markedly by attaching electron-donating alkyl groups on the acetal carbon. The

• simplest of the formaldehyde-type acetals, methoxymethyl (MOM) [2], is rather stable to acidic hydrolysis. The acetaldehyde acetals, 1-ethoxyethyl (EE) [2][3] and tetrahydropyranyl (THP) [2] are widely used as protecting groups, but they have a disadvantage of generating an additional asymmetric center

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• to access functionalized alkylidenecyclopropanes, with creation of a new carbon–carbon bond on the three-membered ring with the control of two contiguous stereocenters. Ireland–Claisen rearrangement of cyclopropenylcarbinyl esters The Ireland–Claisen rearrangement of silyl ketene acetals generated

• ketene acetals of (Z)-configuration 57a–l, arising from O-silylation of the corresponding chelated potassium enolates [60], underwent an efficient [3,3]-sigmatropic rearrangement upon warming to room temperature. After an acidic work-up and treatment of the crude carboxylic acids with

• –Claisen rearrangement of N,N-diBoc glycinates 67a and 67b was explored. The reaction conditions were essentially the same as those described previously with glycolates 56a–l except that LiHMDS was used as the base in the enolization step [69]. The (Z)-silyl ketene acetals 68a and 68b were generated, in

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• ROMP of seven-membered cyclic acetals (2-methyl-1,3-dioxepine and 2-phenyl-1,3-dioxepine) and N-substituted NB dicarboximide derivatives [72]. The subsequent hydrolysis of the prepared copolymers resulted in well-defined telechelics in good yields per initiator molecule and thus significantly improved

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

• )–2.05(2) Å) than with chlorosilanol 8 (OH···2.16(0) Å). Due to its two hydroxy units, the silanediol 9 shows higher catalytic activity as hydrogen bond donor than chlorosilanol 8, e.g., C–C coupling N-acyl Mannich reaction of silyl ketene acetals 11 with N-acylisoquinolinium ions (up to 85% yield and 12

• % ee), reaction of 1-chloroisochroman (18) and silyl ketene acetals 11 (up to 85% yield and 5% ee), reaction of chromen-4-one (20) and silyl ketene acetals 11 (up to 98% yield and 4% ee). Keywords: hydrogen bonds; hydrolysis; ion pairs; organocatalysis; silanediol; Introduction Silanediols are

• ion catalyses The N-acyl Mannich reaction of isochinolin (16), which is activated with 2,2,2-trichloroethoxycarbonyl chloride (17, TrocCl) to carbamate 10, and different silyl ketene acetals 11a–d yielding product 12 (Scheme 6) [45][47], is studied. Mattson et al. proposed a mechanism where the

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• % of TMSOTf with respect to the donor, 0 ºC, CH2Cl2 as solvent). As mentioned before, it has been reported that cyclic protecting groups like 4,6-O-benzylidene acetals in GalNAc trichloroacetimidates lead to the formation of α/β mixtures in glycosylations involving GlcA acceptors [43][47]. However

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• recently showed that 3-alkoxy-substituted N-acylpyrazinium salts can be selectively reduced by tributyltin hydride to afford 1,2-dihydropyrazines in good to excellent yields [9]. There have been other reports involving the addition of TMS-ketene acetals to pyrazinium salts [10][11][12]. A double

• nucleophilic addition of bis(trimethylsilyl)ketene acetals to pyrazines activated with methyl chloroformate was found to afford polycyclic γ-lactones in moderate yields [3][10][11]. The work by Garduño-Alva and co-workers demonstrated that these TMS-ketene acetals can be regioselectively added to substituted N

• Grignard reagent to add regioselectively to give 1,2-dihydropyrazine 3a. DFT calculations support the observations that the isolated regioisomer we obtained was the result of a thermodynamically favored 1,2-addition over a 1,6-addition [9]. It has also been shown that TMS-ketene acetals add selectively to

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• condensation reactions between aldehydes 3 or acetals 5 and ethyl nitroacetate (4). However, the high yield condensations with aldehydes 3 which were reported for some examples [3][4] require more than stoichiometric amounts of titanium tetrachloride thus leading to considerable amounts of metal-containing

• ) and acetals 5 or other approaches further described in the following. Results and Discussion As depicted in Table 1, we first studied the scope of the condensation between ethyl nitroacetate (4) and aryldimethylacetals 5a–s which are easily obtained in situ from the corresponding arylaldehydes 3a–s

• . As seen by 1H NMR monitoring, the treatment of arylaldehydes 3a–s with trimethyl orthoformate and an acid-bearing resin in dry methanol led to full conversion into the corresponding acetals 5a–s. Then, as reported [7][8], heating the crude acetals 5a–s and ethyl nitroacetate (4) in the presence of

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• this resonance structure. These common intermediates are mainly found in acid-catalyzed reactions of aldehydes, ketones, hydrates, hemiacetals and acetals [5], that is, by protonation of a carbonyl group (aldehyde or ketone) or by detachment of a nucleofuge from the alpha position of an alcohol or an

• organylated) carbonyl (1) and hydroxy (or organyloxy) carbenium ion (2): two possible representations of the same intermediate. Oxacarbenium, oxocarbenium, oxycarbenium and carboxonium ions. Acid-catalyzed interconversion of carbonyls, hydrates, hemiacetals and acetals.

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• epoxide to provide the corresponding β-hydroxy sulfide as shown in Scheme 25. In addition to disulfides, other odorless thiol equivalents have also been employed as nucleophiles for the thiolysis of epoxides and provided comparable results. Examples include ketene-S,S-acetals (2-[bis(alkylthio)methylene

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• out by treatment with diacetoxyiodobenzene and iodine under irradiation with visible light to give acetoxy acetals 130 and 131 in good yields with high stereoselectivities. As shown in Scheme 17, the reaction was expected to proceed via the formation of anomeric alkoxyl radicals, which underwent