Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• )ethylene-1,2-dicarbonitrile (R = CF3) [8]. Both five-membered spirotetrahydrothiophenes 3 and seven-membered S,N-heterocycles (ketene imines) 4 were observed in the course of these reactions (Scheme 1). The latter products were trapped with suitable nucleophiles (R = CO2Me) or even isolated and identified

• -deficient ethylenes 2. Cyclic ketene imines 4 are also formed as products of formal [4 + 3]-cycloadditions. Formal [3 + 2]-cycloadditions of thioketones and [4 + 3]-cycloadditions of thiochalcones with donor–acceptor cyclopropanes 5 leading to tetrahydrothiophenes 6 and tetrahydrothiepines 7, respectively

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

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• of a nitrile-stabilized carbanion, in resonance with a ketene iminate anion. It has been calculated that the latter CN double-bonded species is relatively unstable compared to the CN triple-bonded carbanion species, which has the negative charge localized on the α-carbon atom [13]. This carbanion is

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• by cyclocondensation with ketene dithioacetals and substituted acetophenones other cyano-containing derivatives became accessible by desymmetrizing cyclocondensation of 1,2-diaroylacetylenes with ethyl cyanoacetate [27], similar to related studies with dialkyl malonates [28]. Here, we report on

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• new methodologies of butenolide formation. The first butenolide formation started with the reaction of ketone 68 with carbon disulfide (CS2) and iodomethane (MeI) to give the ketene dithioacetal intermediate 69, which was subjected to a Corey–Chaykovsky epoxidation, followed by acid hydrolysis to give

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• -catalysed carbonylation of iodoarylimine 100 to produce acid chloride 102 (Scheme 29). Intramolecular nucleophilic attack of the imine onto the acyl chloride would furnish cyclic N-acyliminium derivative 103, which can then undergo a second palladium-catalysed carbonylation to form a stabilized ketene 104

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• ]. Alternate synthetic pathways include ring formations of open-chained precursors [11][12], reactions of dicarbonyl compounds with ketene diethylacetal followed by hydrolysis [13] or total syntheses [14]; however, none of these alternatives could rival the combination of ease and cost-effectiveness of HDA

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

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

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

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• ) [8]. Attanasi and co-workers described the synthesis of 4-(phenylseleno)pyrazol-3-ones through α-(phenylseleno)hydrazone reagents under basic conditions [9]. In 2015, Yu and co-workers described one example for the condensation reaction of α-oxo ketene dithioacetal with hydrazine hydrate to produce

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• ]quinoxaline-1,2,4(5H)-triones III [23][56] (Scheme 1). According to the literature data, precursors I and II are unsuitable for achieving the proposed goal as the generated ketene IV reacts only at its oxo-diene fragment in intermolecular trapping reactions with various dienophiles [57][58][59][60][61][62

• account the results of the thermal analysis, we examined the feasibility and conditions of the intermolecular reaction of the ketene generated from PQT 1a with benzalaniline (2a). The reaction mixtures obtained were investigated by UPLC–MS and the results are summarized in Table 2. The reaction mixtures

• reaction (Table 1) was not detected. The most likely way of the formation of quinoxalinone 4a is hydration of the ketene with subsequent decarboxylation (Scheme 2); more careful drying the reaction vials and solvents easily reduced the amount of compound 4a. The formation of pyrido[1,2-a]quinoxaline 5a can

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

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• N-Boc-isatin imines 3 with silyl ketene imines 27 catalyzed using a combination of Zn(OTf)2 and chiral N,N’-dioxide ligand 28 [48]. As shown in Scheme 9, this remarkable process afforded a wide range of chiral β-amino nitriles 29 exhibiting two vicinal tetrasubstituted stereocenters as almost single

• -isatin imines with silyl ketene imines. Tin-catalyzed Mannich reaction of N-arylisatin imines with an alkenyl trichloroacetate. Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein catalyzed by β-isocupreidine. Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein (35

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• ]annulenes as a novel series of potent and specific αv integrin antagonists starting from 4,5-benzotropone (11) (Figure 4 and Scheme 13) [73]. TBS-enol ether intermediate 68 was first formed by the Mukaiyama–Michael reaction of O-silyl ketene acetal to 4,5-benzotropone (11) at low temperature in the presence

• structure of 86 was confirmed by the spectroscopic data. The formation of the heptafulvalenes could be explained via an intermolecular [2 + 2] cycloaddition product such as 87 between the carbonyl group of tropones and the ketene C=C double bond of 8-oxoheptafulvene (85) followed by decarboxylation. In a

• -Benzotropone (12) was transformed into the corresponding benzoheptafulvalene 181 using the ketene addition protocol illustrated in Scheme 15 and Figure 6. The thermal decomposition of the obtained tosylhydrazone salt 182 from 2,3-benzotropone (12) afforded a trapping product of 1-naphthylcarbene (185) [128

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• condensation of alkyl-substituted silyl ketene acetals (32) with enantioenriched α-2,2,6,6-tetramethylpiperidinyl-β-benzyloxypropionaldehyde (33) in presence of TiCl2(OiPr)2 to give the β-hydroxyester 34 that is diastereomerically enriched [75][95]. Reductive cleavage of the 2,2,6,6-tetramethylpiperidinyl (TMP

• ) group by Zn and trifloroacetic acid results in cyclization and formation of the C2'- substituted ribonolactone (35). TiCl2(OiPr)2 has been identified as the optimal Lewis acid for the synthesis of most ribonolactones with the exception of unsubstituted silyl ketene acetals (R = R' = H) that leads to

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany 10.3762/bjoc.14.37 Abstract In the presented study, dithi(ol)anylium tetrafluoroborates are added to α,β-unsaturated ketones in a Michael-type reaction yielding diverse substituted ketene diothi(ol)anes. The reactions proceed at room temperature in 1

• or 13 h without the need of further additives. The presented procedure is in particular useful for dithi(ol)anylium tetrafluoroborates without electron-withdrawing groups in α-position. This is advantageous with respect to previous approaches, which were limited to the use of ketene dithioacetals

• dithiolanes by addition of an ynone to α-alkyl or aryl-substitued dithiolanylium TFBs. Keywords: addition to α,β-unsaturated carbonyls; dithiane chemistry; dithianylium tetrafluoroborate (TFB); ketene dithiane; Introduction 1,3-Dithioacetals are a common motif in organic chemistry. They are part of

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• organic synthesis applied most successfully for the construction of natural products and their analogs [1][2]. Later this type of reaction was extended to enolized carboxylic acid derivatives, particularly to silylated ketene acetals, as reaction partners for carbonyl active compounds [3][4][5]. Mild and

• with benzaldehyde, p-nitro-, and p-methoxybenzaldehyde as described recently by Ponomarenko and Röschenthaler et al. [34]. Considering our earlier results [31] on TMSOTf-mediated Claisen-type rearrangements of SF5-acetates of allyl alcohols, we favor the initial formation of (Z)-enolates (ketene

• reaction (see above), the nucleophilic attack of the silicon enolate (in our case the ketene silylacetal) at the TiCl4-activated aldehyde results in the formation of intermediate 6. Under the influence of the electron-donating substituent, the elimination of titanium oxide dichloride (Ti(O)Cl2) is favored

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• facile preparation of thienyl heterocycles 8. The mechanism for this reaction is based on the formation of a sulfur ylide-like intermediate. It was clearly suggested by (i) the intramolecular cyclization of ketene N,S-acetals 7 to the corresponding thiophenes 8, (ii) 1H NMR studies of Meldrum’s acid

• primarily been prepared by base-catalyzed intramolecular Dieckmann-, Thorpe–Ziegler, and aldol-type condensations of the corresponding ketene-N,S-acetals [57][58][59][60][61][62][63][64][65][66][67]. These methods are still need strong bases [60], high temperatures [62][64][65], and are generally low

• %) and, the favorable resonance form is illustrated in Figure 4. According to the recent reports on the multiple isomeric structures of ketene N,S-acetals [80][81][82][83], structural assignments of the ketene N,S-aminothioacetals 7 by 1H NMR are not facile. To overcome these difficulties, we prepared N

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• obtained by flash vacuum pyrolysis of furan-2,3-dione 6 and dimerizes to 1,3-dioxin-4-one 3, which is a stable but reactive ketene. The transannular addition and rearrangement of enols formed by the addition of nucleophiles to the ketene function in 3 generates axially chiral 2,6,9-trioxabicyclo[3.3.1

• , which, upon flash vacuum pyrolysis (FVP) at 350–500 °C at 10−3–10−4 hPa, eliminates a molecule of CO to generate dipivaloylketene (2) in over 90% yield (Scheme 3). Usually, α-oxoketenes are not isolable, but due to the steric hindrance exerted by the pivaloyl groups ketene 2 is kinetically stable at up

• to −20 °C. However, it dimerizes at room temperature to afford an 88% yield of the thermally very stable dimer 3, which still carries a ketene function [16]. Compound 3 is formed through a [2 + 4] cycloaddition between one molecule of the α-oxoketene 2 and the carbonyl C=O bond of a second molecule

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• this reaction sequence, (thio)silyl ketene acetal 10 was united with 2-phenylglycinol and para-anisidine in a two-step, one-pot process to provide β-amino acid derivative 11 in a 60% yield. The overall reaction sequence provides a unique method for the production of the high-value β-amino acid

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• rings 3.1 From alkynes The intramolecular, dehydro-Diels–Alder reaction of ketene dithioacetals 302 leading to formation of various benzo[f]-1-indanones 303–305, has been described in 2015 by Bi et al. [117]. Modulation on the reaction parameters such as addition of DBU and the type of atmospheric gas

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• -membered heterocycles [2]. In addition, some cycloaliphatic thiocarbonyl S-methanides were shown to react with strongly electron-deficient cyano-substituted ethenes via zwitterionic intermediates to yield also seven-membered cyclic ketene imines, which easily undergo further conversions [3][4][5]. In the

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• -workers reported the use of N-alkylated 3,5-di(carbomethoxy)pyridinium ions L13 to catalyze the reaction between 1-chloroisochroman and silyl ketene acetals (Scheme 10A). Catalyst L13 with R3 = C6F5 was found to be particularly active, and was found to efficiently form the product at 2 mol % loading

• followed by anion exchange. The resultant oxocarbenium/tetraphenylborate ion pair undergoes a nucleophilic attack by silyl ketene acetal, which is followed by scavenging the trimethylsilyl cation with a chloride anion to result in chlorotrimethylsilane and the product. Mechanistic studies were conducted to

• bond donors. However, catalytic halogen scavenging with halogen bond donors is also possible if the products are not inhibiting the catalyst. One of such transformations explored by the Huber group is the addition of ketene silyl acetals to 1-chloroisochroman (Scheme 17) [85][87]. The chloride anion

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• cyclohexenone, followed by hydrogenation is 100% atom economical yielding no byproducts. The next best route with an 86% atom economy is the Diels–Alder addition of ketene, generated by pyrolysis of acetone, to 1,3-butadiene to give cyclohex-3-enone, which upon hydrogenation yields cyclohexanone. The only

• Schemes S1 to S3. Among these options the [2 + 2 + 2] strategy of coupling ketene and two equivalents of ethylene is by far the most efficient with an atom economy of 86%. This route matches the closely related second-best performing [4 + 2] route shown in the third entry of Scheme 2. Again, we can