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

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

• base, such as DIPEA, and led to chiral isatin-derived N,O-acetals 57 in good to quantitative yields (69–99%) and good to high enantioselectivities (78–90% ee). Notably, generally excellent yields (93–99%) were obtained in the reactions of variously substituted substrates while the lowest yield of 69

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• was observed instead [23]. Diarylmethanes were also obtained in the Friedel–Crafts reactions of arenes with primary benzyl alcohols, aryl acetals, and benzyl esters [1]. Benzyl fluorides (in 1,1,1,3,3,3-hexafluoroisopropanol in the presence of a catalytic amount of trifluoroacetic acid [24]) as well

• as benzotrifluorides (employed in hydrodefluorinative Friedel–Crafts alkylations catalyzed by alumenium ions [25]) were interesting, alternative substrates for alcohols, acetals and esters. A large group of synthetic procedures for the synthesis of diarylmethanes are deoxygenations of secondary

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• tetrahydropyran acetals [14]. If the Stevens’ hypothesis is true, a nucleophilic reaction with C1, having a pseudo-equatorial phenyl group, should give a trans-2,4-disubstituted product (Figure 5). Similarly, acyliminium ions C3 and C5 should give the cis-2,5- or cis-2,6-disubstituted piperidine derivatives

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

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

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

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

• -substituted aminothioacetals 9, and (iii) substitution studies of the methoxy group on Meldrum’s acid containing N,S-acetals 9b. Notably, in terms of structural effects on the reactivity and stability of sulfur ylide-like intermediates, 2-pyridyl substituted compound 7a exhibited superior properties over

• 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

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• ) and methylated to DMIBF (7) [8]. However, yields in our hands are quite low. It is known that benzyl ethers are prone to oxidative functionalization [20]. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) has been used to selectively oxidize benzyl ethers to acetals in the presence of alcohols [21

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• ]. In synthetic chemistry, DBDMH acts as a thiophilic activator in the conversion of dithioacetals to the corresponding O,O-acetals [28][29][30], as well as in the synthesis of heparin mimetics [31]. We considered DBDMH as a readily available alternative promoter for glycosylations involving

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• , compounds bearing a different number of methoxy groups were selected in order to understand the electronic constrains that might render indole formation competitive. Upon treatment with 70% HClO4, acetals 9a and 9o yielded the respective THIQs 10a and 10o. However, the highly-activated acetal 9p exclusively

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• orthoformates at room temperature in the presence of an acid. Thus, 3,3-dimethoxycamphersulfonylimine 16 and 3,3-diethoxycamphersulfonylimine 16’ were prepared [18][39]. The subsequent reaction of these acetals with one equivalent of lithium phenylacetylide or 1-heptynyllithium under conditions described above

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

• 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

• -workers [52]. (A) Alkylpyridinium catalysts L13-catalyzed reaction of 1-isochroman and silyl ketene acetals by Berkessel and co-workers. (B) Evidence of L13 C–H···X– hydrogen bonding in solid state [55]. Mixed N–H/C–H two hydrogen bond donors L14 and L15 as organocatalysts for ROP of lactide by Bibal and

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

• Serena Traboni,
• Emiliano Bedini and
• Alfonso Iadonisi

Beilstein J. Org. Chem. 2016, 12, 2748–2756, doi:10.3762/bjoc.12.271

• stannylene acetals in the regioselective silylation of saccharide primary alcohols [37]. At this stage, it should be noted that pyridine is frequently employed as the solvent for silylations, but the conditions herein described can be referred to as “solvent-free” because of the very limited amount of

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• aldol products 85 and 86 to acetals 87 and 88, respectively, was achieved using standard transformations and Goodman’s reagent (67) [67] was used to install the guanidine moiety. With both protected amino acids 87 and 88 in hand, the attention turned to the formation of tripeptide 78 (Scheme 17

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• their preparation and modification, it is remarkable that there is only little focus on the pH stability of these compounds in aqueous media. In general, the aminal moiety is known to undergo (similar to the corresponding O,O-acetals) acidic hydrolysis and can be considered as stable only within a

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• to alkyl-containing ketones to give the target products in yields of 30–91% and good regioselectivity 7:1 to 20:1 (Scheme 28) [261]. Asymmetric oxidation: Asymmetric Baeyer–Villiger oxidation reactions can be performed using chiral acetals, organic hydroperoxides, chiral metal complexes and

• observed with the peptide catalyst (Scheme 33) [285]. Versatility of the Baeyer–Villiger reaction with respect to starting reactants: The Baeyer–Villiger reaction cannot only be performed with ketones but also with acetals and aldimines as the starting substrates. The oxidation of cycloalkanone acetals

• involves the formation of solvolytically generated cyclobutyl hydroperoxides 177 followed by the rearrangement of the latter into oxa-bridged, hydroperoxyhemiketals 176 (Scheme 53). The fragmentation of hydroperoxy acetals 178a–e in the presence of Ca(OCl)2 or t-BuOCl as the catalysts in CH3CN generating