Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• . J. K. Taylor and co-workers reported the first total synthesis of inthomycin B ((+)-2) using a Stille coupling of a stannyl-diene with an oxazole vinyl iodide unit followed by a Kiyooka ketene acetal/amino acid-derived oxazaborolidinone procedure as its cornerstones (Scheme 4) [43]. In the beginning

• (Z,E)-52 with silyl ketene acetal 53 in the presence of oxazaborolidinone derived from N-tosyl-ʟ-valine and BH3·THF generated the desired alcohol (Z,E)-(+)-54 in 74% yield and 64% ee. Next, a wide range of catalysts/conditions were screened for the crucial Stille coupling between iodide 48 and (Z,E

• )-diene 66 (E/Z = 19:1, separable) using the standard (E)-selective Horner–Wadsworth–Emmons (HWE) reaction. DIBAL-H reduction of ester 66 followed by MnO2 oxidation produced aldehyde (E,E)-67 stereoselectively. Unfortunately, attempted enantioselective aldol reactions of (E,E)-67 with silylketene acetal

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

• dipolar cycloaddition to produce tricyclic isoxazolidines [40]. The synthesis started from 5-hexyn-1-ol (4, Scheme 2). The alcohol was treated with dihydropyran followed by alkylation using butyllithium and then, acetal deprotection, providing the alcohol 5 as a key starting compound for the (±)-adaline

• , activated by lithium ion in a tricyclic N,O-acetal (−)-46, and an olefin metathesis (RCM) of a dialkenylpiperidine (−)-50 for the construction of an azabicyclononane system [48]. The synthetic sequence described by the authors is shown in Scheme 6. The lactam present in 43 was opened by treatment with

• LiH2NBH3 in THF at 40 °C to provide amino alcohol (−)-44 in 88% yield. This amino alcohol underwent cyclization through a one-pot process in the presence of TPAP-NMO, which involved oxidation in generated aldehyde 45, followed by dehydrocondensation leading to N,O-tricyclic acetal (−)-46 in 80% yield

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

• adduct 105 in 93% yield with 99% ee. The freshly prepared enantioenriched adduct 105 was subjected to ozonolysis [47] followed by decarboxylation to give bisoxindole 106 in 68% yield over two steps. Conversion of 106 to the corresponding acetal and subsequent allylation afforded 108 in 86% yield over two

• 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

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• ] appeared improved under ultrasound-assisted conditions, which also enhanced the yields of the final α-aminonitrile derivatives. The Strecker reaction of cyclopropanone acetal substrates with sodium cyanide and several amines was also facilitated by sonication conditions which afforded cleaner N-alkylated α

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• -bromoacetaldehyde acetal by using aluminum(III) chloride as a Lewis acid catalyst through [1 + 2 + 2] annulation. This new versatile methodology provides a wide scope for the synthesis of different functional N-(hetero)aryl-4,5-unsubstituted pyrrole scaffolds, which can be further derived to access multisubstituted

• expensive and nonrecyclable homogeneous metal catalysts. To alleviate all these problems, herein, we used easily available α-bromoacetaldehyde acetal (2a) and a simple 1,3-dicarbonyl compound as a reagent couple to react with (hetero)arylamines. The established [1 + 2 + 2] annulation reaction provided a

• straightforward approach for accessing various N-(hetero)aryl-4,5-unsubstituted pyrroles, and some of the pyrrole products are not accessible with the methods reported hitherto. Results and Discussion Initially, a mixture of aniline (1a), α-bromoacetaldehyde acetal (2a), and ethyl acetoacetate (3a) was treated

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

• glycol to afford monocyclic acetal 53 with less hindered keto-group in respectable yield. Since the introduction of powerful electron-withdrawing groups such as fluorine atom(s) in any material changes its behavior significantly, in this regard, Sakurai’s group installed six fluorine atoms at the

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• with a poor stereoselectivity, however, a similar reduction of the diethyl acetal of 38, followed by an acetal hydrolysis gave the aldehyde 39 with a good stereocontrol (>10:1). It is not possible to make a direct comparison of the efficiency of these three routes as they do not lead to an identical

• iodine-catalyzed Mukiyama–Michael addition of the ketene silyl acetal 104 to 103 afforded the trans-1,5-disubstituted tetrahydropyranone 105. After the generation of the C-3-exocyclic olefin and functional group manipulation, the Takai olefination [40] of the aldehyde 106 gave the trans-vinyl iodide 107

• generation of the mixed acetal 113 (Scheme 18) [33]. A ring-closing metathesis gave an inseparable mixture of the dihydropyranyl ethers 114a and 14b, which could be equilibrated under acidic conditions (114b/114a > 20:1). A standard functional group manipulation afforded the vinyldihydropyran-2-one (−)-115

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

• compound 13. Then, (2-naphthyl)methylene acetal [21] was used to protect the C-4,6-hydroxy groups using 2-naphthaldehyde dimethyl acetal and 0.2 equiv of camphorsulfonic acid (CSA). These protecting group manipulations resulted in the exposure of the C-3 hydroxy group in compound 14 for further acylation

• FmocCl in the presence of diisopropylethylamine (DIPEA) to give the fully protected compound 17. The regioselective opening of the arylidene acetal at O6 with Et3SiH and PhBCl2 in the presence of molecular sieves at −78 °C [22] gave compound 18 in good yield (80%) having a free C-6 hydroxy group

• phosphorylated using tetrabenzyl diphosphate in the presence of lithium bis(trimethyl)silylamide (LHMDS) in THF at −78 °C [23] to afford the anomeric phosphate 23 exclusively as the α-anomer. Finally, global deprotection of 23 (benzyl phosphate, Nap ethers, and naphthylidene acetal) were accomplished by

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• led to the formation of disaccharide acceptor 5 in 73% yield. The quantity of HClO4-SiO2 present in the reaction mixture was very low, which allowed the selective deprotection of the highly acid labile PMB group without affecting the benzylidene acetal in the molecule in dichloromethane as the solvent

• without the isolation and purification of the intermediate glycosylation products. Finally, compound 7 was subjected to a set of reactions involving (a) transformation of the azido group to an acetamido group by the treatment with thioacetic acid [33]; (b) removal of the benzylidene acetal by the

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• the reaction of trialkyl orthoformate 3 with thiourea (2) to produce imidate intermediate 9, which is nucleophilically attacked by intermediate 10 and transfers the alkyl group R2 to deliver the alkylated intermediate 11. Meanwhile, N,N-dimethylformamide dialkyl acetal might also play a role in this

Recent synthesis of thietanes

• Jiaxi Xu

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

• series of thietanose nucleosides 118 [53]. Similarly, enatiomeric thietanose nucleosides 123 were prepared from L-xylose [53] (Scheme 24). In 2010, Takahata and co-workers designed and synthesized thietane-fused nucleosides. They first prepared a key intermediate spiro acetal 125, which was converted

• yields as well. The compounds were used for the semisynthesis of further sulfur derivatives of taxoids by first converting them into the acetal-protected oxiranemethyl mesylate derivative 164. After the treatment of compound 164 with KSAc, the mesylate 165 generated the corresponding thietane-fused

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• resonances were sectionized into those at carboxy (δC 174.6–164.6), olefinic (δH 6.91–5.09; δC 148.9–122.3), acetal (δC 98.6), oxygenated (δH 5.40–3.66; δC 79.3–69.8), and aliphatic (δH 2.60–0.84; δC 48.9–3.9) regions, which obviously represented a characteristic feature of polyketides. The molecular

• components deduced from 13C NMR and HSQC spectra were three carbonyl carbons, eight olefinic methines, one acetal carbon, eight oxymethines, six aliphatic methines, 14 aliphatic methylenes, and seven aliphatic methyl groups (Table 2). The connectivity analysis of 2 started from the doublet olefinic methine H

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• decomposed at around 41–42 °C (Scheme 1a). Therefore, we achieved the synthesis of 3a by Pd-catalyzed thienylation of TTF using acetal-protected 8, followed by deprotection using PTSA·H2O and P(OEt)3-mediated cross coupling with 11 (Scheme 1b). The cross-conjugated molecule 4 was prepared in two procedures

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• 96 h. The aryl (i.e., 133), ether (i.e., 140a), ester (i.e., 140b), tert-butyldimethylsilyloxy (i.e., 140c), boronic ester (i.e., 140d), acetal (i.e., 140e), and indol products (i.e., 140h) of various bromo-substituted starting materials were successfully obtained. For 1-bromo-3-chloropropane, the

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

• )boronates 320–322. High functional group tolerance and enantioselectivities are characteristics of this reaction. The stereoselective formation of a 3,3-disubstituted cyclopentene scaffold (e.g., 331), containing three contiguous asymmetric centers, was also developed starting from an achiral cyclic acetal

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• products. An acetal-protected aldehyde could also be used providing enol phosphonate 3g in 52% yield. In this case, prolonged reaction times led to partial evolution of 3g into enol ether 4. This transformation may be explained by an acid-mediated elimination of ethanol likely caused by trace formation of

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• chiral acetal ligands have been reported by Lyle et al. where the fluorine–metal exchange was achieved by treatment with potassium tert-butoxide for a relatively long period (24 h) (Scheme 4) [65]. Acid-catalyzed condensation of compound 20 with enantiomerically pure C2-symmetric 1,2-tosylate analogs 21

• (R = Me, iPr and Ph) in benzene produced chiral acetal 22. Subsequent palladium-catalyzed C–C coupling of the acetal with 4-fluorophenylboronic acid (FPBA) in the presence of caesium carbonate and tri-tert-butylphosphine afforded aryl fluorides 23. Pure ligands 24 (63–72%) were obtained by

• of pyridylphosphine ligands. Synthesis of piperidyl- and oxazinylphosphine ligands. Synthesis of linear multi-chelate pyridylphosphine ligands. Synthesis of chiral acetal pyridylphosphine ligands. Synthesis of diphenylphosphine-substituted triazine ligands. Synthesis of (pyridine-2-ylmethyl)phosphine

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• carbonates having a fluoro or acetal substituent were also suitable coupling partners (3ad and 3ae). The synergistic palladium/copper catalysis was used for the reaction of a secondary allylic carbonate. For example, the allylic cross-coupling of 2a’, a constitutional isomer of 2a, with benzaldehyde (1a

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• (Scheme 5). However, the desired acetolysis products 30, 34, and 38 were not obtained. Replacing the more reactive fucose moiety and the benzylidene acetal ring of 29, i.e., using the less reactive complement 33, was also unsuccessful. The branched fucose, benzylidene, and isopropylidene rings of the

• disaccharides were cleaved and acetylated, as shown in Scheme 5. The difficulty of these reactions might have been attributed to the more liable nature of the tertiary acetal center C-1 of fucose as compared to the sterically hindered quaternary ketal functionality C-2 of the 2,7-anhydro skeleton. To our

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

• 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

• and Discussion We started our investigation with the rearrangement of trimethylsilyl ketene acetal (2a) derived from allyl propionate (1a, Scheme 1). Silyl ketene acetals 2 can be observed by NMR in the reaction mixture (see Supporting Information File 1 for NMR spectra of 2c). This reaction afforded

• , as well as trimethylsilyl ketene acetal 2b generated from 1b, proceeded with similar yields and diastereoselectivity (Table 1, entries 3–6). However, the Ireland–Claisen rearrangement attempted with cinnamyl propionate (1c) did not take place when using LDA as a base (Table 1, entries 7 and 8). Next

Carbazole-functionalized hyper-cross-linked polymers for CO₂ uptake based on Friedel–Crafts polymerization on 9-phenylcarbazole

• Dandan Fang,
• Xiaodong Li,
• Meishuai Zou,
• Xiaoyan Guo and
• Aijuan Zhang

Beilstein J. Org. Chem. 2019, 15, 2856–2863, doi:10.3762/bjoc.15.279

• HCPs include solvent knitting methods [10], Scholl coupling reaction [11], the knitting method with formaldehyde dimethyl acetal (FDA) [12], functional group reactions [2][13] and so on. Among these methods, the knitting method with FDA as external cross-linker is the most time-efficient approach [14

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• ) indicative of a molecular formula C22H36O6. The NMR data for 10 (Table 3) were very similar to those for 3, with the main differences being the absence of a signal for the lactone carbonyl group and the presence of additional signals for acetal (δC 101.9; δH 5.31, t) and methoxy (δC 54.1; δH 3.26, s) groups

• . Key HMBC correlations (Table S12 in Supporting Information File 1) from H-7 to C-12 and from 12-OMe to C-12 positioned the methoxy group and acetal proton on C-12. Thus, the structure of 10 was assigned as shown in Figure 1. The configuration of 10 at C-12 was determined to be 12R based on a key ROESY

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

• cationic polyene cyclization, transition-metal- or photocatalyst-mediated radical polyene cyclization [72]. The key to such transformation is to install a proper initiator within the substrate such as an allylic alcohol, an acetal, an aziridine, an N-acetal, a hydroxylactam, or a 1,3-dicarbonyl moiety. van

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• oxidation conditions. Based on this assumption, the corresponding silyl nitronate from 3-nitropropanal or its acetal were not tried for cycloaddition. We then set to liberate the β-hydroxy ketone synthon by ring opening of the isoxazoline 3 (Scheme 3). Raney-Ni-catalyzed hydrogenolysis in the presence of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• . Acetal formation, reduction of the amide function and deprotection completed synthesis of (−)-hygrine (S)-61. To synthesize (−)-hygroline (2S,2'S)-62 and (−)-pseudohygroline (2S,2'R)-62 the carbonyl group in (S)-66 was reduced and the diastereoisomeric alcohols (2S,2'S)-67 and (2S,2'R)-67 were separated