Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• these doublets as 2 protons suggested that the exocyclic alkene was present in only one of the products. In the literature, this exocyclic alkene in β-sesquiphellandrene is observed at 4.72 ppm as a multiplet [39]. A triplet at 5.39 ppm that integrates for 2 protons can be assigned to H10 in both 26 and

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• ) as alkene component had detrimental effects on the yields in the synthesis of 2d, 2f and 2h. Intermediates 5a and 5b were accessible from 3a and 3b via Suzuki–Miyaura or Stille coupling [34]. Biology The influence on deacetylase activity of three human sirtuin isoforms (Sirt1–3) was determined in a

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• enabled the assignment of these signals to the 1,2-disubstituted alkene moiety. Thus, the NMR data presented above indicate the presence of an isolated spin system, O–CH2–CH–CH2–CH=CH. A similar analysis of the remaining complex multiplets at 1.56, 1.77, and 1.93 ppm as well as their correlation with the

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• (Figure S37, Supporting Information File 1) and previously reported congener 5 were almost identical, while 4 displayed no significant UV–vis absorptions, suggesting the absence of both the ester and alkene moieties. This was confirmed by the analysis of the 1H and 13C NMR data for 4 (Table 1), which

• revealed the absence of ester and alkene resonances and the presence of three hydroxylated methylenes at C-12 (δC 62.2; δH 3.79 and 3.65), C-14 (δC 69.8; δH 3.90 and 3.36) and C-15 (δC 62.9; δH 3.77 and 3.47), and one hydroxylated quaternary carbon at C-2 (δC 88.1). This suggested 4 was related to 5, but

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• and two radical C1 synthons, CO and sulfonyl oxime ethers, is known to be feasible [23][24][25], we were tempted to explore a novel class of four-component radical reaction [26][27][28] incorporating a xanthogenate, an alkene, CO, and a sulfonyl oxime ether (Scheme 1, reaction 2). This paper reports

• Gel 60N (spherical, neutral, 40–50 μm)) and, if necessary, were further purified by recycling preparative HPLC (Japan Analytical Industry Co. Ltd., LC-918) equipped with GPC columns (JAIGEL-1H + JAIGEL-2H columns) using CHCl3 as eluent. Xanthogenate 1a,b [20], 1c [36], alkene 2c [37], and oxime ester

• mechanism. Concept: Alkene difuctionalization by four-component radical reaction using xanthates, alkenes, CO and sulfonyl oxime ethers. Four-component coupling reaction of ethyl 2-((ethoxycarbonothioyl)thio)acetate (1a), 1-octene (2a), CO, and sulfonyl oxime ether 3a under radical conditionsa. Supporting

A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes

• Joza Schmitt and
• Scott T. Handy

Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171

• –vis spectrum; Introduction Aurones are a fascinating minor sub-family of the flavonoid natural products [1][2]. While they feature the same C15 composition as other flavonoids, the skeleton is quite different, featuring a benzofuranone connected to an aromatic ring via an exocyclic alkene. This

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• along with 8% of the alkene 22. It is proposed (Scheme 5) that these products arise from stepwise formation of the cyclopropylcarbinyl cation 23. This cation can rearrange via migration of bond a to give the cyclobutyl cation 24. The cis-nature of the phenyl group and the hydrogen in cation 23

• product, the alkene 22. Interestingly, formation of the γ-silyl cation 24 is preferred over the β-silyl cation 25. Reaction of the isomeric mesylate 20 in CD3CO2D gives the same rearranged products 21 and 22. These products are accounted for mechanistically in Scheme 6. The initially formed

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

• moiety (Scheme 13) [51]. Before conversion of the chloromethyl group into a phosphonium salt the chiral auxiliary was removed. The reaction of the ylide (R)-45 prepared from the chloride (R)-44 with benzaldehyde afforded (E)-alkene (S)-46 which after hydrogenation and basic hydrolysis gave ʟ

• corresponding ketone with a NaBH4/ZnCl2 mixture. Treatment of (2S,1'R,1''R)-98 with LiAlH4 to secure the trans-configured alkene, protection of the hydroxy group and the regioselective aziridine ring opening led to the formation of the acetate (2S,3R,1'R)-99. After basic hydrolysis the oxazolidin-2-one (2S,3R,1

• secured in the starting aldehyde introduction of the two others required cis-dihydroxylation of the Z-alkene 111. The highest diastereoselectivity (99:1) was observed at −10 °C providing the aziridine diol (2S,1'S,2'R,1''R)-112 as a major diastereoisomer. The regioselective aziridine ring opening combined

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• reaction of allene 1a with benzene resulted in the formation of alkene Z-11a, as a product of intermolecular hydroarylation of the carbon–carbon double bond (Table 2, entries 4–6). This reaction required 2.1 equivalents of AlCl3, 1.05 equivalents of benzene and five minutes at room temperature (Table 2

• /or indanes 12 (Table 3). Thus, in reactions with benzene, only cis-alkene Z-11b was obtained in 88% yield (Table 3, entry 1). The sole formation of alkenes E-11g, Z-11h and Z-11i, and E/Z-11l was also observed in reactions with 1,2-dimethoxybenzene (veratrole) (Table 3, entry 6), fluorobenzene (Table

• complex mixtures of oligomeric compounds. In the same reaction with benzene, allene 1b afforded alkene Z-11n in high yield (Scheme 5). The use of morpholine for quenching of the superacidic reaction mixture gave amide Z-11o in the reaction of 1a with benzene (Scheme 6). We also conducted a large-scale one

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• explore the diversity of products that could be obtained from these adducts, we carried out a reduction of the alkene in compounds 9 and 10 by using hydrogen and palladium on charcoal (Scheme 4). This provides the tetrahydroquinoline adducts 11 and 12. Additionally, and in contrast, oxidation of the

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• yield. Again, the final product proved to be unstable towards elimination giving rise slowly to the corresponding alkene 8a [18]. In fact, when compound 8 was kept in water or methanol solution at room temperature, the formation of 8a was observed in about 20% within a few hours. Moreover, the same

• elimination occurs even when 8 was stored at −20 °C. To avoid β-elimination we planned the synthesis of a new final sugar devoid of the hydroxy group at position 3. Therefore, we selected the alkene 9 as substrate for the hydroboration reaction (Scheme 2). The hydroboration reaction of the known compound 9

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• steroid biological functions. Such oxygenated and alkene groups represent the entrance door for subsequent synthetic modifications, including the incorporation of MCR reactive functionalities. In the last two decades, MCRs have emerged as effective tools for the rapid derivatization of steroidal skeletons

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• transient η2-alkene complex A (steps a and b). Deprotonation of the pro-nucleophile 1a by the counter-anion of the η3-allyl-Pd complex exchanges the benzoate for the enolate anion (step c) [50], and following C–C bond formation from the resulting anion-scrambled complex C leads to the Pd(0) complex D (step

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

• similar way to that described in Scheme 3. In this case, the coupled alkyne moiety is again activated by Cu(I) and then base-promoted cyclization occurs. A new copper complex formation with the alkene analogue to 13 (see Scheme 3) facilitates the aromatic nucleophilic substitution by indole or pyrrole

• , including a thiophene derivative. With the aid of several dedicated experiments, the researchers proposed a mechanism initiated by the formation of an arylsulfonyl radical 72, which then would add to the alkene moiety in 67 to produce a radical intermediate 73 (Scheme 22). The photocatalyst-assisted

• well and even a N-heteroaryl analogue of 124 was obtained, although the yield was moderate (42%). The formation of compound 124 may be explained by a radical process, starting with the addition of arylsulfonyl radical 72, formed from 69 and aryldiazonium cation 68, onto the alkene moiety of

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• intermediate 5 in good yield (92%, Scheme 2). With intermediate 5 in hand, further elaboration was necessary to obtain the aldehyde required for the proposed reductive amination to access HF-1. Intermediate 5 was acylated with pentenoyl chloride to give alkene 6, which was then oxidatively cleaved using

• corresponding alkene resulted in a mixture of products. We opted to try the synthesis of HF-2 by 1,4-addition, rather than reductive amination. Thus, intermediate 5 was acylated with acryloyl chloride to give the α,β-unsaturated intermediate 10 (Scheme 1). Condensation with a tert-butyl-protected glycine

• obtain an aldehyde that could then be used in a reductive amination. Beginning with the commercially available 4-(4-bromophenyl)butanoic acid, an alkene was installed with a Suzuki reaction, which in turn underwent ozonolysis to give 21, shown in Scheme 4. In parallel, a commercially available piperidine

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

• alkene); it is called a hetero-Diels–Alder (HDA) reaction when one or more heteroatoms (most often oxygen or nitrogen) are present among the reactants, such as the use of carbonyl compounds or imines as dienophiles [1][2][3][4][5]. An asymmetric HDA reaction is capable of introducing up to four

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• ylide 21 [8] followed by alkyne generation [23] with butyllithium in a one-pot process, trienyne 3 was obtained as a 1.6:1 mixture of E and Z olefin isomers. Due to the presence of the isopropyl group at the disubstituted alkene [24] of 3, 30 mol % of the second generation Grubbs catalyst 22 were

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• trichloroacetimidate mannosyl donors 3 and 4 [47][50] and the use of a fluorous tag containing an amino alcohol spacer rather than an alkene that would require late-stage modifications. The aminopentanol spacer 6 used at the reducing end to conjugate to the dendrimer was first protected with fluorous CbzF-NHS 5 to

• used alkene fluorous tag [11][52][53]. The CbzF tag was also removed during global deprotection to readily provide an amine handle for conjugation to the dendrimeric core, avoiding further synthetic manipulations. Synthesis of glycodendrimer Attachment of the 5(6)-TAMRA fluorophore to the dendrimeric

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• generated distonic radical cation can be further trapped by an alkene, alkyne, or triplet oxygen to initiate radical cyclization (Scheme 1) [7][8][9][10][11][12][13][14][15]. Thus, as key synthons, this class of molecules may play an important role in organic synthesis during construction of a series of

• cycloaddition chemistry based on compound 1. Zheng et al. [7] first reported on the [3 + 2] cycloaddition reaction of 1 with an alkene or alkyne mediated by visible light by the aid of the photocatalyst [Ru(bpz)3](PF6)2. Our group reported the metal catalyst itself, particularly the dinuclear rhodium complex

• (Rh2(II,II)), that efficiently catalyzes the ring opening of 1 to achieve cycloaddition with alkene substrates under an argon atmosphere [18]. During the reaction, no metal valence changes were observed. We proposed that Rh2(II,II) may coordinate with the nitrogen in 1 to decrease the bond dissociation

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• combinatorial library [88]. The work carried out by Davis and co-workers led to the metabolic incorporation of unnatural amino acids (uAAs) bearing a terminal alkene as CM substrates for protein modification [89]. The authors investigated the possibility to incorporate methionine (Met) analogues in a Met

• interesting applications in plant biology. Olefin metathesis is also used to cross-link peptide fragments. This technology is known as peptide stapling [92]. Blackwell et al. engineered the first stapled peptide in 1998 by introducing two non-natural amino acids bearing a terminal alkene in a peptide sequence

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• Nicholas L. Reed Madeline I. Herman Vladimir P. Miltchev Tehshik P. Yoon Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States 10.3762/bjoc.15.30 Abstract Oxidative alkene difunctionalization reactions are important in synthetic

• organic chemistry because they can install polar functional groups onto simple non-polar alkene moieties. Many of the most common methods for these reactions rely upon the reactivity of pre-oxidized electrophilic heteroatom donors that can often be unstable, explosive, or difficult to handle. Herein, we

• describe a method for alkene oxyamination and diamination that utilizes simple carbamate and urea groups as nucleophilic heteroatom donors. This method uses a tandem copper–photoredox catalyst system that is operationally convenient. The identity of the terminal oxidant is critical in these studies. Ag(I

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

• tetrasubstituted alkene 11c was obtained as a 67:33 mixture of geometric isomers (Scheme 9) [33][34]. The rearrangement of secondary cyclopropenylcarbinyl acetates 10d–g could be achieved in the presence of Amberlyst® 15 and led exclusively to the (E)-alkylidene(acetoxycyclopropanes) 11d–g (E/Z > 99:1) in good

• (55/55’ = 92:8) because of the preferential addition of hydrogen on the less hindered face of the trisubstituted alkene opposite to the trifluoroacetamide moiety. A reversal of face selectivity can be observed by performing a directed iridium(I)-catalyzed hydrogenation in the presence of Crabtree’s

• by Rh/C occurred on the less hindered face of the alkene and gave rise to cyclopropyl α-alkoxy ester 72 as a single detectable diastereomer. When Pd/C was used as the catalyst, cleavage of the PMB group took place concomitantly and the α-hydroxy ester 73 arising from addition of hydrogen on the less

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• substituted alkene, allowing the synthesis of 1,2-divinylcyclopropane 3k within the typical range of yields and cis/trans selectivities. Finally, 1,2,3-trisubstituted divinylcyclopropane 3l was prepared in 50% (cis/trans = 2.5:1) from cyclopropene 1a and (1E,3E)-1,4-diphenylbuta-1,3-diene through a

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• aldehyde (S)-18 prepared from O-benzyl-L-serine in three standard steps [53] was elongated by a two-carbon fragment employing a Wittig reaction to give Z-alkene 19. To introduce the next center of chirality of the required configuration a iodocyclocarbamation reaction was applied to give trans-oxazolidin-2