Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• ]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively through a hydroboration–oxidation reaction proceeding from the less hindered

• site providing a trans relationship between the hydroxy and the phosphine substituents. Keywords: isopinocamphone; monoterpenes; phosphines; [2,3]-sigmatropic rearrangement; verbanone; Introduction Chiral phosphorus compounds, despite many years of research, still enjoy unflagging interest of many

• phosphine oxide P–H nucleophiles were also realized [15]. The phosphine oxide group can also be introduced starting from allylic alcohols employing the rearrangement of allylic diphenylphosphinites to allylphosphine oxides [16][17]. Recently, we have shown the synthesis and applications of chiral PHOX

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• -electrochemical) mechanism (1a → 1a•− → 2a•− → 2a2− → 2a•− → 2a) in which the dienone portion of the molecule accepted the first electron, followed by a radical anion rearrangement to the long-wavelength isomer, whose radical anion is so much easier to reduce that it immediately accepts a second electron at this

• potential; on the oxidative return wave the subsequent oxidations of the LW dianion to its radical anion and then its neutral state are observed. Thus, in this unusual system, electrochromism proceeds by the same sort of spirocyclic ring-opening as the photochromic rearrangement but occurs from the radical

• , possibly indicating a large overpotential for the oxidation of 5a2−. It is possible that 3a undergoes only a one-electron reduction and rearrangement of 3a → 3a•−→ 5a•− (without further reduction to 5a2−) and subsequently only one oxidation to 5a. But this would make the second one-electron reduction

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• rearrangement. Hong and Tantillo performed the first theoretical study of the reaction mechanism in CotB2 via gas phase density functional theory (DFT) calculations [33]. Simultaneously, Sato et al. also studied the CotB2 reaction mechanism in the gas phase using DFT, combined with experimental deuterium

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• the use in multimodal (PET/OI) medical imaging of mitochondria in cancerous cells. Results: A dihalogenated fluorinatable pyridinyl rhodamine could be successfully synthesized with the high yield of 85% by application of a halogen dance (HD) rearrangement. The near-infrared dye shows a quantum yield

• silicon rhodamine scaffold, we considered using a halogen dance (HD) reaction of 3-bromo-2-chloropyridine (19) to 18 followed by a condensation with silicon xanthone 17, which is accessible in two steps from 3-bromo-N,N-dimethylaniline. The rearrangement of halo pyridine 19, initiated by a halogen metal

• exchange with n-BuLi, was initially published and investigated by Mallet et al. who also investigated and termed the mechanism “homotransmetallation” [47]. The HD rearrangement reaction in general is an excellent method for the construction of highly substituted carbo- and heterocyclic systems (e.g

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• starting material. Next, we tried to trigger the cyclization through a [2 + 2] cycloaddition followed by vinyl cyclobutane rearrangement [19][20]. We reasoned that the initially formed divinyl cyclobutane [21] should undergo an allylic rearrangement to furnish the decalin system [22][23]. Condensation

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Aggregation-induced emission effect on turn-off fluorescent switching of a photochromic diarylethene

• Luna Kono,
• Yuma Nakagawa,
• Ayako Fujimoto,
• Ryo Nishimura,
• Yohei Hattori,
• Toshiki Mutai,
• Nobuhiro Yasuda,
• Kenichi Koizumi,
• Satoshi Yokojima,
• Shinichiro Nakamura and
• Kingo Uchida

Beilstein J. Org. Chem. 2019, 15, 2204–2212, doi:10.3762/bjoc.15.217

• the color changed to yellow, and the intensity was enhanced (Figure 6b). Such a blue shift of ESIPT fluorescence was already reported and it is ascribed to suppression of the stabilization of the excited zwitterionic species through solvent rearrangement and/or further conformational changes of the

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• ]. However, an alternate mechanism was proposed by Paddon-Row and Warraner [74], whereby an initial [6 + 4] cycloaddition of tropone [6π] to fulvene [4π] and subsequent Cope rearrangement produced the formal [6 + 4] adduct. More recently, Yu et al. demonstrated through computations that the initial

• cycloaddition proceeds through an ambimodal [6 + 4]/[4 + 6] transition state leading to both of the proposed [6 + 4] adducts, which can interconvert through a Cope rearrangement (Scheme 6) [107]. Dimerisation cycloadditions Generally, dimerization of fulvenes is an undesired process that may occur upon storage

• (3b’ and 6b’) and anti-aromatic (4a’ and 5a’) ring currents. Reaction of 6,6-dimethylpentafulvene with singlet state oxygen to form an enol lactone via the multistep rearrangement proposed by Harada et al. (supporting information was not provided) [51]. Photosensitized oxygenation of 8

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

• trifluoroacetate 60 by a known electrophilic substitution procedure that was developed by Tahara and co-workers [64]. Curtius rearrangement of 60 gave an isocyanate intermediate, which was reduced with LiAlH4 followed by reductive amination affording tertiary amine intermediate 61. Oxidation of 61 to its

• butenolide 70. The second one is the reaction of alicyclic alcohol 73 with dimethylformamide dimethylacetal to give an allylic amide by means of a [2,3]-sigmatropic rearrangement of a carbene intermediate. Epoxidation the allylic amide with m-CPBA gave 74, followed by lithium hexamethyldisilazide-induced β

• , which could readily be converted to triptolide and its relatives such as triptophenolid, tripdiolide, and 16-hydroxytriptolide via palladium-catalyzed cross-coupling or Claisen rearrangement reactions. Importantly, by modification of the C-2,C3 olefin and late-stage installation of the C-13 isopropyl

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• spectrum of genuine (d0) and deuterium-labeled (d8) calamenene (isomer) as well as α-calacorene. Biosynthesis of sesquiterpene hydrocarbons via germacrene A Faraldos et al. showed that β-elemene is formed by Cope rearrangement when a solution of germacrene A in toluene is heated at reflux [36]. The

• . explaining the conversion of γ-terpinene to p-cymene [38]. May described the formation of δ-elemene from germacrene C via Cope rearrangement [32]. Considering that high temperatures are required for this reaction, our results also indicate that δ-elemene may be formed from germacrene C. The mechanisms

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• in the following ring rearrangement reactions. Phase III: ring rearrangements While C23 is still static in phase III, C20 is relatively flexible, which might serve to decrease the affinity for the enzyme’s binding pocket. Interestingly, although different types of ring rearrangement reactions occur

• during the first half of the cyclization cascade, indicating that they could be determinants of the affinity for the enzyme cavity of sesterterpene synthase. Interestingly, inherent mobility shows the same trend in phase I (5/12/5 tricycle formation) and phase III (ring rearrangement), but not in phase

• and the X axis shows the coordinate in the heat map. The right structural heat map shows the total mobility. Red means high mobility, yellow means moderate mobility, and blue means static. TS: transition state. Energy diagram and heat map analysis of ring rearrangement (A) IM6e–IM11 in quiannulatene

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• [6][7], anhydrides [8], esters [9], and acyl azides [10] with amines by employing coupling reagents [11]. Alternative protocols include the Staudinger–Vilarrasa reaction [12], Schmidt reaction [13][14], Beckmann rearrangement [15], aminocarbonylation of aryl halides [16], Staudinger ligation [17

• ], rearrangement of aldoximes [18], hydration of nitriles [19], dehydrogenative coupling of primary alcohols with amines [20][21] and hydration of organonitriles to amides [22][23][24]. However, these traditional methods have certain disadvantages such as generation of toxic chemical waste, involvement of tedious

• intermediate A. The attack of the ortho-position of the pyridinium moiety by the nucleophilic oxygen of intermediate A is then proposed to generate cyclic oxazolopyridine intermediate B [42][43]. The intermediate B then undergoes a rearrangement to afford N-alkylated benzamide 3 via a C–C bond cleavage with

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

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

• substituents on the 1-position. These substrates all solvolyze in CD3CO2D to give products derived from cyclopropylcarbinyl cations that undergo further rearrangement to give 3-trimethylsilylcyclobutyl cations. These 3-trimethylsilylcyclobutyl cations are stabilized by a long-range rear lobe interaction with

• ; rearrangement; silicon; Introduction Carbocations, positively charged trivalent carbon compounds and reactive intermediates, have continued to fascinate chemists since the early discoveries of tropylium [1][2] and trityl [3][4][5][6][7] salts. Many of the giants of organic chemistry during the last century

• an electron-donating group and E is an electron-withdrawing group, have now been examined. The goal was to evaluate the cyclopropylcarbinyl to cyclobutyl cation rearrangement. Can these substrates lead to γ-trimethylsilyl-substituted cyclobutyl cations 11 and what are the fates of such carbocations

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

• which underwent resonance to give 94. This was followed by intramolecular amination, oxidative dehydrogenation, and rearrangement to yield the final product 37 (Scheme 31). A one-pot, tandem reaction promoted by a I2/CuO system to synthesize imidazo[1,2-a]pyridines was reported by Cai et al. (Scheme 32

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• rearrangement has been developed using a chiral Brønsted acid based on pentacarboxycyclopentadiene (PCCP). This reaction provides rapid access to valuable chiral 4-amino-2-cyclopentenone building blocks from readily available starting material and is operationally simple. Keywords: aza-Piancatelli; Brønsted

• rearrangement (Figure 1). Analogous to the Nazarov cyclization, controlling the absolute stereochemistry can be achieved by governing the direction of the conrotatory electrocyclization, clockwise vs counterclockwise [32][33][34]. Despite the direct relationship to the asymmetric Nazarov cyclization, however

• , it was not until 2016 that the first asymmetric aza-Piancatelli reaction was described. To control the absolute stereochemistry of the aza-Piancatelli rearrangement, Rueping [35], Sun [36], and Patil [37] independently demonstrated that chiral phosphoric acids can be used as an enantioselectivity

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• synthesized in a similar manner. The presence of a NO2 group in the starting hydrazinylpyridine induces a Dimroth-type rearrangement leading to 2-methylphosphonylated [1,2,4]triazolo[1,5-a]pyridines. Keywords: cyclization; fused-ring systems; nitrogen heterocycles; phosphorylation; rearrangement

• -type rearrangement, which is facilitated by the acceptor nitro group in the pyridine ring (Scheme 3) [17][18]. The reaction of 2-hydrazinyl-3-nitropyridine (1i) with dimethyl and diisopropyl chloroethynylphosphonates 2a and 2b proceeded selectively to furnish only [1,2,4]triazolo[1,5-a]pyridines 11

• -promoted Dimroth rearrangement has been previously reported by Potts et al. [19]. In contrast, the reaction of 2-hydrazinyl-5-nitropyridine (1j) with chloroethynylphosphonates at a temperature of 60 °C for 50 hours led to the formation of a mixture of isomers 10 and 12 in a ratio of ≈1:1. Boiling the

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

• considered (Scheme 10). The required catalytic amount of such superacid may be formed due to the presence of traces of HCl (byproduct in acetylene–allene rearrangement step) in the reaction mixture. Next, the protonaton of complex 13 occurs, leading to allylic cation 22. As analogue of cation 16 (Scheme 9

Cyclobutane dication, (CH₂)₄²⁺: a model for a two-electron four-center (2e-4c) Woodward–Hoffmann frozen transition state

• G. K. Surya Prakash and
• Golam Rasul

Beilstein J. Org. Chem. 2019, 15, 1475–1479, doi:10.3762/bjoc.15.148

• aromaticity. The four bridge-head p-orbitals overlap inward in a tetrahedral fashion involving two electrons. We have now extended our study to obtain information on the structure, stabilities and possible rearrangement pathways of the elusive cyclobutane dication. The species is an example of the simplest

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• rearrangement of the so-formed alkynyloxiranyl borates. This stereospecific process overall transfers the cis or trans-stereochemistry of the starting alkynyloxiranes to the resulting 1,3-enynes. Keywords: boron; enyne; lithium; oxirane; rearrangement; Introduction Lithiated oxiranes are useful intermediates

• tetrasubstituted alkenes [6][7]. Capitalizing on these precedents, Aggarwal et al. showed that oxiranes could be homologated to diols through lithiation, borylation, rearrangement and oxidation of the so-formed β-hydroxyboranes [8]. More recently, Blakemore et al. applied this sequence to sulfinyloxiranes [9

• Shimizu [6][7], and our experience on the metalation of alkynyloxiranes and reactivity studies of the so-formed alkynyloxirane anions [12][13], we explored the reaction of such anions with various boron derivatives in order to produce stereodefined α-enynes after Matteson-type rearrangement [14] and

Selective detection of DABCO using a supramolecular interconversion as fluorescence reporter

• Indrajit Paul,
• Debabrata Samanta,
• Sudhakar Gaikwad and
• Michael Schmittel

Beilstein J. Org. Chem. 2019, 15, 1371–1378, doi:10.3762/bjoc.15.137

• 1H DOSY confirms the successful rearrangement. To probe the selectivity of the guest-induced transformation of 5, the structure interconversion was tested with other potential guests, using fluorescence and 1H NMR spectroscopy. In the absence of any external ligand, the rectangle 5 shows its typical

• , DABCO is a highly selective trigger for the structural rearrangement of rectangle 5 to sandwich complex 6. Finally, we tested the reversibility of the system by addition and removal of DABCO using rhodium porphyrin 3 as scavenger of DABCO. In line with the results of the model self-sorting scenarios in

• quite strained and structurally distorted to a spiral shape (Supporting Information File 1, Figures S31 and S32). Conclusion In conclusion we demonstrated three cycles of the fully reversible DABCO-induced structural rearrangement between multicomponent architectures 5 and 6. The multiple, clean and

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• our compound 5. The formation of compound 8 can be explained by the rearrangement of 7 through a hydrogen-shift to form the diazo intermediate 9 which underwent a concerted [2 + 3] intramolecular cyclisation to 3,3-diphenyl-3H-indazole 8 (Scheme 2). The process was facilitated by the presence of a

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• developed for the synthesis of 2,3-unsaturated C-, O-, N- and S-linked glycosides (enosides) using 20 mol % perflurophenylboronic acid catalyst via Ferrier rearrangement. Using this protocol, D-glucals and L-rhamnals reacted with various C-, O-, N- and S-nucleophiles to give a wide range of glycosides in up

• to 98% yields with mainly α-anomeric selectivity. The perflurophenylboronic acid successfully catalyzed a wide range of substrates (both glucals and nucleophiles) under very mild reaction conditions. Keywords: C-; O-; N- and S-linked glycosides; enosides; Ferrier-rearrangement; organocatalyst

• ]. The Ferrier rearrangement is one of the most useful processes to synthesize pseudo-glycosides in a direct and stereoselective fashion. Several classes of catalysts have been successfully applied in the Ferrier rearrangement including Brønsted acids [7][8][9][10][11][12][13], Lewis acids [14][15][16

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• –Stevens-derived diazoesters 23 and 27, respectively. Only triethylsilyl-protected diazoester 27 proved viable to deliver a diazoketone 28. The latter underwent stereoselective carbonyl ylide formation–cycloaddition with methyl glyoxylate and acid-catalysed rearrangement of the resulting cycloadduct 29, to

• glyoxylate (3 → 4 → 5) [14][15], followed by an acid-catalysed rearrangement to generate the desired dideoxysqualestatin core 6 with the requisite tricarboxylate functionality installed. While we had earlier established the viability of this approach in a racemic model study (X = H) [14], extension to an

• (2). Natural product examples containing the monoalkylated tartaric acid motif. Carbonyl ylide cycloaddition–rearrangement to the squalestatin core [12][13]. Tartrate alkylation strategy to cycloaddition substrate. Conversion of α-ketoester to α-diazoester. Seebach’s tartrate alkylation and

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

• undergoing two decarboxylation to give 5a. This type of thermal 1,3-oxygen-to-carbon rearrangement was already described by Trost in the early 80’s [48][49]. In view of the high temperature needed (130 °C for several hours or under microwave irradiation), this decarboxylative rearrangement appears to require

• -forming annulations with dimethyl 3-oxoglutarate (1a). C–C/C–O bond-forming annulations with various bis-nucleophiles. Decarboxylative rearrangement of 4a into 5a. Proposed mechanism for the Pd-catalyzed part of the [3 + 2] annulation reaction. Proposed mechanism for the temperature dependent cyclization

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

• several additional experiments, the authors propose a tentative mechanism based on a Pummerer-type rearrangement. First, dimethyl sulfoxide (3) and carboxylic acid 1 combine to render ester 5 that decomposes, giving a thionium derivative of DMSO (6, Scheme 1). This electrophilic derivative would react

• rearrangement that would lead to isoindolinone 46 through the bridged intermediate 51. Therefore, this mechanistic path shows that the enantioselectivity of the reaction is a consequence of a dynamic kinetic resolution of enamine 50. Cyanide can also be used, instead of isocyanide, in an analogous three

• oxidation of this radical would give rise to the corresponding cation 74, which would add to the nucleophilic nitrile 70. Intramolecular nucleophilic attack of the carboxy group in 75 followed by rearrangement of intermediate 76 delivered isoindolinone derivatives 71. Ortho-functionalized benzoic acids have