Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• -type amine–isothiocyanate coupling reaction (Scheme 4). In the case of secondary amines (piperidine, morpholine and thiomorpholine) and sterically hindered amines (2,4- and 2,6-dimethylanilines), ball milling again resulted in ≥99% yields in 10 minutes, except for the reactions involving 4

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• transformation proved relatively ineffective for alkylcarboxyindolium salts 3 and consequently, we applied alternative conditions using MEK and piperidine [27]. This two-step approach was used to synthesise a range of N-alkylcarboxyspiropyrans derived from bromoalkanoic acids of varying chain length in two-step

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• 6 (3.0 mmol) and silica gel-supported piperidine (SiO2-Pip; 200 mg, 0.22 mmol) were added. The electrolysis was carried out under stirring at a current density of 0.3 A/dm2 at 0 °C until a 2.7–3.75 F/mol charge had passed. Solid SiO2-Pip was filtered off, methanol was evaporated under reduced

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• , 12 h, quant.; b) Fmoc-OSu, NaHCO3, 1,4-dioxane, H2O, 0 °C to rt, 87%; c) 1: O3, DCM, –78 °C, 2: Zn, HOAc, –78 °C to 10 °C, 66%; d) allylmagnesium chloride, 15, Et2O, –78 °C, 84%, 94% ee; e) MOMCl, DIPEA, DCM 0 °C to rt; f) piperidine, DCM, rt; g) 14, NEt3, DCM, 49% (over 3 steps); h) 1: O3, DCM, –78

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• component (Figure 1). Changing the phenylacetylene to other substituted arylacetylenes like p-tolylacetylene, o-bromophenylacetylene, p-bromophenylacetylene or switching from morpholine to other amines like piperidine, 4-benzylpiperidine and pyrrolidine also react smoothly to afford the corresponding

• 80–90 °C (Figure 1, 3k–p). Varying the secondary amine component with 4-benzylpiperidine, piperidine also worked efficiently to produce the corresponding propargylamine derivatives (3q–t). All products were characterized by FTIR, 1H and 13C NMR spectral data. Scaling up the reaction to gram-scale

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

• Knoevenagel olefinations, followed by a Nazarov cyclization using FeCl3 or AlCl3. The 2-phosphorylated chalcones (Z)-145 and non-phosphorylated ones (E)-146 could be obtained from the same substrates, β-ketophosphonates 143 and aromatic aldehydes 144 depending on the reaction conditions used (piperidine

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• ). For this reaction, self-optimisation is important as multiple products were identified that could form in parallel; from 1 the possible products we expected to see were a mixture of piperidine (2a), N-methylpiperidine (2b), N- and O-methylated 1, as well as oligomers. We chose to target 2b only for

• several different alcohols by flowing a starting mixture of 1 with the alcohol as the solvent (Table 2, entries 2–4). As might be expected, the cyclisation to N-alkylated piperidines was observed for the primary alcohols. The yield of the corresponding N-alkylated piperidine falls as the longer chain

• alcohols are reacted. When the secondary alcohol isopropanol was used as the solvent, no N-alkylation was observed and piperidine 2a was found as the major product. As this catalyst system has been used previously for the etherification of alcohols [31][32][33][34][35][36][37][38], it is possible that

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• electronegativity of the R group is probably also important; when more electropositive (as Si), the oxygen atoms become more electron rich and their repulsion becomes larger. Changing the conformation of a heterocycle has, as mentioned, been studied using the piperidine model system. The pKa of the corresponding

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

• conformational rigidity that results in a better alignment of alpha C–H groups, relatively high polarization of the alpha C–H bonds due to the presence of electron-withdrawing ester functionalities, and ease of preparation (1–2 steps from commercially available piperidine). Interestingly, the authors assessed

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• C26H32N3O4, 450.2393; found, 450.2422. (1RS,4'RS)-2'-Benzyl-2-butyl-4'-(piperidine-1-carbonyl)spiro[isoindoline-1,5'-isoxazolidin]-3-one (6d): White sticky oil (Yield: 45 mg, 35%); IR (neat) νmax: 1684, 1631 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.73–7.69 (m, 1H), 7.54–7.43 (m, 3H), 7.37–7.34 (m, 2H), 7.33–7.26 (m

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• piperidine or a pyrrolidine-based precursor, with few reports of alternative approaches. The approach adopted by our research group to the synthesis of these and related bicyclic alkaloids takes advantage of enaminone chemistry [10][11][12][13][14][15][16][17][18][19]. Our interest in the enaminone manifold

• approach most commonly comprise a nitrogen atom in a pyrrolidine or piperidine ring conjugated at C-2 through an exocyclic vinyl fragment to an ester (vinylogous urethane) or another electron-withdrawing substituent (usually ketone, nitrile, nitro or sulfone). When suitable carbon chains bearing terminal

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• showed a Tc of 248 K with a ΔG# of 11.1 kJ/mol [23] whereas piperidine shows a higher ΔG# of 42.3 and N-methylpiperidine a ΔG# = 49.8 kJ/mol [21][28]. X-ray structure analyses of 3a and 4b Single crystals of 3a and 4b were obtained and their molecular structures determined using single crystal X-ray

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• ) with respect to the resin and two hour double couplings. A mixture of DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) and piperidine (2% each) in DMF was used for Fmoc-deprotection (3 × 10 min). The resin was washed between each step with DMF and DCM (3 × 6 mL each). Peptides were cleaved from the resin by

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

• , there are no documented literature examples of constructing cyclohexanone by assembly of three fragments. For comparison we also show a similar nucleophilic–electrophilic centre analysis for the synthesis of piperidine by 2- and 3-partitions in Figures S2 and S3, whose structure is also made up of a six

• patterns for cyclohexanone are the inverse of those for piperidine. The same observation is made when the patterns for cyclopentanone and pyrrolidine are compared. We may conclude that the fewer nucleophilic or electrophilic centres exist in a ring, the more bonding possibilities there are to consider for

• + 2] coupling strategies to synthesize cyclohexanone; Figure S1 to S7 showing nucleophilic-electrophilic centre labels on 3-partition fragment possibilities for cyclohexanone, 2- and 3-partition fragment possibilities for piperidine, 2- and 3- partition fragment possibilities for cyclopentanone, and 2

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

• 102 residue proceeded smoothly giving resin bound peptide 106. Brief (30 seconds) treatment of 106 with piperidine afforded the desired deprotected product, enabling coupling of the final amino acid. Extended exposure of peptide 106 to piperidine led to de-esterification. Final Fmoc removal of 107 and

Thiophene-forming one-pot synthesis of three thienyl-bridged oligophenothiazines and their electronic properties

• Dominik Urselmann,
• Konstantin Deilhof,
• Bernhard Mayer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2016, 12, 2055–2064, doi:10.3762/bjoc.12.194

• , 0.08 mmol), CuI (15.0 mg, 0.08 mmol), PPh3 (21 mg, 0.08 mmol), (trimethylsilyl)acetylene (0.56 mL, 2.00 mmol), and piperidine (5.00 mL, 50.4 mmol) were added. The closed vessel under nitrogen was heated at 55 °C (oil bath) for 16 h. Next, TBAF·3H2O (631 mg, 2.00 mmol) was added and the vessel open to

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• quantitative yield by subjection 7 to a saturated solution of NH3 in MeOH (7 N) (Scheme 2). In addition to the monomeric glycoconjugates 1a–d and 2a–d we also prepared dimer 4 from the glucose containing conjugate 2a and the N-acetylglucosamine containing conjugate 1c. Treatment of 1c with 20% piperidine in

Effect of the π-conjugation length on the properties and photovoltaic performance of A–π–D–π–A type oligothiophenes with a 4,8-bis(thienyl)benzo[1,2-b:4,5-b′]dithiophene core

• Ni Yin,
• Lilei Wang,
• Yi Lin,
• Jinduo Yi,
• Lingpeng Yan,
• Junyan Dou,
• Hai-Bo Yang,
• Xin Zhao and
• Chang-Qi Ma

Beilstein J. Org. Chem. 2016, 12, 1788–1797, doi:10.3762/bjoc.12.169

• ) [Pd2(dba)3]·CHCl3, HP(t-Bu)3BF4, K2CO3, THF; ii) 1. n-BuLi/THF, 2. 2-isopropyloxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane; iii) ICl/THF; iv) Pd(PPh3)4, DMF, 80 °C; v) octyl cyanoacetate, piperidine, CHCl3, reflux. Optical and electrochemical properties of 1–4 in comparison to other compounds in the

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• through the one-pot reaction of phosphonodithioacetate 165, aromatic aldehydes 166 and dienophiles 167 in the presence of piperidine in refluxing toluene (Scheme 36) [74]. The new phosphorylated cycloadducts were isolated in excellent yields and with a trans- or cis-diastereoselectivity. 4 Metal-catalyzed

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• residue required for AviCys formation derives from cysteine rather than serine. Pyridine and piperidine formation in thiopeptides Thiopeptides are a widespread bacterial RiPP family that are characterised by multiple thiazoles, dehydrated residues and a central substituted pyridine, dehydropiperidine or

• piperidine ring [69] (Figure 6A). Micrococcin was the first member to be identified [70], while the most well-studied member of the class is thiostrepton [71], whose gene cluster was the first of this class to be reported [72][73], along with the thiocillin and siomycin A gene clusters [73][74]. Thiopeptides

• , dehydropiperidine or piperidine is consistent with a [4 + 2] cycloaddition across two dehydrated serine residues [79][80]. Genetic disruption of tclM from the thiocillin pathway showed that TclM was responsible for this transformation [81], although the precise cyclisation mechanism (concerted or stepwise) could

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• particularly suited for the construction of the [4.1.0] bicyclic piperidine core of GSK1360707 [27], a triple-uptake inhibitor developed by GlaxoSmithKline [28][29] (Scheme 2c). The construction of this interesting molecular scaffold was a motivator of much of our early work on the ruthenium-catalyzed redox

• amide to the Lewis acidic ruthenium center (Table 5, entry 7). Gratifyingly, utilizing the bulkier 2,4,6-triisopropylbenzenesulfonyl group (Tris) significantly improved the er of protected piperidine 35 to 15.0:85.0. Because of its differential impact on selectivity, this protecting group was pursued

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• pronucleophile to a substituted furanyl nitroolefin catalysed by a bifunctional cinchonine-derived thiourea has been used as the key stereocontrolling step in a new synthetic strategy to the heavily functionalised piperidine core of keramaphidin B. Keywords: bifunctional organocatalyst; enantioselective Michael

• wish to report our preliminary synthetic efforts towards the stereoselective synthesis of the heavily functionalised piperidine core of keramaphidin B (1). Results and Discussion Our overall synthetic strategy is presented in Figure 2. We envisaged that a late stage alkyne RCM reaction of 2 and cis

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• > piperidine (Table 5, entries 1–4). These results suggest that a larger N,N-dialkylamino group leads to a decreased antibacterial activity, with compound 5c showing an unexpectedly high MIC value in comparison to the other three compounds of this group. Having established this, we synthesized diethylamino

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• azomethine ylides generated in situ from the corresponding amines and aldehydes, affording the piperidine-fused spirooxindole frameworks in high yields (up to 93% yield) and with excellent enantioselectivities (>99% ee), albeit with moderate diastereoselectivities (Scheme 54) [71]. Similarly, the same group

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• presence of an attached ring as in 48, the 1,6-insertion produced the bridged-bicyclic product 49 (Scheme 11) [66]. The Compain group leveraged this innovation in the synthesis of functionalized piperidines (Scheme 12) [67]. By using the piperidine 50, an initial insertion into the amine-activated C–H bond

• generated the tosylamine-bridged bicycle 51. The aminal in 51 could be transformed to a methyl hemiaminal, and then later a second C–H bond insertion by another nitrene targeted the less activated C–H bond to form the ring-fused piperidine 52. Thus, the pendant sulfonamide acted as a tool for multiple

• remote functionalizations on the piperidine ring. Many examples of the sequence with different piperidines were also reported. The resulting 3-amino-2,6-disubstituted piperidines like 52 are known to display anti-allergic and anti-inflammatory activities. Rao generated a bridged polycycle via a formal C