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

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• 4–6 were subjected to anomeric deacetylation (Scheme 6). Compound 5 provided 1-O-deacetylated product 49 by treatment with BnNH2 in THF. Since acetylated 4-fluoro-D-GlcNAc 1 under these conditions did not react cleanly, we used piperidine-promoted [60] deacetylation to prepare 2 in 74% yield

• . Similarly, acetylated 4-fluoro-D-GalNAc 4 gave 50 in 60% yield. The attempted anomeric deacetylation of 3-fluoro-D-GalNAc 6 by treatment with piperidine followed by chromatography gave a fraction containing an inseparable side-product in addition to the expected deacetylated product 51. The side-product

• showed no fluorine resonance in 19F NMR and its molecular formula C17H28N2O7 assigned by LC–HRMS corresponded to a formal displacement of fluorine by piperidine, leading probably to compound 53. When pure 51 (prepared by another method, see below) was reacted with excess piperidine, high resolution ESIMS

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• , piperazine ranks among the top three N-heterocycles along with pyridine and piperidine in the U.S. FDA-approved pharmaceuticals [2]. Due to its broad utilization, piperazine has been considered as a privileged scaffold in drug discovery to combat various human diseases (Figure 1). For example, Imatinib (also

• -studied pyrrolidine and piperidine systems, the existence of the second ring-bound nitrogen in piperazines either causes various side reactions or inhibits or diminishes the reactivity of the C–H bond. This review summarizes the current status and challenges of direct C–H bond functionalization of

• atoms [30][31]. Corresponding enantioselective versions have also been developed using chiral diamines as ligands to allow access to enantioenriched α-substituted nitrogen heterocycles. However, most of the success has been made in the territory of N-Boc-pyrrolidine [32][33] and N-Boc-piperidine [34][35

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• 3). The presence of the ligand was essential and the choice of other amines such as tetramethylethylendiamine (TMEDA) (Table 1, entry 4) or piperidine-2-carboxylate did not lead to product formation (Table 1, entry 5). However, (rac)-trans-N,N-dimethyl-1,2-cyclohexanediamine (17) [9] in combination

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• problem was successfully addressed by using a hindered base, pentamethyl piperidine, which was inert towards the products (Scheme 24) [40]. In 2013, Ye disclosed a remarkable NHC-catalysed enantioselective aza-benzoin reaction of enals and activated ketimines leading to the formation of functionalised α

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• chemistry approach involving the copper azide-alkyne-catalyzed cycloaddition (CuAAC) between suitable scaffolds bearing terminal alkyne moieties and an azido-functionalized piperidine as the bioactive moiety. A preliminary biological investigation is also reported towards commercially available and human

• glycosidases. Keywords: dendrimers; glycosidase inhibitors; iminosugars; multivalency; piperidine alkaloids; Introduction Iminosugars are well-known naturally occurring glycomimetics with a nitrogen atom replacing the endocyclic oxygen, mainly recognized as inhibitors of carbohydrate-processing enzymes

• Pd(OH)2/C in MeOH followed by reductive amination of the formed dialdehyde intermediate with 3-azidopropyl-1-amine [34] in the presence of NaBH3CN and AcOH allowed access to N-alkylated piperidine 4 in 67% yield (Scheme 2) [25]. With the key azido intermediate 4 in hands, we proceeded with the

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• quinuclidine moiety in catalyst 4 and the piperidine scaffold in catalyst 6) are the key parameters influencing this different arrangement for the nitroacetate pronucleophile [27]. Conclusion We have developed an asymmetric catalytic diastereodivergent route for the synthesis of 2,4-dinitro esters taking