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

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• affecting the sensitive caryophyllene-like subunit, the methoxy group was replaced with a phenylseleno moiety, which was converted to the alcohol and finally oxidized to lactone 73. In three further steps, lactone 73 was converted to aldehyde ester 74, which upon treatment with piperidine gave a β-enamino

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• piperidine in toluene at 0.5 mL/min. Due to the high volatility of N-chloropiperidine the product was not isolated and was instead obtained as a solution in toluene (0.94 M, 94%) by separation of the organic phase from the aqueous phase of the reaction solution. The yield of product was determined by NMR

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• this method by isolating the RCM product of the ROM–CM byproduct 290, which was recovered in the ROM–RCM–CM cascade (Scheme 62). Kouklovsky and co-workers [62] have described a stereoselective synthesis of 2-(2-hydroxyalkyl)piperidine alkaloids by employing a RRM of NDA adduct 293. The required

An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

• Sundaravel Vivek Kumar,
• Shanmugam Muthusubramanian,
• J. Carlos Menéndez and
• Subbu Perumal

Beilstein J. Org. Chem. 2015, 11, 1707–1712, doi:10.3762/bjoc.11.185

• , entry 5), pyridine (Table 1, entry 6), N,N-dimethylaminopyridine (DMAP, Table 1, entry 7), piperidine (Table 1, entry 8), L-proline (Table 1, entry 9), potassium carbonate (Table 1, entry 10), sodium carbonate (Table 1, entry 11) and caesium carbonate (Table 1, entry 12). After identifying potassium

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• effect [89]. Piperidinic phosphonates derivatives also showed the same enzyme inhibition (Figure 18) [90] and the only chemical resemblance with pyridoacridines is the piperidine ring. Since piperidine is related to pyridine, the dihydropyridone (C) and the pyridine (E) rings in the structure of 99 could

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• case of benzylic amines and piperidine, but aliphatic amines and aniline exhibited poor reactivity. Carboxylic acids are available in great variety from natural and industrial sources. Green synthetic methods based around them as starting materials are undoubtedly worthy of development. That simple

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• ), [27] and this motif is also critical to the activity of drugs like ketamine and phencyclidine (1-(1-phenylcyclohexyl)piperidine, PCP) [28]. Tetrasubstituted carbons bearing amines can provide much higher levels of activity than the corresponding trisubstituted center. For example, fentanyl is an

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• ]. The conjugates NAS were produced by a combination of SPPS and liquid phase synthesis. Scheme 2 shows a representative synthesis route of a NAS conjugate (1). We loaded the first amino acid, Fmoc-Val-OH, on 2-chlorotrityl chloride resin, then removed the Fmoc group with 20% piperidine in

• solid-phase peptide synthesis and liquid-phase synthesis). i) Fmoc-Val-OH, DIPEA; ii) 20% piperidine; iii) Fmoc-Pro-OH, HBTU, DIPEA; iv) Fmoc-Thr(t-Bu)-OH, HBTU, DIPEA; v) thymine-1-acetic acid, HBTU, DIPEA; vi) TFE/DCM 2:8; vii) D-glucosamine hydrochloride, HBTU, DIPEA; viii) TFA/H2O 95:5

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• , 109 [53][54]. The signals at m/z 124, and 109 are abundant. The signal at m/z 154 was assigned to the structure, resulting from elimination of a XOH from the position 4 and 3 of the piperidine ring. The subsequent loss of a NO group (M = 30) and a CH3 group (M = 15), respectively, generates ions at m

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• . Conditions: (a) piperidine, PhCOOH, toluene, reflux 4 h; (b) NaBH4, MeOH/MeCN, rt, 3.5 h; (c) KOH, H2O, reflux, 8 h; (d) H2SO4, H2O, reflux, 20 h; (e) MeOH, SOCl2, reflux, 4 h; (f) Meldum’s acid, HCOOH, Et3N, 100 °C, 4 h. The synthesis of the starting β-enaminones. Conditions: (a) H2SO4, 65 °C, 46 h; (b) 1

Thiazole formation through a modified Gewald reaction

• Carl J. Mallia,
• Lukas Englert,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 875–883, doi:10.3762/bjoc.11.98

• , but generated complicated product mixtures allowing only a moderate isolated yield of 33% for the TMG and negligible recovery for the DBU (Table 1, entries 7 and 8). Interestingly, the use of piperidine led to no conversion under these reaction conditions (Table 1, entry 9), we believe this is due to

Self-assembly of heteroleptic dinuclear metallosupramolecular kites from multivalent ligands via social self-sorting

• Christian Benkhäuser and
• Arne Lützen

Beilstein J. Org. Chem. 2015, 11, 693–700, doi:10.3762/bjoc.11.79

• -bottomed flask was charged with 5-ethynyl-2,2’-bipyridine (11, 109 mg, 0.6 mmol, 2 equiv), 1,3-diiodobenzene (100 mg, 0.3 mmol), [Pd(PPh3)2Cl2] (5.32 mg, 2.5 mol %), and copper(I) iodide (1.44 mg, 2.5 mol %) and flushed with argon. Dry THF (15 mL) and dry piperidine (5 mL) were added and the resulting

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• : 45 bar H2, Pd/C (10%), MeOH sat. with NH3, 60 °C, 5 h, rt, overnight, 37%; f: Mukaiyama’s reagent, NEt3, DMF, 22 h, rt, 56%. Boc-ON: 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile. Synthesis of PNA conjugates. Conditions: a: 1) 9, HOBt, DIC, DMF, rt, 24 h; 2) piperidine, DMF, rt, 30 min; b: 1