Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• products that may be deprotected in situ to provide a new connective route to hindered amines. Keywords: carbamate; carbolithiation; carbometallation; organolithium; stereospecificity; styrene; urea; Introduction Enamines and N-acyl enamines are in general nucleophiles, reacting with electrophiles at the

• manipulated carbamate products bearing a standard Boc protecting group, providing they too could be carbolithiated and trapped without rearrangement. Related carbamates are reactive towards carbolithiation–rearrangement reactions [6]. Thus, Boc-protected carbamates 9–11 were synthesised by acylation of the

• imines 7 and 8 with di-tert-butyl dicarbonate or with (−)-menthylchloroformate (Scheme 4). The N-alkenylcarbamates 10 and 11 were formed exclusively as their E isomers, and the X-ray crystal structure of E-10 is shown in Figure 2. Vinyl carbamate 9 was treated with primary, secondary or tertiary

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• used to terminate polymers prepared by ring-opening metathesis polymerization of norbornenes bearing an activated ester. The terminating agent is a cis-butene derivative bearing a Teoc (2-trimethylsilylethyl carbamate) protected primary amine. Post-polymerization modification of the polymer was

• reaction as well as subsequent polymer modifications, and that can also be removed under mild conditions for the subsequent functionalization of an amine-terminated polymer. We report here the development of the terminating agent 3, which caps a ROMP-derived polymer with a 2-trimethylsilylethyl carbamate

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• bond with the correct stereochemistry and the introduction of the pendant isopropyl group present in the target. The intermediate cyclic carbamate 2 is not isolated but cleaved into aminoalcohol 3 to simplify purification. The conversion of aminoalcohol 3 into (–)-dendrobine (4), hinges on the use of

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• organometallic species (i.e., copper) with a polar functional group in the vicinity of the reactive center should be able to reverse the regioselectivity of the carbometallation, as we have shown for the carbocupration of ethynyl carbamate (XR = OCONR2, Path C, Scheme 1) [24]. Herein we describe our results for

• the carbocupration of an N-alkynylsulfonamide could be easily achieved, we were interested to see whether such a carbocupration reaction could be extended to ynamide 4 bearing an acyclic carbamate moiety. We were pleased to find that this reaction could also be performed on N-alkynylcarbamate 4 with

• carbamate moiety. Molecular structure of 9f (hydrogen atoms except of H9 and H10 are omitted for clarity). Possible regioisomers obtained in the carbocupration reaction of α-heterosubstituted acetylenes 1. Regioselective carbometallation of N-alkynylsulfonamide 2. Regioselective carbometallation of ynamide

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• reaction of chiral imines with enolates derived from Weinreb amides [13][14]. In previous work on the asymmetric synthesis of 2,6-disubstituted piperidines by C–N bond formation, we demonstrated that intramolecular aza-Michael ”type” cyclisation [15] using a β'-carbamate-α,β-unsaturated ketone

• preparation of chiral 2,6-disubstituted piperidines, we wish to report here a facile synthetic route to various β’-carbamate-α,β-unsaturated ketones in good overall yields and good enantioselectivities. Results and Discussion In a preliminary approach, preparation of β-amino ketones was envisaged through a

• ester moiety to a Weinreb amide [18] followed by changing the nitrogen protecting group to a carbamate furnished the key intermediate 6, which could be further alkylated with Grignard reagents to give β’-amino protected α,β-enone 1 in good overall yield and high enantiomeric excess. As Grignard reagents

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• alkynes generally gives the vicinal product 2D (copper locates at the β-position to the O or N) (Scheme 13, path A) [14][70][71][72][73]. On the other hand, the reversed regioselectivity was observed in the carbocupration of O-alkynyl carbamate and N-alkynyl carbamate, in which carbonyl groups worked as a

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• +] calcd for C28H30N4O6, 518.2165; found, 518.2178. Benzyl (((3S,6S,12aS)-3-methyl-2-(2-(methylamino)-2-oxoethyl)-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-6-yl)methyl)carbamate (1a): Compound 6 (165 mg, 0.32 mmol, 518 g/mol) was dissolved in EtOH (3 mL). Aqueous LiOH (0.5

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• by a different procedure [17]; MS m/z: 456.1 [M + H]+. 2-(2-(2-(2-(Diethoxyphosphoryl)ethoxy)ethoxy)ethoxy)ethyl (5-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)pentyl)carbamate (8): A solution of in situ synthesized 5-(biotinamido)pentaneamine, trifluoroacetic acid salt

• [M + H]+. 2-(2-(2-(2-(Ethoxy(hydroxy)phosphoryl)ethoxy)ethoxy)ethoxy)ethyl (5-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)pentyl)carbamate (9): A mixture of lithium azide (200 mg, 4.1 mmol), diethyl phosphonate polyether carbamate 8 (150 mg, 0.22 mmol), and 2 mL of DMF

• ,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)pentyl)carbamate (FP–PEG–biotin; 1): To a solution of monoethyl phosphonate polyether carbamate 9 (46 mg, 0.072 mmol) in 1 mL of anhydrous dichloromethane at −42 °C was added (diethylamino)sulfur trifluoride (DAST; 26.4 μL, 0.022 mmol). The

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• expense of another property, such as the rate of release [7]. For example, GABA caged directly as an ester with coumarin chromophores is photoreleased quickly, but is quite unstable in (frozen) solution [60]. However, when caged via a carbamate, its release is orders of magnitude slower, but the compounds

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• phthalimide in DMF at 90 °C, affording the corresponding N-allylphthalimide. Deprotection of the phthalimide by hydrazinolysis followed by protection of the resulting primary amine as a tert-butyl-carbamate gave the Boc-protected amine 13 required for the synthesis of the substrate of the anionic cyclization

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• the presence of NEt3 afforded a crude carbonate, which was smoothly reacted with amine 4 to provide carbamate 7 with 85% yield. Carbamate 7 was converted to the free acid 9 by simple protection to form THP ether 8 followed by saponification. Finally, coupling acid 9 with 4-sulfamoylbenzoic acid [15

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• products featuring a secondary amine at position C-1, compounds 24 and 25, were further reacted with triphosgene [25]. In this reaction, the anomeric hydroxy group and the amine at position C-1 formed a cyclic carbamate, thereby stabilising the hemiacetal at the anomeric position. Compounds 24 (a and b

• yield of 70%. No β-anomer formation could be observed from NMR analysis. Treatment of compound 29 with triphosgene and sodium carbonate in 1,4-dioxane and H2O gave 1-N-(hydroxyhexyl)amino-α-D-manno-1-N,2-O-carbamate 30 in 75% yield. With 6-aminohexanoic acid hydrochloride, the Amadori rearrangement

• , employing triethylamine for liberation of the free amine from the hydrochloride, gave a 90% yield of the α-anomer 31. Its treatment with triphosgene provided 1-N-2-O-cyclic carbamate 32 in 50% yield. 3-Acetamido-3-deoxy-D-gluco-D-ido/D-gulo-heptopyranose 22 (a and b) gave under Amadori rearrangement

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• . Residual solvent proton signals were used as an internal standard. Synthesis of compounds (S)-tert-Butyl(7-azido-1-diazo-2-oxoheptan-3-yl)carbamate. (S)-6-Azido-2-(tert-butoxycarbonylamino)hexanoic acid (7.38 g, 27.1 mmol, 1.00 equiv) was dissolved in dry THF (108 mL) under an argon atmosphere. The

• -oxoheptan-3-yl carbamate (2.67 g, 9.00 mmol, 1.00 equiv) in THF/H2O 9:1 (45.0 mL) under exclusion of light at −15 °C. The reaction solution was warmed to room temperature after 30 min and stirred for a further 12 h until completion. The solvent was removed under reduced pressure. The residue was dissolved

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

• Takuya Uno,
• Yusuke Kobayashi and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2012, 8, 1499–1504, doi:10.3762/bjoc.8.169

• , carbamate, and phenyl groups, were converted into the corresponding products 5l–o in good yields. The α-branched aldehyde, however, failed to give the desired product 5p, presumably due to the increased steric hindrance along with the inherently low electrophilicity. In order to elucidate the reaction

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• piperidine-based manifold 15 bearing an amino group in order to produce variations of branched precursors leading to distinct scaffolds (Scheme 5). The manifold 15 was readily prepared through Curtius rearrangement of 6 and subsequent removal of the resulting carbamate group. Ugi four-component condensation

Electrochemical generation of 2,3-oxazolidinone glycosyl triflates as an intermediate for stereoselective glycosylation

• Toshiki Nokami,
• Akito Shibuya,
• Yoshihiro Saigusa,
• Shino Manabe,
• Yukishige Ito and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2012, 8, 456–460, doi:10.3762/bjoc.8.52

• prepared by protecting the 2-amino group with phthaloyl or carbamate groups [6]. On the other hand, 1,2-cis glycosidic linkages are still difficult to make with perfect stereoselectivity. Although 2-azido-substituted glycosyl donors are commonly used for the preparation of 1,2-cis glycosidic linkages of

• often observed for pyranosides with a 2,3-trans carbamate group, under acidic conditions. The yield of disaccharide 8 was improved by raising the temperature to 0 °C after the completion of electrolysis at −78 °C (Table 3, entry 5). The fact that disaccharide 8 was obtained in higher yields (59% to 78

• %) and that only a trace amount of α-isomer 9 (4%) was obtained strongly suggests that the isomerization of thioglycoside donor 1a occurs during the electrolysis at 0 °C. It is noteworthy that the α- and β-glycosides could be selectively prepared from the same glycosyl donor with a 2,3-trans carbamate

Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

• Mohamed Abboud,
• Emmanuel Aubert and
• Victor Mamane

Beilstein J. Org. Chem. 2012, 8, 253–258, doi:10.3762/bjoc.8.26

• obtained in this reaction (Table 1, entries 1–6). Aniline 6g bearing an electron withdrawing trifluoromethyl group led to a low yield of 3g (Table 1, entry 7) whereas no cyclized product was observed with other electron-deficient anilines 6h–j and carbamate 7 (Figure 1). Other methods to react 7 with

Carbamate derivatives and sesquiterpenoids from the South China Sea gorgonian Melitodes squamata

• Li-Si Huang,
• Fei He,
• Hui Huang,
• Xiao-Yong Zhang and
• Shu-Hua Qi

Beilstein J. Org. Chem. 2012, 8, 170–176, doi:10.3762/bjoc.8.18

• Road, Guangzhou 510301 Guangdong, China Hainan Key Laboratory of Tropical Marine Biology and Technology, South China Sea Institute of Oceanology, The Chinese Academy of Sciences, 164 Xingangxi Road, Guangzhou 510301, China 10.3762/bjoc.8.18 Abstract Five carbamate derivatives, obtucarbamates C and D

• rarely found in marine natural compounds, and 7 showed moderate antibacterial activity. The possible biosynthesis routes of 1–5 were conjectured. Keywords: carbamate; gorgonian; Melitodes squamata; sesquiterpenoid; Introduction Gorgonians are recognized to mainly produce acetogenins, sesquiterpenoids

• the chemical constituents of the South China Sea gorgonian M. squamata, which led to the obtainment of five carbamate derivatives, obtucarbamates C and D (1, 2), ((carbonylbis(azanediyl))bis(2-methyl-5,1-phenylene))dicarbamate (3) [5], obtucarbamate A (4) [6], obtucarbamate B (5) [6], and four

Synthesis of highly functionalized β-aminocyclopentanecarboxylate stereoisomers by reductive ring opening reaction of isoxazolines

• Melinda Nonn,
• Loránd Kiss,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2012, 8, 100–106, doi:10.3762/bjoc.8.10

• carbamate side (cis to –NHBoc) of the cyclopentane skeleton. This was confirmed by X-ray analysis of 12. In order to increase the number of multifunctionalized amino ester stereoisomers, we next examined the reductions of isoxazoline-fused cispentacin and transpentacin stereoisomers (3–6) [49]. Reactions

• concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/EtOAc), giving the corresponding reduced product. tert-Butyl (3aR*,4R*,5R*,6aR*)-[5-(hydroxymethyl)-3-methyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazol-4-yl]carbamate (8): Light-yellow oil; yield

• *,6aR*)-[5-(hydroxymethyl)-3-methylhexahydro-2H-cyclopenta[d]isoxazol-4-yl]carbamate (9): Colorless oil; yield 12% (31 mg); Rf 0.29 (n-hexane/EtOAc); IR (KBr) ν/cm–1: 3460, 3331, 2978, 1683, 1531, 1174; 1H NMR (400 MHz, CDCl3) δ 0.98–1.05 (m, 3H, CH3), 1.36 (s, 9H, CH3), 1.55–1.75 (m, 2H, CH2), 2.22

Planar-bilayer activities of linear oligoester bolaamphiphiles

• Jonathan K. W. Chui,
• Thomas M. Fyles and
• Horace Luong

Beilstein J. Org. Chem. 2011, 7, 1562–1569, doi:10.3762/bjoc.7.184

• -bromoalcohols prepared by mono-brominating the corresponding diols as described [16]. This gave the bis-bromides, which were subsequently displaced by the protected carboxylate anion of BOC-protected aniline 14 to give precursors 15, 16 and 17. Deprotection of the carbamate protecting groups under various

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• diaryl ether. Benzylic metallation of a diaryl ether α to a carbamate. Diastereo- and enantioselective synthesis of atropisomeric ethers by benzylic lithiation. Atroposelective stannylation. Stereospecific tin–lithium exchange/quench reactions. Proposed stereochemical pathway. Yields and selectivities in

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• , with m/z 734, consistent with the expected coupling products, i.e., the allylic amines. The fourth product had m/z 800, consistent with the carbamate structure 27. The determination of the regiochemistry of the unsaturated ring in 24 was complicated by long-range 1H–1H couplings and correlations in the

Triazole–Au(I) complex as chemoselective catalyst in promoting propargyl ester rearrangements

• Dawei Wang,
• Yanwei Zhang,
• Rong Cai and
• Xiaodong Shi

Beilstein J. Org. Chem. 2011, 7, 1014–1020, doi:10.3762/bjoc.7.115

• summarized in Table 2. As indicated in Table 2, carbonates (entries 1–5) and carbamate (entry 6) were also suitable for this transformation. Compared to the allene-acetates, the allene-carbonates and allene-carbamates were more stable in water. Notably, although the alkene was considered as a readily

• propargyl ester, carbonate and carbamate 3,3-rearrangement for the synthesis of the corresponding substituted allene derivatives. The chemoselective nature of the TA–Au catalysts was clearly demonstrated, which makes them an interesting class of new catalysts for promoting organic transformations. The

Scalable synthesis of (1-cyclopropyl)cyclopropylamine hydrochloride

• Sergei I. Kozhushkov,
• Alexander F. Khlebnikov,
• Rafael R. Kostikov,
• Dmitrii S. Yufit and
• Armin de Meijere

Beilstein J. Org. Chem. 2011, 7, 1003–1006, doi:10.3762/bjoc.7.113

• conversion to the corresponding tert-butyl carbamate and subsequent column chromatography. Thus, this procedure was not easily scalable to 10–50 g quantities. To meet such demands, we have developed an alternative route to 4 from the easily available corresponding carboxylic acid 2 [17][18] by Curtius

• , otherwise the yield of 3 dropped dramatically, and the desired product was accompanied by 1,3-di(bicyclopropyl)urea (5) in up to 50% yield (Scheme 1). The structure of the latter was confirmed by an X-ray crystal structure analysis (Figure 1) [26]. The carbamate 3 was deprotected by treatment with hydrogen

• -BuOH (ca. 1300 mL) was distilled off under ambient pressure in a nitrogen flow. After cooling, the residue mixture was dried at 20 °C/0.1 Torr to give essentially pure carbamate 3 (84.0 g, 76%) as a colorless solid, mp 69–70 °C, Rf 0.38 (hexane/Et2O 5:1), which was used in the next step without further

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• should thus serve as valuable precursors in the preparation of compounds of pharmaceutical interest. Several procedures enabling the construction of the diarylmethylamide and -carbamate core have been described. However, with respect to the substitution pattern of the expected final compound, available

• , prepared in parallel via a cobalt-catalyzed procedure [36] was added and the resulting solution was stirred for 30 minutes at ambient temperature. The chromatographic purification of the crude oil afforded the expected diarylmethylamide or -carbamate 4. Representative experimental results are reported in

• arylzinc reagent. However, the harsh conditions which would probably be required for the deprotection of the amide or carbamate function prompt us to undertake complementary experiments dedicated to the assessment of easier-to-cleave activating groups. Consequently, the evaluation of sulfinyl- or