Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• (lithium (trimethylsilyl)acetylide, THF, −60 °C → −50 °C or lithium phenylacetylide, THF, −78 °C) afforded derivatives 6a–c and carbamates 7a–c as mixtures of diastereomers (Table 2). It should be mentioned that upon storage at room temperature derivatives 6a–c undergo slow intramolecular cyclization to

• the corresponding carbamates 7a–c. The reaction of aldehyde 4 and vinylmagnesium bromide yielded directly carbamate 7d. Surprisingly, the reaction of derivative 5 bearing a N-(TCBoc)2 group with organometallic compounds (methylmagnesium bromide, THF, 0 °C → room temperature, lithium (trimethylsilyl

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• addition of carbamates, sulfonamides and imidazolidinones to linear and cyclic dienes 17 in the presence of catalytic amounts of PPh3AuOTf (Scheme 6). The method featured excellent 1,2-regioselectivity and high chemoselectivity, providing protected allylamines 18, in good yields, using nearly equimolar

• amounts of the diene and nitrogen-based nucleophile. Analogously, Widenhoefer and Han developed the intramolecular addition of carbamates to terminal alkenes affording N-protected pyrrolidines and piperidines 21 (Scheme 7). Best conditions involved the use of a 1:1 mixture of [Au(I)] complex 20a and AgOTf

• importance of the configuration of the carbon bearing the nucleophilic OH group was not considered. In this segment, Widenhoefer has recently documented on the enantioselective dehydrative amination of allylic alcohols with carbamates [70][71]. Pyrrolidines and piperidines 109 were obtained with enantiomeric

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• )}. For the debromination of dihydropyrrole 19, we first tested radical conditions ((n-Bu)3SnH/AIBN), but these led to complete decomposition. This is surprising since carbamates are known to be stable under radical conditions [70]. Indeed, treatment of diastereomer 11b with (n-Bu)3SnH/AIBN afforded the

Self-assembly of 2,3-dihydroxycholestane steroids into supramolecular organogels as a soft template for the in-situ generation of silicate nanomaterials

• Valeria C. Edelsztein,
• Andrea S. Mac Cormack,
• Matías Ciarlantini and
• Pablo H. Di Chenna

Beilstein J. Org. Chem. 2013, 9, 1826–1836, doi:10.3762/bjoc.9.213

• possess a complementary donor–acceptor hydrogen bond motif, such as for instance amides, ureas, carbamates, saccharides, ammonium carboxylate salts, etc. A rod-like molecular shape is also a general structural requirement for steroid derived LMOGs because it allows a good face to face molecular contact to

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• aniline is crucial. Methyl substitution leads to slower addition than phenyl substitution. Carbamates as substituents are suitable only when the radical center is not too electrophilic. No correlations between free reaction barriers and energies (ΔG‡ and ΔGR) are found. Addition reactions leading to

• –HOMO gap. Thus, the polarity of the radical and the arene is reversed in comparison with the related Minisci reaction. The substitution at the N-atom of the aniline is crucial. Methyl substitution leads to slower addition than phenyl substitution. Carbamates as substituents are suitable only when the

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• tert-butyl carbamates 5 prior to undergoing palladium-mediated Suzuki reactions with various boronic acid partners. Under the reaction conditions, the carbamate-protecting group was also cleaved to afford the desired 3-arylindazoles, albeit as the unprotected systems 6. Alkylation with methyl

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• derivatives. The scope of the reaction was investigated and its applicability was extended to different C–H bonds, including benzylic, propargylic, and aliphatic ones. Furthermore, the hydrazine compounds were readily converted to the corresponding carbamates and amines. Conclusion Metal-free oxidation

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• gold-catalyzed synthetic routes to 1,3-oxazinan-2-ones (kinetically controlled products) and 1,3-oxazin-2-one derivatives (thermodynamically favored) from easily accessible allenic carbamates has been carried out. Keywords: allenes; computational chemistry; gold; gold catalysis; heterocycles; reaction

• substrates on gold-catalyzed oxycyclization reactions, a number of new allenic carbamates were synthesized as shown in Scheme 1. Starting materials, tert-butyl (prop-2-ynyl)carbamates 1a–j, were obtained both in the racemic form and in optically pure form by using standard methodologies. Thus

• readily accessed from (S)-prolinol by using a modified known procedure [58]. Alkynylcarbamate 1j was achieved through the reaction of 3-bromo-1H-indole-2-carbaldehyde with the Ohira–Bestmann reagent followed by the addition of Boc2O. Terminal alkynes 1 were conveniently converted into allenic carbamates 2

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• prodrugs for their potential use in the treatment of glutamate toxicity in ALS and other disorders. Potential drug candidates were prepared through the conversion of the exocyclic amine to single alpha amides, carbamates, succinamides, or amide linkages from γ-aminobutyric acids (Figure 2). It is expected

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

• Julien Lefranc Alberto Minassi Jonathan Clayden School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK 10.3762/bjoc.9.70 Abstract N-Alkenyl ureas and N-alkenyl carbamates, like other N-acyl enamines, are typically nucleophilic at their β-carbon. However, by

• incorporating an α-aryl substituent, we show that they will also undergo attack at the β-carbon by organolithium nucleophiles, leading to the products of carbolithiation. The carbolithiation of E and Z N-alkenyl ureas is diastereospecific, and N-tert-butoxycarbonyl N-alkenyl carbamates give carbolithiation

• -alkenyl carbamates. Results and Discussion Simple N-alkenyl ureas 1 were prepared by a reported method [2] entailing N-acylation of an acetophenimine with an isocyanate, followed by N-alkylation of the resulting urea. When urea 1a was treated with t-BuLi or s-BuLi in THF at −78 °C for one hour, followed

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

• preformed organocopper species (Table 2, entries 7–10) [25]. Carbocupration of cyclic N-alkynylcarbamate (chiral oxazolidinone moiety) Recently, our group was particularly interested in the carbometallation reaction of ynamides bearing chiral cyclic carbamates 7, particularly the Evans's oxazolidinone [27

• carbocupration reaction is again at the center of interest but this time for the regioselective addition of organocopper derivatives to various ynamide species. Particularly interesting is the carbocupration of N-alkynyl carbamates 7, bearing Evans’s oxazolidinone chiral auxiliary, which leads to the formation

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• synthesis of chiral aromatics and heteroaromatics, such as isoquinolines or benzofurans, though lower yields and ee were obtained [15]. On the other hand, α-aryl O-(α-arylalkenyl) carbamates (α-carbamoyloxy-substituted styrenes) such as 14 undergo facile intermolecular carbolithiation reactions, via

• secondary α-carbamoyloxybenzyllithiums 15, in the presence of chiral diamines, such as (−)-sparteine (L1) or (−)-α-isosparteine (L3), but only with moderate enantiofacial differentiation. The best results are obtained with unsubstituted alkenes (vinyl carbamates) by using butyllithium/(−)-α-isosparteine (up

• , the first examples reported of asymmetric intramolecular carbolithiation reactions using alkyllithiums took advantage of the (−)-sparteine-mediated enantioselective deprotonation reaction of carbamates [39]. Thus, achiral (Z)- or (E)-6-phenyl-hex-5-enylcarbamates 25 can be cyclized with sec

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT₂ receptor family

• Adam Pigott,
• Stewart Frescas,
• John D. McCorvy,
• Xi-Ping Huang,
• Bryan L. Roth and
• David E. Nichols

Beilstein J. Org. Chem. 2012, 8, 1705–1709, doi:10.3762/bjoc.8.194

• carbamates 11a and 11b (Scheme 2). A brief treatment of these with 3 M HCl at 45 °C cleanly affected N-deprotection and afforded the desired final amines 4 and 5. The stereochemistry of the more potent enantiomer of DOI is (−)-(R) [7], and of 3 is (−)-(1R,2S) [2]. We therefore undertook the resolution of the

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

• ) gave the corresponding 1-N,2-O-cyclic carbamates in 95% yield with a 3:2 ratio of the pyranoid 26a and furanoid 26b forms, and compounds 25 (a and b) reacted accordingly and gave cyclic carbamates 27a and 27b in a 5:3 ratio and a combined yield of 50%. In the D-manno series, the C-elongation employing

• -dioxane as co-solvent (1 mL). When TLC indicated complete consumption of the starting material, the solvents were removed under reduced pressure, and silica-gel chromatography (CHCl3/MeOH 6:1 v/v containing 1% of concd NH4OH) gave a mixture of cyclic carbamates in the pyranoid 27a and furanoid 27b form in

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• carbamates has to be performed manually at the end of an automated sequence. These features make the automated platform very attractive for sialoside synthesis. Based on the encouraging results obtained for the solution-phase synthesis of 16, building blocks 4 and 5 were used for the automated solid-phase

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• corresponding methyl carbamates 10 were obtained in excellent yields (Table 3). The reaction may well occur via the putative N-acetoxy derivative I (up to now this has not been proven). The in situ trapping of the expected isocyanate intermediate (not shown) by methanol would explain the final formation of 10

• . All products were generally purified chromatographically and fully characterized spectroscopically (including HRMS). In addition, two of the final carbamates (10a and 10b) were confirmed by X-ray diffraction analysis (Figure 2 and Table 4) [24]. The carbamates 10 apparently evidenced restricted

• rotation around the amide C–N moiety (partial double-bond character) in the NMR as seen by twin peaks in certain cases [25]. In carbamates 10, the substitution pattern α to the C=O group in 7–9 has shifted to the α-position next to the amino center. Therefore, in this strategy (Scheme 2) the enolate

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

• amidation position of the two molecules of 4. Based on the 1H NMR, 13C NMR HSQC, HMBC and 1H–1H COSY spectral data analysis, the structure of 2 was elucidated to be as shown above and named as obtucarbamate D. Urea derivatives are closely related in structure to carbamates. Urea is synthesized in the body

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• (IN3, 1). In their synthesis of carbamates Wirth and coworkers [10] recently showed that some of the practical problems associated with iodine azide can be circumvented or minimized by generating and immediately consuming iodine azide under flow conditions. Because of low yields, this ingenious process

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• ]. Various chloroformates and imines can participate in this reaction, stannanes being limited to aryl, benzyl or ethyl ones. When vinylstannane was used, the transmetallation step was more rapid than the CO insertion, giving instead substituted carbamates. After removal of the solvents in vacuo, the

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

• assign absolute or relative stereochemistry in this work. However, a few reasonable assumptions allow us to propose likely assignments, and these are the ones used in the structural diagrams in this paper: 1. (−)-Sparteine favours deprotonation of the pro-S proton of carbamates. Invertive quench would

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• and Discussion The original direct meta-zincation reaction. In comparison to tertiary amides and O-carbamates, anilines are relatively modest metallation directing groups [19][29]. Activation of N,N-dimethylaniline transpires primarily from the acidifying effect of the N atom; the coordination effect

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

• products were obtained in excellent yields (generally >90% yields with 1% loading). Besides the typical ester migrating groups, carbonates and carbamates were also found to be suitable for this transformation, which provided a highly efficient, practical method for the preparation of substituted allenes

• 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

• application of the allene-carbonates and allene-carbamates as building blocks for development of new synthetic methodologies is currently underway in our group. Chemoselective activation of alkyne over allene by the TA–Au catalysts. The counter ligands, an important factor in Au(I) catalysis. The challenge of

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

• -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates is described. This route involves the formation of an imine, which is used without isolation, followed by its activation by the carbonyl-containing electrophile and the trapping of the acyliminium by an organozinc reagent. Most

• steps are conducted concomitantly to render the procedure as practical and straightforward as possible. Therefore, the whole experimental protocol takes less than two hours. Keywords: acyliminium; amides; carbamates; multicomponent reactions; organozinc reagents; Introduction Diarylmethylamines

• constitute an important class of nitrogen-containing compounds displaying antihistaminic, anti-arrhythmic, diuretic, antidepressant, laxative, anesthetic and anticholinergic properties [1][2]. In this context, diarylmethylamides and -carbamates represent reliable N-protected diarylmethylamine derivatives and

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• an intramolecular aryl transfer. Treatment of an N-aryl S-benzyl thiocarbamate 92 leads to formation of a lithio derivative 93 comparable with those reported by Hoppe (Scheme 32). As in the case of lithiated N-aryl ureas [76][77][78][79][80] and N-aryl carbamates [81][82], the N-aryl ring is

• contrast to the rearrangement of lithiated carbamates [81][82]), aryl migration proceeds with retention of stereochemistry. Current work is continuing with the aim of expanding the utility of this new mode of reactivity displayed by thiocarbamates. Conclusion Of the methods available for the synthesis of

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

• Benan Kilbas and
• Metin Balci

Beilstein J. Org. Chem. 2011, 7, 246–253, doi:10.3762/bjoc.7.33

• product (Scheme 6). In the case of 8, 16 and 19, the leaving groups, carbamates, are in anti (referred to the cyclopropane ring) positions and, therefore, the palladium complex should approach the double bond in 8, 16, and 19 from the side of the three-membered ring to form a complex. However, the