- Synthesis of N-Oxyureas by Substitution and Cope-Type Hydroamination Reactions Using O-Isocyanate Precursors
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Oxy-carbamate O-isocyanate precursors facilitate access to synthetically valuable N-oxyureas via substitution with amines. This work exploits the reactivity of suitable O-isocyanate precursors, identified by a thorough study highlighting the different reactivity of isocyanate masking groups. This led to bench-stable O-isocyanate precursors, offering improved versatility in the synthesis of N-oxyureas, and demonstrates the controlled reactivity of masked O-isocyanates. Suitable precursors also enabled the first example of Cope-type hydroamination of unsaturated hydroxyureas.
- Allen, Meredith A.,Ivanovich, Ryan A.,Polat, Dilan E.,Beauchemin, André M.
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- An Oxidative Dearomatization Approach to Tetrodotoxin via a Masked ortho-Benzoquinone
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Progress toward a stereoselective synthesis of tetrodotoxin (TTX) is presented. Oxidative dearomatization of a tetrasubstituted guaiacol arene yielded a masked ortho-benzoquinone that intercepted an acyl nitroso species generated in situ by the copper-cat
- Robins, Jacob G.,Johnson, Jeffrey S.
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supporting information
p. 559 - 563
(2022/01/20)
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- Alternating Current Electrolysis as Efficient Tool for the Direct Electrochemical Oxidation of Hydroxamic Acids for Acyl Nitroso Diels–Alder Reactions
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The acyl nitroso Diels–Alder reaction of 1,3-dienes with electrochemically oxidised hydroxamic acids is described. By using alternating current electrolysis, their typical electro-induced decomposition could be suppressed in favour of the 1,2-oxazine cycloaddition products. The reaction was optimised using Design of Experiments (DoE) and a sensitivity test was conducted. A mixture of triethylamine/hexafluoroisopropanol served as supporting electrolyte in dichloromethane, thus giving products of high purity after evaporation of the volatiles without further purification. The optimised reaction conditions were applied to various 1,3-dienes and hydroxamic acids, giving up to 96 % isolated yield.
- F?hrmann, Jan,Hilt, Gerhard
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supporting information
p. 20313 - 20317
(2021/08/12)
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- Synthesis of Sulfinamidines and Sulfinimidate Esters by Transfer of Nitrogen to Sulfenamides
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In this work we report a new synthetic tactic for the straightforward preparation of hardly accessible sulfinamidines and sulfinamide esters, by using a simple metal-free protocol. The process is robust and uses readily available sulfenamides as the S-don
- Andresini, Michael,Spennacchio, Mauro,Romanazzi, Giuseppe,Ciriaco, Fulvio,Clarkson, Guy,Degennaro, Leonardo,Luisi, Renzo
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supporting information
p. 7129 - 7134
(2020/10/02)
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- Palladium-Catalyzed Synthesis of Indolines from Aroyloxycarbamates through a Tandem Decarboxylative Amination/Heck/Annulation Reaction
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A novel synthesis of functionalized indolines via a Pd-catalyzed tandem decarboxylative amination/Heck/annulation reaction has been developed. This process features operational simplicity, mild conditions, and the use of a readily available and environmentally friendly starting material, namely carboxylic acid. Furthermore, the reaction shows good functional group tolerance and chemical selectivity. (Figure presented.).
- Wang, Zheng,Li, Peihe,Fu, Hui,Dai, Qipu,Hu, Changwen
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p. 192 - 200
(2018/11/23)
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- An Effective Method for the Synthesis of 1,3-Dihydro-2H-indazoles via N-N Bond Formation
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The [4+1] cycloaddition reaction of bifunctional amino reagents has been achieved with in situ formed aza-ortho-quinone methides. Specifically, N-(tosyloxy)carbamates were used as an N1 synthon and bifunctional amino reagents for this transformation, which provides a metal-free, catalyst-free, and oxidant-free strategy to form nitrogen-nitrogen bonds. (Figure presented.).
- Zhang, Xiaoke,Pan, Yang,Liang, Peng,Ma, Xiaofeng,Jiao, Wei,Shao, Huawu
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supporting information
p. 5552 - 5557
(2019/11/22)
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- Synthesis process of Ticagrelor intermediate
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The invention discloses a synthesis process of a Ticagrelor intermediate, and belongs to the technical field of medicine synthesis. A compound I is prepared by using hydroxylamine hydrochloride and benzyl chloroformate as raw materials; the compound I and
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Paragraph 0036-0040; 0050-0051
(2018/06/15)
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- Synthesis of indoles from aroyloxycarbamates with alkynes: Via decarboxylation/cyclization
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An efficient Pd-catalyzed decarboxylation/cyclization of aroyloxycarbamates to realize substituted indoles has been disclosed. Terminal alkynes as the coupling partners lead to site specific 2-substituted indoles through two pathways, while internal alkynes with aroyloxycarbamates can be transformed to 2,3-disubstituted indoles directly. This protocol is further demonstrated by the efficient synthesis of indoles as well as the success of employing inexpensive aryl acids as starting materials to construct C-N bonds by releasing CO2.
- Ma, Nuannuan,Li, Peihe,Wang, Zheng,Dai, Qipu,Hu, Changwen
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supporting information
p. 2421 - 2426
(2018/04/12)
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- Base-Mediated Intramolecular Decarboxylative Synthesis of Alkylamines from Alkanoyloxycarbamates
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A general and effective method for the synthesis of alkylamine via intramolecular decarboxylation of alkanoyloxycarbamates is described. The alkanoyloxycarbamates are readily prepared with alkyl carboxylic acids and hydroxylamine. The reaction shows a broad range of substrates (primary and secondary alkyl) with functional tolerance, and the corresponding products were obtained in good yields under mild conditions.
- Li, Peihe,Ma, Nuannuan,Wang, Zheng,Dai, Qipu,Hu, Changwen
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p. 8233 - 8240
(2018/05/31)
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- Regioselective Synthesis of 2-Vinylanilines Using O-aroyloxycarba-mates by Sequential Decarboxylation/Amination/Heck Reaction
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A new sequential approach for 2-vinylanilines utilizing aryl carboxylic acids as stable, inexpensive and widely available arylating reagents is described. Employing a Pd-POVs catalyst system, this protocol is not only overcoming the restriction barrier of decarboxylative coupling to ortho-substituted substrates, but also provides site-special to create new C(sp2)-N and C(sp2)-C(sp2) bonds. Mechanistic experiments suggest the cleavage of C(sp2)-COOH gives priority to C(sp2)-X bond in this reaction.
- Li, Peihe,Ma, Nuannuan,Li, Jikun,Wang, Zheng,Dai, Qipu,Hu, Changwen
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p. 8251 - 8257
(2017/08/14)
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- Base-catalyzed controllable reaction of 3-ylideneoxindoles with O-Boc hydroxycarbamates for the synthesis of amidoacrylates and spiroaziridine oxindoles
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A base-catalyzed divergent reaction of 3-ylideneoxindoles with O-Boc hydroxycarbamates has been developed to provide efficient access to various amidoacrylates and spiroaziridine oxindoles with generally high yields, which should be potentially useful in drug discovery.
- Liu, Yi-Yin,Duan, Shu-Wen,Zhang, Rui,Liu, Yun-Hang,Chen, Jia-Rong,Xiao, Wen-Jing
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supporting information
p. 5224 - 5228
(2016/07/06)
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- Palladium-Catalyzed Decarboxylative Synthesis of Arylamines
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A novel approach has been developed for the synthesis of arylamines via the palladium-catalyzed intramolecular decarboxylative coupling (IDC) of aroyloxycarbamates, obtained in situ by reacting aryl carboxylic acids with hydroxycarbamates. The reaction offers facile access to structurally diverse arylamines with the site-specific formation of the C(sp2)-N bond under mild conditions.
- Dai, Qipu,Li, Peihe,Ma, Nuannuan,Hu, Changwen
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supporting information
p. 5560 - 5563
(2016/11/17)
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- Kinetics of action of a two-stage pro-inhibitor of serine β-lactamases
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β-Lactamase inhibitors are important in medicine in the protection of β-lactam antibiotics from β-lactamase-catalyzed destruction. The most effective inhibitors of serine β-lactamases covalently modify the enzyme active site. We have recently studied O-acyl and O-phosphyl hydroxamates as a new class of such inhibitors. In this paper, we describe our studies of the N-acyl derivatives of a cyclic O-acyl hydroxamic acid, 3H-benzo[d][1,2]oxazine- 1,4-dione, and, in particular, the N-tert-butoxycarbonyl derivative. This compound is not a β-lactamase inhibitor itself but undergoes spontaneous hydrolysis in aqueous solution, yielding an O-phthaloyl hydroxamic acid, which is a β-lactamase inhibitor. This compound spontaneously, but reversibly, cyclizes in solution to form phthalic anhydride, which is also a β-lactamase inhibitor. Both inhibitors react to form the same transiently stable phthaloyl-enzyme complex. Thus, we have a two-step cascade, beginning with a pro-inhibitor, in which each step leads to a different inhibitor, presumably with different enzyme specificities. The kinetics of these transformations have been elucidated in detail. The phthaloyl derivatives, where the free carboxylate is important for facile reaction with the enzyme, represent a new lead for serine β-lactamase inhibitors. Analogues can be conveniently constructed in situ by reaction of nucleophiles with phthalic anhydrides and then screened for activity. Active hits may then become new leads.
- Tilvawala, Ronak,Pratt
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p. 7060 - 7070
(2013/10/22)
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- IMPROVED AMINOHYDROXYLATION OF ALKENES
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The invention relates to a process for the aminohydroxylation of alkenes using N-oxycarbamate reagents, e.g. N-acyloxycarbamate, N-alkyloxycarbonyloxycarbamate and N-aralkoxycarbonyloxycarbamate reagents. The invention particularly relates to an intermolecular aminohydroxylation reaction that can be carried out in the absence of added base. The invention also relates to novel N-oxycarbamate reagents that are stable crystalline materials. The process of the invention is useful in the synthesis of compounds having a vicinal amino alcohol moiety, such as biologically active compounds.
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Page/Page column 74-75
(2012/01/06)
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- Alkyl 4-chlorobenzoyloxycarbamates as highly effective nitrogen source reagents for the base-free, intermolecular aminohydroxylation reaction
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Ethyl-(7), benzyl-(8), tert-butyl-(9), and fluorenylmethyl-4- chlorobenzoyloxycarbamates (10) have been prepared as storable and easy-to-prepare nitrogen sources for use in the intermolecular Sharpless aminohydroxylation reaction and its asymmetric variant. These reagents were found to be effective under base-free reaction conditions. The scope and limitations of these methods have been explored using a variety of alkenes, among which, trans-cinnamates, in particular, proved to be good substrates.
- Harris, Lawrence,Mee, Simon P. H.,Furneaux, Richard H.,Gainsford, Graeme J.,Luxenburger, Andreas
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experimental part
p. 358 - 372
(2011/04/17)
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- Pd-catalyzed intermolecular ortho-C-H amidation of anilides by N-nosyloxycarbamate
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A palladium-catalyzed ortho-C-H amidation of anilides by N-nosyloxycarbamates was developed for the synthesis of 2-aminoanilines. This reaction can be carried out under relatively mild conditions and exhibits excellent regioselectivity and functional group tolerance. The amidation reaction is probably initiated by rate-limiting C-H cyclopalladation (k H/kD = 3.7) to form an arylpalladium complex, followed by nitrene functionalization.
- Ng, Ka-Ho,Chan, Albert S. C.,Yu, Wing-Yiu
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supporting information; experimental part
p. 12862 - 12864
(2010/11/03)
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- General and efficient synthesis of o-sulfonylhydroxylamine derivatives
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A general and efficient synthetic route to O-sulfonylhydroxylamine derivatives is described. The approach involves acylation of hydroxylamine with benzyl chloroformate to give N-carbobenzoxy hydroxylamine, followed by sulfonation and hydrogenolysis to giv
- Qin, Liqiong,Zhou, Zhiming,Wei, Jia,Yan, Ting,Wen, Hongliang
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experimental part
p. 642 - 646
(2011/03/19)
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- Serendipitous discovery of α-hydroxyalkyl esters as β-lactamase substrates
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O-(1-Carboxy-1-alkyloxycarbonyl) hydroxamates were found to spontaneously decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl) hydroxamates. While the former molecules do not react rapidly with serine β-lactamases, the latter are quite good substrates of representative class A and C, but not D, enzymes, and particularly of a class C enzyme. The enzymes catalyze hydrolysis of these compounds to a mixture of the α-hydroxy acid and hydroxamate. Analogous compounds containing aryloxy leaving groups rather that hydroxamates are also substrates. Structure-activity experiments showed that the α-hydroxyl group was required for any substantial substrate activity. Although both d- and l-α-hydroxy acid derivatives were substrates, the former were preferred. The response of the class C activity to pH and to alternative nucleophiles (methanol and d-phenylalanine) suggested that the same active site functional groups participated in catalysis as for classical substrates. Molecular modeling was employed to explore how the α-hydroxy group might interact with the class C β-lactamase active site. Incorporation of the α-hydroxyalkyl moiety into novel inhibitors will be of considerable interest.
- Pelto, Ryan B.,Pratt
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experimental part
p. 10496 - 10506
(2011/10/18)
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- The acyl nitroso Diels-Alder (ANDA) reaction of sorbate derivatives: An X-ray and 15N NMR study with an application to amino-acid synthesis
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We present a study of the acyl nitroso Diels-Alder (ANDA) reaction of sorbate esters and sorbic alcohol derivatives, using alkoxycarbonyl nitroso dienophiles. An optimisation of the reaction conditions for ethyl sorbate is first presented, and the product is used in an efficient synthesis of 5-methylornithine. Structure-reactivity trends in sorbic alcohol (E,E-2,4-hexadien-1-ol) and its acylated analogues are then discussed. We present single-crystal X-ray structural proof for key adducts in both series and present in detail a novel HMBC/HSQC (1H-15N) criterion for ready distinction of regioisomers arising from such ANDA reactions.
- Bollans, Lee,Bacsa, John,Iggo, Jonathan A.,Morris, Gareth A.,Stachulski, Andrew V.
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experimental part
p. 4531 - 4538
(2009/12/25)
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- Efficient preparation of aminoxyacyl amides, aminoxy hybrid peptides, and α-aminoxy peptides
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(Chemical Equation Presented) N-(Pg-α-aminoxy acids) 1a-g are converted to N-(Pg-α-aminoxyacyl)benzotriazoles 2a-g, which react under mild conditions with amines, α-amino acids/α-dipeptides, and α-aminoxy acids to give aminoxyacyl amides 3a-g, (3e+3e′), and (3g+3g′), aminoxy hybrid peptides 4a-h, (4a+4a′), 6a-d, 9a-e, (9a+9a′), and (9b+9b′), and α-aminoxy peptides 10a,b in good yields without racemization. 2009 American Chemical Society.
- Katritzky, Alan R.,Avan, Ilker,Tala, Srinivasa R.
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supporting information; experimental part
p. 8690 - 8694
(2010/01/16)
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- O-aryloxycarbonyl hydroxamates: New β-lactamase inhibitors that cross-link the active site
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O-Aryloxycarbonyl hydroxamates represent a new class of β-lactamase inhibitors. N-Benzyloxycarbonyl-O-(phenoxycarbonyl) hydroxylamine, for example, inactivates the class C Enterobacter cloacae P99 β-lactamase with a rate constant of 6.1 × 103 s
- Wyrembak, Pauline N.,Babaoglu, Kerim,Pelto, Ryan B.,Shoichet, Brian K.,Pratt
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p. 9548 - 9549
(2008/02/11)
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- Highly efficient Friedel-Crafts-type benzylation via benzyl cations generated in multiple spacer-molecule separated ion-pairs
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Deamination, as a facile route to highly reactive carbocations, is of interest to several areas of organic chemistry, industry, and medicine. The reactivity and utility of these carbocations derives from the presence of a lone nitrogenous entity (N2or N2O) interposed between the ion-pair. We report here the synthesis of a new deamination precursor whose nitrosation and subsequent decomposition constitutes a novel deamination method. In this novel approach, multiple spacer-molecules are generated in the inter-ion space. The resultant cations are exceedingly reactive but are longer-lived than carbocations derived from standard deaminations. The result is nearly quantitative yields of solvent-derived products from even poorly nucleophilic solvents such as benzene, toluene, and mesitylene.
- Darbeau, Ron W.,Trahan, Gregory A.,Siso, Luis M.
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p. 695 - 700
(2007/10/03)
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- Piperizinones as modulators of chemokine receptor activity
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The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
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- Heterosubstituted pyridine derivatives as PDE4 inhibitors
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The invention encompasses the novel compound of Formula I useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3′,5′-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE 4). or a pharmaceutically acceptable salt or hydrate thereof. The invention also encompasses pharmaceutical compositions and methods for treatment.
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- From 1-(Silyloxy)butadiene to 4-Amino-4-deoxy-DL-erythrose and to 1-Amino-1-deoxy-DL-erythriol Derivatives via hetero-Diels-Alder Reactions with Acylnitroso Dienophiles
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Acylnitroso dienophiles 4 reacted instantly with 1-(silyloxy)butadiene 5α and led in good yield to the regioisomeric cycloadducts 6 (major) and 7 (minor; Scheme 2, Table 1). cis-Hydroxylation of these primary cycloadducts with OsO4 (catalyst) occurred stereospecifically and in high yield (-> 8 and 9, resp.: Scheme 2).It was followed by reductive ring cleavage to give either 1-amino-1-deoxy-DL-erythriol or 4-amino-4-deoxy-DL-erythrose derivatives 10 and 14, respectively, depending on the nature of the reducing agent (Schemes 3 and 4).
- Defoin, Albert,Pires, Joaquim,Streith, Jacques
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p. 1653 - 1670
(2007/10/02)
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