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

• added to reactions [3][17], however, it has a low atom economy, poor economics, and requires separation of the succinimide byproduct [18]. The tert-butyl hypochlorite (t-BuOCl) reagent is also used regularly, but is similarly expensive, wasteful and hazardous [14][19][20][21]. On the other hand sodium

• literature batch procedures. The atom economy of our process was increased compared to the use of N-chlorosuccinimide [3], or NaOCl/t-BuOH, Table 3, entries 2 and 3 [20]. There are also improvements to the total mass intensity of the flow procedure, primarily by avoiding work-up and purification procedures

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• functional groups and its atom economy [4]. Chemists treasure its extraordinary versatility. From the production of polymers [5][6] and petrochemicals to the synthesis of complex natural products [7], olefin metathesis has been established as a useful tool for solving numerous synthetic challenges. In more

Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis

• Alba Collado,
• Scott R. Patrick,
• Danila Gasperini,
• Sebastien Meiries and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 1809–1814, doi:10.3762/bjoc.11.196

• atom economy. A number of gold complexes have been shown to be active in this transformation [51][52][53][54][55][56][57][58]. Much effort has been devoted to the development of more sustainable gold-promoted protocols and several advances have been made in this field, e.g., very low catalyst loadings

• be efficient catalysts in this transformation [52][59][60] which proceeds with 100% atom economy. In addition, previous findings showed that the digold complex, [{Au(NHC)}2(μ-OH)][BF4], bearing IPent was more efficient than the IPr analogue in this reaction [52]. This result encouraged us to test the

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• -up with a productivity of 70 g fanetizole (87) in 7 h. In 2013 the Jamison group reported the flow synthesis of the important H1-antagonist diphenhydramine·HCl (92) showcasing the potential of modern flow chemistry to adhere to green chemistry principles (minimal use of organic solvents, atom economy

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• require quite different ligands to those needed for enamide hydrogenation. From a synthetic perspective, large scale reduction processes generally prefer the use of hydrogen gas to any other reductant, since it potentially saves on cost, waste, atom-economy, solvent and water use; the catalysts identified

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• current is used more efficiently and a high atom economy is achievable [35]. The latter being the fraction of the molecular mass of all reactants which is transferred to the desired product(s). In Scheme 5, the total atom efficiency is 100% and the electrochemical yield reaches 180% [34]. Moreover

• yields of the C5:C6:C10 product mixture, with C6 as the main product (Table 1, entry 7) [44]. The anodic reaction produces CO2 which can directly be used as reactant at the cathode (Scheme 8), sustaining the atom economy of the process. This way, however, there is no net incorporation of gaseous CO2 into

• when using a sacrificial anode [146]. The major downside in carboxylating organic halides is the release of halides in the system, which can moreover induce a significant number of side reactions in a non-sacrificial setup, and which is in any case disadvantageous for the atom economy. Innovative

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• to minimize the structural complexity of the fluorophores to achieve higher atom economy and reduce the interaction with biomacromolecules. In this context it was critical to realize that the thiazole moiety itself can also act as a fluorophore, especially the class of 4-hydroxythiazoles [4][5]. 4

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• the synthesis of α-amino amidines has been developed using a molecular iodine-catalyzed three-component coupling reaction of isocyanides, amines, and aldehydes. The presented strategy offers the advantages of mild reaction conditions, low environmental impact, clean and simple methodology, high atom

• economy, wide substrate scope and high yields. Keywords: α-amino amidines; iodine; isocyanide; multicomponent reaction; Ugi reaction; Introduction Amidines are a class of organic compounds exhibiting a variety of biological activity that makes them potential candidates for drug development and discovery

Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol

• Marina Caporaso,
• Giancarlo Cravotto,
• Spyros Georgakopoulos,
• George Heropoulos,
• Katia Martina and
• Silvia Tagliapietra

Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149

• Selective oxidations of alcohols are some of the most important transformations in organic synthesis. Therefore, reactions that employ reusable heterogeneous catalysts and molecular oxygen are highly desirable from atom economy and environmental impact point of view [1][2][3]. A number of methods have been

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• ; polymer-supported reagent; rasta resin; triphenylphosphine oxide; Introduction One of the major drawbacks of the Wittig [1] and Mitsunobu [2][3] reactions is that they result in the formation of a stoichiometric quantity of triphenylphosphine oxide (1) as a byproduct. From an atom economy perspective

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• different aryl units. Keywords: aryl bromides; atom economy; C–H bond activation; palladium; regioselectivity; thiophenes; Introduction As thiophenes bearing aryl substituents are known to be present in several bioactive molecules and are used as precursors of materials, the regioselective introduction of

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• product without the need of sacrificial components. The latter process proceeds with a high degree of atom economy [16]. We have recently demonstrated this for the azido-hydroperoxidation of alkenes, a convenient method for the synthesis of 1,2-amino alcohols [17][18]. In the field of C–C coupling

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• functional groups such as esters or amines (Table 13). This approach was also used for the synthesis of phosphinoxazolines [223]. Hydrophosphination of alkynes The addition of P–H to a triple bond is a highly desirable method when taking atom economy principles into account. Activated [224][225] or

Nonanebis(peroxoic acid): a stable peracid for oxidative bromination of aminoanthracene-9,10-dione

• Vilas Venunath Patil and
• Ganapati Subray Shankarling

Beilstein J. Org. Chem. 2014, 10, 921–928, doi:10.3762/bjoc.10.90

• % of the desired dibromo product in 6 h, along with the starting amine and some byproducts. The long reaction time, drastic reaction conditions, isomer formation and their separation (which is a very tedious and difficult task), and reduced bromine atom economy make these approaches economically

• unattractive. Again, in all the above processes, molecular bromine is used as the bromine source which reduces the bromine atom economy by 50% [24], as the HBr generated in the reaction is not used for further bromination and also causes pollution of the environment. This problem can be resolved by employing

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• ]quinolinium/phenanthrolinium dipole precursors and maleimide/acetylenecarboxylate dipolarophiles. High atom-economy, good to very good isolated yield of the products, short reaction time and ease of separation coupled with general applicability are the key features of this methodology. Experimental General

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• reaction efficiency and atom economy. Besides lead finding in pharmaceutical and medicinal chemistry [8][9][10] MCRs have also been recognized as a DOS tool for approaching functional π-systems [11] such as luminescent chromophores [6]. Interestingly, multicomponent syntheses of symmetrically substituted

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ). Multicomponent reactions are convergent one-pot transformations involving three or more substrates that give a single product with high atom-economy. The reagents herein react in a sequential manner and all intermediate-steps are in equilibrium except often the last irreversible step, which provides the product

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• to provide sufficient substance amounts for clinical tests [41][42]. Additionally, alternatives in reactions driven by the formation of phosphine oxides from phosphines (e.g. the Appel and Mitsunobu reaction) are highly desired to improve atom economy (reduced waste amounts) and to circumvent

• phosphites (P(OR)3), activated through oxidants such as iodine, have been reported to give the corresponding phosphates in a Michaelis–Arbuzow type reaction [83][84][85] (Scheme 5). In order to improve atom economy and side product separation, we rationalized that in the phosphonium intermediate III

• , respectively (entries 8–9). Whereas OP(OiPr)3 was hydrolyzed in the work up, OP(OPh)3 was not saponified and therefore still remained in the isolated product 13f. However, considering the atom economy these phosphites do not represent an alternative to P(OEt)3. Even the diols rac-12g and 12h with a sterically

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• with high levels of atom economy. Boron compounds have long been ignored in this attractive area of research despite their wide range of reactivity [10][11]. In 1993, however, Petasis and co-workers reported a new synthesis of allylamines via stepwise condensation of a secondary amine, paraformaldehyde

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• microreactor technology to overcome long-standing problems in synthetic organofluorine chemistry are showcased. Reactions using hazardous fluorinating reagents Direct fluorination employing elemental fluorine (F2) is one of the most straightforward methods to make fluorine-containing molecules with high atom

• economy. However, handling F2 needs special care and there are a lot of practical difficulties associated with direct fluorination. Elemental fluorine is a poisonous pale yellow gas at room temperature (bp −188 °C). Reactions of organic substances with elemental fluorine are typically strongly exothermic

Bis(benzylamine) monomers: One-pot preparation and application in dendrimer scaffolds for removing pyrene from aqueous environments

• Olivia N. Monaco,
• Sarah C. Tomas,
• Meghan K. Kirrane and
• Amy M. Balija

Beilstein J. Org. Chem. 2013, 9, 2320–2327, doi:10.3762/bjoc.9.266

• principles of atom economy [15]. This simple one-step approach is in contrast to the synthesis of the oxygen analogue of 4a, the well-known AB2 bis(benzyl) ether monomer, which is prepared in three steps from 3,5-dihydroxybenzoic acid and benzyl bromide. When synthesizing the bis(benzyl) ether monomer, the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• reaction. Both mono- and bicyclic cyclopropylanilines were viable substrates to provide the annulation products in good to excellent yields. The former gave little to poor diastereoselectivity whereas the later produced modest diastereoselectivity. The reaction has 100% atom economy. It is also overall

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• stereo-controlling of the ring-opening of epoxides is quite challenging, and the background reaction should be suppressed to achieve high enantioselectivities. However, the catalytic asymmetric ring-opening of meso-epoxides gained much attention by its unique advantages of good atom-economy and versatile

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• in asymmetric synthesis, which is one of the most attractive methods from the atom-economy point of view [1] for producing single enantiomers selectively. Over the past three decades, a variety of reactions allowing the formation of C–H, C–C, C–N, C–O and other bonds enantioselectively have been

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

• Ismail Özdemir,
• Nevin Gürbüz,
• Nazan Kaloğlu,
• Öznur Doğan,
• Murat Kaloğlu,
• Christian Bruneau and
• Henri Doucet

Beilstein J. Org. Chem. 2013, 9, 303–312, doi:10.3762/bjoc.9.35

• with heteroarenes. Keywords: aryl chlorides; atom-economy; C–H bond activation; C–H functionalization; carbenes; palladium; pyrroles; Introduction N-Heterocyclic carbenes (NHC) have emerged as an important class of ligands in the development of homogeneous catalysis [1][2][3][4][5][6][7][8][9]. Such