J. D. Sullivan

Bio: J. D. Sullivan is an academic researcher from University of Utah. The author has contributed to research in topics: Moiety & Alkyl. The author has an hindex of 2, co-authored 4 publications receiving 170 citations.

Addition-hydroamination reactions of propargyl cyanamides: rapid access to highly substituted 2-aminoimidazoles.

Abstract: A valuable pharmacophore, the 2-aminoimidazole moiety, can be accessed with a variety of substitution patterns through an addition–hydroamination–isomerization sequence (see scheme; R1,R4,R5=alkyl; R3=alkyl, aryl; R2=H, alkyl, aryl). The synthesis of the propargyl cyanamide precursors through a three-component coupling enables the preparation of this important heterocyclic core structure in just three steps.

2-Aminoimidazoles from Leucetta Sponges: Synthesis and Biology of an Important Pharmacophore

Abstract: This review will focus on the ability of the 2-aminoimidazole to occupy a unique subset of chemical space which makes it an ideal pharmacophore for the development of small molecule collections for discovery based research. These observations rely both on the use of 2-aminoimidazoles as building blocks in medicinal chemistry as well as the recent discovery of alkaloids from sponges of the genus Leucetta which exhibit a diverse range of biological activities around a relatively limited structural core. The preparation of these compounds will also be highlighted. In particular, marine natural products derived from sponges have provided valuable leads for therapeutic small molecules (3, 4). Surprisingly the large majority of these compounds have been isolated from organisms of the class Dermospongiae. In the mid 1980's chemists noted that the other major sponge class, Calcarea, had rarely been subject to chemical investigations. A flurry of efforts through the mid-1990's helped to establish biogenetic relationships among these sponges. Isolated to explore these inter- connections and not necessarily for specific biological responses the activities of these natural products have remained largely uncovered. Since these initial inves- tigations, an emerging structural class has recurrently been identified through bioassay guided isolation which contains the 2-aminoimidazole core. From the viewpoint of small molecule discovery this review will highlight alkaloids isolated from Leucetta sp. This small skeletal family has been shown to interrogate an incredibly diverse range of biological processes and thus represents an important discovery scaffold for both medicinal and discovery based research.

2-Aminoimidazoles from Leucetta Sponges: Synthesis and Biology of an Important Pharmacophore

Abstract: This review will focus on the ability of the 2-aminoimidazole to occupy a unique subset of chemical space which makes it an ideal pharmacophore for the development of small molecule collections for discovery based research. These observations rely both on the use of 2-aminoimidazoles as building blocks in medicinal chemistry as well as the recent discovery of alkaloids from sponges of the genus Leucetta which exhibit a diverse range of biological activities around a relatively limited structural core. The preparation of these compounds will also be highlighted. In particular, marine natural products derived from sponges have provided valuable leads for therapeutic small molecules (3, 4). Surprisingly the large majority of these compounds have been isolated from organisms of the class Dermospongiae. In the mid 1980's chemists noted that the other major sponge class, Calcarea, had rarely been subject to chemical investigations. A flurry of efforts through the mid-1990's helped to establish biogenetic relationships among these sponges. Isolated to explore these inter- connections and not necessarily for specific biological responses the activities of these natural products have remained largely uncovered. Since these initial inves- tigations, an emerging structural class has recurrently been identified through bioassay guided isolation which contains the 2-aminoimidazole core. From the viewpoint of small molecule discovery this review will highlight alkaloids isolated from Leucetta sp. This small skeletal family has been shown to interrogate an incredibly diverse range of biological processes and thus represents an important discovery scaffold for both medicinal and discovery based research.

Addition—Hydroamination Reactions of Propargyl Cyanamides: Rapid Access to Highly Substituted 2‐Aminoimidazoles.

Abstract: A valuable pharmacophore, the 2-aminoimidazole moiety, can be accessed with a variety of substitution patterns through an addition–hydroamination–isomerization sequence (see scheme; R1,R4,R5=alkyl; R3=alkyl, aryl; R2=H, alkyl, aryl). The synthesis of the propargyl cyanamide precursors through a three-component coupling enables the preparation of this important heterocyclic core structure in just three steps.

Transition Metal-Mediated Synthesis of Monocyclic Aromatic Heterocycles

Abstract: Heterocycles constitute the largest and the most diverse family of organic compounds Among them, aromatic heterocycles represent structural motifs found in a great number of biologically active natural and synthetic compounds, drugs, and agrochemicals Moreover, aromatic heterocycles are widely used for synthesis of dyes and polymeric materials of high value 1 There are numerous reports on employment of aromatic heterocycles as intermediates in organic synthesis 2 Although, a variety of highly efficient methodologies for synthesis of aromatic heterocycles and their derivatives have been reported in the past, the development of novel methodologies is in cuntinious demand Particlularly, development of new synthetic approaches toward heterocycles, aiming at achieving greater levels of molecular complexity and better functional group compatibilities in a convergent and atom economical fashions from readily accessible starting materials and under mild reaction conditions, is one of a major research endeavor in modern synthetic organic chemistry Transition metal-catalyzed transformations, which often help to meet the above criteria, are among the most attractive synthetic tools Several excellent reviews dealing with transition metal-catalyzed synthesis of heterocyclic compounds have been published in literature during recent years Many of them highlighted the use of a particular transition metal, such as gold,3 silver,4 palladium,5 copper,6 cobalt,7 ruthenium,8 iron,9 mercury,10 rare-earth metals,11 and others Another array of reviews described the use of a specific kind of transformation, for instance, intramolecular nucleophilic attack of heteroatom at multiple C–C bonds,12 Sonogashira reaction,13 cycloaddition reactions,14 cycloisomerization reactions,15 C–H bond activation processes,16 metathesis reactions,17 etc Reviews devoted to an application of a particular type of starting materials have also been published Thus, for example, applications of isocyanides,18 diazocompounds,19 or azides20 have been discussed In addition, a significant attention was given to transition metal-catalyzed multicomponent syntheses of heterocycles21 Finally, syntheses of heterocycles featuring formation of intermediates, such as nitrenes,22 vinylidenes,23 carbenes, and carbenoids24 have also been reviewed The main focus of the present review is a transition metal-catalyzed synthesis of aromatic monocyclic heterocycles The organization of the review is rather classical and is based on a heterocycle, categorized in the following order: (a) ring size of heterocycle, (b) number of heteroatoms, (c) type of heterocycle, and (d) a class of transformation involved A brief mechanistic discussion is given to provide information about a possible reaction pathway when necessary The review mostly discusses recent literature, starting from 200425 until the end of 2011, however, some earlier parent transformations are discussed when needed

A walk around the A3-coupling

Abstract: In recent years, the transition-metal catalyzed three-component coupling of an aldehyde, an alkyne and an amine, commonly called A3-coupling, has been established as a convenient and general approach towards propargylamines. Furthermore, the A3-coupling has found a broad application as a key step in the construction of various nitrogen-containing heterocycles, biologically active compounds and natural products. Several interesting modifications of the A3-coupling as well as different tandem reactions involving A3-coupling have been developed. This tutorial review aims to highlight the current achievements in the field of A3-couplings and related transformations.

Efficient Microwave‐Assisted Synthesis of Secondary Alkylpropargylamines by Using A3‐Coupling with Primary Aliphatic Amines

Abstract: Multicomponent reactions (MCRs) have attracted much attention in the framework of combinatorial chemistry owing to their synthetic efficiency, intrinsic atom economy, high selectivity and procedural simplicity. These reactions constitute a valuable approach for the creation of large libraries of structurally related, drug-like compounds, thereby enabling rapid lead identification and optimisation in drug discovery. They represent environmentally friendly processes by reducing the number of steps, energy consumption and waste production. The three-component coupling of an aldehyde, an alkyne and an amine, commonly called an A-coupling, is an MCR that has received much attention in recent years. The resulting propargylamines are synthetically versatile key intermediates for the preparation of biologically active compounds and drugs. Classical methods for the synthesis of propargylamines use strong bases, such as butyllithium, organomagnesium reagents or lithium diisopropylamide (LDA), exploiting the relatively high acidity of the terminal acetylene to form alkynyl metal compounds. The stoichiometric quantities of the reagents required, as well as their high sensitivity to moisture, render these processes fairly unattractive. During recent years, substantial progress has been made in A-coupling reactions. Several transition-metal catalysts have been exploited that activate the C H bond of the terminal alkyne. Ag salts, Au/Au salts, Au–salen (salen =N,N’-bis(salicylidene)ethylenediamine) complexes, Cu salts, Ir complexes, Hg2Cl2, [10] Cu/Ru bimetallic systems, InCl3, [12] ZnCl2, [13] FeCl3 [14] and nano CuO compounds have all been used to run this reaction under homogeneous conditions. Moreover, Au, Ag and Cu in ionic liquids and supported Au, Ag, Cu and CuCl were successfully used to catalyse A-coupling reactions under heterogeneous conditions with preservation of the transition-metal catalyst. Additionally, the enantioselective addition of terminal alkynes to imines provides access to optically active propargylamines. A variety of chiral ligands have been used for this reaction. High asymmetric induction has been reported by applying 1-(2-di ACHTUNGTRENNUNGphenyl ACHTUNGTRENNUNGphosphino-1-naphthyl)isoquinoline (QUINAP) ligands. In addition to these ligands, metal complexes of chiral amino acids, chiral alcohols, chiral binaphthylamines and 2,6-bis(2-oxazolinyl)pyridine (PyBOX) ligand have been used successfully. Despite huge advancements, A-coupling reactions have mainly been optimised for reactions involving anilines and secondary amines, which result in the formation of N-arylpropargylamines or tertiary propargylamines. Primary amines are considered to be difficult substrates for A-coupling reactions; this limits access to secondary propargylamines. Nevertheless, secondary alkylpropargylamines are potent synthetic intermediates that have mainly been explored for the synthesis of pyrrolidin, 5-alkylideneselenazolin-2-ones, pyrroles, quinolines and oxazolidinones. The synthesis of secondary alkylpropargylamines by using A-coupling reactions is scarcely reported in the literature and, to the best of our knowledge, no systematic study has ever been described. Herein, we present an optimised protocol for the synthesis of secondary alkylpropargylamines by using a microwave-assisted A-coupling reaction. In an optimisation study, benzylamine (1{1}) was used as a primary amine in combination with phenylacetylene (2{1}) and isobutyraldehyde (3{1}) (Table 1). As stated in the literature, the initial reagent ratio was selected as 1.3 equivalents of amine, 1.0 equivalent of aldehyde and 1.6 equivalents of alkyne with toluene as the solvent. Reactions were carried out in the presence of different copper salts under microwave irradiation at various ceiling temperatures (Table 1). Relatively low concentrations of the CuI catalyst [a] Dr. J. B. Bariwal, Dr. D. S. Ermolat ev, Prof. E. V. Van der Eycken Laboratory for Organic and Microwave-Assisted Chemistry (LOMAC) Department of Chemistry, Katholieke Universiteit Leuven Celestijnenlaan 200F, 3001 Leuven (Belgium) Fax: (+32) 16-32-79-90 E-mail : erik.vandereycken@chem.kuleuven.be Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200903143.

Addition-hydroamination reactions of propargyl cyanamides: rapid access to highly substituted 2-aminoimidazoles.

Abstract: A valuable pharmacophore, the 2-aminoimidazole moiety, can be accessed with a variety of substitution patterns through an addition–hydroamination–isomerization sequence (see scheme; R1,R4,R5=alkyl; R3=alkyl, aryl; R2=H, alkyl, aryl). The synthesis of the propargyl cyanamide precursors through a three-component coupling enables the preparation of this important heterocyclic core structure in just three steps.