DOCSLIB.ORG

1,3-Dipolar Cycloaddition of Azomethine Ylides Generated from Aziridines in Supercritical Carbon Dioxide Paulo J

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
1,3-Dipolar Cycloaddition of Azomethine Ylides Generated from Aziridines in Supercritical Carbon Dioxide Paulo J Tetrahedron Letters 47 (2006) 5475–5479 1,3-Dipolar cycloaddition of azomethine ylides generated from aziridines in supercritical carbon dioxide Paulo J. S. Gomes, Cla´udio M. Nunes, Alberto A. C. C. Pais, Teresa M. V. D. Pinho e Melo* and Luis G. Arnaut Department of Chemistry, Coimbra University, 3004-535 Coimbra, Portugal Received 8 March 2006; revised 26 May 2006; accepted 30 May 2006 Abstract—The 1,3-dipolar cycloaddition of azomethine ylides with DMAD in supercritical carbon dioxide is reported. The photo- lysis reaction conditions were optimized with a suitable adjustment of pressure, temperature, irradiation time and co-solvent concen- tration leading to a more efficient reaction than in neat acetonitrile. Similar results were observed using thermal reaction conditions. Supercritical carbon dioxide with a minute co-solvent addition is shown to be a very efficient medium for promoting this type of cycloadditions. Ó 2006 Elsevier Ltd. All rights reserved. Over the last decade, supercritical fluids (SCF) received ology for the synthesis of nitrogen-heterocyclic significant attention as a new class of environmentally compounds. We chose the 1,3-dipolar cycloaddition friendly solvents for organic synthesis. Supercritical flu- of azomethine ylides generated from aziridines as the ids have properties intermediate between the gas and the model reaction. Aziridines (1) undergo electrocyclic ring liquid phases that can be tuned simply by changing the opening in a disrotatory manner upon irradiation and pressure and temperature. In particular, changes of pres- conrotatory ring opening upon thermolysis, giving sure close to the critical point enable drastic changes in azomethine ylides (2), which participate in 1,3-dipolar density and viscosity. Supercritical carbon dioxide cycloadditions (Scheme 1). (scCO2) has received special attention since it is readily accessible with low critical temperature (Tc =31°C) As the first objective we decided to study the photolysis and moderate critical pressure (Pc = 75.8 bar). Super- of aziridine 3 in the presence of dimethyl acetylene- critical carbon dioxide is also a desirable organic solvent dicarboxylate (DMAD) using conventional reaction replacement because it is abundant, inexpensive, non- conditions (Scheme 2). Ethyl 3-phenylaziridine-2- toxic, non-flammable and easily separated from the carboxylate 3 was prepared as described in the litera- reaction mixture.1 ture.4 We found that irradiation of a solution of 3 and DMAD in acetonitrile using a Hg lamp (20 °C, The study of model reactions is an efficient strategy to k = 254 nm, 1 h) affords 5-phenyl-2,3-dihydro-1H-pyr- 5 get knowledge on the chemical reactivity in scCO2. That role-2,3,4-tricarboxylate 4 in 69% yield. Thus, the ini- is the case of the 1,3-dipolar cycloaddition, an important tially formed 1,3-dipolar cycloadduct isomerizes giving and general route to the construction of five-membered the final product. A 42 min irradiation in acetonitrile heterocyclic ring systems.2 However, 1,3-dipolar cyclo- with the fourth harmonic (266 nm) of the Nd:YAG laser addition in scCO2 is an area almost unexplored and only also gave 4 in 69% yield. Dicyano-sensitized photoreac- reports on the cycloaddition of mesonitrile oxide and of tion of aziridine 3 with DMAD was also carried out 3-phenylsydnone are known.3 The cycloaddition of leading to compound 4 in 68% (20 °C, k = 380 nm, azomethine ylides is a particularly powerful method- 25 min). Keywords: Supercritical carbon dioxide; 1,3-Dipolar cycloaddition; The optimization of the cycloaddition reaction in scCO2 Azomethine ylides; Aziridines. requires the control of one additional variable, pressure, * Corresponding author. Tel.: +351 239 854475; fax: +351 239 in addition to temperature and irradiation time. Cursory 826068; e-mail: [email protected] experiments revealed that the maximum efficiency 0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.05.179 5476 P. J. S. Gomes et al. / Tetrahedron Letters 47 (2006) 5475–5479 3 R3 R R3 R1 N H ΔνN h R1 N R2 1 2 R2 R R H 2b 1 2a Scheme 1. MeO C CO Me MeO2C CO2Me 2 2 H MeO2C CO2Me N MeO2C CO2Me Ph CO2Et hν 380 nm ν Ph N CO2Et N Ph CO Et h 254 nm H MeCN, 25 min 2 MeCN, 1 h H 4 68% DCB 3 4 69% Scheme 2. approached 43% at 110 bar, 45 °C and an irradiation Table 1. The four factors in the 24 factorial design and the respective time of 42 min with the fourth harmonic (266 nm) of yield the Nd:YAG laser. Clearly, the maximum yield in MeO C CO Me H 2 2 scCO2 is much less than in acetonitrile. Further DMAD improvement of the yield required the use of acetonitrile N hν scCO 2 Ph N CO2Et as co-solvent, which introduces a fourth variable in the Ph CO2Et optimization procedure. This optimization was con- H ducted, as a first approach, resorting to a full 2k factorial 3 4 a 6 planning, with k = 4 factors. These comprise pressure It/min V/mL T/°C P/bar Yield/% (P), temperature (T), irradiation time (It) and the vol- 20 0.1 35 110 42 ume of acetonitrile (V) as co-solvent. The initial objec- 20 0.1 45 110 63 tive function has the form 40 0.1 35 140 43 20 0.2 45 110 54 yield ð%Þ¼cte þ aIt It þ aV V þ aT T þ aP P 20 0.2 35 110 31 20 0.1 35 140 35 þ aItV ItV þÁÁÁþaItVT ItVT þÁÁÁ 40 0.2 35 140 21 þ a I VTP ð1Þ 40 0.1 45 110 21 ItVTP t 40 0.2 45 140 27 20 0.1 45 140 18 A summary of factor levels and yields can be found in 40 0.2 35 110 28 Table 1, while Table 2 summarizes the values of coeffi- 40 0.2 45 110 34 cients determined using a standard approach7,8 in which 20 0.2 35 140 44 20 0.2 45 140 28 a normalization to À1 and +1 of the lower and upper 40 0.1 45 140 27 level values was performed. Results in Table 2 suggest 40 0.1 35 110 32 a discrimination of effects based on the interaction a terms. In fact, all power 1 coefficients are negative, but Volume of acetonitrile. interaction terms vary signal. Also, a significant number of interaction terms are, for the ranges used, of the same 4 order of magnitude as the direct effect of each factor. Table 2. Values of coefficients for a full 2 factorial design (Eq. 1) One of the most substantial terms reveals a strong inter- (cte = 0.3425) action between pressure and temperature. Conse- iai ij aij ijk aijk quently, pressure and temperature were transformed It À0.053 ItÆV À0.0071 ItÆVÆT 0.0223 into density, and this variable was taken as the most sig- V À0.0096 VÆT 0.0261 VÆTÆP 0.003 nificant one to characterize scCO2. The original 16 T À0.003 TÆP À0.0511 ItÆVÆP 0.0446 experiments were then transformed in a corresponding P À0.0385 ItÆT À0.0155 ItÆTÆP 0.0443 3 2 full factorial planning, without conducting further ItÆP 0.0422 experiments. The results indicate that the reaction yield VÆP 0.0055 is higher for low density values of the reactant mixture. This allows the use of an additionally simplified form of Eq. 1, which includes only the irradiation time and the volumes. A direct search for It > 34 min lead to yields as volume of added acetonitrile. Again, for normalized val- high as 75% (t = 42 min and V =25lL; Fig. 2). The ues of the levels, we obtain Eq. 2 that can be used to accuracy of the model was tested conducting experi- maximize yield. This function is represented in Figure ments in conditions anticipated to be less than ideal, 1 imposing a yield of 100%. It possesses a singularity and in all cases the yield was less than for the combina- for 15 min irradiation time; also, on the right branch, tion of parameters recommended by the model. The the zone It < 34 min corresponds to unphysical negative actual search along the set of variables anticipated to P. J. S. Gomes et al. / Tetrahedron Letters 47 (2006) 5475–5479 5477 yield ð%Þ¼0:6511 þ 0:0002It þ 0:0157 V À 0:0345ItV ð2Þ The model leads to the unexpected prediction that the maximum yield of the cycloaddition should be observed at low scCO2 densities and minute co-solvent concentra- tions. This was entirely verified experimentally. In par- ticular, the yield is maximized when 23 mol of acetonitrile are present for 1 mol of aziridine and 2.3 mol of DMAD.9 This shows that only a thin solva- tation layer is required to maximize the yield, and addi- tional acetonitrile molecules are not necessary. The work was extended to the study of the reactivity of aziridine 510 towards photolysis and thermolysis, in the presence of DMAD (Scheme 3). The irradiation of azi- ridine 5 in acetonitrile using a Hg lamp (20 C, Figure 1. ° k = 254 nm, 5 h) gave pyrrole 6 (38%) and pyrrole 7 (19%), together with unreacted aziridine 5 (15%). On the other hand, the cycloaddition of azomethine ylide generated by the thermolysis of aziridine 5 with DMAD produced pyrrole 6 in 42% yield as the only product. The irradiation with the fourth harmonic (266 nm) of the Nd:YAG laser of aziridine 5 in the presence of DMAD in scCO2 led to pyrrole 6 in poor yield (3–5%) and no improvement was observed using acetonitrile as co-solvent (Table 3).
Load more

Recommended publications
  • New Methods for the Synthesis of Heterocyclic Compounds*
    Pure Appl. Chem., Vol. 76, No. 3, pp. 603–613, 2004. © 2004 IUPAC New methods for the synthesis of heterocyclic compounds* Aldo Caiazzo1, Shadi Dalili1, Christine Picard2, Mikio Sasaki1, Tung Siu2, and Andrei K. Yudin1,‡ 1Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada; 2Ylektra, Inc., 100 University Ave., 10th Floor, South Tower, Toronto, Ontario M5J 1V6, Canada Abstract: Due to frequent occurrence of nitrogen-containing groups among the biologically active compounds, chemoselective functionalization of organic molecules with nitrogen-con- taining functional groups is an important area of organic synthesis. We have proposed and implemented a new strategy toward design of nitrogen-transfer reactions on inert electrode surfaces with a particular focus on the generation and trapping of highly reactive nitrogen- transfer agents. A wide range of structurally dissimilar olefins can be readily transformed into the corresponding aziridines. The resulting aziridines are precursors to a range of cata- lysts via nucleophilic ring-opening with diaryl- and dialkyl phosphines. Another strategy ex- plored in the context of oxidative nitrogen transfer is cycloamination of olefins using NH aziridines. INTRODUCTION The transformations of organic compounds belong to one of the following two broad categories: car- bon–carbon bond-forming reactions and redox processes. Over the years, remarkable progress has been achieved in design and applications of novel metal-based complexes in oxidation chemistry. The metal center of such a catalyst is surrounded by a ligand, which resembles and emulates the function of the enzyme active site. This strategy is known to adequately address the issues of regio-, chemo-, and stereoselectivity in a number of synthetic transformations.
    [Show full text]
  • Recent Advances in Titanium Radical Redox Catalysis
    JOCSynopsis Cite This: J. Org. Chem. 2019, 84, 14369−14380 pubs.acs.org/joc Recent Advances in Titanium Radical Redox Catalysis Terry McCallum, Xiangyu Wu, and Song Lin* Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States ABSTRACT: New catalytic strategies that leverage single-electron redox events have provided chemists with useful tools for solving synthetic problems. In this context, Ti offers opportunities that are complementary to late transition metals for reaction discovery. Following foundational work on epoxide reductive functionalization, recent methodological advances have significantly expanded the repertoire of Ti radical chemistry. This Synopsis summarizes recent developments in the burgeoning area of Ti radical catalysis with a focus on innovative catalytic strategies such as radical redox-relay and dual catalysis. 1. INTRODUCTION a green chemistry perspective, the abundance and low toxicity of Ti make its complexes highly attractive as reagents and Radical-based chemistry has long been a cornerstone of 5 1 catalysts in organic synthesis. synthetic organic chemistry. The high reactivity of organic IV/III radicals has made possible myriad new reactions that cannot be A classic example of Ti -mediated reactivity is the reductive ring opening of epoxides. This process preferentially readily achieved using two-electron chemistry. However, the − high reactivity of organic radicals is a double-edged sword, as cleaves and functionalizes the more substituted C O bond, the selectivity of these fleeting intermediates can be difficult to providing complementary regioselectivity to Lewis acid control in the presence of multiple chemotypes. In addition, promoted epoxide reactions. The synthetic value of Ti redox catalysis has been highlighted by their many uses in total catalyst-controlled regio- and stereoselective reactions involv- 6−10 ing free-radical intermediates remain limited,2 and the synthesis (Scheme 1).
    [Show full text]
  • The Synthesis and Applications of N-Alkenyl Aziridines
    The Synthesis and Applications of N-Alkenyl Aziridines by Nicholas A. Afagh A thesis submitted in conformity with the requirements for the degree of Master of Science Department of Chemistry University of Toronto © Copyright by Nicholas A. Afagh 2010 The Synthesis and Applications of N-Alkenyl Aziridines Nicholas A. Afagh Master of Science Department of Chemistry University of Toronto 2010 Abstract N-alkenyl aziridines are a unique class of molecules that do not behave as typical enamines as a result of the inability of the nitrogen atom lone-pair of electrons to delocalize. The attenuated nucleophilicity of these enamines presents opportunities for the selective functionalization and reactivity not available to classical enamines. An operationally simple and mild copper-mediated coupling has been developed that facilitates the preparation of a broad range of N-alkenyl aziridines not available through existing methods. The preparation and reactivity of highly- functionalized N-alkenyl aziridines are reported. Also reported is the application of the chemoselective amine/aldehyde/alkyne (A 3) multicomponent coupling involving amphoteric aziridine aldehydes as the aldehyde component. This coupling allows access to propargyl amines with pendent aziridine functionality. ii Acknowledgments First and foremost, I would like to thank my supervisor, Professor Andrei K. Yudin for his continuous support and encouragement over the past two years. His wealth of knowledge and profound insight into all matters chemistry made for many interesting discussions. In addition, I would like to thank all the members of the Yudin group past and present with whom I have had the distinct pleasure of working alongside and shared many late evenings.
    [Show full text]
  • New Chiral Auxiliaries for the [3+2]-Cycloaddition of Nonstabilised Azomethine Ylides
    New Chiral Auxiliaries For The [3+2]-Cycloaddition Of Nonstabilised Azomethine Ylides Allan Rostrup Forup Jensen A thesis submitted in partial fulfilment of the degree of Doctor of Philosophy Christopher Ingold Laboratories University College London London 20 Gordon Street WC1H OAJ ProQuest Number: 10610918 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10610918 Published by ProQuest LLC(2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 /\cjmowieugemenis First and foremost I wish to thank my supervisor, Professor K. J. Hale, for the constant support, encouragement and guidance he has provided throughout the duration of this project. I also wish to take this opportunity to thank my sponsor, Rhone- Poulenc-Rorer, without whom this project would not have been possible. I also wish to thank past and present members of the Hale group for their friendship and encouragement. In particular, Dr. J. Cai was an invaluable help and inspiration. For their friendship and enormous support through good and bad times, Rukpong Tupprasoot, Neha Jogiya, Andrew Calabrese, Dr. Gurpreet Bhatia, Marc Hummersone, Rafaqat Hussain, also deserve to be mentioned.
    [Show full text]
  • Aziridination of Alkenes Promoted by Iron Or Ruthenium Complexes
    Aziridination of Alkenes Promoted by Iron or Ruthenium Complexes Caterina Damiano, Daniela Intrieri and Emma Gallo* Department of Chemistry, University of Milan, Via C. Golgi 19, 20133 Milan (Italy). E-mail address: [email protected]. Keywords: Aziridines, Nitrene reagents, Alkenes, Homogenous catalysis, Iron, Ruthenium. Abstract Molecules containing an aziridine functional group are a versatile class of organic synthons due to the presence of a strained three member, which can be easily involved in ring-opening reactions and the aziridine functionality often show interesting pharmaceutical and/or biological behaviours. For these reasons, the scientific community is constantly interested in developing efficient procedures to introduce an aziridine moiety into organic skeletons and the one-pot reaction of an alkene double bond with a nitrene [NR] source is a powerful synthetic strategy. Herein we describe the catalytic activity of iron or ruthenium complexes in promoting the reaction stated above by stressing the potential and limits of each synthetic protocol. 1. Introduction Aziridines, the smallest N-heterocycle compounds, have attracted considerable attention in the last few decades due to their many applications in biological and synthetic chemistry [1]. The aziridine functionality is often responsible for the activity of biologically active species (such as antitumor compounds, antibiotics and enzyme inhibitors) and aziridine containing molecules [2] are also useful building blocks in the synthesis of fine chemicals and pharmaceuticals [3-6]. The striking chemical properties of aziridines are due to the energy associated to the strained three- membered ring [7], which renders them very active and versatile starting materials for the synthesis of several useful molecules such as amines, amino acids, β-lactams, polymers and α-amido ketones [8, 9].
    [Show full text]
  • Sigmatropic Rearrangement of Vinyl Aziridines: Expedient Synthesis of Cyclic Sulfoximines from Chiral Sulfinimines Toni Moragas,A Ryan M
    Sigmatropic Rearrangement of Vinyl Aziridines: Expedient Synthesis of Cyclic Sulfoximines from Chiral Sulfinimines Toni Moragas,a Ryan M. Liffey,a Dominika Regentová,a Jon-Paul S. Ward,a Justine Dutton,a William Lewis,a Ian Churcher,b Lesley Walton,c José A. Souto,a,d Robert A. Stockmana* Abstract: A novel rearrangement of 2-vinyl aziridine 2-carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, displaying a wide substrate scope under mild conditions. Further development of a one-pot process directly from sulfinimines shows the synthetic applicability of this protocol, providing access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine by transformation of a cyclic sulfoximine into a pyrroline is also disclosed. Since the first isolation of sulfoximines by Bentley and coworkers in 19501 these sulfur containing compounds have found applications in functional group transformations and asymmetric synthesis,2 drug development,3 crop treatment4 and insect control.5 Largely ignored in medicinal chemistry for around 50 years, the sulfoximine group has recently been the object of significant new interest in this area.3 Sulfoximines are three-dimensional motifs with three points of attachment in orthogonal vectors,6 with functionalisation at nitrogen and carbon alpha to the sulfur both versatile and facile. 7-9 Despite the promising biological activity showed by the few previously synthesised cyclic sulfoximines,3 methods describing the synthesis of these compounds are scarce and mainly involve the multistep synthesis of linear sulfoximines10,11 and subsequent cyclisations.12 Furthermore, they generally describe benzo-fused cyclic sulfoximines.
    [Show full text]
  • Electrocyclic Reactions of Aziridines
    ELECTROCYCLIC RUCTIONS OF AZIRIDINES by MUHAMMAD HUMAYOUN AKHTAR M. Sc., University of Moncton, 1966. A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in the Department of Chemistry @ WHAMMAD HUMAYOUN AKHTAR , 1970 SIMON FRASER UNIVERSITY August, 1970 A PPR OVA L Name : Muhammad Humayoun Akhtar Degree : Doc tor of Philosophy Title of' Thesis: Electrocyclic Reactions of Aziridines Examining Committee: ,, A. C . Oehlschlaire'u' Senior supervisa/ . .- ' A. G. SherviooP Examining Committee - - K. ?I.Slessor ~xami~kn~Committee A. Fischer External Examiner Professor Department of Chemistry The University of Victoria Victoria, British Columbia Abstract Temperature dependent nmr spectra have been observed for a series of para-substi tuted 1-aryl-3,3- dimethyltriazenes . The temperature dependence has been interpreted in terms of restricted internal rotation about the N2,Fj bond of these triazenes and activation para- 5 meters AF', AH', and AS have been calculated from the spectral data. The origin of the rotational barrier is considered to lie in partial double bond formation between hT2 and T3 due to the contribution of 1,3-dipolar resonance hybrids to the qround states of these triazenes. This interpretation is supported by a sizable substituent effect o= -2'1 for the rotational process in the series studied. Chemical shift data at low temperatures indicates a stereo- specific association of benzene with the triazenes studied which places the benzene ring closer to the trans N-Me group in the 1,3-dipolar resonance hybrid. The thermal decomposition of ~T-arylazoaziridines follows two routes; one giving arylazide and alkene (stereospecif ically) and the other giving products typical of homolysis of the azo-linkage.
    [Show full text]
  • Asymmetric Nitrene Transfer Reactions with Azides Via Co(II)-Based Metalloradical Catalysis (MRC) Jingran Tao University of South Florida, [email protected]
    University of South Florida Scholar Commons Graduate Theses and Dissertations Graduate School January 2013 Asymmetric Nitrene Transfer Reactions with Azides via Co(II)-Based Metalloradical Catalysis (MRC) Jingran Tao University of South Florida, [email protected] Follow this and additional works at: http://scholarcommons.usf.edu/etd Part of the Chemistry Commons Scholar Commons Citation Tao, Jingran, "Asymmetric Nitrene Transfer Reactions with Azides via Co(II)-Based Metalloradical Catalysis (MRC)" (2013). Graduate Theses and Dissertations. http://scholarcommons.usf.edu/etd/4590 This Dissertation is brought to you for free and open access by the Graduate School at Scholar Commons. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. Asymmetric Nitrene Transfer Reactions with Azides via Co(II)-Based Metalloradical Catalysis (MRC) by Jingran Tao A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Chemistry College of Arts and Sciences University of South Florida Major Professor: X. Peter Zhang, Ph.D. Jon Antilla, Ph.D. Wayne Guida, Ph.D. Xiao Li, Ph.D. Date of Approval: April 3rd , 2013 Keywords: cobalt, porphyrin, catalysis, aziridination, C–H amination, azide, asymmetric Copyright © 2013, Jingran Tao Dedication I dedicate this dissertation to my beloved parents. Acknowledgments I need to begin with thanking Dr. Peter Zhang for his continuous guidance and support. I learned the words “determination” and “believe” from him. I also need to thank my committee members: Dr. Jon Antilla, Dr. Wayne Guida Dr. Xiao Li and Chair Dr.
    [Show full text]
  • Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis Christopher K
    Review pubs.acs.org/CR Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis Christopher K. Prier, Danica A. Rankic, and David W. C. MacMillan* Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States References 5360 1. INTRODUCTION CONTENTS A fundamental aim in the field of catalysis is the development 1. Introduction 5322 of new modes of small molecule activation. One approach 2+ toward the catalytic activation of organic molecules that has 2. Photochemistry of Ru(bpy)3 5323 3. Net Reductive Reactions 5324 received much attention recently is visible light photoredox 3.1. Reduction of Electron-Poor Olefins 5324 catalysis. In a general sense, this approach relies on the ability of 3.2. Reductive Dehalogenation 5326 metal complexes and organic dyes to engage in single-electron- 3.3. Reductive Cleavage of Sulfonium and transfer (SET) processes with organic substrates upon Sulfonyl Groups 5328 photoexcitation with visible light. 3.4. Nitrogen Functional Group Reductions 5329 Many of the most commonly employed visible light 3.5. Radical Cyclizations 5330 photocatalysts are polypyridyl complexes of ruthenium and iridium, and are typified by the complex tris(2,2′-bipyridine) 3.6. Reductive Epoxide and Aziridine Opening 5331 2+ 3.7. Reduction-Labile Protecting Groups 5331 ruthenium(II), or Ru(bpy)3 (Figure 1). These complexes 4. Net Oxidative Reactions 5332 4.1. Functional Group Oxidations 5332 4.2. Oxidative Removal of the PMB Group 5334 4.3. Oxidative Biaryl Coupling 5335 4.4. Oxidative Generation of Iminium Ions 5335 4.5. Azomethine Ylide [3 + 2] Cycloadditions 5338 4.6.
    [Show full text]
  • PERSONAL ACCOUNT Binap and Phosphoramidites As Privileged
    PERSONAL ACCOUNT Carmen Nájera,*[a] and José M. Sansano*[b] Binap and phosphoramidites as Dedication ((optional)) privileged chiral ligands for the metal-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylides and dipolarophiles ((Insert Picture for Frontispiece here [18.0×18.0 cm])) [a] Title(s), Initial(s), Surname(s) of Author(s) including Corresponding Author(s) Department Institution Address 1 E-mail: [b] Title(s), Initial(s), Surname(s) of Author(s) Department Institution Address 2 Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate)) 1 PERSONAL ACCOUNT Abstract: Binap and phosphoramidites are privileged chiral starting from enolizable substrates I and electron-deficient ligands which have been tested in the coinage metal-catalyzed alkenes III promoted by coinage metals and the named chiral 1,3-dipolar cycloadditions of metalloazomethine ylides and ligands on the basis of the dipolarophile employed (Scheme 1). electrophilic alkenes. Silver(I), copper(II) and gold(I) salts have Rigid chiral metallodipoles II control of the final absolute been evaluated in all these reactions. Maleimides, acrylates, configuration of the up to four stereogenic centers of fumarates, 1,2-bis(phenylsulfonyl)ethylene and enones reacted polysubstituted proline derivatives IV. with imino esters giving the corresponding endo-prolinates such as HCV inhibitors in high diastereo- and enantioselectivity. In the case of nitroalkenes exo-4-nitroprolinates were obtained. Azlactones reacted with maleimides and acrylates to give pyrrolines only in the presence of binap-gold(I) complexes. The observed enantioselectivity and the mechanism of these 1,3-DC was studied by means of DFT calculations.
    [Show full text]
  • Anionic Polymerisation of Aziridines
    MAX-PLANCK-INSTITUT FÜR POLYMERFORSCHUNG JOHANNES GUTENBERG‐UNIVERSITÄT MAINZ Anionic Polymerisation of Aziridines Diplomarbeit zur Erlangung des Grades eines Diplom‐Chemikers am Institut für Organische Chemie des Fachbereiches Chemie, Pharmazie und Geowissenschaften der Johannes Gutenberg-Universität Mainz vorgelegt von Laura Thomi geboren in Frankfurt am Main Mainz 2013 Diese Arbeit wurde in der Zeit von November 2012 bis Juli 2013 am Institut für Organische Chemie der Johannes Gutenberg‐Universität Mainz und am Max-Planck-Institut für Polymerforschung in Mainz unter der Betreuung von Herrn Prof. Dr. Holger Frey und Frau Prof. Dr. Katharina Landfester durchgeführt. für meine Eltern “We live on an island surrounded by a sea of ignorance. As our island of knowledge grows, so does the shore of our ignorance.” - John Archibald Wheeler Danksagung Mein Dank gilt Herrn Prof. Dr. Holger Frey und Frau Prof. Dr. Katharina Landfester für die Bereitstellung des Themas und die ausgezeichneten Arbeitsbedingungen. Zudem danke ich Herrn Dr. Frederik Wurm für die freundliche Aufnahme in seine Gruppe und die hervorragende Betreuung der Arbeit. Bei allen Mitgliedern der Arbeitsgruppe Frey bedanke ich mich für die wunderbare Arbeitsatmosphäre und die Unterstützung bei dieser Arbeit. Herrn Christian Moers und Herrn Jan Seiwert danke ich, dass sie mir die anionische Polymerisation von Styrol und Ethylenoxid näher gebracht haben. Bei Frau Anna Hesse und Herrn Christian Moers bedanke ich mich für das Korrekturlesen dieser Arbeit. Frau Katja Weber danke ich für die Bereitstellung des 2-Methyl-N-tosylaziridins. Für die GPC Messungen danke ich Frau Christine Rosenauer und insbesondere Frau Monika Schmelzer. Bei Frau Dr. Elena Berger-Nicoletti möchte ich mich für zahlreiche MALDI Messungen bedanken.
    [Show full text]
  • Synthesis and Biological Activity of N-Acyl Aziridines a Dissertation
    Synthesis and Biological Activity of N-Acyl Aziridines A dissertation presented to the faculty of the College of Arts and Sciences of Ohio University In partial fulfillment of the requirements for the degree Doctor of Philosophy Greggory M. Wells April 2016 © 2016 Greggory M. Wells. All Rights Reserved. 2 This dissertation titled Synthesis and Biological Activity of N-Acyl Aziridines by GREGGORY M. WELLS has been approved for the Department of Chemistry and Biochemistry and the College of Arts and Sciences by Stephen C. Bergmeier Professor of Chemistry and Biochemistry Robert Frank Dean, College of Arts and Sciences 3 ABSTRACT WELLS, GREGGORY M., Ph.D., April 2016, Chemistry Synthesis and Biological Activity of N-Acyl Aziridines Director of Dissertation: Stephen C. Bergmeier The development of new antimicrobial drugs is essential as the human population continues to build resistance to current treatments. Peptidomimetic compounds, those synthesized to mimic the behavior of naturally occurring biological proteins, have demonstrated promise in this area. Using bicyclic aziridine ring opening reactions, a library of N-acyl aziridinyl peptide isosteres has been synthesized and submitted to biological assays for cysteine protease inhibition, a common pathway to suppression of bacteria. Most of the compounds tested showed good activity against cathepsin B. This research required a novel synthetic approach to selectively generating oxazolidinones and aziridinyl ureas from fused bicyclic aziridines, which was accomplished with solvent selection, nucleophilic amine stoichiometry, and aziridine substitution. To extend the peptidic nature of these compounds, some success was achieved with acylation and amide coupling reactions. A practical approach to generating enantiomerically pure bicyclic aziridines was investigated, however the best enantioselective conditions provided only a 3 : 1 ratio.
    [Show full text]