DOCSLIB.ORG

An Intramolecular Prins Double Cyclization Catalyzed by Silyl Triflates1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Intramolecular Prins Double Cyclization Catalyzed by Silyl Triflates1 9182 J. Org. Chem. 1997, 62, 9182-9187 An Intramolecular Prins Double Cyclization Catalyzed by Silyl Triflates1 Michael E. Jung,*,2 Steve Angelica, and Derin C. D’Amico3 Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569 Received July 22, 1997X Several intramolecular Prins double cyclizations are reported. The 2-alkyl 5-hepten-1,2-diols and their analogues, 9-11, were prepared and oxidized to the aldehydes 6-8 under Swern conditions. Treatment of these R-hydroxy aldehydes with TBSOTf and a hindered base gave the products of an intramolecular Prins double cyclization, namely the 7-(silyloxy)-2-oxabicyclo[2.2.1]heptanes, 17- 19,in84-92% yield. These compounds were formed as single diastereomers with only the anti silyl ethers being obtained. The cyclizations occur when five-membered rings are being formed and when the initially formed cation is highly stabilized. Other substrates do not cyclize, e.g., when the R-hydroxy aldehydes 20-22, prepared from 26-28, are treated under similar conditions, none of the corresponding cyclization products, 23-25, were obtained. In the attempted protection of the R-hydroxy aldehyde Scheme 1 1 as the triethylsilyl ether, in addition to the expected product 2, which was isolated in 17% yield, we isolated the double cyclization product 3 in 40% yield as the primary product.4 We discovered that triethylsilyl tri- flate in the presence of collidine catalyzed an intramo- lecular Prins reaction presumably via the silylated aldehyde 4, which was attacked by the trisubstituted alkene to produce the tertiary carbocation 5 as an intermediate which then was trapped by the alcohol in a second intramolecular cyclization (Scheme 1). We wanted to investigate the generality and scope of this novel reaction with related substrates. We also thought that a more hindered reagent such as tert-butyldimeth- ylsilyl triflate (TBSOTf) might give a higher yield of 5 by discouraging the competing protection of the alcohol to give the analogue of 2 and thereby favoring the Scheme 2 production of the analogue of 3. A search of the literature revealed only a few prece- dents for this kind of tandem reaction. Kiyooka demon- strated an intermolecular Prins reaction where a car- bobenzyloxy-protected nitrogen formed the second bond, in that case resulting in a single ring.5 In attempting an ene reaction starting from an acetal, Bertrand ob- served a mixture of products including one in which the liberated alcohol trapped the generated cation.6 But the general use of an intramolecular Prins reaction to prepare 2-oxabicyclo[2.2.1]heptane-7-ol derivatives was unknown. As a general method for accessing these δ-olefinic R-hydroxy aldehydes 6-8, we chose to synthesize the (BOM-Cl)8 and 6-methyl-5-hepten-2-one (12) in the pres- diols 9-11 (Scheme 2) by a variety of routes and then to ence of samarium diiodide (88% yield) followed by dis- use the Swern oxidation7 to produce the desired sub- solving metal reduction of the benzyl group (83% yield). strates. The diol 9 was available in two steps and 74% The diol 10 was prepared by the addition of the Grignard overall yield by coupling (benzyloxy)methyl chloride reagent of the known9 bromide 13 to sodium R-ketobu- tyrate (14) followed by hydride reduction. Finally the X Abstract published in Advance ACS Abstracts, December 1, 1997. cinnamyl diol 11 was prepared by addition of the Grig- (1) Presented at the 213th National Meeting of the American 10 Chemical Society, Las Vegas, NV, September 1997. nard reagent of the known bromide 15 to 1-[(tetrahy- (2) American Chemical Society Arthur C. Cope Scholar, 1995. drofuranyl)oxy]acetone 16 followed by acidic hydrolysis. (3) UCLA Department of Chemistry Prize for Excellence in Research Of the various possible oxidation methods, the Swern 1993-94; UCLA Dissertation Year Fellowship 1994-95. Current address: Zeneca Pharmaceuticals, Wilmington, DE 19850-5437. oxidation proved to be the most reliable, converting the (4) D′Amico, D. C. Ph.D. Dissertation, University of California, Los diols 9-11 into the desired R-hydroxy aldehydes 6-8 in Angeles, 1995. (5) Kiyooka, S., Shiomi, Y., Kira, H., Kaneko, Y.; Tanimori, S. J. Org. Chem. 1994, 59, 1958. (8) Imamoto, T., Takeyama, T.; Yokoyama, M. Tetrahedron Lett. (6) Bertrand, M., Rousmestant, M-L.; Sylvestre-Panthet, P. J. 1984, 25, 3225. Chem. Soc., Chem. Commun. 1979, 529. (9) Biernacki, W.; Gdula, A. Synthesis 1979, 37. (7) Mancuso, A. J.; Swern, D. Synthesis 1981, 165. (10) McCormick, J. P.; Barton, D. L. J. Org. Chem. 1980, 45, 2566. S0022-3263(97)01337-6 CCC: $14.00 © 1997 American Chemical Society Prins Double Cyclization Catalyzed by Silyl Triflates J. Org. Chem., Vol. 62, No. 26, 1997 9183 Scheme 3 Scheme 4 good yields. These compounds proved to be somewhat 22 to give compound 25 would have required the forma- unstable, decomposing on attempted chromatography on tion of a six-membered ring from the initial Prins silica gel and therefore were generally carried forward reaction, a process which is known to be less facile.12 in dichloromethane solution to the next reaction, the key Attempts to use stronger Lewis acids, e.g., various alkyl- double cyclization. substituted aluminum halides, did not give better results. As shown in Scheme 3, treatment of the R-hydroxy Thus, in summary, we have demonstrated a novel aldehydes 6-8 with tert-butyldimethylsilyl triflate and intramolecular Prins double cyclization reaction effective the hindered base 2,6-di-tert-butyl-4-methylpyridine for a family of related R-hydroxy aldehydes with a (DBMP) afforded the desired intramolecular Prins prod- properly spaced and electron-rich double bond. We have ucts 17-19 in yields of 84-92% over the two steps from optimized this reaction to afford yields of 84-92% for the the diols 9-11. Thus this intramolecular Prins double two steps from the corresponding diols including a Swern cyclization works well for systems forming five-membered oxidation. Further research is currently underway in rings in the initial step and where the initially formed this area. cation is highly stabilized, e.g., tertiary or benzylic. In all cases examined, the products were formed with Experimental Section high diastereoselectivity, with only the anti silyl ether being produced. This stereochemistry is presumably due General. Thin-layer chromatography (TLC) was performed to the other possible cyclization, which would give the using Merck silica gel 60 F254 0.2 mm plates. Visualization was accomplished using ultraviolet light or the following silyl ether syn to the dimethyl-substituted carbocation, stain: anisaldehyde (2 mL), acetic acid (10 mL), and sulfuric being subject to severe steric hindrance so that the acid (2 mL) in 95% ethanol (85 mL). Flash chromatography observed cyclization is greatly favored (e.g., 4 f 5). was carried out using ICN Biomedicals silica gel 60 (230-400 However, not all substrates could be induced to un- mesh). Solvent systems are reported as volume percent dergo the double cyclization, even those with quite mixtures. Concentration or evaporation of solvent refers to similar structures. For example (Scheme 4) the olefinic removal at reduced pressure using a Bu¨ chi rotary evaporator R-hydroxy aldehydes 20-2211 did not produce any of the and an aspirator pump. All inorganic solutions are aqueous, and concentrations are indicated in percent weight, except for desired materials, 23 25, under these cyclization condi- - saturated sodium chloride, saturated sodium carbonate, and tions. We believe that the cyclization of 20 failed because saturated ammonium chloride. The following solvents and the disubstituted double bond was not sufficiently electron- reagents were distilled from the indicated agent under argon: rich. In the case of compound 21, the bulky phenyl group tetrahydrofuran (THF) and diethyl ether from sodium ben- R to the aldehyde may have created unfavorable steric zophenone ketyl; dichloromethane, acetonitrile, and triethy- hindrance to the cyclization. Finally, the cyclization of lamine from calcium hydride. Dimethyl sulfoxide (DMSO) was distilled from calcium hydride under reduced pressure. Oxalyl chloride was distilled just prior to use. All solvents were stored (11) The precursors to these substrates were prepared as follows (see Experimental Section for details). (a) Compound 26: reaction of over calcium hydride. 5-hepten-2-one neat with TESCN (prepared from TESCl and TMSCN 2,6-Dimethyl-5-heptene-1,2-diol (9). To a 100 mL oven- by the method of Bither, T. A., Knoth, W. H., Lindsey, R. V., Jr.; dried round-bottom flask under argon were added 30 mL of Sharkey, W. H. J. Am. Chem. Soc. 1958, 80, 4151) and the salt of 18- 0.1 M samarium diiodide (3 mmol) in tetrahydrofuran (THF) crown-6 and KCN as a catalyst. Cf. Corey, E. J., Crouse, D. N.; Anderson, J. E. J. Org. Chem. 1975, 40, 2140. The silyl cyanohydrin was then reduced with DIBAL to give 26. (b) Compound 27: alkylation (12) (a) Snider, B. B. The Prins and Carbonyl Ene Reaction, Chapter of the anion of the triethylsilyl cyanohydrin of benzaldehyde with 2.1 in Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon: 5-bromo-2-methyl-2-pentene (13). Reduction afforded 27. (c) Com- Oxford, 1991; Vol. 2, pp 527-561. (b) Santelli, M.; Pons, J.-M. Lewis pound 28: addition of the Grignard reagent of 5-bromo-2-methyl-2- Acids and Selectivity in Organic Synthesis; CRC Press: Boca Raton, pentene to [(2-ethoxyethoxy)methyl]methyloxirane in the presence of FL, 1996; Chapter 2. (c) In this case, the simple ene product was CuI followed by acidic hydrolysis gave 28. obtained as the major product. 9184 J. Org. Chem., Vol. 62, No.
Load more

Recommended publications
  • Lewis Acid Mediated Reactions of Olefins with Carbonyls
    Lewis Acid Mediated Reactions of Olefins with Carbonyls Submitted by Stephen Flower For the Degree of PhD Of the University of Bath 2002 COPYRIGHT Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without the prior written consent of the author. This thesis may be made available for consultation within the University Library and may be photocopied or lent to other libraries for the purposes of consultation. …………………………..(signed) …………………………..(date) Abstract This thesis is divided into 5 chapters. The first chapter reviews the literature of Carbonyl-ene and Prins reactions. Recent advances in these areas and their application to natural product synthesis and other targeted syntheses are discussed. The second chapter discusses the concept of desymmetrisation using selected examples, including desymmetrising Carbonyl-ene reactions. Chapter Three introduces and discusses the work undertaken in studying the desymmetrising intramolecular carbonyl-ene of a meso-dialdehyde. Chapter Four details the concept of pyruvate-Prins cyclisation giving examples of its potential use. The chapter also gives examples of the use of rigid stereodefined scaffolds and their application. The chapter describes the reactivity of substituted pyruvate esters with cyclic enol ethers, and the elaboration of the cyclised products. The fifth chapter provides experimental details of the procedures reported. i Acknowledgements Many thanks to Dr Mike Willis for all his help and guidance and boundless enthusiasm over the years; and for a detailed investigation of the local pubs.
    [Show full text]
  • BI(III) Initiated Cyclization Reactions and Iodonium Fragmentation Kinetics
    W&M ScholarWorks Dissertations, Theses, and Masters Projects Theses, Dissertations, & Master Projects 2005 BI(III) Initiated Cyclization Reactions and Iodonium Fragmentation Kinetics Yajing Lian College of William & Mary - Arts & Sciences Follow this and additional works at: https://scholarworks.wm.edu/etd Part of the Inorganic Chemistry Commons Recommended Citation Lian, Yajing, "BI(III) Initiated Cyclization Reactions and Iodonium Fragmentation Kinetics" (2005). Dissertations, Theses, and Masters Projects. Paper 1539626842. https://dx.doi.org/doi:10.21220/s2-zj7g-fp23 This Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Dissertations, Theses, and Masters Projects by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. BI(III) INITIATED CYCLIZATION REACTIONS AND IODONIUM FRAGMENTATION KINETICS A Thesis Presented to The Faculty of the Department of Chemistry The College of William and Mary in Virginia In Partial Fulfillment Of the Requirements for the Degree of Master of Science by Yajing Lian 2005 APPROVAL SHEET This thesis is submitted in partial fulfillment of The requirements for the degree of Master of Science A Yajing Lian Approved by the Committee, December 20, 2005 Robert J. Hinkle, Chair Christopher Jl A] Robert D. Pike TABLE OF CONTENTS Page Acknowledgements VI List of Tables Vll List of Schemes V lll List of Figures IX Abstract XI Introduction Chapter I Secondary
    [Show full text]
  • Accessing Light-Sensitive Polycyclic Aromatics Through an Alkynyl-Prins Cyclization
    W&M ScholarWorks Undergraduate Honors Theses Theses, Dissertations, & Master Projects 4-2018 Accessing Light-Sensitive Polycyclic Aromatics through an Alkynyl-Prins Cyclization Daniel John Speer Follow this and additional works at: https://scholarworks.wm.edu/honorstheses Part of the Chemistry Commons Recommended Citation Speer, Daniel John, "Accessing Light-Sensitive Polycyclic Aromatics through an Alkynyl-Prins Cyclization" (2018). Undergraduate Honors Theses. Paper 1244. https://scholarworks.wm.edu/honorstheses/1244 This Honors Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Undergraduate Honors Theses by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. Accessing Light-Sensitive Polycyclic Aromatics through an Alkynyl-Prins Cyclization A thesis submitted in partial fulfillment of the requirement for the degree of Bachelor of Science with Honors in the Department of Chemistry from the College of William and Mary Accepted for Dr. Jonathan Scheerer Dr. Christopher Abelt Dr. Anne Rasmussen Directed by Dr. Robert J. Hinkle By Daniel John Speer April 26, 2018 Table of Contents Acknowledgements 3 Abstract 4 List of Figures 5 Introduction 6 Prins Chemistry and the alkynyl-Prins Cyclization 6 Photochromic Compounds 9 Cannabinoids 12 Results and Discussion 16 Development of Synthetic Procedure 16 Synthesis of Starting Material 17 Proposed Mechanism for the Cyclization 21 Synthesis and NMR Properties of Chromene Products 24 X-ray Crystallographic Analysis 27 UV/Visible Spectrophotometric Analysis 30 Conclusion 33 Experimental Methods 34 Materials and Methods 34 Synthetic Procedures 35 References 43 Supporting Information 46 Mass Spectrum of 11 46 X-ray Crystal Data and Structure Refinement for 11 47 2 Acknowledgements I would like to thank everyone involved in this process.
    [Show full text]
  • Synthetic Strategies for the Lepadiformines and Cylindricine C Via Tandem Schmidt Reactions
    Synthetic Strategies for the Lepadiformines and Cylindricine C via Tandem Schmidt Reactions By Angelica M. Meyer Submitted to the graduate degree program in the Medicinal Chemistry and the Graduate Faculty of The University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. ________________________________ Chairperson: Jeffrey Aubé ________________________________ Dr. Thomas E. Prisinzano ________________________________ Dr. Ryan A. Altman ________________________________ Dean Kenneth L. Audus ________________________________ Dr. Paul R. Hanson Date Defended: December 5, 2011 The Dissertation Committee for Angelica M. Meyer certifies that this is the approved version of the following thesis: Synthetic Strategies for the Lepadiformines and Cylindricine C via Tandem Schmidt Reactions ________________________________ Chairperson Jeffrey Aubé Date approved: December 5, 2011 ii Abstract Marine flora and fauna have provided numerous alluring natural products, some of which contribute to treating diseases. The genus Clavelina is the source of a variety of tricyclic alkaloids, including the lepadiformine and cylindricine families. Novel approaches to synthesizing these molecules are sought after to increase their accessibility and for analogue development. In this dissertation, reaction sequences involving an intramolecular Schmidt transformation, which can quickly build up the molecular architecture associated with these targets is described. In one approach, the Lewis acid promoted intramolecular Schmidt reaction is combined in series with a Prins reaction to afford an interesting tricyclic lactam. This methodology culminates in a formal synthesis of lepadiformine A and a total synthesis of lepadiformine C. In another project, a tandem Diels–Alder/Schmidt reaction is utilized to prepare a similar tricyclic lactam. This process is applied toward an asymmetric total synthesis of (–)-cylindricine C.
    [Show full text]
  • Cyclopentane Synthesis
    Cyclopentane Synthesis Dan O’Malley Baran Group Meeting Cyclopentane Synthesis Group Meeting O'Malley 2/9/2005 This presentation is broken down into the following catagories. Some reactions either fit more than one Students of organic chemistry are taught a number of reactions for the synthesis of category or do not fit easily into any of them. Efforts have been made to place all such reactions in the cyclohexanes at a very early stage of their careers. Techniques for the creation of cyclopentanes, most appropriate category. however, are generally taught at a much later stage and are rarely given the same detailed treatment. This may be the result of the fact that there are no equivalents of reactions such as the Diels-Alder and I. General Information Robinson Annulation in terms of generality, extent of use, and historical importance. This may, in turn, II. Ionic Reactions be caused by the fact that the cyclopentane is an inherintly "umpoled" functionality, as illustrated below. III. Metal Mediated Reactions IV. Radical Reactions FG V. Pericyclic and Pseudo-pericyclic Reactions VI. Ring Expansion and Contraction Reactions I. General Information This situation is further exacerbated by the general lack of cheaply available cyclopentane compounds Baldwin's rules in the chiral pool; wheras a number of cyclohexane terpenes are readily available for elaboration, there Baldwin has divided ring closure reactions into those that are "favored" and those that are "disfavored". are no analogous cylcopentane natural products. Cyclopentanes are however, present in many Those that are disfavored are not always impossible, but are frequently much more difficult to effect.
    [Show full text]
  • Catalytic Addition of Simple Alkenes to Carbonyl Compounds by Use of Group 10 Metals
    Catalytic Addition of Simple Alkenes to Carbonyl Compounds by Use of Group 10 Metals The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Ho, Chun-Yu, Kristin Schleicher, Chun-Wa Chan, and Timothy Jamison. “Catalytic Addition of Simple Alkenes to Carbonyl Compounds by Use of Group 10 Metals.” Synlett 2009, no. 16 (October 4, 2009): 2565-2582. As Published http://dx.doi.org/10.1055/s-0029-1217747 Publisher Thieme Publishing Group Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/82119 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike 3.0 Detailed Terms http://creativecommons.org/licenses/by-nc-sa/3.0/ NIH Public Access Author Manuscript Synlett. Author manuscript; available in PMC 2011 September 6. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Synlett. 2009 October 1; 2009(16): 2565±2582. doi:10.1055/s-0029-1217747. Catalytic Addition of Simple Alkenes to Carbonyl Compounds Using Group 10 Metals Chun-Yu Hoa, Kristin D. Schleicherb, and Timothy F. Jamisonb Chun-Yu Ho: [email protected]; Timothy F. Jamison: [email protected] a Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR (P.R. China), Fax: (852) 2603-5057 b Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA), Fax: (+1) 617-324-0253 Abstract Recent advances using nickel complexes in the activation of unactivated monosubstituted olefins for catalytic intermolecular carbon–carbon bond-forming reactions with carbonyl compounds, such as simple aldehydes, isocyanates, and conjugated aldehydes and ketones, are discussed.
    [Show full text]
  • Mechanistic and Stereochemical Studies of Photoinduced Electron Transfer Cyclization Reactions: the Role of Nitrogen
    MECHANISTIC AND STEREOCHEMICAL STUDIES OF PHOTOINDUCED ELECTRON TRANSFER CYCLIZATION REACTIONS: THE ROLE OF NITROGEN. THE AQUEOUS PRINS REACTION AND EFFORTS TOWARDS THE TOTAL SYNTHESIS OF (+)-DACTYLOLIDE by Danielle L. Aubele B.S., Allegheny College, 1999 M.S., University of Pittsburgh, 2002 Submitted to the Graduate Faculty of Arts and Sciences in partial fulfillment of the requirements for the degree of Doctor of Chemistry University of Pittsburgh 2004 UNIVERSITY OF PITTSBURGH FACULTY OF ARTS AND SCIENCES This dissertation was presented by Danielle L. Aubele It was defended on Wednesday, August 18th, 2004 and approved by Dennis P. Curran Kay Brummond Billy Day Paul E. Floreancig Dissertation Director ii Copyright by Danielle L. Aubele, 2004 iii Paul E. Floreancig MECHANISTIC AND STEREOCHEMICAL STUDIES OF PHOTOINDUCED ELECTRON TRANSFER CYCLIZATION REACTIONS: THE ROLE OF NITROGEN. THE AQUEOUS PRINS REACTION AND EFFORTS TOWARDS THE TOTAL SYNTHESIS OF (+)-DACTYLOLIDE Danielle L. Aubele, PhD University of Pittsburgh, 2004 A novel method for catalytic electron transfer initiated cyclization reaction for the formation of cyclic acyl aminals through a unique method of carbon-carbon σ-bond activation has been developed. This new cyclization strategy employs a potent electrophile, generated by a photoinitiated single electron oxidation of a homobenzylic amide or t-butyl carbamate, which reacts with an appended nucleophile allowing for the formation of cyclic acyl aminals. OH NMQPF6, hν , NaOAc O HN R Na2S2O3, O2, DCE, Tol. R N O H O The Lewis acid-surfactant-combined catalyst (LASC) was employed in a novel method for effecting intramolecular Prins cyclization reactions in water. Acetals of 1,2 and 1,3 di- and tri- substituted alcohols with a tethered allyl silane have been converted to 2,6-syn- tetrahydropyrans.
    [Show full text]
  • Condensation Reactions and Beyond
    Review Production of Fuels and Chemicals from Biomass: Condensation Reactions and Beyond Lipeng Wu,1 Takahiko Moteki,2 Amit A. Gokhale,3 David W. Flaherty,2,* and F. Dean Toste1,* Renewable resources and bio-based feedstocks may present a sustainable The Bigger Picture alternative to petrochemical sources to satisfy modern society’s ever-increasing Sustainability of society is demand for energy and chemicals. However, the conversion processes intimately tied to the utilization of needed for these future bio-refineries will likely differ from those currently renewable resources to meet the used in the petrochemical industry. Biotechnology and chemocatalysis offer demand for energy and routes for converting biomass into a variety of molecules that can serve as chemicals. Bio-based feedstocks platform chemicals. While a host of technologies can be leveraged for biomass may present a greener route to upgrading, condensation reactions are significant because they have the satisfy these demands, but the potential to upgrade these bio-derived feedstocks while minimizing the loss conversion processes used in of carbon and the generation of by-products. This review surveys both the bio- future bio-refineries will differ logical and chemical catalytic routes toproducingplatformchemicalsfrom from those in the petrochemical renewable sources and describes advancesincondensationchemistryandstra- industry. Such processes may tegies for the conversion of these platform chemicals into fuels and high-value breakdown sugars, their chemicals. oligomers, and other biomass components into simple molecules that functionally INTRODUCTION resemble petroleum-derived Over the past few decades, improved public awareness of the links between intermediates. Thus, the portfolio climate change and anthropogenic greenhouse gas (GHG) emissions has of fossil and biomass building increased political will around the world to tackle this problem and the demand blocks may intertwine and be for renewable products.1 In parallel, advancements in agronomic and biological upgraded into useful chemicals.
    [Show full text]
  • Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs
    International Journal of Molecular Sciences Review Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs Constantin Tănase 1,* , Lucia Pintilie 1 and Raluca Elena Tănase 2,3 1 Synthesis of Biologically Active Substances Department, National Institute for Chemical-Pharmaceutical Research and Development, 74373 Bucharest, Romania; [email protected] 2 Department of Mathematics, Angstrom Laboratory, Uppsala University, 751 06 Uppsala, Sweden; [email protected] 3 “Simion Stoilow” Institute of Mathematics of the Romanian Academy, 010702 Bucharest, Romania * Correspondence: [email protected] Abstract: In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF2α and 1,15-PGF2α lactones, many 1,15-lactones of E2,E3,F2,F3, A2, and A3 were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and Citation: T˘anase,C.; Pintilie, L.; catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of T˘anase,R.E.
    [Show full text]
  • Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings
    Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings By Larry E. Overman and Emile J. Velthuisen Leading Reference”J. Org. Chem. 2006, 71, 1581-1587 Presented by Zhenyu Zhong Journal Club Presentation April 3rd 2006 Presentation Outline ¾ Overview of the Prins-Pinacol Reaction ¾ Early developments of the acid-promoted Prins-pinacol rearrangement and its potential to be the key strategic element in the total synthesis of heterocyclic and carbocyclic natural products ¾ Exploration of the scope of the Prins-pinacol reaction for assembling attached rings with various sizes and ring substitutions ¾ Rationalization of facial stereoselection in the Prins cyclization ¾ Summary ¾ Future Work Zhenyu Zhong Journal Club 2 Prins Reaction: • The acid-catalyzed condensation of alkenes with aldehyde O Nuc OH OH O O H H R R R R + H 1)H2O O Nuc 2)H+ H H OH OH R H H R carbocation Condensation of formaldehyde with some unsaturated compounds H. J. Prins, Chemisch Weekblad, 16, 64, 1072, 1510 1919 Pinacol Rearrangement HO OH HO O Lewis Acid 1,2-shift R4 R1 R4 R1 R4 R 1 R3 R2 R3 R2 R3 R2 Migratory aptitude: aryl > tBu>> cyclopropyl > 2° alkyl > 1° alkyl R. Fittig. Justus Liebigs Ann. Chem. 110, 23–45 (1859). Zhenyu Zhong Journal Club 3 Serendipitous discovery of the Prins-Pinacol Reaction OH K-10 Clay OHC Acetone O OH Reflux O Pinnacol O Rearrangment H Prins cyclization HO HO O O Oxocarbenium ion β-hydroxy carbenium ion Results two C-C bonds, one C-O bond and two new stereocenters Completely Stereoselective Martinet, P.; Mousset, G.; Michel, M.
    [Show full text]
  • A New Intermediate in the Prins Reaction
    A new intermediate in the Prins reaction Shinichi Yamabe*1, Takeshi Fukuda2 and Shoko Yamazaki2 Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2013, 9, 476–485. 1Fukui Institute for Fundamental Chemistry, Kyoto University doi:10.3762/bjoc.9.51 Takano-Nishihiraki-cho 34-4, Sakyou-ku, Kyoto 606-8103, Japan and 2Department of Chemistry, Nara University of Education, Received: 14 November 2012 Takabatake-cho, Nara 630-8528, Japan Accepted: 31 January 2013 Published: 05 March 2013 Email: Shinichi Yamabe* - [email protected] This article is part of the Thematic Series "New reactive intermediates in organic chemistry". * Corresponding author Guest Editor: G. Bucher Keywords: DFT calculations; hemiacetal intermediate; hydrogen bond; Prins © 2013 Yamabe et al; licensee Beilstein-Institut. reaction; transition state License and terms: see end of document. Abstract + Two Prins reactions were investigated by the use of DFT calculations. A model composed of R–CH=CH2 + H3O (H2O)13 + (H2C=O)2, R = Me and Ph, was adopted to trace reaction paths. For both alkenes, the concerted path forming 1,3-diols was obtained as the rate determining step (TS1). TS stands for a transition state. From the 1,3-diol, a bimolecular elimination (TS2) leads to the allylic alcohol as the first channel. In the second channel, the 1,3-diol was converted via TS3 into an unprecedented hemiacetal intermediate, HO–CH2–O–CH(R)–CH2–CH2–OH. This intermediate undergoes ring closure (TS4), affording the 1,3- dioxane product. The intermediate is of almost the same stability as the product, and two species were suggested to be in a state of equilibrium.
    [Show full text]
  • Reaction of Propylene with Formaldehyde*
    Reaction of Propylene with Formaldehyde* Kenichi Fukui,** Toshio Takino** and Hisao Kitano** Summary: The reaction of propylene with formaldehyde in acetic acid solution catalyzed by sulfuric acid is studied . The optimum mole ratio of sulfuric acid to formaldehyde is found to be about 0.2 and the favorable range of reaction temperature is 35～50℃ at ordinary pressure . The acetic acid containing 30 vol % of acetic anhydride serves as a suitable solvent. The products are 4-methyl-1, 3-dioxane, 1, 3-butanediol diacetate and 4-acetoxytetrahydropyran, and the former two of these compounds can be converted to pyran derivatives via allylcarbinol acetate. However, the formation of 4-acetoxytetrahydropyran from propylene and formaldehyde by the Prins reaction may be explained by the Baker's mechanism of hyper- conjugation of the propylene methyl radical without considering the forma- tion of allylcarbinol acetate. Various reactions of 4-hydroxytetrahydropyran are carried out and its derivatives are prepared, including several new compounds. For the sake of comparison with the reactivity of propylene, some reactions of allyl halides with formaldehyde are also studied and the main products are found to be 4-halomethyl-1, 3-dioxanes. Introduction What is called the Prins reaction, the con- densation of olefins and aldehydes, is generally accelerated by catalysts, heat and light. The reaction of propylene with formaldehyde was investigated by some workers, i. e. by Fitzky,1) Baker,2) Hamblet3) and Arundale,4) since 1938. Our previous paper5) has shown that propy- lene reacted with formaldehyde in acetic acid in the presence of various catalysts, e. g. sulfuric acid, perchloric acid and boron trifluoride, to yield 4-methyl-1, 3-dioxane, 1, 3-butanediol diacetate and 4-acetoxy-tetrahydropyran.
    [Show full text]