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  • 1,3-DIPOLAR CYCLOADDITION OF AN ISOXAZOLINE N-OXIDE TO OLEFINS

    Youn Yuen Shu

    B.Sc., National Chung Hsing University, 1978

    THESIS SUBMITTED IN PARTIAL FULFILLMENT OF

    THE REQUIREMENTS FOR THE DEGREE OF

    MASTER OF SCIENCE

    in the Department

    of

    Chemistry

    @ Youn Yuen Shu 1985

    SIMON FRASER UNIVERSITY

    July, 1985

    All rights reserved. This thesis may not be reproduced in whole or in part, by photocopy

    or other means, without permission of the author.

  • APPROVAL

    Name: Youn Yuen Shu

    Degree: Master o f Science

    Title of thesis: 1 ,3-DI POLAR CYCLOADDI TI ON OF AN I SOXAZOLINE

    N-OXIDE TO OLEFINS

    Examining Committee:

    Chaim: Dr. F. W. B. Einstein, Professor

    Y. L. Chaw, Professor

    Senior Supervlaor /

    B. L. F'unt, Professor

    Internal Exminer Date Approved:

  • PARTIAL COPYRIGHT LICENSE

    I hereby g r a n t t o Simon Fraser U n i v e r s i t y t h e r i g h t t o

    my t h e s i s , p roJec t o r extended essay ( t h e t i t l e o f which i s shown

    t o users o f t h e Simon Fraser U n i v e r s i t y L i b r a r y , and t o make p a r t

    lend

    below)

    i a l o r

    s i n g l e cop ies o n l y f o r such users o r i n response t o a reques t f rom t h e

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    f o r m u l t i p l e copy ing o f t h i s work f o r s c h o l a r l y purposes may be g ran ted

    by me o r t h e Dean o f Graduate S tud ies . I t i s understood t h a t copy ing

    o r p u b l l c a t i o n o f t h i s work f o r f i n a n c l a l g a i n s h a l l n o t be a l lowed

    w i t h o u t my w r i t t e n permiss ion .

    T i t l e o f Thes is /Pro jec t /Ex tended Essay

    "1 .3 -Di~o la r Cvcloaddit ion of an I soxal ine N-Oxide t o Olef ins"

    Author :

    ('XignatWee)

    Youn-Yuen Shu

    ( d a t e )

  • ABSTRACT

    The 1,3-dipolar cycloaddition of 3-methyl-5-phenyl-

    isoxazoline N-oxide to electron-poor olefins, such as methyl

    acrylate, acrylonitrile, styrene, dimethyl fumarate, dimethyl

    maleate, fumaronitrile, vinyl methyl ketone, and maleic

    anhydride, gave diastereoisomeric cycloadducts of

    1-aza-2,8-dioxabicyclo[3.3.01-octanes. The N-oxide failed to

    react with bulky trans-stilbene and electron-rich vinyl acetate.

    The cycloadditions to the mono-substituted olefins gave only one

    type of regioisomer. Out of four possible approaches of the

    1,3-dipole to the olefins, steric effects in the transition

    state control the reaction pathway leading to one predominant

    cycloadduct, the top-exo - adduct. For the cycloaddition with

    maleic anhydride, secondary orbital effects dictate the reaction

    pathway to give the top-endo adduct. The relative configurations

    of the majority of these diastereoisomers were determined from

    their NMR spectra and Nuclear Overhauser Effects.

    The formation constants of the ground state complex between

    the N-oxide and olefins were investigated. Both maleic anhydride

    and fumaronitrile formed ground state complexes and reacted with

    N-oxide , while dimethyl fumarate and dimethyl maleate failed to

    give ground state complex but reacted with N-oxide;

    trans-stilbene showed strong ground state complex formation but

  • no reaction was observed.

    The stereoselectivities of the cycloadditions with maleic

    anhydride, dimethyl fumarate, and fumaronitrile were improved

    under high pressure (1.38 or 2.07 ~ ~ a r ) . However, high pressure

    had no effect on the cycloaddition with methyl acrylate.

  • To my Parents

  • ACKNOWLEDGEMENT

    The author wishes to express his sincere thanks to Dr.Y.L.

    Chow for his guidance and genuine interest throughout this work.

    He also wishes to thank Dr. Slessor, Dr. Gresser and Dr.

    Buono-Core for their helpful discussions and general assistance.

    The collaboration and friendship of fellow members of Dr.Chowls

    group are gratefully acknowledged. The author also wishes to

    thank Dr.K.E. Newman and the technical staff for their valuable

    assistance, and particularly to M.Tracey.

    A special thanks to Marcia Craig for the very helpful

    revision of the manuscript.

    Financial assistance from the Department of Chemistry,

    Simon Fraser University is also acknowledged.

  • TABLE OF CONTENTS

    APPROVAL i i

    ABSTRACT i i i

    DEDI CAT1 ON v

    ACKNOWLEDGEMENTS vi

    LIST OF TABLES x

    LIST OF FIGURES xii

    CHAPTER 1 Introduction ................................ 1 CHAPTER 2 Results ...................................... 6

    1. Preparation of 3-methyl-5-phenyl-isoxazoline'

    N-oxidell ......................................... 7 - 2. 1,3-Dipolar Cycloadditions of N-oxide - 1 to olefins. 9

    2a. Cycloaddition to Methyl Acrylate ..:............. 1 4 2b. Cycloaddition to Styrene ........................ 1 8 2c. Cycloaddition to cryl lo nit rile .................. 19 2d. Cycloaddition to Dimethyl Fumarate .............. 22 2e. Cycloaddition to Fumaronitrile .................. 23 2f. Cycloaddition to Dimethyl Maleate ............... 2 4 2g. Cycloaddition to Maleic Anhydride ............... 26 2h. Reaction of 1 with Nitrosobenzene ............... 27 -

    3. Cycloadditions under High Pressure .............. 28 4. Formation Constants of Ground State Complexes ... 29

    vii

  • 4a . Maleic Anhydride ................................. 30 4b . Fumaronitrile .................................... 35 4c . trans-stilbene .................................... 39 4d . Vinyl Acetate ..................................... 42

    CHAPTER 3 Discussion ................................. 43 1 . Stereochemistry ................................. 44 la . mono-Substituted Olefins ......................... 44 1b . trans-Olefins .................................... 46 1c . &-Olefins ...................................... 48

    2 . Regiochemistry .................................. 49 3 . The Frontier Orbital Theory of Cycloadditions ... 49 4 . Conformational Properties ....................... 59 5 . High Pressure Reaction .......................... 61 6 . The ~ormat'ion Constants of Ground State Complexes . 62

    CHAPTER 4 Experimental ................................ 64 1 . General Techniques ................................ 64 2 . Chemicals ........................................ 65 3 . The General Procedures of Cycloadditions ........ 66 4 . The Preparation of N-oxide 1 .................... 66 5 . Cycloadditions of N-oxide 1 t o Olefins .......... 67 5a . Cycloaddition of N-oxide 1 to Methyl Acrylate .... 67 5b . Cycloaddition of N-oxide 1 to Styrene ........... 69 5c . Cycloaddition of N-oxide 1 to Acrylonitrile ..... 69 5d . Cycloaddition of N-oxide 1 to Dimethyl Fumarate .. 70 5e . Cycloaddition of N-oxide 1 to Fumaronitrile ..... 71 5f . Cycloaddition of N-oxide - 1 to Dimethyl Maleate ... 72

  • ... 5g. Cycloaddition of N-oxide - 1 to Maleic Anhydride 72 5h. Cycloaddition of N-oxide - 1 to Vinyl Acetate ...... 73

    .... 5i. Cycloaddition of N-Oxide - 1 to trans-Stilbene 73 5j. Cycloaddition of N-oxide - 1 to Vinyl Methyl Ketone . 74

    ....... 5k. Reaction of N-oxide - 1 with Nitrosobenzene 74

    ....... 6. . Test for kinetic vs. thermodynamic control 78 .............. 7. Cycloadditions under High Pressure 78 ............. 7a. Reaction of - 1 with Dimethyl Fumarate 79

    ................. 7b. Reaction of - 1 with Fumaronitrile 79 ............... 7c. Reaction of - 1 with Methyl Acrylate 80 .............. 7d. Reaction of - 1 with Maleic Anhydride 80

    .... 8. Formation Constants of Ground State Complexes 82 REFERENCES 1 0 1

  • LIST OF TABLES

    TABLE - 1. REACTION CONDITIONS OF THE

    ......... CYCLOADDITIONS OF 1 TO OLEFINS 11 - - 2. RELATIVE YIELDS OF ADDUCTS FROM THE

    ......... CYCLOADDITIONS OF 1 TO OLEFINS 1 3 - - 3. THE CYCLOADDITION OF N-OXIDE 1 TO -

    OLEFINS UNDER HIGH PRESSURE ............ 23 - 4. OPTICAL DENSITIES OF GROUND STATE

    COMPLEX BETWEEN 1 AND MA AT DIFFERENT -

    CONCENTRATIONS OF MA ................... 3 2 - 5. OPTICAL DENSITIES OF GROUND STATE

    COMPLEX BETWEEN 1 AND FN AT DIFFERENT -

    CONCENTRATIONS OF FN ................... 3 6 - 6. OPTICAL DENSITIES OF GROUND STATE

    COMPLEX BETWEEN 1 AND SB AT DIFFERENT - .................... CONCENTRATIONS OF 1 4 0 -

    - 7. OPTICAL DENSITIES OF THE SOLUTIONS OF VA AND 1 AT DIFFERENT CONCENTRATIONS -

    .................................. OF VA 4 2 .......... - 8. FRONTIER ORBITAL COEFFICIENTS 53

    ..................... - 9. 'H NMR PARAMETERS 8 3

  • ................. . .I0 13c NMR PARAMETERS 85 ..................... . .I1 IR ABSORPTIONS 87 ..................... . .I2 UV ABSORPTIONS 90

    . .................. .I3 MASS SPECTRA DATA 91

    . ........................ .I4 NOE RESULTS 95 ................. . .I5 ELEMENTAL ANALYSES 100

  • LIST OF FIGURES

    FIGURE 2-1. PLOT FOR THE GROUND STATE COMPLEX

    FORMATION CONSTANT

    OF MALEIC ANHYDRIDE AND N-OXIDE 1 ....... 33 - THE UV ABSORPTIONS OF THE GROUND

    STATE COMPLEX BETWEEN 1 AND MA ......... 34 - PLOT FOR THE GROUND STATE COMPLEX

    FORMAT1 ON CONSTANT

    OF FUMARONITRILE AND N-OXIDE 1 ......... 37 - THE UV ABSORPTIONS OF THE

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