Improved Synthesis and Enhanced Reactivity of X-BODIPYs by Travis Lee Lundrigan Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Dalhousie University Halifax, Nova Scotia December 2017 © Copyright by Travis Lee Lundrigan, 2017 TABLE OF CONTENTS List of Tables ..................................................................................................................... vi List of Figures ................................................................................................................... vii List of Schemes .................................................................................................................. ix Abstract .............................................................................................................................. xi List of Abbreviations and Symbols Used ......................................................................... xii Acknowledgements .......................................................................................................... xiv Chapter 1 – Introduction ..................................................................................................... 1 1.1 – Structure and Properties of Dipyrrinato Ligands .................................................. 1 1.2 – Synthesis of Dipyrrins ........................................................................................... 2 1.3 – Dipyrrinato Complexes ......................................................................................... 4 1.4 – Structure and Properties of F-BODIPY Dyes ....................................................... 5 1.5 – F-BODIPY Synthesis ............................................................................................ 6 1.6 – Boron Substitution of BODIPY Dyes ................................................................... 7 1.7 – Thesis Overview .................................................................................................... 8 Chapter 2 – Improved Synthesis of F-BODIPYs ............................................................... 9 2.1 – Background ........................................................................................................... 9 2.2 – Project Goals ....................................................................................................... 13 2.3 – Results and Discussion ........................................................................................ 14 2.3.1 – Development of Synthetic Methodology ........................................... 14 2.3.2 – Synthesis of bis(F-BODIPY)s ........................................................... 21 2.4 - Conclusions .......................................................................................................... 26 Chapter 3 – Cl-BODIPYs ................................................................................................. 27 3.1 – General Background ............................................................................................ 27 3.2 – Project Goals ....................................................................................................... 31 3.3 – Results and Discussion ........................................................................................ 32 3.3.1 – Synthesis of Cl-BODIPYs ................................................................. 32 3.3.2 – Reactivity of Cl-BODIPYs ................................................................ 36 3.3.3 – Conversion of F-BODIPY to Cl-BODIPY ........................................ 40 3.3.4 – Using Cl-BODIPY as a Synthetic Intermediate ................................. 47 3.3.5 – Synthesis of Chiral O-BODIPYs ....................................................... 53 3.3.6 – Chiroptical Properties of Chiral Compounds ..................................... 61 ii 3.3.7 – Comparison of Spectroscopical Properties ........................................ 68 3.4 – Conclusions ......................................................................................................... 70 Chapter 4 – Activation and Deprotection of F-BODIPYs ................................................ 72 4.1 – General Background ............................................................................................ 72 4.2 – Project Goals ....................................................................................................... 73 4.3 – Results and Discussion ........................................................................................ 74 4.3.1 – Deprotection of F-BODIPYs using X-BODIPY intermediates ......... 74 4.3.2 – Activation and deprotection of F-BODIPYs using BF3•OEt2 ........... 82 4.4 – Conclusions ......................................................................................................... 95 Chapter 5 – Experimental ................................................................................................. 97 5.1 – General Experimental .......................................................................................... 97 5.1.1 General Procedure for Emission Measurements ................................... 98 5.2 – Synthesis of Compounds ..................................................................................... 98 1,3,5,7-Tetramethyl-2-octyl-8-H-4-bora-3a,4a-diaza-s-indacene (1BF2) ...... 99 1,3,5,7-Tetramethyl-2-ethyl-8-H-4-bora-3a,4a-diaza-s-indacene (2BF2) ...... 99 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4-bora-3a,4a-diaza-s-indacene (3BF2) ........................................................................................................... 100 1,3,5,7-Tetramethyl-2,6-diethyl-8-phenyl-4-bora-3a,4a-diaza-s- indacene (5BF2)............................................................................................ 101 3-Methyl-1,5,7-triethyl-2-ethylcarboxylato-8-H-4-bora-3a,4a-diaza-s- indacene (6BF2)............................................................................................ 102 1,3,6-Trimethyl-2-(2-methoxy-2-oxoethyl)-7-ethyl-8-H-4,4’-difluoro- bora-3a,4a-diaza-s-indacene (7BF2) ............................................................. 103 8-Phenyl-4-bora-3a,4a-diaza-s-indacene (8BF2) ......................................... 104 1,7-Bis(5-((Z)-(4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene)methyl)-2,4- dimethyl-1H-pyrrol-3-yl)hexane dihydrobromide (12•2HBr) ..................... 104 1,7-Bis(1,3,5,7-tetramethyl-2-ethyl-8-H-4-bora-3a,4a-diaza-s- indacene)hexane (12BF2) ............................................................................. 106 1,7-Bis(5-((Z)-(4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene)methyl)-2,4- dimethyl-1H-pyrrol-3-yl)heptane dihydrobromide (15•2HBr) .................... 106 1,7-Bis(1,3,5,7-tetramethyl-2-ethyl-8-H-4-bora-3a,4a-diaza-s- indacene)heptane (15BF2) ............................................................................ 108 1,3,5,7-Tetramethyl-2,6-diethyl-8-phenyl-4,4’-dichloro-bora-3a,4a- diaza-s-indacene (3BCl2) ............................................................................. 108 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-dimethoxy-bora-3a,4a-diaza- s-indacene (3B(OMe)2) ................................................................................ 111 iii 1,3,5,7-Tetramethyl-2,6-diethyl-8-phenyl-4,4’-dimethoxy-bora-3a,4a- diaza-s-indacene (5B(OMe)2) ...................................................................... 111 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-diphenyl-bora-3a,4a-diaza-s- indacene (3BPh2).......................................................................................... 112 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-diethyl-bora-3a,4a-diaza-s- indacene (3BEt2) .......................................................................................... 113 1,3,5,7-Tetramethyl-2,6-diethyl-8-phenyl-4,4’-diethyl-bora-3a,4a- diaza-s-indacene (5BEt2) .............................................................................. 114 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-dimethoxy-bora-3a,4a-diaza- 11 s-indacene (3 B(OMe)2) ............................................................................. 114 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-difluoro-bora-3a,4a-diaza-s- 11 indacene (3 BF2) ......................................................................................... 115 1,3,5,7-Tetramethyl-2-ethyl-8-H-4,4’-diethyl-bora-3a,4a-diaza-s- indacene (2BEt2) .......................................................................................... 116 1,3,6-Trimethyl-2-(2-methoxy-2-oxoethyl)-7-ethyl-8-H-4,4’-diethyl- bora-3a,4a-diaza-s-indacene (7BEt2) ........................................................... 116 8-Phenyl-4,4’-diethyl-bora-3a,4a-diaza-s-indacene (8BEt2) ....................... 117 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-[propane-1,3-bis(olate)]-bora- 3a,4a-diaza-s-indacene (17) ......................................................................... 117 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-[(1,1'-binaphthalene)-2,2'- bis(olate)]-bora-3a,4a-diaza-s-indacene (18) ............................................... 118 1,3,5,7-Tetramethyl-2,6-diethyl-8-H-4,4’-[(1,1'-binaphthalene)-2,2'- bis(olate)]-bora-3a,4a-diaza-s-indacene (19) ............................................... 119 1,3,5,7-Tetramethyl-2,6-diethyl-8-phenyl-4,4’-[(1,1'-binaphthalene)- 2,2'-bis(olate)]-bora-3a,4a-diaza-s-indacene (20) ........................................ 120 1,3,5,7-Tetramethyl-2,6-diethyl-8-phenyl-4,4’-[(1,1'-binaphthalene)- 2,2'-bis(olate)]-bora-3a,4a-diaza-s-indacene (21) .......................................