Tài liệu Palladium and cobalt catalyzed functionalization of sp2 and sp3 carbon hydrogen bonds

PALLADIUM AND COBALT-CATALYZED FUNCTIONALIZATION OF sp2 AND sp3 CARBON-HYDROGEN BONDS TUNG THANH NGUYEN UNIVERSITY OF HOUSTON AUGUST 2018 PALLADIUM AND COBALT-CATALYZED FUNCTIONALIZATION OF sp2 AND sp3 CARBON-HYDROGEN BONDS -----------------------------------------------------A Dissertation Presented to the Faculty of the Department of Chemistry University of Houston -----------------------------------------------------In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy -----------------------------------------------------By Tung Thanh Nguyen August 2018 PALLADIUM AND COBALT-CATALYZED FUNCTIONALIZATION OF sp2 AND sp3 CARBON-HYDROGEN BONDS ____________________________________________ Tung Thanh Nguyen APPROVED: ____________________________________________ Dr. Olafs Daugulis, Chairman ____________________________________________ Dr. Jeremy A. May ____________________________________________ Dr. Loi Do ____________________________________________ Dr. Steven Baldelli ____________________________________________ Dr. Gregory D. Cuny ____________________________________________ Dean, College of Natural Sciences and Mathematics ii ACKNOWLEDGEMENTS First, I would like to thank my advisor Dr. Olafs Daugulis, who not only supports me since the first day I come here but also challenges me to do such chemistries that are impactful. I also want to thank my committee members Dr. Jeremy May, Dr. Loi Do, Dr. Steven Baldelli, and Dr. Greg Cuny for their invaluable comments on this dissertation. To my labmates that I have opportunities to work with; Dr. James Roane, Dr. Kristine Klimovica, Dr. Ilya Popov, Andrew Kocen, thank you for your recommendations and encouragement throughout the years. A special thank to Dr. Liene Grigorjeva, who worked with me in two projects of aminoquinoline directing group and developed conditions for the carboxylate project. To my friends who has supported me; Trang Nguyen, Ky Le, Ha Le, thank you for accepting me no matter how bad I am. To Dr. Thanh Truong who introduced me to Dr. Olafs Daugulis, thank you for believing in me. Last, to my parents and my younger sister, who have sacrificed so much, thank you for being always patient and confident in me. iii PALLADIUM AND COBALT-CATALYZED FUNCTIONALIZATION OF sp2 AND sp3 CARBON-HYDROGEN BONDS -----------------------------------------------------An Abstract of a Dissertation Presented to the Faculty of the Department of Chemistry University of Houston -----------------------------------------------------In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy -----------------------------------------------------By Tung Thanh Nguyen August 2018 iv ABSTRACT Directed functionalization of C–H bonds has emerged as a practical method for new carbon-carbon and carbon-heteroatom bond formation. Despite the achieved successes, many challenges still remain. First, use of the methodology for functionalization of C–H bonds in phosphorus and sulfur-containing compounds is still rare. Second, functionalization of C–H bonds directed by simple functional groups is limited to second and third-row metal catalysis. This dissertation describes methods for cobalt and palladium-catalyzed, aminoquinoline-directed functionalization of sp2 and sp3 C–H bonds in phosphinic and sulfonic amides. The use of cobalt catalyst for simple carboxylate-directed sp2 C–H functionalization is also reported. Directed functionalization of C–H bonds in aminoquinoline phosphinic acid amides under cobalt catalysis was developed. A simple cobalt salt was used to catalyze the coupling of amide C–H bonds with alkynes, ethylene, and morpholine. To our knowledge, this marks the first example of ortho-functionalization C–H bonds in phosphinic acid derivatives using first row transition metals. Subsequently, -arylation of sp3 C–H bonds in alkylphosphinic acid amiquinoline amides with aryl iodides was also described. Furthermore, cobalt-catalyzed, directed carbonylation of C–H bonds in aminoquinoline sulfonamides was developed. Directing group removal affords saccharin derivatives. Finally, carboxylate-directed coupling of sp2 C–H bonds with alkynes, styrenes, and 1,3dienes under cobalt catalysis was investigated. This reaction is a rare example using simple directing groups for first row metal-catalyzed functionalization of C–H bonds. v TABLE OF CONTENTS ACKNOWLEDGEMENT iii ABSTRACT v TABLE OF CONTENTS vi LIST OF SCHEMES xi LIST OF FIGURES xv LIST OF TABLES xvi LIST OF ABBREVIATIONS xvii Chapter 1 TRANSITION METAL-CATALYZED FUNCTIONALIZATION OF CARBONHYDROGEN BONDS USING PHOSPHORUS AND SULFUR-CONTAINING DIRECTING GROUPS 1 1.1. Introduction 2 1.2. Phosphorus-containing directing groups for functionalization of C–H bonds 2 1.2.1. Phosphine oxide and phosphine sulfide directing groups for C–H functionalization 2 1.2.2. Phosphinite and phosphine directing groups for C–H functionalization 8 1.2.3. Phosphorus-containing acids and their derivatives as directing groups for C–H functionalization 11 1.3. Sulfur-containing directing groups for functionalization of C–H bonds 15 1.3.1. Thioamide, thioketone, and thioether directing groups for C–H functionalization 15 1.3.2. Sulfoxide directing groups for C–H functionalization 19 1.3.3. Sulfonic acid, sulfonamide, sulfoximine, and sulfone directing groups for C–H functionalization 20 1.3.4. Conclusions 23 1.4. References 24 vi Chapter 2 COBALT-CATALYZED, AMINOQUINOLINE-DIRECTED FUNCTIONALIZATION OF PHOSPHINIC AMIDE CARBON-HYDROGEN BONDS 30 2.1. Introduction 31 2.2. Development of aminoquinoline-directed, cobalt-catalyzed sp2 C–H alkenylation 31 2.3. Cobalt-catalyzed, in aminoquinoline-directed functionalization of C–H bonds phenylphosphinic amides with other coupling reagents and auxiliary removal 34 2.4. Conclusion 35 2.5. Experimental 35 2.5.1. General considerations 35 2.5.2. Synthesis of arylphosphinic amides and phosphonamidate ethyl ester 36 2.5.3. Optimization of reaction conditions and control experiments 40 2.5.4. Cobalt-catalyzed, aminoquinoline-directed alkenylation of phenylphosphinic amides C–H bonds in 41 2.5.5. Cobalt-catalyzed coupling of phenylphosphinic amide C–H bonds with ethylene and morpholine 57 2.5.6. Auxiliary removal 59 2.6. References 60 Chapter 3 PALLADIUM-CATALYZED, DIRECTED FUNCTIONALIZATION OF sp3 CARBON-HYDROGEN BONDS 61 3.1. Introduction 62 3.2. Palladium-catalyzed, aminoquinoline-directed arylation of sp3 C–H bonds in phosphinic amides 62 3.3. Palladium-catalyzed, directed amidation of sp3 C–H bonds in amides 66 3.4. Conclusions 68 3.5. Experimental 68 vii 3.5.1. Synthesis of phosphonamidate and phosphonic amide starting materials 68 3.5.2. Optimization of reaction conditions 73 3.5.3. Palladium-catalyzed arylation and alkenylation of phosphonamidate/phosphinic amide sp3 C–H bonds 74 3.5.4. Aminoquinoline removal for synthesis of -arylphosphonate 88 3.5.5. Palladium-catalyzed, directed amidation of sp3 C–H bonds 89 3.6. Refererences 95 Chapter 4 COBALT-CATALYZED, AMINOQUINOLINE-DIRECTED CARBONYLATION OF SULFONAMIDE sp2 CARBON-HYDROGEN BONDS 97 4.1. Introduction 4.2. Development 98 of cobalt-catalyzed, aminoquinoline-directed carbonylation of sulfonamide C–H bonds 99 4.3. Conclusion 101 4.4. Experimental 101 4.4.1. Synthesis of 8-aminoquinoline benzenesulfonamides 101 4.4.2. Optimization of reaction conditions 108 4.4.3. Cobalt-catalyzed carbonylation of aminoquinoline sulfonamide C–H bonds 110 4.4.4. Directing group removal 119 4.5. References 120 Chapter 5 TRANSITION METAL-CATALYZED FUNCTIONALIZATION OF CARBONHYDROGEN BONDS DIRECTED BY SIMPLE FUNCTIONAL GROUPS 5.1. Introduction 121 122 5.2. Second- or third-row metal-catalyzed functionalization of C–H bonds directed by oxygen-containing functional groups 122 5.2.1. Carboxylate directing groups 122 viii 5.2.1.1. Palladium catalysis 122 5.2.1.2. Ruthenium catalysis 124 5.2.1.3. Rhodium catalysis 126 5.2.1.4. Iridium and platinum catalysis 127 5.2.2. Alcohol and phenol directing groups 129 5.2.2.1. Palladium catalysis 129 5.2.2.2. Ruthenium catalysis 130 5.2.2.3. Rhodium catalysis 131 5.2.3. Carbonyl directing groups 132 5.2.3.1. Palladium catalysis 132 5.2.3.2. Ruthenium catalysis 133 5.2.3.3. Rhodium catalysis 135 5.3. First-row metal-catalyzed functionalization of C–H bonds directed by oxygencontaining functional groups 138 5.3.1. Carboxylate directing groups 138 5.3.2. Phenol directing groups 139 5.3.3. Carbonyl directing groups 140 5.4. Conclusions 140 5.5. References 141 Chapter 6 COBALT-CATALYZED, CARBOXYLATE-DIRECTED FUNCTIONALIZATION OF CARBON-HYDROGEN BONDS 145 6.1. Introduction 146 6.2. Development of cobalt-catalyzed, carboxylate-directed sp2 C–H alkenylation 146 6.3. Development of cobalt-catalyzed, carboxylate-directed sp2 C–H alkylation with styrenes and 1,3-dienes 149 ix 6.4. Mechanistic considerations 151 6.5. Conclusions 152 6.6. Experimental 153 6.6.1. General considerations 153 6.6.2. Optimization 153 6.6.3. Cobalt-catalyzed, carboxylate-directed alkenylation of C–H bonds with alkynes 154 6.6.4. Cobalt-catalyzed, carboxylate-directed alkylation of C–H bonds with styrenes and 1,3-dienes 168 6.6.5. Control experiments 173 6.6.5.1. Cobalt-catalyzed intramolecular cyclization of ortho-alkenyl benzoic acid 173 6.6.5.2. Cobalt-catalyzed intramolecular cyclization of ortho-alkynyl benzoic acid 174 6.6.5.3. Cobalt-catalyzed directed alkenylation of C–H bonds with deuteriated terminal alkyne 175 6.7. References 176 x LIST OF SCHEMES Scheme 1.1. An example of iridium-catalyzed, phosphine oxide-directed alkenylation of C–H bonds. 2 Scheme 1.2. Ruthenium-catalyzed ortho- alkenylation and alkylation of phosphine oxides. 3 Scheme 1.3. High valent rhodium complexes for directed C–H alkenylation of phosphine oxides. 3 Scheme 1.4. Palladium-catalyzed, directed coupling of biphenylphosphine oxide C–H bonds and ethyl acrylate. 4 Scheme 1.5. Phosphine oxide-directed arylation of C–H bonds in biphenyls. 5 Scheme 1.6. Group 9 metal-catalyzed ortho-arylation of arylphosphine oxides. 6 Scheme 1.7. Palladium-catalyzed, directed acylation of C–H bonds in phosphine oxides. 6 Scheme 1.8. Rhodium-catalyzed, phosphine sulfide-directed sp2 C–H functionalization. 8 Scheme 1.9. A possible mechanism for phosphinite-directed ortho-arylation of phenols. 9 Scheme 1.10. Rhodium-catalyzed, phosphinite-directed arylation of phenols. 10 Scheme 1.11. Rhodium-catalyzed, phosphine-directed arylation of C–H bonds. 11 Scheme 1.12. Palladium-catalyzed, directed functionalization of C–H bonds in benzylphosphonic acid monoalkyl esters. 12 Scheme 1.13. Palladium-catalyzed enantioselective ortho-arylation of phosphinamides. 13 Scheme 1.14. Ruthenium-catalyzed, ortho-alkenylation of phenylphosphonic acid monoethyl esters. 14 Scheme 1.15. Copper-catalyzed, phosphinamide-directed C–H functionalization of indoles with aryliodonium triflates. 14 Scheme 1.16. Palladium-catalyzed -arylation amine C–H bonds. 15 Scheme 1.17. Iridium-catalyzed -alkylation C–H bonds in cyclic amines. 17 xi Scheme 1.18. Rhodium-catalyzed, thioamide-directed alkenylation of sp2 C–H bonds with alkenes and alkynes. 17 Scheme 1.19. Thioketone-directed arylation of ferrocene C–H bonds under palladium catalysis.18 Scheme 1.20. Transition metal-catalyzed, thioether-directed C–H functionalization. 18 Scheme 1.21. Palladium-catalyzed diastereoselective alkenylation of biarylsulfoxides. 19 Scheme 1.22. Rhodium-catalyzed ortho-alkenylation of phenylsulfoxides and synthesis of benzothiophene. 20 Scheme 1.23. Sulfonic acid-directed alkenylation C–H bonds in the presence of ruthenium and rhodium catalysts. 21 Scheme 1.24. Pyridylsulfonamide-directed alkenylation of sp2 C–H bonds. 21 Scheme 1.25. Sulfonamide-directed sp2 C–H functionalization. 22 Scheme 1.26. Rhodium-catalyzed, directed alkenylation of sp2 C–H bonds in sulfoximines. 23 Scheme 1.27. Sulfone-directed C–H functionalization with unsaturated carbon-carbon bonds. 23 Scheme 2.1. Cobalt-catalyzed, aminoquinoline-directed C–H alkenylation of phenylphosphinic amide with alkynes. 33 Scheme 2.2. Cobalt-catalyzed ortho-alkenylation of phosphinic amide sp2 C–H bonds with 2butyne. 34 Scheme 2.3. Cobalt-catalyzed ortho-alkylation of phenylphosphinic amide. 34 Scheme 2.4. Cobalt-catalyzed ortho-amination of phenylphosphinic amide and auxiliary removal. Scheme 3.1. Palladium-catalyzed, 35 aminoquinoline-directed arylation of ethylphosphonamidate sp3 C–H bonds. ethyl 64 Scheme 3.2. Arylation of C–H bonds in ethyl alkylphosphonamidates and phosphinic amides. 65 Scheme 3.3. Alkenylation of phosphinamidate sp3 C–H bonds and auxiliary removal. 66 Scheme 3.4. Palladium catalyzed, directed amidation of sp3 C–H bonds. xii 67 Scheme 4.1. Cobalt-catalyzed, aminoquinoline-directed carbonylation of sulfonamide C–H bonds. 100 Scheme 4.2. Auxiliary removal. 101 Scheme 5.1. Palladium-catalyzed, carboxylate-directed coupling of C–H bonds with styrene. 123 Scheme 5.2. Palladium-catalyzed, carboxylate-directed arylation of C–H bonds. 123 Scheme 5.3. Carboxylate-directed, palladium-catalyzed arylation of sp2 C–H bonds with aryl iodides and chlorides. 124 Scheme 5.4. Ruthenium-catalyzed, directed alkenylation and alkylation of benzoic acid C–H bonds. 125 Scheme 5.5. Ruthenium-catalyzed ortho-arylation of benzoic acids. 125 Scheme 5.6. Rhodium-catalyzed, directed C–H/C–H cross coupling. 127 Scheme 5.7. Iridium-catalyzed, directed C–H functionalization in amino acids. 127 Scheme 5.8. Iridium-catalyzed, directed coupling of ortho C–H bonds in benzoic acids with thiophenes. 128 Scheme 5.9. Iridium-catalyzed, directed coupling of ortho C–H bonds in benzoic acids with different electrophiles. 128 Scheme 5.10. Palladium-catalyzed, directed arylation of phenol C–H bonds with aryl iodides. 129 Scheme 5.11. Palladium-catalyzed, alcohol-directed functionalization of sp2 C–H bonds. 130 Scheme 5.12. Ruthenium-catalyzed, alcohol-directed functionalization of sp2 C–H bonds. 131 Scheme 5.13. Rhodium-catalyzed, phenol-directed coupling of C–H bonds with alkynes. 132 Scheme 5.14. Palladium-catalyzed ortho-arylation of aryl methyl ketones with aryl iodides. 132 Scheme 5.15. Palladium-catalyzed, carbonyl-directed C–H functionalization using catalytic directing groups. 133 Scheme 5.16. Possible mechanism of ruthenium-catalyzed, directed ortho-alkylation of methyl phenyl ketone. 134 xiii Scheme 5.17. Possible mechanism of ruthenium-catalyzed, directed ortho-arylation of methyl phenyl ketone. 135 Scheme 5.18. Rhodium-catalyzed ortho-alkylation of aryl methyl ketones. 135 Scheme 5.19. Possible mechanism of rhodium-mediated C–H activation of methyl phenyl ketone. 136 Scheme 5.20. Rhodium-catalyzed -alkylation of ketones with ethylene. 137 Scheme 5.21. High valent rhodium complex for ortho-olefination of aryl ketones. 138 Scheme 5.22. Copper-catalyzed decarboxylative functionalization sp2 C–H bonds in benzoic acids. 138 Scheme 5.23. Iron-catalyzed ortho-methylation of benzoic acids. 139 Scheme 5.24. Cobalt-catalyzed, carboxylate-directed alkenylation of sp2 C–H bonds with alkynes. 139 Scheme 5.25. Cobalt-catalyzed, phenol-directed carbonylation of vinyl C–H bonds. 140 Scheme 5.26. Iron-catalyzed, directed alkylation of C–H bonds in phenyl alkyl ketones. 140 Scheme 6.1. Scope of alkynes for cobalt-catalyzed, directed alkenylation of C–H bonds. 148 Scheme 6.2. Scope of benzoic acid C–H bonds in coupling with 1-hexyne. 149 Scheme 6.3. Cobalt-catalyzed, carboxylate-directed alkylation of sp2 C–H bonds. 150 Scheme 6.4. Mechanistic considerations for cobalt-catalyzed, carboxylate-directed alkenylation. 151 Scheme 6.5. Control experiments. 152 xiv LIST OF FIGURES Figure 1.1. An iridium(III) iodide complex for enantioselective amidation. 7 Figure 1.2. Nickellacycle complex obtained from phosphinite-directed C–H activation. Figure 1.3. Cyclopentandienyl-rhodium complexes for enantioselective alkenylation of 10 phenylphosphinamide C–H bonds. 12 Figure 4.1. 98 Representation of saccharine derivatives. xv LIST OF TABLES Table 1.1. Iridium-mediated activation of sp2 C–H bonds directed by phosphine oxides. Table 1.2. Rhodium-catalyzed kinetic resolution of phenylphosphinic amides. Table 1.3. Effect of substituents at  position to carbonothioyl on cobalt-catalyzed, thioamide- directed amidation of unactivated sp3 C–H bonds. 7 13 16 Table 2.1. Optimization of cobalt-catalyzed alkenylation sp2 C–H bonds. Table 2.2. Optimization of cobalt-catalyzed, directed alkenylation of 8-aminoquinoline 32 phenylphosphinic amide and control experiments. 40 Table 3.1. Optimization conditions of palladium-catalyzed, directed arylation. 63 Table 3.2. Development of arylation conditions and control experiments. 74 Table 4.1. Optimization conditions of cobalt-catalyzed, directed carbonylation. 99 Table 4.2. Optimization of sulfonamide carbonylation. Table 5.1. Effect of rhodium salts on directed ortho-alkenylation of benzoic acid with 109 diphenylacetylene. Table 6.1. Development of reaction conditions and control experiments. 147 Table 6.2. Optimization and control experiments. 154 xvi LIST OF ABBREVIATIONS acac acetylacetonate Ad adamantane BArF tetrakis(3,5-trifluoromethyl)phenylborate Boc tert-butyloxycarbonyl Bn benzyl Bpin boronic acid pinacol ester Bq benzoquinone Bz benzoyl cod 1,5-cyclooctadiene coe cyclooctene Cp* (pentamethyl)cyclopentadienyl Cy cyclohexyl DIAD diisopropyl azodicarboxylate hfacac hexafluoroacetylacetonate HFIP 1,1,1,3,3,3-hexafluoro-2-propanol KHMDS potassium bis(trimethylsilyl)amide Mes mesityl NFSI N-fluorobenzenesulfonamide NIS N-iodosuccinimide Nphth N-phthalimide NTf bis(trifluoromethanesulfonyl)imide OTf trifluoromethanesulfonate PivOH pivalic acid Q 8-quinolinyl xvii tAm tert-amyl TFA trifluoroacetate TIPS triisopropylsilyl TMS trimethylsiyl Ts p-toluenesulfonyl xviii CHAPTER 1 TRANSITION METAL-CATALYZED FUNCTIONALIZATION OF CARBON-HYDROGEN BONDS USING PHOSPHORUS AND SULFUR-CONTAINING DIRECTING GROUPS 1