TRANSITION METAL CATALYZED STEREOSELECTIVE TRANSFORMATIONS OF ALKYNES AND DONOR/ACCEPTOR CARBENOIDS Open Access

Briones, John Frederick Brucal (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/sj1392036?locale=en
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Abstract

Transition metal-stabilized carbenoids are versatile intermediates in organic synthesis. In particular, donor/acceptor-substituted carbenoids have been demonstrated to undergo highly stereoselective transformations owing to their modulated reactivity and therefore high chemo- and stereoselectivity. These characteristics were crucial to the discovery and development of powerful asymmetric synthetic transformations that are discussed in this thesis.

The first part of this dissertation focuses on the rhodium-catalyzed cyclopropenation of terminal alkynes. By using the prolinate-based catalyst Rh2(S-DOSP)4, highly enantioselective synthesis of vinylcyclopropenes using vinyldiazoacetates was achieved. These vinylcyclopropenes were also found to undergo rhodium-catalyzed ring expansion to the corresponding cyclopentadiene derivatives. Further expanding the scope of donor/acceptor cyclopropenation chemistry, we have developed the Rh2(S-PTAD)4-catalyzed highly enantioselective cyclopropenation of aryl alkynes with siloxyvinyldiazoacetates. This methodology allowed us to synthesize cyclopropene derivatives bearing germinal acceptor groups.

Rhodium catalysts have been shown to be highly effective in cyclopropenating terminal alkynes, however it fails when internal alkynes are used as substrates. This led us to the development of the silver-catalyzed cyclopropenation of internal alkynes which is the focus of the second part of this dissertation. By taking advantage of the highly reactive and sterically less demanding silver carbenoids, highly substituted cyclopropenes have been accessed. Enantioselective variant of this reaction was achieved using gold(I)-BINAP complexes.

The third part of this dissertation focuses on the gold-catalyzed stereoselective cascade reaction of propargyl alcohols and aryldiazoacetates. The reaction involves oxonium ylide formation followed by [2,3]-sigmatropic rearrangement followed by cycloisomerization leading to dihydrofuran derivatives. The reaction can also be extended to homopropargyl alcohols leading to the formation of tetrahydrofuran derivatives. The conventional O-H insertion reaction was minimal in most cases making these reactions very attractive.

The final chapter of this dissertation focuses on the asymmetric Au(I)-catalyzed vinylogous [3+2] cycloaddition reaction of vinyl ethers and styryldiazoacetates. These substrates, under rhodium catalysis, undergo the classical C-H insertion/Cope rearrangement. On the other hand, gold(I)-stabilized carbenoids possess highly electrophilic character at the vinylogous position and therefore undergo vinylogous attack instead of carbenoid attack. Highly functionalized cyclopentene derivatives were accessed using this methodology.

Table of Contents

Table of Contents

Chapter I Reactions of Donor/Acceptor Metallacarbenoids...1

1.1 Introduction...1
1.2 Metal Carbenoid...1
1.3 Dirhodium Catalysts...5

1.3.1 Cyclopropanation...12
1.3.2 Cyclopropenation...19
1.3.3 Ylide Chemistry...22
1.3.4 Vinylogous Reactivity...28

1.4 References...36

Chapter II Rhodium-Catalyzed Cyclopropenation of Terminal Alkynes with Donor/Acceptor-Substituted Carbenoids...42

2.1 Introduction...42
2.2 Rh2(S-DOSP)4-Catalyzed Cyclopropenation of Alkyl Alkynes with Methyl Styryldiazoacetate...43

2.2.1 Background...43
2.2.2 Results and Discussion...46
2.2.3 Summary...65

2.3 Rh2(S-PTAD)4-Catalyzed Cyclopropenation of Aryl Alkynes and Donor/Acceptor-Carbenoids...65

2.3.1 Introduction...65
2.3.2 Enantioselective cyclopropenation of alkynes and cyano-, and keto-substituted aryldiazo compounds...67
2.3.3 Highly enantioselective cyclopropenation of alkynes and siloxyvinyldiazoacetate...72

2.3.3.1 Background...72
2.3.3.2 Results and Discussion...76
2.3.3.3 Summary...84

2.4 References...85

Chapter III Silver-catalyzed Cyclopropenation of Internal Alkynes with Donor/Acceptor-Substituted Carbenoids...91

3.1 Introduction...91
3.2 Background...91

3.2.1 Silver Catalysis...91

3.2.1.1 Silver as Lewis Acid...91
3.2.1.2 Silver Nitrenes and Silylenes...96

3.2.2 Silver Carbenes...55

3.3 Results and Discussion...107
3.4 Summary...107
3.5 References...120

Chapter IV Highly Enantioselective Gold-Catalyzed Cyclopropenation of Internal Alkynes with Donor/Acceptor-Substituted Carbenoids...125

4.1 Introduction...125
4.2 Asymmetric Silver-Catalyzed Cyclopropenation...126
4.3 Asymmetric Gold-Catalyzed Cyclopropenation...126
4.4 Gold versus Ag/Au Complex-Catalyzed Cyclopropenation...142
4.5 Gold versus Ag/Au Complex-Catalyzed Cyclopropanation of olefins...157

4.5.1 Toste's Cyclopropanation with Propargyl Esters...157
4.5.2 Cyclopropanation with Donor/Acceptor Carbenoids...159

4.6 Summary...165
4.7 Future Directions...166
4.8 References...168

Chapter V Stereoselective Transformations of Propargyl Alcohols with Donor/Acceptor-Substituted Carbenoids...171

5.1 Introduction...171
5.2 Results and Discussion...175
5.3 Summary...192
5.4 Future Directions...192
5.5 References...195

Chapter VI Highly Enantioselective Au(I)-Catalyzed Vinylogous/[3+2] Cycloaddition of Enol Ethers and Vinyl Carbenoids...197

6.1 Introduction...197
6.2 Results and Discussion...198
6.3 Summary...208
6.4 Future Directions...209
6.5 References...211

Experimental Section...215

General Methods...215
Experimental Section for Chapter II...211
Experimental Section for Chapter III...271
Experimental Section for Chapter IV...294
Experimental Section for Chapter V...321
Experimental Section for Chapter VI...350
References...367

Appendix: X-Ray Crystallographic Data...370


List of Figures
Figure 1.1: Catalytic cycle for metal-catalyzed intermolecular cyclopropanation...1
Figure 1.2: Three classes of metal carbenoids...4
Figure 1.3: General structures of dirhodium tetracarboxylates and tetracarboxamidates...7
Figure 1.4: Doyle's dirhodium tetracarboxamidates catalysts...8
Figure 1.5: D2 symmetry representation of Rh2(S-DOSP)4...9
Figure 1.6: Structure of Rh2(S-PTTL)4 and Rh2(S-NTTL)4...10
Figure 1.7: C2 symmetry representation of Rh2(S-PTAD)4...10
Figure 1.8: Davies/Singleton's model for Rh2(S-DOSP)4-catalyzed cyclopropanation...11
Figure 1.9: Applications of donor/acceptor vinyl carbenoids...29
Figure 2.1: Various important synthetic transformations of cyclopropenes...44
Figure 2.2: nOe Analysis of cyclopentadiene 84...47
Figure 2.3: 1H NMR monitoring of the Rh-catalyzed rearrangement of 88...51
Figure 2.4: X-ray structure of cyclopropene 106...57
Figure 2.5: X-ray structure of cyclopentadiene 127...61
Figure 2.6: Extreme orientations of incoming substrate in cyclopropenation chemistry...62
Figure 2.7: Transition state for the cyclopropenation of propyne with 20...63
Figure 2.8: Predictive model for the asymmetric induction in Rh2(S-DOSP)4-catalyzed cyclopropenation...64
Figure 2.9: Typical catalyst-diazo combination in the Davies carbenoid chemistry...66
Figure 2.10: X-ray structure of cyclopropene 136...68
Figure 2.11: X-ray structure of furan 154...78
Figure 3.1: Proposed catalytic cycle for AgTp-catalyzed C-H amination...98
Figure 3.2: Proposed catalytic cycle for Ag-catalyzed silylene transfer to styrene...100
Figure 3.3: Jørgensen's proposed catalytic cycle for Ag(I)-catalyzed N-H insertion...104
Figure 3.4: Steric clash between rhodium catalyst wall and internal alkyne substrate...109
Figure 3.5: X-ray structure of cyclopropene 199...113
Figure 4.1: Chiral ligands in asymmetric silver catalysis...127
Figure 4.2: Chiral digold catalysts used in Toste's alkyne and allene chemistry...131
Figure 4.3: X-ray structure of cyclopropene 234...134
Figure 4.4: X-ray structure of cyclopropene 258...136
Figure 4.5: X-ray structure of cyclopropene 261...140
Figure 4.6: Diastereomers of the proposed Ag-Au bimetallic complex...143
Figure 4.7: 31P NMR of different Au(I) samples...144
Figure 4.8: X-ray structure of 240...150
Figure 4.9: Mass spec analysis for complexes (a) Ag-240 and (b) Ag-237...152
Figure 4.10: Exptl and theoretical isotope patter for Ag-Au containing compound...153
Figure 4.11: Computational model for the Au-Ag complex...155
Figure 4.12: Computational models for the carbene bound Ag-Au complex...156
Figure 4.13: Computational model of alkyne coordination with Au-Ag carbenoid...157
Figure 4.14: X-ray structure of cyclopropane 280...160
Figure 5.1: X-ray structure of allenol 327-Br...181
Figure 5.2: X-ray structure of allenol 336...182
Figure 5.3: Proposed cycle for the CuAAC reaction based on DFT calculations...185
Figure 5.4: Dihydrofuran and tetrahydrofuran structures in natural products...187
Figure 6.1: X-ray structure of 390...203
Figure 6.2: Enantioerosion of enol ether (S)-388...204
Figure 6.3: X-ray structure of 394...205


List of Schemes
Scheme 1.1: Resonance structure of a metal-stabilized carbenoid...3
Scheme 1.2: Rh2(OAc)4-catalyzed decomposition of diazo carbonyl compound...3
Scheme 1.3: Nozaki's Cu-catalyzed asymmetric cyclopropanation...3
Scheme 1.4: Doyle's Rh(II)-catalyzed enantioselective cyclopropanation of allyl diazoacetates...8
Scheme 1.5: Rh2(S-DOSP)4-catalyzed cyclopropenation of styrene with 18 and 20...11
Scheme 1.6: Rh2(S-PTAD)4-catalyzed carbenoid reactions of diazophosphonates...13
Scheme 1.7: Synthesis of Rh2(R-BTPCP)4...15
Scheme 1.8: Rh2(R-BTPCP)4-catalyzed cyclopropanation of styrene...15
Scheme 1.9: Rh-catalyzed cyclopropenation of terminal alkyne...19
Scheme 1.10: Rh-catalyzed cyclopropenation of terminal alkyne...22
Scheme 1.11: Rh-catalyzed cyclopropenation of terminal alkyne...23
Scheme 1.12: Rh-catalyzed cyclopropenation of terminal alkyne...24
Scheme 1.13: Rh-catalyzed tandem ylide/[2,3]-rearrangement of racemic alcohols...26
Scheme 1.14: Stereocontrolling elements of the tandem ylide/[2,3]-rearrangement reaction...27
Scheme 1.15: Rh-catalyzed tandem ylide/[2,3]-rearrangement of propargyl alcohols and 20...27
Scheme 1.16: Vinylogous & carbenoid reactivity of Rh(II)-stabilized vinylcarbenoid...28
Scheme 1.17: Vinylogous reactivity of Rh(II)-stabilized vinylcarbenoid...31
Scheme 1.18: Vinylogous reaction of (Z)-vinylcarbenoid 72 with substituted indoles...32
Scheme 1.19: Asymmetric vinylogous reaction of vinylcarbenoid with indoles...33
Scheme 1.20: Hu's silver-catalyzed X-H insertion to styryldiazoacetate...34
Scheme 1.21: Mechanistic proposals for vinylogous O-H insertion...35
Scheme 2.1: Reactivity profile of gold-activated cyclopropenes...45
Scheme 2.2: Rh2(S-DOSP)4-catalyzed reaction of propargyl siloxyether 81 with 20...46
Scheme 2.3: Proposed mechanism for the formation of cyclopentadiene 84...47
Scheme 2.4: Rh2(S-DOSP)4-catalyzed rearrangement of 88 to 89...50
Scheme 2.5: Rh2(S-DOSP)4-catalyzed reaction of disubstituted alkynes with 20...52
Scheme 2.6: Rh2(S-DOSP)4-catalyzed reaction of phenylacetylene and 107...55
Scheme 2.7: Determination of the absolute configuration of the cyclopropenes...56
Scheme 2.8: Mechanism for the Rh-catalyzed formation of cyclopentadienes...59
Scheme 2.9: One-pot synthesis of trifluoromethyl-substituted cyclopropenes...67
Scheme 2.10: Katsuki's Ir(salen)-catalyzed enantioselective cyclopropenation...73
Scheme 2.11: Zhang's asymmetric cyclopropenation using chiral cobalt porphyrin...74
Scheme 2.12: Rh-catalyzed cyclopropenation of with iodonium ylide...75
Scheme 2.13: Relationship between siloxyvinyldiazoacetate 146 and diazoacetoacetate 148...76
Scheme 2.14: Rh-catalyzed reaction of phenylacetylene and 150...77
Scheme 2.15: Mechanism for the Rh-catalyzed formation of furan product...83
Scheme 3.1: Synthetic applications of Yamamoto's Ag(I)/BINAP catalyst system...93
Scheme 3.2: Asymmetric silver-catalyzed Mannich reaction...94
Scheme 3.3: Asymmetric silver-catalyzed addition of silyl enol ether to α-keto esters...94
Scheme 3.4: Ag(I)-catalyzed synthesis of heterocycles...95
Scheme 3.5: He's silver-catalyzed aziridination of olefins...96
Scheme 3.6: Diaz and Perez's silver-catalyzed C-H amination of hydrocarbons...97
Scheme 3.7: Applications of Wolff rearrangement...101
Scheme 3.8: Rearrangement of silver carbenes by Mass Spectrometry...102
Scheme 3.9: Jørgensen's asymmetric silver-catalyzed aziridination of iminoesters...102
Scheme 3.10: Jørgensen's asymmetric silver-catalyzed N-H insertion with ethyl phenyldiazoacetate 181...103
Scheme 3.11: Burgess's Ag(I)-catalyzed intramolecular C-H insertion...104
Scheme 3.12: Silver-catalyzed insertion into C-Halogen bonds...105
Scheme 3.13: Perez's AgTpBr3-catalyzed C-H insertion...106
Scheme 3.14: Silver-catalyzed decomposition of diazoacetate 188 in methanol...107
Scheme 3.15: AgSbF6-catalyzed cyclopropanation of styrene...108
Scheme 3.16: AgOTf-catalyzed cyclopropenation of alkyne 193 with diazoacetate 18...109
Scheme 3.17: Ag-catalyzed reaction of acceptor- and acceptor/acceptor-substituted diazo compounds with 193...112
Scheme 3.18: Ag-catalyzed reaction of vinyldiazoacetates with 193...118
Scheme 3.19: Burgess's Ag(I)-catalyzed intramolecular C-H insertion...104
Scheme 4.1: Synthesis of Perez's gold(I) catalyst...128
Scheme 4.2: Au(I)-catalyzed cyclopropenation of diyne 252 with 253...135
Scheme 4.3: Au(I)-catalyzed cyclopropenation of enyne 255 with 18...135
Scheme 4.4: Silver(I) and gold(I)-catalyzed cyclopropenation of diaryl alkyne 257...137
Scheme 4.5: Cu(I)-catalyzed formation of indene derivatives from aryl alkynes and aryl diazoacetates...138
Scheme 4.6: Cu(I)-catalyzed formation of indene derivatives from aryl alkynes and aryl diazoacetates...139
Scheme 4.7: "Silver-effect" in gold(I)-catalyzed hydroarylation...143
Scheme 4.8: Cyclopropenation of 193 with 276...148
Scheme 4.9: Cyclopropenation of 193 with isolated gold complex...149
Scheme 5.1: Rh-catalyzed tandem ylide formation/[2,3]-rearrangement of allylic alcohols...171
Scheme 5.2: Rh-catalyzed tandem ylide formation/[2,3]-rearrangement of propargylic alcohols...172
Scheme 5.3: Proposed mechanism for the silver carbenoid C-Cl insertion...173
Scheme 5.4: Ag(I)-catalyzed rearrangement of allylic and propargyl sulfides...175
Scheme 5.5: Proposed mechanisms for the formation of dihydrofuran derivatives...178
Scheme 5.6: Ag(I)-catalyzed reaction of 2o alcohols and 18...181
Scheme 5.7: Ag(I)-catalyzed reaction of 3-butyn-1-ol with 18...183
Scheme 5.8: Plausible mechanism for the formation...184
Scheme 5.9: Au(I)-catalyzed reaction of 18 and propargyl alcohol 354...189
Scheme 5.10: Synthesis of allenol derivative 362...191
Scheme 5.11: Ag(I)- and Au(I)-catalyzed cycloisomerization of allenol...191
Scheme 5.12: Au(I)-catalyzed reaction of 364 and 18...192
Scheme 5.13: Au(I)-catalyzed reaction of 18 and primary allylic alcohol...194
Scheme 6.1: Rh2(S-DOSP)4-catalyzed CHCR reaction of vinyl ethers and 20...198
Scheme 6.2: Au(I)-catalyzed reaction of vinyl ethers and 20...199
Scheme 6.3: Au(I)-catalyzed reaction of mixed vinyl ether 374 and 20...200
Scheme 6.4: DKR in the Au(I)-catalyzed vinylogous [3+2] reaction...202
Scheme 6.5: Proposed mechanism for the formation of 390 and 391...206
Scheme 6.6: Au(I)-catalyzed reaction of 399 and 20...208
Scheme 6.7: Au(I)-catalyzed reaction of 399 with 146...210



List of Tables
Table 1.1: Comparison between Rh2(S-DOSP)4 and Rh2(S-PTAD)4 on the cyclopropanation of styrene with different aryl diazo compounds...14
Table 1.2: Catalyst effect in the cyclopropanation of trans-beta-methylstyrene...16
Table 1.3: Silver-catalyzed cyclopropanation with 18...17
Table 1.4: Silver-catalyzed cyclopropanation with 20...18
Table 1.5: Rh2(S-DOSP)4-catalyzed cyclopropenation of terminal alkynes with methyl phenyldiazoacetate 18...20
Table 1.6: Rh2(S-DOSP)4-catalyzed cyclopropenation of phenylacetylene with various aryldiazoacetates...21
Table 1.7: Relative free energies of the two competing pathways for various catalyst systems used in the O-H insertion reaction...25
Table 1.8: Effect of the ester group on the Rh-catalyzed reaction with 65...30
Table 2.1: Rh2(S-DOSP)4-catalyzed reaction alkynes with 20 at room temperature...49
Table 2.2: Rh2(S-DOSP)4-catalyzed cyclopropenation alkyl alkynes and at -45 °C...53
Table 2.3: Rh2(S-DOSP)4-catalyzed synthesis of cyclopentadiene derivatives...58
Table 2.4: Rh2(S-DOSP)4-catalyzed reaction of 1-pentyne using various styryldiazoacetates...60
Table 2.5: Rh2(S-PTAD)4-catalyzed cyclopropenation of aryl alkynes using various aryldiazo compounds...69
Table 2.6: Rh2(S-PTAD)4-catalyzed cyclopropenation of various aryl alkynes using 2-diazo-2-phenylacetonitrile 138...71
Table 2.7: Rh-catalyzed reaction of phenylacetylene with diazoacetoacetate 148...79
Table 2.8: Rh-catalyzed cyclopropenation of phenylacetylene with siloxyvinyldiazo-acetate 146...80
Table 2.9: Rh2(S-PTAD)4-catalyzed cyclopropenation of various aryl alkynes using 5...82
Table 3.1: Silver-catalyzed silacyclopropanation of various olefins...99
Table 3.2: Silver-catalyzed C-H insertion to hydrocarbons with ethyl diazoacetate...106
Table 3.3: Cyclopropenation of 193 with 18 using readily available silver(I) salts...110
Table 3.4: AgOTf-catalyzed cyclopropenation of various alkynes with 18...114
Table 3.5: Chemoselectivity studies: cyclopropanation versus cyclopropenation...116
Table 3.6: AgOTf-catalyzed cyclopropenation of 193 with aryl diazo compounds...119
Table 4.1: Ag(I)-catalyzed cyclopropenation using various chiral ligands...128
Table 4.2: Reaction of EDA catalyzed by 236 and NaBARF...130
Table 4.3: Gold(I)-catalyzed cyclopropenation of 193 with 18...132
Table 4.4: Cyclopropenation of 193 with 18 catalyzed by monogold catalysts...133
Table 4.5: Enantioselective gold(I)-catalyzed cyclopropenation of various alkynes...134
Table 4.6: Au(I)-catalyzed cyclopropenation of 193 with various aryl diazoacetates...141
Table 4.7: Au/Ag-catalyzed hydration of internal alkyne...145
Table 4.8: Effect of Au:Ag mol ratio on the cyclopropenation of 193...146
Table 4.9: Control experiments for cyclopropenation of 193...147
Table 4.10: Au(I)-catalyzed cyclopropanation of styrene with propargyl ester 276...158
Table 4.11: Au(I)-catalyzed cyclopropanation of styrene...159
Table 4.12: Gold(I)-catalyzed cyclopropanation of β-methylstyrene 278 with 18...161
Table 4.13: Gold(I)-catalyzed cyclopropanation of various olefins...162
Table 4.14: Gold(I)-catalyzed cyclopropanation of β-methylstyrene 280 with various diazoacetates...163
Table 4.15: Gold(I)-catalyzed cyclopropanation of β-methylstyrene 280 with 18...164
Table 4.16: Silver-free vs Au/Ag-catalyzed cyclopropanation of 278 with 276...165
Table 5.1: Ag(I)-catalyzed ylide/rearrangement of allylic and propargylic halides with EDA...174
Table 5.2: Ag(I)-catalyzed reaction of primary propargylic alcohols and 18...176
Table 5.3: Ag(I)-catalyzed reaction of 3o propargylic alcohols and 18...179
Table 5.4: Ag(I)-catalyzed reaction of 2o propargylic alcohols and 18...180
Table 5.5: Ag(I)-catalyzed reaction of 3o chiral propargylic alcohols and 18...182
Table 5.6: Ag(I)-catalyzed reaction of homopropargylic alcohols and 18...186
Table 5.7: Au(I)-catalyzed reaction of 1o propargylic alcohols and 18...188
Table 5.8: Au(I)-catalyzed reaction of 3o propargylic alcohols and 18...190
Table 6.1: Au(I)-catalyzed vinylogous [3+2] reaction of enol ethers and 20...201
Table 6.2: DKR in the Au(I)-catalyzed vinylogous [3+2] reaction...205
Table 6.3: Au(I)-catalyzed vinylogous [3+2] with enol ethers and siloxyvinyldiazoacetates...210

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