TRANSITION METAL CATALYZED STEREOSELECTIVE TRANSFORMATIONS OF ALKYNES AND DONOR/ACCEPTOR CARBENOIDS Público
Briones, John Frederick Brucal (2012)
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
About this Dissertation
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| Palavra-chave | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
TRANSITION METAL CATALYZED STEREOSELECTIVE TRANSFORMATIONS OF ALKYNES AND DONOR/ACCEPTOR CARBENOIDS () | 2018-08-28 10:27:44 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|