Organocatalytic asymmetric aldol reactions with ketone acceptors:
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| Format: | Thesis Book |
| Language: | English |
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2013
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Zsfassung in dt. und engl. Sprache |
| Physical Description: | IV, 168 S. graph. Darst. |
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| adam_text | Titel: Organocatalytic asymmetric aldol reactions with ketone acceptors
Autor: Duangdee, Nongnaphat
Jahr: 2013
TABLE OF CONTENTS
1 Summary...................................................................................... 1
1.1 The organocatalytic asymmetric direct aldol addition of acetone to aryl
trifluoromethyl ketones......................................................................1
1.2 Attempted organocatalytic asymmetric aldol-type reactions between
simple ketones................................................................................4
2 Introduction................................................................................... 6
3 Background................................................................................... 9
3.1 Aldol reactions................................................................................9
3.2 Stereoselectivity in typical aldol reactions.............................................10
3.3 Concepts of catalytic asymmetric aldol reactions....................................11
3.4 Enamine-catalyzed asymmetric aldol reactions......................................12
3.5 Mukaiyama-type catalytic asymmetric aldol reactions..............................18
3.5.1 Silicon Lewis-acids for aldol reactions..................................................20
3.5.1.1 Silylated Bransted acids as powerful Lewis acids..............................21
3.5.1.2 Lewis base activation of Lewis acids.............................................. 25
3.6 Organocatalytic kinetic resolution based on a retro-aldol reaction...............28
4 Concept....................................................................................... 31
4.1 The organocatalytic asymmetric direct aldol addition of acetone to aryl
trifluoromethyl ketones......................................................................31
4.2 Large-scale synthesis of Singh s catalyst in a one-pot procedure
starting from proline.........................................................................32
4.3 Organocatalytic asymmetric aldol-type reactions between simple ketones... 33
5 Results and Discussion.....................................................................34
5.1 Large-scale synthesis of Singh s catalyst 1 in a one-pot procedure............34
5.1.1 Synthesis of Singh s catalyst (S,S)-1 starting from Boc-L-proline [(S)-2]......34
5.1.2 Synthesis of Singh s catalyst (S,S)-1 starting from L-proline [(S)-4]....-........35
5.1.3 Synthesis of Singh s catalyst (R,R)-1 starting from Boc-L-proline [(R)-2]......38
5.2 Organocatalytic asymmetric aldol addition of acetone to aryl trifluoromethyl
ketones at room temperature using Singh s catalyst................................39
5.2.1 Catalyst screening...........................................................................39
5.2.2 Kinetic investigations on the direct aldol addition of acetone to
trifluoroacetophenone (7a) in the presence of catalyst 1...........................41
5.2.2.1 Effect of solvents...........................................................................42
5.2.2.2 Effect of additives..........................................................................44
5.2.2.3 Effect of workup/product isolation.....................................................46
5.2.3 Effect of catalyst loadings..................................................................48
5.2.4 Substrate scope of the reaction..........................................................50
5.2.5 Absolute configuration of the aldol adducts............................................52
5.2.6 Characterization of a substrate-catalyst adduct formed in the reaction of
acetone with trifluoroacetophenone (7a) in the presence of the catalyst 1....53
5.3 Configurational assignment of 1,3-diols................................................57
5.4 Attempted organocatalytic kinetic resolution based on retro-aldol reaction
of 4-hydroxy-4-phenylpentan-2-one.....................................................60
5.5 Attempted chiral Bransted acid-mediated Mukaiyama aldol-type reaction
of acetone silyl enol ether and acetophenone dimethyl acetal...................65
5.6 Preliminary results on the chiral Lewis base catalyzed addition of
silyl enol ethers to ketones.................................................................71
6 Outlook.........................................................................................75
6.1 Synthesis of chiral 1,3-diols...............................................................75
6.1.1 Biocatalytic aldol reduction................................................................75
6.1.2 Diastereoselective aldol reduction.......................................................75
6.2 Organocatalytic asymmetric cross-aldol reactions between simple ketones..76
6.2.1 The catalyst design......................................................................... 76
6.2.2 The development of a novel synthetic method.......................................76
7 Experimental................................................................................. 77
7.1 General Experimental Conditions........................................................77
7.2 Preparation of Singh s catalyst 1.........................................................81
7.2.1 Preparation of (S)-2-amino-4-methyl-1,1-diphenylpentan-1-ol [(S)-3)]..........81
7.2.2 Preparation of (R)-2-amino-4-methyl-1,1-diphenylpentan-1-ol [(R)-3)].........82
7.2.3 Preparation of (S)-A/-[(S)-1-hydroxy-4-methyl-1,1-diphenylpentan-2-yl]
pyrrolidine-2-carboxamide[(S,S)-1]......................................................83
7.2.4 Preparation of (R)-N-[(R)-1-Hydroxy^-methyl-1,1-diphenylpentan-2-yl]
pyrrolidine-2-carboxamide[(R,R)-1]......................................................86
7.3 Synthesis of rac-/V-methyl-1-(trifluoromethyl)isoindolin-1-ol (rac-25)...........88
7.3.1 Synthesis of fV-methyl-2-bromobenzylamine (27)...................................88
7.3.2 Synthesis of rac-N-methyl-1-(trifluoromethyl)isoindolin-1-ol (rac-25)...........89
7.4 Asymmetric aldol addition of acetone to aryl 2,2,2-trifluoromethyl ketones... 91
7.4.1 General procedure for kinetic investigations: monitoring by 19F NMR..........91
7.4.2 General procedure for kinetic investigations: monitoring by HPLC..............92
7.4.3 General procedure for the synthesis of aldol adduct (S)-9a-f.
preparative scale..........................................................................................92
7.4.3.1 5,5,5-Trifluoro-4-hydroxy-4-phenylpentan-2-one [(S)-9a]......................92
7.4.3.2 5,5,5-Trifluoro-4-hydroxy-4-p-tolylpentan-2-one[(S)-9b].......................93
7.4.3.3 5,5,5-Trifluoro-4-hydroxy-4-(4-methoxyphenyl)pentan-2-one[(S)-9c]......94
7.4.3.4 5,5,5-Trifluoro-4-hydroxy-4-(2-methoxyphenyl)pentan-2-one [(S)-9d].....95
7.4.3.5 4-(4-Fluorophenyl)-5,5,5-trifluoro-4-hydroxypentan-2-one[(S)-9e]..........96
7.4.3.6 4-(4-Chlorophenyl)-5,5,5-trifluoro-4-hydroxypentan-2-one [(S)-9f]..........96
7.5 Synthesis of 1,3-diols 20a and its derivative..........................................99
7.5.1 Synthesis of (2S,4S)-1,1,1-trifluoro-2-phenylpentane-2,4-diol
[(2S,4S)-20a-l.................................................................................99
7.5.2 Synthesis of (2S,4S)-5,5,5-trifluoro-4-hydroxy-4-phenylpentan-2-yl
3,5-dinitrobenzoate (62)....................................................................101
7.6 Organocatalytic kinetic resolution based on the retro-aldol reaction of
4-hydroxy-4-phenylpentan-2-one (rac-12).............................................103
7.6.1 Catalyst screening for the kinetic resolution based on retro-aldol reaction
of rac-12.........................................................................................................104
7.6.2 Improvement of the kinetic resolution based on retro-aldol reaction
of rac-12 with NH2-ep/-quinine 14........................................................104
7.6.3 Synthesis of the rac-4-hydroxy-4-phenylpentan-2-one (rac-12)..................105
7.6.4 Synthesis of (S)-(6-methoxyquinolin-4-yl)[(2S,4S,8R)-8-vinylquinuclidin-
2-yl]methanamine (14)......................................................................106
7.7 Chiral Bransted acid-mediated Mukaiyama aldol-type reaction of
acetone silyl enol ether with acetophenone dimethyl acetal......................108
7.7.1 Catalyst screening for the chiral Bransted acid-mediated Mukaiyama aldol-
type reaction of acetone silyl enol ether and acetophenone dimethyl acetal. 108
7.7.2 Synthesis of rac-4-methoxy-4-phenylpentan-2-one (rac-18)......................109
7.8 Preliminary results on the chiral Lewis base catalyzed addition of
silyl enolate to ketones.....................................................................110
7.8.1 Preparation of trichlorosilyl triflate (SiCI3OTf).........................................110
7.8.2 Catalyst screening for the SiClaOTf-mediated asymmetric aldol aadition
of acetone to acetophenone using Lewis base as an organocatalyst..........110
8 Reference......................................................................................112
9 Appendix.......................................................................................119
9.1 Abbreviations................................................................................. 119
9.2 Compound index.............................................................................121
9.3 Supporting information..................................................................... 122
9.3.1 Large-scale synthesis of Singh s catalyst in a one-pot procedure...............122
9.3.2 The organocatalytic asymmetric direct aldol addition of acetone to
aryl trifluoromethyl ketones and 1,3-diols..............................................137
9.4 Abstract - Kurzzusammenfassung...................................................... 165
9.5 Erklarung...................................................................................... 167
9.6 Curriculum Vitae............................................................................. 168
|
| any_adam_object | 1 |
| author | Duangdee, Nongnaphat 1974- |
| author_GND | (DE-588)103556761X |
| author_facet | Duangdee, Nongnaphat 1974- |
| author_role | aut |
| author_sort | Duangdee, Nongnaphat 1974- |
| author_variant | n d nd |
| building | Verbundindex |
| bvnumber | BV041231453 |
| ctrlnum | (OCoLC)861470893 (DE-599)HBZHT017664867 |
| dewey-full | 547.215 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 547 - Organic chemistry |
| dewey-raw | 547.215 |
| dewey-search | 547.215 |
| dewey-sort | 3547.215 |
| dewey-tens | 540 - Chemistry and allied sciences |
| discipline | Chemie / Pharmazie |
| format | Thesis Book |
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| institution | BVB |
| language | English |
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| physical | IV, 168 S. graph. Darst. |
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| spelling | Duangdee, Nongnaphat 1974- Verfasser (DE-588)103556761X aut Organocatalytic asymmetric aldol reactions with ketone acceptors vorgelegt von Nongnaphat Duangdee 2013 IV, 168 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. und engl. Sprache Köln, Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026205811&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Duangdee, Nongnaphat 1974- Organocatalytic asymmetric aldol reactions with ketone acceptors |
| subject_GND | (DE-588)4113937-9 |
| title | Organocatalytic asymmetric aldol reactions with ketone acceptors |
| title_auth | Organocatalytic asymmetric aldol reactions with ketone acceptors |
| title_exact_search | Organocatalytic asymmetric aldol reactions with ketone acceptors |
| title_full | Organocatalytic asymmetric aldol reactions with ketone acceptors vorgelegt von Nongnaphat Duangdee |
| title_fullStr | Organocatalytic asymmetric aldol reactions with ketone acceptors vorgelegt von Nongnaphat Duangdee |
| title_full_unstemmed | Organocatalytic asymmetric aldol reactions with ketone acceptors vorgelegt von Nongnaphat Duangdee |
| title_short | Organocatalytic asymmetric aldol reactions with ketone acceptors |
| title_sort | organocatalytic asymmetric aldol reactions with ketone acceptors |
| topic_facet | Hochschulschrift |
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