Epoxidations and Hydroperoxidations of α,β-Unsaturated Ketones: An Approach through Asymmetric Organocatalysis

265 Pages·2012·21.2 MB·English

by  Corinna Reisinger (auth.)

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Corinna Reisinger
Epoxidations and
Hydroperoxidations of
a,b-Unsaturated Ketones
An Approach Through Asymmetric
Organocatalysis
Doctoral Thesis accepted by the
University of Cologne, Germany
Research was carried out at the Max-Planck-Institut für
Kohlenforschung, Mülheim an der Ruhr, Germany
123
Author Supervisor
Dr. CorinnaReisinger Prof.Dr. BenjaminList
Max-Planck-Institut für Max-Planck-Institut für
Kohlenforschung Kohlenforschung
Mülheiman derRuhr Mülheiman derRuhr
Germany Germany
ISSN 2190-5053 ISSN 2190-5061 (electronic)
ISBN 978-3-642-28117-4 ISBN 978-3-642-28118-1 (eBook)
DOI 10.1007/978-3-642-28118-1
SpringerHeidelbergNewYorkDordrechtLondon
LibraryofCongressControlNumber:2012932956
(cid:2)Springer-VerlagBerlinHeidelberg2012
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Parts of this thesis have been published in the following journal articles:
‘‘Catalytic Asymmetric Hydroperoxidation of a,b-Unsaturated Ketones: An
Approach to Enantiopure Peroxyhemiketals, Epoxides, and Aldols’’: C.
M.Reisinger,X.Wang,B.List,Angew.Chem.,Int.Ed.2008,47,8112–8115;
Angew. Chem., 2008, 120, 8232–8235.
‘‘CatalyticAsymmetricEpoxidationofCyclicEnones’’:X.Wang,C.M.Reisinger,
B. List, J. Am. Chem. Soc. 2008, 130, 6070–6071.
‘‘Preparation of chiral a,b-epoxy ketones’’: B. List, C. M. Reisinger, X. Wang,
PCT Int. Appl. WO 2009112014 2009; Ger. Offen. DE 102008013962 2009.
Supervisor’s Foreword
The enantioselective catalysis of olefin epoxidations has traditionally defined the
stateoftheartinasymmetricsynthesis.Remarkablythough,despitethewonderful
advancements in this area, which led to many name reactions such as those by
Sharpless,Jacobsen-Katsuki,Julia-Colonna,andShi,amongothers,simpleenones
have remained elusive substrates for highly enantioselective and general epoxi-
dation catalysis. With this thesis, Corinna Reisinger has now delivered a close to
perfect solution to this problem.
CorinnaReisingerhas joined myresearch group at theMax-Planck-Institut für
Kohlenforschung as a Ph.D. candidate after having completed her studies in
chemistry at the University of Ulm with first-class honors. Her academic
achievements had already been rewarded with an undergraduate fellowship from
the Fonds der Chemischen Industrie and a diploma award of the Dr. Barbara
Mez-Starck Foundation in 2006. During her stay in my group, she was supported
byahighlyprestigiousKekuléfellowshipforgraduateresearchfromtheFondsder
Chemischen Industrie.
My group focuses on the development of new organocatalytic methods for
asymmetricsynthesis.Amongthese,methodsforgeneratinghighlyenantioenriched
epoxidesareofparamountimportance,duetotheversatilityofepoxidesasbuilding
blocksinacademicandindustrialorganicsynthesis.CorinnaReisinger’sworkhas
focused on the development of a general and efficient catalytic asymmetric
epoxidationofa,b-unsaturatedketonesandaldehydesviaiminiumioncatalysiswith
primaryaminesalts.Shehasdevelopedthefirsthighlyenantioselectiveepoxidation
of cyclic enones in collaboration with another group member (J. Am. Chem. Soc.
2008, 6070–6071). To the best of my knowledge, this work constitutes a break-
throughinthefieldofasymmetricepoxidationchemistry,standingtothisdateasthe
single most efficient method in the literature to generate the corresponding cyclic
epoxyketones with exquisitely high enantioselectivities. It is a testament to her
successthatherseminalpaperhascollectedover70citationsonlyduringthefirst
2 years after publication. Subsequently, she went on and implemented a highly
enantioselective,primaryaminesalt-catalyzedhydroperoxidationoflinearaliphatic
enones to provide enantiomerically pure 3-hydroxy-1,2-dioxolanes. Corinna first
vii
viii Supervisor’sForeword
identified these peroxy hemiketals as by-products of the epoxidation process and
immediatelyrecognizedtheirsyntheticpotential.Indeed,shedemonstratedthatthe
productscouldbeconvertedtothecorrespondingepoxidesandtob-hydroxyketones
inaone-potsequencewithoutlossofenantioselectivity(Angew.Chem.Int.Ed.2008,
8112–8115).
Very recently, solely based on Corinna’s encouragement, another graduate
student of mine together with Corinna extended her epoxidation method to
a-branchedenals.Thisworkprovidesthesolutiontoyetanotherentirelyunsolved
probleminasymmetricepoxidationcatalysisandwasjustpublished(J.Am.Chem.
Soc. 2010, 10227–10229).
Corinna’s work could have far-reaching applications in asymmetric catalysis
andapatentcoveringheroxidationmethodiscurrentlypending.Indeed,theuseof
hydrogen peroxide as a safe inorganic oxidant that generates only water as a by-
product, combined with the operational simplicity of this reaction (inexpensive
cinchona alkaloids as catalysts, no requirement for inert atmosphere or scrupu-
lously dried solvents) could well lead to commercial applications.
Based on her wonderful achievements, she has already won several awards,
including being selected among the prestigious DSM Science and Technology
awardeesof2010,andtheOtto-Hahn-MedaloftheMax-Planck-Society.Reading
thisthesishasbeendelightfulandremindedmeofthegreatprivilegeithasbeento
work with her.
Mülheim an der Ruhr Prof. Dr. Benjamin List
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1 Asymmetric Organocatalysis. . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1.1 Historical Development. . . . . . . . . . . . . . . . . . . . . . . . 5
2.1.2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2.1.3 Aminocatalysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.2 Catalytic Asymmetric Epoxidation of Electron-Deficient
Olefins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.2.1 Milestones in Catalytic Asymmetric
Olefin Epoxidations. . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.2.2 Weitz–Scheffer Epoxidation. . . . . . . . . . . . . . . . . . . . . 17
2.2.3 Synthetic Versatility of a,b-Epoxy Ketones . . . . . . . . . . 19
2.2.4 State of the Art: Catalytic Asymmetric Epoxidation
of a,b-Unsaturated Ketones . . . . . . . . . . . . . . . . . . . . . 19
2.2.5 Recent Advances: The Organocatalytic Approach. . . . . . 24
2.2.6 Asymmetric Epoxidation of Cyclic a,b-Unsaturated
Ketones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.3 Synthesis and Relevance of 3-Hydroxy-1,2-dioxolanes
and 1,2-Dioxolanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.3.1 Peroxidic Natural Products. . . . . . . . . . . . . . . . . . . . . . 31
2.3.2 General Methods for the Synthesis
of 3-Hydroxy-1,2-dioxolanes . . . . . . . . . . . . . . . . . . . . 32
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3 Objectives of This Ph.D. Work. . . . . . . . . . . . . . . . . . . . . . . . . . . 41
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
4 Results and Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.1 Catalytic Asymmetric Epoxidation of Cyclic Enones. . . . . . . . . 45
ix
x Contents
4.1.1 Screening Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.1.2 Reaction Scope and Discussion. . . . . . . . . . . . . . . . . . . 55
4.1.3 Summary and Conclusions. . . . . . . . . . . . . . . . . . . . . . 73
4.2 Catalytic Asymmetric Epoxidation and Hydroperoxidation
of Acyclic Enones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
4.2.1 Screening Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
4.2.2 Reaction Scope and Discussion. . . . . . . . . . . . . . . . . . . 85
4.2.3 Summary and Conclusions. . . . . . . . . . . . . . . . . . . . . . 103
4.3 Synthetic Transformations of Optically Active a,b-Epoxy
Ketones and 3-Hydroxy-1,2-dioxolanes . . . . . . . . . . . . . . . . . . 105
4.3.1 One-Pot Synthesis of Aldol Products From
a,b-Unsaturated Ketones . . . . . . . . . . . . . . . . . . . . . . . 105
4.3.2 Synthesis of Aldol Products by Reductive Cleavage
of a,b-Epoxy Ketones . . . . . . . . . . . . . . . . . . . . . . . . . 108
4.3.3 Synthesis of 1,2-Dioxolanes From Peroxyhemiketals. . . . 111
4.4 Summary and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.5 Mechanistic Considerations. . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.5.1 Evaluation of Modified Catalysts: Structure-Activity
Relationships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.5.2 ESI-MS Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
4.5.3 Further Mechanistic Investigations . . . . . . . . . . . . . . . . 120
4.5.4 Summary and Conclusions. . . . . . . . . . . . . . . . . . . . . . 121
4.6 Preparation of Starting Materials. . . . . . . . . . . . . . . . . . . . . . . 126
4.6.1 Preparation of Cyclic a,b-Unsaturated Ketones. . . . . . . . 126
4.6.2 Preparation of Acyclic a,b-Unsaturated Ketones. . . . . . . 128
4.7 Catalyst Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
4.7.1 Synthesis of Chiral Primary Amines Based
on the Quinuclidine Scaffold . . . . . . . . . . . . . . . . . . . . 131
4.7.2 Synthesis of Amino Acid-Derived Diamines . . . . . . . . . 134
4.7.3 Synthesis of BINOL-Derived Phosphoric Acids . . . . . . . 135
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
5 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
6 Outlook. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
7 Experimental Part. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
7.1 General Experimental Conditions . . . . . . . . . . . . . . . . . . . . . . 153
7.2 Catalytic Asymmetric Epoxidation of Cyclic Enones. . . . . . . . . 156
7.2.1 General Procedure. . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
7.2.2 Scope of Optically Active Cyclic a,b-Epoxyketones. . . . 157
7.3 Catalytic Asymmetric Hydroperoxidation and Epoxidation
of Acyclic Enones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
Contents xi
7.3.1 Catalytic Asymmetric Hydroperoxidation
of Acyclic Enones. . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
7.3.2 Synthesis of (R)-4-(Tert-butylperoxy)decan-2-one
((R)-95a) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
7.3.3 Catalytic Asymmetric Epoxidation of Acyclic Enones. . . 182
7.3.4 Hydroperoxidation of 4,8-Dimethylnona-3,7-
dien-2-one (100). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
7.3.5 Hydroperoxidation of Cycloheptenone (46s)
and Cyclooctenone (46v). . . . . . . . . . . . . . . . . . . . . . . 196
7.4 Synthetic Transformations of Optically Active Products. . . . . . . 198
7.4.1 One-Pot Synthesis of Aldol Products. . . . . . . . . . . . . . . 198
7.4.2 Organoselenium-Mediated Reductive
Epoxide Opening . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
7.4.3 Synthesis of (3R,5S)-3-Hexyl-5-methyl-1,2-
dioxolane (127). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
7.5 Preparation of Starting Materials. . . . . . . . . . . . . . . . . . . . . . . 206
7.5.1 Preparation of Cyclic a,b-Unsaturated Ketones. . . . . . . . 206
7.5.2 Preparation of Acyclic a,b-Unsaturated Ketones. . . . . . . 216
7.6 Catalyst Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
7.6.1 Synthesis of 9-Amino(9-deoxy) Cinchona Alkaloid
Derivatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
7.6.2 Synthesis of 9-epiquinine (147) . . . . . . . . . . . . . . . . . . 238
7.6.3 Synthesis of 60-isopropoxycinchonidine (146). . . . . . . . . 240
7.6.4 Synthesis of 9-amino(9-deoxy)epi-60-
hydroxycinchonidine (68). . . . . . . . . . . . . . . . . . . . . . . 242
7.6.5 Synthesis of 2-(a-aminobenzyl)quinuclidine (86a). . . . . . 243
7.6.6 Synthesis of Amino Acid-Derived Diamines . . . . . . . . . 246
7.6.7 Synthesis of (1R,2R)-N-iso-propyl-1,2-
diphenylethylene-1,2-diamine (61) . . . . . . . . . . . . . . . . 251
7.6.8 Synthesis of (S)-3,30-bis(triphenylsilyl)-1,10-
binaphthyl-2,20-diol phosphate ((S)-7b) . . . . . . . . . . . . . 252
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257