Chiral phosphoric acids and alkaline earth metal phosphates chemistry

173 Pages·2015·6.28 MB·English

University of South Florida
Scholar Commons
Graduate Theses and Dissertations Graduate School
7-10-2014
Chiral phosphoric acids and alkaline earth metal
phosphates chemistry
Tao Liang
University of South Florida, [email protected]
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Liang, Tao, "Chiral phosphoric acids and alkaline earth metal phosphates chemistry" (2014).Graduate Theses and Dissertations.
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Chiral Phosphoric Acids and Alkaline Earth Metal Phosphates Chemistry

by

Tao Liang

A dissertation submitted in partial fulfillment
of the requirements for the degree of
Doctor of Philosophy
Department of Chemistry
College of Arts and Sciences
University of South Florida

Major Professor: Jon Antilla, Ph.D.
Mark McLaughlin, Ph.D.
James Leahy, Ph.D.
Jianfeng Cai, Ph.D.

Date of Approval:
July 10, 2014

Keywords: Enantioselective synthesis, Pinacol rearrangement, hetero-Diels-Alder reaction,
Mukaiyama-Michael reaction, Phosphoric acid, Chiral metal phosphate, Organocatalysis.

Copyright © 2014, Tao Liang
Acknowledgments
To finish a PhD, working hard is not enough. The great support and help from others is also
the key to one’s success. I would like to thank all the people who supported and assisted me
during my research.
First and foremost, I would like to thank professor Jon C. Antilla for being an encouraging
and supportive mentor during my graduate study. The “find your own project” way helped me
think independently and lead the research in my own way. His insightful suggestion would point
my study to the right direction, especially in the bad times. I have learnt not only chemistry
knowledge but also living skills in US from Dr. Antilla. The invaluable time we spent in the lab,
office and even gym on the discussions science, politics and sports surely benefits me the rest of
my life.
I would like to thank all the group members in Antilla’s lab that I have worked with all these
years. I would especially like to thank Dr. Wenhua Zheng for training me to be an excellent
organic chemist. I would also like to thank Dr. Guilong Li, Dr. Zuhui Zhang and Dr. Ying Dou
for our great discussions on chemistry in the lab and over the party time. I like to thank Dr.
Sunliang Cui, Shawn Larson, Gajendra Ingle, Sri Krishna, and Matt Kaplan for all of our fun
time working together in the Antilla group. Also, I am thankful to Youngran Ji and Susana Lopez
for their continuous support.
Thanks go out to my committee members Dr. Mark McLaughlin, Dr. James Leahy and Dr.
Jianfeng Cai. Their suggestions are intriguing and their knowledge in chemistry is really
amazing.
I would like to thank all of the chemistry professors at USF. I would like to thank Dr. Wayne
Guida and Dr. Edward Turos for being insightful advisors.
I appreciate all the help I get from the chemistry staff. Particularly I thank Dr. Edwin Rivera
for the help on NMRs and Dr. Lukasz Wojtas for the help on X-ray crystallography.
I would next like to thank my family. I thank my mother for giving me every bit of her love
and my father for being a good life coach over the years. I could not imagine finishing my
research if without their love and support. I thank my uncle and aunt for all they have taught me
and support they given me. Lastly and importantly, I thank Siqi for being everything to me in my
life. The joy she brings and the patience she gives help me conquer all the obstacles.
Table of Contents
List of Tables ................................................................................................................................. iii

List of Figures ................................................................................................................................. v

List of Schemes .............................................................................................................................. vi

Abstract ........................................................................................................................................ viii

Chapter 1: Organocatalytic Enantioselective Pinacol Rearrangement ........................................... 1

1.1 Asymmetric catalysis .................................................................................................... 1

1.2 Organocatalysis ............................................................................................................. 2

1.3 Enantioselective phosphoric acid catalysis ................................................................... 8

1.4 Pinacol rearrangement ................................................................................................ 10

1.5 Chiral phosphoric acid-catalyzed asymmetric Pinacol rearrangement ....................... 13

1.6 Conclusions ................................................................................................................. 21

1.7 Reference .................................................................................................................... 21

Chapter 2: Chiral Alkaline Earth Metal Phosphate-Catalyzed hetero-Diels-Alder Reaction ....... 25

2.1 Chiral phosphoric acids and chiral metal phosphates, the real catalysts .................... 25

2.2 Chiral metal phosphates .............................................................................................. 29

2.3 Chiral alkaline metal phosphates ................................................................................ 31

2.4 Asymmetric hetero-Diels-Alder reaction of aldehydes and ketones .......................... 33

2.5 Catalytic asymmetric HDA reaction of ketones by chiral alkaline metal
phosphates ................................................................................................................... 37

2.5.1 Asymmetric HDA reaction of α-keto esters ................................................ 37

2.5.2 Asymmetric HDA reaction of isatins ........................................................... 45

2.5.3 Mechanistic studies ...................................................................................... 47

2.6 Conclusion .................................................................................................................. 52

2.7 References ................................................................................................................... 53

Chapter 3: Chiral Alkaline Earth Metal Phosphate-Catalyzed Mukaiyama-Michael
reaction .................................................................................................................................... 58
3.1 Mukaiyama-Michael addition ..................................................................................... 58

3.2 Catalytic enantioselective Mukaiyama-Michael addition ........................................... 59

3.3 Catalytic asymmetric Mukaiyama-Michael reaction by alkaline earth metal
i
phosphates ................................................................................................................... 60

3.4 Conclusion .................................................................................................................. 69

3.5 Future direction ........................................................................................................... 70

3.6 Reference .................................................................................................................... 72

Chapter 4: Experimental Procedures ............................................................................................ 73

4.1 Experimental procedures for Chapter 1 ...................................................................... 73

4.1.1 General consideration .................................................................................. 73

4.1.2 General procedure for the preparation of substrates 1 ................................. 74

4.1.3 Procedure for the preparation of catalyst P14 .............................................. 75

4.1.4 General procedure for asymmetric Pinacol rearrangement ......................... 76

4.2 Experimental procedures for Chapter 2 ...................................................................... 85

4.2.1 General consideration .................................................................................. 85

4.2.2 Procedure for the preparation of catalyst Ca[P6] ....................................... 86

2
4.2.3 General procedure for asymmetric HDA reaction of α-keto esters
and isatins ........................................................................................................ 86

4.3 Experimental procedures for Chapter 3 ...................................................................... 99

4.3.1 Procedure for the preparation of catalyst Mg[P18] .................................. 100

2
4.3.2 General procedure for asymmetric Mukaiyama-Michael reaction of
β,γ-unsaturated α-keto esters ......................................................................... 100
4.4 Reference .................................................................................................................. 108

Appendix A 1H and 13C NMR Spectra for Compounds ............................................................. 110

Appendix B Permission .............................................................................................................. 160

ii
List of Tables
Table 1.1 Catalysts survey of asymmetric Pinacol rearrangement ............................................... 15
Table 1.2 H8-BINOL-phosphoric acids as catalysts ..................................................................... 17
Table 1.3 Solvent survey of asymmetric Pinacol rearrangement ................................................. 17
Table 1.4 Substrate scope of asymmetric Pinacol rearrangement ................................................ 19
Table 2.1 Asymmetric Pinacol rearrangement using different batches of catalysts ..................... 25
Table 2.2 Ishihara's finding of contamination of phosphoric acid during purification on
silica gel .................................................................................................................................. 27
Table 2.3 Trace element analysis of TRIP by ICP-OES ............................................................... 28
Table 2.4 Asymmetric Pinacol rearrangement: real acid .............................................................. 29
Table 2.5 Catalysts survey of asymmetric HDA reaction of ethyl pyruvate ................................ 39
Table 2.6 Catalysts optimization of asymmetric HDA reaction of ethyl pyruvate ....................... 40
Table 2.7 Solvent survey of asymmetric HDA reaction of ethyl pyruvate ................................... 41
Table 2.8 Substrate scope for asymmetric HDA reaction of α-keto ester .................................... 43
Table 2.9 Substrate scope for asymmetric HDA reaction of α-keto ester, continued ................... 44
Table 2.10 Asymmetric HDA reaction of isatin ........................................................................... 46
Table 2.11 Molecular sieves studies ............................................................................................. 48
Table 3.1 Catalyst survey of asymmetric Mukaiyama-Michael reaction ..................................... 63
Table 3.2 Catalyst survey of asymmetric Mukaiyama-Michael reaction, continued ................... 64
Table 3.3 Asymmetric Mukaiyama-Michael reaction of methyl ester ......................................... 66
Table 3.4 Solvent survey of asymmetric Mukaiyama-Michael reaction ...................................... 67
iii
Table 3.5 Substrate scope for asymmetric Mukaiyama-Michael reaction .................................... 68

iv
List of Figures
Figure 1.1 Different enantiomers .................................................................................................... 1
Figure 1.2 Catalytic cycle of enamine catalysis .............................................................................. 4
Figure 1.3 Catalytic cycle of iminium catalysis .............................................................................. 5
Figure 1.4 Chiral phosphoric acid ................................................................................................... 9
Figure 1.5 Hypothesis of phosphoric acid-catalyzed Pinacol rearrangement ............................... 14
Figure 1.6 Proposed mechanism for PA-catalyzed asymmetric Pinacol rearrangement .............. 20
Figure 2.1 Chiral metal phosphates .............................................................................................. 29
Figure 2.2 Hypothesis ................................................................................................................... 33
Figure 2.3 Chiral alkaline earth metal phosphates ........................................................................ 38
Figure 2.4 ORTEP representation of Ca[P6] ............................................................................... 49
2
Figure 2.5 Raman spectra ............................................................................................................. 50
Figure 2.6 Transition state model for observed absolute stereochemistry .................................... 51
Figure 2.7 Transition state model ................................................................................................. 52

v
List of Schemes
Scheme 1.1 Hajos-Parrish-Eder-Sauer-Wiechert process ............................................................... 3
Scheme 1.2 Proline-catalyzed intermolecular Aldol reaction ......................................................... 4
Scheme 1.3 Imidazolidinone-catalyzed enantioselective Diels-Alder reaction .............................. 6
Scheme 1.4 Thiourea-catalyzed enantioselective Strecker reaction ............................................... 7
Scheme 1.5 TADDOL-catalyzed enantioselective hetero-Diels-Alder reaction ............................ 8
Scheme 1.6 Akiyama and Terada’s chiral phosphoric acid-catalyzed Mannich reaction .............. 9
Scheme 1.7 Pinacol rearrangement ............................................................................................... 10
Scheme 1.8 Synthesis of hydroxyphensatatin ............................................................................... 11
Scheme 1.9 Synthesis of (±)-Furoscrobiculin B ........................................................................... 11
Scheme 1.10 Semipinacol rearrangement ..................................................................................... 12
Scheme 1.11 Stereocontrolled semipinacol rearrangement .......................................................... 12
Scheme 1.12 Enantioselective semipinacol rearrangement of 2-oxo allylic alcohols .................. 13
Scheme 1.13 Enantioselective semipinacol rearrangement of vinylogous α-ketol ...................... 13
Scheme 2.1 Synthesis of arylpropionic acids using Pd-Phosphate ............................................... 30
Scheme 2.2 Chlorination and oxidation of oxindole catalyzed by VAPOL Ca phosphate .......... 32
Scheme 2.3 Diels-Alder reaction and hetero-Diels-Alder reaction .............................................. 33
Scheme 2.4 HDA reaction of aldehydes catalyzed by Cr salen complexes .................................. 34
Scheme 2.5 HDA reaction of aldehydes catalyzed by Ti-BINOL complexes .............................. 35
Scheme 2.6 HDA reaction of aldehydes catalyzed by dirhodium complex ................................. 35
Scheme 2.7 HDA reaction of aldehydes catalyzed by BAMOL .................................................. 36
vi