Amino acid-derived Lewis basic catalysts for asymmetric allylation of aldehydes and silylation of

346 Pages·2014·4.45 MB·English

Amino acid-derived Lewis basic
catalysts for asymmetric allylation of
aldehydes and silylation of alcohols
Author: Yu Zhao
Persistent link: http://hdl.handle.net/2345/357
This work is posted on eScholarship@BC,
Boston College University Libraries.
Boston College Electronic Thesis or Dissertation, 2008
Copyright is held by the author, with all rights reserved, unless otherwise noted.
Boston College
The Graduate School of Arts and Sciences
Department of Chemistry

Amino Acid-Derived Lewis Basic Catalysts for Asymmetric Allylation
of Aldehydes and Silylation of Alcohols

a dissertation
by
YU ZHAO

Submitted in partial fulfillment of the requirements
for the degree of
Doctor of Philosophy

June 2008
© Copyright by YU ZHAO
2008
Amino Acid-Derived Lewis Basic Catalysts for Asymmetric allylation of
Aldehydes and Silylation of Alcohols
Yu Zhao
Thesis Advisor: Professor Marc L. Snapper
ABSTRACT

• Chapter 1. Review of concept and methodology development for asymmetric
allylation of carbonyls and imines.
Chapter 2. Description of the catalytic asymmetric addition of allyltrichlorosilane
(cid:122)
to aldehydes catalyzed by a proline-based N-oxide catalyst.
10mol% O Me
O OH
O R1 SiCl3
N Ph
+ N H R
R H R2 R1 R2
DCE,23oC,24h upto92% ee,>98%dr
• Chapter 3. Introduction of the first catalytic asymmetric silylation of alcohols for
desymmetrization of meso-diols.
t-Bu
20-30mol% Me H
HO OH N N Me R3SiO OH
N
H
N O t-Bu
HO OH R3SiO OH
R SiCl,DIPEA
3
R Si=TBS,TIPS,TES,etc.
3
87-96%ee
• Chapter 4. Presentation of asymmetric silylation for synthesis of chiral
syn-1,2-diols by kinetic resolution or divergent reaction on a racemic mixture.
20-30mol% t-Bu
Me H
HO OH N N Me TBSO OH HO OH
N
+
H
R R N O t-Bu R R R R
S L S L S L
(+/-) TBSCl,DIPEA krelupto>200, eesmupto>99%
I
TABLE OF CONTENTS
Acknowledgements vi
List of Abbreviations viii
Chapter 1
Asymmetric Allylations of Carbonyls and Imines:
Concept and Methodology Development
1.1. Importance of Asymmetric Allylation 1
1.2. General Considerations for Development of Asymmetric Allylation 3
1.3. Types of Allylations 5
1.4. Asymmetric Allylboration of Carbonyls and Imines 6
1.4.1. Chiral Allylborane Reagents 6
1.4.2. Catalyzed Asymmetric Allylboration 8
1.4.2.1. Allylboration Catalyzed by External
Lewis/Brønsted Acid-Type I Allylation 8
1.4.2.2. Allylboration Catalyzed by Lewis Acid-
Transmetalation to Cu or Zn 10
1.4.2.3. Diol Catalyzed Allylboration of Ketones and Imines 12
1.5. Asymmetric Allylation Mediated by Transition Metals 14
1.5.1. Asymmetric Allyltitanation-Type III Allylation 14
1.5.2. Asymmetric Zinc-mediated Allylation 15
1.5.3. Asymmetric Indium-mediated Allylation 16
1.5.4. Nozaki-Hiyama-Kishi Allylation 19
II
1.6. Lewis Acid Catalyzed Asymmetric Allylstannanation and Allylsilylation 23
1.6.1. LA Catalyzed Asymmetric Allylation with Chiral Allylsilanes 27
1.6.1.1. Use of α-Chiral Allylsilanes 27
1.6.1.2. Use of Allylsilanes Modified with a Chiral
Ligand or Chiral at Silicon 29
1.6.1.3. Diastereoselective Addition of Allylsilanes to carbonyls 30
1.6.2. Chiral Lewis Acid Catalyzed Asymmetric Allylation 31
1.6.2.1. Boron Based Lewis Acid Catalyzed
Asymmetric Allylation of Aldehydes 31
1.6.2.2. Ti/Zr-BINOL Complex Catalyzed Asymmetric Allylation 32
1.6.2.3. Ag -BINAP Complex Catalyzed Asymmetric Allylation 36
1.6.2.4. Pd-π-Allyl Catalyzed Asymmetric Allylation of Imines 38
1.6.2.5. Other Transition Metal-Catalyzed Asymmetric Allylation 40
1.6.2.6. In-Catalyzed Asymmetric Allylation 42
1.6.2.7. SiCl /Bisphosphoramide-Catalyzed Asymmetric Allylation 44
4
1.7. Activation of Allylsilanes through Hypervalent Silicon Species 45
1.7.1. Chiral Allylsilanes/Allylstannanes with Hypervalent Si/Sn 50
1.7.2. Diol Promoted Allylation of Ketones with Tetraallystannane 57
1.7.3. LB Catalyzed Asymmetric Allylation Using Allyltrichlorosilane 58
1.7.3.1. Chiral Phosphoramide Catalyzed Asymmetric
Allylation of Aldehydes 59
1.7.3.2. Chiral Formamide Catalyzed Asymmetric Aldehydes Allylation 62
1.7.3.3. Chiral N-Oxide Catalyzed Asymmetric Allylation of Aldehydes 62
III
1.7.3.4. Lewis Base Promoted Asymmetric Allylation of Imines 65
1.8 New Concepts and Discoveries in Asymmetric Allylation of Carbonyls 67
1.8.1. Asymmetric Allylation of Aldehydes using Allylic Alcohols/Esters 67
1.8.2. Asymmetric Allyl-Transfer Reaction 69
1.8.3. Asymmetric Conjugate Allylation of Activated Enones 70
1.9 Conclusions and Outlook 72
Chapter 2
Development of Novel Lewis Basic Catalysts for Asymmetric Allylation
of Aldehydes and Imines using Allyltrichlorosilane
2.1. Background 73
2.2. Catalyst “Design” Criteria 75
2.3. Initial Catalyst and Substrate Screening 80
2.4. Proline N-Oxide Catalyzed Allylation of Aldehydes 83
2.4.1. Initial Tests 83
2.4.2. Positional Optimization of Catalyst 85
2.4.3. Reaction Condition Optimization 89
2.4.4. Reaction Quench Optimization 93
2.4.5. Substrate Scope for Allylation with 2.60 95
2.4.6. Preliminary Mechanistic Studies and Proposed Transition State 97
2.5. Investigation into Asymmetric Allylation of Aliphatic Aldehydes 99
2.6. Summary 102
2.7. Experimental and Supporting Information 103
General Information 103
IV
Procedures for the Synthesis of Proline Based N-Oxide Catalysts 105
General Procedure for the Catalytic Asymmetric Allylation
of Aldehydes with Allyltrichlorosilane and Catalyst 2.60 114
Spectra 125
Chapter 3
Desymmetrization of meso-Diols through Asymmetric Silylation
3.1. Introduction to Enantioselective Desymmetrization of meso-Diols 130
3.2. Desymmetrization of meso-Diols through Diastereoselective Reactions 131
3.3. Desymmetrization of meso-Diols through Catalytic Group Transfer Reactions 135
3.4. Desymmetrization of meso-Diols by Functional Group Transformation 142
3.5. Desymmetrization of meso-Diols: Why Asymmetric Silylation? 144
3.6. Mechanistic Basis for Silylation and Asymmetric Silylation of Alcohols 146
3.7. Catalyst “Design” Criteria 151
3.8. Initial Catalyst Screens and Reaction Condition Optimization 153
3.9. Positional Optimization of the Catalyst for Asymmetric Silylation 155
3.9.1. Catalyst Optimization for Asymmetric Silylation of 3.5 156
3.9.2. Catalyst Optimization for Asymmetric Silylation of 1,2-Diols 159
3.9.3. Catalysts of Different Structures for Asymmetric Silylation 160
3.10. Mechanistic Studies for Asymmetric Silylation 162
3.11. Substrate Scope of Asymmetric Silylation 166
3.12. Asymmetric Silylation with Functionalized Silylating Reagents 173
3.13. Asymmetric Silylation for Synthesis of Chiral Silanes (Stereogenic at Si) 175
3.14. Conclusions 178
V
3.15. Experimental and Supporting Information 179
General Information 179
Representative Procedure for the Synthesis of the Catalyst 180
General Procedure for Desymmetrization of meso-Diols
through Asymmetric Silylation 196
Representative Procedure for the Intramolecular Allylation of Siloxyketones 214
Spectra 217
Chapter 4
Enantioselective Synthesis of 1,2-Diols through Asymmetric Silylation
4.1. Introduction to Enantioselective Synthesis of syn-1,2-Diols 248
4.2. Rational for Asymmetric Silylation of syn-1,2-Diols 251
4.3. Initial Tests and Optimization of Asymmetric Silylation of syn-1,2-Diols 253
4.4. Substrate Scope for Kinetic Resolution of syn-1,2-Diols through AS 255
4.5. Unsuccessful Substrates for Kinetic Resolution 264
4.6. Summary of Kinetic Resolution of 1,2-Diols through Asymmetric Silylation 265
4.7. Divergent RRM of 1,2-Diols through Asymmetric Silylation 266
4.8. Experimental and Supporting Information 269
General Information 269
General Procedure for the Kinetic Resolution of 1,2-Diols
through Catalytic Asymmetric Silylation 270
Procedure for the Synthesis of 1,1-Diethoxybutane-2,3-diol (4.47) 295
Spectra 297
VI
Acknowledgements
Going abroad for graduate school was without doubt the most important decision
in my life so far. I feel really fortunate that I was admitted to Boston College, where I
have spent six substantial years as an organic chemist.
First of all I would like to thank Prof. Marc Snapper and Prof. Amir Hoveyda for
all their education, support and help throughout these years. Marc welcomed me to his
group as an international student who had no clue about organic chemistry at all.
Amir’s class on organic synthesis literally converted me into a passionate organic
chemist. As my advisors, they have inspired me in the research and helped me out with
a lot of things in life. I was very lucky to have had these two great advisors of different
types. Their influence on me will be a fortune for the rest of my life.
Special thanks are expressed to Dr. John Traverse, who has had a significant
impact on my graduate career. He trained me from ground zero and made me a capable
chemist. He also taught me a lot of English and presentation skills. The collaboration
with John on asymmetric allylation chemistry was for quite some time a disappointing
process of test and failure; his optimistic attitude and perseverance are important lessons
for me.
Jason Rodrigo has been a terrific collaborator; together we went through much
pains and excitements and developed the catalytic asymmetric silylation chemistry.
This precious experience will always be a vivid memory to me.
Then I had much fun working with Aurpon Mitra for two years. His early days
really reminded me what a big trouble I must have been to John when I first started. But
very quickly, he started to help me out in many aspects, including running reactions,