CaltechTHESIS
  A Caltech Library Service

Palladium-Catalyzed Decarboxylative and Decarbonylative Transformations in the Synthesis of Fine and Commodity Chemicals

Citation

Liu, Yiyang (2015) Palladium-Catalyzed Decarboxylative and Decarbonylative Transformations in the Synthesis of Fine and Commodity Chemicals. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9NZ85NC. http://resolver.caltech.edu/CaltechTHESIS:05292015-170352881

Abstract

Decarboxylation and decarbonylation are important reactions in synthetic organic chemistry, transforming readily available carboxylic acids and their derivatives into various products through loss of carbon dioxide or carbon monoxide. In the past few decades, palladium-catalyzed decarboxylative and decarbonylative reactions experienced tremendous growth due to the excellent catalytic activity of palladium. Development of new reactions in this category for fine and commodity chemical synthesis continues to draw attention from the chemistry community.

The Stoltz laboratory has established a palladium-catalyzed enantioselective decarboxylative allylic alkylation of β-keto esters for the synthesis of α-quaternary ketones since 2005. Recently, we extended this chemistry to lactams due to the ubiquity and importance of nitrogen-containing heterocycles. A wide variety of α-quaternary and tetrasubstituted α-tertiary lactams were obtained in excellent yields and exceptional enantioselectivities using our palladium-catalyzed decarboxylative allylic alkylation chemistry. Enantioenriched α-quaternary carbonyl compounds are versatile building blocks that can be further elaborated to intercept synthetic intermediates en route to many classical natural products. Thus our chemistry enables catalytic asymmetric formal synthesis of these complex molecules.

In addition to fine chemicals, we became interested in commodity chemical synthesis using renewable feedstocks. In collaboration with the Grubbs group, we developed a palladium-catalyzed decarbonylative dehydration reaction that converts abundant and inexpensive fatty acids into value-added linear alpha olefins. The chemistry proceeds under relatively mild conditions, requires very low catalyst loading, tolerates a variety of functional groups, and is easily performed on a large scale. An additional advantage of this chemistry is that it provides access to expensive odd-numbered alpha olefins.

Finally, combining features of both projects, we applied a small-scale decarbonylative dehydration reaction to the synthesis of α-vinyl carbonyl compounds. Direct α-vinylation is challenging, and asymmetric vinylations are rare. Taking advantage of our decarbonylative dehydration chemistry, we were able to transform enantioenriched δ-oxocarboxylic acids into quaternary α-vinyl carbonyl compounds in good yields with complete retention of stereochemistry. Our explorations culminated in the catalytic enantioselective total synthesis of (–)-aspewentin B, a terpenoid natural product featuring a quaternary α-vinyl ketone. Both decarboxylative and decarbonylative chemistries found application in the late stage of the total synthesis.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:decarboxylation, decarbonylation, decarbonylative dehydration, palladium, enantioselective, commodity chemical, fine chemical, natural product
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Stoltz, Brian M.
Group:Resnick Sustainability Institute
Thesis Committee:
  • Reisman, Sarah E. (chair)
  • Stoltz, Brian M.
  • Agapie, Theodor
  • Grubbs, Robert H.
Defense Date:14 May 2015
Funders:
Funding AgencyGrant Number
NIHR01 GM080269
Resnick Sustainability Institute Graduate Research FellowshipUNSPECIFIED
Record Number:CaltechTHESIS:05292015-170352881
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:05292015-170352881
DOI:10.7907/Z9NZ85NC
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nchem.1222DOIEnantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams
http://dx.doi.org/10.1002/adsc.201301109DOIPalladium-Catalyzed Decarbonylative Dehydration of Fatty Acids for the Production of Linear Alpha Olefins
http://dx.doi.org/10.3762/bjoc.10.261DOIFormal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation
http://dx.doi.org/10.1021/ar5004658DOICatalytic Enantioselective Construction of Quaternary Stereocenters: Assembly of Key Building Blocks for the Synthesis of Biologically Active Molecules
http://dx.doi.org/10.1002/anie.201505161DOIPalladium-Catalyzed Decarbonylative Dehydration for the Synthesis of α-Vinyl Carbonyl Compounds and Total Synthesis of (−)-Aspewentins A, B, and C
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8935
Collection:CaltechTHESIS
Deposited By: Yiyang Liu
Deposited On:02 Jun 2015 15:35
Last Modified:10 Nov 2016 23:33

Thesis Files

[img]
Preview
PDF (Full Thesis) - Final Version
See Usage Policy.

42Mb
[img]
Preview
PDF (Table of Contents) - Final Version
See Usage Policy.

262Kb
[img]
Preview
PDF (Chapter 1) - Final Version
See Usage Policy.

456Kb
[img]
Preview
PDF (Chapter 2) - Final Version
See Usage Policy.

1215Kb
[img]
Preview
PDF (Chapter 3) - Final Version
See Usage Policy.

3227Kb
[img]
Preview
PDF (Chapter 4) - Final Version
See Usage Policy.

639Kb
[img]
Preview
PDF (Chapter 5) - Final Version
See Usage Policy.

1100Kb
[img]
Preview
PDF (Appendix 1) - Final Version
See Usage Policy.

6Mb
[img]
Preview
PDF (Appendix 2) - Final Version
See Usage Policy.

7Mb
[img]
Preview
PDF (Appendix 3) - Final Version
See Usage Policy.

1424Kb
[img]
Preview
PDF (Appendix 4) - Final Version
See Usage Policy.

6Mb
[img]
Preview
PDF (Appendix 5) - Final Version
See Usage Policy.

1317Kb
[img]
Preview
PDF (Appendix 6) - Final Version
See Usage Policy.

5Mb
[img]
Preview
PDF (Appendix 7) - Final Version
See Usage Policy.

297Kb
[img]
Preview
PDF (Appendix 8) - Final Version
See Usage Policy.

329Kb
[img]
Preview
PDF (Appendix 9) - Final Version
See Usage Policy.

76Kb
[img]
Preview
PDF (Index) - Final Version
See Usage Policy.

51Kb
[img]
Preview
PDF (Bibliography) - Final Version
See Usage Policy.

90Kb
[img]
Preview
PDF (About the Author) - Final Version
See Usage Policy.

39Kb

Repository Staff Only: item control page