Gold (I) and Platinum (II)-Catalyzed Hydrofunctionalization of Allenes and Alkenes with

164 Pages·2012·5.16 MB·English

by  Hugh Crumley

Gold(I) and Platinum(II)-Catalyzed Hydrofunctionalization of Allenes and Alkenes with
Carbon and Nitrogen Nucleophiles
by
Kristina L. (Toups) Butler
Department of Chemistry
Duke University

Date:_______________________
Approved:

___________________________
Ross A. Widenhoefer, Supervisor

___________________________
Don M. Coltart

___________________________
Jiyong Hong

___________________________
Cynthia M. Kuhn

Dissertation submitted in partial fulfillment of
the requirements for the degree of Doctor
of Philosophy in the Department of
Chemistry in the Graduate School
of Duke University

2012

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ABSTRACT
Gold(I) and Platinum(II)-Catalyzed Hydrofunctionalization of Allenes and Alkenes with
Carbon and Nitrogen Nucleophiles
by
Kristina L. (Toups) Butler
Department of Chemistry
Duke University

Date:_______________________
Approved:

___________________________
Ross A. Widenhoefer, Supervisor

___________________________
Don M. Coltart

___________________________
Jiyong Hong

___________________________
Cynthia M. Kuhn

An abstract of a dissertation submitted in partial
fulfillment of the requirements for the degree
of Doctor of Philosophy in the Department of
Chemistry in the Graduate School
of Duke University

2012
i
v
Copyright by
Kristina L. (Toups) Butler
2012
Abstract
The wide-spread occurrence of biologically active nitrogen-containing
heterocycles and allylic amines inspired us to develop atom-economical methods for
their syntheses.
A cationic gold(I) N-heterocyclic carbene complex catalyzed the intermolecular
hydroarylation of allenes with indoles to form (E)-allylic indoles in modest to good yield
at room temperature. The protocol was effective for monosubstituted, 1,3-disubstituted,
and tetrasubstituted allenes and various indoles.
Platinum(II) bis(phosphine) complexes catalyzed the intermolecular
hydroamination of monosubstituted allenes with secondary alkylamines in good yield
with selective formation of (E)-allylic amines. The scope of the protocol included aryl
and alkyl monosubstituted allenes as well as a variety of both cyclic and acyclic
secondary alkylamines.
The scope of gold(I)-catalyzed intermolecular hydroamination of 1-alkenes with
1-methyl-2-imidazolidinone was expanded to include additional 1-alkenes
functionalized with carboxylic acid derivatives. However, a nucleophile screen failed to
identify nucleophiles other than cyclic ureas and 2-oxazolidinone that efficiently
undergo hydroamination with 1-alkenes. Various carbamates, arylamines, amide

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derivatives, sulfur-containing amide derivatives, and α-heteroatom compounds failed to
react with 1-octene under gold(I)-catalyzed conditions.
A chiral bis(gold) phosphine complex catalyzed the stereoconvergent,
intermolecular enantioselective hydroamination of chiral, racemic 1,3-disubstituted
allenes with carbamates to form N-allylic carbamates in good to high yield with up to
92% ee. In addition, enantiopurity experiments suggested the nature of the catalytically
active species changes with increasing concentration of N-allylic carbamate.

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Dedicated to the memory of Leta Taylor Chesson and Jo Anne Taylor.

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Contents
Abstract ......................................................................................................................................... iv
List of Tables ................................................................................................................................. xi
List of Figures ............................................................................................................................ xiii
List of Schemes ............................................................................................................................ xv
Acknowledgements ...................................................................................................................xvi
Chapter 1. Gold(I)-Catalyzed Intermolecular Hydroarylation of Allenes with Indoles .... 1
1.1 Introduction ....................................................................................................................... 2
1.2 Results and discussion ..................................................................................................... 8
1.2.1 Au(I)-catalyzed intermolecular hydroarylation of allenes with 1,2-
dimethylindole ...................................................................................................................... 8
1.2.2 Au(I)-catalyzed intermolecular hydroarylation of allenes with additional
indoles .................................................................................................................................. 12
1.2.3 Proposed mechanism ................................................................................................ 13
1.2.4 Conclusions ................................................................................................................ 16
1.3 Experimental section ...................................................................................................... 16
1.3.1 General Methods ....................................................................................................... 16
1.3.2 Allenes ......................................................................................................................... 17
1.3.3 Hydroarylation products ......................................................................................... 18
1.3.4 Control experiments.................................................................................................. 24
Chapter 2. Platinum(II)-Catalyzed Intermolecular Hydroamination of Monosubstituted
Allenes with Secondary Alkylamines ...................................................................................... 25
2.1 Introduction ..................................................................................................................... 26

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2.2 Results and discussion ................................................................................................... 31
2.2.1 Optimization and substrate scope .......................................................................... 31
2.2.2 Proposed mechanism ................................................................................................ 39
2.2.3 Conclusions ................................................................................................................ 41
2.3 Experimental section ...................................................................................................... 42
2.3.1 General methods ........................................................................................................ 42
2.3.2 Bis(phosphine) platinum dichloride complex ....................................................... 43
2.3.3 Hydroamination products ....................................................................................... 43
2.3.4 Control experiments.................................................................................................. 50
Chapter 3. Gold(I)-Catalyzed Intermolecular Hydroamination of Functionalized 1-
Alkenes with 1-Methyl-2-imidazolidinone and Related Nucleophiles ............................... 52
3.1 Introduction ..................................................................................................................... 53
3.2 Results and discussion ................................................................................................... 60
3.2.1 Nucleophile scope ..................................................................................................... 60
3.2.2 Alkene scope .............................................................................................................. 62
3.2.3 Mechanistic studies ................................................................................................... 66
3.2.3.1 Reversibility ........................................................................................................ 66
3.2.3.2 Rate dependence on acid .................................................................................. 67
3.2.3.3 Deuterium-labeling experiments ..................................................................... 68
3.2.4 Conclusions ................................................................................................................ 69
3.3 Experimental section ...................................................................................................... 70
3.3.1 General methods ........................................................................................................ 70

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3.3.2 Deuterated 1-methyl-2-imidazolidinone ................................................................ 71
3.3.3 Hydroamination products ....................................................................................... 71
Chapter 4. Gold(I)-Catalyzed Enantioselective Intermolecular Hydroamination of
Allenes with Carbamates ........................................................................................................... 74
4.1 Introduction ..................................................................................................................... 75
4.2 Results and discussion ................................................................................................... 79
4.2.1 Optimization and substrate scope .......................................................................... 79
4.2.2 Enantiopurity experiments ...................................................................................... 84
4.2.3 Conclusions ................................................................................................................ 89
4.3 Experimental section ...................................................................................................... 89
4.3.1 General methods ........................................................................................................ 89
4.3.2 4-Aryl-but-3-yn-2-ols ................................................................................................ 91
4.3.3 Allenes ......................................................................................................................... 92
4.3.4 Hydroamination products ....................................................................................... 96
4.3.5 Enantiopurity experiments .................................................................................... 113
Appendix A. Platinum(II)-Catalyzed Intramolecular Hydroamination of o-Allyl Aniline
Derivatives ................................................................................................................................. 115
A.1 Introduction.................................................................................................................. 116
A.2 Results and discussion ................................................................................................ 117
A.3 Experimental section ................................................................................................... 118
A.3.1 General methods .................................................................................................... 118
A.3.2 Hydroamination products .................................................................................... 119

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Appendix B. Gold(I)-Catalyzed Tandem Intermolecular Hydroamination/1,6-Enyne
Cycloisomerization ................................................................................................................... 122
B.1 Introduction .................................................................................................................. 123
B.2 Results and discussion ................................................................................................ 124
B.3 Experimental section ................................................................................................... 131
B.3.1 General methods ..................................................................................................... 131
B.3.2 Tandem hydroamination/1,6-enyne cycloisomerization products .................. 132
B.3.3 Control experiments ............................................................................................... 134
References .................................................................................................................................. 136
Biography ................................................................................................................................... 147

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