Development and Applications of a New Dirhodium(II) Tetracarboxylate Catalyst and Asymmetric Cyclopropanation of Heterocyclic Compounds Open Access
Fu, Jiantao (Summer 2020)
Abstract
Rhodium-stabilized carbene reactions have been extensively studied within the past decades, and one of the most promising applications is intermolecular C–H functionalization reactions. Even though once thought to be synthetically insignificant, these reactions have benefitted from the donor/acceptor carbenes that have tempered reactivity but enhanced selectivity. With the recent introduction of new chiral catalysts, rhodium-carbene chemistry has continued to evolve to become a powerful synthetic methodology for C–H functionalization and relied on in organic synthesis.
The first chapter of the dissertation discusses some general knowledge on dirhodium catalysis in C–H functionalization and recent progress on the development of new catalysts.
The second chapter focuses on the discussion of the development of new dirhodium catalysts for N-sulfonyl-1,2,3-triazoles as alternative precursors to donor/acceptor carbenes. These triazoles are capable of undergoing ring-opening to generate an α-imino diazo compound, which can then be trapped by a dirhodium catalyst. One interesting catalyst that stood out from the study was Rh2(S-TPPTTL)4, and although Rh2(S-NTTL)4 remained to be the chiral catalyst of choice for the triazoles, follow up studies on Rh2(S-TPPTTL)4 indicated that it was also capable of highly selective transformations using aryldiazoacetates.
The third chapter discusses further exploration of the selectivity profile of the Rh2(S- TPPTTL)4 in C–H functionalization of cyclohexanes, which are challenging substrates for C–H functionalization if they are unactivated or lack directing functionalities. Rh2(S-TPPTTL)4, however, can catalyze highly selective reactions at the C-3 equatorial C–H bond. The observed selectivities were explained via computational studies. The chapter will also discuss how Rh2(S- TPPTTL)4 contributed to the inception of a few other studies that aimed to explore other aspects of the new catalyst.
The last chapter covers a collaborative effort between the Davies and the Reiser group on asymmetric cyclopropanation of N-protected pyrroles. These nitrogen-containing heterocycles are ubiquitous in pharmaceutical research and can react with rhodium-carbenes in a number of pathways. Using Rh2(R-p-PhTPCP)4 as the chiral catalyst, N-protected pyrroles were found to undergo exceptionally clean monocyclopropanation with donor/acceptor carbenes. The synthetic potential was demonstrated via the synthesis of two biologically relevant compounds.
Table of Contents
Table of Contents
List of Figures
List of Schemes
List of Tables
Chapter 1. Overview of Donor/acceptor Dirhodium Carbene Chemistry.................…………1
1.1 Introduction…………………………………………………………….………….1
1.2 Conclusions………………………………………………………………………14
1.3 References………………………………………………………………..………15
Chapter 2. Asymmetric C-H Functionalization via N-Sulfonyl-1,2,3-Triazoles……..……..20
2.1 Introduction………………………………………………………………………20
2.2 Results and Discussions………………………………………………………….29
2.2.1 Synthesis of Chiral Dirhodium(II) Tetracarboxylate Catalysts………….29
2.2.2 Synthesis of 4-Phenyl-1-(N-methanesulfonyl)-1,2,3-triazole……………35
2.2.3 Evaluation of New Catalysts in Styrene Cyclopropanation Reactions…..36
2.2.4 Evaluation of New catalysts in Site-selective C-H Functionalization......40
2.2.5 Follow-up studies of Rh2(S-TPPTTL)4 and Rh2(S-TPPTPA)4 in Aryl Diazoacetate Chemistry………………………………………………….46
2.3 Conclusions………………………………………………………………………51
2.4 References………………………………………………………………………..52
Chapter 3. Desymmetrization of Cyclohexanes by Site- and Stereoselective C-H Functionalization using Donor/acceptor Carbenes…………..…………….….....55
3.1 Introduction………………………………..……………………………………..55
3.2 Results and Discussions………………………………..………………...............60
3.2.1 Site- and Stereoselective C-H Functionalization of Monosubstituted Cyclohexanes.............................................................................................60
3.2.2 Site- and Stereoselective C-H Functionalization of Disubstituted Cyclohexanes.............................................................................................71
3.2.3 Analysis of Regio- and Stereochemistry..........................................................................................75
3.2.4 Rationale of Selectivity through X-ray Crystallographic Analysis and Computational Studies...............................................................................79
3.2.5 Regio- and Stereoselective Functionalization of Organosilanes...............84
3.2.6 Development of New Catalysts that are related to Rh2(S-TPPTTL)4........86
3.2.7 Aryl Diazoketones as New Donor/acceptor Carbene Precursors for Selective Intermolecular C-H Functionalization Reactions......................91
3.3 Conclusions………………………………………………………………………98
3.4 References…………………………………………………………..……………99
Chapter 4. Monocyclopropanation of Pyrroles by Rh(II)-donor/acceptor Carbenes............102
4.1 Introduction………………………………………………………..……………102
4.2 Results and Discussions…………………….....…………………..……………107
4.2.1 Optimization and Scope of Monocyclopropanation of N-protected
Pyrroles...................................................................................................107
4.2.2 Synthetic Applications………………..…….....…………………..……121
4.3 Conclusions…………………………………..…………………………………123
4.4 References……………………………………....………………………………123
Experimental Section……….....……………………………....………………………………126
General considerations……………………………………....………………………….126
Experimental Section for Chapter 2……………………………………………………..127
Experimental Section for Chapter 3……………………………………………………..153
Experimental Section for Chapter 4……………………………………………………..220
X-Ray Crystallography Studies of Key Compounds........................................................273
Appendix - Spectra.....................................................................................................................287
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