A Methodological Study of Enantioselective Dirhodium(II)-Catalyzed Cyclopropanations at Low Catalyst Loadings 公开

Wade Wolfe, Michael McCreery (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/6d56zw98z?locale=zh
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Abstract

Dirhodium(II) catalyzed carbene chemistry has proven to be one of the most effective ways to selectively transform bonds that are traditionally difficult to functionalize. However, rhodium is a rare and expensive metal. With a serious demand for cost efficient methods in synthetic chemistry, rhodium must be used sparingly. This study investigates dirhodium(II) catalyzed cyclopropanations at low catalyst loading ranging from 0.001 mol% to 0.00001 mol% with a variety of dirhodium(II) catalysts, diazo substrates, solvents in order to optimize for reaction conditions that provide high turnover numbers (TONs) and excellent enantioselectivity. The best conditions for high turnover numbers yielded 5.7 million TONs with 20% ee. The best conditions for high enatioselectivity at low catalyst loading yielded 780,000 TONs with 85% ee.

Table of Contents

Table of Contents
1) Introduction ................................................................................................................................ 1

1.1) Diazo Decomposition and Carbene Formation ....................................................................... 1

1.2) Catalyst Structures and Background........................................................................................ 3

1.3) Cyclopropanation..................................................................................................................... 6

1.4) High Turnover Numbers for Rh2 Catalyzed Cyclopropanation .............................................. 7

2) Results and Discussion ............................................................................................................... 9

2.1) The Initial Cyclopropanation Study at 0.0001 mol% Catalyst Loading.................................. 9

2.2 ) Optimization of Solvent and Substituent Effect at 1 mol% Catalyst Loading ..................... 11

2.3) The Effects of Low Catalyst Loading on Enantioinduction .................................................. 13

2.4) Systematic Cyclopropanation Study at 0.001 mol% Catalyst Loading................................. 14

2.5) Highly Selective Cyclopropanation at 0.0001 mol% Catalyst Loading ................................ 18

2.6) Discussion and Outlook......................................................................................................... 18

3) Conclusions .............................................................................................................................. 22

4) Experimental Part ..................................................................................................................... 23

4.1) General Remarks ................................................................................................................... 23

4.2) General Procedure for the Synthesis of Diazo Compounds .................................................. 24

4.3) General Procedure for Cyclopropanation Reactions ............................................................. 25

4.4) General Procedure for Experimental and Data Analysis for ReactIR® ................................ 25

4.5) Analysis Data for 2,2,2-trichloroethyl 1-(4-methoxyphenyl)-2-phenylcyclopropane-1- carboxylate.................................................................................................................................... 27

4.6) HPLC Traces ......................................................................................................................... 30 References..................................................................................................................................... 41

Figures and Tables

Figure 1 ........................................................................................................................................... 1

Figure 2 ........................................................................................................................................... 3

Figure 3 ........................................................................................................................................... 4

Figure 4 ........................................................................................................................................... 6

Table 1 .......................................................................................................................................... 10

Figure 5 ......................................................................................................................................... 11

Table 2 .......................................................................................................................................... 13

Figure 6 ......................................................................................................................................... 15

Figure 7 ......................................................................................................................................... 16

Figure 8 ......................................................................................................................................... 26

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