Kinetic Studies of Rhodium(III)-Catalyzed Allylic C-H Amination of Disubstituted Olefins Open Access

Salgueiro, Daniel (Spring 2018)

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Allylic substitution reactions have been a powerful tool used by synthetic chemists since the 1960s and 1970s. Traditional allylic substitution reactions have required pre-functionalized olefins and stoichiometric equivalents of transition metals to generate the desired product. The Blakey lab has recently developed methodology for the rhodium (III)-catalyzed allylic C-H amination of 1,2-disubstituted alkenes that is tolerant of a broad array of amine nucleophiles and aryl, alkyl alkenes. However, the complete mechanism of this transformation remains unknown. We have performed kinetics studies on the allylic C-H amination of 1,3-diphenyl propene with benzyl carbamate as the nucleophile and have determined that this reaction proceeds in an overall pseudo-zero order fashion and that the reaction exhibits first order dependence on both rhodium and alkene, and is inhibited by the amine nucleophile. Based on kinetic studies, stoichiometric reactions with rhodium π-allyl complexes, and collaborations with computational chemists we propose that the reaction requires both an oxidant and a carboxylate source, and that it may proceed through a RhII/RhIV catalytic cycle.

Table of Contents

Introduction                                                                                                                                        1

Results and Discussion                                                                                                                      7

      I.         Kinetics                                                                                                                                 7

    II.         Oxidant Screening                                                                                                                   10

  III.         Controls (Role of Carboxylates)                                                                                           11

  IV.         Stoichiometric π-allyl Complex Reactions                                                                          12

    V.         Computational Studies                                                                                                        13

Conclusions and Future Directions                                                                                                 19

Supplemental Information                                                                                                              20

References                                                                                                                                       38


Figure 1: Historical approaches for allylic functionalization via the generation of metal π-allyl intermediates                                                                                                                                         1

Figure 2: Precedence for allylic CH functionalization of terminal olefins                                      3

Figure 3: Allylic C–H Functionalizations of internal olefins with Rh(III)Cp* on ω-unsaturated N-sulfonylamines                                                                                                                                    4

Figure 4: Generation and reactivity of  rhodium π-allyl complexes                                                  5

Figure 5: Representation of inner sphere and outer sphere pathways for allylic CH amination     6

Figure 6: Representative Kinetic Plot                                                                                                8

Figure 7: . Catalyst concentration dependence of the rate of the amination of 1                              9

Figure 8: [1] dependence of the rate of the amination of 1                                                                 9

Figure 9: [2] dependence of the rate of the amination of 1                                                                  10

Figure 10: Oxidants tested for solubility and viability under reaction conditions                           11

Figure 11: Stoichiometric amination of Rh π-allyl complex 4                                                          13

Figure 12: Computational studies depicting one possible pathway for the RhII/RhIV catalyzed allylic CH amination of alkene 1                                                                                                       14

Figure 13: Computational studies depicting one possible pathway for the RhI/RhIII catalyzed allylic CH amination of alkene 1                                                                                                              15

Figure S1: GC-FID of  1,3-diphenyl propene                                                                                      28

Figure S2: GC-FID of benzyl carbamate                                                                                         28

Figure S3: GC-FID of aminated product 3                                                                                           28

Figure S4: GC-FID of the internal standard                                                                                       29

Figure S5: GC-FID of a running reaction as described in the kinetics studies procedure              29

Figure S6: A representative plot of product formation over time under reaction conditions shown in Scheme 1                                                                                                                                           32


Table 1: Reaction screen with monomeric rhodium pre-catalysts                                                     12

Table 2: Reactions with isolated Rh π-allyl complex 4                                                                      13

Table S1: Response factors of kinetically relevant species and response factor ratios relative to nonane                                                                                                                                            32

Table S2: Global reaction rate dependence on [Rh catalyst]                                                         33

Table S3: Global reaction rate dependence on [olefin]                                                                   34

Table S4: Global reaction rate dependence on [nucleophile]                                                         34

Table S5: Global reaction rate dependence on [nucleophile]                                                          34

Table S6: Global reaction rate dependence on [Halide Scavenger]                                                35

Table S7:Oxidant screening reactions                                                                                            36

Table S8: Reaction screen with monomeric rhodium pre-catalysts                                               37


Scheme 1: Allylic CH Amination with p-toluenesulfonamide                                                         7

Scheme 2: Allylic CH Amination with benzyl carbamate                                                              7

Scheme 3: Proposed reaction mechanism                                                                                       16

Scheme 4: Pre-equilibrium and rate determining step                                                                   16

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