Kinetic Studies of Rhodium(III)-Catalyzed Allylic C-H Amination of Disubstituted Olefins Público
Salgueiro, Daniel (Spring 2018)
Abstract
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
Figures
Figure 1: Historical approaches for allylic functionalization via the generation of metal π-allyl intermediates 1
Figure 2: Precedence for allylic C–H 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 C–H 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 C–H amination of alkene 1 14
Figure 13: Computational studies depicting one possible pathway for the RhI/RhIII catalyzed allylic C–H 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
Tables
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
Schemes
Scheme 1: Allylic C–H Amination with p-toluenesulfonamide 7
Scheme 2: Allylic C–H Amination with benzyl carbamate 7
Scheme 3: Proposed reaction mechanism 16
Scheme 4: Pre-equilibrium and rate determining step 16
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