Introduction to the concept of C-H bond activation Industrial processes Applications in total synthesis Oxidative C-H bond functionalization using PhI(OAc)2 and Pd(OAc)2. Crabtree et al. work in the 1990’s. Melanie S. Sanford’s work using benzo[h]quinoline Interesting mechanistic work on the Pd(II)/Pd(IV) catalytic cycle Application of the Pd(II)/Pd(IV) concept to related and different systems. Formation of C-C bonds : mechanistic insights Formation of C-X bonds Synthesis of cyclopropanes through enynes cyclisation Aminooxygenation of alkenes.
Among the most abundant bonds… Among the most abundant bonds… …but also the least reactive bonds. Could be a powerfull tool to convert a common bond into a linear alcohol, amines or α-olefins. Direct conversion of a « unfunctionalized » bond (no oxidation/protection needed).
Usually there is low level of regiochemistry. Usually there is low level of regiochemistry. Harsh conditions are often used. Low TON Low functional group tolerance Significant formation of byproducts Large excess of substrate/oxidant/catalyst loading are typically required. In summary, there is an open space to a lot of groups to circumvent any of these factors and to propose a more efficient transformation.
He found that PhPd(II)OAc intermediate fails to form the carbon-heteroatom bond.
He found that k(H)/k(D) ~4.3 (C-H activation step is rate limiting). He found that k(H)/k(D) ~4.3 (C-H activation step is rate limiting).
Considering the regioslectivity of the acetoxylation of anisole (o:m:p = 44:5:51) the C-H insertion step is rather an electrophilic attack by the Pd (o:m:p ~ 60:0:30) than a oxidative addition/reductive elemination pathway (o:m:p = 12:76:12). Considering the regioslectivity of the acetoxylation of anisole (o:m:p = 44:5:51) the C-H insertion step is rather an electrophilic attack by the Pd (o:m:p ~ 60:0:30) than a oxidative addition/reductive elemination pathway (o:m:p = 12:76:12). Sigma bond methathesis may be considered. PhI(OAc)2 is a more selective and smooth oxidant than Cr2O7-. PhI(OAc)2 favors the formation of C-O bonds from C-H bonds and not C-C homocoupling.
She received her undergraduate degree in chemistry from Yale University in 1996 where she worked with Professor Robert Crabtree studying C-F bond functionalization. She received her undergraduate degree in chemistry from Yale University in 1996 where she worked with Professor Robert Crabtree studying C-F bond functionalization. She then moved to Caltech where she worked with Professor Robert Grubbs investigating the mechanism of ruthenium-catalyzed olefin metathesis reactions. After receiving her PhD in 2001, she worked with Professor Jay Groves at Princeton University as an NIH post-doctoral fellow studying metalloporphyrin-catalyzed functionalization of olefins. Melanie has been a professor at the University of Michigan since the summer of 2003.
Very good yields were obtained without exclusion of air/moisture Very good yields were obtained without exclusion of air/moisture She showed that the reaction tolerates variety of X = OAc, OMe, Br, Cl, OEt. 2.5 equiv. PhI(OAc)2 gives the doubly acetylated products
If mechanism A is the right one, then there should be a radical solvent effect on the speed rate of the reaction. If mechanism A is the right one, then there should be a radical solvent effect on the speed rate of the reaction. BUT!! In polar acetone : ε = 21, krel = 1.0 ± 0.1 In apolar solvent : ε = 2.3 krel = 1.0 ± 0.1
Erying studies gives a value of +4.2 ± 0.4 and -1.4 ± 1.9 in DMSO and CDCl3 for ∆S†. Erying studies gives a value of +4.2 ± 0.4 and -1.4 ± 1.9 in DMSO and CDCl3 for ∆S†. Typically, we see a value of -13 to -49 for C-C and C-Se reductive elimination with Pd(IV)
Benzoate acts as a nucleophilic partner in the transformation (σ = -1.36 ± 0.04) Benzoate acts as a nucleophilic partner in the transformation (σ = -1.36 ± 0.04) σ value of -1.5 with C-S coupling with Pd(II) which goes through a Mechanism type B σ value of + 1.44 for reductive elimination from Pt(IV) (stabilization of the –OR moiety).
With these observations, mechanism A can be ruled out.
Mechanism B and C are kinetically indistinguishable… Mechanism B and C are kinetically indistinguishable…
With these observations, mechanisms C and D can be ruled out. With these observations, mechanisms C and D can be ruled out.
Pd(II)/Pd(IV) can be applied to various catalytic systems to form interesting products (such as new C-O, C-C and C-X bond formation). Pd(II)/Pd(IV) can be applied to various catalytic systems to form interesting products (such as new C-O, C-C and C-X bond formation). Isolation of a variety of stable , purifiable and temperature resistant Pd(IV) catalysts. Various kinetic and crossover studies were done to elucidate the different mechanisms. Diversification of pyridine derivatives via a directed C-H bond activation/diversification concept.
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