Introduction to the concept of c-h bond activation

Yüklə 541 b.

tarix	05.03.2018
ölçüsü	541 b.
	#29628

Introduction to the concept of C-H bond activation

Introduction to the concept of C-H bond activation
Industrial processes
Interesting recent work in this field
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.

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.

Yüklə 541 b.

Dostları ilə paylaş:

Introduction to the concept of c-h bond activation

Introduction to the concept of C-H bond activation

Introduction to the concept of C-H bond activation

Industrial processes

Interesting recent work in this field

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.

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.