Palladium (II)/Palladium (IV) catalytic processes : new options to consider for C?H bonds activation.

1
Palladium (II)/Palladium (IV) catalytic processes
new options to consider for C?H bonds
activation.

• A literature review on Melanie S. Sanfords
  recent work.
• Presented by Guillaume Pelletier.

2
Outline of the presentation.

• 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
  1990s.
• Melanie S. Sanfords work using
  benzohquinoline
• 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.

3
Why C-H bonds are powerful tools to access to
diversification of organic molecules?

• 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 a-olefins.
• Direct conversion of a  unfunctionalized  bond
  (no oxidation/protection needed).

4
A quick overview on the C-H activation in a
simple industrial process.
2 CH4 4 H2SO4-Pd(II) ? CH3CO2H 4 SO4 6H2O
Complimentary to the Mosento process 10 Overall
Yield (could be improved by adding MeOH or
CO) Harsh conditions used
Periana, R. A. Taube, D. J. Gamble, S. Taube,
H. Satoh, T. Fujii, H. Science, 1998, 280, 560.
5
A more complex problematic Applications of C-H
bond functionalisation in total synthesis.
Bore, L. Honda, T. Gribble, G. W. J. Org.
Chem. 2000, 65, 6278-6282.
6
A more complex problematic Applications of C-H
bond functionalisation in total synthesis.
Johnson, J. A. Li, N. Sames, D. J. Am. Chem.
Soc. 2002, 124, 6900-6903.
7
What were the major problematics to C?H bond
functionalisation before 1990s

• 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.

8
Classification of the reactions with two
different concepts.
Dick, A. R. Sanford, M. S. Tetrahedron 2006, 62,
2439-2463.
9
Some pionnier work on efficient C?H bond
activation/transformation.
Chen, H. Schlech, S. Semple, C. T. Hartwig, J.
F. Science, 2000, 287, 1995-1997.
10
Some pionnier work on efficient C?H bond
activation/transformation.
A lot of additive were screened. TfOH promoted
the reaction. (26 to 91 Yields) A large
elctronic dependance over the substrates
(kobs(OMe) kobs(H)gtgtkobs(CF3)) Slow C-H bond
activation (kH/kD 3.5)
Boele, M. D. K. Strijdonck, G. P. F. V. De
Vries, A. H. M. Kamer, P. C. J. De Vries, J.
G. Leeuwen, P. W. N. M. V. J. Am. Chem. Soc.
2002, 124, 1586-1587.
11
Some pionnier work on efficient C?H bond
activation/transformation.
An efficient methodology to form
1,3-difunctionalized amines through a selective
C-H bond oxidation. The sulfamate ester is
forming a nitrene-metal intermediate with the
rhodium.
Espino, C. G. When, P. M. Chow, J. Du Bois. J.
J. Am. Chem. Soc. 2001, 123, 6935.
12
Formation of C-O bonds by using a more friendly
oxidant PhI(OAc)2
Stock et al. reported earlier that Cr2O7- anion
did promoted the oxidation of PhPd(OAc)
species. Eberson et al. proposed previously to
use peroxydisulfate as the oxidant.
Stock, L. M. Tse, I. J. Walstrum, S. A. J. Org.
Chem. 1981, 46, 1757-1761. Eberson, L. Jönsson,
L. Acta Chem. Scand. B. 1976, 30, 361-364.
13
Kinetics of the reaction.

• He found that PhPd(II)OAc intermediate fails to
  form the carbon-heteroatom bond.

The most important fact to remember is that
C-O bond is only formed on oxidation, presumably
via a reductive elimination from a PhPd(IV)OAc
species.
Yoneyama, T. Crabtree, R. H. J. Mol. Cat. A
Chem. 1996, 108, 35-40.
14
Kinetics of the reaction and mechanism.

• He found that k(H)/k(D) 4.3 (C-H activation step
  is rate limiting).

Yoneyama, T. Crabtree, R. H. J. Mol. Cat. A
Chem. 1996, 108, 35-40.
15
Some of Crabtrees conclusions

• Considering the regioslectivity of the
  acetoxylation of anisole (omp 44551) the
  C-H insertion step is rather an electrophilic
  attack by the Pd (omp 60030) than a
  oxidative addition/reductive elemination pathway
  (omp 127612).
• 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.

Yoneyama, T. Crabtree, R. H. J. Mol. Cat. A
Chem. 1996, 108, 35-40.
16
About 10 years later
Dick, A. R. Hull, K. Sanford, M. S. J. Am.
Chem. Soc. 2004, 126, 2300-2301. Hartwell, G.
E. Lawrence, R. V. Smas, M. J. J. Chem. Soc.
Chem. Commun. 1970, 912.
17
Melanie S. Sanford

• 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.
  

18
Her first paper about a Pd(II)/Pd(IV) oxidative
functionalization of C-H bonds.

• 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

Dick, A. R. Hull, K. Sanford, M. S. J. Am.
Chem. Soc. 2004, 126, 2300-2301.
19
Proposed catalytic cycle
Using the cyclopalladated benzohquinoline
catalyst in the reaction without the oxidant does
not form the product.
Dick, A. R. Hull, K. Sanford, M. S. J. Am.
Chem. Soc. 2004, 126, 2300-2301.
20
Precedents on the C-X bond formation in a similar
mechanism.
Han, R. Y. Hillhouse, G. L. J. Am. Chem. Soc.
1997, 119, 8135-8137 Williams, B. S. Goldberg,
K. I. J. Am. Chem. Soc. 2001, 123, 2576-2578
21
Application of the concept to an sp3 carbon C-H
bond.
No ß-hydroelimination product was observed due to
Palladacycle rigidity.
Desai, V. L. Hull, K. L. Sanford, M. S. J.
Am. Chem. Soc. 2004, 126, 9542-9543
22
High selectivity obtained at the ortho position.
Kalyani, D. Sanford, M. S. Org. Lett. 2005, 7,
4149-4172.
23
An important observation the selectivity of the
reaction
Desai, V. L. Hull, K. L. Sanford, M. S. J.
Am. Chem. Soc. 2004, 126, 9542-9543
24
Other important observations
Oxidative cleavage of the C-O bond and C-H
activation step are both highly stereoselective
Desai, V. L. Hull, K. L. Sanford, M. S. J.
Am. Chem. Soc. 2004, 126, 9542-9543
25
Does Pd(IV) exist?
Yamamoto, Y. Kuwabara, S. Matsuo, S. Ohno, T.
Nishiyama, H. Itoh, K. Organometallics, 2004,
23, 3898-3903. Canty, A. J. Patel, J. Rodemann,
T. Ryan, J. H. Skelton, B.W. White, A. H.
Organometallics, 2004, 23, 3466-3469.
26
Does Pd(IV) exist?
Càmpora, J. Palma, P. Del Rio, D. Carmona, E.
Graiff, G. Tiripiccio, A. Organometallics, 2003,
22, 3345-3349.
27
To study the system, Pt(IV) is more suitable
Dick, A. R. Kampf, J. W. Sanford, S. M.
Organometallics, 2005, 24, 482-485.
28
Pt(II) is like Pd(II)
Huang, T. S. Chen, J. T. Lee, G. H. Wang, Y.
Organometallics, 1991, 10, 175-180.
29
Design of new Pt(III) and Pt(IV) complexes
Dick, A. R. Kampf, J. W. Sanford, S. M.
Organometallics, 2005, 24, 482-485.
30
Platinum (III) complex
Treatment of this complex with 10 PhI(OAc)2 does
not over oxidize it.
Dick, A. R. Kampf, J. W. Sanford, S. M.
Organometallics, 2005, 24, 482-485.
31
Platinum (IV) complex synthesis
With benzoh quinoline, with R OMe, the ratio
AB is 21 and with R OiPr AB
0.41. Stable (purified by chromatography)
Dick, A. R. Kampf, J. W. Sanford, S. M.
Organometallics, 2005, 24, 482-485.
32
Platinum (IV) synthesis
C-N ligand Benzohquinoline ROH MeOH
Dick, A. R. Kampf, J. W. Sanford, S. M.
Organometallics, 2005, 24, 482-485.
33
Various tests with the 8-Methylquinoline
We see the same trend that the one observed with
the palladium complex. When R is big for ROH, the
ratio of product with 8-methylquinoline is less
interesting than the one observed with small R
group
Dick, A. R. Kampf, J. W. Sanford, S. M.
Organometallics, 2005, 24, 482-485.
34
New Pd (IV) catalysts isolation
Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791.
35
New Pd (IV) X-Ray
Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791.
36
Reductive elimination step pathways
Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791.
37
Reductive elimination step pathways first
approach.

• 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 e 21, krel 1.0 0.1
• In apolar solvent e 2.3 krel 1.0 0.1

Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791. Willams, B.
S. Goldberg, K. I. J. Am. Chem. Soc. 2001,
123, 2576-2578.
Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791.
38
Reductive elimination step pathways Erying
studies.

• 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)

Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791. Canty, A. J.
Jin, H. Skelton, B. W. White, A. H. Inorg.
Chem. 1998, 37, 3975-3978.
39
Hammet studies with various X substituents.

• Benzoate acts as a nucleophilic partner in the
  transformation (s -1.36 0.04)
• s value of -1.5 with C-S coupling with Pd(II)
  which goes through a Mechanism type B
• s value of 1.44 for reductive elimination from
  Pt(IV) (stabilization of the
• OR moiety).

Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791.
40
Reductive elimination step pathways crossover
reactions.

• With these observations, mechanism A can be ruled
  out.

Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791.
41
How to dicriminate between B and C?

• Mechanism B and C are kinetically
  indistinguishable

Dick, A. R. Kampf, J. W. Sanford, S. M. J. Am.
Chem. Soc. 2005, 127, 12790-12791.
42
How can we push further the concept?
Hull, K. L. Lanni, E. L. Sanford, M. S. J.
Am. Chem. Soc. 2006, 128, 14047-14049.
43
Possible mechanisms
Hull, K. L. Lanni, E. L. Sanford, M. S. J.
Am. Chem. Soc. 2006, 128, 14047-14049.
44
Possible mechanisms
Hull, K. L. Lanni, E. L. Sanford, M. S. J.
Am. Chem. Soc. 2006, 128, 14047-14049.
45
Important results
Hull, K. L. Lanni, E. L. Sanford, M. S. J.
Am. Chem. Soc. 2006, 128, 14047-14049.
46
Important results

• With these observations, mechanisms C and D can
  be ruled out.

Hull, K. L. Lanni, E. L. Sanford, M. S. J.
Am. Chem. Soc. 2006, 128, 14047-14049.
47
Important results
Hull, K. L. Lanni, E. L. Sanford, M. S. J.
Am. Chem. Soc. 2006, 128, 14047-14049.
48
Other methodologies C-F bond formation.
Hull, K. L. Anani, Q. W. Sanford, M. S. J.
Am. Chem. Soc. 2007, 128, 7134-7135.
49
Other methodologies C-Cl, C-Br and C-I bond
formation.
Kalyani, D. Dick, A. R. Anani, W. Q. Sanford,
M. S. Org. Lett. 2006, 8, 2523-2526.
50
Other methodologies C-Cl, C-Br and C-I bond
formation.
Whitfield, S. R. Sanford, M. S. J. Am. Chem.
Soc. 2007, 129, 15142-15143.c
51
Synthesis of cyclopropanes through enynes
cyclisation
Welbes, L. L. Lyons, T. W. Cychosz, K. A.
Sanford, M. S. J. Am. Chem. Soc. 2007, 129,
5838-5839.
52
Aminooxygenation of alkenes.
Desai, L. V. Sanford, M. S. Angew. Chem. Int.
Ed. 2007, 46, 5737-5740.
53
And todayASAP JACS
Yu, W. Y. Sit,W. N. Lai, K. M. Zhou, Z. Chan,
A. S. C. J. Am. Chem. Soc. ASAP
54
Conclusion

• 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.