Transition Metal-Catalyzed Carbon-Carbon Bond Cleavage

(C-C Activation)

Group Meeting

01-15-2008

Timothy Chang

Outlines

- Fundamental considerations, C-H versus C-C activation- Orbital interactions- Evidence of M…C-C agostic interaction, C-C activation- Thermodynamics

- Stoichiometric reactions

- Catalytic reactions- Activation of strained molecules

- Direct cleavage- Utilization of a carbonyl group- b-Alkyl elimination

- Activation of unstrained molecules- b-Alkyl elimination, utilization of a p-allyl intermediate- Chelation assistance

- Conclusion

Orbital Interactions

Kinetic barriers of C-C activation due to:1. High directionality of C-C s bond2. Substituents on both carbons (steric congestion)3. Statistical abundance of C-H bonds

Murakami, M., Ito, Y. Topics in Organometallic Chemistry 1999, 97-129

Evidence of M…C-C Agostic Interaction

C25-H25 0.97(3) ÅC21-H21 0.95(3) ÅNo M…C-H agostic

interaction from Binor-S

Weller, A. S., et. al. ACIEE, 2006, 45, 452-456.

Weller, A. S., et. al. PNAS, 2007, 104, 6921-6926.1

Supports for M…C-C Agostic Interaction, C-C Activation

1H NMRC11, C15, C21 and C25 are all equivalent at 298 K (d(1H) = 3.23ppm , d(13C) = 25.5 ppm)5 signals (298 K) 10 signals (200 K)

Fluxional at RT

Thermodynamic Considerations

C-C bond90 kcal/mol

M-C bond x240-60 kcal/mol

Microscopic reversibility

M-H bonds are generally stronger than M-C bonds by 15 – 25 kcal/mol even though Me-H and H-H have almost the same BDE.

Labinger, J. A., Bercaw, J. E. Organometallics 1988, 7, 926-928.

Crabtree, R. H. The Organometallic Chemistry of the Transition Metals 4th Ed. P80.

Unlike in the gas phase, M-H bonds are generally stronger than M-C bonds in the solution.

Simões, J. A. M., et al. Chem. Rev. 1990, 90, 629-688.

Examples:(η5-C5Me5)(PMe3)2Ru−H 167.4 kcal/mol(η5-C5Me5)(PMe3)2Ru−CH3 142.3 kcal/mol

CRC 88th Ed.

Thermodynamic Considerations

Jun, C.-H Chem. Soc. Rev., 2004, 33, 610-618.

Milstein, D., Rybtchinski B. ACIEE 1999, 38, 870-883.

Strategies to facilitate C-C bond activation:1. Employing strained starting materials

E(C-C) 61 kcal/mol

Tipper (1955)Chatt (1961)

Thermodynamic Considerations

Jun, C.-H Chem. Soc. Rev., 2004, 33, 610-618.

Milstein, D., Rybtchinski B. ACIEE 1999, 38, 870-883.

Strategies to facilitate C-C bond activation (c ontd):2. Use high energy metal complexes

16 e Coordinatively

unsaturated

Thermodynamic Considerations

Jun, C.-H Chem. Soc. Rev., 2004, 33, 610-618

Strategies to facilitate C-C bond activation (contd):3. Extrusion of gas, aromatization

4. Formation of a stable metallacycle and chelation assistance

Five-membered metallacyclic complexes are relatively stable.Rh-Caryl and Ir-Caryl bonds are sometimes stronger than the corresponding M-H bonds.

Outlines

- Fundamental considerations, C-H versus C-C activation- Orbital interactions- Evidence of M…C-C agostic interaction, C-C activation- Thermodynamics

- Stoichiometric reactions

- Catalytic reactions- Activation of strained molecules

- Direct cleavage- Utilization of a carbonyl group- b-Alkyl elimination

- Activation of unstrained molecules- b-Alkyl elimination, utilization of a p-allyl intermediate- Chelation assistance

- Conclusion

Direct Cleavage

a 2.75 mM (PPh3)3RhCl and 0.138 M substrate in anhydrous toluene.b Turnover frequency determined at 18 h.

Chirik, P. J., et. al. JACS 2003, 125, 886.

Direct Cleavage

Murakami, M. et. al. JACS 2007, 129, 12596.

Utilization of a Carbonyl Group

Stoichiometric reactions showed that the insertion of Rh(I) into the a C-C bond is feasible

5 mol%

Murakami, M. et. al. Nature 1994, 370, 540.

Murakami, M. et. al. JACS 1996, 370, 8259.

87 % yield

Predict Products and Propose Mechanisms

Murakami, M. et. al. ACIEE 2000, 39, 2484.Both reactions were carried out under argon.

Utilization of a Carbonyl Group

Murakami, M. et. al. JACS 2002, 124, 13976.

b-Alkyl Elimination (1)

b-Alkyl elimination is the reverse of insertionUemura, S. et. al. JACS, 2000, 122, 12049.

Oxidative Addition

b-Alkyl Elimination (1)

b-Alkyl Elimination (1)

Uemura, S. et. al. JACS, 2003, 125, 8862.

79 % yield

78 % ee

93 % yield

73 % ee

+ 93 % yield

91 % ee

(S)

b-Alkyl Elimination (2)

Uemura, S. et. al. JACS, 2003, 125, 8862.

Murakami, M. et. al. JACS, 1997, 119, 9307.

C-C bond activation by1. Insertion of Rh(I) cat into a

C(O)-C bond2. b-Alkyl elimination

b-Alkyl Elimination (3)

Murakami, M. et. al. JACS, 2005, 127, 6932.

Other Strained Molecules for C-C Activation

O

O

OO

O

O

Mitsudo, T. et. al. Chem. Lett,

2005, 34, 1462.

Mechanism of the Pyranone Formation

Mitsudo, T. et. al. ACIEE,

2004, 43, 5369.

Outlines

- Fundamental considerations, C-H versus C-C activation- Orbital interactions- Evidence of M…C-C agostic interaction, C-C activation- Thermodynamics

- Stoichiometric reactions

- Catalytic reactions- Activation of strained molecules

- Direct cleavage- Utilization of a carbonyl group- b-Alkyl elimination

- Activation of unstrained molecules- b-Alkyl elimination, utilization of a p-allyl intermediate- Chelation assistance

- Conclusion

b-Alkyl Elimination, Utilization of a p-Allyl Intermediate

Mitsudo, T. et. al. JACS, 1998, 120, 5587.

5 mol%

b-Alkyl Elimination, Formation of a Pd-C(Sp2) Bond

Miura, M. et. al. JACS, 2001, 123, 10407.

b-Alkyl Elimination, Formation of a Pd-C(Sp) Bond

33-61 % yield

Uemura. S. et. al. JACS, 2003, 5, 2997.

Sequential b-Alkyl Elimination, Conjugate Addition

Hayashi. T. et. al. JACS, 2007, 129, 14158.

Sequential b-Alkyl Elimination, Conjugate Addition

Hayashi. T. et. al. JACS, 2007, 129, 14158.

Chelation Assistance

Jun, C.-H Chem. Soc. Rev., 1999, 121, 880.

Nickel-Catalyzed Arylcyanation of Alkynes

Hiyama, T. JACS, 2004, 126, 13904.time (h) yield(%)

Conclusion

- Different strategies toward C-C single bond activation have emerged

- Mild reaction conditions need to be developed

- Substrate scopes are limited in many cases

- Only a few enantioselective reactions have been reported

- This technology is still at the exploration stage