by William Schulz Bechara Charette/Collins Literature Meeting November 13 th, 2012

The History of C–H Amination ¨In 1878, the structure of piperidine was still unknown, and A. W. Hofmann made attempts to add hydrogen chloride or bromine to it in the belief that the compound possessed unsaturation.¨ Wolff M. E. Chem. Rev. 1963, 63, 55. 1

The History of C–H Amination (a) Wolff M. E. Chem. Rev. 1963, 63, 55. (b) Hofmann, A. W. Chem. Ber. 1879, 12, 984. ¨Hofmann made the surprising discovery that […] a tertiary amine was obtained, and this product was later shown to be octahydroindolizine.¨ ¨In 1878, the structure of piperidine was still unknown, and A. W. Hofmann made attempts to add hydrogen chloride or bromine to it in the belief that the compound possessed unsaturation.¨ 2

The History of C–H Amination (a) Wolff M. E. Chem. Rev. 1963, 63, 55. (b) Hofmann, A. W. Chem. Ber. 1879, 12, 984. ¨In 1878, the structure of piperidine was still unknown, and A. W. Hofmann made attempts to add hydrogen chloride or bromine to it in the belief that the compound possessed unsaturation.¨ ¨Hofmann made the surprising discovery that […] a tertiary amine was obtained, and this product was later shown to be octahydroindolizine.¨ 2

Isolation of Intermediates Wolff M. E. Chem. Rev. 1963, 63, 55. 3

Isolation of Intermediates Wolff M. E. Chem. Rev. 1963, 63, 55. 3

Hofmann–Löffler–Freytag Reaction ¨In 1909, K. Löffler and C. Freytag extended the scope of this transformation and demonstrated the synthetic utility of the process as exemplified by their elegant synthesis of nicotine.¨ (a) Wolff M. E. Chem. Rev. 1963, 63, 55. (b) Löffler, K.; Freytag, C. Chem. Ber. 1909, 42,

Mechanistic Studies In 1950s and 60s…  Indication that C−H bond cleavage : rate-limiting step of the reaction (a) Wolff M. E. Chem. Rev. 1963, 63, 55. (b) Wawzonek, S.; Thelan, P. J. J. Am. Chem. Soc. 1950, 72, (c) Corey, E. J.; Hertler, W. R. J. Am. Chem. Soc. 1960, 78,

Mechanism -Initiation : -Propagation : -Termination : -Acidic Conditions : -Basic Conditions : 6 Wolff M. E. Chem. Rev. 1963, 63, 55.

Rise of Nitrene Chemistry (a) Breslow, D. S.; Sloan, M. F. Tetrahedron Lett. 1968, 9, (b) Breslow, D. S.; Edwards, E. I.; Linsay, E. C.; Omura, H. J. Am. Chem. Soc. 1976, 98,

Rise of C-H Insertion/ and C-H Activation/Amination C-H Insertion C-H Activation 8 (a) Collet, F.; Dodd, R. H.; Dauban, P. Chem. Commun. 2009, (b) Collet, F.; Lescot, C.; Dauban, P. Chem. Soc. Rev. 2011, 40, 1926.

Selectfluor Mediated Oxidation of Alcohols and Aldehydes 9 Banks, R. E.; Lawrence, N. J.; Popplewell, A. L. Synlett, 1994, 831.

Unexpected Selectfluor Mediated C-H Functionalization 10 Banks, R. E.; Lawrence, N. J.; Besheesh, M. K.; Popplewell, A. L.; Pritchard, R. G. Chem. Commun. 1996, 1629.

Unexpected Selectfluor Mediated C-H Functionalization 10 Banks, R. E.; Lawrence, N. J.; Besheesh, M. K.; Popplewell, A. L.; Pritchard, R. G. Chem. Commun. 1996, 1629.

Selectfluor Mediated C-H Functionalization 11 Banks, R. E.; Lawrence, N. J.; Besheesh, M. K.; Popplewell, A. L.; Pritchard, R. G. Chem. Commun. 1996, 1629.

Proposed Mechanism - Ritter-Type C−H Amination 12 Banks, R. E.; Lawrence, N. J.; Besheesh, M. K.; Popplewell, A. L.; Pritchard, R. G. Chem. Commun. 1996, 1629.

Ritter Reaction 13

Baran… 14 Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

Optimization 15 Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

Optimization 15 Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

C-H Amination with Inexpensive Source of Nitrogen 16 Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

C-H Amination with Inexpensive Source of Nitrogen 17 Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

Isomerization of cis-Decalin 18 Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

Hydrolysis Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134,

Mechanistic Studies 20 Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

Mechanistic Hypothesis - SET 21 (a) Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, (b) Kochi, J. K. Science 1967, 155, 415.

F + Mediated Oxidation of Metal; Pd II / Pd IV – Au I / Au III 22 (a) Nyffeler, P. T.; Duron, S. G.; Burkart, M. D.; Vincent, S. P.; Wong, C.-H. Angew. Chem., Int. Ed. 2005, 44, 192. (b) Mei, T.-S.; Wang, X.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, (c) Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, (d) Rosewall, C. F.; Sibbald, P. A.; Liskin, D. V.; Michael, F. E. J. Am. Chem. Soc. 2009, 131, (e) Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 1474.