byWilliam Schulz Bechara

Charette/Collins Charette/Collins LiteratureLiterature Meeting MeetingNovember 13November 13thth, 2012, 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. 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.

¨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.¨

3

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, 3427. 4

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, 2118.(c) Corey, E. J.; Hertler, W. R. J. Am. Chem. Soc. 1960, 78, 1657. 5

Mechanism

-Initiation :

-Propagation :

-Termination :

-Acidic Conditions :

-Basic Conditions :

6Wolff M. E. Chem. Rev. 1963, 63, 55.

Rise of Nitrene Chemistry

(a) Breslow, D. S.; Sloan, M. F. Tetrahedron Lett. 1968, 9, 5349.(b) Breslow, D. S.; Edwards, E. I.; Linsay, E. C.; Omura, H. J. Am. Chem. Soc. 1976, 98, 4268. 7

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, 5061. (b) Collet, F.; Lescot, C.; Dauban, P. Chem. Soc. Rev. 2011, 40, 1926.

Selectfluor Mediated Oxidation of Alcohols and Aldehydes

9Banks, R. E.; Lawrence, N. J.; Popplewell, A. L. Synlett, 1994, 831.

Unexpected Selectfluor Mediated C-H Functionalization

10Banks, R. E.; Lawrence, N. J.; Besheesh, M. K.; Popplewell, A. L.; Pritchard, R. G. Chem. Commun. 1996, 1629.

Unexpected Selectfluor Mediated C-H Functionalization

10Banks, R. E.; Lawrence, N. J.; Besheesh, M. K.; Popplewell, A. L.; Pritchard, R. G. Chem. Commun. 1996, 1629.

Selectfluor Mediated C-H Functionalization

11Banks, 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

12Banks, R. E.; Lawrence, N. J.; Besheesh, M. K.; Popplewell, A. L.; Pritchard, R. G. Chem. Commun. 1996, 1629.

Ritter Reaction

13

Baran…

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

Optimization

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

Optimization

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

C-H Amination with Inexpensive Source of Nitrogen

16Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

C-H Amination with Inexpensive Source of Nitrogen

17Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 2547.

Isomerization of cis-Decalin

18Michaudel, 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, 2547. 19

Mechanistic Studies

20Michaudel, 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, 2547. (b) Kochi, J. K. Science 1967, 155, 415.

F+ Mediated Oxidation of Metal; PdII / PdIV – AuI / AuIII

22

(a) Nyffeler, P. T.; Duro ́n, 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, 10806. (c) Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 7134. (d) Rosewall, C. F.; Sibbald, P. A.; Liskin, D. V.; Michael, F. E. J. Am. Chem. Soc. 2009, 131, 9488. (e) Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 1474.