1. Mike April 29th 2013
Umpolung of Hemiaminals: Titanocene-Catalyzed Dehydroxylative Radical Coupling Reactions with Activated Alkenes
Zheng, X.; Dai, X.-J.; Yuan, H.-Q.; Ye, C.-X.; Ma, J.; Huang, P.-Q. Angew. Chem. Int. Ed. 2013, 52, 3494 –3498

2. Outline About the authors Basic intro to umpolung chemistry
Intoduction to titanocenes
Titanocene catalysis
Prior work on hemiaminals
Titanocene catalysed umpolung

3. About the Author Pei-Qiang Huang
B.S. in Chemistry Xiamen University
D.E.A. in Organic Chemistry Universite de Montpellier II, France
Ph.D. in Organic Chemistry University of Paris-XI, France, 1987 L’institut de Chimie des Substances Naturelles, CNRS
Postdoctoral Fellow Shanghai Institute of Organic Chemistry, CAS
Associate Professor, Xiamen University
1993-present Professor, Xiamen University
Dean, College of Chemistry and Chemical Engineering, XMU
2008-present Dean, College of Chemistry and Chemical Engineering, XMU
Specializes in natural product synthesis as well as synthetic methodology

4. Umpolung Chemistry Reversal of the traditional polarity of a compound
Commonly used on aldehydes
Dithiane
Benzoin Condensation
Stetter Reaction

5. Our Friend Titanocene Comes in many oxidation states
Straightforward synthesis
Tethered and chiral variants exist
Sikora, D. J.; Moriarty, K. J.; Rausch, M. D., Inorg. Synth. 1990, 28, 248.
Wilkinson, G.; Birmingham, J. M. J. Am. Chem Soc. 1954, 76, 4281–4284.

6. Reactions Catalyzed by Titanium II
Asymmetric Pauson-Khand type cyclisation
Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,
Hydrogenation of an alkyne
Sonogashira, K.; Hagihara, N., Bull. Chem. Soc. Jpn. 1966, 39, 1178.

7. Stoichiometric Reactions of Titanium III
Nugent’s reagent
Nugent, W.A.; RajanBabu, T.V. J. Am. Chem. Soc., 1988, 110,

8. Stoichiometric Reactions of Titanium III
RajanBabu, T.V.; Nugent, W.A. J. Am. Chem Soc. 1994, 116,
Campana, A.G.; Bazdi, B.; Fuentes, N.; Robles, R.; Cuerva, J.M.; Oltra, J.E.; Porcel ,S.; Echavarren, A.M. Ang. Chem. Int. Ed. 2008, 120,

9. Reactions Mediated by Titanium III
Barbier type reaction
Munoz-Bascon, J.; Sancho-Sanz, I.; Alvarez-Manzaneda, E.; Rosales, A.; Oltra, J. E. Chem. Eur. J. 2012, 18, –
Gansauer, Andreas.; Knebel, K.; Kube, C.; van Gastel, M.; Cangonul, A.; Daasbjerg, K.; Hangele, T.; Hulsen, M.; Dolg, M.; Friedrich, J. Chem. Eur. J. 2012, 18, 2591 – 2599.

10. Reactions Mediated by Titanium III
Fleury, L.M.; Kosal, A.D.; Masters, J.T.; Ashfield, B.L. J. Org. Chem., 2013, 78,
Gianino, J. B.; Ashfeld, B. J. Am. Chem. Soc. 2012, 134, 18217−18220.

11. Reactions Catalyzed by Titanium IV
Pop, R.; Cui, J. L.; Adriaenssens, L.; Comte, V. Le Gendre, P. Synlett 2011, 679–683.

12. Samarium Mediated Umpolung of Hemiaminals
Y.-G. Xiang, X.-W. Wang, X. Zheng, Y.-P. Ruan, P.-Q. Huang, Chem. Commun. 2009, 45, 7045 – 7047.

13. Titanocene Catalyzed Reaction
Optimization
Entry
Eq. TMSCl
M (eq.)
Eq. tBuOH
t (h)
Yield (%) 1 2
Mg (2) - 10 54 4 5 74 3 91
Mg (5) 93
Sm (2) 85 6
Mn (2) 72 7
Zn (2) 64 8
Al (2) 20 17
Zheng, X.; Dai, X.-J.; Yuan, H.-Q.; Ye, C.-X.; Ma, J.; Huang, P.-Q. Angew. Chem. Int. Ed. 2013, 52, 3494 –3498.

14. Mechanism

15. Scope

16. Scope (part the second)

17. Scope (part the third)

18. Total Synthesis of rac-9,10-diepi-stemoamide
6 linear steps, 13 % overall yield

19. Conclusions Inverse reactivity of typical hemi-aminal
New route to complex structures
Ability to generate quaternary carbon centres
More stable reagents and better yields than samarium
Lack of diversity in substrate scope
Poor diastereoselectivity
Proposed mechanism suggests asymmetric variant may be impossible