1. Aza-Prins Cyclization
陈殿峰

2. Contents ♦ Introduction ♦ Catalyzed Aza-Prins ♦ Cascade Reactions
♦ Conclusions

3. Introduction Prins Cyclization 1.Condensation of olefins&aldehydes
2.Kriewitz, 1899
8.Aza-Prins
Prins Cyclization
3.Prins, 1917
7.Homoallylalcohol
4.Simple olefins
6.Diene
5.Substituted olefins
E. Arundale; L. A. Mikeska. Chem.Rev
David.R. Adams. Synlett

4. Catayzed Aza-Prins Cyclization
HOAc
p-TSA
CSA……
Brønsted acids
Catalysts Au Fe B ……
Lewis acids

5. General model

6. Brønsted Acid J.S.Yadav. J. Org. Chem. 2010.75. 2081-2084.
BA: HOAc, CSA,,TsOH
p-TSA, PMA
J.S.Yadav. J. Org. Chem

7. Brønsted Acid Aza-Prins or Cope? Indirect evidence :
Adrian P. Dobbs. Org. Biomol. Chem.,2010,8,

8. Lewis Acid 1、Au catalysts
Poor conversion:
AgBF4
AgOTf
4b: more electrophilic
2,6-DBP:
2,6-di-tert-butylpyridine
Young Ho Rhee. J. Am. Chem. Soc

9. 1、Au catalysts
Young Ho Rhee. J. Am. Chem. Soc

10. 1、Au catalysts Two possible pathways: slow unstable Evidence for
Young Ho Rhee. J. Am. Chem. Soc

11. 2、Fe catalysts R. P.Hsung .Org.Lett. 2006.8.3837-3840.
X=Cl、Br、I、acac
Energy Calculation
Proposed Intermediates
R. P.Hsung .Org.Lett
Juan I. Padron. Eur.J.Org.Chem

12. 2、Fe catalysts Solvents screen： CH2Cl2 is the best！
R. P. Hsung .Org.Lett

13. 3、Bi catalysts 4、Ga catalysts R’=alkyl,82-90% ; R’=aryl, ＞90%; dr=9:1
M. S. R. Murty. Tetrahedron.Lett
4、Ga catalysts
R=alkyl or aryl;
Yield 80-92%
dr＞96：4
No GaI3, no reaction;
Only GaI3, yield 20-35%
S. J. Yadav. Tetrahedron.Lett

14. I2 catalysts J. S. Yadav. Tetrahedron.Lett. 2009.50.2256-2260.
HTIB: PhIOH(OTs)
DIB :PhI(OAc)2
J. S. Yadav. Tetrahedron.Lett

15. Other Lewis Acids: Sc 、In 、Sn、 Ti etc. also performed well.
I2 catalysts
Mechanism：
Stereocontrol：
J. S. Yadav. Tetrahedron.Lett
Other Lewis Acids: Sc 、In 、Sn、 Ti etc. also performed well.
Adrian P. Dobbs. Org.Biomol.Chem.,2010,8,

16. 5、Boron catalysts yield:68-93% R=aryl, mainly cis products Substituted
amine failed!
J. S. Yadav. Tetrahedron.Lett

17. Cacade Reactions 1、Formal double Aza-Prins 2、Aza-Prins-Pinacol
3、Aza-Prins-Friedel-Crafts
4、Diels-Alder-Aza-Prins

18. 1、Formal double Aza-Prins
X= O / NTs
X= O / NTs
J. S. Yadav. Tetrahedron.Lett
J. S. Yadav. J.Org.Chem

19. 1、Formal double Aza-Prins
Mechanism:
(1)
(2)

20. 1、Formal double Aza-Prins
Matthew D. Shair. J.Am.Chem.Soc

21. 2、Aza-Prins-Pinacol

22. 2、Aza-Prins-Pinacol Mechanism: 1、preferential cyclization of E-imine
2、avoid bulky siloxy group
Lary. E. Overman. Org.Lett

23. 2、Aza-Prins-Pinacol
Alan. Armstrong. Org.Lett

24. 2、Aza-Prins-Pinacol Overman’s conclusion:
1、Ts-iminium tends to be trapped by enolate
rapidly
2、PathwayⅠgenerally for N-alkyl iminium
L.E. Overman. JACS
Armstrong proposed mechanism
Alan. Armstrong. Org.Lett

25. 3、Aza-Prins-Friedel-Crafts Alkylation
John.A. Porco, Jr. J.Am. Chem. Soc

26. 3、Aza-Prins-Friedel-Crafts Alkylation
Energy Calculation
John.A. Porco, Jr. J.Am. Chem. Soc

27. 3、Aza-Prins-Friedel-Crafts Alkylation
With diene:
John.A. Porco, Jr. J.Am. Chem. Soc

28. 4、Diels-Alder-Aza-Prins
Methyl Homosecodaphniphyllate
Clayton H. Heathcock. J. Am. Chem. Soc ,
J. Org. Chem
K C. Nicolaou. Angrew. Chem. Int. Ed

29. Polystep Reaction Stephen Hanessian. Org. Lett. 2004. 6. 4683-4686
Stephen Hanessian .J. Am. Chem. Soc
Stephen Hanessian .J. Org. Chem ,

30. Reductive coupling followed by Aza-Prins
1st step: reductive coupling between eneyne
Regioselectivity
20:1
Glenn C. Micalizio. Org.Lett

31. Reductive coupling followed by aza-Prins
Glenn C. Micalizio. Org.Lett

32. Aza-Prins followed by Electrocyclic
Tohru Fukuyama. J.Am.Chem.Soc

33. Conclusion
1、 Aza-Prins cyclization is a classical methodology in synthesis of
a lot of natural products, especially alkloids;
2、To the best of my knowledge, aza-cope rearrangment is always
competing with Aza-Prins ,and there is still no effective solution.
3、Few effective catalysts could promot aza-prins crclization behaving
in asymmetric ways.

34. Thank you!