Chiral Phosphine…TheNucleophilic Trigger

3+2 Cycloaddition4+2 Annulation

Cory NewmanFebruary 17, 2006

Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2006, 45, 1426-1429 (3+2)Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234-12235 (4+2)

3+2 Cycloaddition Reaction

Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906-2908

3+2 Cycloaddition using Alkynoates

Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535-544

PR

R

R

PR

R

R

PR

R

R

PR

R

R

PR

R

R

PR

R

R

Nucleophilic Trigger

C

E

C

E

P

3+2 Cycloaddition Mechanism

Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535-544

Du, Y.; Lu, X.; Yu, Y. J. Org. Chem. 2002, 67, 8901-8905.Du, Y.; Lu, X. J. Org. Chem. 2003, 68, 6463-6465.

Uses of non-Chiral Phosphorus

Xu, Z.; Lu, X. Tetrahedron Lett. 1999, 40, 549-552

First Example of Chiral Phosphorus

Cat. PR3

P

CH3

H3C

PPh Ph

7 8

Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Am. Chem. Soc. 1997, 119, 3836-3837

And the Best Chiral Phosphorus is……

Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Am. Chem. Soc. 1997, 119, 3836-3837

And the Best Chiral Phosphorus is……

P

CH3

H3C

PPh Ph

7 8

Proposed Transition State

3+2 Cycloaddition of Allenes & Enones

Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2006, 45, 1426-1429

Survey of Chiral Phosphorus

A B

(R)-2

PPH2

PPH2

(R)-BINAP

P

(R)-nmdpp

Survey of Chiral Phosphorus

A B

(R)-2

(R)-2

Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2006, 45, 1426-1429

Scope

Spiro Example

Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2006, 45, 1426-1429

Dienones

Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2006, 45, 1426-1429

4+2 Cycloaddition Reaction…Kwon Reaction

Zhu, X.; Lian, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716-4717

4+2 Cycloaddition Mechanism

Zhu, X.; Lian, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716-4717

Additional Substrates

Zhu, X.; Lian, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716-4717

Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234-12235

Asymmetric 4+2 Reaction

Allene Scope

Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234-12235

Imine Scope

Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234-12235

Use in SynthesisW

urz,

R. P

.; Fu

, G. C

. J. A

m. C

hem

. Soc

. 200

5, 1

27, 1

2234

-122

35

Why Not…

Ph

PhP R

Ph

PhP ROR