Rh catalyzed asymmetric additions the rise of chiral dienes
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Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes. Tamio Hayashi. Erick Carreira. Daniela Sustac February 16, 2010. Outline. Transition Metal – Olefin Complexes. Alkenes not very basic, backbonding necessary to stabilize M-olefin bond;

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Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes

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Rh catalyzed asymmetric additions the rise of chiral dienes

Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes

Tamio Hayashi

Erick Carreira

Daniela Sustac

February 16, 2010


Outline

Outline


Transition metal olefin complexes

Transition Metal – Olefin Complexes

  • Alkenes not very basic, backbonding necessary to stabilize M-olefin bond;

  • Olefins considered labile, easily displaced from M center.

Crabtree, H.R. The Organometallic Chemistry of Transition Metals. Wiley: New Jersey, 2005.


Transition metal strained alkene complexes

Transition Metal – Strained Alkene Complexes

  • Strained alkenes (cyclopropene, norbornene) bind very strongly to metals;

  • Rehybridization on binding relieves ring strain.

Crabtree, H.R. The Organometallic Chemistry of Transition Metals. Wiley: New Jersey, 2005.


Examples of olefins in complexes and catalysis

Examples of Olefins in Complexes and Catalysis

  • Prepared by Zeise in 1827;

  • Structure elucidated in the 1950’s;

  • Norbornene in the Catellani reaction: “a sort of scaffold to be removed after the building of the molecule is complete; behaves as catalyst, excess necessary to push the reaction”

Wunderlich, A.J.; Mellor, D.P. Acta Crystallogr. 1955, 8, 57.

Catellani, M; Frignani, F.; Rangoni, A. Angew. Chem. Int. Ed. 2007, 36, 119.


Who binds the strongest

Who Binds the Strongest?

  • Electron deficient alkenes bind tighter;

  • Stronger binding with strained alkenes.

Tolman, A.C. Organometallics 1983, 2, 614.


Rh catalyzed 1 4 addition before chiral dienes

Rh-Catalyzed 1,4-Addition (before chiral dienes)

Consequently, the reaction can be done using directly [Rh(OH)(S-binap)]2 at 35 ºC.

Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052.


Chiral dienes first contact

Chiral Dienes: First Contact

Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.

Hydrosylilation: Uozumi, Y.; Lee, S.-Y.; Hayashi, T. Tetrahedron Lett. 1992, 33, 7185.


The only one with a lot of scope

The (Only) One with A Lot of Scope

Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.


Explaining stereochemistry

Explaining Stereochemistry

Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.


Chiral dienes first contact1

Chiral Dienes: First Contact

  • Advantages

  • Highest catalytic activity of all rhodium catalysts used for 1,4-addition;

  • Among the highest enantioselectivities (most over 90% ee);

  • Disadvantages

  • Long synthesis of chiral diene;

  • Bistriflate intermediate hard to isolate.

Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.


New route to chiral dienes

New Route to Chiral Dienes

Berthon-Gelloz, G.; Hayashi, T. J. Org. Chem. 2006, 71, 8957.

Vandyck, K.; Matthys, B.; Willen, M.; Robeyns, K.; Van Meervelt, L.; Van der Eycken, J. Org. Lett. 2006, 8, 363.


One unstable chiral diene one stable rh complex

One Unstable Chiral Diene, One Stable Rh Complex

Berthon-Gelloz, G.; Hayashi, T. J. Org. Chem. 2006, 71, 8957.


One more carbon

One More Carbon

  • Optical resolution by recrystallization inefficient route;

  • Alternatively, can do racemic synthesis and separate by chiral HPLC, either intermediate or final product.

Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503.


To be stable or not to be stable

To Be Stable or Not to Be Stable


The one with imean arylation

The One with iMean Arylation

Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.


Stereochemistry is explained

Stereochemistry is Explained

Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.


The one with a bit of scope

The One with (a Bit) of Scope

Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.


The one where they do it better

The One where They Do It Better?

Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979.

Boezio, A.A; Pytkowicz, J.; Cote, A.; Charette, A.B. J. Am. Chem. Soc. 2003, 125, 14260.


The one with the imean mechanism

The One with the iMean Mechanism

Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979.


More stereochemistry explained

More Stereochemistry Explained

Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979.


Is nine the lucky number

Is Nine the Lucky Number?

Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307.


The one with the deprotection

The One with the Deprotection

By far the mildest approach!

Boezio, A.A; Pytkowicz, J.; Cote, A.; Charette, A.B. J. Am. Chem. Soc. 2003, 125, 14260.

Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979.

Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307.


The one with the cyclization of alkynals

The One with the Cyclization of Alkynals

*[Rh(OH)(cod)]2 used directly

Shintani, R.; Okamoto, K.; Otomaru, Y; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.


The one with the mechanism

The One with the Mechanism

Shintani, R.; Okamoto, K.; Otomaru, Y; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.


The one with the cyclization of alkynals1

The One with the Cyclization of Alkynals

*Et instead of Me.

Shintani, R.; Okamoto, K.; Otomaru, Y; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.


Let s do some cycloadditions

Let’s Do Some Cycloadditions

Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.


Rh catalyzed asymmetric additions the rise of chiral dienes

[4+2]

Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.


Cycloaddition mechanism

Cycloaddition Mechanism

Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.


Stereochemistry explained

Stereochemistry Explained

Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.


1 6 enynes cycloisomerization

1,6-Enynes Cycloisomerization

Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.


Tfb tetrafluorobenzobarrelene diene synthesis

Tfb (tetrafluorobenzobarrelene) Diene Synthesis

  • Chiral HPLC to separate enantiomers;

  • Low yielding steps.

Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem. Commun. 2009, 5713.


The one with the catalyst design

The One with the Catalyst Design

A chiral diene and a phosphine on the same catalyst!

Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.


Dig the mechanism

“Dig” the Mechanism

Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.


Stereochemistry explained1

Stereochemistry Explained

Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.


More chiral dienes

More Chiral Dienes

Most effective ligands reported so far for Rh-catalyzed asymmetric addition!

Okamoto, K.; Hayashi, T.; Rawal, H.V. Org. Lett. 2008, 10, 4387.


Last stereochemistry picture

Last Stereochemistry Picture

Okamoto, K.; Hayashi, T.; Rawal, H.V. Org. Lett. 2008, 10, 4387.


Hayashi s dienes summary

Hayashi’s Dienes: Summary


Ir catalyzed allylic displacement

Ir-Catalyzed Allylic Displacement

Potential for the diene to be synthesized asymmetrically from cheap (R) or (S)-carvone.

Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E.M. J. Am. Chem. Soc. 2004, 126, 1628.


Spin off carreira s diene

Spin-Off: Carreira’s Diene

Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E.M. J. Am. Chem. Soc. 2004, 126, 1628.


Carreira s dienes generation ii the long way home

Carreira’s Dienes Generation II“The Long Way Home”

Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E.M. Org. Lett. 2004, 6, 3873.


Again with the enones

Again with the Enones?

  • Additional substrates in the scope (not covered by Hayashi)

Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E.M. Org. Lett. 2004, 6, 3873.


One ligand one day two papers

One Ligand, One Day, Two Papers


The short way home

The Short Way Home

Carreira

Darses

  • Ortho substituted boronic acids a challenge;

  • Most accessible route;

  • Library of 14 ligands;

  • High enantioselectivities (over 90%).

Gendrineau, T.; Chuzel, O.; Eijsberg, H.; Genet, J.-P.; Darses, S. Angew. Chem. Int. Ed. 2008, 47, 7669.

Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E.M. J. Am. Chem. Soc. 2004, 126, 1628.


Enantioselective diene synthesis

Enantioselective Diene Synthesis

Brown, K.M.; Corey, E.J. Org. Lett. 2010, 12, 172.


Order of addition is important

Order of Addition Is Important

  • Diene is inhibited

  • Less strained system necessary

Brown, K.M.; Corey, E.J. Org. Lett. 2010, 12, 172.


Adding one more carbon

Adding One More Carbon

Brown, K.M.; Corey, E.J. Org. Lett. 2010, 12, 172.


Summary

Summary

Reviews:

Defieber, C.; Grutzmacher, H.; Carreira, E.M. Angew. Chem. Int. Ed. 2008, 47, 4482.

Johnson, B.J.; Rovis, T. Angew. Chem. Int. Ed. 2008, 47, 840.


A bit of shopping chiral dienes at aldrich

A Bit of Shopping: Chiral Dienes at Aldrich


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