Benoît Moreau

Benoît Moreau

Organohypervalent Iodine as Mild and Selective Reagents for Multiple Oxidation Processes

Literature MeetingJune 6th, 2005

www.webelements.com

Iodine

I: [Kr] 4d10 5s2 p5

Oxidation states: 7, 5, 3, 1, and -1Geometry: Orthorhombic

Discovered in 1811, by Bernard Courtois, France

From the Greek word "iodes" meaning "violet"

He isolated iodine from treating seaweed ash with sulphuric acid (H2SO4)while recovering sodium and potassium compounds.

Iodine exhibits some metallic-like properties.

Group 17 (Halogens)

Iodine: Oxidation States

I(+5)

I(+7)

IO

O

AcOOAc

OAcI

O

O

O O

Dess-Martin periodinane IBX

I(+3)

NaIO4

IOAc

OAc

IO

- 1,2-diol cleavage

- mild alcohol oxidation

- Various purposes!

Commonly used for…

Hypervalent Iodine: Timeline

1886 Ph-ICl2 prepared by Willgerodt

Since 1990, ‘‘rediscovery’’ of hypervalent organoiodine compounds

- Applied to total synthesis of a large number of natural products- Many reviews lately- Use extended to various processes

Why?

- similar reactivity to Hg(II), Tl(III), and Pb(IV)- similarities (reductive elimination, ligand exchange, etc.) with organic transition metal complexes- PhI(OAc)2 is commercially available

1914 Nearly 500 compounds known.

Willgerodt, C. J. Prakt. Chem. 1886, 33, 154.Willgerodt, C. Die Organischen Verbindungen mit Mehrwertigen Jod;

Ferdinand Enke Verlag: Stuttgart, 1914.V. V. Zhdankin, P. J. Stang, Chem. Rev. 2002, 102, 2523 – 2584.

1957 First iodonium ylide prepared.

Preparation of PhI=O and PhI(OAc)2

I

IO

IOAc

OAc

OH , H2O

AcOH, H2O2

Ac2O, H2O2

H2O

H2O

Efficient oxidant

Almost insoluble in most solvents(polymeric structure)

Commercially available ca. 500$/kg

Easily recrystallized and stored forextended periods of time without significant decomposition

Hypervalent Iodine

Reaction of Ylides Oxidation of CH-OH bondFunctionnalization to carbonyls

1- Various oxidation processes

3- Phenolic oxidation

Seminal workApplication to natural product synthesisWipf’s contributionPorco’s contribution

2- Radical generation

Suarez’s contributionApplication in total synthesis


Hypervalent Iodine






Iodonium Ylides: Definition

C

I

R R

N

I

RO

I

Ph

Ph

Ph

C

I

R R

N

I

R

Ph

Ph

O

IPh

CR R

H H

NH2R

- H2O

- H2O

Also: P, S, Se iodonium ylides

Iodonium Ylides as Precursors for Epoxidation,Aziridination and Cyclopropanation

Daly, A. M. et al, Org. Lett. 2001, 3, 663.Dauban, P. et al, J. Am. Chem. Soc. 2001, 123, 7707-7708

Koskinen, A. M. P. et al, Acta Chem. Scand.1996, 50, 323-327.Muller, P. Acc. Chem. Res. 2004, 37, 243-251.

Amination through C-H activation

Du Bois, J. et al, J. Am. Chem. Soc. 2001, 123, 6935 – 6936.

Kohmura, Y.; Katsuki, T. Tetrahedron Lett. 2001, 42, 3339.

Intermolecular

Intramolecular

Non-catalyzed C-H activation of Aromatics

Misu, Y. et al, Org. Biomol. Chem. 2003, 1, 1342 – 1346.Kita, Y. et al, Tetrahedron Lett. 2004, 45, 2293 – 2295.

Kikugawa, Y. et al, J. Org. Chem. 2003, 68, 6739 – 6744.

Reaction of Iodonium Ylides:Hoffmann Rearrangement

Zhang, L.-H.; Kauffman, G. S.; Pesti, J. A.; Yin, J. J. Org. Chem. 1997, 62, 6918.

Alcohol Oxidation by PhI=O

Kita, Y. et al, Synlett 2003, 723

Alcohol Oxidation by PhI=O: Mechanism

Kita, Y. et al, Synlett 2003, 723

Alcohol Oxidation with PhI(OAc)2

Margarita, R. et al, J. Org. Chem. 1997, 62, 6974 – 6977.

- Primary alcohol is oxidated selectively over secondary (competition experiment)

- Reaction works best when performed in polar solvents

- This selective oxidation was used twice by Paterson during Discodermolide synthesis

Paterson I. et al, Org. Lett. 2003, 5, 35-38.

Alcohol Oxidation with PhI(OAc)2


Alcohol Oxidation with TEMPO/PhI(OAc)2: Mechanism


tolI(F)2 synthesis: Hara, S. et al, Synthesis 2002, 13, 1802–1803.

Halogenation to Carbonyls

Motherwell, W. B. et al, Tetrahedron Lett 2000, 41, 4463-4466.

Halogenation to Carbonyls: Mechanism

Motherwell, W. B. et al, Tetrahedron Lett 2000, 41, 4463-4466.

Togni, A. et al, Helv. Chim. Acta 2004, 87, 605 – 610.

Halogenation to Carbonyls: Asymmetric Induction

Challenge: suppress uncatalyzed background reaction between the hypervalent iodine reagent and the substrate.

Functionnalization to Carbonyls: Hydroxylation

Moriarty, R. M.; Condeiu, C.; Tao, A.; Prakash, O. Tetrahedron Lett. 1997, 38, 2401.

I(III) source preparation:

Olefin Functionnalization

Mechanism:

Hara, S. et al, Synlett 1998, 495.

R R

F F

IF2

53-70%

R = C10H21, HOC9H18, AcOC9H18, AcOC4H8, MeO2CC8H18, ClC9H18, etc.

Et3N.5HF, CH2Cl2, -78 to 0 oC, 2h

Styrene Rearrangement

Miki, Y.; Fujita, R.; Matsushita, K.-I. J. Chem. Soc., Perkin Trans. 1 1998, 2533.

Olefin functionnalization: Styrene Rearrangement

M.W. Justik, G. F. Koser, Tetrahedron Lett. 2004, 45, 6159 –6163.

Over 25 examples, 70-92%

Mechanism:


2- Radical Generation


Hypervalent Iodine




Hemiacetal Oxidation with PhI(OAc)2

Posner, G. H. et al, Tetrahedron Lett. 2003, 44, 5407-5409.

N. G. Ramesh, A. Hassner, Synlett 2004, 975 – 978.

Hemiacetal Oxidation with PhI(OAc)2: Rationale for Selectivity

‘‘The high stereoselectivity in favor of 10 may be due to the presence of the vicinaltert-butoxycarboxymethyl side chain.’’

N. G. Ramesh, A. Hassner, Synlett 2004, 975 – 978.

Suarez, E. et al, J. Org. Chem. 1998, 63, 2099.

Formation of Alkoxy Radicals

O

ORRO

HO2C OH O

ORHOCO

O ORPhI(OAc)2/I2

43-70%

Mechanism?



O

ORRO

HO2C OH O

ORHOCO

O ORPhI(OAc)2/I2

43-70%

Mechanism:



O

ORRO

OH N

ORHOCO

ORPhI(OAc)2/I2

RHN R

R= Boc or P(O)Ph2

Formation of Radicals: Further Extension of Methodology

O R O RPhI(OAc)2 or PhI=ORN

I2O O

NR

O O

Suarez, E. et al, Tetrahedron: Asymmetry 2000, 11, 3879.

O R O RPhI(OAc)2 or PhI=OHO

I2O O

O

O O

Formation of Radicals: Further Extension of Methodology

Suarez, E. et al, Tetrahedron Letters 2000, 41, 7869–7873.

Formation of Alkoxy Radicals: Mechanism

Alkoxy Radical Generation: Application to Total Synthesis of Avermectin

OOH Me

MeH

OP

RMe

OO Me

MeH

OP

RMe

H

OO

Me

MeH

O

MeH

O

O

OH

HMe

OMe

Me

OMeOO

OMeMe

OHOOMe

Me

Avermectin A1a

HgO

Danishefsky, S. J. et al, J. Am. Chem. Soc. 1989, 111, 2961-2980.

Paquette, L. A.; Hong, F.-T. J. Org. Chem. 2003, 68, 6905.

Dumsin

Alkoxy Radical Generation: Application to Total Synthesis of Dumsin




2- Radical Generation


Hypervalent Iodine


Phenol oxidation

OH O

Nu

PhI(OAc)2

OI

Ph

OAc

NuH

- AcOH - AcOH- Ph-I

R R R

General Scheme

Nucleophiles: water, alcohols, amines, acids

Phenol oxidation: Seminal Work

Kita, Y. et al, J. Org. Chem. 1987, 52, 3927-3930

Pelter, A.; Elgendy, S. J. Chem. Soc., Perkin Trans. 1, 1993, 1891.

Phenol oxidation: Extension of the Methodology

Barret, R.; Daudon, M. Tetrahedron Lett. 1991, 32, 2133.

Mitchell, A. S.; Russell, R. A. Tetrahedron Lett. 1993, 34, 545.

Phenol oxidation: Extension of the Methodology

Breuning, M.; Corey, E. J. Org. Lett. 2001, 3, 1559.

Abrams, S. R. et al, Phytochemistry 1994, 37, 289.

O

OH

OH

HOHO

O

H

Corey, E. J.; Wu, L. I. J. Am. Chem. Soc. 1993, 115, 9327.

Phenol oxidation: Application to Miroestrol Synthesis

Miroestrol

Phenol Oxidation: Application to Natural Product Synthesis

Kita, Y. et al, J. Am. Chem. Soc. 2003, 125, 11235 – 11240.

Asymmetric Synthesis of p-Quinols

Pettus, T. R. R. et al, Org. Lett. 2004, 6, 1535-1538.

Asymmetric Synthesis of p-Quinols: Proposed Model

Pettus, T. R. R. et al, Org. Lett. 2004, 6, 1535-1538.

Extracts from these plants have been used for centuries in eastern cultures for the treatment of various respiratory problems, such as pertussis, bronchitis, and tuberculosis

Isolated in 1934 and in 1936, from Stemona tuberosa and Stemona sessifolia roots.

Tuberostemonine: Natural Product of Interest

Suzuki, K. J. Pharm. Soc. Jpn. 1934, 54, 573.Kondo, H.; Suzuki, K.; Satomi, M. J. Pharm. Soc. Jpn.1939, 59, 443.

Schild, H. Ber. Dtsch. Chem. Ges. 1936, 69B, 74.

Stemona Alkaloids Family

N

OHOH

O

HO O

H

N

O

O

O

O

HO

HO

Oxotuberostemonine Tuberostemonone

N HO O

H

N HO O

H

OO H

Stemoninine

O

O H

HH

H

H

O

Parvistemonine

Kondo, H.; Suzuki, K.; Satomi, M. J. Pharm. Soc. Jpn.1939, 59, 443.

Wipf’s Contribution to Stemona Alkaloids Synthesis

- This motif was used as building block to access various natural products

Key Reaction:

Wipf, P.; Kim, Y. Tetrahedron Lett. 1992, 33, 5477.Wipf, P.; Spencer, S. R. J. Am. Chem. Soc. 2005, 127, 225.

Oxidative Spirocyclization of l-Tyrosine

Wipf, P.; Spencer, S. R. J. Am. Chem. Soc. 2005, 127, 225.

Total Synthesis of Tuberostemonine


Synthesis of Tuberostemonine: Metathesis and Lactone Introduction


Total Synthesis of Tuberostemonine: End Game


Epoxyquinoids: Natural Products of Interest

- Isolated in 1996 from Pestalotiopsis spp., a fungal genus also producing Taxol. Fongus grows on Florida torreya tree.

-Inhibitor of the phosphorylation of the NF-kB inhibitory protein IkB. Potent antiangiogenic activity.

Lee, J. C.; Strobel, G. A.; Lobkovsky, E.; Clardy, J. J. Org. Chem. 1996, 61, 3232.

Epoxiquinoids: Porco’s Contribution

OMe

OH

R

O

RMeO OMe

O

RMeO OMe

OPhI(OAc)2, MeOH Directed epoxidation

General Scheme

- This motif is a common building block to access various natural products

Torreyanic Acid Synthesis

Li, C.; Lobkovsky, E.; Porco, J. A. Jr. J. Am. Chem. Soc. 2000, 122, 10484.

Li, C.; Lobkovsky, E.; Porco, J. A. Jr. J. Am. Chem. Soc. 2000, 122, 10484.

Torreyanic Acid Synthesis

Tandem Oxidation/Electrocyclization/Dimerization Process

Endo cyclization

This is also the proposed biosynthesis of Torreyanic Acid

Asymmetric Syntheses of Torreyanic Acid

Li, C.; Johnson, R. P.; Porco, J. A. Jr. J. Am. Chem. Soc. 2003, 125, 5095.

Asymmetric Syntheses of Torreyanic Acid and Ambuic Acid


Common Intermediate to Torreyanic Acid and Ambuic Acid


(-)-Jesterone Synthesis

MeO

O

HOO

Me

Me

MeO

OH

HOO

Me

Me

MeO

OH

HOO

Me

Me

a

b

Porco, J. A. Jr. et al, Org. Lett. 2001, 3, 1649.

(-)-Cycloepoxydon Synthesis

Porco, J. A. Jr. Et al, J. Am. Chem. Soc. 2001, 123, 11308.

(+)-Panepophenanthrin Synthesis

10% HF, CH3CN/

CH2Cl2, RT, 1 h.

40%

Lei, X.; Johnson, R. P.; Porco, J. A. Jr. Angew. Chem. Int. Ed. 2003, 42, 3913

Takeuchi, T. et al, J. Nat. Prod. 2002, 65, 1491.Xiang Wang and John A. Porco, Jr., Angew. Chem. Int. Ed. 2005, 44, 3067 –3071.

Phenol oxidation: Porco’s Synthesis of the Tetrapetalone Core

Isolated from the mushroom strain Panus rudis Fr. IFO8994.

First naturally occurring inhibitor of ubiquitin-activating enzyme

(abnormal ubiquitination-mediated protein degradation may be associated with human cancers, inflammation, and neurodegenerative disease.)

[O]

Phenol oxidation: Strategy for Access to the Tetrapetalone Core

Xiang Wang and John A. Porco, Jr., Angew. Chem. Int. Ed. 2005, 44, 3067 –3071.

Tetracyclic Core of the Tetrapetalones


Phenol Oxidation: Transannular [4+3] Cyclization

42% yield over 2 steps

Tetracyclic Core of the Tetrapetalones


Hypervalent Iodine: Summary

- Cyclopropanation, Aziridination, Epoxidation- Hoffmann Rearrangement - C-H insertion- Alcohol Oxidation - Functionnalization to carbonyls



OH O

Nu

PhI(OAc)2

OI

Ph

OAc

NuH

- AcOH - AcOH- Ph-I

R R R


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Benoît Moreau