-I

The Many Paths of Hypervalent

Iodine Reactions

O

BF4

O

I

I

HO O

[O]

OH I OTs

Ln-I

OAc AcO I OAc

O

O

In

R I

R'

OTf

h!

R

I

OTf

AcO I OAc

Ryan McFadden

N

Stoltz Literature Group Meeting

C

June 13, 2005

I

OTf

Outline

I. What is Hypervalency?

A. The Martin-Arduengo Notation B. Bonding in Hypervalent Iodine Compounds C. A Brief History of IBX and DMP

II. Oxidation Chemistry of Hypervalent Iodine

Dr. Anastasios Varvoglis Tassos, (University of Thessaloniki)

A. Oxidations of DIols and Amino-alcohols B. !-Oxidations of carbonyl compounds C. Heteroatom Transfer Oxidation: Aziridination D. Oxiations of Phenols E. Elaborations with oxidized phenols

III. Radical Reactions of Hypervalent Iodine

Dr. Hideo Togo, (Chiba University)

A. Oxidations of Anisoles B. Radical Chemistry of IBX C. Radical Chemistry of Iodine (III)

IV. C-C Bond Formation with Hypervalent Iodine

A. Ligand Coupling of Enolates B. Cyclopropanation C. Wolff Rearrangements D. Vinyl Iodonium Chemistry E. Alkynyl Iodonium Salts

Dr. Robert M. Moriarty, (Center), (University of Illinois)

receiving the Award for Creative Research from the president of SQM (Left) and the president

of the ACS (right) in 2005.

V. Conclusion

Reviews: 1. Moriarty, R. M. J. Org. Chem., 2005, 70, 2893. 2. Togo, H.; Katohgi, M. Synlett, 2001, 5, 565. 3. ARKIVOC, 2003, issue vi. (see URL below)

4. Topics in Current Chemistry, 2003, 224 (book)

K. C. Nicolaou

(Scripps)

O

IBX

O

IO

HO

1

What is Hypervalency?

-Hypervalent Compounds contain a central atom bearing more than 8 valence electrons. -The Iodine hypervalent bonds involve a formal 3-center-4-electron bond with both ionic and covalent character. -The Martin-Arduengo nomenclature system has traditionally been used to describe such compounds:

N-C-L = classification

N = Number of Valence electrons on the hypervalent atom

C = Identity of Central Atom

LI

L = Number of Ligands on the Central Atom

-The first hypervalent iodine species, iodobenzene dichloride (10-I-3) was prepared in 1886 by Willgerodt.

8-I-1 Ph I Iodobenzene

Wilgerodt. J. Prakt. Chem., 1886, 33, 155.

-IBX has been around since 1893! Hartmann,C.; Meyer, V. Chem. Ber., 1893, 26, 1727.

L L

I L

L

Examples With Iodine

L

LI L

LI L

8-I-2 [PhI(CN)] OTf "Stang Reagent"

10-I-3

PhI(OAc)2

Iodobenzene Diacetate or "PIDA"

L LL

I L

L

L LL

I LL

L

-Diaryl Iodonium Salts (8-I-2) were first prepared by Hartmann and Meyer in 1894.

Hartmann,C.; Meyer, V. Ber., 1894, 27, 504.

10-I-4 "IBX"

12-I-5 Dess-Martin-Peridinane

14-I-6 ???

Moriarty, R. M. J. Org. Chem., 2005, 70, 2893.

Bonding In Hypervalent Iodine Compounds

-Hypervalent iodine compounds will arange themselves so that the least electronegative group occupies an equatorial position. Both calculations and X-Ray structures support this fact.

O

O

I

!

N

H O

O

O

!

I

N

H O

IO

N

O

H O

0.0 kcal / mol

TS : ???

9.9 kcal / mol

-The process of interconverting axial and equatorial ligands on hypervalent iodine is called pseudorotation (!). Little is known of the mechanism of this process.

-Additionally, the two substituents in 3-center-4-electron bond will be 180? apart, so as to occupy the same hybrid orbital on the iodine atom.

OAc I

OH O

I O

OAc AcO

I OAc

O

OAc

"T - Shaped"

O "See-Saw"

O "Square-Pyrimidal"

-This is one reason for the unusual geometries encountered with hypervalent iodine compounds.

Kiprof, P., Zhdankin, V. ARKIVOC, 2003, 6, 170.

2

Bonding In Hypervalent Iodine Compounds

-In cases where the least electronegative group on iodine CANNOT occupy an equatorial position, intermolecular

bonding arises, forming aggregates.

O

R

electronegative

O

R

O

NI

O

C-O bond is broken

N O

I

OO I

R

O O ON NI

O

non-electronegative (Rigid Geometry)

O

R

-Additionally, some 8-I-2 compounds CANNOT have two electronegative groups to stabilize the hypervalent bond, so they will spontaneously polymerize.

O

I

O

I

PhIO

I

O

O

I

O

I

-In the ground state, Oxo and Imido ligands on iodine situate themselves so that no lone pairs are 180? away from

the I-Oxo or I-Imido bond.

Kiprof, P., Zhdankin, V. ARKIVOC, 2003, 6, 170.

Why IBX may have been Ignored for so Long

-Although IBX was discovered in 1893, little was done with it until the 1980's.

-Possible Reasons why :

Problem

Solution

!IBX is insoluble in just about everything! !There were few ways to make it

!use DMSO as the solvent

Chaudari, S. Synlett 2000, 2, 278. and Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2001, 123, 3183.

!Try Oxone in Water!

O OH

I

(a carcinogen) KBrO3 H2SO4, "

O

O I HO O

+ Br2

O OH

I

Oxone

H2O 70?C to 5?C

O

O I HO O

Greenbaum, F. R. Am. J. Pharm. 1936, 108, 17.

Santagostino, M., et.al. J. Org. Chem. 1999, 64, 4537.

!IBX Goes BOOM!

SIBX :

Plumb, J. B.; Harper, D. J. J. Chem. Eng. News 1990, July 16, 3.

!"Safe" IBX was developed

O

O

O

O

OH

OH

I HO O

I

49%

22%

O OH 29%

Chem. Abstr. 2002, 137, 109123.

3

A Use is Finally found for IBX

-Finally in 1983, Dess and Martin found a good use for IBX: Conversion to what became known as Dess-Martin Periodinane (DMP), a powerful alcohol oxidant.

O

O I HO O

IBX

Ac2O, AcOH Warming

O

AcO

O

Dess, B. D.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.

I OAc

OAc

DMP

-DMP became a method of choice for oxidations of primary and secondary alcohols:

OH RH

H

DMP Solvent

OH R R'

H

DMP Solvent

O RH

O R R'

A Proposed Mechanism

O

OH

O

AcO

O

R R' H

I

OAc -AcOH

OAc

DMP

O I OAc

OAc -AcOH O

H R R'

O

O I

OAc O

R R'

-The reaction can be accelerated in the presence of protic acids, and is largely functional-group-tolerant.

A Comparison of IBX and DMP

-The two comounds have been compared by experimental studies, NMR spectroscopy, and theoretical calculations, and there are numerous differences.

1.

IBX is highly functional-group tolerant, but DMP will oxidize sulfides and amines.

2.

Alcohol oxidation by IBX is adversely affected by water: Rate ! [ H2O ]-1 . IBX Alcohol oxidations

are both first-order in substrate and first-order in IBX: Rate ! [ Alc ] * [ IBX ]

3.

If DMP and 1 equivalent of alcohol are mixed, quantitative ligand exchange occurs at iodine,

but with with IBX, the exchange is reverible. In Both cases, the alcohol comes in anti to the

benzoic acid carboxylate.

IBX Path

OH O

HO

OH

I

O

HH

H

H

HO

O

O

I

O

O

-H2O

O

DMP Path

OAc

HO

OH

AcO

I

OAc O

HH

-2 AcOH O

H H

O O

I OAc

O

O

4.

In the presence of Diols, IBX forms a monodentate complex reversibly, But when diols are mixed with

DMP, a bidentate chelate forms, and the process is irreversible.

5.

As a consequence of all these rules, IBX fails to cleave diols, while DMP succeeds in this reaction.

De Munari, S.; Frigerio, M.; Santagostino, M. J. Org. Chem. 1996, 61, 9272.

4

IBX does the Twist

-Once an alcohol has bound IBX, a series of events occur, leading to oxidation of the substrate:

Barrier heights:

Twisting 9.9 kcal / mol

Ligand Exchange 7.2 kcal / mol (with H+)

Oxidation 2.6 kcal / mol

O

O

OI

+ MeOH OH

- H2O O

O OI

HH H

O

O

OI

O

O

H H

H

-Twisting must occur so that the late-transitional hydroxyl group formed during the oxidation step ends up 180? away from the benzoic acid hydroxyl group.

OH

O

OI

H

O

H

-Rate and selectivity-determining step (in the presence of acid) is twisting, not oxidation!

-Groups ortho to iodine on the phenyl ring are hypothesized to influence the rate of twisting. Goddard, W. A., III; and Su, J. T., unpublished results.

Diol and Amino-Alcohol Oxidation by IBX

-When diols are oxidized by IBX there can be a number or outcomes, none of which involve C-C bond scission.

HO

OH

R

R

HH

IBX (1 equiv)

O R

R OH

H

Excess IBX

O R

R O

HO

OH

R

R''

H R'

IBX (1 equiv)

O R''

R OH

R'

Reaction Stops Here

-1,4 diols, when oxidized with IBX, will form lactols:

OTIPS

Me

H OH OH

Me

IBX

DMSO 2hr, 23?C

(81%)

Me H Me

O OH

H

H OH MeO

OH H

H

H

O

O

O

H

OH

(82%, one diast.) (88%, one diast.)

(60%)

OH

O

n

n = 1 : (80%) n = 2 : (78%)

-1,4 amino alcohols will condensce down to aminals when oxidized with IBX:

BnO

OH NH2

1.1 equiv IBX

BnO

H OH

N H

MeO

N O

DMSO / THF 23?C

(72%)

MeO

N O

This molecule was carried on to an

Anthramycin analog.

7-membered ring closure was slow, taking 4.5 hours, unlike lactol formation. Little if any imine was detected.

Corey, E. J.; Palani, A. Tetrahedron Lett. 1995, 36, 3485. (Lactol Synthesis) Bose, D. S.; Srinivas, P.; Gurjar, M. K. Tetrahedron Lett., 1997, 38, 5839. (Aminal Synthesis)

5

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