Synthesis and Structure of Synthesis and Structure of Hypervalent Iodine CompoundsHypervalent Iodine Compounds

The concept The concept ““hypervalent iodinehypervalent iodine”” refers to the unique refers to the unique bonding interaction in iodine(III) and (V) compounds:bonding interaction in iodine(III) and (V) compounds:

Hypervalent Iodine Hypervalent Iodine CompoundsCompounds

Hypervalent iodine oxidants were the original Hypervalent iodine oxidants were the original ““greengreen”” reagents replacing many toxic metals (lead and reagents replacing many toxic metals (lead and thallium) in important synthetic transformations:thallium) in important synthetic transformations:

R1

R2

PhI(OH)OTs

O

R1

R2

n n95% MeOH, RT

+ +

I

+ TsOH

R1

R2

O

R1

R2

n n

+Tl(NO3)3 + TlNO3 + 2 HNO3MeOH, RT

Resaerch InterestsResaerch Interests

Synthesis and ReactivitySynthesis and Reactivity

Improvement of Improvement of ““greengreen”” synthetic methodology synthetic methodology using hypervalent iodineusing hypervalent iodine

Exploration of Exploration of hetereocyclic syntheseshetereocyclic syntheses

Preparation of novel Preparation of novel iodinanes of interest iodinanes of interest from an intellectual from an intellectual curiosity or synthetic curiosity or synthetic challenge aspectchallenge aspect

StructureStructure

In collaboration with Dr. In collaboration with Dr. John Protasiewicz at John Protasiewicz at Case Western Reserve Case Western Reserve University explore new University explore new iodinanes using X-ray iodinanes using X-ray crystallographycrystallography

Characterize novel Characterize novel iodinanes of interest iodinanes of interest from an intellectual from an intellectual curiosity or synthetic curiosity or synthetic challenge aspectchallenge aspect

Hydroxy(tosyloxy)iodobenzeneHydroxy(tosyloxy)iodobenzene““KoserKoser’’s Reagents Reagent””

HTIBHTIB

A mild and useful oxidant that A mild and useful oxidant that

mimics elemental brominemimics elemental bromine

MW 392.22 g/molMW 392.22 g/mol

11HH-1-hydroxy-5-methyl-1,2,3--1-hydroxy-5-methyl-1,2,3-benziodoxathiole 3,3-benziodoxathiole 3,3-DioxideDioxide

HMBIHMBI

A compact heterocyclic A compact heterocyclic equivalent of HTIBequivalent of HTIB

MW 314.10 g/molMW 314.10 g/mol

I OHO S

O

O

I

O

S

O

O

OH

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Improving Improving ““greengreen”” methods with HMBI - MWJ methods with HMBI - MWJ

R1

R2

PhI(OH)OTs

O

R1

R2

n n95% MeOH, RT

+ +

I

+ TsOH

R1

R2

O

R1

R2

n n95% MeOH, RT

+ +S

OHI

O OS

OI

O O

OH

recover, recycle, reuse

HMBI

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

O

OH

HMBI

MeOH, reflux 20 hrO

O

R'

R R R'

an Isoflavone

NH2

O

HMBI

CH3CN, refluxR R

NH3

reduced HMBI

NaOAc, Ac2OHN

OR

IO

SO

O

OH

O

+H2O

O

OH

-hydroxyketone

+I

OHSO

O

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Heterocyclic SynthesisHeterocyclic Synthesis

R C C I Ph

Nu:

C C I PhNu

R

C CNu

R

H+

C CI PhNu

R H

- PhI

1,2-rearrangement

C CR Nu

NuR

1,5-insertion

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Heterocyclic Synthesis Heterocyclic Synthesis (Melanie Knowlton (Melanie Knowlton ’’10, 10, Rachael Carmichael Rachael Carmichael ‘‘12)12)

C C I C C IO

C CO

O

O CCH

1,5-insertion-aryl C-H

O3S O3S

[Red I]

not observed

C

O

CH

1,5-insertion-alkyl C-H

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Attempted Heterocyclic Synthesis – Attempted Heterocyclic Synthesis – (Heather (Heather Sopher Sopher ‘‘09, Samantha Kristufek 09, Samantha Kristufek ’’11?)11?)

Ph I C C Ph

N O

N OPh

OTs

OTs

???

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Attempted Heterocyclic Synthesis – Attempted Heterocyclic Synthesis – (Heather (Heather Sopher Sopher ‘‘09, Samantha Kristufek 09, Samantha Kristufek ’’11)11)

Ph I C C Ph

N O

NO Ph

OTs

OTs

OTs

I

PhH

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Heterocyclic SynthesisHeterocyclic Synthesis

R C C I Ph

Nu:

C C I PhNu

R

C CNu

R

H+

C CI PhNu

R H

- PhI

1,2-rearrangement

C CR Nu

NuR

1,5-insertion

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Synthesis of a Novel Phenyliodonium Betaine - Synthesis of a Novel Phenyliodonium Betaine - MWJMWJ

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Synthesis of a Novel Phenyliodonium Betaine - Synthesis of a Novel Phenyliodonium Betaine - MWJMWJ

Brianne Sawders (‘12) is currently exploring the limits of the Suzuki reaction with this betaine

Synthesis with Hypervalent Synthesis with Hypervalent IodineIodine

Other long-term targets of interestOther long-term targets of interest

R

I

NaOCl

pH 8.2

R

IOO

TsOHI

OOTsR

I-R and I-S isomers observed

I

OTs

H H

Chirality at Iodine

Aromatic Iodine

base

I

OTs

H

I

" "

iodaanthracene

decomposes

colorless green

Structural StudiesStructural Studies

Structural Confirmation of an alkenyliodonium salt with Structural Confirmation of an alkenyliodonium salt with a pyridine a pyridine NN-oxide moiety-oxide moiety

Structural StudiesStructural Studies

Synthesis of a novel phenyliodinium betaineSynthesis of a novel phenyliodinium betaine

Structural StudiesStructural Studies

First example of a protonated iodosobenzene derivativeFirst example of a protonated iodosobenzene derivative

N

HN

I 1) AcOOH, AcOH, 40 oC

2) TsOH, CH3CN

N

NI

OHTsO

1919

AcknowledgementsAcknowledgements

My Students:Michelle Borkovec ‘06Alyssa Zimmerman ‘08.Heather Sopher ’09Michael Hughes ’09 Amanda Dechant ’09 Alex Ekstrom (biology) ’08 Melanie Knowlton ’09 Rocky Viggiano ‘09Samantha Kristufek ’11 Danielle Bittner ’11 Rachael Carmichael ’12 Brianne Sawders ’12Brandon Blanchard ‘12

Kathryn Sauka ‘14Alexis Rowley‘15Nick Burton‘15Anita Brkic ’15Johnny Lorigan’15 Zak Ekstrom ’15