ATP Lit Seminar5

Hypervalent Iodine Reagents in Organic Synthesis

Andrew T. Parsons

March 23, 2007

Outline

• Background

• Iodine(III) reagents

• Iodine(V) reagents

• Conclusions

Hypervalent Iodine: An Introduction

Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523-2584.

• Hypervalent iodine: Species that exceed eight electrons in the valence shell, typically IIII and IV

– Can accommodate up to 12 valence electrons:

– Species with 10 valence electrons are more common:

I(OAc)2 I(OCOCF3)2 IOTs

OAcOAc

Dess-Martin periodinane

Hypervalent Iodine: A Brief History

• Both Iodine(III) and (V) compounds were first prepared by Willgerodt in 1886 and 1900, respectively

• Iodine(III) compounds are referred to as λ3-iodanes• Iodine(V) compounds are referred to as λ5-iodanes,

periodanes, or periodinanes

Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123-1178.

ICl2 IO O

iodoxybenzene:(caution: explosive)

(dichloroiodo)benzene

Structural Characteristics• λ3-iodanes:

• λ5-iodanes:

o-iodoxybenzoic acid10-I-4

pseudo-trigonal bipyramidal

Dess-Martin periodinane12-I-5

pseudo-octahedral

(dichloroiodo)benzene10-I-3

pseudo-trigonal bipyramidal

diphenyliodonium chloride8-I-2

pseudo-tetrahedral

Outline

• Background

• Conclusions

Preparation of IIII Reagents• Most reagents are prepared directly from iodobenzene:

Varvoglis, A. Tetrahedron 1997, 53, 1179-1255.

I(OAc)2

Ac2O, H2O2

CF3CO2HI(OCOCF3)2H2O

TsOH, H2O

I(OH)OTs

Cl2ICl2

HBF4, H2O

PhIOHBF4

Reactions of Iodine(III) Compounds

• Reactivity is driven by the electrophilic nature of IIII

– Typical reactions proceed through an initial nucleophilic attack of the iodine center:

– PhIX is an excellent leaving group, and therefore subsequent substitutions and reductive eliminations are prevalent

PhI + X-

Reactions of Iodine(III) Compounds: Oxygenations

• Iodosylbenzene, PhIO:– Useful for a number of different oxidations– Exists as a polymer, which is activated through depolymerization when treated with alcoholic solvents and base

– Can also be activated in the presence of a Lewis acid or Br - catalyst

– The active IIII species, PhI(OMe)2, can also be generated from PhI(OAc)2

(PhIO)nMeOH

MeOHIPh

Moriarty, R. M.; Hu, H.; Gupta, S. C. Tetrahedron Lett. 1981, 22, 1283. Moriarty, R. M. J. Org. Chem. 2005, 70, 2893-2903.

Oxidations with Iodosylbenzene

• Useful in the α-hydroxylation of ketones

• α-Hydroxylation of ketones can be carried out using CrO3, typically with higher yields

• PhIO is a non-toxic alternative to CrVI

O (PhIO)n

MeOH, KOH10 C

OMeMeO

Moriarty, R. M.; Gupta, S. C.; Hu, H.; Berenschot, D. R.; White, K. B. J. Am. Chem. Soc. 1981, 103, 686-688.Moriarty, R. M.; Hu, H.; Gupta, S. C. Tetrahedron Lett. 1981, 22, 1283.

Oxidations with Iodosylbenzene

Moriarty, R. M.; Hu, H.; Gupta, S. C. Tetrahedron Lett. 1981, 22, 1283.

O (PhIO)nMeOH, KOH Ar

OHOMeMeO H+

Me MeO F60% 45% 50% 70%

O2N63% 70% 71% 48%

Mechanism of α-Hydroxylation

Moriarty, R. M. J. Org. Chem. 2005, 70, 2893-2903.

R1 R2O -OMe

R1 R2O

I PhMeO

OMeO-OMe

OMeMeO

PhI + -OMe

Applications in Total Synthesis• Synthesis of (-)-Xialenon

• Carrying out this transformation using a Rubottom oxidation provided a dr of 3:1

O 1. PhI(OAc)2KOH, MeOH

2. 10% H2SO470%, over 2 steps TBSO

OHTBAF

dr = 7:1 (-)-Xialenon

Hodgson, D. M.; Galano, J.-M.; Christlieb, M. Tetrahedron 2003, 59, 9719-9728.Rubottom, G.M.; Gruber, J.M. J. Org. Chem. 1978, 43, 1599-1602

Catalytic α-Acetoxylation of Ketones

PhI (0.10 equiv),mCPBA (2.0 equiv) BF3OEt2 (3 equiv)

AcOH-H2O, rt

Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto, K. J. Am. Chem. Soc. 2005, 127, 12244-12245.

Catalytic Cycle

[PhI(III)]

AcOH +

BF3OEt2

Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto, K. J. Am. Chem. Soc. 2005, 127, 12244-12245.

Oxidative Rearrangements of Aryl Alkenes

• Koser’s reagent induces an oxidative rearrangement of aryl alkenes to afford α-aryl ketones

95% MeOH R1Ar

OPhI(OH)OTs

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

84% 89%

95% MeOH R1Ar

OPhI(OH)OTs

IPh OMe

MeOH, H2OOMe

ArH OMe

TsOH, H2OR1

H2O-OTs

Oxidative Cleavage of Alkenes

• Works well for electron-rich olefins• Reaction times typically 0.5-5 h• Safer than ozonolysis, cheaper than transition-metal

reagents

R PhIO (2.2 equiv), HBF4 (2.2 equiv)

CH2Cl2-HFIP-H2O (9:3:1), rtO

Miyamoto, K.; Tada, N.; Ochiai, M. J. Am. Chem. Soc. 2007, 129, 2772-2773.

R PhIO (2.2 equiv), HBF4 (2.2 equiv)

CH2Cl2-HFIP-H2O (9:3:1), rtO

O2N61%

OnC11H23

• Suggests that an epoxidation precedes cleavage

Miyamoto, K.; Tada, N.; Ochiai, M. J. Am. Chem. Soc. 2007, 129, 2772-2773.Moriarty, R. M.; Gupta, S. C.; Hu, H.; Berenschot, D. R.; White, K. B. J. Am. Chem. Soc. 1981, 103, 686-688.

PhIO (2.2 equiv), HBF4 (2.2 equiv)

CH2Cl2-HFIP-H2O (9:3:1), rt25 h

39% 34%

O2N O2NO2N

• Suggests that an epoxidation precedes cleavage

OPhIO (1.1 equiv), HBF4 (1.1 equiv)

CH2Cl2-HFIP-H2O (9:3:1), rt88%

OO2N O2N

PhIO (2.2 equiv), HBF4 (2.2 equiv)

CH2Cl2-HFIP-H2O (9:3:1), rt25 h

39% 34%

O2N O2NO2N

Reactions of Iodine(III) Compounds: Oxidation of Phenols

• Previously:

typically PhIX2 = PhI(OAc)2 or PhI(OCOCF3)2

Application to Spirocyclizations• Tether a nucleophile to the phenol:

• Possible applications in natural product synthesis

solvent

Spirocyclization of Phenols: Early Studies

PhI(OCOCF3)2

K2CO3, CH3CN0 C to rt, 10 min

Tamura, Y.; Yakura, T.; Haruta, J.-I.; Kita, Y. J. Org. Chem. 1987, 52, 3927-3930.

Mechanism

F3COCO

OCOCF3 OCOCF3, PhI

PhI(OCOCF3)2

Tamura, Y.; Yakura, T.; Haruta, J.-I.; Kita, Y. J. Org. Chem. 1987, 52, 3927-3930.

Current Standard: Catalytic Spirocyclizations

Dohi, T.; Maruyama, A.; Yoshimura, M.; Morimoto, K.; Tohma, H.; Kita, Y. Angew. Chem. Int. Ed. 2005, 44, 6192-6196.

OArI(OCOCF3)2 (0.05 equiv)

mCPBA (1.5 equiv)CF3CO2H (1.0 equiv)

CH2Cl2, rtHO2C

66% 76% 73% 77% 91% 80%

Catalytic Cycle

Dohi, T.; Maruyama, A.; Yoshimura, M.; Morimoto, K.; Tohma, H.; Kita, Y. Angew. Chem. Int. Ed. 2005, 44, 6192-6196.

Ar-IIII

Ar-ImCPBA

ArI(OCOCF3)2

Applications in Total Synthesis• Synthesis of Aranorosin:

PhI(OAc)2

MeOH, 0 C O

OHNCbz

Aranorosln

Wipf, P.; Kim, Y.; Fritch, P. C. J. Org. Chem. 1993, 58, 7195-7203.

PhI(OCOCF3)2-Promoted Formation of Lactols

Kita, Y.; Matsuda, S.; Fujii, E.; Horai, M.; Hata, K.; Fujioka, H. Angew. Chem. Int. Ed. 2005, 44, 5857-5860.

PhI(OCOCF3)2 (1.0 equiv)

H2O:CH3CN (1:4)0 C to rt

or ORO

if R1 = H

PhI(OCOCF3)2-Promoted Formation of Lactols

PhI(OCOCF3)2 (1.0 equiv)

H2O:CH3CN (1:4)0 C to rt

or ORO

if R1 = H

72% 65%

Applications in Total Synthesis• Synthesis of (+)-Tanikolide

C11H23

PhI(OCOCF3)2

H2O72%

C11H23

2 steps

C11H23

(+)-Tanikolide

Applications in Total Synthesis

HOCOCF3

OCOCF3Ph

HOCOCF3OH2

PhI(OCOCF3)2

• Synthesis of (+)-Tanikolide

Carbon-Carbon Bond Forming Reactions

Carbon-Carbon Bond Forming Reactions: Cyclizations with PhI(OCOR)2

• PhI(OCOR)2 reagents have been shown to promote attack by carbon nucleophiles:

PhI(OCOCF3)2

CF3CH2OHNH

Kita, Y.; Takada, T.; Ibaraki, M.; Gyoten, M.; Mihara, S.; Fujita, S.; Tohma, H. J. Org. Chem. 1996, 61, 223-227.

C-C Bond Forming Cyclizations

HOCOCF3

PhI(OCOCF3)2

IPh OCOCF3

PhI, HOCOCF3

Kita, Y.; Takada, T.; Ibaraki, M.; Gyoten, M.; Mihara, S.; Fujita, S.; Tohma, H. J. Org. Chem. 1996, 61, 223-227.

Applications in Total Synthesis• Synthesis of (±)-Stepharine

NaBH4NH

(±)-Stepharine

PhI(OAc)2

TFE, 0 C

PhI, -OAc

Honda, T.; Shigehisa, H. Org. Lett. 2006, 8, 657-659.

C-C Bond Forming Reactions: C-H Activation

Kalyani, D.; Deprez, N.; Desai, L. V.; Sanford, M.S. J. Am. Chem. Soc. 2005, 127, 7330-7331.

Deprez, N.; Kalyani, D.; Krause, A.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 4972-4973.

[Ph2I]BF4 (1.1-2.5 equiv)Pd(OAc)2 (0.05 equiv)

Solvent, 100 C

[Ph2I]BF4 (1.1-2.5 equiv)Pd(OAc)2 (0.05 equiv)

Solvent, 100 C

[Ph2I]BF4 (1-3.0 equiv)IMesPd(OAc)2 (0.05 equiv)

AcOH, rt

C-C Bond Forming Reactions: C-H Activation

Ph CHO

81% 71%

Kalyani, D.; Deprez, N.; Desai, L. V.; Sanford, M.S. J. Am. Chem. Soc. 2005, 127, 7330-7331.Deprez, N.; Kalyani, D.; Krause, A.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 4972-4973.

Mechanism of C-H Activation

PdNC X

HXPdX2

PdNC X

[Ph2I]X

Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126, 2300-2301.Kalyani, D.; Deprez, N.; Desai, L. V.; Sanford, M.S. J. Am. Chem. Soc. 2005, 127, 7330-7331.

Outline

• Background

• Conclusions

Preparation of IV Reagents

Boeckman, Jr., R.K.; Shao, P.; Mullins, J.J. Org. Synth. 2000, 77, 141-152. Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 4537-4538.

OHOxone, H2O

o-Iodoxybenzoic acid(IBX)

Ac2O, AcOH I

OAcAcO OAc

Dess-Martin periodinane(DMP)

70 C, 3 h 85 C to rt72%81%

• Caution: There have been reports of violent explosions occurring upon heating of these reagents to >200 °C

Oxidations of Alcohols: A Brief Overview

• DMP and IBX have been widely used for the mild oxidation of alcohols to ketones and aldehydes:

Zoller, T.; Breuilles, P.; Uguen, D. Tetrahedron Lett. 1999, 40, 6253-6256.Myers, A. G.; Zhong, B.; Movassaghi, M.; Kung, D. W.; Kwon, S. Tetrahedron Lett. 2000, 41, 1359-1362.Smith, A.B., III; Kanoh, N.; Ishiyama, H.; Minakawa, N.; Rainier, J.D.; Hartz, R.A.; Cho, Y.S.; Moser, W.H.J. Am. Chem. Soc. 2003, 125, 8228-8237.

HONHFmoc

DMP, CH2Cl2-H2O, rt

99% ee

NHFmoc

R99% ee

Swern: >95% (50% ee)TEMPO: >80 % (95% ee)

DMSO, rt86-100%

CH2Cl2, rt

Dehydrogenation of Saturated Aldehydes and Ketones with IBX

OIBX (2.0-3.0 equiv)

R1 R1DMSO

Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. J. Am. Chem. Soc. 2000, 122, 7596-7597.

Dehydrogenation of Saturated Aldehydes and Ketones with IBX

OIBX (2.0-3.0 equiv)

R1 R1DMSO, 65-85 C

Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. J. Am. Chem. Soc. 2000, 122, 7596-7597.

Mechanism of Dehydrogenation by IBX

• Single electron transfer is likely operative:

Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2002, 124, 2245-2258.

Applications in Total Synthesis

• Efforts toward the synthesis of Phomoidride B

IBXDMSO-Tol80 C, 3 h

CO2MeMeO2C O

Phomoidride B

Ohmori, N. J. Chem. Soc., Perkin Trans. 1 2002, 755-767.

Tandem Conjugate Addition/Dehydrogenation with IBX

Nicolaou, K. C.; Gray, D. L. F.; Montagnon, T.; Harrison, S. T.Angew. Chem. Int. Ed. 2002, 41, 996-1000.

IBXMPO =O

CuBrSMe2, RMgX;then TMEDA, TMSCl

IBXMPO (2 equiv)in DMSO, rt

THF, -78 to -25 C

not isolated

Tandem Conjugate Addition/Dehydrogenation with IBX

1. CuBrSMe2, RMgX;then TMEDA, TMSCl

THF, -78 to -25 C

2. IBXMPO (2 equiv)in DMSO, rt.

O O O O

90% 97% 94%

98% 98%

Cyclization of N-Aryl Amides Carbamates, and Ureas Using IBX

Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Barluenga, S.; Hunt, K. W.; Kranich, R.; Vega, J. A. J. Am. Chem. Soc. 2002, 124, 2233-2244.

IBX (4.0 equiv)

THF:DMSO (10:1)90 C

where X = CH2, O, NR

Cyclization of N-Aryl Amides and Carbamates Using IBX

IBX (4.0 equiv)

THF:DMSO (10:1)90 C

H H Br

NCO2Me

Mechanism

IBXSET N

5-exo-trig

Oxidation of Carboxamides to Nitriles

IBX (2.5 equiv)Et4N+ Br- (2.5 equiv)

CH3CN, 60 CR CN + CO2

Bhalerao, D. S.; Mahajan, U. S.; Chaudhari, K. H.; Akamanchi, K. G. J. Org. Chem. 2007, 72, 662-665.

Oxidation of Carboxamides to Nitriles

CNS CN

75% 85% 95% 72% 80% 60%

IBX (2.5 equiv)Et4N+ Br- (2.5 equiv)

CH3CN, 60 CR CN + CO2

Proposed Mechanism

HN RR CN

Conclusions

• Hypervalent Iodine compounds are versatile reagents that can promote a number of different transformations

• Alternative to toxic metal reagents

• Disadvantages: – Enantioselective transformations are largely

elusive– Safety concerns with some reagents

Acknowledgements

Cory BauchAshley BermanMary Robert NahmJustin PotnickRebecca Duenes

Matthew CampbellShanina SandersAndy SatterfieldSteve GreszlerChris Tarr

The Johnson Research Group:

Prof. Jeff Johnson

Greg BoyceGeanna MinDan SchmittMike SladeAustin Smith

Mechanism of Tandem Conjugate Addition/Dehydrogenation with IBX

Mechanism of THF Activation

Support of a SET Mechanism in IBX Mediated Dehydrogenations

Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2002, 124, 2245-2258.

• Hammet analysis shows the reaction is only slightly dependent on the electronics of aryl-containing substrates (ρ= -.75, σp

Support of a SET Mechanism in IBX Mediated Cyclizations

1. SET

2. 5-exo-trig N

-Hrearomatization

Support of a SET Mechanism in IBX Mediated Cyclizations

PhSBu3SnH

AIBN (cat.)

Nomenclature• Hypervalent compounds are characterized according to

the Martin-Arduengo designation, N-X-L, where:– Number of valence electrons, N– Identity of the hypervalent atom, X– Number of ligands, L

• For example, (diacetoxyiodo)benzene:

I(OAc)2

(diacetoxyiodo)benzene10-I-3

Oxygenation of Silyl Enol Ethers

• Typically assisted by a Lewis acid catalyst

• Similar reactions can be carried out using Tl(lll)– Highly toxic– Tl(III) is approximately three times more expensive

than I(III)

OTMS PhIO, BF3OEt2, ROH

Moriarty, R. M.; Duncan, M. P.; Prakash, O. J. Chem. Soc. Perkin Trans. 1 1987, 1781-1784.

Hydroxylation of Silyl Enol Ethers

Me Cl O2N

65% 72% 68% 70%

74% 78% 80% 83%

OTMS PhIO, BF3OEt2, H2O

OH0 C, 4h

Mechanism of Hydroxylation

• Similarly to the α-hydroxylation of ketones, the reaction initiates through a nucleophilic attack at I(III)

• A second nucleophilic attack on the I(III) bearing followed by elimination affords PhI and the product

OR3Si I Ph

+H + -OBF2

Progress Towards Asymmetric α-Hydroxylation of Ketones

tBu tBu

Cl tButBu

SiR2Me2

1. 1 (7 mol %), PhIO (1.5 equiv)PPNO (0.3 equiv), CH2Cl2

2. HCl, MeOH

Adam, W.; Fell, R. T.; Stegmann, V. R.; Saha-Moller, C. R. J. Am. Chem. Soc. 1998, 120, 708-714.

• Reaction is hampered by low conversion• Only modest enantioselectivity obtained

Progress Towards Asymmetric α-Hydroxylation of Ketones

Adam, W.; Fell, R. T.; Mock-Knoblauch, C.; Saha-Moller, C. R. Tetrahedron Lett. 1996, 37, 6531-6534.Adam, W.; Fell, R. T.; Stegmann, V. R.; Saha-Moller, C. R. J. Am. Chem. Soc. 1998, 120, 708-714.

81% (56% ee) 81% (60% ee) 35% (18% ee)

92% (39% ee)

54% (67% ee)

When SiR3 = TMS

When SiR3 = TBS

(R,R-1)

(S,S-1)(S,S-1)(S,S-1)

tBu tBu

Cl tButBu

α-Oxygenation of Silyl Enol Ethers• In a similar fashion, other oxygen nucleophiles can be employed:

PhIO, TMSOTf

OTfCH2Cl2, -78 C to rt

Moriarty, R. M.; Epa, W. R.; Penmasta, R.; Awasthi, A. K. Tetrahedron Lett. 1989, 30, 667-669.

• Synthesis of (±)-Cephalotaxine

Yasuda, S.; Yamada, T.; Hanoaka, M. Tetrahedron Lett. 1986, 27, 2023-2026.

(PhIO)nMeOH, KOH

(±)-Cephalotaxine

2 stepsOH

ATP Lit Seminar5

Documents

watch Richard Gasquet - atp dubai resultados 2015 - 2015 atp dubai scores - atp dubai 2015 - -

Fixing Army Doctrine - Army University Press · Fixing Army Doctrine ... ATP 3-09.24 ATP 3-09.30 ATP 3-09.32 ATP 3-09.34 ATP 3-09.2 ATP 3-09 ... through every FM and ATP until he

5 esp seminar5-revisionclass_june14

How to watch - Roger Federer - atp dubai streaming 2015 - 2015 dubai atp - atp dubai live 2015 - -

The pay-off phase Generates 4 ATP, 2 ATP/pyruvatecourses.chem.indiana.edu/c483/documents/Lecture30_glycolysispart2.… · • Generates 4 ATP, 2 ATP/pyruvate ... • Regulates the

AdenineRibose3 Phosphate groups ATP Adenosine ATP Structure ATP = Adenosine TriPhosphate High Energy Bonds

Men's Singles - ATP ranking, Shadow ATP ranking, …s3.amazonaws.com/ustaassets/assets/689/15/atp_shadow...2018/12/11 · Men's Singles - ATP ranking, Shadow ATP ranking, and Shadow

ATP Presentation Series Pavement Materials Selection Process Presentation Series... · ATP-1 ATP-2 ATP-3 ATP-4 ATP-6 ATP-7 ATP-8 Metro Statewide ... •Double chip seal •ThinLay

ATP DDR3 DRAM Solutions - ATP Electronics

Energy source for contraction ATP ADP + Creatine phosphate = ATP ATP is constantly broken down and rebuilt

ATP Piper Seminole Training Supplement - ATP Flight … Piper Seminole Training Supplement - ATP Flight School

Cellular Respiration (Making ATP from food) crash-course-bio ATP crash-course-bio ATP crash-course-bio ATP

The Structure Adenine and Hydrolysis of ATP - NSLC Lecture.pdfThe Structure and Hydrolysis of ATP ... • In the cell, ... 2 2 FADH 2 or + 2 ATP + 2 ATP + about 26 or 28 ATP Glycolysis

ApoTox-Glo Triplex Assay - Fisher Scientific„¢ Triplex Assay Sensitive, non- lytic, fluorescent assays quantitate live and dead ... ATP ATP. ATP. ProCaspase-3. Caspase-3. ATP. ATP

Lit & Comp: Women and Lit

watch Andy Murray - atp dubai rezultati 2015 - 2015 atp tour dubai - atp dubai championships 2015 - -

ATP Industrial Grade SD Card Specification v1 · 2019. 10. 13. · 5 ATP Confidential & Proprietary 1 ATP Industrial Grade microSD/microSDHC Card Overview 1.1 ATP Product Availability

[Seminar5] PM Counters

Key Concepts ATP structure ATP – ADP cycle Caloric Values

CHARACTER RECOGNITION - University of Ljubljanalab.fs.uni-lj.si/lasin/wp/IMIT_files/neural/doc/seminar5.pdf · classification with MATLAB INTRODUCTION Character recognition, ... It