reversible generation of carbenes and nitrenes using ...€¦ · carbenes and nitrenes using...

Reversible Generation of Carbenes and Nitrenes using

Hypervalent IodineHypervalent Iodine

Kumar AshtekarMichigan State University

September 16, 2009.

1

Spin States of Carbene and Nitrene

Moss, R. A.; Platz, M.; Maitland, J. Reactive Intermediate Chemistry, Wiley, 2004, p330-331Clayden, J.; Greeves, N.; Warren, S.; Wothers. Organic Chemistry, Oxford, 2001.

2

Hypervalent Iodo-organic Compounds

Perkins, C. W.; Martin, J. C.; Arduengo, A. J.; Lau, W.; Alegria, A.; Kochi, J. K. J. Am. Chem. Soc. 1980, 26, 7753-59.3

Nomenclature

4Perkins, C. W.; Martin, J. C.; Arduengo, A. J.; Lau, W.; Alegria, A.; Kochi, J. K. J. Am. Chem. Soc. 1980, 26, 7753-59.

λ3 – Iodanes Used in Generation of Carbene/Nitrene

IL

L IO

Iodosobenzene

(III)

ILL

8-I-2

ICl

ClIOAc

(III) (III) Iodanes

L10-I-3

Cl OAcDichloroiodo-

benzeneIodobenzene

diacetate

IL

LL

LO

IHO

O

SO

I

O

HOO

O10-I-4 OIBX Super IBX

LL L IOAc

OAcAcO

OO

ILL

LL

12-I-5

OI

ODess Martin

5Perkins, C. W.; Martin, J. C.; Arduengo, A. J.; Lau, W.; Alegria, A.; Kochi, J. K. J. Am. Chem. Soc. 1980, 26, 7753-59.

Dess MartinPeriodinane

Reversible Generation of Carbenes and Nitrenes

Irreversible

6

Bonding in λ3- Iodanes

Three centered four electron bonding

Antibonding orbital

Non-bonding orbital

λ3 – Iodanes (10-I-3)

Bonding orbital

( )sp2 hybridized iodine

5s 5p

Wirth, T. Topicis in Current Chemistry: Hypervalent Iodine Chemistry. Vol. 224. Springer. 2003. 7

Bonding in λ3- Iodanes

Three centered four electron bonding

Antibonding orbital

Non-bonding orbital

Bonding orbital

λ3 – Iodanes (10-I-3)( )sp2 hybridized iodine

Ability to sustain the partial positive charge makes λ3 – Iodanes more stable than λ3 – Bromanes or Chloranes.

Wirth, T. Topicis in Current Chemistry: Hypervalent Iodine Chemistry. Vol. 224. Springer. 2003. 8

Standard Oxidation Potentials

Pauling’s Oxidation StatesElectronegativity -I 0 +I +V

I2 2.5 -0.62 -1.44* -1.19* [Eo] Volts

Br2 2.8 -1.09 -1.60* -1.50* [Eo] Volts

Cl2 3.0 -1.40 -1.61* -1.47* [Eo] Volts

F 4 0 2 87 [Eo] V ltF2 4.0 -2.87 -- -- [Eo] Volts

[Eo] = Standard Reduction Potential*V l ti t d t it ti it f H+

Lee, J. D. Concise Inorganic Chemistry. 5th ed. Wiley. 2008, p. 582-633.

*Values estimated at unit activity of H+

9

Synthetic viability of λ3- Iodanes

Iodobenzene DiacetoxyIodobenzene

IodosobenzeneDichloro-

Iodobenzene

Sharefkin, J. G.; Saltzman, H. Org. Syn. Coll. Vol. 5, p.660,1973.J.Chem. Res.1982, 6, 1649-1660. 10

• How can Hypervalent Iodine compounds be better precursors for carbenes and nitrenes?better precursors for carbenes and nitrenes?

11

Diazo and azido-compounds: Conventional precursors of carbenes/nitrenes

R2

OR

R2 O

O

R

H

H

• Potentially Explosive

C i i

R2

OR2CO2HH

• Carcinogenic

R

R2R2 X R R2

XHX = O, N-R3 R[M]

R2

XR3

R2X

[M]RN2

3

NR3

R3 R2

O

R[M]R

XR3

-N2

N R2 HR3

R

R2

R2

R3

R2 X

Ylide Chemistry

NN R2

H

R2

ON2

R3R R

Fulton, J. R,; Aggarwal, V. K,; Javier de Vicente. Eur. J. Org. Chem. 2005, 1479–1492.Bretherick, L. Handbook of Reactive Chemical Hazards, 3rd. ed,; Butterworth: London, 1985. 12

Reversibility in Generation of Carbenes/Nitrenesusing Hypervalent Iodineg yp

[M]

[M]

Iodonium ylideor Δ

[M]

Iminoiodinane [M] Rh(II) C (I)Iminoiodinane [M] = Rh(II), Cu(I)

13

Proposal for Non-Carbene Character inIodonium Ylides

Possible transient carbene

Moriarty, R. M.; OmPrakash.; Vaid, R. K.; Zhao, L. J. Am. Chem. Soc. 1989, 111, 6443-6444. 14

Proposal for Non-Carbene Character inIodonium Ylides

Actual Proposed mechanism


Basis for proposing Non-Carbene Character inIodonium Ylides

A] Products arising from Wolff rearrangement were not observed

O O

OMe CuCl (1-2 mol%)

O CO

COOMeIPh

OMe ( )

CH2Cl2, 0 C COOMeCOOMe

Wolff - RearrangementH2O

COOHCOOH

COOMe

t b dnot observed



B] Iodonium Ylides can undergo cycloaddition reaction with CS2 via ionic intermediates.

Papadopoulou, M.; Spyroudis, S.; Varvoglis, A. J. Org. Chem. 1985, 50, 1509-1511.17


C] Iodonium Ylides can undergo cycloaddition reaction with alkenes via ionic intermediates.

O O OO2N IPh

CH3CN, h

O2N IPh

O2N IPh

NO2 NO2 NO2

- IPh

OO2N

O

NO2

Spyroudis, S. J. Org. Chem. 1986, 51, 3453-3456.18


Moriarty, R. M.; OmPrakash.; Vaid, R. K.; Zhao, L. J. Am. Chem. Soc. 1989, 111, 6443-6444.19

Experiment that could have been performed to estimate carbene character in the Iodonium ylide

20

Evidence for Carbene Character

"Dimerization"

Hood, N. C.; Lloyd, D.; Shephard, M. T. Tetrahedron. 1982, 38, 3355-3358.March, J. Advanced Organic Chemistry, 4th ed. Wiley, 1992, p.201.

21

Proof for Carbene Character & its Spin Multiplicity

Camacho, M. B.; Clark, A. E.; DeLuca, J. P. J. Am. Chem. Soc. 2000, 122, 5210-11. 22

Stereochemical outcome and spin state of carbene

RRHH

RRHH

CR'

R'

HH

R' R'cis

R'

Singlet Carbene

RRHH

RRHH

R' R'RRHH

R'

RRHH

R'

R'R'cis

R R

HR

HH

spin flip

t ti

Triplet Carbene

CR'

R R'HRRH

R'

HRRH

R' R'

rotationalong

C-C bond

Clayden, J.; Greeves, N.; Warren, S.; Wothers. Organic Chemistry, Oxford, 2001. Skell, S. C.; Woodworth. R.C.J. Am. Chem. Soc.1956, 78, 4496-4497.

p R R' trans

23

Approach of a carbene to a π-system of alkenes

Bonding interaction Bonding interactionR H R H

CR'

R' CR'

R'

R H

RHOMO LUMO

Antibonding interaction Antibonding interaction

LUMO HOMOR H R H

R H

C

R' R'

C

R' R'Bonding interaction Bonding interaction

R H

R HHOMO

C

LUMO

C

HOMOLUMOR H

Clayden, J.; Greeves, N.; Warren, S.; Wothers. Organic Chemistry, Oxford, 2001. 24

Proof for Carbene Character & its Spin Multiplicity

Camacho, M. B.; Clark, A. E.; DeLuca, J. P. J. Am. Chem. Soc. 2000, 122, 5210-11. 25

Hammett Correlation

Muller, P.; Fernandez, D. Helv. Chim. Acta. 1995, 78, 947-958.26

Hammett Correlation

ρ = 0 47 (for 1a)0.4

0.5k A

r/kPh

)

ρ = -0.47 (for 1a)

ρ = -0.49 (for 1b)0.1

0.2

0.3

Y σ+

log(

k

-0.1

0

0.1

-1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8

Y σ+

H 0p-Me -0.31

σ+

-0 4

-0.3

-0.2p

p-OMe -0.78p&m-OMe -0.66

m-NO2 0.71

-0.5

0.4


2

Significance of Hammett Reaction Constant (ρ)

28Clayden, J.; Greeves, N.; Warren, S.; Wothers. Organic Chemistry, Oxford, 2001.

concerted

Hammett Correlation

ρ = 0 47 (for 1a)0.4

0.5k A

r/kPh

)

ρ = -0.47 (for 1a)

ρ = -0.49 (for 1b)0.1

0.2

0.3

Y σ+

log(

k

-0.1

0

0.1

-1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8

Y σ+

H 0p-Me -0.31

σ+

-0 4

-0.3

-0.2p

p-OMe -0.78p&m-OMe -0.66

m-NO2 0.71

-0.5

0.4


2

Transfer of Carbene on Metal Co-ordination Sphere

[α]D22 = +5.9

Muller, P.; Allenbach, Y.; Robert, E. Tetrahedron: Asymmetry. 2003, 14, 779-785. 30

Intramolecular C-H Insertion

Muller, P.; Bolea, C. Helv. Chim. Acta. 2002, 85, 483-494.D. F. Taber, E. M. Petty, K. Raman, J. Am. Chem. Soc. 1985, 107, 196-199.

A. G. H. Wee, Q. Yu, Tetrahedron. Lett. 2000, 41, 587. 31

Intramolecular C-H Insertion

[Catalyst] Solvent, T 0C Time Yield of (R)-4 [α]D20 e.e.[%]

(R)-1 [Rh2(OAc)4] CH2Cl2, 23 30 min 59% 10.2 >98

(R)-1 [Cu(hfa)2] (CH2Cl)2, 60 3 h 54% 10.1 >98

(R)-2 [Rh2(OAc)4] CH2Cl2, 0 3 h 57% 10.0 >98

(R)-2 [Cu(hfa)2] CH2Cl2, 0 3 h 36% 10.1 >98

Muller, P.; Bolea, C. Helv. Chim. Acta. 2002, 85, 483-494.D. F. Taber, E. M. Petty, K. Raman, J. Am. Chem. Soc. 1985, 107, 196-199.

A. G. H. Wee, Q. Yu, Tetrahedron. Lett. 2000, 41, 587. 32

Tuning of Reactivity in terms of Carbene Vs Ylide

OI

Rh2(OAc)4(1 mol%)RT (81%)

ORhLn

Cl O RhLn

Cl

O- PhI

O O

Cl Ph

321

OO

O

Cl

PhO Ph4

Lee, Y. R.; Jung, Y. U. J. Chem. Soc., Perkin Trans. 1 2002, 1309.Moriarty, R. M.; Tyagi, S.; Ivanov, D.; Constantinescu, M. J. Am. Chem. Soc. 2008, 130, 7564-7565.

33

Elucidation of Mechanism

(concerted process)*

75%(88.6% retention)

*Geometry optimization by Gaussian 98

Moriarty, R. M.; Tyagi, S.; Ivanov, D.; Constantinescu, M. J. Am. Chem. Soc. 2008, 130, 7564-7565. 34

at B3LYP/6-31 level.

Switching to Carbon Nucleophiles

Moriarty, R. M.; Tyagi, S.; Ivanov, D.; Constantinescu, M. J. Am. Chem. Soc. 2008, 130, 7564-7565. 35

Tuning of Reactivity in terms of Carbene Vs Ylide

36Moriarty, R. M.; Tyagi, S.; Ivanov, D.; Constantinescu, M. J. Am. Chem. Soc. 2008, 130, 7564-7565.

Intermolecular C-H Aminations

or

37


or

Kwart, H,; Khan, A. A.; J. Am. Chem. Soc., 1967, 89, 1950-1951 and 1951-1953.Cenini, S.; Gallo, E.; Penoni, A.; Ragainia, F.; Tollarib, S. Chem. Commun. 2000, 2265-2266.Liang,C.; Peillard, F.; Muller, P.; Dodd, R. H.; Dauban, P. Angew. Chem. Int. Ed. 2006, 45, 4641-4644.

Dick, A. R.; Sanford, M. S. Tetrahedron. 2006, 62, 2439 – 2463.38


or

Is it possible to get away with 1 equiv. by tuning the electronics to achive equilibrium ?

39


Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568. 40


NHTces NHTces NHTces NHTces

OAc

NHTces

N

NHTces NHTces

MeO

NHTces

COCF3 OTBS

MMe

74% 65% 51% 60%

Rh2(esp)2(2 mol%)

Me

Me

Me

NHTcesPhI(O2CtBu)2(2 mol%)

TcesNH2, PhH3h, 23 C (25%)

PhOAc

Me

PhOAc

Me NHTces

, ( )

PhI(O2CtBu)2

Rh2(esp)2(2 mol%)


99.9% e.e99.9% e.e TcesNH2, PhH3h, 23 C (10%)

Intramolecular Vs Intermolecular C-H Aminations


Radical Clock Studies



45Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568.

Radical Clock Studies (Conclusion)

or

47Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568.

Hammett Correlation & Competition Studies

0.6

0.8

k Ar/k

Ph)

ρ = -0.73

0 2

0.4 log(

k

0

0.2

1 2 0 8 0 4 0 0 4 0 8 1 2σ+

Ar σ+ Ar/Ph

p-OMe -0.78 5.0 : 1.0

‐0.4

‐0.2‐1.2 ‐0.8 ‐0.4 0 0.4 0.8 1.2 tBu -0.26 2.3 : 1.0

Br 0.15 1.0 : 1.0

CF3 0.61 1.0 : 2.3

Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568. 48‐0.6

3

NO2 0.79 1.0 : 2.6


NHTces NHTces NHTces NHTces

OAc

NHTces

N

NHTces NHTces

MeO

NHTces

COCF3 OTBS

MMe

74% 65% 51% 60%

Rh2(esp)2(2 mol%)

Me

Me

Me

NHTcesPhI(O2CtBu)2

(2 mol%)

TcesNH2, PhH3h, 23 C (25%)

PhOAc

Me

PhOAc

Me NHTces

, ( )

PhI(O2CtBu)2

Rh2(esp)2(2 mol%)

Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568.

99.9% e.e99.9% e.e TcesNH2, PhH3h, 23 C (10%)

49

Application towards Total Synthesis

SOO

Rh (esp) SOO NH

NMbs

H2NO

NH2

O

14 steps

OO

OS

H2N Rh2(esp)2(0.3 mol%)

PhI(OAc)2M O CH Cl

OO

OS

HN

N

NH

NMbs

O14 steps

(+) Glycerolacetonide

MgO, CH2Cl2(76%)

NH

NMbsO O

NH

NHH2NO

NH2

O

NHNHO

HO

NH2 O NH2

HN

2(C3F7CO2 )3 steps

NH

NH

NMbs

HONHHN

H2N (+)-saxitoxin

50Fleming, J. J.; McReynolds, M. D.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 9964-9975.

Getting Better Hold of the Equilibrium

NTsOOS

NH2

NTsO

(S)-nta = N

O

OCOOH

H (1) =

O

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 51

Getting Better Hold of the Equilibrium


Efficient Access to Allylic C-H AminationsNT

ORh2{(S)nta}4

(3 mol%)1.2 equiv. (1)R

R'

HH

R

R'

p-Tol SNH

NTs

R

R'

NHS

1.4 equiv. PhI(OCOtBu)2(Cl2CH2)2/MeOH: 3/1, -35 C

R' R' R'

(S)-nta = N

O

H

NHS NHS

82% 75%( )

OCOOH

H

Ph NHS Ph NHS

82%(87% e.e.)

75%(90% e.e.)

SNH2

NTsO

(1) =

Ph NHS Ph NHS

79% 85%(89% e.e.)

85%(94% e.e.)


Access to C-H Aminations in CycloalkanesNT

ORh2{(S)nta}4

(3 mol%)1.2 equiv. (1)

R'

HH

R'

p-Tol SNH

NTs

R'

NHSR R R

1.4 equiv. PhI(OCOtBu)2(Cl2CH2)2/MeOH: 3/1, -35 C

R R R'

(S)-nta = N

O

H

NHS NHS

OCOOH

H

48% 66%

SNH2

NTsO

(1) =NHS

83%83%


Mechanism of C-H Insertion of the Metallonitrene


Kinetic Resolution

Without EquilibriumQuenching reaction at 50% conversion

≤[A][ ]

[B][B]


Dynamic Kinetic Resolution

Under EquilibriumQuenching reaction after 100% conversion

s2 S 4 matched case

kSS[A]

s2t :

SS[ ]

t R2 :

kRSkSS

R

2 S 4 mismatched case[B] kRS[B]



If there was no Equilibrium

59

Its All About Reversibility!

[M]

Iodonium ylideor Δ

[M]

Iminoiodinane[M] = Rh(II), Cu(I)

60

Conclusions

• Iodonium ylides and Iminoiodinanes are excellent substitutesfor the diazo-precusors of carbenes and nitrenes.

• Their stability and ease of synthesis enhances the syntheticTheir stability and ease of synthesis enhances the synthetic viability.

• Their reversibility and capability to be tuned, opens access t l tito new explorations.

61

My Group

Babak, Chrysoula, Tanya, Aman, Atefeh, Arvind, Sarah,y fMercy, Roozbeh, Camille, Carmin,

Sing, Calvin, Wenjing, Dan,. Sing, Calvin, Wenjing, Dan,Xiaoyong, Stewart.

62

reversible generation of carbenes and nitrenes using ...€¦ · carbenes and nitrenes using...

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