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

Moriarty, R. M.; OmPrakash.; Vaid, R. K.; Zhao, L. J. Am. Chem. Soc. 1989, 111, 6443-6444. 15

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

Moriarty, R. M.; OmPrakash.; Vaid, R. K.; Zhao, L. J. Am. Chem. Soc. 1989, 111, 6443-6444. 16

Basis for proposing Non-Carbene Character inIodonium Ylides

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

Basis for proposing Non-Carbene Character inIodonium Ylides

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

Basis for proposing Non-Carbene Character inIodonium Ylides

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

Muller, P.; Fernandez, D. Helv. Chim. Acta. 1995, 78, 947-958.27

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

Muller, P.; Fernandez, D. Helv. Chim. Acta. 1995, 78, 947-958.29

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

Intermolecular C-H Aminations

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

Intermolecular C-H Aminations

or

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

39

Intermolecular C-H Aminations

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

Intermolecular C-H Aminations

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. 41

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

Intramolecular Vs Intermolecular C-H Aminations

Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568. 42

Intramolecular Vs Intermolecular C-H Aminations

Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568. 43

Radical Clock Studies

Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568. 44

Radical Clock Studies

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

Radical Clock Studies

Fiori, W. K.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562-568. 46

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

Intermolecular C-H Aminations

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

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 52

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.)

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 53

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%

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 54

Mechanism of C-H Insertion of the Metallonitrene

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 55

Kinetic Resolution

Without EquilibriumQuenching reaction at 50% conversion

≤[A][ ]

[B][B]

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 56

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]

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 57

Dynamic Kinetic Resolution

Liang,C.; Collet, F.; Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343-350. 58

Dynamic Kinetic Resolution

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