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