Photochemical Reactions as Key steps In Organic Synthesis

Photochemical Reactions as Key steps In Organic Synthesis

Photochemical Reactions as Key steps
In Organic Synthesis.
Romain Blanc
Seminaire 29.05.08
Contents
Introduction
Photocycloadditions :
a) [2+2]
a.1) cyclobutane in natural product
a.2) cyclobutane fragmentation
a.3) the De Mayo reaction
a.4) Paternò-Büchi photocycloaddition
b) [4+2]
c) [5+2] and [4+4]
d) aromatic compound
Photochemical rearrangement
Conclusion
2
Introduction
Generalities :
2 options to induce radical reactions :
• Photochemical (light as energy source) : hν
• Thermochemical (∆ as energy source) : peroxyde, diazo…
Radical stability :
CH2
85 kcal
>
>
91 kcal
H
H
> > >
H
H
95 kcal
H
96 kcal
H
100 kcal
H
108 kcal
>
R O
110 kcal
3
Introduction
Photochemistry :
- initiated by light
- Chemically useful light is generally in the range of 200-400nm
- Absorption of a photon induce an electronic transition
(ground state
excited state)
usually C=O and C=C
LUMO
HOMO
π∗
π∗
π∗
n
n
n
π
π
ground
state
∗
π
n to π
singlet
π∗
∗
n to π
triplet
π
π∗
∗
π
π to π
singlet
π to π∗
triplet
4
C=O
C=C
Introduction
Rayonet (New England Ultraviolet & Co)
Immersion hν reactor
external irradiation
Internal irradiation
5
Introduction
Why using photochemical reaction in total synthesis ?
advantages :
- obtention complex, polycyclic, or highly functionalised structures
- form thermodynamically disfavoured products
- diminish formation of byproducts
- often occurs without additional reagents
- the reagent is cheap (sunlight), easily accessible and renewable
constraints :
- wavelength choice
- reactivity is often unpredictable
- many substrates are not compatible
- solvant choice
- material expensive
6
1) PHOTOCYCLOADDITION
The Woodward-Hoffmann-Fukui rules of
cycloadditions
Number of
Electrons
Mode of activation
Dewar-Zimmerman
4n
thermal
photochemical
suprafacial (pair)
antarafacial (impair)
4n + 2
thermal
photochemical
antarafacial
suprafacial
n : an integer
[Π 2s + Π 2a]
antarafacial
[Π 4s + Π 2s]
suprafacial
(a) R. B. Woodward, R. Hoffmann, J. Am. Chem. Soc. 1965, 87, 395 (b) R. B. Woodward, R. Hoffmann, J. Am. Chem.
Soc. 1965, 87, 2046 (c) R. B. Woodward, R. Hoffmann, Acc. Chem. Res. 1968, 1, 17 (d) R. B. Woodward, R. Hoffmann,
Angew. Chem. Int. Ed. 1969, 8, 781
7
1) PHOTOCYCLOADDITION
• [2+2] photocycloadditions :
with 1 alkene and 1 α,β−unsatured carbonyl :
O
O
O
hν
+
R
R
R
CH2
R = Alkyl, O-alkyl
with 1 alkyne and 1 alkene :
hν
+
with 1 allene and 1 alkene :
•
hν
+
8
1) PHOTOCYCLOADDITION
a.1) Cyclobutane-containing natural product :
[2+2] Intermolecular
Me
H
Me
O
Me
O
H
hν
H
H
+
H
DCM, r.t
H
H
Me
H
Me
Me
(±)-kelsoene
E. Piers, A. Orellana, Synthesis. 2001, 2138
O
O
O
Cl
+
Cl
O
acetone,
benzophenone
85%
O
Cl
hν
O
O
Cl
HO
O
O
O
O
Merrilactone A
M. Inoue, T. Sato, M. Hirama, J. Am. Chem. Soc. 2003, 125, 10772
9
1) PHOTOCYCLOADDITION
a.1) Cyclobutane-containing natural product :
[2+2] Intramolecular
OMe O
OMe O
hν
(λ = 350 nm)
O
Me
O
OMe O
H
H
+
DCM
O
Me
H
O
O
Me
H
(−)-elecanacin
25%
O
H
(−)-isoelecanacin
38%
L. B. Nielsen, D. Wege, Org. Biomol. Chem. 2006, 868
HOOC
H
O
hν
(λ = 300 nm)
O
O
O
OBn
PhH/ acetone
9:1, r.t, 5h
60%
O
O
H
OBn
O
O
O
OH
HO
O
O
OMe
O
Solanoeclepin A
B. T. B. Hue, J. Dijkink, S. van Schaik, J. H. van Maarseveen, H. Hiemstra, Eur. J. Org. Chem. 2006, 127
10
1) PHOTOCYCLOADDITION
a.2) Cyclobutane fragmentation :
[2+2] Intermolecular
•
O
(±)-pentalenene
+
hν
pyrex
TiCl4
DCM
86%
DCM
92%
O
O
O
Mechanism :
H
H
A.L
O
O
A.L
OA
OA
O
T. Morimoto, T. Horiguchi, K. Yamada, K. Tsutsumi, H. Kurosawa, K. Kakiuchi, Synthesis. 2004, 753
11
1) PHOTOCYCLOADDITION
AcO
a.2) Cyclobutane fragmentation :
Me
Me
OH
Me
H
OH
H
[2+2] Intermolecular
MeO2C
H
O
+
H
HO
hν
pyrex, 0 °C
MeO2C
O
O
H
dodecane, BHT
H
51%
OAc
H
O
Fusicoplagin A
OH
OH
MeO2C
H
Benzene, 235 °C
70%
H
OH
Mechanism :
MeO2C
O
O
H
∆
MeO2C
H
H
H
OH
OH
M. L. Randall, P. C. K. Lo, P. J. Bonitatebus Jr, M. L. Snapper, J. Am. Chem. Soc. 1999, 121, 4534
P. C. K. Lo, M. L. Snapper, Org. Lett. 2001, 3, 2819
12
1) PHOTOCYCLOADDITION
H
a.2) Cyclobutane fragmentation :
H
Me
HO
NMe
H
[2+2] Intramolecular
(−)-incarvilline
O
NTs
H
H
hν
acetone
H
O
53%
H
SmI2
NTs
THF, DMPU
H
H
O
Me
NTs
H
Mechanism :
H
H
I2Sm
O
H
NTs
H
I2Sm
O
H
H
CH2
NTs
H
M. Ichikawa, S. Aoyagi, C. Kibayashi, Tetrahedron Lett. 2005, 46, 2327
13
1) PHOTOCYCLOADDITION
O
O
a.2) Cyclobutane fragmentation :
OH
O H
O
O
H
HO
O
OH
[2+2] Intramolecular
O
Ginkgolide B 1
O
CO2Et
O
O
hν
(λ > 350 nm)
CO2Et
1) PPTS
PhH, reflux
O
O
H
O
100%
O
2) SePhCl, HCl
NaIO4, EtOAc
Me3SiO
Et3SiO
O
tBu
dimethyldioxirane
H2O, acetone
94%
O
O
O
H
O
OH
O
OH
tBu
O
OH
O
H OH
H
O
O
OH
tBu
O
O
O
H
O
p-TsOH
O
OH
tBu
OH
O
H
O
O
H2O
O
tBu
M. T. Crimmins, J. M. Pace, P. G. Nantermet, A. S. Kim-Meade, J. B. Thomas, S. H. Watterson, A. S. Wagman,
14
J. Am. Chem. Soc. 2000, 122, 8453
1) PHOTOCYCLOADDITION
a.3) The De Mayo reaction :
O
H
O
O
hν
+
retro-aldol
O
O
OH
P. De Mayo, H. Takeshita, A. B. M. A. Sattar, Proc. Chem. Soc. London. 1962, 119
P. De Mayo, H. Takeshita, Can. J. Chem. 1963, 41, 440
Example :
O
O
N
O
H
O
O
OH
hν
H
H
N
MeCN
72%
O
O
N
O
O
H
H
Piperidine,
benzene, reflux
78%
OH
N
galanthane tetracyclic skeleton
O
15
D. E. Minter, C.D. Winslow, J. Org. Chem. 2004, 69, 1603
1) PHOTOCYCLOADDITION
a.4) The Paternò-Büchi reaction :
O
hν
+
O
O
E. Paternò, G. Chieffi, Gazz. Chim. Ital. 1909, 39, 341
Example :
EtO
O
O
Me
O
hν
O
MeCN
93%
EtO
O
O
O
HO
O
O
O
O
Merrilactone A
J. Iriondo-Alberti, J. E. Perea-Buceta, M. F. Greaney, Org.Lett. 2005, 7, 3969
16
1) PHOTOCYCLOADDITION
b) [4+2] photocycloadditions :
OH
α
β
OH
O
α
O
hν
H
H
H
OH
H
H
β
91%
O
α
+
H
OH
H
β
O
H
2:1
OH
O
O
H
O
H
(±)-5-epi-10-epi-Visbarin E
H. M. L Davies, Ο. Loe D. G. Stafford, Org.Lett. 2005, 7, 5561
17
1) PHOTOCYCLOADDITION
O
c) [5+2] Photocycloadditions :
N
H
HO
OMe
(–)-cephalotaxine
HO
O
O
hν
MeCN
73%, dr = 3.5:1
N
N
O
H
HO
O
O
O
N
O
N
H
O
O
OH
H
K. I. Booker-Milburn, L. F. Gray, C. E. Anson, S. D. Guile, Org.Lett. 2001, 3, 3005
18
1) PHOTOCYCLOADDITION
HH
c) [4+4] Photocycloadditions :
H
HO
H
Ceroplastol
OTBS
N
Me
O
hν
pyrex
MeN
OCH3
methanol
MeN
HO OH O
OTBS
MeN
O OTBS
OsO4
Me
Me
O
NMe
OCH3
97%
O
O
NMe
OH
O
Y.-g. Lee, K. F. McGee, Jr, J. Chen, D. Rucando, S. M. Sieburth, J. Org. Chem. 2000, 65, 6676
19
1) PHOTOCYCLOADDITION
d) photocycloadditions with aromatic compound :
for these compounds :
- a strong tendency to lose aromaticity at the excited state
- 3 types of photocycloaddition [2+2], [3+2], [4+2]
R
ortho
[2+2]
R
R
+
hν
metha
R
[3+2]
R
R
para
[4+2]
R
R
20
1) PHOTOCYCLOADDITION
HO
OH
[3+2] photocycloaddition :
H
HO
H
OH
Aphidicoline
MeO
2
5
3
4
1
hν
(λ = 254 nm)
5
6
90%
8
OH
7
MeO
4
6
2
3
1
2
1
7
8 OMe
H
H
OH
MeO
4
3
H
2
H
H
OH
3
4
5
6
6
8
8
OH
OMe
+
1:1.2
1
5
H
7
OH
7
J. W. Boyd, N. Greaves, J. Kettle, A. Russel, J. W. Steed, Angew. Chem. Int. Ed. 2005, 44, 944
21
2) REARRANGEMENTS
a) Example of pericyclic reaction :
N
H
(S)-Pipecoline
O
hν
(λ = 254 nm)
N
O
Ph
N
O
N
50%, de = 75%
NaBH4
Ph
O
N
Ph
[3+2]
Ph
F. Bois, D. Gardette, J.-C. Gramain, tetrahedron. Lett. 2000, 122, 8769
• transformation of cyclopropylimine into pyrroline :
Ph
hν
pyrex
Ph
80%
N
Ph
N
Ph
D. Sampedron, P. J. Campos, A. Soldevilla, M. A. Rodriguez, M. Olivucci, J. Am. Chem. Soc. 2005, 127, 441
22
2) REARRANGEMENTS
b) [4+2] photorearrangement :
Ar
E
Me
hν
Me
Ar
60%
Ar
E
Me
O
Me
Me
Me
Me
E
OMe
OMe
O
Me
Me
Me
O
Me
crispatene
J. E. Moses, J. E. Baldwin, R. Marquez, R. M. Adlington, T. D. W. Claridge, B. Odell, Org.Lett. 2003, 5, 661
23
2) REARRANGEMENTS
• Norrish-Yang reaction : H atom in the γ position
O H
R'
1
O
hν
H
OH
shift
R
R
1
R'
R'
R
1-5 H
OH
+
R'
R
3
3
O
R
H
R'
shift
1-5 H
OH
R'
R
OH R'
R
24
2) REARRANGEMENTS
• Norrish-Yang reaction : examples
H
H2NOC
H
N
iPr
N
H
O
iPr
1) hν
crystal
O
N
HO
O
2)CH2N2
conv 99%
COO
CO2Me
94%, 99% ee
J. R. Scheffer, K. Wang, Synthesis. 2001, 1253
O H
Ph
hν
(λ > 300 nm)
OH
Ph
Ph
OMs
OMs
O
O
-HOMs
86%
Ph
H
H
P. Wessig, O. Mühling, Angew. Chem. Int. Ed. 2001, 40, 1064
25
2) REARRANGEMENTS
• di-π−methane rearrangement :
R
R
hν
R
R
R
R
R
R
• Examples :
Cl
Cl
Cl
Cl
hν
(λ = 300 nm)
O
O
O
94%
O
O
O
O
O
O
O
O
O
V. Nair, M. V. Nandakumar, G. N. Anikumar, D. Maliakal, M. Vairamani, S. Prabhakar, N. P. J. Rath,
J. Chem. Soc. Perkin Trans. 1. 2000, 3795
26
2) REARRANGEMENTS
• oxa di-π−methane rearrangement :
R
R
R
hν
R
O
O
R
R
R
R
O
O
• Examples :
O
O
OMe
OMe
H
O
MeO
92%
O
O
OMe
OMe
O
O H
H
hν
(λ = 300 nm)
H H
OMe
N
H H
OH
Magellanine
O
OMe
OMe
O
O
OMe
OMe
O
27
C.-F, Yen, C.-C, Liao, Angew. Chem. Int. Ed. 2002, 41, 4090
2) REARRANGEMENTS
• example of hydroxyquinodimethane derivative
OMe O
H
CO2Me
OMe OH
CO2Me
OMe OH
CO2Me
hν
91%
H
OMe O
Br
OMe O
OH
CO2Me
O
or
H
5-epi-Hamigerane A
Br H
5-epi-4-Bromohamigerane B
K. C. Nicolaou, D. Gray, J. Tae, Angew. Chem. Int. Ed. 2001, 40, 3679
28
Conclusions
• access to polycyclic complex molecules
• installation of quaternary carbons atoms
• stereocontrol of multiple stereocenter
• powerfull set of fragmentation
Perspectives
• asymmetric reaction
• using solar ligth for green chemistry
29
References
Norrish-Yang reaction :
Wagner, P. J. In Molecular and Supramolecular Photochemistry; Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New York, 2005; Vol. 12: Synthetic Organic Photochemistry
(Griesbeck, A. G.; Mattay, J.; Eds.), p 11.
Wessig, P.; Mu¨hling, O. In Molecular and Supramolecular Photochemistry; Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New York, 2005; Vol. 12: Synthetic Organic
Photochemistry (Griesbeck, A. G., Mattay, J., Eds.), p 41.
di-π−methane rearrangement :
Demuth, M. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, p 215. (b) Demuth, M. In Organic
Photochemistry; Padwa, A., Ed.; Marcel Dekker: New York, 1991; Vol. 11, p 37. (c) Singh, V. In CRC Handbook of Organic Photochemistry and Photobiology, 2nd ed.; Horspool,
W., Lenci, F., Eds.; CRC Press: Boca Raton, 2004; Chapter 78. (d) Rao, V. J.; Griesbeck, A. G. In Molecula and Supramolecular Photochemistry; Ramamurthy, V., Schanze, K. S.,
Eds.; Marcel Dekker: New York, 2005; Vol. 12: Synthetic Organic Photochemistry (Griesbeck, A. G.; Mattay, J.; Eds.), p 189.
oxa di-π−methane rearrangement :
Zimmerman, H. E. In Organic Photochemistry; Padwa, A., Ed.;Marcel Dekker: New York, 1991; Vol. 11, p 1. (b) deLucchi, O. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, p 193. Zimmerman, H.; Armesto, D. Chem. ReV. 1996, 96, 3065. (c) Armesto, D.; Ortiz, M. J.; Agarrabeitia,
A. R. In Molecular and Supramolecular Photochemistry; Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New York, 2005; Vol. 12: Synthetic Organic Photochemistry
(Griesbeck, A. G., Mattay, J., Eds.), p 161. See also: (d) Tsuno, T.; Sugiyama, K. In CRC Handbook of Organic Photochemistry and Photobiology, 2nd ed.; Horspool, W., Lenci, F.,
Eds.; CRC Press: Boca Raton, 2004; Chapter 30.
Reviews
N. Hoffmann, Chem. Rev. 2008, 108, 1052
J. Iriondo-Alberti, M. F. Greaney, Eur. J. Org. Chem. 2007, 4801
30