Professional Documents
Culture Documents
Photo Chemistry
Photo Chemistry
Sunlight (h) O
One Year
Carvone Carvonecamphor
Course content
Principles of photochemical reactions; Excited states and
their properties; experimental set up for photochemical
reactions(1); Several useful photochemical reactions and
their applications in organic synthesis (isomerization,
Patterno-Buchi reaction (1), Norrish type I and II
reaction(1), Photoreduction, Rearrangements: di-π-
methane, oxa di-π- and aza di-π-methane
rearrangements(2), Photocycloaddition (2), Photochemical
aromatic substitution reaction (1), Reactions with singlet
oxygen (1), Photochemical methods for protection and
deprotection(2). Photochemistry of biological systems
(photosensitized reactions of DNA/RNA, DNA damage and
repair-1).
Books
• CRC Handbook of Photochemistry and
Photobiology. Eds by. William M. Horspool
and Pill-Soon Song. 1994. CRC Press.
ISBN: 0-8493-8634-9
• Synthetic organic photochemistry. Eds by.
William M. Horspool, Plenum press. 1984.
ISBN: 0-306-41449-X
Organic E = h
Compound Excited electronic states
(selective excitation)
Photo products
Thermally activated state
(change in vibrational, rotational and
transtational energy levels which is governed
by Boltzman distribution law)
h
R P
h
R R* I P
h ISC
1R*
R 3R* 3I 1I P
Antibonding orbital (*, *)
E2 E2>E1
E Atomic orbital
E1
Bonding orbital (, )
*
Anti bonding
*
E
non bonding (n)
Bonding
E2>E3>E1
n-* (E3)
Functional group
Bonding
S0 S1 T1
S0 S1 T1
Excited states
X
(S2)
10-11s IC no radiative
(S1) ISC
(T1) ISC (Spin inversion)
10-8s
10-3s-1s Deactivation
F F
h RD P RD
radiative
(S0) P
IC
S2 : The higher vibrational level of the excited singlet state S1
IC: Internal conversion; RD: Radiative deactivation
F: Fluorescence (spin consevation); ISC: Inter system crossing
P: Phosphorescence (Spin inversion).
S1
+
T1
+ +
photosensitization
O
S2
*
100 Kcal/mole 1012/s
1011/s
S1
T2 (*)
n-*
74 Kcal/mole T1 (n-*)
69 Kcal/mole
106/s
1.8X 102/s
S0
CHO O O
2-acetonaphthone fluorenone
pyrene aldehyde
S1
S1 ISC
Energy transfer
T1
T1
74 Kcal
.mole-1 69 Kcal/mole
120 Kcal/mole 60 Kcal/mole
S0 S0
Benzophenone Butadiene
h ISC 3[Ph
Ph2CO 1[Ph
2CO] 2CO]
3
Dimeric products + Ph2CO
Criteria of an ideal sensitizer
• It must be excited by the irradiation to be
used, small singlet triplet splitting. High
ISC yield.
• It must be present in sufficient
concentration to absorb more strongly than
the other reactants under the condition.
• It must be able to transfer energy to the
desired reactant, low chemical reactivity in
Triplet state.
Experimental set up for
photochemical reactions
Synthetic organic chemist (high intensity
light source, easy to handle, various
Flask size, specially designed systems)
Hg (3P1) Hg (1S0) + h
Hg (1P1) Hg (1S0) + h
Ideal lamp characteristic : Need of spectral overlap between the lamp and the absorption
spectrum of the compound to be irradiated.
Lamps in conjugation with filters
Problems
# A greater degree of selectivity is required if irradiation into one of
the absorption bands of the molecule is required.
# Or if the product of the irradiation is sensitive to a wavelength different
from the one used to excite the starting molecule.
Solution
# Monochromatic source of light (Lamp and a diffraction grating)
# In conjugation with filters (solution or glass)
Short and Long cutoff filter solutions
O O* O
h
~ C
n-*
carbonyl chromophore
Dipolar species
O O* O O*
CF3 CF3
2.9 D 2.1 D 1696 cm-1 1326 cm-1
1665 cm-1 1225 cm-1
O
S2
*
100 Kcal/mole 1012/s
1011/s
S1
T2 (*)
n-*
74 Kcal/mole T1 (n-*)
69 Kcal/mole
106/s
1.8X 102/s
S0
CHO O O
2-acetonaphthone fluorenone
pyrene aldehyde
O O
MeO
= 0.0064 s, 77oK = 0.45 s, 77oK
n-* *
O O
Me F
A D A E
B E B D
3 *
3S*
h
triplet
donor
h
h
185 nm
h
sens
h heat
H
H
Ph Ph
h
Dimer
Max = 380 nm
= 9 s
Ph
Ph Ph
4+2 [1, 3] H
h
sens
H OR OR H
H h H
O2N O2N
R = H, Me
h N N
N N
heat
H
H h N
N
heat
*
Ph
N
H OH
Ph
h or NH Ph NH2
h-sens H O
O
oxaaziridine
Ph OH
N
H
H
N
OH
h or
h-sens
H O
N
H
H
N
HO
O
+ h or O CN
N +
N
CN
h-sens
h
h
O
N
CN
H
H R2 N
N h
R1 R2
R1
H
H N R H
N
h N
N R
N
N H
R h
N N N N
R R R
R = Me R = CHMe
R= R=
R= R=
h
N N
N N
N N
N N
h (405nm)
h(436nm)/heat
h (313nm)
-N2 h (313nm)
-N2
C C
R
R
R
h 1,7-H
HO
HO
previtamin D
Ergosterol
HO
Vitamin D
R= R=
Vitamin D2 Vitamin D3
R
h
HO
previtamin D OH
tachysterol
Photochemical synthesis of
oxetans
Paternò-Büchi Reaction
O
O
+
OH
Thromboxane A2
OEt Oxetanocine
Insecticidal activity
OAc O
HN O O OH
O O
O OR
NH2 O
O
H2N H
Merrilactone A OBz OAc
O
Bradyoxetin Palitaxel
Reaction mechanism
CHO
h ISC
[PhCHO] S1 [PhCHO] T1
(n-*)
O O
O
C C C
C C
H + +
Biradical intermediate
electrophile nucleophile
O
O
Major Minor
Intermediacy of biradical
O h
O O
+ +
1 1.6
O
O tBu
tBu h
+
1 atm O2
tBu
O O
O
O O
h, 11 atm O2
O
O O O
h O
Ph Ph + Ph
O
Ph C C
O O Ph
Ph
lifetime = 1.6 ns
Substrate spectrum of Paterno-Buchi Reaction
h
+ R = H, X = S, 46%
X R X
R = Ph, X = O, 27%
O R = Ph, X = S, 76%
O
h
X Me + X + X
+ [4+2]
O O O
Me
X=O 8% 33% 0%
O O H
O
OMe h
+ Ph
H
H 33% 34%
O
O Ph O O O OAc
h [2+2]
+ O Ph H2 O
Ph OMe OMe Ph
O H OMe
1,7 sigmatropic
O
MeO
Ph O
OH
C + Ph OMe
O
Ph OMe CH . O O H
2 1
7
O O
OH H
O 1, 3 Bz shift Ph
-MeOH 1,3 H shift Ph
Ph O
OMe
Ph O O O
N
CN
h
+
N
66%
Ph
CN O h
+
O
CN
O O
h O
O COMe
O Me
O O
h O
CN O CN
R
-55oC R = Ph, endo/exo = 5.3:1
Oxetane formation: addition to heterocycles
h
+
O* T1 O* T1
X X
C C C
O O
O X X
X
+.
Ph
O O N
N h Ph C C N
+ O
and Ph C C
Ph Ph N
N N Ph
more stable
OH
Ph Ph H
Ph N N
Ph
N O
N
H
CO2Me
Ph Ph h O
O
CO2Me *T1 +
O Ph
O
Ph
Methyl coumarilate
R1 R3 R1 R4
R1
O h R4 R3
+ +
R3 R4 O O
R S R2 R S R S
R2 R2
R1 R1 Ph
O h Ph
+
R2 Se R Ph Ph O
R2 Se
R
R1 = R2 = H, R = Me
R = R2 = H, R1 = Me
R1 = H, R = R2 = Me
Ph
O h, 436 nm O
+ Ph
Ph Si Ph
Ph + O
Ph Ph Ph Si Ph Ph
Me Me MeCN Ph Si Ph
Me Me Me Me
18% 51%
Ph
O Ph
h
+ O
N Ph Ph N
COR COR
COMe
COMe
O N
N h O
Ph Ph Ph
Ph
Enones and Ynones
O O O
+ +
42% 47%
O O
O
Low T
+ + 3% oxetane
Me CCl3 Me CCl3
O O O
F F F
+ +
Me Me
10% 9 0%
O O O
Cl Cl Cl
+ +
Me Me
90% 10%
O h O
O
+ +
14% 86
O h O
+ + O
O O
C C
..
Alkenes substituted with electron donor
OAc
O h OAc
O
OAc OAc
OTMS OTMS
O
OEt ZnCl2 O
EtO O
+ O O h
O O EtO2C O
CO2Et
H
O O h
O
+
O
H
SiMe3
O h O
O
+ Ph
+ Ph
Ph Ph SiMe3
Ph Ph
SiMe3
24 1
h O O
O
Ph
+ Ph
OTMS
Ph Ph
+
OTMS Ph OTMS Ph
94 6
h O O SMe
O H
+
Ph SMe + Ph
Ph Ph Ph H Ph H
H SMe
100 0
Miscelleneous Paterno-Buchi Reaction
O COM O
O h
+ +
H
O Ph Ph
h Ph Ph
+
Ph Ph O 300oC O
O h
+ O O
Ph R Ph C C
Ph
R
R
O O
Ph C Ph
R R
C
CHO
OAc
O h
+ O
O OAc O
O
O
O CO2Me
HO
HO
The Paterno-Buchi reaction as a photochemical aldol equivalent
OH O OR OH OH
R' H 2O O R'
R H R R"MgX R R"
R'
h
O
O
R
R'
OAc CHO
O O OH-/H2O
h O O H OH
O + OAc OAc
H CH2OH
O OAc O O
CH2OH
O NaBH4
O
H+ O
O O
a a
b' d
O R O
R
b c
R R*
A B
a' b
enantiotopic faces a,a' and b,b' diastereotopic faces a,b and c,d
# Nucleophilic attack of carbonyl (half filled *) #Nucleophilic attack of alkene toward carbonyl
towards the alkene empty * half filled n orbital
# Electron defficient alkenes favored this approach # Electron rich alkenes favored this approach
O-.
# nucleophilic attack of the filled -orbitalof the olefin to the excited carbonyl oxygen (n-orbital) to form an exciplex
# the attack results either in full or partial electorn transfer to generate a radical ion pair
# the ion pair or exciplex combines to form a C-O bond resulting a diradical intermediate
# the diradical if triplet lives long and undergoes other reactions before ISC
O-.
# the attack results either in full or partial electorn transfer to generate a radical ion pair
# the ion pair or exciplex combines to form a C-C bond resulting a diradical intermediate
# the diradical if triplet lives long and undergoes other reactions before ISC
n
A
D
* LUMO
D
LUMO
HOMO
LUMO * D
A
HOMO
n
HOMO
A
D
NC EtO OEt
O O
CN
"edges" "faces"
(n-orbital attack) (-orbital attack)
1.2
5.1
OR
O O O NC
1.0 1.5
OR
CN
Fast Slow
OR
O NC
O O
0.48 <0.03 OR
CN
Slow
Slow
O O
h R H H R
+ R CHO
+
O benzene
O H
O H
Endo Exo
R endo:exo
Me 45:55
ethyl 58:42
isobutyl 67:33
phenyl 88:12
o-tolyl 93:7
mesityl >98:2
R
H
O O
ISC ISC
endo 1A H R 1B exo
H H
X X
3A 3B
Perpendicular approach
Enantiocontrol and diastereocontrol inPaterno-Buchi Reaction
H H
O h
O O O
O O
+ O Ph + Ph O
Ph CO2R* O
H CO2R* R*O2C H
O
Pri
O O
Ph
O O
Ph Me
O
H
O
Ph
O
H CO2R*
OHC O O
O N O N
H H
O NR O h
O
O NR O NR O
O + O
O
O N
H
R = H acetonitrile 1:1
benzene 83:17
toluene 95:5
R = Me, benzene 1:1
O
O
H
H
N O
N O H
H NRO
O
O NHO O
O
Intramolecular oxetane formation
O OH
O R
h
R R
R +
O R R Me
R = H, Me
O O
h
H +
O
O
h
O
O
O
O O
O h O h
Me2CO O
O
O O
h O
H
O Ph Ph O
Ph O
h Silica gel O
O O O O
O O
h Pd
h
Me heat
O
O
azulene
O OH
h LAH
O
H H
H
OH
h HI
O
AcO AcO AcO
O
intermediate for 1 -hydroxy-vitamin D3
O O
h
h LAH
CHO
O OH
R
O OMe R
h MeOH O
O O
O O R O OH
O
H H
O
h O O O OH
+ H
H H
Fruit fly attractant
R
H
R H+ R
OH
O OH+
O O O
R = Me, Ph, CO2nBu
Carboxydroxylation strategy by reductive cleavage of oxetanes
R4 R4
R3 R4
h XY OX
R3 O R3
+ R CHO
R2 R2
R2 R1 R CHRY
R1 R1
O H2
OTMS Ph OH Ph OH
Ph R OTMS R OH
R
H2 HO
O
Ph O O
Ph
Total synthesis of (+)-Preussin
HO
Ph
N
HO
O O
+ Ph
Ph H N Ph N N
PG PG PG
H HO
O H2, Pd(OH)2/C
PhCHO/h
R Ph
N Ph R R
MeCN N LAH/THF N
CO2Me H
CO2Me Me
endo
H2, Pd(OH)2/C
HO
PhCHO/h O
LAH/THF Ph
N MeCN Ph N N
Ph
H
H O
Ph O
Si
R R Re
Favored
H1 H1
MeO2C N MeO2C N
H H
H2 H2
PB
COMe
O O
Et3Al
LDBB
HO
O O
N Ph N O N O
O Ph Ph
MeCHO PhCHO/h O O
N Ph +
H 2N Ph
Ac2O, TEA Ph NAc Ph NAc
O
Ph Ph
2 1
H H H H
H Me Me
Ph H Ph
Ph
N Ph
Me N H N H
N Me
O O O O
O O
N O N O
Ph Ph
O O
MeCH(OEt)2 PhCHO/ h O
HN O N O O +
CSA O
Ph Ph Ph N O Ph N
Ph Ph
O O
H2, Pd/C
Ph OH Ph OH
Li, NH3
N O NH2
Ph
O
Ring opening of cis-aminooxetanes obtained by PB photocycloaddition
O LAH/ THF OH
O
Ph N H Ph
H
NHMe
OH
R1
Ph Ph
O TFA R1 O TFA OH
R1 O NBn NBnBoc O NBn
Ph Ph R1
NBnBoc
O O
H OH OH
+ Ph Ph
O H+ O -tBu+
R1 R1
R1 R1 O + NBn O NBn
Ph Ph NBn C
NBn
OtBu O
O OtBu O OtBu
OH
LAH/THF
Ph
NMe2
Ph OTs
O NMe
OH
O NaBH4, KOH/EtOH, water
Ph
NHMe
1 1
1
6 2
3
2 5
4 4
ortho
+ para
meta
prefulvene 6
C*
+
*
6 - 2
3
C 5 1
4 2
C 3
+ Exciplex
para cycloaddition
C* C*
C C
(2C + 2C)
C C C C
O O
O O
z
O z z
O O
O
z = OMe
z = CONH2, CN, Me
C
C
R
-a
b
R
a c C C
+
R
R -b R
R
R
-ac
C C
R
R
C
endo exciplex
O h
+ secondary orbital intercation is not favored
O
O due to presence of non bonded "O" electron
O
exo adduct
O
O O
O O
h O
+ O +
O
endo exo
5 1
*
11
C 10 2
8 h 1
2 C 3
7 1 7
3
6 5 4
6 4
5
Favored
3
8 11
2 C
1 10 2
C 1
4 3
6
5 7
Disfavored 6 5 4
Isocomene
Br Li, CuI Li
+ +
Li, NH3
Br
O O
OMe
OMe OMe
exo
endo
H OMe
OMe
favored
disfavored
O Li, Et2O
+
Br Li, NH3
OMe OMe
Allylic stereocontrol: for the synthesis of silphiperfolene
Me Me
h
Me vs Me
H
Me H
Me
H Me
disfavored favored
h, CH3CHO
H H
O O H
HO
Me OH Me Me
PhNO2SeCN
Bu3P
H 2 O2
Li, NH3(l)
H
Me H
Silphiperfolene Me
H H
H CO2H
hirsutene
-cedrene retigeranic acid
O
O H HO2C
O
O
O
O O H
OH
3-oxosilphinene subergorgic acid
isoiridomyrmecin coriolin
Li, NH3
Silphene
h C LAH
+ OAc OAc
O
OAc C MnO2
Me Me Me Me
LDA, -780C Me2CuLi, THF
MeI
O
(Me2N)2POCl
OR + OR
Me
H2, PtO2
Me
O3, MeOH O NaBH3CN
OR
NaBH4 O
Me Me
OMe
O
Me
Iso iridomyrmecin
CHO
Br O O
Zn(BH4)2
TsCl, PCC O NBS, AIBN H2, Pt
O KOH
OTs
OTs
O O
O O O O O OH
LDA, DMPU
h
O
Li, MeNH2 O P NMe2 Li, EtNH2
O
NMe2
KHMDS Me2N P O
(Me2N)2POCl NMe2
Laurenene
h C
h
C
HCONH2
OHC +
C*
H2NOC H2NOC CO2H
C*
4+2
HO2C R2NOC
R2NOC
Retigeranic acid
(Ph3P)3RhCl, H2
Br2, AcOH
O KOH
CO2H
Ph3P+CH3Br-,
nBuLi
(-)-Carvone
Li, Et2O PCC
h, 3C + 2C
Br EGC/CSA
CHO O
OH O
C (PhCO)2O, h
K, 18-C-6
C NC O
O O CH3CN
O
O O
OH
O Cl
mCPBA LICA, THF SOCl2
O O O
O O O
O
HO
NaClO2 HO2C
O O
Subergorgic acid
Seven membered ring synthesis based on arene-olefin cycloaddition
OMe OMe
H H
h, 3C+ 2C Hg(OAc)2
OH O
OTBS
OH
THF, H2O
OTBS OTBS
NaBH4
MnO2,H2 H H
H
(PhCO)2O OR MsCl, Pyr
OR
O OH
KHMDS, allyl-I LAH, Heat
OTBS OTBS OTBS
OBn
OTBS OTBS
H
H H
O O
O
OBn CO2H O HO
OBn O O
OH
O
HO
OH O
Tet. Lett, 1986, 27, 1857
Rudmollin
OAc OAc
OMe OAc OMe
OTBS OMe OTBS
h
OTBS
C C
OAc PhSeCl
OMe
OTBS C*
OAc OAc
C* H
H
OTBS OTBS
OTBS Cl
O O
O Cl
KOH
O
O H
H OH OTBS H
HO
OH H OMe OAcOTBS OMe OAc
OTBS
OTBS OH
OH
O Grayanotoxin
Disfavored Favored
COX
COX R R ClOC
h R
R R
R
X = OMe, R = Me
O
O
COCHN2
R
R
R
R
Fenestrane derivative
+ .
X
X
X
X OMe
Si-face of olefin in exo-adduct
(Re-face in endo-adduct)
Introduction OMe
of PD tether C
OMe
.
X
X
X OMe
Re-face of olefin in exo-adduct
* *
O O (Si-face in endo-adduct)
6-substituted 7-substituted
O O
O OH OEt O O
Hg(OAc)2
OH
HO OH O O
O OH
+
O Rn Rn O
O O O O
O
O
2R + + 2S
O O O O
O O
O O
Rn Rn
Si- face attack to the olefin Re- face attack to the olefin
O O
C C Abolished stereochemistry at C-4 O
O O C
C C
O
C
Re-face Re-face
MeO MeO MeO
OMe CuCN
9-BBN
MeO OMe
MeO MeO
MeO
OTBS
OH OTBS OH
OTBS
endo (favored)
exo ( disfavored)
OH
HO
HO
H H
OH
aphidicolin stemodinone
Norish Type I Processes of Ketones
Basic Concepts
O O
h C
+ C
R
O O O
O O
O
2 X 107
2 X 108 1 X 107
O O
O
OMe
7 X 105 >109
not measured
# Norish type I reaction is much faster for n-* compared to * excited states
# n-* reactivity is due to the weakening of the -bond by overlap of this bond with the half
vaccant n-orbital of oxygen.
# Electron releasing group at para position lead to stabilization of * excited states hence decrease in reactivity
R
R
R1
R1 .
C C
C C
O C C
O O O
O* O*
O*
< <
O O O
Me
C NO
h C NO
acyl-alkyl diradical
O O
O O
h C
-780C C C
C
O O
h O
H
C Me
Me C H
C H
C Me
Ph Ph
Ph
retention disproportionation
O
H O
Me
Ph H H
H
racemization
Ph H
O O O O
C C
h C C
O O O O
C C
h C C
O O
recombination
(CH2)n (CH2)n
h
decarbonylation
C C (CH2)n-1CH3
(CH2)n (CH2)n
+
O (CH2)n-1CH3
C
C O
disproportionation
(CH2)n H
enal
(CH2)n-1
O O
ring expansion ROH
OR
n
n
ketene
C OR
O
ROH O
(CH2)n
(CH2)n
oxacarbene
C
O C O
C C
O O O C
h
C ring opening C
C
-cleavage
cyclization
O O
ring opening and cyclization
O h O O
C
(CH2)n (CH2)n (CH2)n
ROH OR O
(CH2)n
O O O
h C H
C
OMe
C MeOH
O O
O OEt
O C O
O h O EtOH O
O O O O O
O
O O* O*
h C C
+ CO
C C
S1 (n-*)
Ring expansion
Oxa carbene
O
.. cycloelimination
ROH + O
O OR
O
O
O
h
O
.. O
O
O
OH R1 O R1 H
h O
.. HO O
R1 CN R2 R2
CN CN
R2
H
E Ph Ph
Ph Ph Ph Ph
Si O Si
h Si E O E
O ..
E
O h O h
MeOH
ROH
O O h
h
ROH
tBuOH
S h
S
MeOH
Me O Me Me
Cl Cl Zn O Zn/Cu O
+ Cl +
OTBS COCl
NH4Cl
OTBS OTBS OTBS
3 1
O OMe O CN O CN
TMSCN
h/ MeOH +
1 1
BH3:SMe2 BH3:SMe2
O O
N+Me3I- MeI O
NH2 NH2
HO OTBS OTBS
Muscarine
O
N+Me3I-
HO
Tet.Lett, 1988, 29, 159 allo-muscarine
NaOH O2, h O O H2, Pd-C
OH
+
Cl Rose bengal O
Cl TBSCl
NaOAC/EtOH
iPrOH PTSA
MeO2C
OTBS
SiMe3
O OR
O O OR
OMe OMe OsO4, NaIO4 O
OMe
BF3:OEt2 O
OTBS TBS-Cl OTBS
OTBS
OR
O PhCOCl
LiAlH(OtBu)3 OMe NaH, MeI F-
OH H2
OTBS
BzO
O
OMe
OMe
OBz
J. Org. Chem. 1987, 52, 2335
Pederol dibenzoate
OH OH O
h
O O O
C
O
OH
OH
h O
Wittig R'
R R
HO R
OH OH
R' = CO2H
R=
OH
OH OH
O O C O O
h
C
H
+ H
R
OTHP R
R=
O O
O
O O
MeCO3H LDA, PhSeCl Me2CuLi
H H H H H
Bu H 2 O2
Bu Bu
OTBS OTBS OTBS
O OH
O O
DIBAL-H
H Me H Me +
CO2- Ph3P+
Bu Bu
OTBS OTBS
CO2Me OP OH
OP
H Me
(CH2)6CO2Me (CH2)6CO2Me
C Bu ..
C MeO O Bu
O Bu
O
Thromboxane analogue
• Norish type II photoelimination of ketones:
Cleavage of 1,4-biradicals formed by γ-
hydrogen abstraction
O 1O*
h
R' R'
R R
R'
1O* 1K OH a OH R'
H
R'
R R R
n
1O*
1K
d O
R'
R R'
R
1O*
3K
Kisc 3O* d O
R' R' R'
R R R
R'
3O* OH R'
3K
H OH
R'
R R R
n
OH
R'
O R
R'
R
S1 (n-*) T1 (n, *)
H H H
O C O O
C
C C racemic
Ph Ph Ph
H
O
Ph
optically active O OH
Ph
Ph
# Yang cyclization
# cleavage
# hydrgen reversal
Solvent effect
Ph Solvent Ph Ph
C H C
solvent OH racemization
O O
H
C C
R' R R'
R R R'
O
R
+
R'
O
# racemization is suppressed in H-bonding solvent
such as t-BuOH
O
O
107 108
OMe O O
O
1X105
O* MeO
*
Conformational effects
O O
h
+
no -further reaction
O Ph HO
Ph
h
h
Ph PhCHO
O
O Ph
105/s
Ph
h h
O
Ph 105/s K cleavage = 2.5 x 107/s
H O* Ph
C C
KH = 1.7 x 108/s
+
O*
CHO
HO
Ph
+
H
O
H
O
H
O Ph
7 X 109 KH
1.3 x 108 6 X 108
#The mobility of parcipating molecules (carbonyl compound and hydrogen donor) is severely restricted at the TS
during intermolecular hydrogen abstraction process.
H OH
HO
O
R
R +
O
H h
O Ph
Ph
OMs
H O
O h
Ph
Ph
OTs
Photoenolization
R R R
H-Transfer OH O
O
H spin-inversion CH3
R
R CO2Me R OH
CO2Me CO2Me
OH
+
CO2Me CO2Me
CO2Me
H H
R R R
Ph Ph Ph
O O* OH
H H D
R'OD R R
R
Ph Ph Ph
OH OD O
Me
.
h
O OH
C
Ph Ph
Me
.
OH
C Ph
HO
Ph
OH
O Ph
OH
Ph
Synthetic applications
OAc OAc
OAc
O
O h O
O
OAc OAc
OAc
O
O
CHO
h
O O
O
N
N h
O O
O O
O OH O
h (-)Ephidrine
O O
O O
O CO2Et
O CO2Et
h 4+2
OH
O O
O
Photoenolization
MeO OMe
MeO OMe
OMe
OMe
O O
O
CO2Et
O OH
MeO OMe
OMe
Podophyllotoxin derivative
Norish type II process involving 1,6 and greater H transfer reactions
OH O OH
1, 7 H abstraction
C 1, 5 H abstraction C
T1
C C
h
OH
OH
S1
Photocyclization of cyclodecanones
Ph Ph
Ph Ph
C
O O
OH
O h Ph n
Ph nC
n OH
O
n = 0, 1
photocyclization of -[o-(benzoyl) phenyl ] acetophenone
O O O
h
OH
H H
O O O O
C C
C C
n
R R R
OH Ph
C C Ph
O h OH
O Ph
O HO
OH OR
OR
h
O
OO O O O
OR
Long distance H abstraction
X X O
Ph O O
h
O
OH
O 1, 9 H
O O Ph
h X 1, 5 H
X O X O
X
C Ph Ph
O C O C
O C O
O H O H
X = H or D
Me
n
Me (CH2)x (CH2)y
O O O
h
HO
Ph O O
Ph
n = 12-18
O O
Ph Ph
h OH
O
O O
n=1
O
(CH2 )n O
(CH2)n
O
O
O
HO
h
n=2
O
O
(CH2)n
(CH2)n
O
O
HO
HO
Ph
h
Ph
Ph Ph
Ph Ph
O
Tol O
h
Ph
Ph Ph
Tol Ph
Ph Ph C
h Ph
C
Ph Ph Ph Ph
Ph Ph
Ph Ph
h Ph
..
Ph Ph
Ph Ph Ph Ph
R2 R2
h R1
..
Ph R1
Ph R1 R2 Ph
The triplet rearrangement
a
Ph Ph
C Ph C
h
. b Ph
sens C
Ph Ph Ph Ph
Ph Ph
Ph Ph
a
Tol Tol
h C Tol C Tol
a
. b
C
Ph Ph
Ph Me Ph
b Me
Tol Ph
The triplet rearrangement of 3-phenyl regioisomer
a
Ph Ph
C Ph C
h Ph
. a
b
sens C
Tol Me Tol Me
Tol Me
Tol Me
Ph Tol
The triplet rearrangement of 3-methyl regioisomer
a
Me Me
C Me C
h Me
. a
b
sens C
Tol Ph Tol Ph
Tol Ph
Tol Ph
Ph
Me Tol
Proof of cyclobutenylcarbinyl diradical as an intermediate
a
Ph Ph C
h
N . b
-N2
Tol N a
Tol
b Ph
Tol
Ph Tol
The acylcyclopropene triplet rearrangement
O a
Tol O O
Tol Tol
h b
C .
sens
Ph Ph Ph Ph Ph Ph
b a
Tol O Me
O Ph
Ph Ph
Tol Ph
The Di- Methane Rearrangement
C
h
C C C
h C
Ph Ph
C C C
h
Barrelene Semibullvalene
C
C A A B B
Ph
C
Ph C Ph C C
Ph
Ph Ph
h
Ph
Ph
Ph
Ph
Ph Ph
Major
Minor
# Stabilty of benzyhydryl biradical
C C
Ph Ph
C
Ph C Ph
Ph
Ph
Ph
Ph
Electronic factor on regiochemical outcome
h
+ NC
Ph direct NC
Ph CN
Ph Ph Ph Ph
h
Ph + Ph
Ph OMe direct
Ph Ph Ph
OMe MeO
# there is a strong tendency for electron donors to appear on the residual - bond of the photoproduct
# and for electron withdrawing groups to be found on the product three membered ring
Reaction regioselectivity
CN
CN
Ph
Ph
Ph
Ph
CN
CN
OMe Ph
Ph
Ph Ph
MeO OMe
OMe
Multiplicity control of regioselectivity
Ph Ph
Ph Ph Ph
C Ph s s t t C
Ph CO2Me
C CO2Me C C Ph C
Ph CO2Me
Ph CO2Me Ph CO2Me Ph CO2Me
Ph Ph
Ph Ph Ph Ph
Ph
CO2Me Ph
CO2Me Ph CO2Me
Ph MeO2C CO2Me
CO2Me
Ph Ph
S1
S1
2K
E 2K
T1 T1
Large K vs. small K control of excited state selectivity
Effect of excited state multiplicity on reaction outcome
h, Direct Ph
Ph
Ph
Ph
h, sens
2,3-naphthobarrelene
# di--methane triplets which have double bonds not incorporated in a ring structure or not inhibitited from free rotation
in some other manner are commonly unreactive.
# In contrast cyclic di-enes tend to be perfectly reactive as triplets, and this can be ascribed to their inability to undergo
free rotation in the excited state.
# If rate of radiationless conversion of the triplet reactant is slower than the rate of reaction, despite in the presence of free
rotor group, triplet reactivity in an acyclic system was observed. Generally in this case free rotation is inhibited by effects
such as steric hindrance, so that the triplet may be reactive.
h, sens Ph
Ph Ph Ph
PhPh
Ph Ph
# The original generalization is that cyclic molecules are more likely to react successfully from the triplet
excited state via sensitization while acyclic molecule tend to perform better as singlets (obviously in the
case of triplet reactivity absence or presence of free rotor is important).
h, sens
h, Direct
# For many cyclic molecules, direct irradiation with formation of the singlet excited state does not lead to a
successful di-p-methane rearrangement. This behaviour arises not because the singlet excited state is incapable
of a di-p-methane rearrangement but rather because many cyclic systems have potentially available facile alternative
pericyclic process which competes all too successfully.
h
MeO
h
MeO
h
NC
NC
JACS, 1977, 99, 3723-33
The Oxa-di--methane rearrangement
Ph H H
Ph
Ph Ph
h
Ph
Ph O O
OPDM Ph H
Ph
O C
O
O C
O
C
X O
O
OAc OAc
OAc
h, Direct
+
O O
O O O
CD3 CD3 O
CD3
h
Ph
O Chrysene/sens.
Ph O
racemization
Retention of Configuration
h
Chrysene Sens.
O O
h
Chrysene Sens.
O O
Inversion of conviguration
H
CH2CO2H
CH2CO2H h
O acetone snes.
O
O tBu O
H
But h
tBu tBu
H Direct H H
O tBuH
tBu
O
O R2
R1
Me h
R3
R2
acetone snes. R1
R3
Mechanism I
The OPDM rearrangement of acyclic -unsaturated ketones
Key structural features favoring OPDM
# Conjugation of the alkene moiety with phenyl, vinyl or oxo groups (efficient triplet energy transfer,
biradical stabilization)
# disubstitution or alternatively, monosubstitution by bulky groups at the central carbon
O O O
D Me O O
Ph Me
O
Me O O O O
Me Me Me Me
O
OH OEt
Me Ph Me Me O
O O O
Me Ph O
Me
O Me
Ph Ph
O
Ph O
O O Ph Ph
Ph Ph
Ph Ph
O O
Ph Ph O
Ph
Ph
O
O O
Ph
O
O
O
h
n O n
n = 1, 2 n = 1, 2
X
O
n
n = 1, 2, 3
O
h
O
The OPDM rearrangement s of monocyclic and
condensed polycyclic -unsaturated ketones
O
O
O
O O
O
O O
O O
O CO2Me
O CO2Me
O O
+
O
The OPDM rearrangement of Bridged cyclic -unsaturated ketones
R
O
R2
h, sens
R1 O
R1 = Me, R2 = H
R1 = H, R2 = Me
R1 = R2 = H
O h, sens
O
O O
h, sens
Synthetic application of OPDM rearrangement
OMEM
Me H
OMEM
O
O
h/ sens
O OMEM
7 steps H
H
(-)-Silphiperfol-6-en-5-one
CO2Me
h CO2Me
MeO2C
O
Sens
MeO2C O H
O O
OH
Cedrol
O O
CO2Me
CO2Me
COMe
COMe
OAc
H
H
O
NC Cl
+
h/ sens
(racemic)-modhephene
OPiv
OPiv OPiv
Li/NH3
h/sens Ac2O, DMAP/TEA
O
OPiv
O H
OAc MeO
O
OHC
Swern
O O O
H H H
O MeO
O O O
O
CO2Me OTf
CO2Me
H H
H
Pentalenolactone P methylester
HO
O
h
acetone
H
O
OP H
(-) Hirsutene
sens
O
3-OH-Peristylane
R R
h
O R = CH2CH2OMe
Acetone/iPrOH
MeO O
O H
- Me
R R R
H Donor
O O OH
C C
O H O H O H
O
b
O O
O
h
O O
O
a
O O
OH O
O
O
OH
OH
(-) Coriolin
O
Competition between all-carbon DPM and OPDM rearrangement
b
a
O O
h h
O O
a = benzo vinyl
b = keto vinyl
O
O
DPM
MeO2C
CO2Me
MeO2C MeO2C
O O
O
MeO2C O
H MeO2C H O
O
DPM
ODPM Not observed
O
O
ODPM
O O
O
O DPM X
R X O
R
O
O O
. C O
C
O
R X R X
Stable biradical O O
The OPDM rearrangement of -unsaturated aldehydes
OAc
H
O
H h
Direct or sens
+ +
O O O
O CHO
OH
h, sens
H
Ph
Ph O CHO
Ph Ph
h, sens
H H
Ph
Ph O CHO
H H
CHO
CHO
h, sens
CHO
CHO
h, sens
CHO CHO
H
h, sens
n
Ph Ph
n = 1, 90%
n = 2, 25%
n = 3, 25%
Direct
CHO
Ph
h
Ph CHO
Sens
CHO +
Ph
Ph
CHO
CHO
CHO
O
O
h CHO O
R
R = H, Bioallethrin
R = vinyl, pyrethrin
The Aza-di--methane (ADPM) Rearrangement
Ph N
Ph Ph Ph Ph
N O
Ph
*T1
h, sens Ph
N C N
Ph Ph R N
Ph Ph R Ph R
Ph N
Ph C N R R
Ph
N Ph
R Ph Ph
N
Ph Ph R N
Ph Ph Ar
Ar = Ph
Ar = 4-OMe
Ar = 4 Cl
SET Ar = 3 Me
Ar = 4 CN
-.
N
N Ph
Ph R Ph +. R
Ph
N Ar
Ph Ph
Ar = Ph
Ph Ar = 4 Me
Ph R Ar = 4 Cl
C N Ph Ar = 3 F
N Ar = 4 CF3
Ph R
N N
Ph Ph OH Ph Ph OMe
SET from "N" lone pair to the alkene moiety is restricted due to low IP of oxime and oxime ether
N
OAc
N N
OAc OAc
N
OAc
N OAc
OAc
N N
OAc
H
N n
n OAc N OAc
n = 1, 2, 3
Photorearrangement of cyclohexenones
O O
2 h 2
5 3
5 3
R R
R R
4 4 Type A
OAc
OAc
h/ tBuOH
O
O
O
Ph H
h Ph
O O
+
Ph Ph Ph Ph
h O O
Type B +
Me Me
Me
Mechanism and stereochemistry of Type A rearrangement
R1 R1
R2 R2
O
H H
O
R1
O
R2
H H
O
H
R1 H R1 O
R2 R2
O
5
2
3
R1
R2
4
Inversion occurs at C-4
Me
Me
O
O
O O O
hn
+
Me nPr Me nPr
nPr Me
Inversion occurs at C-4
# Cleavage of the bond between C4 and C5 of the enone is concerted with dformation of bond
between C3 and C5 and C2-C4.
# In a fuse ketone the rearrangement occurs on only one face of the enonebcause of steric constraints
(i.e, the necessary of cis-fusion of the cyclopropaneto both five and six membered ring), hence yielding one product.
R R
O
O
h
R R No reaction
R = Me
R=H
O
Twisted ( around C=C bond) relaxed excited triplet state of ketone
Competiting reactions
O O O O
h
+
C +
C
AcOH
OAc
Mechanism and stereochemistry of Type B rearrangement:
Aryl and vinyl migration
O O O
H H
hdirect
+
h-sens Ph H
Ph Ph H Ph
Ph Ph
Major (endo) Minor (exo)
Ph
C
Ph H
Ph
O O
Me
h
H O
Ph
Me Ph H Me
Ph
H O
X
Me
H
H O Ph
Me C O
Me
Ph
R R R R
h
Ph
Ph Ph
Ph
R
R
R C
R C
+
C
Ph Ph Ph
+
C
Photochemical cycloaddition reaction
(enone olefin cycloaddition)
O O
h
+
ISC
alkene
1(enone)* 3(enone)* 3(enone-alkene)*
Exciplex
h
biradical
enone
cycloadduct
O O
n
+
n n
Reversion
ISC
O O
O
+
n n
n
O
H h
C closure
CHO
C CHO
fission
abstraction
O CHO
furopelargone
Regiochemistry of enone cycloaddition
O CN O OEt O
CN
OEt
OEt OEt
O
-
head to tail
O - O
OEt
h
- CN N O
CN
head to head
reversal of polarity
OAc
O O
OMe OAc
+
O O
OMe
98% 96%
O O O O O
OAc nBu
+
nBu
nBu nBu OAc
only 81 19
O O O
CO2Et OEt
CO2Et
OEt
+
OEt
EtO OEt
OEt CO2Et
82.5 17.5
O O O
SiMe3 SiMe3
SiMe3
+
1 1
O O O
O O
O O
+
OAc OAc OAc
O O
95 5
X
X=O
head to tail
O
O
O
O O O
OEt
CO2Et CO2Et
OEt
+ OEt
EtO OEt
OEt CO2Et
RT 82.5 17.5
O -40OC 94 6
O O O
OEt
CO2Et CO2Et
head to head OEt
+ OEt
EtO OEt
OEt CO2Et
RT 83.5 16.5
-40OC 91.5 8.5
O O O
OEt
CO2Et CO2Et
OEt
+ OEt
EtO OEt
OEt CO2Et
RT 71 29
-40OC 100 0
O O O
OAc
h
O
OAc
h OAc
K+ Aqueous phase O
O
K+
O O O
O O
nHex nHex
nBu nBu
O
O
O nBu
O
O O O O
Y Y
+ + z
a b z
Y Y
X X X X
O O O O
O
+ or or or
always cis
H
O
O
H
always cis
O
H
O
H
H
Regiochemistry of the intramolecular [2+2] photocycloaddition of 1,4; 1,5 and 1,6 dienes
"Rule of FIVE"
h C
h
C
h
C
Intramolecular enone cycloadditions
O O
OMe
HH : HT = 0 : 100
OMe h
O O
HH : HT = 26 : 74
h
O O
O*
HH : HT = 70 : 30
O h d+ d-
O
O d- R
O d+
HH : HT = 87 : 13
h Me
O
O O
R
C
C
OMe HH : HT = 100 : 0
h
OMe
enone cycloadditions in organic synthesis
h H
MeOH H
O O
O H
OMe
hirsutene
O
O
h Ph3P=CH2
TsOH
isocumene
O O
H H H H OH
h MeLi H+
+ OH
H H
-caryophyllene alcohol
O O
vinyl chloride, h O
CO protect TsOH
Na/ NH3, H+
Cargill rearrangement
modhephene
O O O
H h H
+ H
+
H
H H
MgBr
O
O
H HO
KH
H
H H 18-C-6 H
O
O O
O periplanone B
O O
H H
+
MeO2C MeO2C
MeO2C
OH
MeOH/H+
H H
(-) Grandisol
CN HO
JACS, 1986, 108, 306-307
O OP
O OP
Intramolecular 2+2
photocycloaddition h
OP OP
O O
X OP Fragmentation
elimination OP
enolate trapping
OP O CHO
O OH
OP
AcO
Guanacastepenes
Guanacastepene A
JACS, 2006, 128, 7025-35
O O
NOR
H
H
N N
O
CO2Me CN H
H
O
H
O
Dendrobine
O
O
TBHP, SeO2
h
NCS, DCM Cl
O O O
H H H
Cl Me
Li, NH3 LTMP, MeI
H H H
O OEt
O P OEt
Me
LDA, ClPO(OEt)2 Li, NH3
H
Acoradiene
[6,6,5,4] Fenestrane
h
CO2Et O O
NaH, HCO2Et
h
TSN3, TEA O
CO2Me
N2
[5,5,4,4] Fenestrane ester
Tet. Lett, 1982, 23, 711
SiMe3
CO2Me
CO2Me
h
O
O
O
CO2Et
LAH, Swern CO2Et
Li, NH3
O
Ph3P=CHCO2Et H2, Pd/C O
Laurenene
O h
O
+
OH O
OH
O
h
OTBDPS OTBDPS OTBDPS
O TiCl3
O
aq. HF
Azulene intermediate
CO2Me
MeO2C CHO CO2Me
R1 h R1 R1
CHO
+
O
R2 H OH R2 R2
OH
OH
methyl diformylacetate
tetrahydrocoumalate
OH
H
HO H h HO O
+ OAc OAc OAc
OHC
OHC CO2Me
MeO H
CO2Me
O
loganin aglucone acetate
H OH
HO H h
+ O HO O
O O
OHC
OHC CO2MeMeO OMe
H OMe
MeO O CO2Me
O O
O
CO2Me
Sarracenin
O
O O HO O
h
OH
cis fused
O acid or base
OAc O O
O
base
trans fused
h
OAc
O
O O O O
H
Cl Cl Cl
h base
+
Cl Cl Cl
OAc OAc
O HO
O O O
CO2Me CO2Me
h
+
Cl HO
OAc Cl CO2Me
CO2Me OH
MeO2C CO2Me
O
O OAc
O OAc
h
+
OAc
O O
O O OH
O
O
H
H
-himachalene
O O
OAc
O O OAc
O O OAc
h
O O O
OAc
O O OH
OAc
OAc h base
+ CO
MeO
Pb(OAc)4
O
O O
O h O
O
O +
O O
CO2Me
HO CO2Me HO CO2Me
O
O O
OHC
OAc h base
+
OHC
CO2Me
HO O
methyl isomarasmate
CO Pb(OAc)4 O
CO2Me
acorenone
Non symmetrical -diketones
O OH O O OH O
Ph Ph Ph
major
O OH O O OH O
O OH OH O
O O
CO2Me CO2Me
CO2Me
OH
OHC CHO
OHC CHO OHC
O OH
O OH
CHO CHO
O HO
O N
h
+
O O O
O CHO NC
O
h
+
OH HO
O O
O
O h DIBAL-H
O
+
O CHO
O
CHO
h X
+
OH
OBn OBn OBn
OAc OAc
OAc O
h O O
+
O
O
O O
OH OBn
OAc
CHO
OH
genipic acid
OMe
CO2Me
O
O
O
NMe CHO
N
NMe O h
N O
CO2Me
CO2Me CO2Me
+ X
OH h OH
OH h OH
CHO
+
O O O
valerane isovalerane
OH
h CHO
O +
O
O
1,3 -dicarbonyl compounds (intramolecular De-Mayo reaction)
O O O
(CH2)n
(CH2)n
(CH2)n
X OR OR
X = O, NR
O O
O (CH2)n OR
(CH2)n
Different templates
O
OH O O O
H
HO2C h, MeCN
DCC
O
O + O
OTBS
O OTBS O O H
OTBS
O O OH
H
H
O
O
MeO
H MeO
OBn H
OBn
O
H H
Stoechospermol
H H
OBn
O h
O O O
O O
O O OH
O H H O
CO2Me O
O O O
O O O
O
H
O
H
O CO2Me Methyl ester of Pentalenolactone G
CO2Me
O
O
O O
O JOC, 1988, 53, 227
Intramolecular De-Mayo reaction
O
O
Ph
COCl N
O O
h
+
O O
O
OCO2 Ph
OH-
O
O
O
h HO OMs
OAc
OAc OAc O
-bulnesene
O
O HO
O TBS-Cl, h/Pyrex Me3CuLi2
OTBS
O OTBS
O Me
HF, THF, H2O Ph3P=CH2 Me BF3:OEt2
Me
RhCl3, 3H2O
Me
Me
Me Me
Me
Pentalene
O O OAc
Ac2O
+
O OAc O
h
O
O O
O
+
O
OAc OAc
O
OTs
O O O
L-selectride
KTB
Ts-Cl
HO
HO
Dioxolenones as -keto ester equivalents
O
O
O
h, acetone O PTSA/MeOH CO2Me
O
O (CH2)n
(CH2)n
O (CH2)n
O O
O
O O PTSA, MeOH OTBS CHO
h
O O
DIBAL-H
OTBS
OTBS cis:trans = 4:1
OTBS O O H O O
Trans Cis
H O O
OTBS
O O O O
h PTSA/MeOH
O O
H CO2Me H
O O
H H
O
h O KOH, MeOH
O
O
O
O
O O
CO2H
Ingenane skeleton
MeO2C MeO2C
O
HN HN
O h, MeCN O
O O
O
O O O O
NaBH4
CO2Me MeO2C
HN HN
HN
O
NaH
O O
OH O OH O
O
Perhydrohistrionicotoxin
O O
h
+
O O
HO
O
O O
RuO4 KOH/H2O
O
O
O CO2H
O
O O O
O
O OTMS
H nPr
nPr nPr HCl, H2O
TMSOTf
O O O
O O
MeLi HO OH
O O
h HO
grandisol
O O O
O
OH
h HO2C
fragrantol
O O O OH
h
O
OH
O
HO2C
O O O
OAc
OAc h
+ +
OAc
O
OAc O O O
OAc O
+
OAc
78
22
OSiMe3
OAc
O MeMgI O
HO
O O CHO
OAc CO2Me HO HO OH
n
O
lineatin
O
CO2R
O O
CO2R CO2R
+
h
H H
O
OH O P OEt
OH OH OH
OEt
H
H
epijunenol
O O O
OH
+
h H+ C
heat
+ OMe
MeO OMe
OMe OMe
OMe
OMe OHC O
CO
OMe CHO
O sativine
helminthosporal
Copper (I) catalyzed intra and intermolecular photocycloaddition of alkenes
h
M + S M-S M + P
MLCT
*
4s (-acceptor)
3d (-donor)
LMCT
h, LMCT
+ +
Cu+ + Cu+
Cu+ -
-
h, MLCT
.
Cu++
Cu+ +
. . Cu
-
CuOTf, h
trans fused
CuOTf, h
+
trans fused
h
CuOTf
CuOTf
trans fused
+
1,3 H shift C - Cu+
+
C
Cu Cu
CuOTf, h
O O
CuOTf, h
HO HO
O
NaIO4/RuO4
O O
Cu+
OH Cu+
OH
HO HO
H H
H H
exo
endo (favored)
HO Cu+
HO
H
Cu+
HO HO
-panasinsene -panasinsene
HO HO
CuOTf, h
H
CuOTf, h
HO HO
HO
grandisol
HO HO
CuOTf, h
MeO OMe MeO OMe
CuOTf, h
HO HO
OMe OMe
OH
OHC CHO
HO O
Robustadial A; H =
Robustadial B; H =
H JACS, 1986, 108, 1311.
Photoreduction: Addition to a C-H bond
O
O
Meo
Me CH2.
Ph Ph
OH HO
h
O + C + Ph
Ph Ph Ph
Ph OH + Ph
Ph
Ph
Ph
Ph h OH HO H OH
O + CH3OH C + .CH2OH
Ph
Ph
+
Ph Ph OH CH2OH
Ph PH
Ph
Ph
HO H
Ph OH
H
O
Ph CH2OH
OH OH
Ph h
O + Me2CHOH C + C
Ph Ph Ph Me Me
Ph
O
Ph
Ph
HO OH
Ph
Ph OH Ph
C
Ph
+ O
Ph
Ph Ph OH Ph
+
Ph h
O + N
Ph C O N C + N
Ph Ph Ph
Ph
Ph
HO
Ph
Ph OH
Ph
OH OH
coupling
h disproportionation OH
O 2 C OH + OH
OH
H -transfer
O +
OH
O
OH
OH
C
1 X 103
Ph
Ph
O OH
OH
C
1.6 X 106
O OH
OH
C 1.6 X 105
Me Me
O OH
OH
C 3.2 X 104
Me Me
Me Me
X
H
X
In plane approach
Perpendicular approach
* LUMO * LUMO
*
n
HOMO
HOMO
H
H
C. O.
H
H
In plane approach
O. C. O
H
H .X * LUMO
X
E2
*
n E1
HOMO
H
C. O.
R O
O O OH
h Ph
Ph
OR
OH
Ph
h
Ph
h OH
O
Ph
O
O h
Ph O
O
O
Ph OH
Ph H OH
Ph Ph
O h
O Ph
O
h
Ph
C Ph
Ph O Ph Ph OH Ph OH
O OH OH H
NMe2
h
Ph NMe2 Ph H + Ph NMe2
O NMe2
O NMe2
C
Ph C C
Ph
CO2Me
CO2Me
N z
O CO2Me HO
h HO N z
Ph N
+ Ph
Ph Ph
Ph z Ph
Photoreduction of carbonyl (n*) state via electron and charge transfer
Ar Ar
NR'2 Ar
Ar + Ar Ar
OH OH
R OH
n n n
N O
O
H H
n*
H
+
O N
H H
Competition between H-abstraction and charge transfer
O O
O N O
XAN(n*) AZAX(*)
Quencher
# the rate constants for photoreduction by CT are higher than those expected for
H abstraction
# The quantum yields are solvent-polarity dependent
# Direct spectroscopin evidence proved it
Deuterium isotope effects quenching constants (H abstaction or ekectron transfer)
Kq
H-abstraction
Electron
transfer
O
NH2
R'
HN
260 nm (*) N
PYRIMIDINES 270 nm (*)
O N
O N
R
R
Ura R'=H R=H
Urd R'=H R = ribose Cyt R=H
UMP R'=H R = ribose phosphate Cyd R = ribose
CMP R = ribose phosphate
O
NH2
N
N HN
N PURINES
H2 N N N
N N
R
R
h
NH2 NH2 NH2
O OH
N N O H N
NH N O N O
h O N O N
O N
N O N N
O O O
O O
O O O
O
OH OH
HO HO O P O HO O P O
O P O
OH
O O O
NH2 NH2
O
OH OH
OH
N N
N O N O HN
N O
h heat
O N O N
N O N
N N
O O
O O O
O O
O O
OH OH
HO HO O P O OH
O P O HO O P O
O O
O
O O
NH2 NH2
HN N
N HN
N
O N N
N h O N N
N
N
O O OH
O
O O O
HO O P O HO
OH O P O
O O
NH2 N
NH2
N N NH2
N N
N O
N N N NH2
N N h
N N
O N
O
O O P O
O N
O N
HO O P O O
OH
O
OH
h OH
N N H N
H +
EtOH
O N O N O N
OH
O O O
H N h H N NH
Thy H
O N O N N O
H H
H H
O
O HN
O
HN O N CO2H
O h CO2H HN
HO N heat NH2
O +
Lysine H2N N O NH
H O
HO NH2
O
OH HO
OH
HO
X O
X NH2
HN HN OH H
H
N N H
O N N O
O N OH
O N H O N
N H
Cytosine photohydrate
Cyclobutyl pyrimidine dimer Dewar pyrimidinone
O
NH2 O O
N H OH
NH
HN Me HN Me
N
N N O OH OH
O N O N
N H H
Adenine-thymine heterodimer Thymine phohydrates
DNA repair: photochemistry
O O O O O R2 O R2
R3 R1 R1 R1 R1 R1 R1 R1 R1
R3 R3 R3 R3 N O R3 N O
N N N N N N
N N
O N N O O N N O O N R3 O N R3
H H H H H H H H
R2 R2 R2 R2 R2 O R2 O
O
N OH
Cl Cl
N Cl Cl
H
O
c-s[TT]; c-s[DMTD] c-s[DMTD]; c-s[DMUD] c-s[DMTD]; t-s[DMTD]; c-a[DMTD]
OH
(CHOH)3
N N O N N O
N N O
NH NH
N NH
O O
O
c-s[TT] c-s[TT]
c-s[TT]
O
O R O O
N h R
N N
N +
O N O N O N
O N
OMe
MeO
R=
N N
H H N H
H OMe
O O
N N O
HN NH
NH
+ Complex
X O N N O
H H
O h
X = N, CH
1 flavin----------Thymine dimer
3 flavin----------Thymine dimer
O O
N N O
HN NH
C NH
+
X O N N O electron transfer
H
O
radical pair
O O
O
1 e from
HN HN
HN 2
+
flavin O NH
O N O NH
O O
N N
O N N O
O
HO2C
N
H
HO N N O
NH
COR1
N CO
N O
CO N O
N H N
R2
R2 N H N N
NH ON Bu
NH O Bu
CO
NCOR1
CO
MeO
R1 =
N N
H H
Photo reactivating enzyme (PRE) or photolyase (EC : 4.1.99.3)
O 5 O
5
Me Me 3
3 Reduction NH
NH
+ Dimer splitting
HO N N O HO N N O
e- 1
CH 2 1
CHOH 8-OH-5-deaza-isoalloxazine H2
CHOH
CHOH
OH
O P OR
O
8-hydroxy-5-deaza-isoalloxazine
OHOH
Bioluminescence
Fireflies
HO S S
N N
OH
Oxyluciferin
Firefly luciferin
Image of bioluminescent red tide event of 2005 at a beach in Carlsbad California showing brilliantly glowing crashing waves
containing billions of Lingulodinium polyedrum dinoflagellates
Chemistry of vision
Cys-NH2
h
Opsin
CHO Rhodopsin
11-cis retinal NH+
P
H+
NH+ N
P P
Metarhodopsin II
Bathorhodopsin (contains all trans retinal)
H 3 O+ retinal isomerase
CHO
Tyr-66 O Gly-67 O
N N
H
HN O HN O
HO HO O HO HO OH
NH NH
Ser-65
-H2O
O
O
N
+ O2 N
N O
HO H N O
HO
NH
HO NH
HO
# Meisenheimer complex
ex
L L Nu
L Nu
hn Nu- - L-
-
EWG EWG EWG
EWG
# the rate determining step is addition of nucleophile to the leaving group bearing carbon atom
18-
O
OPO3=
h + HPo4=
+ 18 OH-
H 2O
NO2
NO2
NHCH3
OPO3= h + HPo4=
+ MeNH2
H2O
NO2
NO2
O
OMe
h + MeOH
+ OH-
H2O
NO2
NO2
OH
OMe
heat
OMe NO2
OMe OH-
H2O/THF OMe
OH
NO2 h
NO2
X NO2 X NO2
h, NO2-
h, NO2-
MeOH
MeOH
NH2 NH2 NMe2 NMe2
X = Cl, Br, I
SO2X Nu
h/Nu-
NH2 NH2
Cl SO3Na
h/Na2SO3
R R
R = NH2, NMe2, OH
OMe OMe OMe
h, CN- CN
MeOH
+
CN
OMe
OMe CN
OMe h, CN-
tBUOH
OMe OMe
h, CN-
MeOH
OMe CN
NO2 CN
h, CN-
MeCN/H2O
h, CN-
NO2 CN
tBuOH/H2O
CN
h, CN-
tBuOH/H2O
CN
h, CN-
tBuOH/H2O
Alternate mechanism SN(ET)Ar
L L L
h Nu- Nu.
-.
EWG EWG EWG
L Nu Nu
-L-
-
EWG EWG
NHhex
OMe
SN(ET)Ar*
OMe
OMe
NO2
+ n-HexNH2
OMe
NHhex
NO2 SN2Ar
NO2
n-HexNH2
NO2 O2N NHhex
SN(ET)Ar*
SN2Ar
MeO GlyEt
OMe
NH2CH2CO2Et
SR+N1Ar* mechanism
L L L
h -e- Nu-
.+
L Nu Nu Nu
-L-
.
ArL
.+
L : Leaving group; EDG : Electron donating group; Nu: nucleophile: ArL: ground-state substrate
Synthetic applications
CN
h, KCN
Bu4N+CN-/ MeCN
OMe OMe
h, CN-
tBuOH/H2O
CN
CN
OMe h, CN- OMe
tBuOH/H2O
NO2
OMe
h, NaOMe
MeOH
OMe OMe OMe
N O H2 O NH2
h, OCN-
H2O, O2
1O
2
O2 1O
?
h
2
The fate of singlet oxygen
# 2+2, 4+2 cycloaddition and ene reaction are the probable reactions
# Weak electron acceptors TPP, metaloporphyrins, with low triplet energies should used as
sensitizers. RB is possible (in polar solvents) in some cases, use of MB should be avoided.
# Regio and stereoselectivity for certain transformation should be determined directly at the peroxide stage.
In many cases further transformation (reduction, rearrangement and cleavage) clearly
change the regio as well as stereochemistry of the products.
HO OH
MeOH/RB HO HO
O2, h/redn
+ + +
25% 21%
31% 11%
(+)-Limonene
General effects controlling the regioselectivity of allylic oxidations of C-C double bond
1O
2
X O X
Y O Y
Cis effect
CH3 (7) CH3 (<2)
Me Me OOH
Acetone/ R.B
Pri
OOH + Me
Ph R.T/ O2/ h Pri Ph Pri Ph
D H D H
Me
OOH
Me OSiRMe2
Me
CCl4, TPP NC
Me OSiRMe2
h , O2
+
H CN
Me OOH
OSiRMe2
H CN
-unsaturated carbonyl compounds
CO2Me
CO2Me
CO2Me
OOH
CHCl3/TPP OOH
+
0oC/ O2/ h
E dr = 90:10
Z dr = 65:35
Cycloalkenes with excocyclic C-C double bond
MeOH, RB/ RT
O2/ h OH OH
+ +
Na2SO3 OH
35 12 23
O
H
OMe
CO2H
O
H O
H
MeOH/ RB
OOH
-78oC/ O2/ h MeO
OMe H
CO2H OMe
H CO2H
H
DCM/ MB
RT/ O2/ h HCO2H/ DCM
H
O
H
O
O
OOH H
H
O H
OMe
CO2H
O
H
qinghaosu
CCl4/ TPP Ph3P
OOSiMe3 OSiMe3
O2/ h
OSiMe3 O O
H
HO
O2/ h OOH
R'
R
HO
R' = H, R = OH
R', R ; = O O O
EtOH/MB/O2/h
+
OOH OOH
H
H
Major
Photooxygenation of 1,3-dienes
1O
2 1O
O 2
O O
O + O
O
Ph Ph
Ph
Ph 1O Ph Ph
2
O O
+ O
O Ph
Ph
Ph
Ph Ph
Ph
O 1O
2 O O
O 1O
2 O O
O O O
O O O
H
H'
H' H
H H'
H
H'
tBu
1O
2
tBu O O
62%
1O
2
O O
23%
(CH2)n
1O
2
n
O
O
X
1O
2 O
X
O
1O
2
Ph O Ph
O
O
O
O O
O
+
1O
O O O
2 heat O
O
O O
Ph3P
MeOH
O O
H H
OMe
O
H
S S
1O
2 HN=NH
O O
S O O
Chemoselectivity in photooxygenations of 1,3 dienes
1O (CH2)n
2
(CH2)n O + ene products
MeOH/DCM
O
RB
n=1 16 84
n=2 20 80
n=3 22 78
n=4 50 50
n=5 67 33
1O
2
O
O
1O
2
OOH
H H
H Me
Me H
1O
2
OMe
OMe O
O
OMe OMe
1O
2 OMe
O +
OMe OMe
O
OMe CHO
OMe
OMe
OMe
O
O
O
O
1O
2 O
+ + +
O OOH
MeOH
OOH
1O OOH
2
+
-Myrcene OOH
O
1O O
2
-Myrcene
OtBu
OtBu OtBu
1O
2
O
+ OMe
OMe O
OMe
O O
Ar O O
h/O2
H + Ar
Ar H
H Cl OH
N
Ar
N
epibatidine OH
OH OTBS 1O
OTBS
2
O O
OH OTBS h OTBS
OH
OH
MeO OH
O
HO OH
OH
OH
Pinitol
O
OH O
OH
OH
OH
b
a c
O
+ O O d
O O
e O
g f
O
O
HO O
O
a, b, c; Reduction
d, e; Thermolysis
f; Deoxygenation
g; Acid/base Catalyzed reactions
Photo removable protecting
groups
O O
h
R S OR' R S OR' R .SO2OR SO2.OR
O O
H abstraction from
solvent
R OH
R H
O
O
O
OR
OTs RSO2O OTs R = Ts O
O
O O OTs
HO O O
O O O
O
O
OTs O
OHOTs
O
O O
O h/MeOH O
CHPh OMe CHPh OMe
O O
O OTs O
O
O
CHPh OMe
X O
h/MeOH O OH
OTs OTs
h
No deprotection observed
O O
O O
O O
h/ (Me2N)3PO
H
O H2 O O
OSO2CF3 O H O
NO
NO2 CHO
h
CH2OR
ROH +
n-
O NO
+
N OH OH
OR
CH.OR H
O +
N O H
O OR
+
N OH H
CHOR
Acinitro intermediate
OBn
OH
NO2
NO2 O O
O O
OBn
OH
BnO
HO
OBn R
OH R MeO
R
R = H, OMe
HO B
O
NO2
OR O
O-Nitrobenzyl group known as Caged group
NH2
N
NO2 O O O N
O P O P O P O N O O CO2-
O N
O O O NO2
HO O
H
NH2
OH OH
NH2
CO2- CO - CO2- CO2- N
2
N
N N NO2 O O N
Ca+2 O N
P
O O O
NO2 O
OH
ONO2
O
O O O
O
O
R1
O O
R2 O O
R 1 = H; R2 = ONO2, 100%
R1 = ONO2; R2 = H, 92 %
O H NO2 OH OH
O O
h/ MeOH NO TFA NO2
O
O O
OMe
AcO O OMe
AcO O OMe
NO2 O
CH2OH
O
O O
O O
NO2
NO2
O O
O
O
O2N OMe
O
OAc NO2
O OMe
O
O
O
NO2
OAc
O OMe
OAc
O
O
O OH
O
NO
NO2
O O
C O
O
OH
N OH
+
NO
O
O
O O
O
OH OH+
+
N N
O O
O O
NO2 N OH N
OH
OR O OR
O OR C O
O H O O
NO
NO
O OR
+ CO2 + ROH
OH O CHO
2-(o-nitrophenyl)-ethoxycarbonyl [NPEOC]
O
NO2 N
O OH O NO2
+ CO2 + ROH
O OR O OR
1. light absorption and
intersystem crossing
Covalent linkage O
O
2. Energy 3. H- Transfer
NH
transfer
O O
N O 4. -elimination and fragmentation
O
O
NO2
OH
O
O
NH
HO
N O
O
+ CO2
+
NO2
OH
O
NO2 O
O
O OR
NPPOC Protecting group O OR
O
NO2 O
NO2
O O OR
O OR O O
NO2
O
NO2
O OR
S S O O
NO2
O O
O
Angew. Chem. Int. Ed. Engl, 2006, 45, 2975-78
NO2
MeNPOC [(-methyl-2-nitropiperonyl)-oxy] carbonyl
O O O O
O O O O
NO2 O
NO2 O
B O O B
HO O O
O Cl Pyridine
+ O
O O
OH OH
O
HO B
NO2 O O
O O B h O
O
+ O + CO2
O O O P OMe
O O
O O
O P OMe
O CN
S-H
ArOH + RCO2H
or
RH + CO
Proposed mechanism for the photochemical cleavage and rearrangement of aryloxy esters
O oNB
OCOR O oNB
R1 OCOR2
O
photochemical deprotection of ketones protected as
ketals of 1-(o-nitrobenzyl)-1,2-ethane diol
OH O R1
O R1
O R2
R2 h O
OH O
+ R1 R2 + OH
NO 2 N
NO 2
O
OH O R1 O R1
O R2 R2
O O
O OH OH+
+ R1 R2
NO N
NO
O
Photochemical deprotection of carboxylic acids and amides
protected as o-nitrobenzyl ester and amide derivatives
NO2
NO2
O R2
O R2
O2N O
R1 O
R1 = H, R2 = Ph
R1 = ph = R2
R1 = Ph, R2 = (CH2)14 Me R2 = Ph, Bn, CH2-naphthyl, -Boc Ala, Boc-Phe
R1 = Ph, R2 = Bn
NO2
O
H
N R
N
H O
(P)
R = Boc-Gly
R = Boc-Val
R = protected decapeptide
Carboxylic acid
OAc
OAc
O
C OMe
H
O
OMe
OAc
OAc OMe MeO
MeO
C O O
O H
MeO
O
O
+ O S
+
SOCOR S R
NO2
+
N O NO2
h
O + RCO2-
C6H6
S
NO2
+ RCO2H
NO2
O O R2
R2 h
R1. S N
R1 S N
R3 O R3 SH
O
R2
SO2. N
R3
H2N
N
O2N N
O O
N
O P OH O P O N
O
OBn O
O2N
O O
O2N NO2
S RCOCl/ NaH S S
S S S
R
N N N
H O
O R
h/ R'OH O S
+ S
R OR'
N
H
Photolysis of N-acyl-2-thionothiazolidines
S S
h R
S C SH O
N H N R R'
C
R R2OH
O R' O R'
R
Photochemical activation in N-Acyl-2-thionothiazolidine OR2
R'
O
h
S
O
S H H
O
S S
R3 R1 h R3 R1
R2 R2
Photolytic dethioacetalization
Remote functionalization by Nitrites: The Barton Reaction
H H H
ONO h O C O
+ NO + NO
O
+ + OH N H ON
N N HO OH OH
OH
O +
heat
six membered cyclic TS for hydrogen abstraction
H
ONO O
C
C
+ NO.
+ NO.
HO HO
NO
HO
O O
OAc OAc
HO O N O
NOCl/ Pyr H
H h, PhMe
H H H H
O O
O O
H OAc
C OAc
O OH
NO
H H
H atom abstraction
H H H H
O O
O OH
ON O
OAc N OAc
OH OH
H H
tautomerization
H H H H
HNO2
O O
OH O
O OAc
H
Aldosterone 21-acetate
H H
O
OH NOCl O N O
h, n-hexane, RT
Pyr, 0oC iPrOH, reflux
OH
N OH
OH O OH
H
Grandisol
O
OH
OH
OH O O
-cleavage OHC
H h H
H H
H H
O
O
O
O
NOH C
H
H
H H
H H
O
O
HO
N
ONO O
h
O X
H
benzene
N
OH
(CH2)n (CH2)n
R R
ONO h
R O
R CS2
NO
ONO O
h
H H + .NO
benzene
H H
O O
H
H C H
H
H
OH OH
N OH
C
H H
H H
Barton-McCombie reaction [R1R2CHOH to R1R2CH2]
H
H R2
R1 OH
R2
R1 OH
2,4,6-Cl3C6H2OC(S)Cl, Pyr
C6F5OC(S)Cl, Pyr [X = 2,4,6-Cl3C6H2O]
[X = C6F5O]
N PhOC(S)Cl, Pyr
X= N [X = PhO]
H
R2
R1 OH
H S
R2
R1 O X
nBu3SnH, h
.Sn-nBu3
H S H S Sn-nBu3
R2 R2 C
R1 O X O X
H S R1
R2
R1 O X
H nBu3SnH R1 S Sn-nBu3
R1
.Sn-nBu3 + C +
R2 H R2 H O X
Barton's thiohydroxamate ester chemistry: synthesis of alkyl pyridyl sulfides
+ N
N-Hydroxypyridine-2-thione sodium salt
R Cl
O-Na+
S
DMF or POCl3
O
N .R + + CO2
R O N
S
SR
thiohydroxamate ester
h
O O
N N
R O R O C
S S R
.R
R-Cl
R-Br
R-I
CCl4
BrCCl3 CHI3
R N R-SPh
RSePh PhS-SPh
PhSeSePh
O S
nBu3SnH O2
R-H R-OH
h
O
O S
S N
N O C
O
S
S
-CO2
C
5-exo-trig C
+ N
C S
S
Organocatalytic enantioselective photoreactions (OCEP)
K
A
A-K
A K AB
B
h (S)
B B*
The photochemical excitation and the enantioselective key step are decoupled
# Reactants A & B do not react with each other (or if they do so very slowly in GS or ES)
# One of the reactants B is, through sensitization (S), converted into excited state B*
# While A forms a complex A-K with the chiral catalyst (not necessarliy covalent)
# The complex A-K now reacts with B* because of its changed electronic properties to give B-A-K
# Complex B-A-K dissociates into product A-B, releases K and the cycle continues.
R4 3O
2
R3 h, TPP
N CO2H R4
H R4 1O R3
R3
2 N COO-
O N CO2H OOH
R1
R1 R1 R2
R2 R2
O O
OH OOH
R1 R1
R2 R2
PET
SK*
A+B A B
# Which at the same time acts as a sensitizer and transfers th energy to the substrate
# After the excitation of SK, a complex with A and B is formed, in which the excitation energy is transferred
# The important points of this approach are high facial differentiation in the complex SK-AB and the
exclusion of intermolecular sensitization
H
O NN O
CO2H CO H
2
CO2H
Kemp's triacid
O N O X
H
Ph H
O N
H
O NN O
OMe R R
OMe OMe
h
H H
N O
H O O
R
endo
R
R
R = CH2CH2CH2OH OMe
R = CH2OAc OMe
R = OAc H
H
R = Ph O
R = CO2Me O
exo
OMe
N O
H H H
O NO N O NN O
h O
H > 90% ee
N O
H N O
H
OMe
N O
H
H H
N O
O NO N N
O
O O
h C Ph
Ph
ISC
N O NH O NH O
H
H H
O N N O O N N O
-H+
N
N
O OH
N C
Ph C Ph
NH O NH O
H H
N O O O
H N N O N N O
70% ee
O
OR
OR HN
O O O
O O
NH NH Me
NH HN Me O
CDCl3 N R
N R NH
R= COPh
h
OR
O O
O
NH NH Me
HN
O
N R
O NH