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Energies 100 kcal/mol= 4.3 eV= 286 nm= 35000 /cm (near UV)nano= 10-9 286 kcal/mol= 12.4 eV= 100 nm= 100000 /cm (far UV) Typical Bond Energies C-H = 110 kcal/mol C-C = 80 C=C = 150 C=O = 170 Uv light 150 -40 nm wavelength, so this is sufficient energy to break bonds knock electrons out of bonding orbitals (electronic excitation).
Chemically useful light is generally in the range of 200-400 nm Often employ filters to regulate the wavelength of the radiation
T*
T*
T*
T*
T*
T T-T* (S1)
T T-T* (T1)
n-T* (S1)
n-T* (T1)
A Jablonski diagram, named after the Polish physicist AleksanderJab o ski, is a diagram that illustrates the electronic states of a molecule and the transitions between them. The states are arranged vertically by energy and grouped horizontally by spin multiplicity. Radiative transitions are indicated by straight arrows and nonradiative transitions by squiggly arrows. The vibrational ground states of each electronic state are indicated with thick lines, the higher rotational states with thinner lines.
Drawback
Reactivity is often unpredictable Many substrates are not compatible Selectivity and conversion are sometimes low
imple leavage Decomposition Intramolecular Rearrangement Photoisomerization Hydrogen Atom Abstraction Photodimerization Photosensitization
1) -Cleavage (Norrish type I reaction). In solution the radicals undergo further reactions to give products.
hv 0n
h hv h
h C
2) Hydrogen Abstraction followed by cleavage = Norrishtype II cleavage.The radicals can abstract a Hydrogen atom from a donor. The resulting radicals can then undergo further reactions.
hv 1 % H H
9 %
An intramolecular example:
Chang, S.-Y.; Huang, S.-L.; Villarante, N. R.; Liao, C.-C. Eur. J. Org. Chem. 2006, 4648-4657.
Cheng, A.-C.; Chuang, G.; Villarante, N.; Liao, C.-C. J.Org. Chem. 2007, 72, 6 0- 6 7
Substituent Effects on the Bridging Modes of Photochemical Rearrangements of Pyrazino-, quinoxalino-, and benzoquinoxalinobarrelenes
Chen, A.-C.; Lin, S.-Y.; Villarante, N.R.; Chuang, G.J. Tetrahedron, 2008, 62, 8 088 21
Nelson R. Villarante
Department of Chemistry National Tsing Hua University Hsinchu 300, TAIWAN
28
Oxidant : TTN = Thallium(III) nitrate [Tl(NO3)3] BTIB = Bis(trifluoroacetoxy)iodobenzene [PhI(OCOCF3)2] DAIB = Diacetoxyiodobenzene [PhI(OAc)2]
Self-dimerization of MOBs
The formation of a dimer occurs via Diels-Alder reaction between two molecules of MOB The reaction is highly siteselective regioselective stereoselective
Ref: 1) Anderson, G.; Berntsson, P. Acta Chem. Scand. B 1975, 29, 48. 2) Liao, C.-C.; Chu, C.-S.; Lee, T.-H.; Rao, P. D.; Ko, S.; Song. L.-D.; Shiao, H.-C. J. Org. Chem. 1999, 64, 4102.
30
DA
Dieno
ile
DI DA
Dieno
ile
as ed - enzo
inone
31
OMe X OMe X
1 2
R = R = CH3 C60
=C H
X = CH2, O, NBz,
Rn O
OMe
R = R = CH3 X = O, NH OR
1
OMe R OH X OMe
DAIB R MeOH, 0 C
OR2 O
O
R1 = R2
OMe
=C H
OMe
3 CH
O X R
=C H2 C
HX =C H HC
O OMe
Rn O
OMe
O H MeO OMe
32 Ref: Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856.
O OMe O X
H O OMe O
O R O OMe
OX
33
Ref: Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856
O Xc R2 R1 O OMe R
3
O R1
+
Xc R2
O MeO
R3 R4
R4
OMe
R4 3 R OMe
Products 2a2a' 2b/2b' 2c/2c' 2d/2d' 2e/2e' 2f/2f' 2g/2g' 2h/2h' 2i/2i' 2j/2j' 2k/2k'
Diastereoselective Diels-Alder Reactions of MOBs with Homochiral Furans: Enantioselective Synthesis of Highly Substituted Tricyclic K-Lactones
OH MeO HO R1 R
3
OH O R3
OH MeO R3 R2 R
1
O R'
'
O R1 R2 OMe + 3 R3 OMe R O R2 R1
R2
DAIB MeOH
MeO O
R R
1
R R R'
+
R
2
7 7 Yield/ %[b]
Entry 1 2 3 4
Furan T/[oC][a] Products (R)-3 (R)-3 (R)-3 (R)-4 rt rt 80 rt (+)-5a/5a' (+)-5b/5b' (+)-5c/5c' (+)-6a/6a'
Yield/%[b] de/%[c] 77 74 60 76 98 96 99 97
----7c/14 ---
[a] Reaction temperature; [b] Yields of isolated products; [c] Determined by HPLC (Si60 column); [d] 20 oC, CHCl3; [e] c = 1.75; [f] c = 2.20; [g] c = 3.00; [h] c = 2.50.
Ref: Chou, Y.-Y.; Peddinti, R. K.; Liao, C.-C. Org. Lett. 2003, 5, 1637-1640. 35
CO2H Clerodane diterpenic acid Synlett 1998, 912 H CO2Me O MeO2C H R' (+)-Forsythide aglucone dimethyl ester Tetrahedron Lett. 1989, 30, 2255 HO2C
OAr
OR1 R OR2 O O
HO O
O H
(+)-Capnellene
36
O OR1 HO H R OR2 O O OH
(+)-Conidiogenone (+)-Drechslerine D
CO 2CH 3 O OH O O O
OH
H 3COCO H 3CO 2C
OH O
37
Azadirachtin
38
ISC Sen*
3
O2
Sen*
O2
Photosensitizers
ye: ose engal (
Cl Cl Cl I NaO I O I Cl ONa O I O N N N N
), Tetraphenylporphyrin (TPP)
Reference: http://www.rsbs.anu.edu.au/ResearchGroups/PBE/Oxygen/O2_1_%20ElectronicConfig.htm
40
[4+2] O
t-Bu
N2
O 3
O 26
t-Bu
O t-Bu O O N2
8 %
h , O2 O t-Bu O O t-Bu 6% Ryang, H-S.; Foote, C. S. J. Am. Chem. Soc. 1981, 103, 495 O
OO + 1.5
OO
O O O 2, CH2Cl2 O O O O
41
O Me O O OMe OMe
S H2N NH2
HO
Me O OMe
rt, CDCl3 OH O
OMe
3a 87%)
RB / MeOH, O2, hR -25 oC, 4h O Me OMe O OOH PPh3 Me
5a 80%)
O
2a
OH
OMe
4a
O O TPP / CHCl3, O2, hR O OMe OMe 0 oC, 2 h RB / MeOH-drop of AcOH, O2, hR -10 oC, 5 h Me O
6a 69%)
OMe OMe
3b 82%)
O O OMe OH
Me
2b
6b 72%)
42
O O
O O
O OM OOH
l3
OM OM
3c (35%)
O OM OM
2c
O i RB / M OH O
hR
O OM OH
C 4h
ii PPh3
6c (69%)
43
/ CHCl , O , R O O O O C,
O O O
O O
R /
OH, O , R C,
2f
3f (98%)
/ CHCl , O , R O O O O
C,
O r O O O
(i) R /
OH, O , R C,
O O
3g (98%)
2g
O
2h
44
.
O
7
O O O
(60%)
O O
O R
i
O O O
8 (41%)
O
O O
(ii) R
OH
45
(i) RB / OH, O , R - 5 C, 4
O O O
t l O O
(68%)
O R t O
O O
8i (46%)
Condition 1
eOH, 0 oC
O O O e OOH
O O
O e O e
Recovery of starting
aterial
46
R3 R4
OMe OMe
O2
O R4
R 4 OMe O OH
O R4 OMe OMe O O
O R
1
AcOH OMe R4 = H O O
R3
ISOLATED
R3
47
O O OMe OH C 16H33
MeO2C C16H33
H C16H33 CO2Me
O CO2Me O OH O C16H33
HO2C
H O
Untenone A
Plakevulin
Inhibitory activity against N polymerases E and K including the Cytotoxicity against murine Leukemia L1210 and carcinoma KB cells
ll the above 3 natural products were isolated from an Okinawan sponge, Plakortis sp.
References 1. Ishibashi, M.; Takeuchi, S.; Kobayashi, J. Tetrahedron Lett. 1993, 34, 3749. 2. Tsukamoto, S.; Takeuchi, S.; Ishibashi, M.; Kobayashi, J. J. Org. Chem. 1992, 57, 5255. 3. Tsuda, M.; Endo, T.; Perpelescu, M.; Yoshida, S.; Watanabe, K.; romont, J.; Mikami, Y.; Kobayashi, J. Tetrahedron 2003, 59, 1137. Few earlier synthetic works 1. Saito, .; Takeuchi, R.; Kamino, T.; Kuramochi, K.; Sugawara, .; Sakaguchi, K.; Kobayashi, S. Bioorg. Med. Chem. Lett. 2004, 14, 1975. 2. Saleh, -B.; Jermy, R. .; Michael, G. B. .; ndrew, C. R.; Roger, C. W. J. Chem. Soc. Perkin Trans I 2002, 476. 2. Saito, .; Takeuchi, R.; Kamino, T.; Kuramochi, K.; Sugawara, .; Sakaguchi, K.; Kobayashi, S.; Tsuda, M.; Kobayashi, J. Tetrahedron Lett. 2004, 45, 8069.
48
1
O OMe OMe i 4
2
PP / CHCl3, O2, R ,
5 (+/-)-U tenone A
ref. 1 O O O CO2Me OH C16H33
(+/-)-Manzamenone A
(+/-)-Plakev lin
References 1. Saito, .; Takeuchi, R.; Kamino, T.; Kuramochi, K.; Sugawara, .; Sakaguchi, K.; Kobayashi, S. Bioorg. Med. Chem. Lett. 2004, 14, 1975.
Ph O N Ph
O O O Ph R1 R2 O N O Ph
-CO2Et H
Ph -CH2OH H O N N R1 R2 R
2 1
1
R 2 R
O N O
2
H MS OT
O N H OH O + O N HO H Ph Ph 3. : 1
OH Ph H
H H, Me, OTBS
O R2
References 1.50 Yamamoto, Y.; Yamamoto, . Eur. J. Org. Chem. 2006, ASAP. 2. Wang, Y.-C.; Lu, T.-M.; Elango, S.; Lin, C.-K.; Tsai, C.-T.; Yan, T.- . Tetrahedron: Asymmetry 2002, 13, 691.
Elango, S.; Yan, T.-H. J. Org. Chem. 2002, 67, 6954 O OMOM OMOM Martin, S. .; Tso, H.-H. Heterocycles 1993, 35, 85.
R1 = R4 =H R2 = R3 =Me R R
2 1
PhH2CO
OH
O N
H Ph
O O N Ph
Me Me
O N
Ph R1 = R2 = R3 = R4 =Me Me Me
R3 R4
Me Me
Me N Ph O
1 : 1 Me
51
Ami
lit l
Pa
ati tati
Tet
52
-
t xi
OMe OH
PhI(OAc)2/Bu4NIO 4 MeOH-CH2Cl2, 0 oC
1a-i
OMe OMe O
N O O
R=Boc or Cb for 3a, 4a, 5a-i: R = Boc for 3b, 4b, 6a-i: R = Cb
R N O
OMe OMe
3a,b
R2 R1
2a-i MOB R1 2a 2b 2c 2d H H H R2 H Me
O O
5a-i 6a-i Adduct (Yield/ )c with 3a with 3b 5a (90) 6a (96) 5e (69) 6e (81) 5c (93) 6c (95) 5d (92) 6d (96)
R3 Te p/oCa Ti e/hb H H H H 0 0 0 0 1 1 1 1
Me H
53
a) Reaction te perature. b) Reaction ti e after the addition of RNHOH. c) Yields of pure and isolated adducts.
R3 R
OMe OH R
1
PhI(OAc)2/Bu4NIO4 MeOH-CH2Cl2, 0 oC
1a-i
OMe OMe O
R3 R
R=Boc or Cbz for 3a, 4a, 5a-i: R = Boc for 3b, 4b, 6a-i: R = Cbz
N O R2 R1 O
OMe OMe
R1
3a,b
2a-i MOB R R 2e 2f 2g 2h 2i
1 2
5a-i 6a-i
o a
Temp/ C 0 0 50 50 50
Time/h 1 1 3 12 12
Adduct (Yield/ )c with 3a with 3b 5e (71) 6e (81) 5f (70) 6f (74) 5g (84) 6g (90) 5h (91) 6h (90) 5i (71) 6i (92)
H CO2Me H CO2Me H H H H H H H H Me Br
O O
a) Reaction temperature. b) Reaction time after the addition of RNHOH. c) Yields of pure and isolated adducts.
54
MNC Ea = 24.0
MNT Ea = 21.0
MXC Ea = 47.2
MXT Ea = 48.5
ONC Ea = 36.5
OXC Ea = 45.4
OXT Ea = 48.2
ButO endo N
HF/6-31G
exo X
55
4c-g
1a
O OMe OMe O O O O Ar O N O
N O
Ar
2a
Entry 1 2 3 4 5
56
3c-g
Ar Ph 4-t-BuC6H4 4-TMSC6H4 4-OMeC6H4 2-nathathyl Temp/oC -10 -10 -10 -10 -10 Time/h 24 24 24 24 24
5c-g (major)
Products Yield/ 6 83 91 82 96
4c
MeOH-CH2Cl2, -10oC
1a-f
R3 R
2
OMe OMe O R1
O O
O N OMe OMe O
O Ph R3 R2 O R1
O Ph
N O
+ MeO O
MeO O R1
O R3 R2 Ph
2a-f ntry 1 3 4 5 6
1
5c-10c (major) Products 5c/5c' 6c/6c' 7c/7c' 8c/8c' 9c/9c' 10c/10c' ield/ 6 85 2 6 86 75
5c'-10c' (minor) de ( )a 78 8 8 87 46 52
H Me H H H H
O O
57
L - IL column)
HOH
4g
MeOH CH2Cl2, 10 oC
1a d
R3 R2 R
1
OMe OMe O
O O O R2 O R3 O R1 MeO MeO O O R1
O O R3 R2
OMe OMe O
2a d 3g Entry 1 2 3 4
1 2 3
5g-8g (major) Temp/o -10 -10 -10 -10 Time/h 24 24 24 24 Products 5g/5g' g/6g' 7g/7g' 8g/8g' Yield/% 96 92 92 96 de (%)a 90 80 88 90
5g'-8g' (minor)
Me Me
O O
hydrolysis
H OH
(+/-)-Valienamine
Entry 1 2 3 4 5 6
ondition F3(OEt)2, u4 I, 2 l2 , reflux MSI, 2 l2, F, 1 l, 2O, F, 1 l, reflux 2O, 0.1 l : Acetone 1 : 1 0.1 l : Acetone 1 : 1 70 o
3
bz O OMe OMe
5 ntry 1 2 3 4 5 6 7 ondition AcO , 2 l2 , 0.1eq Oxalic Acid, F, 2 O, 50% FA : 2 l2, 1 : 5, 50% FA : 1: 5, 60 o 2 l2 O2 , entane, 0.1 l : MeO 1 : 1, 0.1 l : MeO 1 : 1, 70 o
6
bz O O O O
recovery of SM
60
OMOM 1. IBD, MeOH,0 C OH 2. Bu4NIO4, CbzNHOH CH 2Cl2, 0 oC 81% Cbz N O OMe OMOM
Cbz O
OMOM OMe
OMOM OMe
O Cbz N O O
10
OH
10OH Entry 1 2 3 4 5 6 7 8 9
61
11 OH Product (11) 37% Trace Recovery of SM Recovery of SM Recovery of SM Trace Messy Messy Messy 60%
Reagent 6N HCl, THF 6N HCl, CH2Cl2 5% Oxalic acid, THF 70% AcOH, THF (CH3)2S : MeOH= 1 : 5 PTSA, Acetone BF3.OEt2, Bu4NI, CH2Cl2 MeSiCl3, NaI, CH3CN TMSI, CH2Cl2 50% TFA : CH2Cl2 = 1 : 2
10
11 OH
Cbz Acetone pTSA HC(OMe)3 NH O O
12
13
OH
14 OH
Cbz NH OH OH OH NaOMe, MeOH quant. OH NH2 OH OH
13
Conduramine A-1
62
Tetrodotoxin
OH HO HO O O O H NH N H OH NH2 OH
isolated from the ovaries and liver of the Japanese puffer fish the tora fugu (tiger puffer)
()-tetrodotoxin (TTX)
total syntheses
( )-TTX: (a) Kishi, Y.; Aratani, M.; Fukuyama, F.; Nakatsubo, F.; Goto, T.; Inoue, S.; Tanino, H.; Sugiura, S.; Kakoi, H. J. Am. Chem. Soc. 1972, 94, 217. (b) Kishi, Y.; Fukuyama, F.; Aratani, M.; Nakatsubo, F.; Goto, T.; Inoue, S.; Tanino, H.; Sugiura, S.; Kakoi, H. J. Am. Chem. Soc. 1972, 94, 21 . ()-TTX: Ohyabu, N.; Nishikawa, T.; Isobe, M. J. Am. Chem. Soc. 2003, 125, 87 8. ()-TTX: Hinman, A.; Du Bois, J. J. Am. Chem. Soc. 2003, 125, 11510. ( )-TTX: Sato, K.; Akai, S.; Sugita, N.; Ohsawa, T.; Kogure, T.; Shoji, H.; Yoshimura, J. J. Org. Chem. 2005, 70, 74 6.
63
Retrosynthetic Analysis
O OH OMe H N MeO O O O O
OH HO HO O O O
H NH N H OH NH2 OH TBSO
OAc
H H N
O O NAc
TBSO
AcO O O OAc
OAc NHAc
OH O-t-Bu
tetrodotoxin
OMe OMe O OR O OH
TBSO
OTBS OMe O OR O O OH
OH OMe
CHO
vanillin
64
O OMe
DAIB
R2 O O
RO
OMe OMe R2
t- u-O
O N
MeOH, rt
O O
O O
OR1 O OMe
R2 OMe
2a-d Product (Yield/%) 2a (95) Solvents MeOHCH2Cl2 ClCH2CH2Cl 2b (96) 2c (95) 2d (94) MeOHCH2Cl2 MeOHCH2Cl2 MeOHCH2Cl2 Temp./oC 55 85 55 55 55
3a-d Product (Yield/%) 3a (46) / 2a (48) 3a (0) / 2a (95) 3b (0) / 2b (70) 3c (0) / 2c (91) 3d (0) / 2d (75)
65
Conclusions
The iels- lder adducts obtained from MOB chemistry were realized as powerful intermediates for the preparation of various molecular skeleta. New synthetic methodologies were successfully applied for the syntheses of biologically intriguing and pharmacologically important natural products. The potentiality of MOB chemistry was further validated by the reactions with hetero dienophiles in an effort to provide methodologies in the domain of heterocyclic chemistry. The substituent effect and solvent effect on the reaction between singlet oxygen and MOBs will be studied in detail. Nitroso compounds have emerged as important hetero dienophiles for MOBs; which delivered iels- lder adducts with excellent selectivities and yields. The applicability of the methodology is exemplified by the synthesis of conduramine- 1; studies towards the synthesis of related conduramines are underway.
66
Acknowledgements
National Tsing Hua University National Science Council Ministry of Education, Taiwan
67
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70
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