photo chemistry mob

8/6/2019 Photo Chemistry Mob

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Organic Photochemistry

Introduction to Photochemistry

Classifications of Photochemical Reactions

Application of Photochemistry in OrganicSynthesis


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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).


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Chemically useful light is generally in the range of 200-400 nm

Often employ filters to regulate the wavelength of the radiation

T

n

T*

T

n

T*

T

n

T*

T

n

T*

T

n

T*

ground state (S0) n-T* (S1) n-T* (T1) T-T* (S1) T-T* (T1)


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A Jablonski diagram, named after the Polish physicist AleksanderJaboski, 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.


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Physical Processes Undergone by Excited Molecules

So + hv --- S1 Excitation

S1v -- S1 + heat Vibrational Relaxation

S1 ----- So + hv Fluorescence

S1 ---- So + heat Internal Conversion

S1 --- T1 Intersystem Crossing T1

v -- T1 + heat Vibrational Relaxation

T1v -- So + hv Phosphorescence

T1 --- So + heat Intersystem Crossing

S1 + A (So) --- So + A (S1) Singlet-Singlet Energy Transfer

T1 + A (So) -- So + A (T1) Triplet-Triplet Energy Transfer


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Why Use Photochemistry

Overcome large kinetic barriers in a short amount of time

Produce immense molecular complexity in a single step

Form thermodynamically disfavored products

Allows reactivity that would otherwise be inaccessible by almostany other synthetic method

The reagent (light) is cheap, easily accessible, and renewable

Drawback Reactivity is often unpredictable

Many substrates are not compatible

Selectivity and conversion are sometimes low


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Chemical Processes undergone by Excited Molecules

(A-B- ) A-B. + . imple leavage

(A-B- ) E + F Decomposition

(A-B- ) A- -B Intramolecular Rearrangement

(A-B- ) A-B- ' Photoisomerization

(A-B- ) A-B- -H + R. Hydrogen Atom AbstractionRH

(A-B- ) (AB )2 Photodimerization

(A-B- ) AB + A* PhotosensitizationA


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1) -Cleavage (Norrish type I reaction). In solution the radicals undergofurther reactions to give products.

hv

0 n

C

h

h

hv

h

h

h

h

C


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An intramolecular example:


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Chang, S.-Y.; Huang, S.-L.; Villarante, N. R.; Liao, C.-C. Eur. J. Org. Che

m.2006, 4648-4657.


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Chemoselective Photorearrangement of Diazinobarrelenes.

Deuterium Labeling Study

Cheng, A.-C.; Chuang, G.; Villarante, N.; Liao, C.-C. J.Org. Chem. 2007, 72,

6 0- 6 7


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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 08-8 21


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28

Recent Advances in the Chemistry of

Masked o-Benzoquinones

Nelson R. Villarante

Department of ChemistryNational Tsing Hua University

Hsinchu 300, TAIWAN


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2

Generation of Masked o-

Benzoquinones

Oxidant : TTN = Thallium(III) nitrate [Tl(NO3)3]

BTIB = Bis(trifluoroacetoxy)iodobenzene [PhI(OCOCF3)2]

DAIB = Diacetoxyiodobenzene [PhI(OAc)2]

OMe

O

[Oxidant]

'OO

O '

OMe


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30

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

Out of eight-possible isomers, only a single isomer is observed

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.


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31

Dimerization (DI) vs Diels-Alder

Reaction (DA)

RateDI DI

RateDA DA Dieno ile

RateDI DIRateDA DA Dieno ile

as ed - enzo inone

X


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32

Reactions of MOBs

Ref: Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856.

O

OR1

OR2R

XOMe

OMe

O

R

O

XR

OMeMeOH

R

X

OMe

OMeO

O

OMeOMe

R

C60

CH2=CH

CH=C

HX

CH2

=CHX

R1=R2=CH3R1 =R

2 =CH 3

+

h, OBn, h, ePh

X=CHO, COMe, CO2CH3

X

Rn

X

O

OMe

OMe

Rn

X

O

OMe

OMe

R1=R2=CH

3

R1=R2=CH3

X=CH2,

O, NBz,

X

R1=R2=CH3

X=O, NH

O

R1=R2=CH3

OMe

Rn

O

O

OMe

OMe

O

OMe

OH

R

DAIB

MeOH, 0

C


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33

Reactions of MOBs

Ref: Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856

O

OR1

OR2O

OMe

O

R

O

XH

O OMeH

O

OMe

O

X

R1

= CH3R2 = CH2CH=CH2

R2 = CH2CH=CHCH=CHX

R1 = CH3

+R1 = R2 = CH3

R3 = OX( )n

n = 1 - 3X = H or TBS

R4 = H

O

OMeOMe

OX

( )n

O

OMeOMe

OX

( )n

+

R1 = R2 = CH3

R4 =

X = TBS

R3 = H

O

MeOMeO

OX

O

MeOMeO

OX

+

OX

4 eq. SmI2/-78oC

THF/MeOH

O

OX

O

H

OXH

OXO

OBz

H

H

H

.. O

BzO

R4

R3


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34

Diastereoselective Intermolecular Diels-Alder Reactions of

MOBs

O

O

O

OMeOMe

R1

R2

R3

R4

O

OMe

Xc

O

O

MeO

OMe

Xc

O

+

R3 R3R4

R2

R1 R1

R2

R4

R1 R2 R3 R4 t/h de/%* Yield/%

1a

1b

1c

1d

1e

1f

1g

1h

1i

1j

1k

H Ketal

H Ketal Br

H H COMe

H H CO2Me

H H TMS

H H Br

H H H OMe

H Me Br

H Me TMS

1 2a2a' 71 53

1 2b/2b' 71 57

48 2c/2c' 67 66

48 2d/2d' 73 65

36 2e/2e' 62 8372 2f/2f' 81 68

24 2g/2g' 83 98

48 2h/2h' 82 95

48 2i/2i' 78 77

48 2j/2j' 74 95

48 2k/2k' 1 98Me H Br

CH2Cl2, r

OMe

Ketal =O

O* eter ined by 1H NMR (400 MHz) analysis.

2a-k( ajor) 2a-k'( inor)

H

H

H

H

H

H

H

H

H

H Br Ketal H

1a-k

Products


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36

Syntheses of Natural Products

O

O

O

(+)-3F-Angeloyloxy-furanoeremophilane

O

OR1

OR2R

NNH

MeOH H

H

MeO2C OAr

OMe(+)-Reserpine

Chem. Commun. 1996,1537

HO

CO2HClerodane diterpenic acid

Synlett1998, 912

HO

CO2H

HO

HO

O

O

H

HMeO2C R'

CO2Me

O

N

OH

HO

H

H

H

(+)-Bilosespenes A and B

(+)-Magellaninone

(+)-Eremopetasidone

(+)-Pallescensin B

(+)-Forsythide aglucone dimethyl ester

Clerodane diterpenic acid

Angew. Chem. Int. Ed.

2002,41, 4090

Org. Lett. 2003,24, 4741

Org. Lett. 2001,3, 263

Tetrahedron Lett. 1989,30, 2255

Chem. Commun.1999,117

Tetrahedron Lett. 1996,37, 6869

H

(+)-Capnellene

HO2C

Pure Appl. Chem.

2005,7,1221

Pure Appl. Chem.

2005,7,1221

H

H

H H


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37

Current Synthetic Targets

O

OR1

OR2RHO

H

(+)-Conidiogenone

O

OH

O

(+)-Eudesmadieneolide

O

O

OH

(+)-Drechslerine D

OH3CO2C

O

H OHH3COCO

O

O

CO2CH3OH

OO

OHO

Azadirachtin


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1


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3

Production of1O2 by

Photochemical MethodSen

hR1Sen*

3Sen*

ISC3

O2 1O2

Photosensitizers

ye: ose engal ( ), Tetraphenylporphyrin (TPP)

O O

Cl

Cl

Cl

Cl

I

NaO

I I

IO

ONaN

N

N

N


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40

Electronic Configuration of Ground State and

Excited State O2

2p

(3Wu)

(1 g)

(3Wu)

(1 u)

Reference:

http://www.rsbs.anu.edu.au/ResearchGroups/PBE/Oxygen/O2_1_%20ElectronicConfig.htm

157 KJmol-194 KJmol-1

Ground State Excited State Excited State

( 37g- ) (1(g

- ) (17g+)

(0.9772 eV) (1.6266 eV)


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41

ON2t-Bu

t-Bu

h, O2

MB, CH2Cl2- 8 oC

h, O2

8 %

6%

Ryang, H-S.; Foote, C. S. J. Am. Chem. Soc.1981, 103, 495

OO

O

O2, CH2Cl2

OO

O

OO

95%

Wood, J. L.; Graeber, J. K.; Njardarson, J. T.Tetrahedron, 2003, 59, 8855

O

O

N2

O

t-Bu

t-Bu

O

O

O

O

t-Bu

t-Bu

[4+2]

+OO

OO

3 26

OO OO

2.1 1.5

OO OO

14

Ene

Ene

+

+

OO

2.

3

Ene

atusch, .;Sch idt, G.Angew.

hem. Int. Ed.1988, 27, 717


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42

TPP / CHCl3, O2,hR

0oC,2h

O

O

OMe

OMe

O

Me

O

O

OMe

OMe

OMe

S

H2N NH2

rt, CDCl3 OH

HO

OMe

OMe

OMe

3b 82%)

3a 87%) 5a 80%)

TPP / CHCl3, O2,hR

0o

C,3h

RB / MeOH, O2,hRO

O

OH

Me

OMe-25oC,4h

PPh3

6a 69%)

OOMe

OOH

Me

O

4a

RB / MeOH-dropof

AcOH, O2,hR

-10oC,5h

O

O

OHOMe

6b 72%)

O

OMe

OMe

Me

O

OMeOMe

Me

2a

2b


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43

l3

R

4

i RB / M OH O hR

C 4 h

ii PPh3

OO

OM

OH

6c (69%)

O

O

OM

OM

O

3c (35%)O

OM

OM

2c

OO

OM

OOH

4c(Yield is not

yet determined)

:


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45

OO

O

R

(i) RB / OH, O , R

- 5

C, 4

(ii) OH

R t

R t l

R i r

OO

O

OO

OO

O

(46%)

(68%)

OO

O

(41%)

O

O

O

2

8i

8

8


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46

O

O

OOH

e

O e

O

O

O e

O e

Oe

Condition 1 eOH, 0 oC

Condition 2: R / eOH, O2, hR

Recovery ofstarting aterial

OR


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47

Plausible Mechanisms for the Observed Products

OOMe

O

R3

O

O

O

O

O

OO

OMe

OMe

1O2

R3

R1

R1

R3

R1

4+ 2]

R4

R4

O

R3

O

O

O

OR1

R4

OMe

R4

O

O

OMe

OMe

OR1

R3 R4

O

OOHO

OMe

R3

R1 R4 + H2O

-MeOH

ISOLATED

PPh3

AcOHO

O

OMe

R3

R1

O

R4 = H

O

OHO

OMe

R3

R1 R4


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4

A Short Synthesis of (+/-)-Untenone A

References

1. Saito, .; Takeuchi,R.; Kamino, T.; Kuramochi, K.; Sugawara, .; Sakaguchi, K.; Kobayashi, S. Bioorg.Med. Chem. Lett.

2004,14, 1975.

OH

OMe

CHO

i C15H31MgBr

ii H4Cl s t.

OH

OMe

C15H31HO

Pt/H2

80%

99%

OH

OMe

C16H33

DAIB

MeOH, 0

C

95%

OMe

OMeO

C16H33

i PP / CHCl3, O2, R,

4

ii PPh3

78%

O

OH

C16H33

O

OMe

5 (+/-)-U tenoneA

ref. 1

ref. 1

C16H33

CO2Me

C16H33

OHO2C

H

H

MeO2C

CO2Me

OH

C16H33

O

O

O

(+/-)-ManzamenoneA

(+/-)-Plakev lin

1 2 3

4


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51

Diels-Alder Reactions of Nitroso Compounds

Hart,H.; Ramaswami, S. K.; Willer,R. J. Org. Chem. 1979,44,1.

R

O

O

PhH2CO NHOH

O

N

OBr

Cbz

O

O

R = BrR = H

MeO2

C

NO

Cl

NH2+

Cl-O

O

O

OMOM

OMOM

PhH2CO NHOH

O

N

O

Br

Cbz

MOMO

MOMO

NO

Ph

H OHOH

O

NPh

Elango, S.; Yan, T.-H. J. Org. Chem. 2002,67, 6954 Hudlicky, T.; Olivi,H. . J.Am. Chem. Soc. 1994,116, 5108.

Yamamoto,Y.; Yamamoto,H. Eur.J. Org. Chem. 2006,ASAP.Martin, S. .; Tso,H.-H.Heterocycles 1993,35, 85.

OR2

R3

N

O

Me Me

Me

Me

O

Ph

O

N

Me Me

Me

Me

O

+

1 : 1

Ph

R1 = R4 =H

O

NPh

R1

R4

N

O

Me

Me

O

Ph

R2= R3 =Me

R1 = R2=

R3= R4 =Me


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53

Hetero-Diels-Alder Reactions of

Masked o-Benzoquinones with Nitroso Compounds

OMe

OH

R1R2

R3

OMe

OMe

OR1

R2

R3

PhI(OAc)2/Bu4NIO4

MeOH-CH2Cl2, 0oC

RNHOH(4a,b)

MeOH-CH2Cl2,

N OR O

NOMe

OMe

OR1R

2

R3

R

+

R=Boc orCb0 oC or 50 oC

Te p/oCa Ti e/hbAdduct (Yield/ )c

a)Reaction te perature. b)Reaction ti e after the addition ofRNHOH.c)Yields ofpure and isolated adducts.

R1 R2 R3MOB

1a-i

2a-i

3a,b5a-i6a-i

for3a,4a,5a-i: R = Bocfor3b,4b,6a-i: R = Cb

with 3a with 3b

2b Me H H 0 1 5e(69) 6e(81)

2c H Me H 0 1 5c(93) 6c(95)

O

O2d H H 0 1 5d(92) 6d(96)

2a H H H0

1 5a(90) 6a(96)


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54

OMe

OHR1

R

R3

OMe

OMe

O

R1R

R3

PhI(OAc)2/Bu4NIO4

MeOH-CH2Cl2,0oC

RNHOH(4a,b)

MeO

H-CH2Cl2,

N OR O

NOMe

OMe

OR1R

2

R3

R

+

R=Boc orCbz0 oC or50 oC

Temp/oCa Time/hbAdduct (Yield/ )c

a)Reaction temperature. b)Reaction time after the addition ofRNHOH.c) Yields ofpure and isolated adducts.

R1 R2 R3MOB

1a-i

2a-i

3a,b5a-i

6a-i

for3a,4a,5a-i: R = Bocfor3b,4b,6a-i: R = Cbz

with 3a with 3b

O

O2i H H 50 12 5i(71) 6i(92)

2g H H Me 50 3 5g(84) 6g(90)

2h H H Br 50 12 5h(91) 6h(90)

2e H CO2Me H 0 1 5e(71) 6e(81)

2f H H CO2Me 0 1 5f(70) 6f(74)


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58

Diastereoselective Hetero-Diels-Alder Reactions of

Masked o-Benzoquinones with Nitroso Compounds

OMe

OH

R1R2

R3

OMeOMe

O

PhI(OAc)2/Bu4 IO4

MeOH CH2Cl2, 10oC MeOH CH2Cl2, 10

oC

+

2a d

1a d

3g

O O OMe

OMe

O

O

O

MeOMeO

O

OO

O

+

5g-8g (major) 5g'-8g'(minor)

R1R2

R3

R1R2

R3

R1 R2

R3

O HOH

O

4g

O

O

Entry

1

2

3

4

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

a. etermined y PL (Shim-peak L -SILcolumn)

1

Me

2

Me

3

O

O


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5

Towards the Total Synthesis of (+/-)-Valienamine

2

(+/-)-Valienamine

OMe

OHO

O

O

NOMe

OMe

O

O

O

Cbz

O

NOMe

OMeO

O

Boc

OH

H

CbzNHOH DAIB,Bu4NIO4 DIBALH, THF

O

HN

OOH

H

Ohydrolysis

85%

97%MeOH

1 2 3

4


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61

ON

OH

OMe

OMOM

Cbz

ON

OH

Cbz

O

Entry

12

3

4

56

7

8

9

10

Reagent

6N HCl, THF

6N HCl, CH2Cl2

5% Oxalic acid, THF

70%AcOH, THF

(CH3)2S : MeOH= 1 : 5PTSA,Acetone

BF3.OEt2,Bu4NI, CH2Cl2

MeSiCl3, NaI, CH3CN

TMSI, CH2Cl2

50% TFA : CH2Cl2 = 1 : 2

Product (11)

37%

Trace

Recovery ofSM

Recovery ofSM

Recovery ofSMTrace

Messy

Messy

Messy

60%

OMOM

OH

O

N

O

OMOM

OMe

Cbz1. IBD, MeOH,0oC

O

NOMOM

OMe

Cbz

OH

DIBALH,

THF-78 oC

81%

96%2. Bu4NIO4, CbzNHOH

CH2Cl2,0oC

8 9 10

10 11

A Sh T l S h i f C d i A 1


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62

A Short Total Synthesis of Conduramine A-1

O

NCbz

OH

H

O

NCbz

OH

O

L-Selectride,

THF-78 oC

NH

OH

OH

OH

Cbz

SmI2, THF

NH2

OH

OH

OH

76% 74%

NaOMe,MeOH

quant.

11 12 13

ConduramineA-1

NH

OH

OH

OH

Cbz

13

NH

OH

Cbz

14

O

OAcetonepTSA

HC(OMe)3

OH


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63

Tetrodotoxin

O OH

N

NH

O

()-tetrodotoxin (TTX)

OHHO

HO

H

HOH

NH2

O

isolated from the ovaries

and liver of the Japanesepuffer fish the tora fugu(tiger puffer)

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.

i i


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64

Retrosynthetic Analysis

O

O

OAcTBSO

OAc

HN

H

NHAc

NAc

O

O

OAc

AcOO OH

N

NH

O

tetrodotoxin

OHHO

HO

H

HOH

NH2

O

O

OHTBSO

OH

HN

O-t-Bu

O

O

MeO

OMe

O

OO

N

O

O

OMe

OMe

O

O

t-Bu-O

O

OR

O

OH

TBSO

O

TBSO

O O

OR

O

OH

OMeOMe

OTBS

OMeTBSO

O O

OR

O

OH

OH

CHO

OMe

vanillin

H Di l Ald R i f MOB i h B NO


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65

Hetero Diels-Alder Reaction of MOBs with BocNO

O

R1

O

O O

R2

OMeOMe

OH

OMeR

1O

O O

R2

N

O

O

OMe

OMeO

O

R2

OR1

t- u-O

O

DAIB

MeOH, rt

n-Bu4NIO4,BocNHOH

solvent, temp, 5 h

R1 R2Entry

1

2

3

4

5

1a

1a

1b

1c

1d

1a-d 2a-d 3a-d

TBS

TBS

H

H

H

Me

Me

CH2OMe

CH2OBn

CHO

Product (Yield/%)

2a(95)

2b(96)

2c(95)

2d(94)

Solvents Temp./oC

55

85

55

55

55

MeOHCH2Cl2

ClCH2CH2Cl

MeOHCH2Cl2

MeOHCH2Cl2

MeOHCH2Cl2

Product (Yield/%)

3a(46) / 2a(48)

Phenol

3a(0) / 2a(95)

3b(0) / 2b(70)

3c(0) / 2c(91)

3d(0) / 2d(75)


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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 ofbiologically intriguing and pharmacologically important natural products.

The potentiality of MOB chemistry was further validated by the reactions with heterodienophiles in an effort to provide methodologies in the domain of heterocyclicchemistry.

The substituent effect and solvent effect on the reaction between singlet oxygen andMOBs will be studied in detail.

Nitroso compounds have emerged as important hetero dienophiles for MOBs; whichdelivered iels- lder adducts with excellent selectivities and yields. Theapplicability of the methodology is exemplified by the synthesis of conduramine- 1;studies towards the synthesis of related conduramines are underway.

Conclusions


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Acknowledgements

National Tsing Hua University

National Science Council

Ministry of Education, Taiwan


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photo chemistry mob

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