9. Synthesis of conjugated dienes and polyenes |
399 |
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SO2 |
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1. n-BuLi |
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O |
I |
3. |
(COCl)2 , ∆ |
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4. |
(CH3 )2 CHCH2NH2 |
(75) |
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5. |
680 °− 700 ° C |
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O |
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2. n-BuLi, CO2
O
O
N
H
O |
Pipercide |
o-Quinodimethanes can be made in situ by sulphur dioxide extrusion from 1,3-dihydro- 4,5-benzo[c]thiophene-2,2-dioxide derivatives (equation 76)124,124j . o-Quinodimethanes undergo facile intramolecular Diels Alder reaction with an internal alkene to result in polycyclic compounds. An expedient synthesis of estrone derivative, an enantioselective synthesis of (C)-esterdiol and a short synthesis of a lignane: were achieved following this strategy (equations 77 and 78)125,126. Heteroaromatic o-quinodimethanes can be prepared in situ by sulphur dioxide extrusion from the appropriate sulpholene precursors which readily undergo Diels Alder reactions (equation 79)127.
OAc |
OAc |
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Toluene
SO2
180˚C
Ph
Ph
(76)
MeOOC
OAc
COOMe
COOMe
COOMe
Ph
400
O
O
O
O
Ph
N O
S
O2
O
Ph
N
Goverdhan Mehta and H. Surya Prakash Rao
O
O |
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di-n-butyl phthalate |
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SO2 |
210 °C |
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H |
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H |
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(77) |
∆ |
O |
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SO2 |
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O |
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Ar |
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Ar |
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O |
(78) |
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O |
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O |
O
O
Ar O
O
K2 |
CO3 |
Ph |
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∆ |
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N
O |
(79) |
O |
N Ph |
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O
N Ph
O
9. Synthesis of conjugated dienes and polyenes |
401 |
2. Nitrogen
Butadiene can be obtained by thermal extrusion of a nitrogen molecule from a cyclic diazene (equation 80)128. However, this reaction has found only limited synthetic applications.
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Na2N2O3 |
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(A ngeli’s salt) |
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H2 C |
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CH |
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CH |
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CH2 |
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H + |
+ |
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− N2 |
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N |
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H |
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N − |
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3. Carbon dioxide and carbon monoxide
Isochromones lose carbon dioxide on heating via retro-Diels Alder pathway to result in o-quinodimethanes (equation 81)124i,129. An isochromone route to podophyllotoxin derivative has been described (equation 82)130. Diels Alder adducts of ˛-pyrone readily extrude carbon dioxide on thermal activation to furnish cyclohexadienes, which are useful substrates in tandem Diels Alder reactions (equation 83)131.
O
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∆, 300˚C |
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(81) |
O |
− CO2 |
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O |
MeO |
O |
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MeO |
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∆, 300˚C, −CO2 |
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N Ph |
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MeO |
O |
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MeO |
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O |
O |
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N |
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O |
Ar |
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Ar |
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Ph |
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Ar = 3, 4, 5-(MeO)3 C6 H2 |
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(82) |
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O |
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O |
220 ˚C |
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(83) |
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Photoand thermal decarbonylation of cyclic unsaturated ketones leads to the formation of cyclic 1,3-dienes. Such decarbonylations are commonly observed in 7-ketonorbornenes and related bridged bicyclic systems to give cyclohexadienes (equation 84)132.
O
(84)
∆
− CO
402 |
Goverdhan Mehta and H. Surya Prakash Rao |
C. Ring Opening of Cyclobutenes
Cyclobutenes undergo facile, thermally induced conrotatory ring opening to generate 1,3-dienes133. Highly oxygenated butadienes are useful in Diels Alder and heteroDiels Alder reactions. A number of such oxygenated 1,3-butadienes can be readily prepared from the corresponding cyclobutenes by thermal ring opening. Examples are given in Table 11.
1,3-Dienes generated in this fashion can be trapped with dienophiles, either intramolecularly or intermolecularly, and this strategy has been exploited for the synthesis of natural products (equations 85 and 86)135,136.
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OMe |
O |
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OMe |
OMe |
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OMe |
150 − 170 ˚C |
+ |
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O |
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O |
O |
(85)
O OMe
O O
O
100˚C
O ∆
EtOOC
COOEt
(86)
O
H
H
COOEt
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9. Synthesis of conjugated dienes and polyenes |
403 |
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TABLE 11. Substituted butadienes through cyclobutene ring-opening reactions |
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Substrate |
Conditions |
Product |
Reference |
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OMe
OMe
340 ˚C
134a
SPh
OSiMe3
180 ˚C
OSiMe3
OSiMe3
25 ˚C
EtO
EtO OSiMe3
25 ˚C
EtO
Cl
80 ˚C
MeO
MeO
80 ˚C
MeO
OHC
− 78 ˚C
POCH2
P = 4-MeOC6 H4 CH2
HO
SPh
OSiMe3
134b
OSiMe3
OSiMe3
134c
OEt
OEt
OSiMe3
134c
OEt
Cl
134d
OMe
MeO
134d
OMe
OHC
134e
CH2 OP
CHO
PCC, RT |
134e |
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S |
S |
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S |
S |
ROOC |
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COOR |
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∆ |
134f |
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ROOC |
ROOC |
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Me |
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Me |
404 |
Goverdhan Mehta and H. Surya Prakash Rao |
Several ingenious syntheses of natural products have been developed by exploiting benzcyclobutene ring opening to o-quinodimethane. Particularly, the intramolecular Diels Alder strategy employing o-quinodimethane intermediates has been very effective for the construction of polycyclic structures. Selected examples are gathered in Table 12.
[n.2.0]Bicyclic butenes having a dialkylamino substituent on the bridge head carbon undergo facile ring opening to result in 2-carbon ring enlarged cyclic 1,3-dienes (equation 87)138. This approach has been utilized for the synthesis of several natural
TABLE 12. Polycycles through benzocyclobutene ring opening
Substrate |
Product |
Reference |
t-BuO
OBut
H
H |
H |
137a |
MeO |
MeO |
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o |
o |
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MeO |
NC |
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MeO |
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H |
O |
O |
N |
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O |
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O |
Ar |
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Ar :(MeO)3 C6 H2 ;R = H, Me COOR
O
O
O
RO
O N
O
R = C7H7
o |
o |
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NC |
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MeO |
137b |
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H |
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MeO |
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O |
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O |
NH |
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O |
137c |
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O |
COOR |
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Ar |
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O |
O |
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RO N |
O |
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O |
137d |
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O
Chelidonine intermediate
9. Synthesis of conjugated dienes and polyenes |
405 |
products which contain medium or large rings such as steganone139, muscone140 and velleral141.
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N |
COOMe |
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N |
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COOMe (87) |
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(CH2 ) |
n |
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∆ |
(CH2 )n−2 |
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R |
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R |
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trans-7,8-Diacetoxy[4.2.0]octa-2,4-diene derived from cyclooctatetraene, on reduction with lithium aluminium hydride and oxidative ring opening of the cyclobutane ring, results in octa-2,4,6-triene-1,8-dial (equation 88)142. This synthon has been used for the construction of the heptaene portion of the macrolide antibiotic amphotericin B143.
OCOCH3
Hg(OAc)2
OCOCH3
1. LAH
(88)
2. O2 , KOH
3. H3O+
O−
OHC
CHO
O−
D. Retro-Diels Alder Reactions
Retro-Diels Alder reactions can be used to regenerate dienes or alkenes from ‘Diels Alder protected’ cyclohexene derivatives under pyrolytic conditions144. Most of the synthetic utility of this reaction comes from releasing the alkene by diene-deprotection. However, tetralin undergoes cycloreversion via the retro-Diels Alder pathway to generate o-quinodimethane under laser photolysis (equation 89)145. A precursor of lysergic acid has been obtained by deprotection of the conjugated double bond and intramolecular Diels Alder reaction (equation 90)146.
IR laser, 947 cm−1
(89)
− C2 H4
406 |
Goverdhan Mehta and H. Surya Prakash Rao |
COOCH3
COOCH3
N |
200˚C |
N |
|
OCH3 |
OCH3 |
N |
|
N |
H |
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H |
(90)
COOCH3
N
OCH3
N
H
E. Orthoester Claisen Rearrangements
Allylic alcohols undergo symmetry-allowed orthoester Claisen rearrangement, when treated with trialkyl orthoacetate in the presence of an acid catalyst. When this reaction is applied to 2-butyne-1,4-diols, one of the products formed is a 1,3-diene147. 1,3-Dienes also result when this reaction is performed on bisallylic alcohols (equation 91)148. Regiospecific conversion of allylic alcohols to two-carbon extended dienoate esters, by performing
an orthoester Claisen rearrangement with phenylsulfinyl orthoacetate, has been described (equation 92)149.
H3 CC(OEt)3 |
EtOOC |
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EtCOOH, ∆ |
(91) |
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OH |
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PhSOCH2C(OEt)3 |
(92) |
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EtCOOH, ∆ |
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COOEt |
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OH |
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9. Synthesis of conjugated dienes and polyenes |
407 |
V.WITTIG AND RELATED REACTIONS
A.The Wittig Reaction
The Wittig reaction is a classical method for the transformation of a carbonyl group to an olefin150. The stereoselectivity of the olefin formation in the Wittig reaction depends highly on the ylide structure and the reaction conditions151. Generally, non-stabilized ylides give predominantly the Z-alkenes and stabilized ylides give higher selectivity of E-alkenes. The nature of the base also plays a role in stereoselectivity of olefins derived from unsaturated ylides152. Wittig carbonyl olefination is used extensively in olefin, diene and polyene synthesis and has found new areas of application in industrial practice. Application of the Wittig reaction for the synthesis of natural products, especially carotenoids, has been extensively reviewed150c,153.
When one of the reacting partners of the Wittig reaction, i.e. the carbonyl compound or the ylide, has a double bond already present in it, the resulting product is a diene. Usually, when polyenes are synthesized following the Wittig method, a mixture of stereoisomers is formed. However, all trans-polyenes can be obtained by equilibrating the mixture with a catalytic amount of iodine, or under photolytic conditions. Examples of dienes and polyenes generated via a Wittig reaction are given in Tables 13 and 14, respectively.
The Wittig methodology can also be employed for diene synthesis in an intramolecular version. Propenylidinephosphoranes having a carbonyl group undergo intramolecular Wittig reactions to generate cyclic dienes (equation 93)156.
PPh3
(93)
O
The butadienylphosphonium salt reacts with dianions on the end-carbon atom to result in an intermediate Wittig ylide, which undergoes normal olefination to generate (E,Z)- dienes of high stereoselectivity. This reaction is in effect a three-component coupling of a nucleophile, Wittig salt and an electrophile157. This strategy of three-component coupling was utilized for the diene construction of macrolide latrunculin A (equation 94)158.
CHO
O O
TMS +
O
|
+ |
− |
OP |
OP′ |
1. |
PPh3 Br |
|
||
|
|
|
2 eq. LDA |
|
(94)
O
O
O
TMS
OP OP′
P = [2-(trimethylsilyl) ethoxy] methyl; P′ = t-BuMe2Si
408
TABLE 13. Dienes through Wittig reaction
Carbonyl Compound |
Wittig Yilide |
Product |
Reference |
|
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|
Ph |
H |
O |
O |
|
CHO |
|
H |
CHO
N
OHC
PPh3
PPh3
PPh3
Me
Ph
P
Ph
Ph
O
H
O
154a
Swainsonine
154b
|
MeO |
|
MeO |
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MeO |
OMe |
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MeO |
OMe |
|
154c |
||
O |
||
N |
O |
Fredericamycin