6.2.6 Ring-cleavage reactions
H2SO4, MeCO2H
1. BuLi
2. Br(CH2)2CH=CHEt Ph3P+-CHEt CH2=CHCHO, H+
Me O
O
Et
Me
O Et
Me O
Et
Me O O
Me O
Synthesis of cis-jasmone from 2-methylfuran.
R1 O R2
O R2 OMe R1
MeO
O O O
Me Me
R2 R1
O
O
OHC CHO
MCPBA, or PCC
Br2
MeOH H+
ac et one, 0oC
Oxidative cleavage of furans to enediones.
O Br
CO2Me Br
O Br
CO2Me R
RM[Pd(0)]
66-94 %
MeZnCl or SnMe4 [Pd(Po-Tol3)2Cl2]
65-75 %
8
N O
OMe MeLi
MeO O Me2N
CH2Ph
O
OMe N
H Me
toluene, -95 oC, 91 % ee
Heterocyclics, 1998, (56) 165.
X X
O
E (i) n-BuLi, electrophile HO
(ii) resin cleavage PS-trityl resin
X=O, S
Synlett, 1998, 405.
R O
OTHP
I
SPh
Bu3SnH AIBN
OTHP R
O
Synlett, 1998, 1215.
O
R1
O R1
R2 O
Me
R2
R1 O
O O
O O
O
O Me
R2 or
R1 = H, OH R2 = Me, Ac R1 = H, OH R2 = Me
R1 = H, OH R2 = Me, H
Heterocyclic 1998, (48), 1631.
O
O
R*
O OH
R* O O OTMS
-78 oC
Lewis acid O
O O H
H
OH R* O
O O
O H
H CH2Cl2
Tetrahedron. Asymmetry, 1998, 1257.
O
N O O
Oi-Pr
O O
O O
O
TMSO
H O
4 steps
(i) asymmetric Michael reaction (ii) Ti(Oi-Pr)4
Tetrahedron. Asymmetry, 1998, 1165.
O O
HO O
O R1
R2 OH
R2 R1 (i) BuLi OH
(ii) R1R2CO
H+
J. Org. Chem. 1998, 5169.
O O
RO
O HO
H H
6 steps
11 : R = H 12 : R = Me
Eur. J. Org. Chem. 1998, 2073.
O O
R1
R2 OH R2
HO TsOH
R2 O R2
TsO R1
O PhH, reflux
Tetrahedron Lett. 1998, 2051.
O O
OH R
O
OH [O] R
13 14
Heterocyclics, 1998, (48) 129.
R1
O R1 [O]
EtO
O OEt O O
O N
O
O N O
N H
H H
H HO HO
O
O N
O H
H H H
O N
H HO
2
17
18 19
20
Synlett, 1998, 277.
N N
R3
R1 Bt
R2
H
O
N NH. BF4 R1
R2
H H
O 21
n n
Synthesis, 1998, 704.
O
O O
O Me
H H
H
Me TMSOTf
CH2Cl2 -78 oC Me
OO
Me
22
Heterocyclic, 1998, (47) 283.
6.3 Thiophenes 6.3.1 Introduction
S
N N Me
S N N
O H H
(CH2)4CO2H H
H
pyrantel anthelmintic agent
biotin (vitamin H)
S
O
S NH2
H2N Me
S S S
S COCH3 H3COC
O
O
S N
H
Me S
O
OHC CHO
Me
148 149
150 151 152
kahweafuran polyamine inverse agent
terthiophene
PKC inhibitory activity naphtho[2,3-b]thiophene-4,9-dione thieno[2,3-d][1,3]
oxazin-4-one
S N
H B N OH
CO2H
O S N
H N S O CN O
S
N
S S
N N MeO2C
153 154 155 156
thieno[3,2-c][1,5,2]
diazoborim-3-(2H)-one
thieno[3,2-d][1,2,3]
thiadiazole thiadizine thieno[b]quinolizidine
S O
H N
O O
S S
N
Ph N
N
S CO2H Cl
157 158 S
159 thiaisatoic
anhydride dithienopyridine thienoimidazothiazole
S B
S B B
S B S
S S
S N
N Ph Ph
Ph Ph
N(i-Pr)2 (i-Pr)2N
N(i-Pr)2
N(i-Pr)2
160 161
tetrathiaporphryrinogen porphyrin (thiophene substituted)
S
S
S
N N
N N
162
thiophene-containing porphyrin
S S S S
N N
Ph
Me Me
Ph O
O
CN
OMe Me
O O
CN
OMe Me
163 164
S S S S
S S S S
S S
S TMS
SMT
SPO(H2C)10 (CH2)10OPS
10
SMT
TMS 165
166
octithiophene
dodecithiophene
BnO2C S S S
S S S
S
S S S
S S S
CO2Bn
C8H17
C8H17 C8H17
C8H17
C8H17 C8H17
5 2 2
167
168
hexadecithiophene
hexithiophene
S
S S
C6H13 C6H13
C6H13 C6H13
C6H13 C6H13
S S
S
2 2
2
169 170
6
oligomeric vinylthiophene star-shaped hexithiophene
S S
S S S
S S
S S MeO2C S
C8H17 C8H17
C8H17
TBDMS TBDMS
O O
171
172
pentithiophene
quaterthiophene
S
S
CN CN
S S
173 anthradithiophene 174 dithiophene
Conducting materials
S S
S NO2
S S S
N CH2OH
CN CN
S
S S
S Bu2N
175
176
177
N N O S
N N
O S
Ph B
Ph
Cl 178
n n
S S
S S
N H
NH
O
O
O
n
C12H25 CO2NMe4
n
180 181
Se
Se
Se S
Se S
S
S Se t-Bu
t-Bu O
Ph
Ph Ph
Ph
O O
CHO
CH(OEt)2 Me2N
182 183 184
185
6.3.2 Ring synthesis
R1
R2 o
o
S R2
R1 P4S10
or H2S/HCl Paal synthesis
EtO S
O
OEt O
R R
O
O NaOEt/EtOH
O OEt
S OEt
O R R O-
O
S EtO O O-
R
H R CO2Et
O
R S O
R CO2Et
-O2C
S
R R
CO2Et
-O2C Hinsberg synthesis
R1 R2
SH O
R1 R2
SH X C N XCH2CN/ Et3N
( X = CN, COR, CO2R)
S
R1 X
NH2 R2
Gewald synthesis
8 2 % H B r,
A cO H 3 ste p s
S B B u t
OB u t B rSH B u t O S C P h 3
B r
P P
MeO
S OMe
S
1 Lawesson's reagent S
S
Me Ar
Me S Ar Me S Ar
O
O
O O
1, BF3
4 5 6
Tetrahedron lett. 1998, 9191.
N
N N
NH S S, piperidine
DMF Me
CN N
NMe2
7 8
J. Chem. Res. Synop. 1998, 294.
Ph
S NHAc
SMe Me OEt
O O
Ph S CO2Et NHAc Hg(OAc)2
10 11
12
J. Org. Chem. 1998, 5903.
Me
SH S
O Br
Me
Me
Me 14
S N CHO
Me Me
Ph
Cl S N Ph
Me
S
O O Cl O O
S, Et3N, DMF
16 17
J. Heterocycles Chem. 1998, 1449.
Li
OMe S
OMe
NHMe S
OMe NMe 1. MeNCS
2. t-BuOK
18 19 20
H H
Eur. J. Org. Chem. 1998, 253.
CHO
Cl
MeS MeS
S F
CO2H HO2CCH2SH, Et3N
F
21 22
Chem. Pharm. Bull. 1998, 279.
Me
Me TBDMSO
Me
Br
S R
S Me
Me TBDMSO
Me
Me R
S Me
Me TBDMSO
Me
Me Me Bu3SnH,
AIBN
27 R = H
29 R = Me 28 R = H
30 R = Me
31
J. Org. Chem. 1998, 3318.
S Br
SO2
S
SO2
S
SO2
Bu3SnH, AIBN NBS
32 33 34
J. Org. Chem. 1998, 4645.
Cl
S MeO OMe
S Cl
PPA, toluene, 70 oC
35 36
Syn. Commun. 1998, 3479.
S
Ph Ph
S Ph S
Ph
Ph Ph PPh3
37 38
J. Org. Chem. 1998, 163.
O t-Bu
S O
t-Bu
S
t-Bu t-Bu
OH OH
S t-Bu
TiCl4, Zn p-TsOH t-Bu
39 40 41
J. Org. Chem. 1998, 4912.
Me2N
S S
NMe2
Me2N NMe2
S SH hv
42
43
Eur. J. Org. Chem. 1998, 2365.
S S CN
NC
Cl
NC
N N
S Cl
hv
44 45 46
Terahedron, 1998, 5587.
Tetrahedron, 1998, 11603.
Ph O Br
Ar O
Se Ph O
Ar Et NEt2
Se
187
186 188
J. Heterocyclic Chem. 1998, 71.
Br
Br
1. t-BuLi Te 2. Te power
189 190
Te
J. Heterocyclic Chem. 1998, 725.
Te O Ph Ph
COCl
NaHTe
191
192
J. Heterocyclic Chem. 1998, 165.
6.3.3 Electrophilic substitution
Table 6.2 Electrophilic substitution of thiophene.
Substituents introduced Reagents and conditions NO2 HNO3, (MeCO)2O, -10oC
Cl SO2Cl2, heat
Br NBS, CHCl3, MeCO2H
CHO Me2NCHO, POCl3
COMe MeCOCl, SnCl4
SO3H SO3-pyridine
-CMe2- Me2CO, 70% H2SO4
CH2NMe2 Me2NCH2+
Cl-, MeCN, heat
Br S Br Br S Br COMe
Br S COMe
AcCl, AlCl3
ispo-Substitution of bromine by an electrophile.
R1 S R1
Li
R1
SLi
R1
R1
SR2
R1 R2X
Ring cleavage of 3-thienyllithium derivatives.
S+ Me
S+
-C(CO2Me)2
S+
-NCO2Et
S O
S
O O
-OSO2F
S S
S TMS
TMS
O O
Br Br
TMS TMS Br2
50 51
52
Heterocycles, 1998, 227.
S TBDMS TBDMS
S R
TBDMS TBDMS Br
O
m-CPBA BF3-ether
m-CPBA
O S O
53 54 R = Br
55 R = TBDMS 56
Heterocycles, 1998, 793.; J. Org. Chem. 1998, 5497.
6.3.4 Nucleophilic and radical substitution RNH2
S O2N NO2
S O2N
H PhS
NO2
PhS S
NO2
-
PhS H
NO2 O2N
S PhS- -
S NO2 S
H
R2N - NO2 R2N S- NO2 disulfide
R2NH
cine-substitution and ring cleavage by nucleophiles.
S Br
CO2H
S
CH2CO2Et
CO2H MeCOCHCO2Et, Cu
S Br S Br
S
NH2 KNH2, NH3
Nucleophilic substitution in unactivated thiophenes.
S Cl
S S
S S
Me O
Me
O Me
NO2
Ar NO2
Cl NO2
Na2S
TFA,
SiEt3H 57
58
59 60
Cl Cl
J. Heterocyclic Chem. 1998, 1521.
S Cl S N
H S N
NO2 NO2 HN
Ph O O PhCH2NH2
K2CO3
61 62 63
Heterocycles, 1998, (48)1555.
S O
S O TMS
TMS S Me
O OH TFA
S O TMS
O Me 1. n-BuLi
2. NMe2COMe 1. n-BuLi
2. TMSBr
64 65
66
67 polystyrene resin
J. Org. Chem. 1998, 5324.
S EtO2C S CO2Et
1. n-BuLi 2. ClCO2Et
68 69
Tetrahedron, 1998, 7075.
S S S
OCONEt2 OCONEt2 OCONEt2
Me
TBDMS TBDMS
1. n-BuLi 2. TBDMSCl
1. n-BuLi 2. Mel
70 71
72
J. Chem. Soc. Perkin Trans. 1, 1998, 2559.
S Br Me Br
Me S B(OH)2
Me Br
Me S
Me Br
Me O
O O
O O
O 1. n-BuLi
2. (n-BuO)3B 3. HCl
Pd(0), Arl
73 74
75
J. Org. Chem. 1998, 6643.
S S
S
S S S
C6H13 SnBu3
Br C6H13
C6H13 C6H13
Pd(AsPh3)4
O O
80
79 81
O O
J. Org. Chem. 1998, 5497.
S S
S S
Br Br
Br Br
Ph
Pd(PhCN)2Cl2 S S
S S
Ph Ph
Ph Ph
82
83
Eur. J. Org. Chem. 1998, 525.
S S CO2Me
OH
O CO2Me
Br 85
84 86
Pd(OAc)2
Heterocycles, 1998, (48), 1537.
6.3.5 Addition and cycloaddition reaction
I+Ph CO2-
S S heat
Diels-Alder reaction of thiophene with benzyne.
. Table. Some cycloaddition reactions of thiophenes
Ph Ph
N
N S
CO2Me
CO2Me
S H H
H
CO2Bu
S
CN CN Me Me Me
Me Thi ophene
subst i t uent s Reagent s Condi t i ons Pr oduc t s
None PhC CPh 200- 280oC
44 h None
(al so wi t h 2,5- Me2)
N
N N
N CO2Me
CO2Me
Room t emp.
None N2CHCO2Bu Rh(I I ), 85oC
2,3,4,5- Me4 NCC CCN Al Cl3, 0oC
S S
S S
O NMe2
OTf
88
87 89
J. Org. Chem. 1998, 6132.
S S
S
O HO O
S S
S
O SnCl4 O
S S N
O
Br
COPh
Pd(OAc)2 N
COPh
92 93
O
Syn. Commun. 1998, 1839.
S S
H N N(OH)
DIBAL
94 95
Heterocycles, 1998, (48), 919.
S MeO2C
N NHCO2Et
SOCl2
S MeO2C
N S N
96 97
J. Chem. Soc. Perkin Trans. 1, 1998, 853.
S
NO2
O N
O
Ph Ph
CH2Ph
S
O N CH2Ph O2N Ph
Ph O
-HNO2
-CO2 S
NCH2Ph Ph
Ph 99
98
100 101
Synlett, 1998, 1061.
S O
O N
Cl PhHN N
S O
O
S N N
O O
Ph Ag2CO3
102
104 N N
Ph - +
J. Chem. Soc. Perkin Trans. 1, 1998, 4103.
S MeO2C S CO2Me Ph Ph
105
106 DMAD
toluene, heat
CO2Me MeO2C
DMAD = Dimethyl acetylenedicarboxylate
Syn. Commun. 1998, 2531.
OMe CO2H
Br
OMe S NH O
S
CN LiO2C
OMe
S LiN C
Li
S CO2Li
OMe C N
S LiO2C
OMe NLi LDA
107 108
109
110
111 112
113
J. Chem. Soc. Perkin Trans, 1. 1998, 1461.
S
N H
N
Br
Br CH2OH
115 CH2OH
O O
114 116
Tetrahedron, 1998, 1817.
N Cl N
Cl Cl
n-BuLi
1. NCS
S O O
Br
Br I
NH2
N Ts
SO2 I
N H
SO2 Bu3SnH AIBN
N Ts
SO2 N H
SO2
TsCl, Et3N NBS, AIBN
122 123 124 125
126 127
J. Org. Chem. 1998, 4645.
O2S
S S
S
S CO2Me CO2Me
Ph3P O2S
S S
S
S CO2Me CO2Me
128 129 130
+ -
J. Am. Chem. Soc. 1998, 330.
S S S
N N NPh N N
SO2
S
O2 N
Ph Ph Ph NHAc
NHAc
O O
1,2,4 -trichlorobenzene,
O O
131
132
133 heat
Synthesis, 1998, 1331.
N
SO2
210 oC N
134
135
Tetrahedron, 1998, 12609.
O
SO2
O
SO2 Me O
Me
CO2Me CO2Me 1. LiHMDS
2. Mel
1. DMAD 2. DDQ
136 137
138
J. Org. Chem. 1998, 4645.
S
Br Br
Br Br
NPh O
O
NPh Br
Br Br
Br
O
O
SO NPh
O electrochemical O
extrusion of SO m-CPBA
BF3-ether 139
140
141
J. Chem. Rev. (S), 1998, 346.
S Br
Me Me CO2Me
CO2Me Br
142 143
DMAD m-CPBA BF3-ether
Eur. J. Org. Chem. 1998, 1841.
OS O
SO2Ph O2 S
SO2Ph R
R
-SO2
145 -PhSO2H
144
146 147
J. Org. Chem. 1998, 4912.
6.3.6 Reductive desulfurization
R1 S R2
Me
R1 R2
Raney Ni
Et CHO, NaOH baker s' yeast
6.3.7 Photochemical isomerization
S R
S R
S R S
R S
R
S R S
R hv
hv hv hv
Alternative methods of photoisomerization of thiophenes.
S CN
S CN
S
CN
hv furan O
(exo and endo) Interception of a valence tautomer of thiophene-3-carbonitrile.
