furan reaction with electrophiles - protonation
TRANSCRIPT
FURAN
O The least aromatic 5-membered ring
S O
H
H
H
H
7.1 ppm127 ppm
7.2 ppm126 ppm
6.3 ppm110 ppm
7.4 ppm144 ppmS O
1.71Å
1.37Å
1.42Å
1.37Å
1.35Å
1.44Å
Reaction with electrophiles - Protonation
O O
HH
Ring opening
OH
Much less basic than ordinary ethers
OHH
Major protonated form
Conc. H2SO4
Lewis acids (i.e. AlCl3)Decomp.
O
HH H2O
O OHHemiacetal
OO
Reaction with electrophiles - Nitration Cannot use conc. HNO3 / H2SO4
S
AcO NO2
conc. HNO3, Ac2O
X
X=S - ThiopheneX=O - Furan
XNO2H
AcO NO2X=S
X=O
ONO2H
AcOH
PyridineO NO2
Halogenation
OBr2
Dioxane, oC XBrH
Br O
BrH
BrH
Seen on low temp NMR
- HBr O BrBr2
O BrBrcan be isolated
OMeO2CBr2
OMeO2C
Br
Br O
Br
Br
HO OH Br2
HBr
Br
Br OH
HO
Br
H OH
HO
see 15.14.1.2O
Br
O
BrBr1. t-Buli2. H2O
1. n-BuLi2. DMF
O
Br
CHO
Reaction with electrophiles - Acylation
ODMF, POCl3
OO"Vilsmeyer"
FurfuralAlso very readily available by other routesO
R'COCl or(R'CO)2OBF3 . Et2O
R
R: H, MeO
R
OR'
Alkylation Generally not practical (polyalkylation, polymerisation)
Condensation with Aldehydes and Ketones
ORCHO, H+
O OHR
Further react.
O OHCCl3
stableFrom chloral
C.f.
NH
H+, RCHONHR=H, alkyl H
OHR
H±H+
NH R H
OH2- H2O N
H RH Polymer
Reaction with electrophiles - Condensation with imines / iminium ionsCH2O, R2NH, H+
NR
RO
Unsubst furan: iminium ion must be preformed
OH
NR
RH-
ON RR
X
B(OH)2
X=OX=S
Ph2CHNH2HO2CCHO
NHR
O2CX
X=OX=S
CO2HPh2HCHN
ipso subst.Reaction with oxidating agents
O R'R
(Ox)R'R O O
Div. ox. agents p 300E-isomer in most cases
O
Br2, MeOHOH H
OMeMeO
Pb(OAc)4
O OAcAcO
Reaction with nucleophilesSome ex. on furans activated with -NO2 group
Metallation and further react.
On-BuLi
Et2O, Δ O Li
On-BuLi
THF, -78oC
Br
O
Li
> -40 oC
n-BuLi TMEDAhexane, Δ O LiLi
O
Li
OLi
O
Br LDA
O
Br
Li
(ODG)n-BuLi
O CO2HLDA
O CO2LiLiO CO2Li
Li
O Li
B(OR)3 HydrolysisO B(OH)3
BR3
O BR
RR
Li
I-I ORBR2
HI
IO R
Pd-cat couplings
O
Li
O
Met Ar-X (or related)cat Pd
O
Ar
O
Br
O
Br
Br
Ar-Metcat Pd
O
Br
Ar
NR
Pd(OAc)2N
H PdOAc
R
OAc
NR
PdOAcEWG
NR
EWG
Heck
+ Pd(0)
Cu(II)
c.f.
O
EWGcat. Pd
O EWG
Ocat. Pd
Ar-X
O Ar
like an alkene in Heck
Heteroaryl-Heck
O ArAr-Pd-X
O O
H
ArHPdX
H-Pd-X
Cycloadditions
X+
O OO
XOO
OHH
X=O: r.t.; 80%X=S: 100 oC, 15kbar; 42%
Furanes as diene - one of the first DA examplesFuran reacts with many dienophiles (alkenes, alkynes, allenes)
exo isolated (termodyn favoured)endo (kinetic prod.)
With 1O2
O
O OOO
O
H
H
OOH
OO O
HOH
O O
1O2 (singlet)hν
O O
3O2 (triplet)
Diradical3 lines ESR
No unpaired el.1 line ESRFuran as dienophile (only intramolec. ex)
X
OX: EWG
O
XH
O
XH
H
H
H
Photochemical cycloaddition
O O
R1R [2+2]
OO
RR'
acid
acetalO
'R RO
Furyl-CH2-X
OCl
Nu
ONu
ONu
Oxyfurans
O OH O OR RR=Me: α-angelica lactoneR=Me: β-angelica lactone
Most stable
HH
O OHR
not detectable
Butenolides (natural prod.)O
OHHO
named as der. of
O
OH
O
OHH
major
O OHH
HO
tetronic acid
O O
HO
ascorbic acid
OHH
OHHO Luffarin W
OO
Luffarin B
OO
Isol. marine spongescytotoxic
Aminofurans-Aminoform-Unstable
Synthesis of Furans
Strategy a1 Paal Knorr (1,4-dikacarbonyl)
X
a1
bX
X
X
cO
R'O
R
NH2R''
NR''
OHR'
HOR N
R''R'R
- 2 H2O
R''=H, alkyl, aryl
Strategy a - pyrrolesPaal Knorr
X
aX
OO
R4 R3
R5 R2
TsOHOR5
R4 R3
OH R2O
R4 R3
R5 R2OH
H
- H2O O
R4 R3
R2R5
HO OH Br2
HBr
Br
Br OH
HO
Br
H OH
HO
see 15.14.1.2O
Br
O
BrBr
HO OHK2Cr2O7, acid
HO OO OH
H+
O- H2O
Carbonyl condensations
X
a1
bX
X
X
c
Strategy b
Cl
O O
O R'
OR
Aldehyde
HO H
O R'Cl
CO2RB
O
HO CO2R
R' O
CO2R
R'
H2O
R''
ClO
O R'
OR
Ketone
O
H
O R'''R
CO2R
O
acid"Paal Knorr" O
CO2R
R'''R
O
OH
R
EtO
PPh3
O
OR
OEt
PPh3 "Wittig"O
R
OEt - EtOH O
R
Pd-cat. Cyclisations etc.
OR
HB
Pd(II)
OPdX
R
H+
OR
taut.OR
Ar-X OAr
Rtaut.
OR Ar
R'
OHR
HO
I2
OR
HO
R'
I
-H2O OR R'
I
OR
R'Pd(0)
OR
R'
R'
OR
Pd(0)
Pd(0) cat. ??OR R'
Pd(II), H2O R'
OHR
Pd(II)O R'R
PdX
H+
Also known termal cycl.
OR R'OR
R'
heat
Cycloadditions
NO
Ph R'R N
O
Ph
R(R')
R(R')- PhCN
OR
R'R / R': i.e. -SnBu3, -SIMe3, alkyls etc.
NS
Ph R'R- PhCN
SR
R'
c.f.