Stereochemical relay through oligoureas 24/02/2005.
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Stereochemical relay through oligoureas n ( 1, 21+6n)diastereoselectivity N O N N O N N O N N O N A* B 24/02/2005
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Transcript of Stereochemical relay through oligoureas 24/02/2005.
Stereochemical relay through oligoureas
n
(1, 21+6n) diastereoselectivity
N
O
NN
O
N N
O
N
N
O
NA* B
24/02/2005
Synthesis
Unsymmetrical
Symmetrical
ii) H2, Pd/C iv) NaH, MeI
OCN NO2i) OCN
A
iii)
NH2
BNN
O
NN
O
MeMeMeMe AB
n
n times
H
C
DD
C
NH2+ NN
CO
CO
N
O
N N N
O
Me Me Me Me
ii) NaH 5 eqMeI 5 eq
THF
B B B
(2 steps)
A
C
A
C
A
C
Alkyl group on meta
NO
N
NO
N
H5.99 ppm
H
H
6.49 ppm
LL -2 -51 300 MHz 23C
LL -2 -51 300MHz 40C
LL -2 -51 300 MHz -10C
LL -2 -51 300 MHz -30C
ppm (t1)6.006.507.00
LL -2 -51 300 MHz -50 C
6.52
6.47
6.42
6.39
6.36
6.03
5.98
5.90
5.84
5.80
40°C
23°C
-10°C
-30°C
-50°C
Alkyl group on meta or ortho position
NO
N
NO
N
H6.01 ppm
H
H
6.46 ppm NO
N
NO
N
H (i-Pr) 5.88 ppm
Effect of the chiral sulfoxide
The X-ray analysis confirmed that the sulfoxide control the first axis
But not the entire helix
5.82 ppm
NO
N
NO
N
H
SO
Two different Et groupsand
diastereotopic CH2
6.06 ppm
NO
N
NO
N
H
SO
Diastereotopic CH3
5.82 ppm
NO
N
NO
N
H
Br
Identical Et on 1H NMR
Effect of the chiral sulfoxide
N N
O
N
O
N
STol O
N N
O
N
O
N
STol O
N N
O
N N
O
N
O
N
STol O
N N
O
N N
O
N N
O
N
O
N
Br
n
n=1 39% n = 2 XX% n = 3 XX%
Circular Dichroism
13C i-Pr sensor
The helix exists in two conformations (cis and trans)
At 50°C, it seems we can clearly see the two diastereomers.
N
Me
N
O
Me
N
Me
N
O
Me13
SO
Tol
1) n-BuLi
2)O
S
O
13
H2NH2N1) PivCl
2) Buli, sparteine 13CH3I3) HCl 51% (3 étapes)
81% eeN
Me
N
O
Me
N
Me
N
O
Me13
Br
71%
54%, 4 steps
2)
OSTol
O
Tol
1) n-BuLi
73%
N
Me
N
O
Me
N
Me
N
O
Me13
SO
Tol
ppm (t1)0.901.001.101.201.30
13C i-Pr sensor
N
Me
N
O
Me
N
Me
N
O
Me13
SO
Tol
N
Me
N
O
Me
N
Me
N
O
Me13
SO
Tol
ppm (t1)0.901.001.101.201.30
23°C
N
Me
N
O
Me
N
Me
N
O
Me13
Br
90/10
90/10
90/10
ppm (f1)0.901.001.101.201.30
ppm (f1)0.901.001.101.201.30
13C i-Pr sensor
N
Me
N
O
Me
N
Me
N
O
Me13
SO
Tol
N
Me
N
O
Me
N
Me
N
O
Me13
SO
Tol
50°C
N
Me
N
O
Me
N
Me
N
O
Me13
Br
90/10
90/10
90/10
ppm (f1)0.901.001.101.201.30
ppm (f1)0.901.001.101.201.30
23°C
Benzylic sensor
The Br-Li exchange didn’t work.
The benzylic position might be the problem
N
Me
N
O
Me
N
Me
N
O
BnSO
TolN
Me
N
O
Me
N
Me
N
O
BnBr
1) n-BuLi
2)
OS
O
HNNCOO2N
+ H2N N
H
N
O
Bn
2) SnCl2 H2O,AcOEt reflux 3h
NCO
Br1)
2) NaH, MeITHF
NH2
OCN NO2
+ N
H
N
O
H
NH2
2) Pd/C, H2THF / MeOH
1) THF
OCN
N N
O
N N
O
NaH / MeI5 eq.
THF, 12h
25% (4 steps)
2 eq.
OCN
Br
2 eq.
NaH / MeI5 eq.
THF, 12h
1)
2)
N N
O
N N
O
Br
48% (4 steps)1) 2)
Oligoureas connected on the ortho position
Broad signals on the 1H NMR
The helix crystallised in a chiral
space group as a single enantiomer
