Angewandte Chemie International Edition
10.1002/anie.202109519
qualitative thermal isomerization pathway[3,6,7]
enantiomers
‡
S
S
Rh (R-PTAD) (ent-C3)
2
4
Rh (S-PTAD)4 (C3)
2
MeO
MeO
then
then
OMe
OMe
*
*
E
a
(S )
P(NMe
2
)
3
,
P(NMe
2 3
) ,
toluene, 60 °C, 18 h
toluene, 60 °C, 18 h
S
S
(
2
M-E)-4a, 96%
.8:1 d.r. (E/Z)
:98 e.r. (E)
:96 e.r. (Z)
(P-E)-4a, 95%
2.7:1 d.r. (E/Z)
98:2 e.r. (E)
96:4 e.r. (Z)
2
4
1
+ 2a
Twisted
Twisted
(Figure 3)
(P-Z)
(M-E)
S
S
Rh
2
(R-PTAD)
4
(ent-C3)
Rh
2
4
(S-PTAD) (C3)
OMe
then
then
MeO
*
*
9
5 °C
Bu
3
SnH, BEt
3
,
3 3
Bu SnH, BEt ,
heptane
(
(
M-E)-4a
M-E)/(P-Z) = 1:1.1
S
CH Cl , –78 °C, 5 h
2
2
CH Cl , –78 °C, 5 h
2
2
S
(P-Z)-4a
(P-Z)-4a
OMe
M-Z)-4a, 81%
:2.7 d.r. (E/Z)
MeO
124.5 kJ/mol
(
1
enantiomers
(P-Z)-4a, 82%
1:2.7 d.r. (E/Z)
87:13 e.r. (E)
97:3 e.r. (Z)
I
, RT
2
(M-E)-4a
M-E)/(P-Z) = 1:1.4
(
9
:91 e.r. (E)
hν
3:97 e.r. (Z)
(370 nm)
all isomers
PSS: (E)/(Z) = 45:55
(P-Z)-4a
90 min
Figure 4. Stereodivergent Catalytic Barton–Kellogg Olefination and Isomerization Studies. Isolated yields over both steps.
[
[
1]
2]
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Conclusion
1
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The catalyst-controlled stereoselective Barton–Kellogg ole-
[
[
[
[
[
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5]
6]
7]
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fourfold stereogenicity was developed. The reaction provides ac-
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2 4
Rh (S-PTAD) catalyst and an exceptionally stereospecific thiirane
1
993, 288–290.
reduction. The scope of the method also comprises the possibility
for divergent stereocontrol, rendering all four stereoisomers acces-
sible from the same substrates. Based on the generality of the Bar-
ton–Kellogg olefination and the viability of forming the central C=C
double bond of the overcrowded alkene in a direct catalyst-con-
trolled stereoselective coupling, we envision that the rational de-
sign and synthesis of various catalyst structures, bioactive com-
pounds and functional molecular scaffolds are feasible with the
method presented herein.
[8]
The stereogenicity of (irreducible) stereogenic units allows the prediction
of the number of stereoisomers according to an extended Le Bel–Van 't
Hoff rule, as: s n * s n
1
2
,... (s: stereogenicity, n: number of stereogenic units
1 2
with the specific stereogenicity). See compound 2e in reference [32] for an
example with six- and twofold stereogenicity.
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Financial support from the Swiss National Science Foundation
(
155902 and 175746), the University of Basel, and the NCCR Mo-
[
[
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(
ERC) under the European Union’s Horizon 2020 research and in-
4
novation programme (grant agreement No. 101002471). We thank
Dr. Alessandro Prescimone for X-ray crystallography and Andreas
Ostertag for support in the scale-up synthesis of substrates.
[
3
[
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Conflicts of Interest
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There are no conflicts of interest to declare.
[
[
8
Keywords: Barton–Kellogg olefination • higher-order stereo-
genicity • overcrowded alkenes • stereodivergent catalysis • stere-
oselective catalysis
1
[
[
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