Rhodium-Catalyzed Parallel Kinetic Resolution of Racemic Internal Allenes Towards Enantiopure Allylic 1,3-Diketones

Article abstract of DOI:10.1002/anie.201903365

A rare case of a parallel kinetic resolution of racemic 1,3-disubstituted allenes by means of a rhodium-catalyzed addition to 1,3-diketones furnishing enantiopure allylic 1,3-diketones is described. Mechanistic experiments demonstrate that the different allene enantiomers react in parallel to either the diastereomeric E- or Z-allylic 1,3-diketones with the same absolute configuration of the newly formed stereogenic center. A broad substrate scope demonstrates the synthetic utility of this new method.

Full text of DOI:10.1002/anie.201903365

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
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Accepted Article
Title: Rhodium-Catalyzed Parallel Kinetic Resolution of Racemic
Internal Allenes Towards Enantiopure Allylic 1,3-Diketones
Authors: Bernhard Breit and Lukas Hilpert
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201903365
Angew. Chem. 10.1002/ange.201903365
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http://dx.doi.org/10.1002/ange.201903365

10.1002/anie.201903365
Angewandte Chemie International Edition
COMMUNICATION
Rhodium-Catalyzed Parallel Kinetic Resolution of Racemic
Internal Allenes Towards Enantiopure Allylic 1,3-Diketones
Lukas J. Hilpert and Bernhard Breit*
Abstract: A rare case of a parallel kinetic resolution of racemic
O
O
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
TFA 50 mol%
1,3-disubstituted allenes by means of a rhodium-catalyzed addition
to 1,3-diketones furnishing enantiopure allylic 1,3-diketones is
described. Mechanistic experiments demonstrate that the different
allene enantiomers react to either the diastereomeric E- or Z-allylic
1,3-diketones with the same absolute configuration of the newly
formed stereogenic center. A broad substrate scope demonstrates
the synthetic utility of this new method.
Me
Ph
Me
O
O
•
+
Ph
Ph
Ph
Me
Me
DCM, RT, 16 h
rac-1
(1.0 equiv.)
2
(2.0 equiv.)
4
99% yield
E/Z 55:45, 98/98% ee
O
P
N
O
(R)-L1
Scheme 2. Optimized reaction conditions for the rhodium-catalyzed addition of
acetylacetone (2) to racemic internal allene rac-1 using the depicted
(R)-P-amidite ligand. Reaction was performed on a 0.25 mmol scale; DCM
(c = 0.2 M). X/Y % ee (X: E-isomer, Y: Z-isomer). E/Z-value was determined by
crude 1H-NMR. The enantiomeric excess (ee) was determined by chiral HPLC.
The absolute configuration of the product was determined by structural
modification and comparison with previously reported literature.
The development of novel catalytic and atom efficient C-C and
C-heteroatom-bond forming reactions is fundamental to propel a
more sustainable catalytic organic synthesis. We recently
reported on
a series of catalytic addition reactions of
pronucleophiles to allenes and alkynes,[1-3] which can be seen as
atom economic variants[4] of the Tsuji-Trost reaction.[5-9] In this
context we developed a regio- and enantioselective addition of
1,3-diketones to terminal allenes to form tertiary and quaternary
stereocenters in high yields as well as regio- and
enantioselectivities (Scheme 1).[10] Upon studies towards the
extension of the substrate scope to racemic 1,3-disubstituted
allenes we now came across an interesting phenomenon
reported herein.
Hydrogenation of 4 delivered the single enantiomer (R)-5 as
evidenced by chiral HPLC, proving that the absolute
configuration of the newly formed stereocenter of E- and Z-4
was the same (Scheme 3).
O
O
O
O
H2 (1 atm)
Pd/CaCO3 (5 mol%)
Me
Ph
Me
Me
Ph
Me
MeOH, RT, 3 h
Ph
Ph
previous work
(R)-5
quant.
99% ee
4
O
O
E/Z 55:45
98/98% ee
R1
O
O
[Rh]/L*
R3
R4
+
R2
R3
R4
•
R2
Scheme 3. Hydrogenation reaction to prove absolute configuration of E- and
Z-4. E/Z-ratio was determined by crude 1H-NMR. The enantiomeric excess
(ee) was determined by chiral HPLC.
R1
this work
O
R
O
O
O
[Rh]/L*
•
+
R
R
R’
R’
However, given the fact that our earlier studies on addition
reactions of pronucleophiles to internal allenes showed that
either E- or Z-allylic products were obtained selectively, we were
curious about the origin of this low E/Z-selectivity. One
possibility was that an E/Z-isomerization during the reaction
could occur. Therefore we analyzed the products’ E/Z-ratio at
different levels of reaction progress (Scheme 4). Interestingly, at
10 min reaction time, product 4 was already formed in 51 %
yield in an E/Z-ratio of 13:87 and with 99/98 % ee. After 16 h
and even 48 h the same results as displayed in Scheme 2 were
obtained (99 % yield, E/Z 55:45, 98/98 % ee). This suggested
that either a subsequent slower isomerization of the Z-product to
the E-isomer occurred or that there were different reaction
pathways for each allene enantiomer. To exclude an
R’
R’
rac
resolution ?
R
Scheme 1. Previous work on the Rh-catalyzed addition of 1,3-dicarbonyl
compounds to allenes in contrast to the addition to internal allenes.
Thus, the reaction of racemic internal allene 1 with
acetylacetone in the presence of a rhodium-catalyst modified
with phosphoramidite L1 and TFA as
a
Brønsted acid
co-catalyst at room temperature furnished the addition product 4
in quantitative yield as a mixture of E- and Z-stereoisomers both
in high enantioselectivities (Scheme 2).[11,12]
isomerization process we subjected isolated product
4
(E/Z 15:85) to the same catalysis conditions and as the E/Z-ratio
remained unchanged after a reaction time of 16 h, we could rule
out the scenario of a subsequent alkene isomerization.
[*]
Lukas J. Hilpert, Prof. Dr. Bernhard Breit
Institut für Organische Chemie
Albert-Ludwigs-Universität Freiburg
Albertstraße 21, 79104 Freiburg im Breisgau (Germany)
E-mail: bernhard.breit@chemie.uni-freiburg.de
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201903365
Angewandte Chemie International Edition
COMMUNICATION
O
O
O
O
O
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
TFA 50 mol%
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
TFA 50 mol%
O
CF3
Me
Ph
Me
O
O
Me
Ph
Me
O
O
•
+
Ph
+
Ph
Ph
Ph
Ph
•
+
Me
Me
Ph
Ph
DCM, RT, t
Ph
Me
Me
DCM, RT, t
(R)-1
2
rac-E-3
4
90% ee
(0.5 equiv.)
(2.0 equiv.)
rac-1
(1.0 equiv.)
2
(2.0 equiv.)
4
60% yield
E/Z >95:5
traces
t = 5 min
t = 16 h
51% yield
E/Z 13:87, 99/98% ee
t = 10 min
0% yield
99% yield
E/Z 80:20, 97/88% ee
99% yield
E/Z 55:45, 98/98% ee
t = 16 h
t = 48 h
O
O
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
TFA 50 mol%
Me
Ph
Me
O
O
99% yield
E/Z 55:45, 98/98% ee
•
+
Ph
Ph
Ph
Me
Me
DCM, RT, t
(S)-1
99% ee
(0.5 equiv.)
2
4
48 h
(2.0 equiv.)
99% yield
E/Z 12:88, 90/97% ee
t = 5 min
16 h
Z
E
10 min
Scheme 6. Addition of acetylacetone (2) to enantioenriched allene (R)/(S)-1.
Reactions display a cutout of actual catalyses starting from racemic allene 1.
0.5 equivalents of enantioenriched allene 1 correspond to the concentration in
actual catalysis starting from racemic allene 1. Yield is based on 0.5 equiv.
starting material.
0
10 20 30 40 50 60 70 80 90 100
yield [%]
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
TFA 50 mol%
O
O
O
O
Me
Ph
Me
Me
Ph
Me
This result suggested that TFA-esters could be
intermediates in this reaction. For this reason, rac-E-3 and
rac-Z-4 were prepared separately and were subjected to the
catalysis reaction conditons respectively (Scheme 7). Notably,
rac-E-3 was transformed quantitatively and with high
enantioselectivity to (S)-E-4, while rac-Z-3 reacted cleanly to
give (S)-Z-4.
DCM, RT, 16 h
Ph
Ph
E/Z 15:85
4
E/Z 15:85
4
Scheme 4. Time-dependent E/Z-ratios for the rhodium-catalyzed addition of
acetylacetone (2) to racemic internal allene rac-1. Reaction was performed on
a
0.25 mmol scale; DCM (c = 0.2 M). Additional experiment with
acetylacetone (2) (1.0 equiv.) showed the same result. X/Y % ee (X: E-isomer,
Y: Z-isomer). E/Z-ratio was determined by crude 1H-NMR. The enantiomeric
excess (ee) was determined by chiral HPLC.
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
NO TFA
O
O
O
O
CF3
Me
Ph
Me
acac 2.0 equiv.
Ph
Ph
Ph
Hence, the only possible interpretation was a selective
reaction pathway for each allene enantiomer to form one product
diastereomer (Scheme 5). In such a scenario, the racemic
substrate would undergo a rhodium-catalyzed parallel kinetic
resolution (PKR). PKR is a rarely observed phenomenon in
synthetic organic chemistry.[13,14]
DCM, RT, 16 h
rac-E-3
(0.5 equiv)
(S)-E-4
99% yield,
99% ee
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
NO TFA
O
O
O
O
CF3
Me
Ph
Me
acac 2.0 equiv.
Ph
DCM, RT, 16 h
Ph
Ph
O
O
rac-Z-3
(0.5 equiv)
(S)-Z-4
99% yield,
97% ee
(R)-1
(S)-E-4
Me
Me
Ph
•
Ph
Ph
Ph
Ph
Ph
Scheme 7. Reactions to prove and clarify the role of TFA-ester 3. Reactions
display cutout of actual catalysis starting from racemic allene 1.
0.5 Equivalents of TFA-esters correspond to concentration in actual catalysis
parallel
kinetic
resolution
+
a
O
O
Me
Ph
Me
(S)-Z-4
starting from racemic allene 1. Yield is based on 0.5 equiv. starting material.
•
(S)-1
An additional control experiment starting from allene 1 in the
absence of TFA showed no product formation. To further clarify
the role of TFA, a mixture of the corresponding TFA-ester 3 and
allene 1 was subjected to the catalysis conditions without adding
additional TFA (Scheme 8). After 16 h reaction time, both
TFA-ester and allene were completely converted to the allylation
product 4. This indicates that the TFA-ester 3 is an intermediate
and the TFA is released as a leaving group to serve as the
co-catalyst upon reaction with allene rac-1.
Ph
Scheme 5. Proposed parallel kinetic resolution for the rhodium-catalyzed
addition of acetylacetone (2) to racemic internal allene rac-1.
To gain deeper insights into the reaction mechanism,
enantiopure allenes (R)-1 and (S)-1 were prepared and
subjected to the catalysis conditions respectively (Scheme 6).
After 5 min (R)-1 was converted to TFA-ester rac-E-3, whereas
(S)-Z-4 (E/Z 12:88) was formed starting from (S)-1. After 16 h
TFA-ester rac-E-3 was completely transformed to the final
product (S)-E-4 (E/Z 80:20).
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
NO TFA
O
O
O
O
CF3
Me
Ph
Me
acac 2.0 equiv.
•
+
Ph
Ph
Ph
Ph
Ph
DCM, RT, 16 h
rac-E-3
ester:allene 2:1
rac-1
4
99% yield,
E/Z 75:25, 98/98% ee
Scheme 8. Reaction to prove and clarify the role of TFA as additive.
Reactions were performed in 0.25 mmol scale, DCM (c = 0.2 M). E/Z-value
was determined by crude 1H-NMR. The enantiomeric excess (ee) was
determined by chiral HPLC.
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10.1002/anie.201903365
Angewandte Chemie International Edition
COMMUNICATION
To check whether the allene substrate is racemized in a
background isomerization, we performed the catalysis with
enantioenriched allene (R)-1 (Scheme 9). As expected no
racemization occured.[15] In an additional experiment rac-1
reacted with acetylacetone (2) and the reaction was stopped
after 2 min. This allowed to isolate remaining allene, which was
essentially enantiopure with R-configuration.
stereochemistry of the P-amidite ligand of the rhodium catalyst
from (R) to (S) led via the opposite diastereomeric intermediates
and to the opposite absolute configuration in the final product.
Hence, the first step, the rhodium-catalyzed addition of TFA
to internal allene, determined the olefin geometry but delivered
TFA-esters 3 as racemates. Only the second step, the rhodium-
catalyzed allylic substitution of the TFA-esters with
acetylacetone determined the absolute configuration C-C
coupling products in high enantioselectivity while preserving
alkene geometry (see experiments shown in Scheme 7).
[Rh(COD)Cl]2 5 mol%
(R)-P-amidite 10 mo%
•
•
Ph
Ph
Ph
Ph
DCM, RT, 16 h
(R)-1
(R)-1
90% ee
90% ee
[Rh(COD)Cl]2 5 mol%
(R)-P-amidite 10 mo%
TFA 50 mol%
O
O
O
O
CF3
•
+
Ph
Ph
•
+
(S)-Z-4
Ph
Ph
Me
Me
DCM, RT, 2 min
Ph
Ph
rac-1
(1.0 equiv.)
2
(R)-1
99% ee
rac-E-3
(R)-Cat.: (S)
(S)-Cat.: (R)
(2.0 equiv.)
(R)-Cat.
fast
slow
Scheme 9. Experiments to exclude background racemization. Reactions were
performed in 0.25 mmol scale, DCM (c = 0.2 M). E/Z-ratio was determined by
crude 1H-NMR. The enantiomeric excess (ee) was determined by chiral HPLC.
E-4
O
O
Me
Ph
Me
•
Ph
Ph
Ph
Ph
diastereomers
(R)-1
(S)-Cat.
PKR
To get further mechanistic insights we performed the
reaction in an NMR tube to monitor the reaction progress by
1H-NMR spectroscopy. Under such diffusion-controlled
conditions (no stirring) the reaction was significantly slower.
Thus, a conversion reached in the flask experiment after 5 min
reaction time needed 140 min in the NMR tube experiment.[16]
The observed reaction profile is depicted in Figure 1. Indeed we
were able to observe now both allylic TFA-esters rac-Z-3 and
rac-E-3 as intermediates during catalysis. Thus, rac-Z-3 is
formed rapidly and reacts fast to the C-C-coupling product (S)-Z-
4. Conversely, the E-TFA-ester is formed somewhat slower, and
reacts much slower to the C-C-coupling product (S)-E-4.
O
O
Me
Ph
Me
•
Ph
(S)-1
Ph
Z-4
fast
fast
O
(R)-Cat.
(R)-Cat.: (S)
(S)-Cat.: (R)
O
CF3
Ph
Ph
rac-Z-3
Scheme 10. Summarizing flow chart of PKR to highlight selectivity aspects
depending on absolute configuration of P-amidite-ligand.
With a detailed mechanistic understanding and optimized
reaction conditions in hand we explored the substrate scope
(Table 1). Variations in the 1,3-diketone backbone were well
tolerated. Both aliphatic (4-8), aromatic (9-17) and
O
O
O
O
O
O
O
CF3
Me
Ph
Me
O
CF3
Me
Ph
Me
Ph
•
Ph
Ph
Ph
Ph
Ph
Ph
Ph
(S)-Z-4
(S)-E-4
rac-1
rac-Z-3
rac-E-3
heteroaromatic
(18)
substituents
were
incorporated.
Conspicuously, the E/Z-ratio was heavily depending on the
obtained yield, highlighting that the formation of E- and
Z-product must proceed through different pathways. Only if a
ratio of nearly 50:50 is reached a quantitative yield could be
achieved (cf. formation of 4). Steric hindrance was a determining
factor. Increase of hindrance from methyl- (3) to tBu-substitution
(8) decreased the yield from 99 % to 24 %. Relating thereto, 8
was received only as Z-diastereomer since the reaction pathway
towards the Z-product is in all cases significantly faster, and less
susceptible to less steric factors. For diaryl-substituted 1,3-
diketones both electron-rich (10) and electron-poor (11) as well
as halogen substituents (11-14) were well tolerated. A methyl
substitutuent is well tolerated in para, meta and even ortho
position (15-17). Furthermore, several other 1,3-disubstituted
allenes could serve as reaction partners (19-24) including a
macrocyclic allene substrate (21).
rac-1
rac-E-3
(S)-Z-4
rac-Z-3
(S)-E-4
Figure 1. Reaction profile to show time depending interconversion of allene 1
and intermediates towards product 4.
Merging all experimental data allowed to draw the
mechanistic scenario depicted in Scheme 10. Thus, allene (R)-1
was converted via the TFA-ester rac-E-3 to (S)-E-4 in 98% ee
by the (R)-catalyst system (R-Cat). In a parallel pathway the
allene (S)-1 reacted via the TFA-ester rac-Z-3 furnishing the
C-C-coupling product (S)-Z-4 in 98% ee. Switching the
This article is protected by copyright. All rights reserved.

10.1002/anie.201903365
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Scope of the Rh-catalyzed PKR of 1,7-diphenyl-hepta-3,4-diene (1)
with different 1,3-diketones and PKR of different internal allenes with acetyl
acetone (2).
Acknowledgements
This
work
was
supported
by
the
Deutsche
O
O
[Rh(COD)Cl]2 5 mol%
(R)-L1 10 mol%
TFA 50 mol%
O
O
Forschungsgemeinschaft (DFG) and the Fonds der Chemischen
Industrie. Jan Klauser (University of Freiburg) is acknowledged
for technical assistance. We thank Dr. Manfred Keller for
extensive NMR experimentations and Joshua Emmerich for
challenging HPLC separations.
R3
R3
O
O
R3
R3
R1
R2
•
+
+
R1
R3
R3
DCM (0.2 M)
RT, 16 h
R1
R2
4-25
rac
2
R2
(1.0 equiv.)
(2.0 equiv.)
O
O
O
O
O
O
O
O
Et
Et
Me
Ph
Me
tBu
tBu
iPr
iPr
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Conflict of interest
4
6
7
8
99% yield,[a]
E/Z 55:45,[b] 98/98% ee[c]
78% yield,
E/Z 44:56, 99/98% ee
53% yield,
E/Z 21:79, 95/93% ee
24% yield,
E/Z <5:95, 52% ee
O
O
O
O
The authors declare no conflict of interest.
O
O
Ph
Ph
Ph
F3C
CF3
Ph
MeO
OMe
Keywords: Parallel Kinetic Resolution • Rhodium • Asymmetric
Ph
Ph
Ph
Ph
Catalysis • 1,3-Diketones • Allenes
9
10
11
60% yield,
E/Z 16:84, 86/90% ee
70% yield,
E/Z 27:73, 98/95% ee
42% yield,
E/Z 12:88, 97/88% ee
O
O
O
O
O
O
[1]
[2]
For recent reviews, see: a) P. Koschker, B. Breit, Acc. Chem. Res.
2016, 49, 1524-1536; b) A. M. Haydl, B. Breit, T. Liang, M. J. Krische,
Angew. Chem. Int. Ed. 2017, 56, 11312-11325; Angew. Chem. 2017,
129, 11466-11480.
F
F
Cl
Cl
Ph
Br
Br
Ph
Ph
Ph
Ph
Ph
12
68% yield,
E/Z 19:81, 94/98% ee
13
62% yield,
E/Z 15:85, 91/95% ee
14
49% yield,
E/Z 9:91, n.d./95% ee
For recent publications of our group, see: a) J. P. Schmidt, B. Breit,
Chem. Sci. 2019, 10, 3074-3079; b) J. Zheng, B. Breit, Angew. Chem.
2019, 131, 3430-3435; Angew. Chem. Int. Ed. 2018, 58, 3392-3397; c)
L. J. Hilpert, S. V. Sieger, A. M. Haydl, B. Breit, Angew. Chem. 2019,
131, 3416-3419; Angew. Chem. Int. Ed. 2018, 58, 3378-3381; d) C. P.
Grugel, B. Breit, Chem. Eur. J. 2018, 24 , 15223-15226; e) P. Spreider,
B. Breit, Org. Lett. 2018, 20, 3286-3290.
O
O
O
O
O
O
Me
O
O
Me
Me
Me
Ph
Me
S
S
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
15
60% yield,
E/Z 21:79, 92/95% ee
16
17
61% yield,
E/Z 35:65, 91/96% ee
18
62% yield,
E/Z 24:76, 88/80% ee
52% yield,
E/Z 20:80, 91/98% ee
[3]
For examples on C-C-bond formation, see: a) C. Li, B. Breit, J. Am.
Chem. Soc. 2014, 136, 862-865; b) T. M. Beck, B. Breit, Org. Lett. 2016,
18, 124-127; c) F. A. Cruz, Z. Chen, S. I. Kurtoic, V. M. Dong, Chem.
Commun. 2016, 52, 5836-5839; d) C. Li, C. P. Grugel, B. Breit, Chem.
Commun. 2016, 52, 5840-5843; e) T. M. Beck, B. Breit, Eur. J. Org.
Chem. 2016, 93, 5839-5844; f) F. A. Cruz, V. M. Dong, J. Am. Chem.
Soc. 2017, 139, 1029-1032; g) F. A. Cruz, Y. Zhu, Q. D. Tercenio, Z.
Shen, V. M. Dong, J. Am. Chem. Soc. 2017, 139, 10641-10644; h) P. P.
Bora, G.-J. Sun, W.-F. Zheng, Q. Kang Chin. J. Chem. 2018, 36, 20-24.
B. Trost, Science 1991, 254, 1471-1477.
O
O
O
O
O
O
Me
Me
Me
Me
Me
Ph
Me
Ph
Ph
Ph MeO
OMe
4
19
20
99% yield,[a]
98% yield,
98% yield,
E/Z 50:50, 98/98% ee
E/Z 55:45,[b] 98/98% ee[c]
E/Z 52:48, 98/97% ee
O
O
O
O
O
O
O
O
O
O
Me
Me
[4]
[5]
Me
Me
Me
Me
Me
Me
Bn
Me
Me
Me
For selected reviews on transition-metal-catalyzed allylic substitution,
see: a) B.M.Trost, D. L. VanVranken, Chem. Rev. 1996, 96, 395-422;
b) B.M.Trost, M. L. Crawley, Chem. Rev. 2003, 103, 2921-2944; c)
J.Tsuji, I. Minami, Acc. Chem. Res. 1987, 20, 140-145; d) Z.Lu, S. Ma,
Angew. Chem. Int. Ed. 2007, 47, 258-297; Angew. Chem. 2007, 120,
264-303; e) G.Helmchen, A. Dahnz, P. Dubon, M. Schelwies, R.
Weihofen, Chem. Commun. 2007, 675-691.
H23C11
Me
H11C5
13
C11H23
C5H11
Cy
Me
Me
21
22
94% yield,
23
86% yield,
24
91% yield,
25
53% yield,
95% yield,
E/Z 56:44, 79/71% ee E/Z 50:50, 95/93% ee E/Z 43:57, 96/97% ee E/Z 44:56, 98/97% ee E/Z 9:91, n.d./97% ee
[a] Reported yields are of isolated 1,3-diketones. For substrates with steric
hindrance the lower yields were accompanied by full conversion of allene 1
and detection of the E-TFA-ester 3 in the crude 1H-NMR. [b] E/Z-ratio was
determined by crude 1H-NMR. [c] ee was determined by chiral HPLC; X/Y %
ee (X: E-isomer, Y: Z-isomer).
[6]
[7]
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To conclude, we herein described a rare case of a parallel
kinetic resolution in the course of a rhodium-catalyzed addition
of 1,3-diketones to racemic allenes. Mechanistic investigations
revealed that allylic TFA-esters are passed as intermediates. In
this first step alkene geometry is controlled while the second
step occurs as an allylic substitution and controls the
enantioselectivity in this process while preserving alkene
geometry.
For selected examples of Ir-catalyzed allylic alkylation to achieve
branched products, see: a) W. Chen, J. F. Hartwig, J. Am. Chem. Soc.
2013, 135, 2068-2071; b) J. F. Hartwig, L. M. Stanley, Acc. Chem. Res.
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[8]
For selected examples of Rh-catalyzed allylic alkylation to achieve
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[15] For further experiments, see supporting information.
[16] For detailed overview about NMR-spectra monitoring the reaction, see
supporting information.
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10.1002/anie.201903365
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Layout 2:
COMMUNICATION
Lukas J. Hilpert and Bernhard Breit*
O
O
[Rh(I)L*]
Page No. – Page No.
R3
R3
R1
O
R2
Rhodium-Catalyzed Parallel Kinetic
Resolution of Racemic Internal
Allenes Towards Enantiopure Allylic
1,3-Diketones
R1
R2
•
E
parallel
kinetic
resolution
(R)
O
O
rac
R1
+
O
R3
R3
R2
•
R3
R3
(S)
[Rh(I)L*]
R1
Z
R2
A rare case of a parallel kinetic resolution in the course of a rhodium-catalyzed addition of 1,3-diketones to racemic allenes is
reported. Mechanistic analysis shows that each allene enantiomer reacts in parallel to either the E- or Z-allylation product in high
enantioselectivity with the same absolute configuration of the newly formed stereocenter.
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