Asymmetric Hydroacylation Involving Alkene Isomerization for the Construction of C3-Chirogenic Center

Article abstract of DOI:10.1002/anie.202017190

A new transformation pattern for enantioselective intramolecular hydroacylation has been developed involving an alkene isomerization strategy. Proceeding through a five-membered rhodacycle intermediate, 3-enals were converted to C₃- or C₃,C₅-chirogenic cyclopentanones with satisfactory yields, diastereoselectivities, and enantioselectivities. A catalytic cycle has been theoretically calculated and the origin of the stereoselection is rationally explained.

Full text of DOI:10.1002/anie.202017190

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How to cite: Angew. Chem. Int. Ed. 2021, 60, 8997–9002
International Edition: doi.org/10.1002/anie.202017190
German Edition: doi.org/10.1002/ange.202017190
Asymmetric Synthesis Very Important Paper
Asymmetric Hydroacylation Involving Alkene Isomerization for the
Construction of C3-Chirogenic Center
Chong Liu, Jing Yuan, Zhenfeng Zhang,* Ilya D. Gridnev, and Wanbin Zhang*
Abstract: A new transformation pattern for enantioselective
intramolecular hydroacylation has been developed involving
an alkene isomerization strategy. Proceeding through a five-
membered rhodacycle intermediate, 3-enals were converted to
C3- or C3,C5-chirogenic cyclopentanones with satisfactory
yields, diastereoselectivities, and enantioselectivities. A catalytic
cycle has been theoretically calculated and the origin of the
stereoselection is rationally explained.
Introduction
Chiral ketones are ubiquitous skeletons in natural prod-
ucts and synthetic pharmaceuticals.[1] Among the various
developed methods, the enantioselective hydroacylation of
alkenes is one of the most efficient and atom-economic
approaches for the construction of these valuable com-
pounds.[2] Since the pioneering work of James and Young,[3]
the area of metal-catalyzed asymmetric intramolecular hydro-
acylations for the generation of chiral cycloketones has seen
considerable progress, especially for methodologies focused
on 5-substituted 5-enals and 4-substituted 4-enals (Sch-
eme 1a,b).[4] Since the corresponding seven- and six-mem-
bered rhodacycle intermediates tend to undergo reductive
elimination, they can only provide a single pattern of trans-
formation, which results in limitations to the construction of
C5- and C4-dominated chirogenic centers (numbered from the
formyl group). Recently, Dong has reported the efficient
creation of C2-chirogenic center via an asymmetric desym-
metrization strategy.[5] However, to the best of our knowl-
Scheme 1. Different formations and enantioselective transformations
of rhodacycle intermediates.
edge, research on the efficient generation of only C3-
chirogenic center via asymmetric hydroacylation of alkenes
still remains a great challenge.[6] In order to expand the
capacity and diversity of asymmetric hydroacylation, it is still
highly desirable to develop distinctive transformation pat-
terns and reaction strategies.
Compared to the commonly utilized seven- and six-
membered rhodacycle intermediates, the five-membered
rhodacycle intermediate is too thermodynamically stable to
achieve reductive elimination. In turn, it provides the
possibility to realize transformation diversity through dynam-
ically feasible sequential reactions such as Rh-C addition and
b-C elimination.[7] To date, five-membered rhodacycle inter-
[*] C. Liu, J. Yuan, Prof. Dr. W. Zhang
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,
Frontier Science Center for Transformative Molecules, School of
Chemistry and Chemical Engineering, Shanghai Jiao Tong University
800 Dongchuan Road, Shanghai 200240 (China)
E-mail: wanbin@sjtu.edu.cn
Dr. Z. Zhang, Prof. Dr. W. Zhang
mediates are mainly produced from 5,4-migratory insertion of
[7]
School of Pharmacy, Shanghai Jiao Tong University
800 Dongchuan Road, Shanghai 200240 (China)
E-mail: zhenfeng@sjtu.edu.cn
À
4-enals or C C activation of cyclobutanones (Scheme 1c).
However, the alternative route via 3,4-migratory insertion of
3-enals, which could generate the challenging C3-chirogenic
center, remains unexplored (Scheme 1d).
Prof. Dr. I. D. Gridnev
Department of Chemistry, Graduate School of Science
Tohoku University
In order to further transform the five-membered rhoda-
cycle intermediate, we envisaged that an external b-H
elimination could be introduced to enable the final synthesis
of C3-chirogenic cyclopentanones via a six-membered rhoda-
cycle intermediate (Scheme 1d). The key strategy for this
Aramaki 3–6, Aoba-ku, Sendai 980-8578 (Japan)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202017190.
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À
transformation is an unusual “alkene isomerization” from the
thermodynamically favored 3-position to the thermodynami-
cally unfavored 4-position, which is completely different from
the reported examples in asymmetric hydrogenations, hydro-
borations, and hydrosilylations.[8] In addition, in combination
with our previous findings by using an internal 4-enals,[9] an
extra C5-chirogenic center could be constructed during the
last reductive elimination step. This work provides a new
transformation pattern for asymmetric hydroacylations, as
well as a new reaction strategy for the construction of
C3-chirogenic center.
BArFÀ to SbF6 had almost no effect on the reaction
(entry 5). However, using the comparatively smaller counter-
ion, BF4À, and other coordinating ions resulted in no reaction
(entry 6 and Table S2 in SI). Shortening the reaction time
from 36 to 24 h and further lowering the reaction temperature
from 120 to 1108C suppressed the side reaction and increased
the yield of the desired product from 76% to 98% and the
enantioselectivity from 98/2 to 99/1 er (entries 7,8). Further
lowering the temperature to 1008C dramatically reduced the
reactivity with no product detected (entry 9).
With an optimized protocol prepared, we evaluated a wide
range of (E)-2,2-dialkyl-3-arylpent-3-enals containing differ-
ent substituents on the aromatic ring (Scheme 2). Substrates
((E)-1a,c–p) bearing substituents at the meta- and para-
positions underwent hydroacylation smoothly to give the
desired products in 95–98% yield and with 96/4–99/1 er,
regardless of the presence of electron-withdrawing/electron-
donating substituents, or mono-/di-substituted groups on the
aromatic ring. The hydroacylation of substrates with an ortho-
substituted group ((E)-1b,q) requires a higher catalyst load-
ing (10 mol%) to give the corresponding products in ex-
cellent yields (both are 98%), but with moderate enantio-
Results and Discussion
With this hypothesis in mind, (E)-2,2-dimethyl-3-phenyl-
pent-3-enal ((E)-1a) was chosen as the model substrate for
condition optimization (Table 1, Table S1 and S2 in SI).
Solvents and ligands play critically important roles in this
reaction. The desired product 2a could only be obtained in
1,4-dioxane. Additionally, only the bulky tBu substituted
bisphosphine ligands, DTBM-SegPhos (L3) and BipheP*
(L4),[10] could afford 2a (entries 1–4 and Table S1 in SI). The
latter gave the desired product in 24% yield (remainder being
unreacted (E)-1a) and 64/36 er, while the former provided
a promising result of 76% yield (with the rest of the material
being the decarbonylated byproduct 2a’[11]) and 98/2 er.
Changing the counterions of the catalyst precursors from
Table 1: Condition optimization for (E)-1a.
Entry[a]
Ligand
Yield [%][b]
er [%][c]
1
2
3
L1
L2
L3
L4
L3
L3
L3
L3
L3
trace
trace
76
24
73
NR
78
98
–
–
98/2
64/36
98/2
–
98/2
99/1
–
4
5[d]
6[e]
7[f]
8[f,g]
9[f,h]
NR
[a] Conditions: (E)-1a (0.2 mmol), ligand (5 mol%), [Rh(COD)Cl]2
(2.5 mol%), NaBArF (5 mol%), 1,4-dioxane (2 mL), 1208C, 36 h, unless
otherwise noted. [b] Isolated yields of 2a. [c] The er values of 2a were
determined by HPLC using a chiral AS-H column. [d] [Rh(COD)2]SbF6
(5 mol%) used instead of [Rh(COD)Cl]2 and NaBArF. [e] [Rh(NBD)2]BF4
(5 mol%) used instead of [Rh(COD)Cl]2 and NaBArF. [f] Reaction time is
24 h. [g] 1108C. [h] 1008C.
Scheme 2. Substrate scope of (E)-3-enals. [a] Conditions:
(E)-1 (0.2 mmol), (R)-DTBM-SegPhos (5 mol%), [Rh(COD)Cl]2
(2.5 mol%), NaBArF (5 mol%), 1,4-dioxane (2 mL), 1108C, 24 h,
unless otherwise noted. Isolated yields. The er values were determined
by HPLC using chiral columns. [b] Catalyst loading is 10 mol%. [c] The
configuration of 1r,s is Z.
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selectivities (83/17 and 85/15 er, respectively). The hetero-
aromatic substrate (Z)-1r and (Z)-1s is tolerated under the
reaction conditions to form the corresponding product 2r and
2s in excellent results. By replacing the methyl to ethyl at the
2-position, the substrate (E)-1t could also give its corre-
sponding product with satisfactory results (98% yield and
94/6 er).
After achieving excellent performance with (E)-sub-
strates, we turned our attention to exploration with (Z)-
substrates (Table S3 and S4 in SI). Taking (Z)-2,2-dimethyl-3-
phenylpent-3-enal ((Z)-1a) as a model substrate, the bulky
tBu substituted bisphosphine ligand BipheP* (L4) gave
positive results. With an optimized protocol for (Z)-1a in
hand, the substrate scope of the (Z)-2,2-dialkyl-3-arylpent-3-
enals was explored (Scheme 3). In most cases, the corre-
sponding products were obtained quantitatively with 91/9–
96/4 er, especially for substrates bearing meta-F and meta-Cl
substituents. However, a Me-substituent at the ortho-position
of aromatic ring significantly reduced the reactivity and
enantioselectivity ((Z)-1b), and substrates possessing para-Ph
and 2-Et substituents gave relatively poor results ((Z)-1k,t).
These are consistent with the results obtained with the (E)-
substrates.
Scheme 4. Asymmetric construction of C3,C5-chirogenic cyclopenta-
nones.
In order to verify the feasibility of this catalyst system for
the construction of discontinuous C3-,C5-chirogenic cyclo-
pentanones, a number of 3-enals bearing long alkyl substitu-
ents were chosen as the substrates (Scheme 4). By using
DTBM-SegPhos (L3) as the ligand, (E)-2,2-dimethyl-3-phe-
nylhex-3-enal ((E)-1u) was successfully converted to the
desired product trans-2u in 76% yield and moderate enantio-
and diastereoselectivity (3.5:1 dr, 89/11 er). When the ligand
was changed to DM-MeO-BIPHEP, the trans-cyclopentanone
was obtained with promising results (95% yield, 3.5:1 dr, 96/4
er). According to substrate scope, substituents at the meta-
and para-positions of the aromatic skeleton have little impact
on the catalytic performance. As expected, the hydroacyla-
tion of (E)-1v occurred to form the corresponding trans-2v
with excellent results (95% yield, 3.3:1 dr, 97/3 er). The
absolute configuration of this product was confirmed to be
(R,S) according to the single crystal XRD analysis (see SI for
details). Another substrate, (E)-1w, also afforded its corre-
sponding product trans-2w with acceptable results (91%
yield, 2.3:1 dr, 92/8 er). Similar results are also observed for
(Z)-substrates. To our delight, contrary to the trans-products
derived from (E)-substrates, the chiral cyclopentanones were
obtained with a cis-configuration using BipheP* as the ligand
(Scheme 4). The highest dr value of 12.4:1 was obtained
during the hydroacylation of (Z)-1u, giving the desired
product cis-2u with 89/11 er. Another two substrates, (Z)-1v
and (Z)-1x, also gave the desired cis-products with compa-
rable yields, diastereoselectivities, and enantioselectivities.
To gain insight into the mechanism, we prepared deute-
rium-labeled substrates (E- and Z-1a-d) and performed the
hydroacylation reactions under the optimized conditions
(Scheme 5). These experiments showed that the proton on
the C3-chirogenic center originates completely from the
aldehyde group, which gave the evidence for the oxidative
addition of CO-H to rhodium and Rh-H addition to the C3-
position.
Scheme 3. Substrate scope of (Z)-3-enals. [a] Conditions:
(Z)-1 (0.2 mmol), [Rh(COD)2]SbF6 (10 mol%), (RP,Sa,RP)-BipheP*
(10 mol%), 1,4-dioxane (2 mL), 1108C, 24 h. Isolated yields. The er
values were determined by HPLC using chiral columns.
In order to gain a clearer insight into the reaction
mechanism and stereocontrol mode, the catalytic cycle and
corresponding energies of the intermediates and transition
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states were calculated as shown in Figure 1. Coordination of
the prochiral substrate to the catalyst is endergonic, and
provides the catalyst-substrate complexes 1R and 1S. Sub-
sequent oxidative addition of the aldehyde group to the metal
affords the corresponding hydrides 2 which are capable of
transferring the hydride to the prochiral carbon, thus
producing chelating diastereomeric complexes 3R and 3S.
Note that this step is stereoselective favoring the formation of
the S-stereocenter thermodynamically. The next stage, being
also stereoselective, is also rate-limiting due to the high
activation barriers of the rearrangements bringing the methyl
groups on the opposite site of the chelate cycle of 3R and 3S
Scheme 5. Deuteration experiments.
Figure 1. A) Computed catalytic cycle and B) potential energy profile.
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into a proper position to enable
abstraction of a hydride. The an-
gles of Rh-C-CH3, which corre-
spond to the distance between
Rh···b-H, have been shown as q in
3R/4R and 3S/4S. The b-H elimi-
nation will occur only when this
angle is small enough. The TS3S is
4.2 kcalmolÀ1 less stable than
TS3R, strongly indicating the ste-
reoselective formation of the R-
enantiomer. The Rh-P bond in the
TS3S must dissociate to effectuate
the hydride transfer, since other-
wise the methyl group of the sub-
Figure 2. Optimized structures for the competing transition states.
strate would overlap with the methyl group of the catalyst. Conclusion
This is additionally illustrated by the opposite relative
stabilities of 4R and 4S: while in the latter the rhodacycle is
In summary, we have realized the first enantioselective
intramolecular hydroacylation reaction of 3-enals for the
À
closed, the former cannot form a proper Rh C bond due to
the potential overlap of the CHCH3 group with the t-Bu group
of the catalyst.
construction of C3-chirogenic cyclopentanones. The reaction
proceeds through alkene isomerization via a five-membered
rhodacycle intermediate. The C3-chirogenic and C3,C5-chiro-
genic products are obtained with satisfactory yields, diaste-
reoselectivities, and enantioselectivities (up to 99/1 er). We
have also proposed a catalytic mechanism for the reaction and
have rationalized the outcome of the enantioselectivity based
on theoretical calculation.
Further rearrangements are necessary to place the newly
=
formed Rh-H and C C bonds in a proper position for the
hydrorhodation resulting in 7. There are numerous possibil-
ities that are illustrated by computing different rearrange-
ments leading to 7 for the R and S pathways. In the
transformations computed for the R-pathway, b-H elimina-
tion of the agostic intermediate 4R results in the Rh hydride
=
5R with the coplanar Rh-H and C C bonds. However, to
avoid the reverse transformation via hydrorhodation, the
double bond must first rotate via TS5R yielding 6R. The latter
gives the rhodacycle 7R in a hydrorhodation via TS6R, and
after reductive elimination provides the reaction product 2aR
and releases the catalyst. For the S-pathway another conse-
quence for the catalytic steps was computed. The agostic
intermediate 4S can undergo b-H elimination and reductive
elimination providing a coordinated 4-enals. Rotation of the
aldehyde group or small relocation would give 6S upon
hydrorhodation via TS6S yielding 7S, and eventually the
reaction product 2aS. It can be seen that the free energies of
either of the computed pathways are much lower than those
of the transition states of the rate-limiting steps. Hence, they
do not affect the origin of the stereoselection.
Acknowledgements
This work was supported by National Key R&D Program of
China (No. 2018YFE0126800), National Natural Science
Foundation of China (Nos. 21620102003, 21831005,
91856106, 21991112, 22071150), and Shanghai Municipal
Education Commission (No. 201701070002E00030). We
thank the Instrumental Analysis Center of Shanghai Jiao
Tong University. We acknowledge the generous gifts of the P-
chirogenic bisphosphine ligands from Nippon Chemical
Industrial Co. Ltd.
Conflict of interest
The optimized structures with selected interatomic dis-
tances for the competing transition states TS3S and TS3R has
been shown in Figure 2. In TS3S, approach of the methyl
group of the catalyst to the Rh atom (to enable further
hydride transfer) requires dissociation of the catalyst chelate
cycle leading to an increase in one of the Rh-P interatomic
distances to 2.73 Š. In TS3R, this interatomic distance is only
2.49 Š (i.e. it is 0.24 Š shorter). Maintaining the same Rh-P
distance in the TS3S would require the methyl groups of the
catalyst and the substrate to approach at 1.94 Š (2.18–0.24),
and it is known that a weak attraction between two aliphatic
protons in the range 2.3–2.7 Š switches to repulsion if they are
closer than 2.1 Š.[12]
The authors declare no conflict of interest.
Keywords: b-H elimination ·alkene isomerization ·
cycloketones ·hydroacylation ·rhodacycle
[1] a) T. I. Richardson, J. A. Dodge, G. L. Durst, L. A. Pfeifer, J.
Shah, Y. Wang, J. D. Durbin, V. Krishnan, B. H. Norman, Bioorg.
Med. Chem. Lett. 2007, 17, 4824; b) S. A. Snyder, A. L. Zografos,
Y. Lin, Angew. Chem. Int. Ed. 2007, 46, 8186; Angew. Chem.
2007, 119, 8334; c) L. Liu, S. Liu, X. Chen, L. Guo, Y. Che,
Bioorg. Med. Chem. 2009, 17, 606; d) J. Li, D. Zhang, X. Wu,
Bioorg. Med. Chem. Lett. 2011, 21, 130; e) A. Prandi, S.
Franchini, L. I. Manasieva, P. Fossa, E. Cichero, G. Marucci,
M. Buccioni, A. Cilia, L. Pirona, L. Brasili, J. Med. Chem. 2012,
55, 23; f) M.-L. Tang, C. Zhong, Z.-Y. Liu, P. Peng, X.-H. Liu, X.
Angew. Chem. Int. Ed. 2021, 60, 8997 –9002
ꢀ 2021 Wiley-VCH GmbH
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Angewandte
Research Articles
Chemie
À
Sun, Eur. J. Med. Chem. 2016, 113, 63; g) J. Yang, X.-M. Zhang,
F.-M. Zhang, S.-H. Wang, Y.-Q. Tu, Z. Li, X. C. Wang, H. Wang,
Angew. Chem. Int. Ed. 2020, 59, 8471; Angew. Chem. 2020, 132,
8549.
3310; For selected examples of C C activation, see: b) X. Zhou,
H. M. Ko, G. Dong, Angew. Chem. Int. Ed. 2016, 55, 13867;
Angew. Chem. 2016, 128, 14071; c) L. Deng, T. Xu, H. Li, G.
Dong, J. Am. Chem. Soc. 2016, 138, 369; d) L. Deng, L. Jin, G.
Dong, Angew. Chem. Int. Ed. 2018, 57, 2702; Angew. Chem.
2018, 130, 2732; e) L. Deng, Y. Fu, S. Y. Lee, C. Wang, P. Liu, G.
Dong, J. Am. Chem. Soc. 2019, 141, 16260.
[2] For selected reviews on metal-catalyzed asymmetric hydro-
acylations, see: a) M. C. Willis, Chem. Rev. 2010, 110, 725;
b) J. C. Leung, M. J. Krische, Chem. Sci. 2012, 3, 2202; c) S. K.
Murphy, V. M. Dong, Chem. Commun. 2014, 50, 13645; d) A.
Ghosh, K. F. Johnson, K. L. Vickerman, J. A. Walker, L. M.
Stanley, Org. Chem. Front. 2016, 3, 639.
[3] a) B. R. James, C. G. Young, J. Chem. Soc. Chem. Commun.
1983, 1215; b) B. R. James, C. G. Young, J. Organomet. Chem.
1985, 285, 321.
[4] For selected examples, see: a) R. W. Barnhart, X. Wang, P.
Noheda, S. H. Bergens, J. Whelan, B. Bosnich, J. Am. Chem. Soc.
1994, 116, 1821; b) K. Kundu, J. V. McCullagh, A. T. More-
head, Jr., J. Am. Chem. Soc. 2005, 127, 16042; c) T. J. Hoffman,
E. M. Carreira, Angew. Chem. Int. Ed. 2011, 50, 10670; Angew.
Chem. 2011, 123, 10858; d) J. Yang, N. Yoshikai, J. Am. Chem.
Soc. 2014, 136, 16748; e) A. Ghosh, L. M. Stanley, Chem.
Commun. 2014, 50, 2765; f) X.-W. Du, A. Ghosh, L. M. Stanley,
Org. Lett. 2014, 16, 4036; g) K. F. Johnson, A. C. Schmidt, L. M.
Stanley, Org. Lett. 2015, 17, 4654; h) E. J. Rastelli, N. T. Truong,
D. M. Coltart, Org. Lett. 2016, 18, 5588; i) K. F. Johnson, E. A.
Schneider, B. P. Schumacher, A. Ellern, J. D. Scanlon, L. M.
Stanley, Chem. Eur. J. 2016, 22, 15619; j) K. L. Vickerman, L. M.
Stanley, Org. Lett. 2017, 19, 5054; k) J. Yang, A. RØrat, Y. J. Lim,
C. Gosmini, N. Yoshikai, Angew. Chem. Int. Ed. 2017, 56, 2449;
Angew. Chem. 2017, 129, 2489; l) Z. Chen, Y. Aota, H. M. H.
Nguyen, V. M. Dong, Angew. Chem. Int. Ed. 2019, 58, 4705;
Angew. Chem. 2019, 131, 4753.
[8] For review on alkene isomerization, see: a) A. Vasseur, J.
Bruffaerts, I. Marek, Nat. Chem. 2016, 8, 209; For selected
examples of hydrogenations, see: b) R. Wu, M. G. Beauchamps,
J. M. Laquidara, J. R. Sowa, Jr., Angew. Chem. Int. Ed. 2012, 51,
2106; Angew. Chem. 2012, 124, 2148; c) N. Arai, Y. Okabe, T.
Ohkuma, Adv. Synth. Catal. 2019, 361, 5540; For selected
examples of hydroborations, see: d) A. J. Ruddy, O. L. Sydora,
B. L. Small, M. Stradiotto, L. Turculet, Chem. Eur. J. 2014, 20,
13918; e) M. L. Scheuermann, E. J. Johnson, P. J. Chirik, Org.
Lett. 2015, 17, 2716; f) X. Chen, Z. Cheng, J. Guo, Z. Lu, Nat.
Commun. 2018, 9, 3939; g) N. G. LØonard, W. N. Palmer, M. R.
Friedfeld, M. J. Bezdek, P. J. Chirik, ACS Catal. 2019, 9, 9034;
For selected examples of hydrosilylations, see: h) S. Azpeitia,
M. A. Garralda, M. A. Huertos, ChemCatChem 2017, 9, 1901;
i) S. Hanna, T. W. Butcher, J. F. Hartwig, Org. Lett. 2019, 21,
7129; For other examples of alkene isomerization, see: j) C.
Romano, C. Mazet, J. Am. Chem. Soc. 2018, 140, 4743; k) X. Liu,
W. Zhang, Y. Wang, Z.-X. Zhang, L. Jiao, Q. Liu, J. Am. Chem.
Soc. 2018, 140, 6873; l) W. Wang, C. Ding, Y. Li, Z. Li, Y. Li, L.
Peng, G. Yin, Angew. Chem. Int. Ed. 2019, 58, 4612; Angew.
Chem. 2019, 131, 4660; m) Y. He, C. Liu, L. Yu, S. Zhu, Angew.
Chem. Int. Ed. 2020, 59, 9186; Angew. Chem. 2020, 132, 9271;
n) R. Yu, S. Rajasekar, X. Fang, Angew. Chem. Int. Ed. 2020, 59,
21436; Angew. Chem. 2020, 132, 21620.
[5] J.-W. Park, K. G. M. Kou, D. K. Kim, V. M. Dong, Chem. Sci.
2015, 6, 4479.
[9] J. Yuan, C. Liu, Y. Chen, Z. Zhang, D. Yan, W. Zhang,
Tetrahedron 2019, 75, 269.
[6] The C3-chirogenic center has been obtained during the forma-
tion of C4-chirogenic center via a strategy of asymmetric
desymmetrization: a) X.-M. Wu, K. Funakoshi, K. Sakai,
Tetrahedron Lett. 1993, 34, 5927; b) M. Tanaka, M. Imai, M.
Fujio, E. Sakamoto, M. Takahashi, Y. Eto-Kato, X. M. Wu, K.
Funakoshi, K. Sakai, H. Suemune, J. Org. Chem. 2000, 65, 5806;
c) M. Tanaka, M. Takahashi, E. Sakamoto, M. Imai, A. Matsui,
M. Fujio, K. Funakoshi, K. Sakai, H. Suemune, Tetrahedron
2001, 57, 1197; The example to construct only the C3-chirogenic
center has been reported with poor enantioselectivity and yield
via a strategy of kinetic resolution: d) R. W. Barnhart, B.
Bosnich, Organometallics 1995, 14, 4343.
[10] a) J. Jia, Z. Ling, Z. Zhang, K. Tamura, I. D. Gridnev, T.
Imamoto, W. Zhang, Adv. Synth. Catal. 2018, 360, 738; b) J. Jia,
D. Fan, J. Zhang, Z. Zhang, W. Zhang, Adv. Synth. Catal. 2018,
360, 3793.
[11] A plausible mechanism for the generation of byproduct 2a’ via
decarbonylation and alkene isomerization has been proposed in
the Supporting Information, Scheme S1.
[12] I. D. Gridnev, ChemCatChem 2016, 8, 3463.
Manuscript received: December 26, 2020
Accepted manuscript online: January 28, 2021
Version of record online: March 9, 2021
[7] For selected examples of 5,4-migratory insertion of 4-enals, see:
a) J.-W. Park, Z. Chen, V. M. Dong, J. Am. Chem. Soc. 2016, 138,
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