Palladium/TY-Phos-Catalyzed Asymmetric Intermolecular α-Arylation of Aldehydes with Aryl Bromides

Article abstract of DOI:10.1002/anie.202106109

Despite much progress has been made in the asymmetric α-arylation reactions of cyclic ketones, lactones and lactams, the enantioselective α-arylation of acyclic carbonyl compounds lagged much behind due to the in situ generated Z/E-enolate intermediates l

Full text of DOI:10.1002/anie.202106109

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Palladium/TY-Phos-Catalyzed Asymmetric Intermolecular α-
Arylation of Aldehydes with Aryl Bromides
Authors: Junliang Zhang, Zhangjin Pan, Wenbo Li, Shuai Zhu, Feng
Liu, and Hai-Hong Wu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202106109
Link to VoR: https://doi.org/10.1002/anie.202106109

10.1002/anie.202106109
Angewandte Chemie International Edition
COMMUNICATION
Palladium/TY-Phos-Catalyzed Asymmetric Intermolecular α-Arylation of
Aldehydes with Aryl Bromides
Zhangjin Pan,[a] Wenbo Li,[a] Shuai Zhu,[a] Feng Liu,[a] Hai-Hong Wu,[a] and Junliang Zhang*[a] [b]
Abstract: Despite much progress has been made in the asymmetric
α-arylation reactions of cyclic ketones, lactones and lactams, the
enantioselective α-arylation of acyclic carbonyl compounds lagged
much behind due to the in-situ generated Z/E-enolate intermediates
leading to opposite enantiomers. Especially, the asymmetric α-
arylation of acyclic aldehydes is a long-standing challenge, because
of the highest activity among carbonyl compounds leading to various
competitive side reactions. Herein we reported an efficient Pd-
catalyzed asymmetric intermolecular α-arylation reaction of α-alkyl-α-
aryl disubstituted aldehydes with aryl bromides, which provides a
rapid access to chiral aldehydes bearing an α-all-carbon quaternary
stereocenter in moderate to good yields with good er in most cases.
In addition, a pair of enantiomers could be easily prepared with the
use of the same ligand by exchanging the aryl groups of aldehyde and
aryl bromide
arylation of alkylnitriles under the catalysis of the chiral palladium
complex.[10] Many achievements have been made in the allylation
and alkylation and other functionalization of aldehydes,[11] even
arylation of aldehydes was achieved via organic catalysts through
dynamic kinetic resolution.[12] In contrast, the transition-metal-
catalyzed asymmetric direct α-arylation of acyclic aldehydes,
especially in intermolecular case, poses formidable challenges
due to: 1) competitive aldol condensations easily occurred under
basic conditions;[13] 2) acylation byproduct of aldehydes obtained
via C(sp2)-H activation of aldehydes by metal catalysis;[14] 3) the
highest sensitivity and reactivity of aldehydes among these
carbonyl-containing compounds (amide < ester < aryl ketone <
aldehyde);[15] 4) it is hard to control the Z/E-selectivity of the
enolate intermediate, which would deliver the opposite
enantiomers (Scheme 1b).[10]
After spending a lot of effort, the group of Buchwald[16] achieved
the first Pd-catalyzed asymmetric intramolecular α-arylation of
Chiral all-carbon quaternary centers are important motifs in
biologically active natural products and pharmaceutically active
molecules.[1] Therefore, the development of versatile approaches
towards the synthesis of those compounds bearing all-carbon
quaternary stereocenters has received widespread attention from
synthetic chemists.[2] With regard to the ready availability of the
coupling partners, the α-arylation of carbonyl compounds is one
of the most efficient and straightforward one among various
emerging methods.[3] Since 1997, the Pd-catalyzed direct α-
arylation of cyclic ketones was reported independently by
Buchwald, Hartwig, and Miura, and this protocol[4] has been
widely extended to enantioselective α-arylation of other cyclic
carbonyl compounds such as ketones,[3d][5] lactone,[6] and
amides[3e][7] or lactam[8]. In addition, the mechanism was
confirmed by Orlandi that the keys to the success of the reaction
is the enolate transmetallation and C−C bond-forming reductive
elimination[5g] (Scheme 1a). However, the asymmetric α-arylation
of acyclic carbonyl compounds to construct quaternary
stereocenters has been much less explored due to the in situ
generated Z/E-enolate intermediates leading to a pair of opposite
enantiomers. The field of enantioselective α-arylation of acyclic
carbonyl compounds remained virtually dormant and, to date,
there are only two examples reported. In 2006, the group of Ma
reported a seminal copper-catalyzed coupling reaction of β-keto
esters with ortho-iodo-trifluoroacetanilides.[9] Ten years later,
Zhou and co-workers successfully realized the asymmetric
[a]
[b]
Z. Pan, W. Li, S. Zhu, F. Liu, H.-H. W and Prof. Dr. J. Zhang*
Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, School of Chemistry and Molecular Engineering,
East China Normal University
Shanghai, 200062 (P. R. China)
Prof. Dr. J. Zhang
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry,
345 Lingling Road, Shanghai 200032, China
E-mail: junliangzhang@fudan.edu.cn; jlzhang@chem.ecnu.edu.cn
Supporting information for this article is given via a link at the end
of the document.((Please delete this text if not appropriate))
Scheme 1. Enantioselective α-arylation of carbonyl compounds to build
quaternary stereocenters
This article is protected by copyright. All rights reserved.

10.1002/anie.202106109
Angewandte Chemie International Edition
COMMUNICATION
aldehydes, delivering the corresponding indane-derived
aldehydes bearing a quaternary stereocenter in good yields and
enantioselectivities in 2008 (Scheme 1c). Four years later, Mazet
and co-workers revisited the same reaction with a new type of
axially chiral P-stereogenic ligand.[17] With regard to the
importance of chiral aldehyde and the formidable challenge for
the construction of all-carbon quaternary stereocenter, we
became interested in asymmetric intermolecular direct α-arylation
of aldehydes, hoping to overcome these difficulties to furnish
acyclic all-carbon α-quaternary aldehydes. Our group has been
committed to the exploration of novel chiral sulfinamide-
please see supporting information. And it is worth noting that AgF
is necessary, it may play the role like Lewis acid to promote
transmetallization.[19]
With the optimal reaction conditions in hand, we next turned to
explore the scope of reaction via the variation of two reaction
components (Scheme 2). We first examined the scope of aryl/
heteroaryl bromides in couplings with model phenylacetaldehyde
1. In general, not only electron-rich but also electron-poor aryl
halides are compatible to give the desired products in good yields
and enantioselectivities (4-15, 35-75% yields, 92:8-97:3 er).
Interestingly, the yield of 9 was increased from 35% to 63%, with
the temperature rising from 25 °C to 35 °C, but the er value
remains good. Owing to some products are not easily purified with
impurities or the starting materials, the aldehyde products were
further reduced by NaBH4 to the corresponding alcohol (14).
Polysubstituted aryl halides, 2-naphthalenyl and heteroaryl
bromides were also well applicable to the present transformation,
delivering the products in 42-84% yields with 92:8-95:5 er (16-21).
Moreover, we were delighted to find that the corresponding
products 22−28 could be obtained in moderate yields with good
enantioselectivities, irrespective of existing diverse functional
groups and complex molecular structures.
phosphine (Sadphos), which have shown great performance in
asymmetric palladium catalysis
[18]
and are also commercially
available from Strem and Daciel now. Herein, we wish to report
our effort to realize Pd-catalyzed enantioselective intermolecular
direct α-arylation reaction of aldehydes with aryl halides under
mild conditions. The new electron-rich TY-Phos L24 bearing an
N-allyl group is finally identified after systematic finetuning and
responsible for the reactivity, enantioselectivity, and mild
conditions (Scheme 1d).
This asymmetric α-arylation protocol was also applied to a wide
range of α-substituent aldehyde with commercially available aryl
bromide. Both electron-donating and electron-withdrawing groups
on the phenyl moiety of the aldehydes were well tolerant,
delivering the desired products 29-39 in moderate to good yields
with 94:6-96:4 er. Moreover, disubstituted phenyl group, naphthyl
and heteroaryl groups were also compatible to give the desired
products (40-48) with 95:5-96:4 er. Extension of the chain length
from the methyl group to the ethyl or 3-fluoropropyl or n-hexyl
group was found to have adverse effect on enantioselectivity (49-
51), implying that mixtures of Z/E-enolate generated and
produced the opposite enantiomers. In addition to the chain
aldehydes, the cyclic aldehyde also proceeded cleanly to furnish
the α-arylation products (52-54) in 64-70% yields with 92:8-94:6
er. It is worth noting that tetralin aldehyde 54 was always obtained
with a low er value among the existing intramolecular arylation
strategy.[16][17] However, target product 55 bearing isopropyl and
triarylaldehyde 56 could not be achieved due to steric hindrance
and low reactivity. And α-dialkyl aldehyde 57 has no good result
either, these results indicate further ligand modification and even
new ligand design is necessary.
We also proved the robustness of TY-Phos derived palladium
complex to prepare enantiomers by adjusting the functional
groups on aldehydes and aryl bromides. Five sets of enantiomers
were obtained efficiently with similar enantioselectivities (92:8-
97:3 er) by using the same ligand L24. A little decrease in
enantioselectivity was observed when the substrates 58 and ent-
58 containing a benzodioxazole moiety. This result shows that the
reaction system has good compatibility and tolerance with
functional group of the substrates. Furthermore, the absolute
configuration of 3 was confirmed by X-ray crystallography.[20]
Having demonstrated outstanding results for the α-arylation of α-
branched aldehydes, we then explored the effect of the leaving
groups on the aryl electrophiles (Supporting Information, part 6
(1)). The reaction of aldehyde 1 with low activity p-chlorobiphenyl
formed the coupling product in 30% yield and 93:7 er, whereas
the same reaction with triflates formed the coupling product in
90.5:9.5 er. However, only a small amount of the required 3 was
obtained in 84:16 er when using high activity p-iodobiphenyl as
Figure 1. Screened modified TY-Phos ligands
Readily available 2-phenylpropionaldehyde
1
and 4-
bromobiphenyl 2 were selected as model substrates for screening
chiral ligands. A series of commercially available chiral ligands
were first examined (Fig S1, L1-L10, supporting information),
but did not provide the desired product under the standard
conditions. Only ligand BINAP (L1) delivered the product 3 in 30%
yield with 73:27 er at 90 °C. We next turned to examine Sadphos
(L11-L17) in present transformation. To our delight, the desired
α-arylation product 3 was obtained in 45% yield with 62:38 er with
the utilization of electron-rich and bulkyl tert-butyl phosphine
derived TY-Phos (L15) as the chiral ligand. However, the ligand
TY-Phos L14 with the free NH moiety is not effective. With this
finding in mind, further systematic fine-tuning the structure of TY-
Phos was carried out (Fig 1). When employing L19 containing
triptycene moiety as ligand, the reaction gave rise to 3 in 46%
yield with 63:37 er. The yield and enantioselectivity could be
improved slightly with the introduction of electron-donating groups
on the phenyl backbone of the ligand (L20 and L21). After
replacing triptycene with 3,5-di(naphthalen-1-yl) phenyl (L22),
which can further enhance the reactivity and enantioselectivity.
When the substituent on the nitrogen atom is changed from
methyl to allyl (L22 vs L23), the enantioselectivity is significantly
increased from 82:18 er to 94.5:5.5 er. The electron-donating
NMe2 group on the phenyl substituent (L24) was beneficial in
terms of catalytic activity and enantioselectivity (80% yield, 96:4
er). With the optimal ligand (L24), other parameters were studied,
This article is protected by copyright. All rights reserved.

10.1002/anie.202106109
Angewandte Chemie International Edition
COMMUNICATION
Scheme 2. Reaction conditions: aldehydes (0.5 mmol), ArBr (0.2 mmol), Pd(TFA)2 (7.5 mol%), L24 (12 mol%), Cs2CO3 (0.5 mmol), AgF (30 mol%) and (nBu)2O (2
mL) at 25 °C under Ar atmosphere for 48 h. [a] at 35 °C. [b] NaBH4 (0.4 mmol) was added. [c] Cs2CO3 (0.4 mmol). [d] at 100 °C. NR = No Reactio
the reaction partner. The aryl electrophiles were recovered and
biphenyl was detected. Furthermore, the kinetics and
thermodynamics of deprotonation of aldehyde 1 in deuterated
solvent was carried out (Supporting Information, part 6 (2)).
The gram-scale synthesis was conducted, delivering 1.38 g of
product 3 in 80% isolated yield with 95:5 er. After recrystallization,
diaryl methyl aldehyde 3 was isolated in 97:3 er (Supporting
Information, part 6 (3)). To prove the synthetic value, several
transformations of the acyclic quaternary aldehyde were
conducted (Scheme 3). Under the oxidation of NaClO2/H2O2,
aldehyde 3 is transformed into the acid 62 in 65% yield without
the loss of enantioselectivity. The treatment of aldehyde 3 with
BnNH2 and NaBH3CN provided the corresponding product 63 in
70% yield with 98:2 er. The addition of methyl lithium to chiral
aldehyde 3 would furnish alcohol 64 in 90% yield with 1:1 dr.
Moreover, the hydrazone was constructed via the condensation
of 3 and sulfonyl hydrazine, which was subsequent allowed to
react with triethylsilane under Pd(tBu3)2 catalysis leading to
product 65 with a C-Si bond formation. Notably, Wittig reaction of
29 with Ph3P+MeBr- could be achieved to access the expected
product 66 in 81% yield with 95.5:4.5 er.
This article is protected by copyright. All rights reserved.

10.1002/anie.202106109
Angewandte Chemie International Edition
COMMUNICATION
Keywords: α-arylation • all-carbon quaternary centers • Z/E-
enolate • Asymmetric catalysis • Acyclic aldehyde
[1]
a) K. C. Nicolaou, Z. Yang, J. J. Liu, H. Ueno, P. G. Nantermet, R. K.
Guy, C. F. Claiborne, J. Renaud, E. A. Couladouros, K. Paulvannan, E.
J. Sorensen, Nature. 1994. 367, 630; b) P. Yates, F. N. MacLachlan, I.
D. Rae, M. Rosenberger, A. G. Szabo, C. R. Willis, M. P. Cava, M.
Behforouz, M. V. Laksh-mikantham, W. Zeiger, J. Am. Chem. Soc. 1973,
95, 7842. c) C. R. Jamison, J. J. Badillo, J. M. Lipshultz, R. J. Comito, D.
W. C. MacMillan, Nat. Chem. 2017, 9, 1165. d) Y. Que, H. Shao, H. He,
S. Gao, Angew. Chem. Int. Ed. 2020, 59, 7444; Angew. Chem. 2020,
132, 7514.
[2]
For selected reviews of construction of quaternary stereocenters: a) K.
W. Quasdorf, L. E. Overman, Nature 2014, 516, 181; b) Y. Liu, S. J. Han,
W. B. Liu, B. M. Stoltz, Acc. Chem. Res. 2015, 48, 740; c) X.-P. Zeng,
Z.-Y. Cao, Y.-H. Wang, F. Zhou, J. Zhou, Chem. Rev. 2016, 116, 7330;
d) C. Li, S. S. Ragab, G. Liu, W. Tang, Nat. Prod. Rep. 2019, 37, 276; e)
Y. Ping, Y. Li, J. Zhu, W. Kong, Angew. Chem., Int. Ed. 2019, 58, 1562;
Angew. Chem. 2019, 131, 1576; f) X. Li, M. Duan, Z. Deng, Q. Shao, M.
Chen, G. Zhu, K. N. Houk, J. Sun, Nat Catal, 2020, 3, 1010.
Scheme 3. Application of the synthetic methodology
In order to gain insights into this transformation, several control
experiments were conducted (Figure S3, Supporting
Information). Firstly, a linear relationship between the ee value
of TY-Phos L24 and product 3 was investigated (Figure S3a),
which reveals that the active Pd/ligand catalytic species is a
monomeric nature. Secondly, when the reaction time was
shortened to 13 hours, the racemic starting material 1 and the
product 3 (50% yield, 96:4 er) were observed (Figure S3b). This
result implies that the transformation has experienced a dynamic
kinetic resolution path. Thirdly, N-Propyl-TY-Phos (L26) was
prepared and subjected to this transformation, which decreased
asymmetric induction ability of this transformation (L26 vs L24).
We proposed that the allyl on the nitrogen atom of L24 may have
a coordination effect with the center metal Pd (Figure S3c).
Therefore, we proposed a stereoinduction model to dictate the
configuration in the final products (Figure S3d). Further
investigations are conducting in our laboratory to discover the
detailed mechanism.
In summary, we have developed an efficient palladium/TY-
Phos-catalyzed asymmetric intermolecular α-arylation of
alkylaldehydes to construct enantioselective acyclic all-carbon α-
quaternary aldehydes for the first time. The method allowed a
facile access to a wide range of α-alkyl-α-aryl disubstituted
aldehydes in 30-80% yield and good er in most cases. The key to
the success of this methodology lies on the application of
electron-rich TY-Phos ligand with an allyl substituent on nitrogen
atom, which makes the α-arylation occurred in good
[3]
For selected reference: a) R. Jiang, L. Ding, C. Zheng, S.-L. You,
Science 2021, 371, 380; b) Z. Wang, Z.-P. Yang, G. C. Fu, Nat. Chem.
2021, 13, 236; c) C. J. Douglas, L. E. Overmann, Proc. Nat. Acad. Sci.
U.S.A. 2004, 101, 5363; d) J. Åhman, J. P. Wolfe, M. V. Troutman, M.
Palucki, S. L. Buchwald, J. Am. Chem. Soc. 1998, 120, 1918; e) S. Lee,
J. F. Hartwig, J. Org. Chem. 2001, 66, 3402; f) J. Han, W. Zhou, P. Zhang,
H. Wang, R. Zhang, H. Wu, J. Zhang, ACS Catal. 2019, 9, 6890; g) Y.
Liang, G. C. Fu, J. Am. Chem. Soc. 2014, 136, 5520.
[4]
[5]
a) M. Palucki, S. L. Buchwald, J. Am. Chem. Soc. 1997, 119, 11108; b)
B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1997, 119, 12382; c) T.
Satoh, Y. Kawamura, M. Miura, M. Nomura, Angew. Chem., Int. Ed.,
1997, 36, 1740; Angew. Chem. 1997,109, 1820.
For selected references on α-arylation of α-substituted ketones, see: a)
T. Hamada, A. Chieffi, J. Åhman, S. L. Buchwald, J. Am. Chem. Soc.
2002, 124, 1261; b) X. Liao, Z. Weng, J. F. Hartwig, J. Am. Chem. Soc.
2008, 130, 195; c) S. Ge, J. F. Hartwig, J. Am. Chem. Soc. 2011, 133,
16330; d) J. Cornella, E. P. Jackson, R. Martin, Angew. Chem., Int. Ed.
2015, 54, 4075; Angew. Chem. 2015, 127, 4147; e) X. Rao, N. Li, H. Bai,
C. Dai, Z. Wang, W. Tang, Angew. Chem. Int. Ed. 2018, 57, 12328;
Angew. Chem. 2018, 130, 12508; f) J. Guo, L. Lin, Y. Liu, X. Li, X. Liu,
X. Feng, Org. Lett, 2016, 18, 5540; g) M. Orlandi, G. Licini, J. Org. Chem.
2020, 85, 11511–11518.
[6]
[7]
D. J. Spielvogel, S. L. Buchwald, J. Am. Chem. Soc. 2002, 124, 3500.
For selected references on α-arylation of α-substituted amides, see: a) J.
Guo, S. Dong, Y. Zhang, Y. Kuang, X. Liu, L. Lin, X. Feng, Angew. Chem.
Int. Ed. 2013, 52, 10245; Angew. Chem. 2013, 125, 10435; b) A. M.
Taylor, R. A. Altman, S. L. Buchwald, J. Am. Chem. Soc. 2009, 131,
9900; c) T. Liu, J. Feng, C. Chen, Z. Deng, R. Kota-giri, G. Zhou, X.
Zhang, Q. Cai, Org. Lett. 2019, 21, 4505; d) Y. Jin, M. Chen, S. Ge, John
F. Hartwig, Org. Lett. 2017, 19, 1390.
enantiocontrol at room temperature. Moreover,
a pair of
enantiomers could be obtained efficiently through changing the
functional groups of aryl bromides with aldehydes. This protocol,
featuring mild conditions and good functional group tolerance,
represents a significant improvement on previous work. We
anticipate that current TY-Phos will be used in other asymmetric
transformations, and will be welcomed by academic and industrial
researchers.
[8]
[9]
C. I. Jette, I. Geibel, S. Bachman, M. Hayashi, S. Sakurai, H. Shimizu, J.
B. Morgan, B. M. Stoltz, Angew. Chem., Int. Ed. 2019, 58, 4297; Angew.
Chem. 2019, 131, 4341.
X. Xie, Y. Chen, D. Ma, J. Am. Chem. Soc. 2006, 128, 16050.
[10] Z. Jiao, K. W. Chee, J. S. Zhou, J. Am. Chem. Soc. 2016, 138, 16240.
[11] For selected references: a) I. Marek, Y. Minko, M. Pasco, T. Mejuch, N.
Gilboa, H. Chechik, J. P. Das, J. Am. Chem. Soc. 2014, 136, 7, 2682; b)
B, Bhaskararao, R. B. Sunoj, J. Am. Chem. Soc. 2015, 137, 50, 15712;
c) L. Næsborg, K. S. Halskov, F. Tur, S. M. N. Mønsted, K. A. Jørgensen,
Angew. Chem. Int. Ed. 2015, 54, 10193; Angew. Chem. 2015, 127,
10331. d) F. A. Cruz, V. M. Dong, J. Am. Chem. Soc. 2017, 139, 1029.
e) S. Mukherjee, B. List, J. Am. Chem. Soc. 2007, 129, 11336; f) G. Jiang,
B. List, Angew. Chem. Int. Ed. 2011, 50, 9471; Angew. Chem. 2011, 123,
9643; g) P.-S. Wang, H.-C. Lin, Y.-J. Zhai, Z.-Y. Han, L.-Z. Gong, Angew.
Chem. Int. Ed. 2014, 53, 12218; Angew. Chem. 2014, 126, 12414; h) B.
List, I. Čorić, O. O. Grygorenko, P. S. J. Kaib, I. Komarov, A. Lee, M.
Leutzsch, S. C. Pan, A. V. Tymtsunik, M. v. Gemmeren, Angew. Chem.
Int. Ed. 2014, 53, 282; Angew. Chem. 2014, 126, 286.
Acknowledgements
We gratefully acknowledge the funding support of NSFC
(22031004, 21921003, 22071060) and Shanghai Municipal
Education Commission (20212308) and the China Postdoc-toral
Science Foundation (2019M650071, 2019M661418).
This article is protected by copyright. All rights reserved.

10.1002/anie.202106109
Angewandte Chemie International Edition
COMMUNICATION
[12]
N. M. Rezayee, V. J. Enemærke, S. T. Linde, J. N. Lamhauge, G. J.
Reyes-Rodríguez, K. A. Jørgensen, C. Lu, and K. N. Houk, J. Am. Chem.
Soc. 2021, doi: 10.1021/jacs.1c02193
[13] a) R. Martín, S. L. Buchwald, Angew. Chem., Int. Ed. 2007, 46, 7236;
Angew. Chem. 2007, 119, 7374; b) G. D. Vo, J. F. Hartwig, Angew.
Chem., Int. Ed. 2008, 47, 2127; Angew. Chem. 2008, 120, 2157; c) Y.
Terao, Y. Fukuoka, T. Satoh, M. Miura, M. Nomura, Tetrahedron Lett.
2002, 43, 101.
[14] a) T. Wakaki, T. Togo, D. Yoshidome, Y. Kuninobu, M. Kanai, ACS Catal.
2018, 8, 3123; b) J. Ruan, O. Saidi, J. A. Iggo, J. Xiao, J. Am. Chem. Soc.
2008, 130, 10510; c) L. Wang, T. Wang, G.-J. Cheng, X. Li, J.-J. Wei, B.
Guo, C. Zheng, G. Chen, C. Ran, C. Zheng, ACS Catal. 2020, 10, 7543.
[15] C. Mazet, Synlett, 2012, 23, 1999.
[16] J. Garcia-Fortanet, S. L. Buchwald, Angew. Chem., Int. Ed. 2008, 47,
8108; Angew. Chem. 2008, 120, 8228.
[17]
P. Nareddy, L. Mantilli, L. Guénée, C. Mazet, Angew. Chem. Int. Ed.
2012, 51, 3826; Angew. Chem. 2012, 124, 3892.
[18]
a) H. Wang, H. Luo, Z. Zhang, W. Zheng, Y. Yin, H. Qian, J. Zhang, S.
Ma, J. Am. Chem. Soc. 2020.142, 9763; b) Z.-M. Zhang, B. Xu, Y. Qian,
L. Wu, Y. Wu, L. Zhou, Y. Liu, J. Zhang, Angew. Chem. Int. Ed. 2018, 57,
10373; Angew.Chem. 2018, 130, 10530; c) P. Zhang, J. Han, J. Zhang,
Angew. Chem. Int. Ed. 2019, 58, 11444; Angew. Chem. 2019, 131,
11566; d) L. Wang, K. Zhang, Y. Wang, W. Li, M. Chen, J. Zhang, Angew.
Chem. Int. Ed. 2020, 59, 4421; Angew. Chem. 2020, 132, 4451; e) T. Lin,
Z. Pan, Y. Tu, S. Zhu, H. Wu, Y. Liu, Z. Li, J. Zhang, Angew. Chem. Int.
Ed. 2020, 59, 22957; Angew. Chem. 2020, 132, 23157; f) Q. Dai, W. Li,
Z. Li, J. Zhang, J. Am. Chem. Soc. 2019, 141, 20556; g) C. Zhu, H. Chu,
G. Li, S. Ma, J. Zhang, J. Am. Chem. Soc. 2019, 141, 19246.
[19] a) Y.-Y. Che, Y. Yue, L.-Z. Lin, B. Pei, X. Deng, C. Feng, Angew. Chem.
Int. Ed. 2020, 59, 16414; Angew. Chem. 2020, 132, 16556; b) S. Y. Lee,
J. F. Hartwig, J. Am. Chem. Soc. 2016, 138, 15278.
[20]
The crystal structure of 3 was determined by X-ray crystallographic
analysis. CCDC 2071925.
This article is protected by copyright. All rights reserved.

10.1002/anie.202106109
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Z. Pan, W. Li, S. Zhu, F. Liu, H.-H. Wu, and
J. Zhang*
Page No. – Page No.
Palladium/TY-Phos-Catalyzed Asymmetric
Intermolecular α-Arylation of Aldehydes with
Aryl Bromides
The first example of asymmetric intermolecular α-arylation of α-alkyl-α-aryl disubstituted
aldehydes with aryl bromides, which provides a rapid access to chiral aldehydes bearing an α-
all-carbon quaternary stereocenter in moderate to good yields with good er in most cases.
Moreover, enantiomers could be obtained efficiently with one same ligand through changing the
functional groups of aryl bromides with aldehydes.
This article is protected by copyright. All rights reserved.