Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl Copper Species

Article abstract of DOI:10.1002/anie.202014425

We report the diastereo- and enantioselective conjugate addition of chiral secondary borylalkyl copper species derived from borylalkenes in situ to α,β-unsaturated diesters. In the presence of a chiral bisphosphine-ligated CuH catalyst, the conjugate addition provides a direct access to enantioenriched alkylboron compounds containing two contiguous carbon stereogenic centers in good yield with high diastereo- and enantioselectivity (up to >98:2 dr, >99:1 er) by assembling readily available starting alkenyl reagents in a single operation without using preformed organometallic reagents or chiral auxiliaries. The resulting products were used in various organic transformations. The utility of the synthetic approach was highlighted by the synthesis of (?)-phaseolinic acid.

Full text of DOI:10.1002/anie.202014425

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
International Edition Chemie
www.angewandte.org
Accepted Article
Title: Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl
Copper Species
Authors: Jaesook Yun, Won Jun Jang, and Jeongkyu Woo
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.202014425
Link to VoR: https://doi.org/10.1002/anie.202014425

Angewandte Chemie International Edition
10.1002/anie.202014425
COMMUNICATION
Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl
Copper Species
Won Jun Jang, Jeongkyu Woo, and Jaesook Yun*
Dedication ((optional))
[*]
Dr. W. J. Jang, J. Woo, Prof. J. Yun
Department of Chemistry and Institute of Basic Science
Sungkyunkwan University
Suwon 16419, Korea
E-mail: jaesook@skku.edu
Supporting information for this article is given via a link at the end of the document.
Abstract: We report the diastereo- and enantioselective conjugate
addition of chiral secondary borylalkyl copper species derived from
borylalkenes in situ to α,β-unsaturated diesters. In the presence of a
chiral bisphosphine-ligated CuH catalyst, the conjugate addition
provides a direct access to enantioenriched alkylboron compounds
containing two contiguous carbon stereogenic centers in good yield
with high diastereo- and enantioselectivity (up to >98:2 dr, >99:1 er)
by assembling readily available starting alkenyl reagents in a single
operation without using preformed organometallic reagents or chiral
auxiliaries. The resulting products were used in various organic
transformations. The utility of the synthetic approach was highlighted
by the synthesis of (–)-phaseolinic acid.
Asymmetric conjugate addition of organometallic reagents to
Michael acceptors is an efficient and powerful method for the
[1]
construction of new carbon stereogenic centers. In general, the
conjugate addition reaction has been extensively investigated
via a stoichiometric use of preformed organometallic reagents
[
2]
[3]
[4]
[5]
[6]
such as Mg, Zn, Al, and Zr, and B-based reagents in the
presence of a chiral catalyst (Scheme 1A, a). Despite several
important research advances have been made in this research
field, the conjugate addition with a chiral secondary alkyl metal
nucleophile for the C–C bond formation with two contiguous
stereogenic centers has been rarely reported and represents an
enormous challenge. Early advances include diastereo- and
enantioselective conjugate additions based on the stoichiometric
strategy using preformed, configurationally stable chiral
organolithium reagents via enantioselective deprotonation of
[
7]
alkyl pronucleophiles (Scheme 1A, b). Other examples were
limited to the use of stoichiometric chiral nucleophiles derived
[
8]
from compounds containing chiral auxiliaries.
Catalytic asymmetric tandem reactions convert readily
available starting materials to complex chiral building blocks in a
[
9]
single step. A variety of catalytic tandem reactions have been
developed in the past in which the precise control of
chemoselectivity between the catalyst and competing reagents
is essential to ensure the desired reaction pathway. Recently,
CuH-catalyzed asymmetric hydrofunctionalization has been
used for the synthesis of chiral organic molecules from π-
Scheme 1. Overview of asymmetric conjugate addition.
This strategy accessing
a catalytic amount of a chiral
[
10]
alkylcopper from olefin successfully avoids stoichiometric
unsaturated pronucleophiles with appropriate electrophiles.
1
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202014425
COMMUNICATION
[
a]
Table 1. Optimization of reaction conditions.
preparation of chiral auxiliary-attached substrates or
[
11]
organometallic reagents.
reported several
We and others have recently
examples of CuH-catalyzed
hydrofunctionalization of borylalkenes with various electrophiles,
which efficiently yielded valuable chiral organoboron
[
12,13]
compounds.
enantioselective catalytic conjugate addition of
borylalkyl NHC-copper complex generated by transmetalation
More recently, our group described the
a
primary
[
b]
[c]
[d]
Entry
BY2
Bpin
L
Yield [%]
er (major)
dr
[
14]
from 1,1-diborylmethane.
While it was the first asymmetric
1
2
3
4
5
6
7
8
9
L1
L2
–
0
–
–
conjugate addition of a catalytically generated borylalkyl copper,
the conjugate addition of a branched borylalkyl copper species
derived from 1,1-diborylethane was not successful under our
previous reaction conditions. Pursuing the diastereo- and
enantioselective conjugate addition of chiral secondary
borylalkyl copper complexes, we tried to access the chiral
borylalkyl copper species via enantioselective hydrocupration of
prochiral borylalkenes in the presence of Michael acceptors
Bpin
73
0
52:48
–
95:5
–
Bpin
Bmac
Bdan
Bdan
Bdan
Bdan
Bdan
Bdan
L2
L2
L3
L4
L5
L6
L3
89
76
82
82
74
59
85
66:34
90:10
95:5
>98:2
88:12
94:6
36:64
35:65
48:52
95:5
(
Scheme 1B). However, such an asymmetric conjugate addition
of catalytically generated chiral nucleophiles has yet to be
established. The success of the reaction strategy is determined
by two important issues: 1) distinguishing the two alkenes by the
CuH catalyst chemoselectively in order to generate the
corresponding borylalkyl copper species, and 2) adequate
reactivity of a secondary chiral borylalkyl copper complex to
facilitate the conjugate addition. It is plausible that the catalytic
cycle is composed of enantioselective formation of a borylalkyl
copper intermediate (Ⅱ), diastereoselective conjugate addition,
and the regeneration of the CuH catalyst with the formation of
the silylated alkylboron product Ⅳ.
55:45
58:42
55:45
95.5:4.5
[
e]
10
We initiated our study with vinylboronic acid pinacol ester
(
1a-Bpin) and diethyl benzylidenemalonate (2a) in the presence
of copper chloride with chiral NHC ligand (L1), which was the
[
14]
optimal ligand in our previous asymmetric conjugate addition
Table 1, entry 1). Under the reaction conditions, only reduced
diethyl benzylmalonate was obtained without the desired product
a, which suggests low chemoselectivity of the NHC-Cu catalyst.
However, with the chiral bisphosphine ligand (R,S)-Josiphos
L2), surprisingly, the desired product was obtained in 73% yield
with high diastereoselectivity, but with low enantiomeric ratio
entry 2). The reaction was then carried out in the absence of a
chiral ligand to determine the possible background reaction
(
3
(
(
(
(
entry 3), and no conversion of starting material was observed
entry 3), indicating the importance of ligands in reactivity and
[a] General reaction conditions: 1a-BY2 (0.75 mmol), 2a (0.5 mmol), CuCl
(0.025 mmol), ligand (0.025 mmol), LiOtBu (1 mmol), and TMDSO (1 mmol)
in THF (1 mL) at 40 ºC; see the Supporting Information for details. [b]
Isolated yield as a mixture of diastereomers. [c] Enantiomeric ratio (er) was
determined by chiral HPLC analysis. [d] Diastereomeric ratio (dr) was
enantioselectivity of this transformation. Next, the effect of boryl
group (BY ) on the enantio- and diastereoselectivity of this
reaction was investigated. The reactions with 1a-Bmac (mac =
2
[
15]
1
methylated acenaphthoquinone)
and 1a-Bdan (dan = 1,8-
instead of 1a-Bpin yielded the
corresponding addition products with 66:34 er and >98:2 dr
entry 4) and 90:10 er and 88:12 dr (entry 5). With 1a-Bdan and
determined by H NMR analysis of a crude reaction mixture. [e] Cu(OAc)2
was used instead of CuCl.
[
16]
diaminatonaphthalene)
We next explored the scope of the asymmetric conjugate
addition of various alkenylboron compounds (1) with α,β-
unsaturated diesters (2) under optimized reaction conditions
(
tBu-Josiphos ligand (L3) containing bulkier tBu groups on the
phosphine, most promising results were obtained in terms of
both enantio- and diastereoselectivity (95:5 er, 94:6 dr) (entry
(
Table 2). A range of enantioenriched alkylboron products with
[
17]
two adjacent stereogenic centers were efficiently synthesized
in high yield and with high levels of enantio- and
diastereoselectivity. First, a large scale reaction (2 mmol) of
6
).
the C
L5), and (S,S)-Ph-BPE (L6) containing two phospholane rings
were less efficient than L3 (entry 6–9; 55:45–58:42 er, 48:52–
6:64 dr). Finally, the use of Cu(OAc) as the copper precursor
furnished the desired product with increased yield and thus, it
Further evaluation of bisphosphine ligands revealed that
2
-symmetric ligand (R)-Segphos (L4), (R,R)-Me-Duphos
(
1a with a reduced amount of catalyst and ligand (2.5 mol %)
was also effective and generated the chiral product 3a similar
to the 0.5 mmol scale reaction. Next, we investigated various
α,β-unsaturated diesters (2) in the conjugate addition with a
terminal vinylboron compound (1a-Bdan). A variety of aryl-
3
2
[
18]
was selected as the optimal precursor for reaction (entry 10).
2
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202014425
COMMUNICATION
[
a]
Table 2. CuH-catalyzed asymmetric reductive conjugate addition of borylalkenes to α,β-unsaturated diesters.
[
a] Isolated yields containing a mixture of two diastereomers. Enantiomeric ratio (er) was determined by chiral HPLC analysis. Diastereomeric ratio (dr) was
1
determined by H NMR analysis of a crude reaction mixture. 0.5 mmol scale reaction. Isolated yields on a 0.5 mmol scale. The enantiomeric ratio was determined
by HPLC analysis. [b] 2.5 mol% of copper/ligand on a 2 mmol scale. [c] The reaction was carried out with 1 equivalent of LiOtBu, 2.5 mol % copper catalyst and
3.75 mol % ligand on a 3 mmol scale. [d] Isolated yield of pure syn-diastereomer.
substituted α,β-unsaturated diesters (2) with halogen, electron-
withdrawing, and electron-donating substituents at ortho-, meta-,
para-positions of the aryl group resulted in the desired products
with high yield (76–85%), high enantiomeric (94.5:5.5–97:3),
and diastereomeric ratios (93:7–98:2) (3b–3h). Substrates
containing a napthyl, and a heteroaryl group such as thiophene,
3
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202014425
COMMUNICATION
furan, indole were also compatible under the optimal reaction
conditions (3i–3l). Furthermore, primary alkyl substituted
diesters afforded the corresponding chiral alkylboron
compounds (3m and 3n) without significantly affecting the
Bpin, and decarboxylation. Conversion of the C–B bond of 5 to
[
23]
[24]
C–C bonds by vinylation and heteroarylation yielded chiral
organic molecules 6 and 7, respectively. In addition, (–)-
phaseolinic acid (9), isolated from culture filtrates of fungi such
as Macrophomina phaseolina, was synthesized from 3s via the
[
19]
reactivity and selectivity of the reaction.
However, β-
[
25]
cyclohexyl substituted α,β-unsaturated diester yielded the
desired product (3o) with moderate yield and slightly decreased
er value. We also tested the 1,4- vs. 1,6-selectivity of the
addition with α,β,γ,δ-unsaturated dienoate 2p, and exclusively
obtained the corresponding 1,4-addition product 3p in high er
chiral γ-lactone intermediate (8).
In summary, we developed a CuH-catalyzed asymmetric
reductive conjugate addition of borylalkenes to α,β-unsaturated
diesters with high chemo-, diastereo-, and enantioselectivity.
This method provides efficient and direct access to
enantioenriched alkylboron compounds carrying two contiguous
stereogenic centers by assembling readily available starting
alkenyl reagents in a single operation without using preformed
organometallic reagents or chiral auxiliaries, which greatly
expands the scope of asymmetric conjugate addition. Moreover,
the utility of the resulting products was demonstrated in the
efficient synthesis of (–)-phaseolinic acid and other derivatives.
Efforts to expand the use of other chiral alkylcopper species in
the asymmetric conjugate addition are currently underway.
[
20]
and dr.
Next, we investigated the addition reaction with
internal borylalkenes (3q–3v). Notably, the challenging internal
borylalkenes containing phenyl-, primary-, and secondary alkyl
substituents were all efficient, yielding the corresponding chiral
products in moderate to good yields with high enantio- and
diastereoselectivity. However, other Michael acceptors such as
α,β-unsaturated monoester, ketone, diethyl fumarate and
dinitrile were not effective for producing desired products under
our conditions; a methyl diester substrate yielded the coupled
[
21]
product in 79% yield with slightly decreased dr and er.
Acknowledgements
This work was supported by Samsung Science and Technology
Foundation under Project Number SSTF-BA2002-08.
Keywords: Asymmetric catalysis • Borylalkene • Conjugate
addition • Copper • Enantioselective synthesis
[
1]
For reviews, see: a) A. Alexakis, J. E. Bäckvall, N. Krause, O. Pàmies,
M. Diéguez, Chem. Rev. 2008, 108, 2796–2823; b) S. R. Harutyunyan,
T. D. Hartog, K. Geurts, A. J. Minnaard, B. L. Feringa, Chem. Rev.
2008, 108, 2824–2852; c) T. Jerphagnon, M. G. Pizzuti, A. J.
Minnaard, B. L. Feringa, Chem. Soc. Rev. 2009, 38, 1039–1075; d) A.
Cordova, Catalytic Asymmetric Conjugate Reactions; Wiley-VCH:
Weinheim, 2010; e) K. Zheng, X. Liu, X. Feng, Chem. Rev. 2018, 118,
7586–7656.
[
2]
3]
For selected examples, see: a) D. Martin, S. Kehrli, M. d'Augustin, H.
Clavier, M. Mauduit, A. Alexakis, J. Am. Chem. Soc. 2006, 128, 8416–
8417; b) S.-Y. Wang, S.-J. Ji, T.-P. Loh, J. Am. Chem. Soc. 2007, 129,
276–277; c) J. C. H. Lee, D. G. Hall, J. Am. Chem. Soc. 2010, 132,
5544–5545; d) R. Jumde, P. F. Lanza, M. J. Veenstra, M, S. R.
Harutyunyan, Science 2016, 352, 433–437; e) X. Yan, S. R.
Harutyunyan, Nat. Commun. 2019, 10, 3402.
[
For selected examples, see: a) A. W. Hird, A. H. Hoveyda, J. Am.
Chem. Soc. 2005, 127, 14988–14989; (b) K. Endo, M. Ogawa, T.
Shibata, Angew. Chem. Int. Ed. 2010, 49, 2410–2413; c) K. Endo, D.
Hamada, S. Yakeishi, M. Ogawa, T. Shibata, Org. Lett. 2012, 14,
2
342–2345; d) S. Drissi-Amraoui, M. S. T.Morin, C. Crévisy, O. Baslé,
Scheme 2. Organic transformation of the conjugate addition products (3):
Reaction conditions: [a] H SO , pinacol, THF/H O, rt. [b] NaBO , THF/H O, rt.
O, 160 °C. [d] Vinylmagnesium bromide, I , THF, -78 °C.
e] Furan, nBuLi, NBS, THF, –78 °C. [f] H SO , THF/H O, 50 °C. [g] RuCl
, CCl /MeCN/H O, rt. [h] NaHMDS, MeI, THF, –78 °C.
R. M. de Figueiredo, M. Mauduit, J.-M. Campagne, Angew. Chem. Int.
Ed. 2015, 54, 11830–11834.
2
4
2
3
2
[
[
c] NaCl, DMSO/H
2
2
2
4
2
3
,
[4]
For selected examples, see: a) M. d’Augustin, L. Palais, A. Alexakis,
Angew. Chem. Int. Ed. 2005, 44, 1376–1378; b) T. L. May, J. A.
Dabrowski, A. H. Hoveyda, J. Am. Chem. Soc. 2011, 133, 736–739; c)
D. Müller, M. Tissot, A. Alexakis, Org. Lett. 2012, 14, 2342–2345; d) S.
Goncalves-Contal, L. Gremaud, A. Alexakis, Angew. Chem. Int. Ed.
NaIO
4
4
2
To demonstrate the potential synthetic power of the current
asymmetric conjugate addition protocols in practical organic
synthesis, we performed various organic transformations with
the resulting chiral alkylboron products (3a and 3s) (Scheme 2).
A chiral γ-lactone (4) with two chiral centers was prepared via
hydrolysis of the Bdan group of 3a, intramolecular
2013, 52, 12701.
[
5]
For selected examples, see: a) K. C. Nicolaou, W. Tang, P. Dagneau,
R. Faraoni, Angew. Chem. Int. Ed. 2005, 44, 3874–3879; b) R. M.
Maksymowicz, P. M. C. Roth, S. P. Fletcher, Nat. Chem. 2012, 4,
649–654; c) M. Sidera, P. M. C. Roth, R. M. Maksymowicz, S. P.
Fletcher, Angew. Chem. Int. Ed. 2013, 52, 7995–7999; d) Z. Gao, S. P.
Fletcher, Chem. Sci. 2017, 8, 641–646.
[
22]
transesterification,
and
decarboxylation.
β,γ-Chiral
alkylboronate ester (5) was obtained via conversion of Bdan to
4
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202014425
COMMUNICATION
[
6]
For selected examples, see: a) Y. Takaya, M. Ogasawara, T. Hayashi,
M. Sakai, N. Miyaura, J. Am. Chem. Soc. 1998, 120, 5579–5580; b) T.
Hayashi, K. Ueyama, N. Tokunaga, K. Yoshida, J. Am. Chem. Soc.
[17] The absolute stereochemistry of major product 3a was determined by
comparing the optical rotation of corresponding γ-lactone compound
with literature value. See the Supporting Information for details.
[18] a) D.-W. Lee, J. Yun, Tetrahedron Lett. 2004, 45, 5415–5417; b) D.-W.
Lee, J. Yun, Tetrahedron Lett. 2005, 46, 2037–2039.
2003, 125, 11508–11509; c) K. Kikushima, J. C. Holder, M. Gatti, B. M.
Stoltz, J. Am. Chem. Soc. 2011, 133, 6902–6905; d) K. Takatsu, R.
Shintani, T. Hayashi, Angew. Chem. Int. Ed. 2011, 50, 5548–5552; e)
M. Yoshida, H. Ohmiya, M. Sawamura, J. Am. Chem. Soc. 2012, 134,
[19] W. J. Jang, S. B. Song, S. Lee, S. Y. Yoo, Y. K. Chung, J. Huh, J. Yun,
Org. Chem. Front. 2020, 7, 3427–3433.
1
1896–11899; f) C. Wu, G. Yue, C. D.-T. Nielsen, K. Xu, H. Hirao, J.
[20] Selected examples for the copper-catalyzed 1,6-conjugate addition
reactions: a) T. den Hartog, S. R. Harutyunyan, D. Font, A. J.
Minnaard, B. L. Feringa, Angew. Chem. Int. Ed. 2008, 47, 398–401; b)
H. Hénon, M. Mauduit, A. Alexakis, Angew. Chem., Int. Ed. 2008, 47,
9122–9124; c) Y. Luo, I. D. Roy, A. G. E. Madec, H. W. Lam, Angew.
Chem. Int. Ed. 2014, 53, 4186–4190; (d) T. den Hartog, Y. Huang, M.
ꢀꢁꢂꢁnꢃs-Mastral, A. Meuwese, A. Rudolph, M. Pérez, A. J. Minnaard,
B. L. Feringa, ACS Catal. 2015, 5, 560–574; e) F. Meng, X. Li, S.
Torker, Y. Shi, X. Shen, A. H. Hoveyda, Nature 2016, 537, 387–393.
[21] See Table S1-3 in the Supporting Information for details.
[22] A. P. Krapcho, A. J. Lovey, Tetrahedron Lett. 1973, 14, 957–960.
[23] R. P. Sonawane, V. Jheengut, C. Rabalakos, R. Larouche-Gauthier, H.
K. Scott, V. K. Aggarwal, Angew. Chem. Int. Ed. 2011, 50, 3760–3763.
[24] A. Bonet, M. Odachowski, D. Leonori, S. Essafi, V. K. Aggarwal, Nat.
Chem. 2014, 6, 584–589.
Zhou, J. Am. Chem. Soc. 2016, 138, 742–745; g) Q. Chong, Z. Yue, S.
Zhang, C. Ji, F. Cheng, H. Zhang, X. Hong, F. Meng, ACS Catal. 2017,
7
, 5693–5698.
a) Y. S. Park, G. A. Weisenburger, P. Beak, J. Am. Chem. Soc. 1997,
19, 10537–10538; b) D. J. Pippel, G. A. Weisenburger, S. R. Wilson,
[
7]
1
P. Beak, Angew. Chem. Int. Ed. 1998, 37, 2522–2524; c) M. D. Curtis,
P. Beak, J. Org. Chem. 1999, 64, 2996–2997; d) T. A. Johnson, M. D.
Curtis, P. Beak, J. Am. Chem. Soc. 2001, 123, 1004–1005; e) T. A.
Johnson, D. O. Jang, B. W. Slafer, M. D. Curtis, P. Beak, J. Am. Chem.
Soc. 2002, 124, 11689–11698; f) S. J. Lee, P. Beak, J. Am. Chem.
Soc. 2006, 128, 2178–2179.
[
8]
9]
For selected examples, see: a) D. H. Hua; R. Chan-Yu-King, J. A.
McKie, L. Myer, J. Am. Chem. Soc. 1987, 109, 5026–5029; b) S.
Hanessian, A. Gomtsyan, A. Payne, Y. Hervé, S. Beaudoin, J. Org.
Chem. 1993, 58, 5032–5034; c) K. Tanaka, Y. Ohta, K. Fuji, J. Org.
Chem. 1995, 60, 8036–8043; d) S. Hanessian, A. Gomtsyan, N. Malek,
J. Org. Chem. 2000, 65, 5623–5631.
[25] a) S. B. Mahato, K. A. I. Siddiqui, G. Bhattacharya, T. Ghosal, K.
Miyahara, M. Sholichin, T. Kawasaki, Nat. Prod. 1987, 50, 245–247; b)
M. Amador, X. Ariza, J. Garcia, J. Ortiz, J. Org. Chem. 2004, 69,
8172–8175; c) R. A. Fernandes, A. K. Chowdhury, Tetrahedron:
Asymmetry 2011, 22, 1114–1119.
[
[
For reviews, see: a) P. J. Parsons, C. S. Penkett, A. J. Shell, Chem.
Rev. 1996, 96, 195–206; b) J. Zhou, Chem. Asian J. 2010, 5, 422–434;
c) H. Pellissier, Tetrahedron 2013, 69, 7171–7210; d) X. Yang, S. J.
Kalita, S. Maheshuni, Y.-Y. Huang, Coord. Chem. Rev. 2019, 392, 35–
48.
10] For reviews, see: a) C. Deutsch, N. Krause, B. H. Lipshutz, Chem.
Rev. 2008, 108, 2916–2927; b) A. J. Jordan, G. Lalic, J. P. Sadighi,
Chem. Rev. 2016, 116, 8318–8372; c) H. Wang, S. L. Buchwald,
Copper-Catalyzed Enantioselective Hydrofunctionalization of Alkenes.
(Eds.: S. E. Denmark), John Wiley & Sons, Inc.: Hoboken, NJ, 2019,
pp 121–205.
[
11] For selected Examples, see: a) D. Noh, H. Chea, J. Ju, J. Yun, Angew.
Chem. Int. Ed. 2009, 48, 6062–6064; b) D. Noh, S. K. Yoon, J. Won, J.
Y. Lee, J. Yun, Chem. Asian J. 2011, 6, 1967–1969; c) A. Saxena, B.
Choi, H. W. Lam, J. Am. Chem. Soc. 2012, 134, 8428–8431; d) Y. Miki,
K. Hirano, T. Satoh, M. Miura, Angew. Chem. Int. Ed. 2013, 52,
10830–10834; e) S. Zhu, N. Niljianskul, S. L. Buchwald, J. Am. Chem.
Soc. 2013, 135, 15746–15749; f) Y. Yang, I. B. Perry, G. Lu, P. Liu, S.
L. Buchwald. Science, 353, 144–150; g) Y. Yang, I. B. Perry, S. L.
Buchwald. J. Am. Chem. Soc. 2016, 138, 9787–9790; h) W. J. Jang, S.
M. Song, J. H. Moon, J. Y. Lee, J. Yun, J. Am. Chem. Soc. 2017, 139,
13660–13663; i) Y. Ye, S.-T. Kim, J. Jeong, M.-H. Baik, S. L.
Buchwald, J. Am. Chem. Soc. 2019, 141, 3901–3909.
[
[
12] a) X. Feng, H. Jeon, J. Yun, Angew. Chem. Int. Ed. 2013, 52, 3989–
3992; b) J. T. Han, W. J. Jang, N. Kim, J. Yun, J. Am. Chem. Soc.
2016, 138, 15146–15149; c) W. J. Jang, J. T. Han, J. Yun, Synthesis
2017, 49, 4753–4758; d) W. J. Jang, J. Yun, Angew. Chem. Int. Ed.
2018, 57, 12116–12120.
13] a) D. Nishikawa, K. Hirano, M. Miura, J. Am. Chem. Soc. 2015, 137,
15620–15623; b) M. K. Armstrong, G. Lalic, J. Am. Chem. Soc. 2019,
141, 6173–6179; c) D.-W. Gao, Y. Gao, H. Shao, T.-Z. Qiao, X. Wang,
B. B. Sanchez, J. S. Chen, P. Liu, K. M. Engle, Nat. Catal. 2020, 3,
3–29.
2
[
[
14] a) W. J. Jang, J. Yun, Angew. Chem. Int. Ed. 2019, 58, 18131–18135.
15] a) J. A. Myhill, C. A. Wilhelmsen, L. Zhang, J. P. Morken, J. Am. Chem.
Soc. 2018, 140, 15181–15185; b) S. M. Koo, A. J. Vendola, S. N.
Momm, J. P. Morken, Org. Lett. 2020, 22, 666–669; c) Y. Meng, Z.
Kong, J. P. Morken, Angew. Chem. Int. Ed. 2020, 59, 8456–8459.
[
16] a) H. Noguchi, K. Hojo, M. Suginome, J. Am. Chem. Soc. 2007, 129,
7
58–759; b) H. Noguchi, T. Shioda, C.-M. Chou, M. Suginome, Org.
Lett. 2008, 10, 377–380; c) N. Iwadate, M. Suginome, Org. Lett. 2009,
1, 1899–1902.
1
5
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202014425
COMMUNICATION
Entry for the Table of Contents
Catalytic diastereo- and enantioselective conjugate addition of chiral secondary borylalkyl copper species derived from borylalkenes
in situ to α,β-unsaturated diesters is reported. This method provides enantioenriched alkylboron compounds containing two
contiguous carbon stereogenic centers in good yield with high diastereo- and enantioselectivity (up to >98:2 dr, >99:1 er).
6
This article is protected by copyright. All rights reserved.