Tertiary α-Silyl Alcohols by Diastereoselective Coupling of 1,3-Dienes and Acylsilanes Initiated by Enantioselective Copper-Catalyzed Borylation

Article abstract of DOI:10.1002/anie.201903174

An efficient synthesis of functionalized tertiary α-silyl alcohols by an enantio- and diastereoselective copper-catalyzed three-component coupling of 1,3-dienes, bis(pinacolato)diboron, and acylsilanes is reported. The reaction proceeds well with different 1,3-dienes and a broad range of aryl- as well as alkenyl- but also alkyl-substituted acylsilanes. The target compounds are formed with high regio-, diastereo-, and enantioselectivity (up to 99 % ee and d.r. >20:1) and are highly versatile synthetic building blocks.

Full text of DOI:10.1002/anie.201903174

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Tertiary α-Silyl Alcohols by Diastereoselective Coupling of 1,3-
Dienes and Acylsilanes Initiated by Enantioselective Copper-
Catalyzed Borylation
Authors: Jian-Jun Feng and Martin Oestreich
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.201903174
Angew. Chem. 10.1002/ange.201903174
Link to VoR: http://dx.doi.org/10.1002/anie.201903174
http://dx.doi.org/10.1002/ange.201903174

10.1002/anie.201903174
Angewandte Chemie International Edition
COMMUNICATION
Tertiary α-Silyl Alcohols by Diastereoselective Coupling of 1,3-
Dienes and Acylsilanes Initiated by Enantioselective Copper-
Catalyzed Borylation
Jian-Jun Feng and Martin Oestreich*
Abstract: An efficient synthesis of functionalized tertiary α-silyl
alcohols by an enantio- and diastereoselective copper-catalyzed
three-component coupling of 1,3-dienes, bis(pinacolato)diboron, and
acylsilanes is reported. The reaction proceeds well with different 1,3-
dienes and a broad range of aryl- as well as alkenyl- but also alkyl-
substituted acylsilanes. The target compounds are formed with high
regio-, diastereo-, and enantioselectivity (up to 99% ee and d.r. >
20:1) and are highly versatile synthetic building blocks.
Interest in α-chiral silanes and those with α-heteroatom
substitution continues to grow because of their great potential in
stereoselective synthesis and medicinal chemistry.[1] As an
example, chiral α-hydroxysilanes (= α-silyl alcohols) and their
derivatives have been utilized in stereocontrolled C–C bond
formation and rearrangements.[2] Consequently, catalytic
asymmetric methods for their preparation are in demand, and
several approaches are available such as additions to either
acylsilanes with hydrides[3] or aldehydes with silicon
nucleophiles[4] and hydrogenation of α-silyl enol carbamates.[5]
These protocols do provide access to enantioenriched
secondary α-silyl alcohols but the reductions are not applicable
to tertiary systems. Hence, the construction of chiral tertiary α-
silyl alcohols remains challenging. The most straightforward way
of preparing them would be the enantioselective addition of
carbon nucleophiles to acylsilanes,[6,7] and several advances
have been disclosed recently.[8-10] Marek[8] and Chan[9] reported
zinc-promoted alkynylations of acylsilanes with terminal alkynes
as pronucleophiles (Scheme 1, top). Harutyunyan later
substantially expanded the scope with the development of a
copper-catalyzed alkylation of aryl- and alkenyl-substituted
acylsilanes with Grignard reagents as nucleophiles (Scheme 1,
top).[10]
Scheme 1. Enantioselective transition-metal-catalyzed nucleophilic addition
reactions to acylsilanes for the construction of enantiopure tertiary α-silyl
alcohols.
Based on Ito’s[11a] and Miyaura’s[11b] seminal work on the
catalytic generation of copper-based boron nucleophiles, their
addition across π-systems followed by coupling of the copper
intermediate with an impressive variety of electrophiles has
recently flourished.[12–19] By this, densely functionalized boron
compounds are made available with high levels of regio- and
stereocontrol. 1,3-Dienes, particularly low-cost isoprene, are an
often-employed π-system,[20] and their use in these three-
component reactions currently attracts much attention.[14a,15b,16c–
e,18c,d,19a]
Just four of these reports are enantioselective variants,
namely the beautiful work of Hoveyda,[15b] Liao,[14a] and
Brown.[16d,e] Again, different electrophiles were used but none
lead to
a fully substituted stereocenter. Acylsilanes as
electrophiles do fulfill this role, and the corresponding coupling
with 1,3-dienes would lead to tertiary α-silyl alcohols (Scheme 1,
bottom). However, this plan could be thwarted by direct
borylation of the acylsilane and undesired Brook rearrangement
in basic media.[2a–c] We describe here the realization of this
delicate three-component reaction.
[*]
Dr. Jian-Jun Feng, Prof. Dr. M. Oestreich
Our study commenced with acylsilane 1a and isoprene (2a)
as the model substrates (Table 1; see the Supporting
Information for the complete set of optimization data). To our
disappointment, this model reaction yielded only 9% of syn-3aa
along with 69% of Brook-rearranged 3aa in the presence of
CuCl/rac-L1 and 1.5 equiv NaOtBu (see the Supporting
Institut für Chemie, Technische Universität Berlin
Strasse des 17. Juni 115, 10623 Berlin (Germany)
E-mail: martin.oestreich@tu-berlin.de
Homepage: http://www.organometallics.tu-berlin.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.201903174
Angewandte Chemie International Edition
COMMUNICATION
determined by 1H NMR spectroscopy with CH2Br2 as an internal standard. [c]
Determined by HPLC analysis on chiral stationary phases after oxidative
degradation of the C–B bond in 3aa (see 4aa in Table 2). [d] 50 mol% NaOtBu
used. [e] The other enantiomer was obtained. [f] Run at –30 °C. [g] Toluene
instead of THF. [h] Toluene/THF 10:1 instead of THF. [i] KOtBu instead of
NaOtBu.
Information for details and characterization data). Reducing the
amount of base to 0.4 equiv improved the yield to 74% but
afforded both diastereomers of 3aa in racemic form (entry 1).
Other ligands L2–L6 were tested (entries 2–6). All of them
furnished anti-3aa as the major diastereomer at room
temperature. The enantioselectivity with phosphoramidite ligand
L2 was promising but the diastereoselectivity was poor (entry 2).
The situation was reversed with NHC ligand L5 (entry 5), and
the excellent anti selectivity was somewhat retained at better
enantioinduction with L6 (entry 6). Interestingly, temperatures
With the optimized conditions established, we examined the
substitution pattern at the silicon atom of the acylsilane (Table 2).
The isolated yields and enantiomeric excesses were determined
after oxidative degradation of the C–B bond in 3 to afford the
1,3-diols 4. The steric properties of the silyl group had hardly
any effect on the stereoselectivity of the reaction. Replacement
of Me2PhSi (1a) by bulkier tBuMe2Si (1c) was a little exception
as the enantiomeric excess increased from 92 for 4aa to 97% for
4ca (entry 1 vs entry 3). Acylsilane 1b delivered desired 3ba in
79% NMR yield but 3ba did not withstand the strongly basic
reaction medium (entry 2); it can nevertheless be transformed
into 4ba by oxidation with H2O2/KHCO3. Acylsilanes with the
smaller (allyl)Me2Si (1d → 4da, entry 4) or Et3Si groups (1e →
4ea, entry 5) yielded the tertiary α-silyl alcohols with
stereoselectivities similar to that obtained with Me2PhSi (entry
1); acylsilane 1e had not been compatible with Harutyunyan’s
catalytic system (cf. Scheme 1, top).[10]
lower than
0 °C increased both the syn selectivity and
enantioselectivity with L2 as the ligand, and –30 °C was found to
be optimal (entry 7). Further improvement of the enantiomeric
excess was achieved with toluene instead of THF as the solvent
(entry 8). The solvent change was detrimental to the yield but
not to the stereocontrol; the good yield was restored in
toluene/THF 10:1 (entry 9). Finally, the syn-selective reaction
with L2 afforded the target compound 3aa in 85% NMR yield
and with 92% ee and d.r. = 89:11 when KOtBu was used instead
of NaOtBu (entry 10).
Table 1. Selected examples of the optimization of the reaction conditions.[a]
Table 2. Scope I: Variation of the substituents at the silicon atom in the
acylsilane.
Entry
Acylsilane
Yield [%][a]
80 (4aa)
40 (4ba)[d]
71 (4ca)
72 (4da)
70 (4ea)
d.r. (syn:anti)
89:11
ee [%][b]
92
1
1a (Me2PhSi)
1b (MePh2Si)
1c (tBuMe2Si)
1d [(allyl)Me2Si]
1e (Et3Si)
2[c]
3
86:14
93
88:12
97
4
92:8
93
5
89:11
91
Entry
Ligand
Yield
[%][b]
d.r.[b]
(syn:anti)
ee [%][c]
[a] Combined isolated yield. [b] Determined by HPLC analysis on chiral
stationary phases. [c] H2O2/KHCO3 instead of H2O2/NaOH. [d] 79% NMR
yield of 3ba.
syn-4aa
from syn-3aa
anti-4aa
from anti-3aa
1
L1
L2
L3
L4
L5
L6
L2
L2
L2
L2
74
84
90
25
45
52
76
53
78
85
11:89
48:52
30:70
44:56
2:98
0
69
63
39
12
54[e]
88
92
92
92
0
50
46
8
We next investigated the scope of acylsilanes (Scheme 2).
Aromatic acylsilanes with substituents in the para and meta
positions were compatible with our catalyst system and afforded
the corresponding tertiary α-silyl alcohols in good yield and
stereoselectivity (4fa–ma). Notably, acylsilane 1h containing an
allyl ether in the para position furnished 4ha in high yield along
with a trace amount of the side product resulting from allylic
borylation. Lower yield and diastereoselectivity was observed for
ortho-methyl-substituted acylsilane 1n, and the α-silyl alcohol
3na decomposed quickly. The coupling of furan-2-yl-containing
2
3
4
5[d]
6[d]
7[f]
8[f,g]
9[f,h]
10[f,h,i]
14
49[e]
20
0
12:88
84:16
86:14
86:14
89:11
acylsilanes
was
also
successful
yet
with
eroded
diastereoselectivity, e.g., d.r. = 70:30 for 1o → 4oa. Aliphatic
acylsilanes such as 1p, which had not been compatible with
Harutyunyan’s catalytic system,[10] provided the tertiary α-silyl
alcohol 4pa in acceptable yield with d.r. = 97:3 and 99% ee. The
product 3qa did not withstand the oxidation step but can be
purified by flash column chromatography on silica gel with
7[e]
8[e]
[a] Unless otherwise noted, the reactions were performed with 1a (0.2 mmol),
2a (1 mmol), and B2(pin)2 (0.3 mmol) in THF (2 mL). [b] Combined yield
This article is protected by copyright. All rights reserved.

10.1002/anie.201903174
Angewandte Chemie International Edition
COMMUNICATION
reasonable yield; no conjugate addition to 1q was seen
alcohol (as in 4ci), and a silyl ether (as in 4cj), were also
compatible with our catalytic system. As a trend, substituents at
C2 closer to the reactive site led to erosion of the yield but
resulted in better diastereocontrol (4cj vs 4cl). Cyclohexa-1,3-
diene did not furnish the desired branched homoallylic alcohols;
the reaction stopped at the stage of borylcupration,[22] probably
due to the low reactivity of the borylcopper intermediate towards
acylsilanes. In turn, 2,3-dimethylbuta-1,3-diene (2m) did react to
yield the desired three- component adduct 3am with vicinal
quaternary stereocenters in good yield and with excellent
diastereomeric ratio (gray box).
(Scheme 2, bottom).
CuCl (10 mol%)
L2 (12 mol%)
KOtBu (40 mol%)
Me2PhSi OH
R1
O
B2(pin)2 (1.5 equiv)
Me
OH
+
Me
2a
R1 SiMe2Ph
toluene/THF 10:1
–30 °C
1f–p
syn-4
then H2O2/NaOH
and syn-3ja/syn-3na
w/o H2O2/NaOH
Me2PhSi OH
Me2PhSi OH
Me2PhSi OH
Me
OH
Me
OH
Me
OH
Me
iPr
O
4fa: 70%
4ga: 90%
4ha: 72%
d.r. = 89:11, 92% ee
d.r. = 93:7, 94% ee
d.r. = 92:8, 84% ee
Me2PhSi OH
Me2PhSi OH
Me2PhSi OH
Me
OH
Me
Bpin
Me
OH
F
F3C
OMe
4ka: 70%
3ja: 89%[a,b]
4ia: 75%
d.r. = 87:13, 92% ee
Me2PhSi OH
Me
d.r. = 82:18, 90% ee
Me2PhSi OH
Me
d.r. = 71:29
Me2PhSi OH
Me
Me
OH
OH
Me Bpin
[a,c]
Me
4la: 77%
Me
4ma: 76%
3na
: 49%
d.r. = 90:10, 90% ee
d.r. = 90:10, 89% ee
d.r. = 76:24
Me2PhSi OH
Me2PhSi OH
Me
Me
OH
O
OH
4oa: 81%
4pa: 50%
d.r. = 97:3, 99% ee
d.r. = 70:30, 90% ee
standard
Me2PhSi OH
O
setup
Me
Me
Me
Bpin
+
Me
SiMe2Ph
Me
w/o H2O2/NaOH
Me
1q
(1.0 mmol)
2a
3qa: 66%[c]
d.r. = 60:40
Scheme 2. Scope II: Variation of the acylsilane. [a] Unstable compound; the
yield was estimated by 1H NMR spectroscopy. [b] Oxidation resulted in Brook
rearrangement (84%, d.r. = 69:31; see the Supporting Information for details).
[c] Oxidation led to decomposition, and the enantiomeric excess could not be
determined.
Scheme 3. Scope III: Variation of the 1,3-diene. [a] Run at –40 °C. [b] Run at
–10 °C. [c] 15 mol% CuOAc, 18 mol% L3, and 50 mol% KOtBu used. [d] 10
mol% CuOAc, 12 mol% L3, and 50 mol% KOtBu used. [e] Oxidation led to
decomposition, and the enantiomeric excess could not be determined. TBS =
tert-butyldimethylsilyl.
An array of 1,3-dienes was also tested with acylsilanes 1a
and 1c as coupling partners (Scheme 3). Yields were generally
good, and enantiomeric excesses ranged from good to excellent.
Isoprene (2a) could be replaced by buta-1,3-diene (2b), and 4cb
was isolated in 98% yield with 91% ee; the diastereoselectivity
was diminished though. Subjecting 2-aryl-substituted 1,3-dienes
to the standard setup afforded the desired products with
excellent diastereomeric ratios and ee values but in markedly
diminished yields. However, using CuOAc/L3 as the catalyst and
raising the temperature to –10 °C significantly improved the yield
without loss in stereoselectivity (4cb–ce). The absolute
configuration of syn-4cc was confirmed by X-ray diffraction
analysis,[21] and all other α-silyl alcohols were correlated
accordingly. Myrcene (2f) and its derivatives 2g–j with a variety
of functional groups on the diene, including an alkene (as in 4af
and 4cf), an ester (as in 4cg), an acetal (as in 4ah), a free
To explore synthetic transformations of these tertiary α-silyl
alcohols (Scheme 4), a scale-up synthesis of 4ca (1.0 mmol)
was done without any loss in efficiency and selectivity (see the
Supporting Information). The 1,1-disubstituted double bond in
4ca was hydrogenated over Pd/C to produce 5 in 81% yield.
TBAF-promoted [1,2]-Brook rearrangement of 4ca afforded 1,3-
diol 6 in good yield and with acceptable diastereoselectivity. The
primary hydroxy group in 4aa was converted into an iodo group
in 7. Also, vinylcyclopropane 8 was synthesized from 4aa by
sequential [1,2]-Brook rearrangement and intramolecular SN2
reaction. Of note, protection of the primary hydroxy group in 4da
followed by ring-closing metathesis allowed for the construction
of chiral tetrahydrosiline 9.
This article is protected by copyright. All rights reserved.

10.1002/anie.201903174
Angewandte Chemie International Edition
COMMUNICATION
9175–9206; for a recent beautiful example, see: e) K. Yabushita, A.
Yuasa, K. Nagao, H. Ohmiya, J. Am. Chem. Soc. 2019, 141, 113–117.
a) N. Arai, K. Suzuki, S. Sugizaki, H. Sorimachi, T. Ohkuma, Angew.
Chem. Int. Ed. 2008, 47, 1770–1773; Angew. Chem. 2008, 120, 1794–
1797; b) J. Matsuo, Y. Hattori, H. Ishibashi, Org. Lett. 2010, 12, 2294–
2297.
hydro-
Appel
Me
Me2PhSi OH
tBuMe2Si OH
genation
reaction
Me
Me
[3]
[4]
[a]
[c]
I
OH
Si OH
5: 81% from 4ca
7: 85% from 4aa
Me
d.r. > 99:1, 97% ee
d.r. = 89:11, 92% ee
V. Cirriez, C. Rasson, T. Hermant, J. Petrignet, J. D. Alvarez, K.
Robeyns, O. Riant, Angew. Chem. Int. Ed. 2013, 52, 1785–1788;
Angew. Chem. 2013, 125, 1829–1832.
OH
4aa, 4ca,
and 4da
OH
[b]
[d]
Me2PhSiO
Me
Ph
Me
cyclopropane
Brook
[5]
[6]
L. Panella, B. L. Feringa, J. G. de Vries, A. J. Minnaard, Org. Lett. 2005,
7, 4177–4180.
OH
6: 85% from 4ca
d.r. = 78:22, 96% ee
formation
rearrangement
8: 71% from 4aa
(two steps)
ring-closing
For authoritative reviews of acylsilane chemistry, see: a) H.-J. Zhang, D.
L. Priebbenow, C. Bolm, Chem. Soc. Rev. 2013, 42, 8540–8571; b) M.
Nahm Garrett, J. S. Johnson in Science of Synthesis Knowledge
Updates 2012/2 (Ed.: M. Oestreich), Thieme, Stuttgart, 2012, pp. 1–84;
see also: c) G. R. Boyce, S. N. Greszler, J. S. Johnson, X. Linghu, J. T.
Malinowski, D. A. Nicewicz, A. D. Satterfield, D. C. Schmitt, K. M.
Steward, J. Org. Chem. 2012, 77, 4503–4515.
d.r. = 86:14
[e]
metathesis
(two steps)
Me2Si
Ph
HO
Me
OTBS
9: 86% from 4da
[7]
For selected examples of 1,2-addition reactions to acylsilanes, see: a)
R. B. Lettan II, C. C. Woodward, K. A. Scheidt, Angew. Chem. Int. Ed.
2008, 47, 2294–2297; Angew. Chem. 2008, 120, 2326–2329; b) R. B.
Lettan II, C. V. Galliford, C. C. Woodward, K. A. Scheidt, J. Am. Chem.
Soc. 2009, 131, 8805–8814; c) D. A. Nicewicz, J. S. Johnson, J. Am.
Chem. Soc. 2005, 127, 6170–6171; d) G. R. Boyce, S. Liu, J. S.
Johnson, Org. Lett. 2012, 14, 652–655; e) F.-G. Zhang, I. Marek, J. Am.
Chem. Soc. 2017, 139, 8364–8370; for organocatalytic aldol reactions
of silyl glyoxylates, see: f) M.-Y. Han, X. Xie, D. Zhou, P. H. Li, L. Wang,
Org. Lett. 2017, 19, 2282–2285; g) M.-Y. Han, W.-Y. Luan, P.-L. Mai, P.
H. Li, L. Wang, J. Org. Chem. 2018, 83, 1518-1524.
d.r. = 92:8
Scheme 4. Tertiary α-silyl alcohols as versatile building blocks. [a] Pd/C (10%),
H2 (1 atm), MeOH, RT, 26 h. [b] TBAF (1.1 equiv), THF, 0 °C, 3 h. [c] I2 (2
equiv), Ph3P (2 equiv), 1H-imidazole (2 equiv), Et2O/CH3CN (4/1), RT, 1 h. [d]
1) TsCl (2.4 equiv), pyridine, 0 °C to RT, 24 h; 2) nBuLi (1.1 equiv), –78 °C to
RT, 4 h. [e] 1) TBSCl (2.4 equiv), DMAP (2.4 equiv), CH2Cl2, 0 °C to RT, 24 h;
2) Grubbs II (5 mol%), CH2Cl2, Δ, 16 h. TBAF = tetrabutylammonium fluoride,
Ts = p-toluenesulfonyl, DMAP = 4-(dimethylamino)pyridine.
[8]
[9]
a) R. Unger, F. Weisser, N. Chinkov, A. Stanger, T. Cohen, I. Marek,
Org. Lett. 2009, 11, 1853–1856; b) P. Smirnov, J. Mathew, A. Nijs, E.
Katan, M. Karni, C. Bolm, Y. Apeloig, I. Marek, Angew. Chem. Int. Ed.
2013, 52, 13717–13721; Angew. Chem. 2013, 125, 13962–13966; c) P.
Smirnov, E. Katan, J. Mathew, A. Kostenko, M. Karni, A. Nijs, C. Bolm,
Y. Apeloig, I. Marek, J. Org. Chem. 2014, 79, 12122–12135.
F.-Q. Li, S. Zhong, G. Lu, A. S. C. Chan, Adv. Synth. Catal. 2009, 351,
1955–1960.
In summary, we have introduced here a new approach to the
asymmetric synthesis of densely functionalized tertiary α-silyl
alcohols. This has been achieved by diastereoselective addition
of chiral allylic copper intermediate to acylsilanes, the former
generated by copper-catalyzed regio- and enantioselective
addition of an in-situ-formed boron nucleophile across 1,3-
dienes. The net reaction is a three-component coupling of 1,3-
dienes, a diboron reagent, and acylsilanes. The substrate scope
is broad, thereby enabling the flexible synthesis of chiral silicon
building blocks. The enantiomerically enriched α-silyl alcohols
may serve as precursors for other useful motifs that would
otherwise be more cumbersome to prepare.
[10] J. W. Rong, R. Oost, A. Desmarchelier, A. J. Minnaard, S. R.
Harutyunyan, Angew. Chem. Int. Ed. 2015, 54, 3038–3042; Angew.
Chem. 2015, 127, 3081–3085.
[11] a) H. Ito, H. Yamanaka, J. Tateiwa, A. Hosomi, Tetrahedron Lett. 2000,
41, 6821–6825; b) K. Takahashi, T. Ishiyama, N. Miyaura, Chem. Lett.
2000, 982–983.
[12] For selected reviews, see: a) K. Semba, T. Fujihara, J. Terao, Y. Tsuji,
Tetrahedron 2015, 71, 2183–2197; b) H. Yoshida, ACS Catal. 2016, 6,
1799–1811; c) Y. Tsuji, T. Fujihara, Chem. Rec. 2016, 16, 2294–2313;
d) A. P. Pulis, K. Yeung, D. J. Procter, Chem. Sci. 2017, 8, 5240–5247;
e) D. Hemming, R. Fritzemeier, S. A. Westcott, W. L. Santos, P. G.
Steel, Chem. Soc. Rev. 2018, 47, 7477–7494; f) K. Semba, Y. Nakao,
Tetrahedron 2019, 75, 709–719.
Acknowledgements
J.-J. F. gratefully acknowledges the Alexander von Humboldt
Foundation for a postdoctoral fellowship (2017–2019). M.O. is
indebted to the Einstein Foundation Berlin for an endowed
professorship. We are grateful to Dr. Elisabeth Irran (TU Berlin)
for the X-ray crystal-structure analysis and Professor Junliang
Zhang (Fudan University) for a generous gift of chiral phosphine
ligands.
[13] Aldehydes and ketones: a) F. Meng, F. Haeffner, A. H. Hoveyda, J. Am.
Chem. Soc. 2014, 136, 11304–11307; b) F. Meng, H. Jang, B. Jung, A.
H. Hoveyda, Angew. Chem. Int. Ed. 2013, 52, 5046–5051; Angew.
Chem. 2013, 125, 5150–5155; c) X.-C. Gan, L. Yin, Org. Lett. 2019, 21,
931–936; d) A. R. Burns, J. S. González, H. W. Lam, Angew. Chem. Int.
Ed. 2012, 51, 10827–10831; Angew. Chem. 2012, 124, 10985–10989.
[14] Imines: a) L. Jiang, P. Cao, M. Wang, B. Chen, B. Wang, J. Liao,
Angew. Chem. Int. Ed. 2016, 55, 13854–13858; Angew. Chem. 2016,
128, 14058–14062; b) K. Yeung, R. E. Ruscoe, J. Rae, A. P. Pulis, D. J.
Procter, Angew. Chem. Int. Ed. 2016, 55, 11912–11916; Angew. Chem.
2016, 128, 12091–12095; c) J. Rae, K. Yeung, J. J. W. McDouall, D. J.
Procter, Angew. Chem. Int. Ed. 2016, 55, 1102–1107; Angew. Chem.
2016, 128, 1114–1119; d) H. Jang, F. Romiti, S. Torker, A. H. Hoveyda,
Nat. Chem. 2017, 10, 1269–1275; e) T. Itoh, Y. Kanzaki, Y. Shimizu, M.
Kanai, Angew. Chem. Int. Ed. 2018, 57, 8265–8269; Angew. Chem.
2018, 130, 8397–8401; f) K. Yeung, F. J. T. Talbot, G. P. Howell, A. P.
Pulis, D. J. Procter, ACS Catal. 2019, 9, 1655–1661.
Keywords: asymmetric catalysis • boron • copper •
multicomponent reactions • silicon
[1]
a) K. Miura, A. Hosomi in Main Group Metals in Organic Synthesis
(Eds.: H. Yamamoto, K. Oshima), Wiley-VCH, Weinheim, 2005, pp.
409–592; see also: b) G. K. Min, D. Hernandez, T. Skrydstrup, Acc.
Chem. Res. 2013, 46, 457–470; c) A. K. Franz, S. O. Wilson, J. Med.
Chem. 2013, 56, 388–405.
[2]
For authoritative reviews, see: a) N. Lee, C.-H. Tan, D. Leow, Asian J.
Org. Chem. 2019, 8, 25–31; b) W. H. Moser, Tetrahedron 2001, 57,
2065–2084; c) A. G. Brook, Acc. Chem. Res. 1974, 7, 77–84; also of
relevance: d) G. Eppe, D. Didier, I. Marek, Chem. Rev. 2015, 115,
[15] α,β-Unsaturated acceptors: a) P. Liu, Y. Fukui, P. Tian, Z.-T. He, C.-Y.
Sun, N.-Y. Wu, G.-Q. Lin, J. Am. Chem. Soc. 2013, 135, 11700–11703;
b) X. Li, F. Meng, S. Torker, Y. Shi, A. H. Hoveyda, Angew. Chem. Int.
Ed. 2016, 55, 9997–10002; Angew. Chem. 2016, 128, 10151–10156; c)
This article is protected by copyright. All rights reserved.

10.1002/anie.201903174
Angewandte Chemie International Edition
COMMUNICATION
Y. Huang, S. Torker, X. Li, J. del Pozo, A. H. Hoveyda, Angew. Chem.
Int. Ed. 2019, 58, 2685–2691; Angew. Chem. 2019, 131, 2711–2717.
[16] Aryl and alkyl halides: a) K. Semba, Y. Nakao, J. Am. Chem. Soc. 2014,
136, 7567–7570; b) B. Chen, P. Cao, X. Yin, Y. Liao, L. Jiang, J. Ye, M.
Wang, J. Liao, ACS Catal. 2017, 7, 2425–2429; c) K. B. Smith, M. K.
Brown, J. Am. Chem. Soc. 2017, 139, 7721–7724; d) S. R. Sardini, M.
K. Brown, J. Am. Chem. Soc. 2017, 139, 9823–9826; e) K. B. Smith, Y.
Huang, M. K. Brown, Angew. Chem. Int. Ed. 2018, 57, 6146–6149;
Angew. Chem. 2018, 130, 6254–6257; f) B. Chen, P. Cao, Y. Liao, M.
Wang, J. Liao, Org. Lett. 2018, 20, 1346–1349; g) K. M. Logan, S. R.
Sardini, S. D. White, M. K. Brown, J. Am. Chem. Soc. 2018, 140, 159–
162; h) A. M. Bergmann, S. K. Dorn, K. B. Smith, K. M. Logan, M. K.
Brown, Angew. Chem. Int. Ed. 2019, 58, 1719–1723; Angew. Chem.
2019, 131, 1733–1737.
[17] Allylic electrophiles: a) F. Meng, K. P. McGrath, A. H. Hoveyda, Nature
2014, 513, 367–374; b) K. Semba, N. Bessho, T. Fujihara, J. Terao, Y.
Tsuji, Angew. Chem. Int. Ed. 2014, 53, 9007–9011; Angew. Chem.
2014, 126, 9153–9157; c) T. Jia, P. Cao, B. Wang, Y. Lou, X. Yin, M.
Wang, J. Liao, J. Am. Chem. Soc. 2015, 137, 13760–13763; d) J. Lee,
S. Radomkit, S. Torker, J. del Pozo, A. H. Hoveyda, Nat. Chem. 2018,
10, 99–108.
[18] Electrophilic cyanating reagents: a) Y. Yang, S. L. Buchwald, Angew.
Chem. Int. Ed. 2014, 53, 8677–8681; Angew. Chem. 2014, 126, 8821–
8825; b) W. Zhao, J. Montgomery, J. Am. Chem. Soc. 2016, 138,
9763–9766; c) T. Jia, Q. He, R. E. Ruscoe, A. P. Pulis, D. J. Procter,
Angew. Chem. Int. Ed. 2018, 57, 11305–11309; Angew. Chem. 2018,
130, 11475–11479; d) L. Wen, H. Zhang, J. Wang, F. Meng, Chem.
Commun. 2018, 54, 12832–12835.
[19] For selected examples, see: a) Y. Huang, K. B. Smith, M. K. Brown,
Angew. Chem. Int. Ed. 2017, 56, 13314–13318; Angew. Chem. 2017,
129, 13499–13503; b) T. Fujihara, A. Sawada, T. Yamaguchi, Y. Tani, J.
Terao, Y. Tsuji, Angew. Chem. Int. Ed. 2017, 56, 1539–1543; Angew.
Chem. 2017, 129, 1561–1565; c) A. Sawada, T. Fujihara, Y. Tsuji, Adv.
Synth. Catal. 2018, 360, 2621–2625.
[20] For reviews of transition-metal-catalyzed couplings with 1,3-dienes,
see: a) M. Holmes, L. A. Schwartz, M. J. Krische, Chem. Rev. 2018,
118, 6026-6052; b) H. Y. Cho, J. P. Morken, Chem. Soc. Rev. 2014, 43,
4368-4380.
[21] CCDC [1902300] (4cc) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
[22] Y. Sasaki, C. Zhong, M. Sawamura, H. Ito, J. Am. Chem. Soc. 2010,
132, 1226-1227.
This article is protected by copyright. All rights reserved.

10.1002/anie.201903174
Angewandte Chemie International Edition
COMMUNICATION
Suggestion for the Entry for the Table of Contents
COMMUNICATION
J.-J. Feng, M. Oestreich*
Page No. – Page No.
Tertiary α-Silyl Alcohols by
Diastereoselective Coupling of 1,3-
Dienes and Acylsilanes Initiated by
Enantioselective Copper-Catalyzed
Borylation
All at once. A copper-catalyzed three-component coupling of 1,3-dienes,
bis(pinacolato)diboron, and acylsilanes affords densely functionalized tertiary α-silyl
alcohols regioselectively in high yields as well as with excellent enantioselectivity
(up to 99% ee) and diastereoselectivity (d.r. > 20:1). Subsequent transformations
illustrate the versatility of these chiral building blocks.
This article is protected by copyright. All rights reserved.