Copper-Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N-Heterocyclic Carbene Chiral Ligand

Article abstract of DOI:10.1002/anie.201605125

Copper-catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z-acyclic or cyclic allylic phosphates using a new chiral N-heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′-type regioselectivities and high enantioselectivities to deliver chiral 1,5-diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.

Full text of DOI:10.1002/anie.201605125

Angewandte
Communications
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International Edition: DOI: 10.1002/anie.201605125
German Edition: DOI: 10.1002/ange.201605125
Asymmetric Catalysis
Copper-Catalyzed Enantioselective Allyl–Allyl Coupling between
Allylic Boronates and Phosphates with a Phenol/N-Heterocyclic
Carbene Chiral Ligand
Yuto Yasuda, Hirohisa Ohmiya,* and Masaya Sawamura*
Abstract: Copper-catalyzed enantioselective allyl–allyl cou-
pling between allylboronates and either Z-acyclic or cyclic
allylic phosphates using a new chiral N-heterocyclic carbene
ligand, bearing a phenolic hydroxy, is reported. This reaction
occurs with exceptional SN2’-type regioselectivities and high
enantioselectivities to deliver chiral 1,5-diene derivatives with
a tertiary stereogenic center at the allylic/homoallylic position.
occurred with exceptional SN2’-type regioselectivity and high
enantioselectivities to deliver chiral 1,5-diene derivatives with
a tertiary carbon stereogenic center at the allylic/homoallylic
position. Acid- or base-sensitive functional groups were
compatible with this enantioselective reaction. Z-Aliphatic
allylic substrates including acyclic and cyclic 2-alkene-1,4-diol
derivatives can be used. In this regard, the present copper-
catalyzed system is complementary to Morkenꢀs palladium
system, which was applied to primary E-allylic electrophiles.
Importantly, this study demonstrated that the phenol/NHC
A
llylic substitution using allylic nucleophiles and electro-
philes (allyl–allyl coupling) to form 1,5-dienes raises the issue
of the allylic regiochemistry on both the nucleophiles and
chiral ligands have utility not only in the reaction of
3
2
À
À
À
electrophiles, but affords a powerful strategy for C(sp )
pronucleophiles with C(sp) H or C(sp ) H bonds but also
C(sp3) bond formation in organic synthesis.[1] In particular,
the enantioselective allyl–allyl coupling under the influence
of chiral transition-metal catalysts serves as an efficient entry
to chiral 1,5-dienes with a stereogenic center at the allylic/
homoallylic position. 1,5-Dienes are found in many important
biologically active molecules and also serve as useful synthetic
intermediates because of the versatility of the two alkene
functionalities for further transformations.[2] Nevertheless,
such enantioselective reactions had been underdeveloped
until Morken and co-workers reported the palladium-cata-
lyzed regio- and enantioselective allyl–allyl coupling between
substituted allylboronates and (E)-allylic carbonates.[3]
Remarkably, this palladium catalysis delivered chiral 1,5-
dienes containing two adjacent stereogenic centers with high
diastereo- and enantioselectivities. More recently, Feringa
and co-workers reported the copper-catalyzed enantioselec-
tive coupling between allylmagnesium bromide and (E)-allyl
bromides, but the SN2’-type regioselectivity was moderate.[4]
Carreira and co-workers developed the irridium-catalyzed
regio- and enantioselective coupling between allylsilanes and
secondary aromatic allylic alcohols.[5] Despite these efforts,
the allyl–allyl coupling using either acyclic or cyclic allylic
electrophiles involving a Z-alkene moiety is yet to be
explored.
in those of organoboron compounds.[9]
Earlier, we reported enantioselective SN2’-type allylic
substitution reactions between non-allylic alkylboron (alkyl-
9-BBN) compounds and achiral primary allylic substrates
under the influence of a catalytic amount of a copper(I)
complex and a stoichiometric potassium alkoxide base.[10] On
the basis of this knowledge, we developed an unprecedented
copper-catalyzed enantioselective allylic substitution with
allylboron compounds. In the screening of the reaction
conditions, we used readily available allylboronic acid pina-
colate esters instead of the allyl-9-BBN reagents (Table 1).[11]
In studies aimed toward finding achiral copper systems which
enable the selective formation of the racemic, branched
g-substitution product 3aa, we found that a Cu/NHC (SIMes)
complex, prepared in situ from 1,3-bis(2,4,6-trimethyl-
phenyl)imidazolinium chloride (SIMes·HCl), CuCl, and
KOMe, gave exclusive g-selectivity (g/a > 99:1) in the reac-
tion between 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(1a) and the Z-allylic phosphate 2a in THF at À208C to form
the branched allyl–allyl coupling product (R)-3aa in high
yield (93%; entry 1). In contrast to the excellent ligand
performance of the ring-saturated NHC ligand SIMes, the
corresponding unsaturated NHC ligand IMes, which is
derived from 1,3-bis(2,4,6-trimethylphenyl)imidazolium chlo-
ride (IMes·HCl), gave a mixture of branched and linear
products with a low g/a regioselectivity (62:38) in a moderate
total product yield (entry 2). The reaction either without
a ligand or with 1,10-phenanthroline (Phen) or DPPE ligands
did not proceed at all (entries 3–5). Monodentate phosphine
ligands such as Ph3P gave the linear a-substitution product
(E)-4aa exclusively (entry 6).
Herein, we report copper-catalyzed enantioselective
allyl–allyl coupling between allylboronates and (Z)-allylic
phosphates using a new chiral N-heterocyclic carbene (NHC)
ligand bearing a phenolic hydroxy group.[6À8] This reaction
[*] Y. Yasuda, Prof. Dr. H. Ohmiya, Prof. Dr. M. Sawamura
Department of Chemistry, Faculty of Science, Hokkaido University
Sapporo 060-0810 (Japan)
Based on these results, we decided to investigate various
ring-saturated chiral NHC ligands (Table 1, entries 7–14). The
C2-symmetric NHC ligand (S,S)-L1,[12] which has two stereo-
genic carbon centers in the imidazolidine ring with two
N-mesityl groups, gave nearly racemic 3aa with exclusive
g-regioselectivity and moderate product yield (entry 7).
E-mail: ohmiya@sci.hokudai.ac.jp
sawamura@sci.hokudai.ac.jp
Homepage: http://wwwchem.sci.hokudai.ac.jp/~orgmet/index.php
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201605125.
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Table 1: Ligand effects in reaction between 1a and (Z)-2a.[a]
À408C (entry 12). However, the naphthol/NHC chiral ligands
(S,S)-L6 and (S,S)-L7[9b] did not lead to improvement of the
enantioselectivity (entries 13 and 14).
Effects of leaving groups and bases are summarized in
Table 2. Changing the leaving group to either a bromide or
chloride under the reaction conditions used in entry 11 of
Table 1, caused a decrease in the g-regioselectivity and
enantioselectivity (Table 2, entries 2 and 3).
Entry
Ligand
T [8C]
Yield [%][b]
g/a
ee [%][d]
(3aa/4aa)[c]
1
2
3
4
5
6
7
8
SIMes
IMes
none
Phen
DPPE
À20
À20
À20
À20
À20
À20
À20
À20
À20
À20
À20
À40
À20
À20
93
65
0
0
0
57
49
13
10
77
83
80
34
56
>99:1
62:38
–
–
–
1:>99
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
92:8
–
–
–
–
–
Table 2: Effects of leaving groups and bases.[a]
Entry Leaving group
Base
Yield
g/a
ee
[%][b] (3aa/4aa)[c] [%][d]
1[e]
2
3
4
5
OP(O)(OEt)2 ((Z)-2a) KOMe
83
89
85
91
0
>99:1
94:6
82:18
89:11
–
92
64
20
74
–
PPh3
–
2
Cl[f]
KOMe
KOMe
(S,S)-L1
(S,S)-L2
(S,S)-L3
(S,S)-L4
(S,S)-L5
(S,S)-L5
(S,S)-L6
(S,S)-L7
Br[g]
50
54
85
92
99
67
82
OP(O)(OEt)2 ((Z)-2a) NaOMe
OP(O)(OEt)2 ((Z)-2a) LiOMe
OP(O)(OEt)2 ((Z)-2a) KOtBu
OP(O)(OEt)2 ((Z)-2a) K2CO3
9
10
11
12[e]
13
14
6
7
67
0
63:37
–
50
–
[a] Reaction conditions: 1a (0.24 mmol), (Z)-2 (0.15 mmol), CuCl/(S,S)-
L5 (10 mol%), base (0.18 mmol), THF (0.6 mL), À208C for 20 h.
[b] Yield of isolated product. [c] Determined by 1H NMR analysis of the
crude reaction mixture. [d] The ee value was determined by HPLC
analysis. [e] Reraction conditions used in entry 11 of Table 1. [f] (Z)-(5-
Chloro-3-penten-1-yl)benzene. [g] (Z)-(5-Bromo-3-penten-1-yl)benzene.
>99:1
[a] Reaction conditions: 1a (0.24 mmol), (Z)-2a (0.15 mmol), CuCl/
ligand (10 mol%), KOMe (0.18 mmol), THF (0.6 mL) for 20 h. [b] Yield
of isolated product. [c] Determined by 1H NMR analysis of the crude
reaction mixture. [d] The ee value was determined by HPLC analysis.
[e] 1a (1.9 mmol) and (Z)-2a (1.2 mmol) were used. The reaction was
carried out for 48 h. DPPE=1,2-bis(diphenylphosphino)ethane,
THF=tetrahydrofuran.
The nature of the base had a strong impact on the yield,
g-regioselectivity, and enantioselectivity. The use of NaOMe
instead of KOMe decreased the regioselectivity and enantio-
selectivity (entry 4). The use of LiOMe resulted in no reaction
(entry 5). The inefficiency of LiOMe may reflect higher
solubilities of either LiCl or LiOP(O)(OEt)2, which may form
inactive copper species through ionic interactions. The
structure of the alkoxide moiety of the base also had
a significant impact on the reaction efficiency and selectivity.
Thus, when KOMe was changed to a sterically more
demanding base, KOtBu, the product yield was moderate
and both regioselectivity and enantioselectivity decreased
significantly (entry 6). This result suggests that trialkoxy-
boron ROBpin may participate in the reaction since Lewis
acids activate the phosphate leaving group (see Figure 2). No
reaction occurred with K2CO3 (entry 7).
Similar chiral NHC ligands bearing either 2-methylphenyl
[(S,S)-L2)] or 2-methoxyphenyl [(S,S)-L3] groups, instead of
one of the mesityl groups in (S,S)-L1, induced moderate
enantioselectivities, but yields were low (entries 8 and 9).
Next, we used the NHC ligand (S,S)-L4 bearing a 2-hydroxy-
phenyl group, which exhibited high ligand performance in the
enantioselective copper-catalyzed allylic substitutions with
terminal alkyne pronucleophiles, as we reported previously
(entry 10).[9a] To our delight, the Cu/(S,S)-L4 catalyst system
gave higher product yield (77%) and enantioselectivity (85%
ee) than the system with either (S,S)-L2 or (S,S)-L3, and the
exclusive regioselectivity was unchanged. This result suggests
a functional role of the phenolic hydroxy group in L4.
Changing the N-mesityl group of (S,S)-L4 to an N-2,4-
dicyclohexyl-6-methylphenyl group to afford the new
phenol/NHC chiral ligand (S,S)-L5 gave even better enantio-
selectivity with exceptional regioselectivity (g/a > 99:1) and
high yield (entry 11). Furthermore, the enantioselectivity
jumped to 99% ee by decreasing the reaction temperature to
Z-Allylic phosphates with different aliphatic g-substitu-
ents were subjected to the reaction of 1a with the Cu/(S,S)-L5
catalyst system (Table 3). The 2-phenylethyl group of (Z)-2a
could be replaced with either benzyl or octyl groups and
excellent g-selectivities without a significant decrease in the
enantioselectivies (entries 1 and 3).
A sterically more
demanding g-substituent, such as a cyclohexyl group ,was
also tolerated with the high level of enantioselectivity
retained (entry 4).[13] Notably, the enantioselective reaction
with 2-butene-1,4-diol derivatives, which have two potential
leaving groups at different allylic positions, proceeded with
À
the allylic C O bonds in either the ether or carboxylic ester
leaving groups untouched (entries 5–13).
Various functional groups were tolerated (entries 2 and 5–
15). For example, allylic phosphates bearing 1,3-benzodioxole
[(Z)-2c], THP ether [(Z)-2 f], benzyl ether [(Z)-2g], silyl
2
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Table 4: Scope with respect to the allylboronates.[a]
Entry Allylboronate (Z)-2 Product
Table 3: Scope with respect to the allylic phosphates.[a]
Yield
[%][b]
g/a[c] ee
[%][d]
Entry Phosphate (2)
3
T
Yield
ee
[8C] [%][b,c] [%][d]
1
2
3
4
5
(Z)-2a
(Z)-2a
(Z)-2a
(Z)-2a
77
50
87
59
89
>20:1 95
>20:1 80
84:16 80
87:13 82
78:22 83
1
2
À50
À30
62
97
86
86
3
4
À40
À50
85
59
84
80
[a] Reaction conditions: 1 (0.24 mmol), (Z)-2 (0.15 mmol), CuCl/(S,S)-L5
(10 mol%), KOMe (0.18 mmol), THF (0.6 mL), À508C (entry 1) or
À308C (entries 2–5) for 48 h. [b] Yield of isolated product. [c] Determined
by 1H NMR analysis of the crude reaction mixture. [d] The ee value was
determined by HPLC analysis. OP=OP(O)(OEt)2.
5
6
7
R=THP [(Z)-2 f]
R=Bn [(Z)-2g]
R=tBuMe2Si
[(Z)-2h]
(R)-3af
(R)-3ag
(R)-3ah
À30
À50
À50
83
75
78
90
85
97
8
R=Piv [(Z)-2i]
(R)-3ai
À30
70
91
give the corresponding chiral 1,5-dienes with enantiomeric
excesses over 80%, while the g-selectivities were moderate
(entries 3–5).[14] Unfortunately, g-substituted allylborons such
as trans- or cis-crotylboronates did not react under identical
reaction conditions.
The coupling between 1a and cis-4-cyclopentene-1,3-diol
diphosphate (Z)-2r catalyzed by Cu/(S,S)-L5 system occurred
with a useful level of enantioselectivity, thus giving the trans-
1,2-isomer 3ar [Eq. (1)].[13] The reaction with the cis-4-
cyclohexene-1,3-diol derivative (Z)-2s afforded the trans-
1,2-isomer 3as with moderate enantiocontrol [Eq. (2)]. These
stereochemical outcomes indicate that the present copper-
catalyzed reaction proceeded through an anti-SN2’-type
reaction pathway. Notably, Morkenꢀs palladium-catalyzed
protocol has not been applied to this type of cyclic allylic
electrophile involving a Z-alkene moiety.[3]
9
R=MeO [(Z)-2j]
R=F3C [(Z)-2k]
R=Br [(Z)-2l]
(R)-3aj
(R)-3ak
(R)-3al
À30
À30
À30
À30
85
61
65
87
92
90
90
91
10
11
12
R=Me2N [(Z)-2m] (R)-3am
13
À30
80
90
14
15
À40
À30
78
88
96
92
[a] Reaction conditions: 1a (0.24 mmol), (Z)-2 (0.15 mmol), CuCl/(S,S)-
L5 (10 mol%), KOMe (0.18 mmol), THF (0.6 mL) for 48 h. [b] Yield of
isolated product. [c] Constitutional isomer ratio g/a>20:1 (determined
by 1H NMR analysis of the crude reaction mixture). [d] The ee value was
determined by HPLC analysis. Cbz=benzyloxycarbonyl, OP=
OP(O)(OEt)2, THP=tetrahydropyran, Ts=4-toluenesulfonyl.
ether [(Z)-2h,o],[13] pivalate [(Z)-2i], and p-toluenesulfonate
[(Z)-2p] groups as the aliphatic g-substituent reacted to
afford the corresponding 1,5-diene products in good yields
with high enantioselectivities (entries 2, 5–8, 14 and 15).
Methoxy, trifluoromethyl, bromo, and dimethylamino sub-
stituents on the aromatic ring of the benzoate groups were
tolerated (entries 9–12). A carbamate group was compatible
with this enantioselective reaction (entry 13).
The reactions of b-substituted allylboronate derivatives
were examined with the Cu/(S,S)-L5 catalyst system
(Table 4). Methallylboronate (1b) and 2-ethyl-2-propen-1-
ylboronate (1c) reacted with (Z)-2a with excellent g-selec-
tivity and with high enantioselectivities (entries 1 and 2).
Allylboronate derivatives (1d–f) with hexyl, benzyl, and
phenyl groups at the b-position underwent the coupling to
The alkene geometry of the allylic phosphates had
a strong impact on both the regioselectivity and enantiose-
lectivity. Thus, the reaction between 1a and (E)-2a under the
reaction conditions used for entry 11 in Table 1, afforded the
linear a-substitution product (E)-4aa as a major product
together with a minor formation of (S)-3aa, the antipode of
the product derived from (Z)-2a [Eq. (3)]. This a-substitution
product (E)-4aa seemed to be produced by allylic 1,3-
migration of copper in the allylcopper(III) species. To gain
deeper insight into the nature of the postulated allylcopper-
(III) species, we conducted the reaction of the secondary
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allylic phosphate 2a“, a constitutional isomer of (Z)-2a
[Eq. (4)]. Interestingly, this reaction gave almost the same
product distribution as the reaction with (E)-2a. The
quently, the oxidative addition forms the (p-en-s-yl)copper-
(III) complex E1 with a secondary sp3-carbon atom bound to
Cu. Facile reductive elimination of E1 is faster than allylic 1,3-
Cu-migration to form E2, and thus produces the branched
g-substitution product 3 and regenerates A for the next
catalytic cycle (see the Supporting Information for enantio-
discrimination models).
Based on this assumption, the crucial dependence of the
regioselectivity on the E/Z geometry of the allylic substrate
(2) can be explained by higher instability of E2, compared to
the corresponding CuIII species produced from the E sub-
strate, because of greater steric repulsion in the allyl moiety
derived from the Z substrate (see Figure 1). In this regard, E1
may be better described as a (h1-allyl)copper(III) complex
without alkene coordination.
observed convergency in the regioselectivity and stereochem-
ical outcome suggest that (E)-2a and 2a” lead to a common
equilibrium mixture of the allylcopper(III) species prior to
reductive elimination to form the product mixture
(Figure 1).[15]
In summary, we have developed the enantioselective SN2’-
type allyl–allyl coupling between allylboronates and Z-acyclic
and cyclic allylic phosphates. This coupling was enabled by
catalysis of a copper(I) complex with a new phenol/NHC
chiral ligand, thus demonstrating the utility of this class of
chiral ligands for enantioselective copper catalysis with
organoboron compounds.[9] Various functional groups are
tolerated in the aliphatic allylic phosphates. This copper-
catalyzed protocol provides efficient access to functionalized,
enantioenriched chiral 1,5-dienes with a tertiary carbon
stereogenic center at the allylic/homoallylic position, which
can be further applied in the synthesis of complex molecules.
The broad functional-group compatibility and the use of
earth-abundant and relatively low toxicity copper as a metal
are attractive features of this protocol.
Figure 1. Allylcopper(III) species.
Based on the assumption that the g-selective reaction of
(Z)-2 also occurs via allylcopper(III) intermediates, we
postulated a catalytic reaction pathway for the enantioselec-
tive allyl–allyl coupling catalyzed by Cu/(S,S)-L5, as shown in
Figure 2.[15] The reaction of CuCl, (S,S)-L5, and KOMe forms
an alkoxycopper(I) complex (A), in which the chiral NHC
ligand coordinates to Cu as an anionic C,O-bidentate ligand.
Next, transmetalation between A and an allylborate (B)[16]
produces a potassium phenoxo(allyl)cuprate (C). C forms a
p-complex (D) with the allylic phosphate 2, in which Cu is anti
to the phosphate leaving group, which may be activated
through participation of MeOBpin Lewis acid.[10d] Subse-
Acknowledgements
This work was supported by Grants-in-Aid for Scientific
Research (B) (No. 15H03803), JSPS, to H.O. and by CREST
and ACT-C, JST, to M.S.
Keywords: allylic compounds · asymmetric catalysis · boron ·
copper · synthetic methods
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4
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[9] a) A. Harada, Y. Makida, T. Sato, H. Ohmiya, M. Sawamura, J.
Am. Chem. Soc. 2014, 136, 13932. See also: b) H. Ohmiya, H.
Zhang, S. Shibata, A. Harada, M. Sawamura, Angew. Chem. Int.
Ed. 2016, 55, 4777; Angew. Chem. 2016, 128, 4855.
[14] The linear a-substitution product was the E isomer.
[15] Nakamura and co-workers conducted DFT calculations on the
mechanism of the reaction between [MeCu(CN)Li] and allyl
acetate to form
a square planar four-coordinate (g-s-
enyl)copper(III) species [(p-en-s-yl)copper(III) complex]. Our
mechanistic proposal is in accord with the Nakamuraꢀs mecha-
nism, in which the (g-s-enyl)copper(III) species is not in
equilibrium with the corresponding (a-s-enyl)coppor(III) spe-
cies. The regioselectivity is determined at the oxidative addition
step as a consequence of the asymmetric nature of MeCuCNÀ.
Our proposed mechanism is in accord with the Nakamuraꢀs
mechanism in that the reaction proceeds through oxidative
addition of a cuprate to form the (g-s-enyl)copper(III) species
followed by reductive elimination. However, the coordination
number of Cu in the allylcopper(III) complex is different by
virtue of bidentate coordination of the anionic phenol/NHC
chiral ligand (L). The strongly electron-donating NHC coordi-
nation should render the p–en coordination weaker, thus making
the allylic 1,3-copper migration in the allylcopper(III) complex
more feasible. See: a) N. Yoshikai, S.-L. Zhang, E. Nakamura, J.
Am. Chem. Soc. 2008, 130, 1286. For the effect of a s-donor
ligand, see: b) M. Yamanaka, S. Kato, E. Nakamura, J. Am.
Chem. Soc. 2004, 126, 6287.
[10] a) Y. Shido, M. Yoshida, M. Tanabe, H. Ohmiya, M. Sawamura,
J. Am. Chem. Soc. 2012, 134, 18573; b) K. Hojoh, Y. Shido, H.
Ohmiya, M. Sawamura, Angew. Chem. Int. Ed. 2014, 53, 4954;
Angew. Chem. 2014, 126, 5054. See also: c) H. Ohmiya, U.
Yokobori, Y. Makida, M. Sawamura, J. Am. Chem. Soc. 2010,
132, 2895; d) K. Nagao, U. Yokobori, Y. Makida, H. Ohmiya, M.
Sawamura, J. Am. Chem. Soc. 2012, 134, 8982.
[16] Rapid formation of a tetravalent borate (B) was confirmed by
11B NMR spectroscopy. See the Supporting Information for
details.
[11] The use of allyl-9-BBN reagent instead of 1a under the reaction
conditions used for entry 12 in Table 1, resulted in decreases in
both enantioselectivity (87% ee) and product yield (30%) but
with the exclusive regioselectivity (g/a > 99:1) unchanged.
[12] M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1,
953.
Received: May 25, 2016
Revised: June 28, 2016
Published online: && &&, &&&&
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Asymmetric Catalysis
Y. Yasuda, H. Ohmiya,*
M. Sawamura*
&&&& — &&&&
Copper-Catalyzed Enantioselective Allyl–
Allyl Coupling between Allylic Boronates
and Phosphates with a Phenol/N-
Heterocyclic Carbene Chiral Ligand
Novel NHC: Copper-catalyzed enantio-
selective allyl–allyl couplings between
allylboronates and either Z-acyclic or
cyclic allylic phosphates are accom-
plished by using a new chiral NHC ligand
bearing a phenolic hydroxy group. This
reaction occurs with exceptional SN2’-type
regioselectivities to deliver chiral 1,5-
dienes with a tertiary stereogenic center
at the allylic/homoallylic position.
6
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
These are not the final page numbers!