Diastereodivergent Hydrosilylative Enyne Cyclization Catalyzed by N-Heterocyclic Carbene-Ni(0)?

Article abstract of DOI:10.1002/cjoc.202000651

Catalytic diastereodivergent hydrosilylative enyne cyclization with high generality and broad scope was achieved using electronic activated N-heterocyclic carbene-Ni(0) as a catalyst and R₃SiH as silane (IPr^Cl, syn- : anti-selectivit

Full text of DOI:10.1002/cjoc.202000651

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Diastereodivergent Hydrosilylative Enyne Cyclization Catalyzed by NHC-Ni(0)
Authors: Meng Yu, Xuefeng Yong, Weiwei Gao, Chun–Yu Ho*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2021, 39, 10.1002/cjoc.202000651.
The final Version of Record (VoR) of it with formal page numbers will soon be
published online in Early View: http://dx.doi.org/10.1002/cjoc.202000651.
ISSN 1001-604X • CN 31-1547/O6
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Ho Chun-Yu (Orcid ID: 0000-0002-1064-8682)
Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Diastereodivergent Hydrosilylative Enyne Cyclization Catalyzed
by NHC-Ni(0)
Meng Yu,a Xuefeng Yong,b Weiwei Gao,b Chun–Yu Ho*a,b
a Guangdong Province Key Laboratory of Catalysis, Department of Chemistry, Southern University of Science and Technology (SUSTech),
1088 Xueyuan Avenue, Shenzhen, 518055, Guangdong, China.
b Shenzhen Grubbs Institute, Department of Chemistry, Southern University of Science and Technology (SUSTech), 1088 Xueyuan Avenue,
Shenzhen, 518055, Guangdong, China.
Dedicated to Department of Chemistry, SUSTech, on the occasion of her 10th founding anniversary.
Keywords
N-heterocyclic carbenes | nickel | diastereodivergent synthesis | enyne | silylative hydroalkenylation
Main observation and conclusion
Catalytic diastereodivergent hydrosilylative enyne cyclization with high generality and broad scope was achieved using electronic ac-
tivated NHC-Ni(0) as a catalyst and R3SiH as silane (IPrCl, syn-:anti-selectivity from up to 98:2 to 7:93 by Z = O, NH vs NMs, R1 =
n-pentyl). Heterocycles bearing homoallylsilane rather than vinylsilane was obtained chemoselectively. The undesired yet highly
competitive reactivity was suppressed, like direct hydrosilylation of alkene and alkyne concurrently. Optionally, the homoallylsilane
products could be reduced further in 1-pot using IPrMe as ligand and (EtO)3SiH as silane under otherwise the same standard condition
as the above, offers practical access to additional stereocenters and more diverse product structures from enynes.
Comprehensive Graphic Content
-
-
-
-
,
,
P3Z
Z
an
R2
R2
s
n
P3
y
1 3 ti
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iR
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a
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il
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en ne somers
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i
Z
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1
Z
NH
O
-
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r
( )
4
4
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. .
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Z
S
S
r
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3
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-
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-
,
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o
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*E-mail:
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Supporting Information
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.202000651
This article is protected by copyright. All rights reserved.

First author et al.
Report
nickelacyclopentene with a suitable silane (Scheme 1d). Yet, the
above complications involved silanes and enynes can be very sig-
nificant. Key challenges ahead are the highly competitive
NHC-Ni(0) catalyzed alkyne or alkene hydrosilylations through
NHC-Ni(II)H(SiR3) formation at r.t. (Scheme 2, pathway I).41, 42 In-
deed, unless a gem-difluoromethylene was used as alkene termi-
nus, the hydrosilylative enyne cyclization was unable to proceed
with Ni(0) (Scheme 1c).24 Moreover, the silane needs to be more
reactive than the enyne in the nickelacyclopentene ring-opening
step to avoid undesired enyne homo-reaction (Scheme 2, pathway
II). At the same time, it has to be less reactive toward the Pathway
I.
Background and Originality Content
Transition metal-catalyzed hydrosilylative cyclization is a re-
nowned strategy to prepare key intermediates for more compli-
cated products.1-4 Notable methodologies have been developed
over the years to utilize those silylated products, in which Hiyama
coupling5-9 and Fleming-Tamao oxidations are often exploited.10-12
In particular, the catalytic hydrosilylative enyne cyclizations have
received a lot of attention over decades and efficiently construct
various carbo-/hetero-cycles (Scheme 1a).13-15 Unlike the hydrosi-
lylative diyne cyclization, most of the enyne mechanism's first step
is the corresponding metal hydride or metal silyl insertions to the
alkyne rather than metalacycle formation. That is because of the
relatively lower oxidative cyclization reactivity of the enyne and
the somewhat easier oxidative addition of silane.16,17 After subse-
quent insertion and reductive elimination steps, homoal-
lyl-/vinyl-silanes products are formed, and the catalyst is regener-
ated accordingly. Common complications are those related to
premature reductive elimination after alkyne insertion, competi-
tive intermolecular alkyne versus alkene insertions, as well as re-
,
,
,
o
v
e
ose ec
e
r n
a s o
T iti
n m
e a ca a
z
n n
z
n
a
/
e
d
e
e c c a o s
R
i
g
l
ti
t l t l
y
y
y
li ti
by
Rh Pd
C
Y
R1
R1
R1
R1
or
or
i
S
[ ]
R2
Z
.
a
t
C
Z
Z
Z
H
i
S
[
]
R2
v n
n
m
n
ane re uc on
s a es
o
h
oa s a es
llyl il
il
S
ti
i yl il
d
r
(
)
(
)
(
)
*
v
ti
as ereose ec
e
v
e e
n n
e c c a o ca a e
z
z
n
os
a
Di
t
l
b/
hyd ilyl ti
y
y li ti
t ly d by Cp 2YH
Cy
Cy
ductive cyclization without silyl group incorporation (Scheme 1a,
.
Cy
a
t
C
19
reduction).18,
Therefore, many well-designed catalysts and
*
n
e
2YM
Cp
or
2
3
e
iH Ph
S
iHM Ph
S
strategies have been developed recently in order to cope with
different enyne structural characteristics for high regioselectivity.
For example, Rh4(CO)12,20, 21 Rh2Co2(CO)12,20, 21 NHC−Rh,22 Rh-Co
nanoparticle23 and PBu3-Ni24 complexes for products with vi-
2
R1
S
ane
il
3
2
2
3
R1
n:
TBDM
O
n:
S
=
n
<
n
:
:
A ti 13 87
Sy
A ti 20 80
Sy
(
)
(
)
u
PB
c
/
ros a ve en ne c c za on ca a ze
Hyd ilyl ti
y
y li ti
.
t ly d by
R
Ni 0
( )
3
iR
S
3
nylsilane and allyl silane, while Cp*2Y25-27, IP.CoCl2 and a few
28
R
a
C
t
E
E
E
E
E
π-allyl-Pd29 complexes for homoallylsilane derivatives (Scheme
1a-c). Asymmetric and diastereoselective versions have also been
achieved using chiral Rh and Y catalysts.30, 31 Yet, diastereodiver-
gent synthesis development has been limited often by the delicate
balance of the above highly competitive reactivity, especially when
unfavorable or ineffective steric repulsions are involved.32-34 In
cases of 1,n-enynes without a cyclic template or quaternary center
in Ni(0) catalysis, non-selective oligomerization may lower the
yield and selectivity further sometimes (e.g. n = 7).35-37 Overall,
there is a great demand to develop a new methodology to meet
the new challenges in the catalytic hydrosilylative enyne cycliza-
tion and quickly provide products with more diverse substitution
patterns.
iR
S
R
3
u
PB Ni 0
( )
E
3
F
F
ane
il
F
S
a or
nor
Mi
M
j
F
F
F
o
-
w r
r
v r
s
:
as e eo
t
e
e
n
g
r
v
n n
y
z
n
os
a
e e
e c c a o
Thi
k Di
di
t
NH
C Ni 0
d/
hyd ilyl ti
y li ti by
( )
-
-
-
,
-
,
-
P3Z
Z
an
R2
R2
s
y
n
P3
1 3 ti
ro ar
P
p
1 3
gyl Z
P1Z
R2
Z
Z
Z
iR
iR
iR
iR
S
S
ane
a
2
il
3
3
S
R1
e
R1
R1
1
3
1
3
.
,
=
NM
t
=
C
n ne somers
s
y
i
Z
Z
1
Z
NH
O
-
IP Cl Ni 0
r
( )
4
4
. .
Z
R2
A1Z
Z
S
S
o uene r
t l
t
3
3
-
-
s n :an
y
ti
R1
R1
-
,
R1
1
-
u
o
:
:
p t 98 2 & 7 93
A
llyl Z
-
,
-
-
Z R2
Z R2
s n
y
a
n
A4
A4
1 4
1 4 ti
omoa s ane on
H
llyl il ly
We have recently achieved a diastereodivergent 1,n-aza-
enynes reductive hydroalkenylation38 and hydroacylation39 using
IPr–Ni(0) as catalysts. Alcohols and aldehydes have been used as
reductants and hydroacylating reagents, respectively. Our mecha-
nistic study has shown that nickelacyclopentene formation is cru-
cial in those reactions. Electronic manipulations of the 1,n-enyne’s
hetero-substituent can work with 1,3-allylic strain and govern the
heterocycles’ C-Z-C bond angles as shown in our DFT calculation.39
As a result, the product’s preferred configurations can be con-
trolled logically.
Scheme 1 Catalytic Hydrosilylative Enyne Cyclizations.
Herein, we report our continuous effort in diastereodivergent
heterocycle synthesis, illustrating the scope and selectivity further
by the practical catalytic synthesis of structurally more diverse
heterocycles bearing homoallylsilanes (Scheme 1d, c.f. preliminary
study: R1 = Ph, R2 = H, Z = NH and NMs38,40). Interestingly, the op-
timization showed that the exocyclic olefin on the heterocycle
could be hydrogenated using a suitable combination of catalyst
and siliane in one-pot. That discovery offers an option to access an
additional stereocenter for structurally more diverse product
structures at high efficiency.
Next, we envisioned
a diastereodivergent hydrosilylative
enyne cyclization that could be achieved by trapping the
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Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
NHC
Ni
R1
X
X
=
=
H
X
X
H
Cl
Z
1.7-enyne
v.s.
H
SiEt3
NHC
Ni
Si(OEt)3
Z
N
N
DIPP
R1
DIPP
H
SiR3
I
II
Pathway
Pathway
homo
[2+2+2] cycloaddition
Z
Addition)
Z
(Oxidative
Alkyne
insertion
(Oxidative Cyclization)
Diastereodivergent
Nickelacyclopentene
Formation
Ni(0)
1.7-enyne
H
SiR3
R1
Z
NHC directed,
Silane assisted
Selectivity Control
SiR3
R1
SiR3
R1
1
3
1
3
=
=
Z
NMs
-
Z
NH
O,
-
Z
anti
1,3-
H
3Z
3
SiR3
syn
1,3-
Vinylsilanes
Homoallylsilanes
Scheme 2 Competitions in NHC-Ni(0) Catalyzed Enyne Hydrosilylation Cyclizations.
enynes with various R1, like linear/cyclic alkyls, alkenyls, and (het-
ero-)aryls (Set 1a, 1,7-enyne P1Z with propargyl-Z). Moreover, the
method was found equally effective in the catalytic preparation of
1,4-diastereomers using 1,7-enynes A1Z with allyl-Z (Set 1b,
syn-:anti- > 5:95 for Z = O and NH; > 95: 5 for Z = NMs). This switch
of the product’s syn-/anti-configurations preference resembled
well with our former diastereodivergent reductive hydroalkenyla-
tion and hydroacylation. Enynes with internal alkenes were found
incompatible due to the more apparent terminal alkyne oligomer-
ization. On the other hand, enynes with internal alkynes are de-
cent substrates under our condition (Set 2a-b). That serves as a
new method to synthesize stereodefined trisubstituted homoal-
lylsilane on the ring. Finally, the method helps set up contigu-
ous/skipped stereocenters on heterocycles (Set 3-4). The pre-
ferred outcomes in these hydrosilylative enyne cyclizations still
follow the choice of Z selected as indicated above.
Results and Discussion
Our study commenced with enyne P1Oxya as a substrate and a
triethoxylsilane 2a as a hydrosilylating reagent (Scheme 3). Un-
fortunately, this initial attempt using IPr-Ni(0) catalyst did not
offer good chemoselectivity and yield. Direct hydrosilylation of
43
alkyne41,
and non-selective [2+2+2] cycloaddition44 occurred
significantly as the literature implied. The desired hydrosilylative
enyne cyclization product 1,3-syn-P3Oxyaa was formed only in a
small amount, yet the diastereoselectivity and homoallylsilane
formation selectivity were remarkably high (no 1,3-anti-P3Oxyaa
1
and no vinylsilane by H NMR). Interestingly, an unexpected exo-
cyclic methylene reduction of 1,3-syn-P3Oxyaa was observed and
resulted in a significant amount of 1,3-syn-P3Oxyaa-H product.
Notable advances in yield and selectivity came by screening
46
ligands and silanes.45,
First, ligand screening was conducted
using a less reactive triethylsilane 2b to avoid those undesired
reactivities related to hydrosilane oxidative addition, like exocyclic
methylene reduction, as well as direct alkyne and/or alkene hy-
drosilylations. While very low reactivity and basically no im-
provement were observed using PCy3, SIPr and IMes,24 much bet-
ter results were observed using sterically bulkier NHCs like IPrMe
and IPrCl than the IPr itself (Table 1, entry 1-4). Since the differ-
ence in V%bur of IPrMe and IPrCl is relatively small,45-48 the better
yield and higher catalyst reactivity obtained from IPrCl was at-
tributed mainly to the electronic property change (entry 3 and 4).
That could result in a more selective nickelacyclopentene opening
with 2b over [2+2+2] reactivity. It should be noted that the IPrCl
catalyst has a lower alkyne hydrosilylation reactivity than IPr, as
evidenced by a model study using a terminal alkyne for a compar-
ison (see SI), which may also help the desired pathway. To our
delight, the use of IPrCl also provided good results in the synthesis
of azacycle 1,3-syn-P3NHab (entry 5). Yet, the decisive improve-
ment brought by the use of IPrCl is even more apparent in the
synthesis of azacycle 1,3-anti-P3NMsab (entry 6-9). With the key
NHC identified, other combinations of R3SiH with various steric
and electronic properties could be used (Table 2). Desired prod-
ucts could be obtained in reasonably good yield, high d.r. and
homoallyl-:vinyl-silane selectivity in general (syn-:anti- > 95:5 for Z
= O and NH; > 5:95 for Z = NMs).
O
O
SiR3
SiR3
Ph
1,3-
Ph
1
3
1
3Zaa
-
-
Za
a
(13%)
2a
H
P3
P3
-H
(31%)
Si(OEt)3
Cat.
IPr-Ni(0)
syn
syn
1,3-
O
O
O
Ph
SiR3
1
3
SiR3
toluene
r.t.
Ph
Ph
1
anti
1
3
3
Za
P1
-
-
Za
a
Zaa
anti
P3
P3
-H
(n.d.)
1,3-
(n.d.) 1,3-
Ph
=
Z
Oxy
O
rac-
mix. of
[2+2+2]
(40-50%)
O
Ph
Scheme 3 Initial attempt in catalytic hydrosilylative oxaenyne cyclization
(product structures are shown in relative configurations).
Table 1 Screening of Ligands for Hydrosilylative Enyne Cyclization.[a]
entry
1[b]
2[c]
3[c]
4
1
2 Ligand
P3Z
yield (%) Syn:Anti[d] P3Z-H
PCy3
18
53
68
84
71
32
35
56
n.d.
< 5
< 5
<5
IPr
> 95:5
> 95:5
> 95:5
97:3[d]
13:87
10:90
8:92
P1Oxy
a
2b
P3Oxyab
IPrMe
IPrCl
< 5
< 5
< 5
< 5
< 5
Next, such an NHC and silane cooperation effect in preparing
sterically more challenging and diversely substituted heterocycles
was tested (Table 3). Even though the changes in enyne substitu-
ents could cause undesired steric repulsions and reactions, the
desired selectivity and reactivity were maintained very well. First,
highly consistent 1,3-syn-/anti-configuration preferences and high
homoallyl-:vinyl-silane ratio were observed in general among
5
P1NH
a
2b IPrCl
PCy3
P3NHab
6
7
P1NMs
a
2b IPr
IPrMe
P3NMsab
8
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
9
IPrCl
87
6:94
< 5
.
.
.
=
=
=
=
υ
[e]
[f]
co
X
X
NHC
IPr
X
V%Bur
(Aver)
H
34.9
2023.9
2021.3
2028.3
IPrMe
IPrCl
Me
Cl
35.7
35.5
N
N
DIPP
DIPP
[a] See scheme 3 for the reaction equation, enyne and product structures.
See Experimental Section for procedure except otherwise indicated. [b] 2
equiv. of PCy3. [c] 20 mol% catalyst. [d] By GCMS. [e] From [(NHC)AuCl3].47
[f] From [IrCl(CO)2(NHC)].50
Table 2 Screening of Silanes for Hydrosilylative Enynes Cyclization.[a]
entry
P1Z
Silane 2
(EtO)3SiH 2a
BnMe2SiH 2c
PhMe2SiH 2d
Ph3SiH 2e
P3Z
yield (%) Syn:Anti
1
2
3
4
5
6
7
8
9
P3Oxyaa
P3Oxyac
P3Oxyad
P3Oxyae
P3Oxyaf
P3NHaa
P3NMsaa
P3NHae
P3NMsae
66
68
> 95:5
> 95:5
> 95:5
> 95:5
> 95:5
98:2[b]
5:95[b]
> 95:5
8:92
P1oxy
a
71
67
tBuMe2SiH 2f
61
P1NH
a
68
(EtO)3SiH 2a
Ph3SiH 2e
P1NMs
a
83
P1NH
a
65
P1NMs
a
82[c]
See scheme 1d for the reaction equation, enyne and product structures.
See Experimental Section for procedure except otherwise indicated. [a]
IPrCl was used as ligand. [b] Determined by GC-MS. [c] Major product
structure was confirmed by XRD.
Overall, the product’s syn-/anti-configurations control here is
consistent with the related examples that we noted before. So, we
surmised that the diastereodivergent hydrosilylative enyne cy-
clization went through the same set of nickelacyclopentenes suc-
cessfully when we employed a suitable choice of electronic acti-
vated bulky NHC and silane (Scheme 2, the pathway I vs II). Next,
it might involve
a regioselective silane metathesis at the
nickelacyclopentene Csp3-Ni over the Csp2-Ni site according to the
product structure we obtained. That high regioselectivity was
similar to the regioselective hydroacylation. That was presumably
a result of the longer Csp3-Ni bond and the steric repulsion control
based on NHC and silane substituents. The undesired oligomeriza-
tion and [2+2+2] reactivity was suppressed mainly by the NHC
electronic and steric properties as shown in Table 1.
Table 3 Scope of the diastereodivergent hydrosilylative enyne cyclization by IPrCl-Ni(0) catalyst and Et3SiH 2b.[a]
=
Z
NH
R2
=
Z NMs
O,
R2
Z
Z
Z
+
+
R2
P1Z
1
2
eq
eq
2
2
SiEt3
SiEt3
rac-
rac-
R1
R1
R1
1
1
3
3
x
R3 R4
R3 R4
R
3 R4
2b
HSiEt3
Cat.
-
-
Z
P3Z
P3
x
b
x
b
anti
syn
1,3-
1,3-
IPrCl-Ni(0)
4
4
R2
r.t.
Z
toluene,
Z
Z
SiEt3
SiEt3
2
2
R1
R1
R1
1
A1Z
1
x
R3 R4
3 R4
R
3 R4
-
R2
A4
R2
R
-
A4Z
Z
x
b
x
b
anti
syn
1,4-
1,4-
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© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
e
a
e
t 1
S
t 2
S
I
-
,
e a ons
ro ar
n erna
t
ne
1 3 R l ti
Z
Z
l Alky
. .
v s
-
by P
P3Z
p
gyl Z
iEt
iEt
3
S
S
3
R1
R1
1
3
3
1
Z
n:
a
n
e
)
Z
P3Z
s
P3Z
P3O
s
n:
a
n
e
s
n:
a
n
e
ti yi ld
( )
y
ti yi ld
(
. .
v s
y
ti yi ld
y
(
)
iEt
e
S
iEt
e
S
3
R1
1
3
3
R1
1
3
x
x
y
x
yc
b
y
P3O db 95
P3NHdb 96
P3NMsdb
P3O bb 95
P3NHbb 97
P3NMsbb
%
)
>
:
>
:
:
92
5 79
5 80
8 73
%
%
(
(
)
( )
Z
n:
n
s
a
P3Z
s
n:
a
n
a
a
a
[ ]
y
ti yi ld
(
y
ti yi ld
(
:
[
]
NHc
P3NM
:
P
3
:
[
]
)
)
4 91
(
P3
b
sc
98
%
)
3 65%
2
76
%
(
)
(
)
10 . 72
(
90
. 91
(
%
:
:
92
:
b
7
93
%
)
8
67%
x
(
)
)
x
y
c
P3O yib 95
P3O hb 95
P3NHhb 94
P3NMshb 94
%
:
:
[
]
5 70
5 71
(
%
(
)
)
c
P3NHib 93
[ ]
P3NMsib
x
y
x
y
x
ye
:
7 52
(
:
P3O fb 95
P3O gb 95
P3NHgb 93
P3NMsgb
P3O
b
95
%
)
%
>
>
%
)
:
:
5 92
(
>
6 51%
( )
:
5 90
5 72
%
(
)
(
)
[
>
. 94%
(
. 81%
a
]
:
92
a
:
6
P3NHfb 95
)
NHe
:
]
8
:
:
[
5 32
7 90
P3
P3NM
b
se
97
%
%
( )
3 86%
(
)
)
(
)
(
)
)
10 . 81
(
97
. 81
(
8
. 90%
(
P3NMsfb
:
90
:
3
:
92
b
%
%
)
4
4
Z
iEt
S
Z
iEt
S
3
e
4
4
3
t 1b
S
Z
Z
iEt
S
iEt
S
. .
v s
. .
v s
-
3
3
,
e a
o
ns
1 4 R l ti
by Allyl Z
R1
1
R1
-
1
R1
1
R1
1
A4Z
A4Z
s
n:
y
s
n:
a
n
e
a
n
e
A4Z
A4O
A4Z
A4Z
A4O
s
n:
a
n
e
s
n:
a
n
e
s
n:
a
n
e
(
y
ti yi ld
ti yi ld
y
ti yi ld
y
ti yi ld
y
ti yi ld
(
)
(
)
(
)
(
)
)
x
x
ya < :
95
x
x
x
A4O yhb
A4NHhb
95
:
95
y
5
83
%
66
%
%
<
yc
NHc
sc
<
:
95
A4O bb
95
b
%
<
A4O yib
b
:
:
:
<
5
5
68
61
(
)
5
7
5
6%
80%
)
6 %
5
87
%
(
)
)
)
(
)
)
)
(
(
(
(
)
)
)
NHa < :
A4NHbb
95
A4
A4NM
%
<
:
5
95
A4NHib
94
A4
A4NM
b
sa
95
5
<
<
:
b 95
5
:
(
)
)
5
7
6 %
6
62%
(
(
)
)
.
.
.
.
.
A4NMshb 91
:
A4NMsbb 95
b
:
96
s
A4NM ib 72
b
:
4 67
:
:
95
9 70%
(
(
5 75
5 52
%
%
28 94
%
(
(
(
R1
Ph
R2 R3 R4
e
t 3
S
S
S
A4Z
s n: an
y
e
)
ti yi ld
4
4
(
e
Z
Z
a
iEt
iEt
S
3
S
kipp d
. .
1
H
H
H
H
H
H
H
M
M
H
H
H
H
H
H
H
H
H
H
H
H
H
M
M
M
H
H
H
H
H
H
H
H
H
H
M
H
H
3
v s
a
NHn
ereocen ers
t
:
[ ]
t
A4
b
99
:
1
71
%
(
)
e
1b
M
Ph
1
Ph
1
sn
A4NM
b
87
13 84
%
)
(
-
n
en
c
1
p
tyl
P3Z
1d Cy
s n: an
y
e
ti yi ld
e
t 4
tig
(
)
S
C
. .
s
Z
Z
on uous
ereocen ers
x
v
e
1
P3O y b
>
95
:
5 87
(
%
j
)
t
S
t
N
iEt
iEt
iEt
S
3
S
3
P3NH b
j
93
:
:
7 62
%
)
Ph
Ph
1
3
3
Ph
Ph
1
3
1f
(
24 . 64
(
P3NMs b
j
76
%
)
1g
S
-
Z
Z
n
en
p
e
e
. .
tyl
1h
v s
x
P3O ykb
95
:
5 68
%
)
S
iEt
S
(
3
3
1i Ph
1
1
3
P3NHkb
P3NMskb
95
:
5 81
%
)
(
e
e
e
e
:
20
1
j
Ph
Ph
80
92
%
(
)
. .
v s
Z
Z
1k
1l
P3NHlb
P3NMslb
95
:
5 78
%
)
iEt
S
iEt
S
(
3
3
S
. 81%
94
(
1
3
1
3
:
6
)
n
1
e
M
Ph
S
S
See Experimental Section for general procedure, structures are shown in relative configuration. Syn-:Anti-selectivity and yield (in parenthesis) were de-
termined by NMR and isolation except otherwise indicated. [a] By GCMS. [b] 20 mol% catalyst.
Table 4 Diastereoselective reduction and effect of R1 by using IPrMe-Ni(0) catalyst and (EtO)3SiH 2a.
R1
Ph
product
-
yield (%)
61%
69%
67%
71%
87%
64%
82%
76%
77%
68%
:anti
entry
1
starting materials
syn
3,4-
4
P1Oxy
a
O
O
O
88:12[a]
87:13[b]
-or-
-
-
-
aa
H
SiR3
-
SiR3
P3Oxy
P3Oxy
P3Oxy
aa
aa
R1
R1
2
R1
syn
syn
syn
1,3-
1,3-
1,4-
3
1
3
-
2a
H
Si(OEt)3
Cat.
-
P3Oxy
syn
H
67
:33
P3Oxy
[c]
P1Oxy
3
1,3-
1,3-
syn
1,3-
A1Oxy
a
83:17[a]
83:17[b]
12:
88[c]
4
Ph
IPrMe-Ni(0)
4
-
-
-
-
4
Oxy
Oxy
aa
aa
aa
anti
anti
anti
A4
A4
A4
H
5
1,4-
O
O
SiR3
O
SiR3
r.t.
toluene,
-or-
Oxy
6
1,4-
R1
3
R1
R1
1
-
-
ca
P1Oxy
A1Oxy
c
c
90:10[a]
7
-
-
-
=
n-pentyl
Cy
SiR3
P3Oxy
H
A1Oxy
anti
A4
anti
1,4-
A4
H
Oxy
Oxy
syn
anti
1,3-
1,4-
1,3-
1,4-
Si(OEt)3
1,4-
-
-
Oxy
ca
[a]
8
A4
H
H
75
:25
-
-
P1Oxy
A1Oxy
d
P3Oxy
d
a
a
90:10[a]
80:20[a]
9
syn
anti
-
-
Oxy
A4
d
H
d
10
Structures are shown in relative configuration, selectivity was determined by NMR. [a] one-pot reaction by using P1Z or A1Z and 2a as substrates. [b] Re-
duction by using isolated cyclization products P3Z or A4Z. [c] Reduction of the isolated cyclization products P3Z or A4Z by using cat. Pd/C H2.
Given the above proposed mechanism, a one-pot reduction
was examined to provide an additional stereocenter from the
exocyclic olefin (Table 4). Again, P1Oxya and A1Oxya were selected
as model substrates for such a development, but at this time
(EtO)3SiH 2a and IPrMe were used to provide the right balance in
enyne oxidative cyclization and the silane oxidative addition reac-
tivities for later on reduction. To our delight, that could be done
easily under otherwise the same condition except for 24 hrs reac-
tion time (entry 1 and 4).49 This discovery offered an new option
to prepare vicinal side chains at 3,4-positions with high
syn-diastereoselectivity. That selectivity was presumably a direct
result of minimizing undesired steric repulsions between the si-
lylated side chain and the NHC-Ni catalyst. Additional control ex-
periments using isolated 1,3-syn-P3Oxyaa and 1,4-anti-A4Oxyaa as
substrates showed highly comparable reduction selectivities as
the one-pot hydrosilylative enyne cyclization-reduction (Table 4,
entry 1, 2, 4, 5), indicating that the reduction might occur inde-
pendently and after the primary catalytic cycle. Interestingly, our
reduction showed a much stronger 3,4-syn-selectivity preference
than the traditional Pd/C catalyzed hydrogenation, showing a
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
strong catalyst control character of our reduction (entry 3 and 6).
Finally, enynes with different R1 were examined briefly in the cat-
alytic one-pot diastereoselective reduction (entry 1, 4, 7-9). The
reactions proceeded smoothly, and the 3,4-syn-selectivity in P1Oxy
was higher than A1Oxy in general.
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Manuscript received: XXXX, 2021
Manuscript revised: XXXX, 2021
Tekavec, T. N.; Louie, J., Nickel-catalyzed cycloadditions of unsatu-
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
Manuscript accepted: XXXX, 2021
Version of record online: XXXX, 2021
Accepted manuscript online: XXXX, 2021
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
Entry for the Table of Contents
Diastereodivergent Hydrosilylative Enyne Cyclization Catalyzed by NHC-Ni(0)
Meng Yu,a Xuefeng Yong,b Weiwei Gao,b Chun–Yu Ho*a,b
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
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Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX