Nickel-catalyzed coupling of terminal allenes, aldehydes, and silanes

Article abstract of DOI:10.1016/j.tet.2006.05.006

The development of a nickel-catalyzed coupling of terminal allenes, aldehydes, and silanes is described. This transformation selectively provides 1,1-disubstituted allylic alcohols, protected as a silyl ether. The choice of the reducing agent is essential

Full text of DOI:10.1016/j.tet.2006.05.006

Tetrahedron 62 (2006) 11350–11359
Nickel-catalyzed coupling of terminal allenes,
aldehydes, and silanes
*
Sze-Sze Ng and Timothy F. Jamison
Massachusetts Institute of Technology, Department of Chemistry, Cambridge, MA 02139, USA
Received 16 February 2006; revised 1 May 2006; accepted 4 May 2006
Available online 26 May 2006
Abstract—The development of a nickel-catalyzed coupling of terminal allenes, aldehydes, and silanes is described. This transformation
selectively provides 1,1-disubstituted allylic alcohols, protected as a silyl ether. The choice of the reducing agent is essential for achieving
selectivity in this coupling process. A trialkylphosphine (Cyp P) and an N-heterocyclic carbene (IPr) are complementary in this reaction.
3
Ó 2006 Elsevier Ltd. All rights reserved.
cat. Ni(cod)2,
IPr
OSiR3
1
. Introduction
H
O
+
H
R
•
+
+
R3SiH
R1
Ar ð1aÞ
1
R2
Ar
H
Nickel is a versatile metal that catalyzes several important
transformations, such as, Ziegler–Natta polymerization,
hydrogenation, cross coupling, hydrometallation, and multi-
R2
1
component coupling reactions. We and others have devel-
R1 OSiR3
R3
R1
R2
cat. Ni(cod)2,
O
oped several nickel-catalyzed coupling reactions that
provided synthetically useful alcohol and amine deriva-
tives. The most effort has been directed toward coupling
R3SiH Cyp3P or IPr
THF
•
+
ð1bÞ
R2
R3
H
2
reactions of aldehydes with either an alkyne or a 1,3-diene,
and an organophosphine has often served as a supporting
ligand. Also, in these reactions a third coupling partner pro-
vides either a hydrogen atom (reductive coupling) or an
organic substituent (alkylative coupling), and organozinc
and organoboron are the most common such reagents. More
recently, organosilanes and N-heterocyclic carbene (NHC)
ligands have also been reported to be useful alternatives in
Allylic alcohols are often prepared by reactions that involve
the addition of an alkenyl metal reagent to an aldehyde or
a ketone. Two examples are the Nozaki–Hiyama–Kishi reac-
3
4
tion and the addition of alkenyl zinc species to aldehydes.
The use of transition metals in these two methods allows
coordination of chiral ligands to induce asymmetric addition
to the carbonyl, providing enantiomerically enriched allylic
3
g–j,4
2
g
alcohols.
The nickel-catalyzed reductive coupling of
nickel-catalyzed alkyne–aldehyde (Montgomery) and 1,3-
diene–aldehyde (Mori)
2
w–bb
allenes and aldehydes described in this work is distinct from
these strategies since the preparation of a vinyl halide or a
vinyl metal species is not required.
reductive coupling reactions.
We have found the silane/NHC combination to be useful in
related allene–aldehyde coupling reactions as well. When
employed in nickel-catalyzed coupling of chiral 1,3-disub-
stituted allenes and aldehydes, Z-trisubstituted allylic alco-
hols are afforded with high selectivity and with complete
Most intramolecular and intermolecular coupling reactions
of allenes and aldehydes afford homoallylic alcohols, in
which one of the sp -hybridized carbons of the allene is the
2
5
2
r,s
site of C–C bond formation. Catalyzed by several transition
metals, cyclization of allenylaldehydes provided homo-
chirality transfer (Eq. 1a).
Herein, we summarize our
work on nickel-catalyzed coupling reactions of terminal
allenes, aldehydes, and silanes, a process that affords allylic
alcohols that differ from those obtained in the allene cou-
pling reactions that were described previously in high regio-
selectivity and site selectivity (Eq. 1b).
5
a–j
allylic alcohols in high diastereoselectivity.
Transition
metal-catalyzed intermolecular couplings of allenes and
aldehydes also provided homoallylic alcohols in most
5
k–w,2r–t
cases.
lecular coupling of allenes and aldehydes include the single
Other methods of intermolecular and intramo-
6
a–c
electron transfer process from Pattenden and Crandall,
as well as the recently developed SmI mediated reductive
coupling from Gillmann, Reissig, and Molander.
keywords: Allene; Allylic alcohol; N-Heterocyclic carbene; Nickel; Silane.
*
Corresponding author. Tel.: +1 617 253 2135; fax: +1 617 324 0253;
e-mail: tfj@mit.edu
2
6
d–f
The
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.006

S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
Table 2. Examination of reducing agents
11351
a
SmI mediated process gave either allylic or homoallylic
2
alcohols, depending on the nature of the substrates.
cat. Ni(cod)2,
Cyp3P
OR'
i-Pr
O
•
+
Cy
reducing agent
THF
The three-component couplings of allenes, aldehydes, and
silanes described herein are differentiated from the others
in that an allylic alcohol derivative is the major product,
where C–C bond formation occurs at the sp-hybridized
i-Pr
H
1a
3a
b
Entry
1
Reducing agent
Et SiH
Yield (%)
3a:2a
2r,s
carbon of the allene.
h
51
3
>95:5
>95:5
>95:5
n.d.
c
2
t-BuMe
i-Pr SiH
Ph MeSiH
Me PhSiH
(EtO) SiH
Ph SiH2
Et
2
fSiH
53
24
d,e
3
3
d
f
f
2. Results
4
2
<5
<5
<5
<5
<5
d
5
2
n.d.
n.d.
n.d.
n.d.
6
7
8
3
Triethylborane (Et B) has emerged as an efficient and func-
3
2
tional group-tolerant reducing agent in several nickel-
catalyzed reactions developed by our group and by others,
such as reductive coupling reactions of a diene, an alkyne,
g
f
2
Zn
a
General procedure: to a solution of Ni(cod)
(10 mol %) were added the reducing agents (200 mol %) and the aldehyde
200 mol %). Allene 1a (100 mol %) in THF was added to the reaction
2 3
(10 mol %) and Cyp P
7
or an enyne with an aldehyde, ketone, epoxide, or imine.
(
Thus the starting point for our investigations of the reductive
coupling reactions between allenes and aldehydes com-
menced with a Ni(cod) /Et B system. A mixture of allene
mixture over 8–12 h. The reaction mixture was stirred for 18 h at room
temperature.
Isolated yield.
Cyp P (20 mol %) was used instead of 10 mol %.
3
Cyclohexanecarboxaldehyde (300 mol %) was used instead of isobutyral-
dehyde.
b
c
d
2
3
1
a, isobutyraldehyde, Ni(cod) , an additive, and Et B pro-
2 3
0
vided two major coupling products, 2a and 3a (Table 1).
Certain additives improved the yield significantly. Phos-
phines Cyp P and (o-anis) P provided slightly better yields
e
f
ꢀ
The reaction was heated to 50 C in toluene.
3
3
Reducing agent (300 mol %) was used.
Diethylether was used as the solvent.
Average of two runs.
g
h
(
2
entries 3 and 5) than tributylphosphine and NMDPP (entries
and 4). Dropwise addition of the allene further increased
the yield, possibly due to a minimization of oligomerization
of the allene (entries 8 and 9). Without this mode of addition,
a substantial amount of 1b oligomerized under the reaction
conditions, affording 2k in <5% yield (entries 6 and 7).
Allylic alcohol 2 predominated over 3 in all cases regardless
of the presence of additives (entries 1–9).
trisubstituted allylic alcohol 2a was not observed in an NMR
spectrum of any of the crude reaction mixtures. Several com-
mercially available silanes were examined next. With Cyp3P
as the supporting ligand, Et SiH and tert-butyldimethyl-
3
silane (t-BuMe SiH) provided moderate yields of 3a
2
0
(
Table 2, entries 1 and 2). Triisopropylsilane afforded 3a
In contrast to these cases using Et B, those in which triethyl-
3
silane (Et SiH) was employed afforded geminally disub-
3
stituted allylic alcohol as the exclusive three-component
coupling product, along with a product corresponding to
hydrosilylation of the allene (Table 2, entry 1). Remarkably,
only upon heating (entry 3). Under similar conditions other
silanes did not provide 3a in significant yields (entries 4–7).
Diethylzinc in ether did not provide the desired reductive
coupling (entry 8).
Solvent and ligand effects were briefly examined (Tables 3
and 4). Although toluene, ethyl acetate, and methanol could
also be used, tetrahydrofuran (THF) was found to be the best
a
Table 1. Additive effects in the Ni(cod)
2
/Et
3
B system
cat. Ni(cod)2,
OH
OH
i-Pr
[
additive]
O
a
R
•
+
+
i-Pr
R
R
Table 3. Ligand ratio and solvent effects
i-Pr
H
Et3B
THF
Me
cat. Ni(cod) ,
2
OSiEt3
1a : R = Cy
2a : R = Cy
2k : R = Ph
3a' : R = Cy
3k' : R = Ph
O
Cyp P
3
•
1b : R = Ph
+
i-Pr
i-Pr
H
Et3SiH
THF
b
Yield (%) 2+3
0
0
Entry
Allene
Additive
None
2:3
1a
3a
1
2
3
4
5
6
7
1a
1a
1a
1a
1a
1b
1b
1b
1a
9
10
25
15
26
<5
<5
24
50
n.d.
n.d.
6:1
n.d.
2:1
n.d.
n.d.
n.d.
8:1
Bu
Cyp
NMDPP
3
P
b
Entry
Ligand (mol %)
Solvent
Yield (%)
c
3
P
c
1
2
3
4
5
6
7
8
None
10
20
10
20
10
20
10
THF
THF
THF
EtOAc
EtOAc
MeOH
MeOH
Toluene
<5
51
c
(o-Anis)
(o-Anis)
3
P
P
3
50
40
21
36
27
46
Cyp
Cyp
Cyp
3
P
3
P
3
P
d
8
d
9
a
General procedure: to a mixture of Ni(cod)
2
(20 mol %) and an additive
40 mol %) in THF were added the aldehyde, Et B, and the allene at
3
room temperature under argon. The reaction was stirred for 18 h at
room temperature.
(
a
2 3
General procedure: to a solution of Ni(cod) (10 mol %) and Cyp P were
added Et SiH (200 mol %) and the aldehyde (200 mol %). Allene 1a
3
b
c
d
0
Isolated yield of 2 and 3 .
(100 mol %) in THF was added to the reaction mixture over 4 h. The
reaction mixture was stirred for 18 h at room temperature.
Isolated yield.
Cyp¼cyclopentyl. NMDPP¼neomenthyldiphenylphosphine.
The allene was dissolved in THF and added to the reaction mixture via
a syringe pump over 1–3 h.
b
c
Average of two runs.

11352
S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
a
a
Table 4. Ligand screen
Table 5. Reaction scope
R1 OSiR3
cat. Ni(cod)2,
R1
Ni(cod)
2
OSiEt3
O
O
ligand
Cyp3P
R3SiH
•
+
R2
1
R3
R2
Cy
i-Pr
•
H
R
THF
i-Pr
H
Et3SiH
THF
a : R = Cy, R2 = H
2
1
1a
3a
1
2
1
b : R = Ph, R = H
1
2
1
c : R = R = n-C5H11
b
Entry
Ligand
Cyp
Yield (%)
c
1
2
3
4
5
6
7
3
P
51
Entry Allene Aldehyde Silane
Product
Yield
(%)
b
Cy
Bu
3
P
P
41
<10
<10
<10
<10
<10
3
OSiEt3
Me
(o-Anis)
3
P
Ph
3
P
1
2
3
4
5
6
7
1a
1a
1a
1a
1a
1a
1c
i-Pr
i-Pr
Cy
Et SiH
3
3a 52
NMDPP
BINAP
Me
a
OSit-BuMe2
General procedure: to a solution of Ni(cod)
10 mol %) were added Et
2
(10 mol %) and ligand
SiH (200 mol %) and the aldehyde (200
mol %). Allene 1a (100 mol %) in THF was added to the reaction mixture
over 4 h. The reaction mixture was stirred for 18 h at room temperature.
Isolated yield.
Me
(
3
t-BuMe
2
SiH
3b 71
Me
b
c
OSiEt3
Average of two runs.
Et
3
SiH
3c 46
solvent for this coupling reaction (Table 3, entry 2). The
nickel/ligand ratio was also found to be an important vari-
able. A 1:1 ratio of Ni(cod) and Cyp P was optimal, regard-
less of the choice of solvent (Table 3, entries 2–7). Most
strikingly, among phosphines examined, only large and elec-
tron donating ones such as Cy P and Cyp P were compatible
OSit-BuMe2
3d 73
Cy
2
t-BuMe SiH
2
3
OSii-Pr3
3
3
Cy
i-Pr SiH
3
3e 24
with the Ni/Et SiH system (Table 4, entries 1 and 2). The
3
N-heterocyclic carbene IPr, which is also large and is also
a strong electron donor, was also an excellent ligand for
this coupling reaction (vide infra). Smaller phosphines
such as Bu P and Ph P and bidentate ligand BINAP only
afforded a trace amount of coupling product 3a (Table 4,
entries 3–7). Finally, increasing the amount of aldehyde and
silane to 300 mol % further increased the yield (Table 5).
OSit-BuMe2
3f 86
c
Ph
t-BuMe
2
2
2
SiH
SiH
3
3
C5H11 OSit-BuMe2
Me
i-Pr
t-BuMe
3g 75
C5H11
Me
C5H11 OSit-BuMe2
N
N
N
N
8
9
1c
1c
1b
Cy
t-BuMe
t-BuMe
t-BuMe
SiH C H
3h 68
5
11
IPr =
,
IMes =
C5H11 OSit-BuMe2
n-Bu
Ph
2
2
SiH
SiH
3i 35
C5H11
Me
The catalyst system derived from Ni(cod) and Cyp P was
2
3
found to promote the coupling of 1a, 1b, and 1c with various
aliphatic and aromatic aldehydes in good yield and excellent
regioselectivity when a silane was employed as a reducing
agent (Table 5). In all cases, carbon–carbon bond formation
OSit-BuMe2
d
e
1
0
3j 56 (5)
2
occurred at the sp-hybridized carbon (rather than the sp -
a
General procedure: to a solution of Ni(cod)
10 mol %) were added Et
2
(10 mol %) and Cyp
SiH (300 mol %) and the aldehyde (300
3
P
hybridized carbons) of the allenes (regioselectivity). No
trace of homoallylic alcohol product was observed in any
case. Also noteworthy was the fact that the more hindered
double bond reacted with the aldehyde, rather than the
less substituted double bond. This site selectivity was not
affected by the steric bulk around the allene. Allene 1c, pos-
sessing two geminal alkyl substituents, also underwent cou-
pling with aliphatic aldehydes with the same sense of site
selectivity as 1a and 1b (Table 5, entries 7–9).
(
3
mol %). Allene 1a (100 mol %) in THF was added to the reaction mixture
over 5–9 h. The reaction mixture was stirred for 18 h at room temperature.
Isolated yield.
b
c
3
Cyp P was replaced by IPr, and the reaction mixture was cooled to
ꢀ
78 C before the addition of allene 1a in one portion. The reaction
was warmed to room temperature over 8 h.
The general procedure was followed except that Cyp
IPr.
ꢁ
d
e
3
P was replaced by
3
Cyp P was employed as the ligand. Yield was determined by NMR of the
crude mixture versus DMF as an external standard.
The size of the silane, in contrast, did affect the yield of the
coupling product significantly. Switching from t-BuMe SiH
to Et SiH lowered the yield substantially (Table 5, entries
3
case. This phenomenon might be related to the relative size
of those two organosilanes. Triisopropylsilane (i-Pr SiH),
2
3
1–4) due to competing hydrosilylation of the allene and
more hydrosilylation of allene was observed in the latter
however, appeared to be too bulky for either the coupling
or hydrosilylation to occur efficiently (entry 5).

S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
11353
With Cyp P as the supporting ligand, oligomerization of 1b
3
excellent ligand for the coupling of allenes and aromatic al-
dehydes. Slow addition of 1a to the reaction mixture resulted
in smooth coupling with benzaldehyde, giving 3b in 65%
yield (entry 7). Furthermore, in contrast to the results ob-
tained with aliphatic aldehydes, slow addition of 1a was un-
necessary. When 1a was added to the reaction system in one
was pronounced, and 3j was obtained in only 5% yield (entry
10). Nevertheless, this problem was alleviated when Cyp3P
was replaced by IPr (entry 10), and the same regioselectivity
and site selectivity were observed as with Cyp P.
3
ꢀ
We have recently reported the nickel-catalyzed coupling of
chiral 1,3-disubstituted allenes and aromatic aldehydes us-
portion at ꢁ78 C, an increase in yield was observed (entry
8). In fact, in this case the reaction could also be conducted
at 0 C without the use of dropwise addition, but a slight
2
r,s
ꢀ
decrease in yield was observed (entry 9).
ing the Ni(cod) /Et SiH system.
While N-heterocyclic
carbene IPr provided similar site selectivity and regioselec-
2
3
tivity as Cyp P, only IPr provided complete chirality transfer
3
from an enantiomerically enriched allene to the product.
Moreover, it was also found that slow addition of these
Success with IPr as the supporting ligand in the allene–
aldehyde coupling reactions led us to explore other NHC
derivatives. A few chiral NHC ligands were evaluated in
the terminal allene–aldehyde coupling reaction, but thus
far the highest observed enantioselectivity is 24%. The enan-
tiomeric excess remains to be improved (Scheme 1).
1
,3-disubstituted allenes was not necessary as long as the
ꢀ
ingly, a set of experiments were conducted to determine
allene was added to the reaction mixture at ꢁ78 C. Accord-
whether Cyp P or IPr was the better ligand for the coupling
3
of terminal allenes and aldehydes and whether the mode of
addition affected the yield of the reaction (Table 6).
O
2
Ni(cod) (10 mol%)
4
(20 mol%)
Si
O
Cyp P was the more efficient ligand for the coupling of ter-
3
KOt-Bu (20 mol%)
t-BuMe2SiH (300 mol%)
minal allenes and aliphatic aldehydes (Table 6, entries 1–4).
The N-heterocyclic carbene IPr, however, was the ligand of
choice for the coupling with aromatic aldehydes (entries
THF RT
(100 mol%) (300 mol%)
5
mixture allowed coupling with isobutyraldehyde to proceed
smoothly to afford 3b in good yield when Cyp P was the
3
–8). Slow addition of cyclohexylallene 1a to the reaction
Ph
Ph
Ph
N
Ph
N
N
N
Cl
Mes
N
N
Mes
Mes
Mes
O
O
ligand (entry 1). Under the same condition IPr afforded
3
N
N
BF4
b only in 12% yield (entry 3). Starting the reaction
at ꢁ78 C did not improve the yield of the coupling with
BF4
ꢀ
aliphatic aldehydes, regardless of whether Cyp P or IPr
was used (entries 2 and 4). On the other hand, IPr was an
4a
4b
4c
3
8
6% yield
4% ee
81% yield
< 5% ee
< 5% yield
2
Table 6. Comparison of Cyp
3
P and IPr as ligands
Ph
Ph
t-Bu
t-Bu
Ni(cod)2
Ligand
OSit-BuMe2
O
•
Me
Ph
Me
t-BuMe SiH
o-anis
N
N
o-anis
2
R
N
N
R
H
THF
Ph
1a
BF4
4d
< 5% yield
Br
4e
a
Entry R (aldehyde) Ligand Condition
Product
Yield
(
b
< 20% yield
%)
OSit-BuMe2
Scheme 1. Evaluation of chiral N-heterocyclic carbene ligands.
c
Me
1
i-Pr
3
Cyp P
A
3b 70
Me
3
. Discussion
2
3
4
i-Pr
i-Pr
i-Pr
B
A
B
<5
12
8
d
IPr
Since the first stable N-heterocyclic carbene (NHC) was iso-
lated by Arduengo, derivatives of NHCs were developed
and applied extensively as ligands on transition metals and
as organocatalysts. As ligands on metal catalysts, NHCs
are electron rich s donors, enabling processes such as the
oxidative addition of aryl chlorides
more reactive and stable olefin metathesis catalysts. The
Ni/NHC system catalyzed several transformations such as
reduction of aryl halides and imines, polymerization,
Heck reaction, and cycloaddition and annulation.
8
OSit-BuMe2
3f 23
c
5
Ph
Cyp
3
P
A
9,10
9
d,e
6
7
8
9
Ph
Ph
Ph
Ph
B
A
B
C
<5
65
86
71
and providing
d
IPr
9d
1
2a,b
12c,d
a
1
2e
12f
12g
Condition A: allene was diluted in THF and added to the reaction over 4 h
at room temperature and the reaction mixture continued to stir for 12 h.
Condition B: silane, aldehyde, and allene were each added consecutively
ꢀ
N-Heterocyclic carbene ligands have also been used in other
Ni-catalyzed reactions. In the nickel-catalyzed reductive
coupling of 1,3-diene and aldehydes, Mori and Sato showed
in one portion to the catalyst mixture at ꢁ78 C. The reaction was slowly
warmed to room temperature over 15 h. Condition C: same as condition B
except that the allene was added to the reaction mixture at 0 C instead
ꢀ
ꢀ
of ꢁ78 C.
that regioselectivity can be tuned by using either a phosphine
b
Yield was determined by NMR of the crude mixture versus DMF as an
external standard.
2w–bb
ligand or an N-heterocyclic carbene. Montgomery dem-
onstrated that the N-heterocyclic carbene IMes had a broad
substrate scope of alkynes in the nickel-catalyzed coupling
c
Ni(cod)
2
: PCyp
3
ratio was 1:1.
d
Ni(cod) : IPr ratio was 1:2.
2

11354
S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
2
g
of alkynes, aldehydes, and silanes. However, the same reac-
tion was sluggish when IMes was replaced by Bu P. A cross-
substitution pattern is obtained in a related nickel-catalyzed
coupling of alkenes, aldehydes, and silyl triflates that we
recently reported.
3
2
u
over experiment indicated that different mechanisms were
operating in these two cases and also explained the difference
in reactivity.
A further distinguishing characteristic is that the regioselec-
tivity and site selectivity of the nickel-catalyzed coupling of
allenes and aldehydes are distinctly different among the
R SiH, Et B, and R Zn systems (Scheme 3). C–C bond for-
The nickel-catalyzed coupling of allenes and aldehydes de-
scribed herein demonstrated that phosphines and N-hetero-
cyclic carbenes are complementary as supporting ligands
for nickel, depending on the nature of the aldehyde coupling
partner (aliphatic vs aromatic). In the nickel-catalyzed cou-
pling of allenes and aldehydes, N-heterocyclic carbene IPr
had a larger substrate scope with respect to the allene, en-
abling the coupling of alkyl allenes 1a and 1c and aryl allene
3
3
2
mation occurred between the sp-hybridized carbon of the
allene and the aldehyde in the R SiH and Et B systems
(Scheme 3, Eqs. 5 and 6). These two systems, however,
3
3
have the opposite site selectivity. Whereas in the R SiH sys-
3
tem addition occurs across the internal double bond, the less
substituted double bond reacts in the Et B system. The orga-
3
1
b. Although Cyp P did not tolerate aryl allene 1b, it did pro-
3
nozinc system developed by Montgomery also affords C–C
bond formation between the less substituted sp -hybridized
carbon of the allene and the aldehyde, but homoallylic alco-
hols are obtained (Scheme 3, Eq. 7). A related process, the
nickel-catalyzed dicarboxylation of an allene by Mori and
Sato C–C bond formation occurs between the sp-hybridized
2
mote coupling reactions with aliphatic aldehydes with
allenes bearing one aliphatic substituent (1a and 1c). The re-
duced yield that was observed with aliphatic aldehydes when
IPr was employed may have its origins in the basicity of this
supporting ligand. Being more basic than Cyp P, it is possible
3
that IPr was inactivated by deprotonation of the a-protons of
carbon of the allene and CO (Scheme 3, Eq. 8). Given these
2
1
1
aliphatic aldehydes. More experiments are necessary to
confirm this hypothesis, however, since there are examples
of aliphatic aldehydes being tolerated in reactions using
observations, it appears that R SiH, Et B, and R Zn each di-
3
3
2
rect the allene–aldehyde coupling through different mecha-
nisms. The formation of a nickellacycle has been proposed
as the first step in the catalytic cycle in all of these examples,
and thus R SiH, Et B, and R Zn may play a large role in di-
1
3
NHC ligands.
3
3
2
The nickel-catalyzed allene–aldehyde coupling described
herein is complementary also to the nickel-catalyzed cou-
pling reactions of alkynes and aldehydes (Scheme 2). The
allene–aldehyde coupling provides a different type of disub-
stituted allylic alcohol product (geminal, Eq. 2) from the
alkyne–aldehyde couplings (vicinal, Eqs. 3 and 4). For exam-
ple, the reductive coupling of the terminal alkyne 1-octyne
with benzaldehyde affords a trans-1,2-disubstituted allylic
alcohol with high selectivity using either the Ni(cod) /Bu P–
recting the formation and subsequent reactions of such
a nickellacycle species. One possibility is that Et B and
3
R Zn, being more Lewis acidic than R SiH, interact with
2
3
the aldehyde, giving a larger species that may be accommo-
dated in the nickellacycle in a very different arrangement
than the aldehyde itself. More studies are required to further
understand the mechanism of these nickel-catalyzed cou-
1
4
pling reactions of allenes and aldehydes.
2
3
Ni(cod)2
O
OSit-BuMe2
Et B system developed in our group (Eq. 3) or the Ni(cod) /
2
3
Cyp3P or IPr
NHC–Et SiH system developed by Montgomery (Eq. 4). In
3
contrast, the allene–aldehyde coupling described here pro-
vided 1,1-disubstituted allylic alcohol (Eq. 2). The same
H
t-BuMe2SiH
THF RT
Major
(
(
5)
6)
O
Ni(cod)2 (10 mol%)
IPr (20 mol%)
Si
Ni(cod)2
Cyp3P
O
OH
O
H
t-BuMe2SiH (300 mol%)
THF RT
H
Et3B
THF RT
1
00 mol%
300 mol%
86 % yield (2)
Major
Montgomery:
Jamison:
O
Ni(cod)2 (10 mol%)
Bu3P (20 mol%)
O
Ni(cod)2
Me OH
OH
Ph
Me
Me
n-hex
H
H
Me2Zn
Me
H
Ph
Et3B (200 mol%) n-hex
THF 0°C
THF RT
Me
Major
2
00 mol%
100 mol%
76 % yield
(7) 2t
(
(
3) 2b
Mori and Sato:
Montgomery:
O
Ni(cod)2 (10 mol%)
IMes (10 mol%)
1. Ni(cod)2
DBU
OH
Ph
CO2Me
n-hex
H
H
Me2Zn
Et3SiH (200 mol%)
n-hex
CO2
(1atm)
CO2Me
Ph
•
SiMe3
THF RT Ph
THF RT
2
. HCl
. CH2N2
SiMe3
1
20 mol%
100 mol%
82 % yield
4) 2g
3
Major
(
8) 2q
Scheme 2. Comparison between allene–aldehyde coupling and alkyne–
aldehyde coupling.
Scheme 3. Nickel-catalyzed allene couplings.

S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
11355
4
. Conclusion
Facility. Chiral GC analysis was performed on a Varian
CP-3800 gas chromatograph fitted with Chiraldex B-PH,
B-DA, and G-TA capillary columns. Chiral HPLC analysis
was performed on a Hewlett-Packard 1100 chromatograph
equipped with a variable wavelength detector and Chiralcel
In summary, the nickel-catalyzed coupling of allenes, alde-
hydes, and silanes provides 1,1-disubstituted allylic alcohols
with high regioselectivity and high site selectivity. The opti-
mal ligand, however, is different for aliphatic (Cyp P) and
3
OD or OD-H columns. Specific rotations ([a] ) were mea-
D
aromatic (IPr) aldehydes. These transformations are com-
plementary to other allene–aldehyde coupling reactions.
Carbon–carbon bond formation occurs between the sp-hy-
bridized carbon of allene and aldehyde, regardless of ligand
type, as long as a silane is used as the reducing agent. The use
of chiral NHCs resulted in low enantiomeric excess to the
coupling product, but nevertheless represents the first exam-
ple of an enantioselective, nickel-catalyzed coupling of
sured on a Perkin–Elmer 241 polarimeter at 589 nm.
5.2. Preparation of allenes
5.2.1. Propa-1,2-dienyl-cyclohexane (1a). Prepared by the
method of Brandsma. Cyclohexyl-magnesium chloride
(50 mL, 100 mmol, 2 M in ether) was dissolved in anhy-
1
6
ꢀ
drous THF (80 mL) and cooled to ꢁ78 C under argon. After
14
allene and aldehyde. Applications to natural product syn-
thesis and further investigations to develop a highly enantio-
selective version of this reaction are ongoing.
10 min of cooling, a THF (8 mL) solution of anhydrous lith-
ium bromide (2 g) and anhydrous copper(I) bromide (1 g)
was added to the Grignard solution in one portion. The reac-
ꢀ
tion mixture was stirred for 20 min at ꢁ78 C. Propargyl
bromide (13.4 mL, 120 mmol) was dissolved in anhydrous
THF (10 mL) in an oven-dried round bottom flask and was
5. Experimental
ꢀ
cooled at ꢁ78 C for 15 min. Thepropargylbromide solution
5
.1. General
was taken up by a 50 mL syringe and added to the reaction
mixture over 30 min. During this time the reaction mixture
ꢀ
Unless otherwise noted, all reactions were performed under
an oxygen-free atmosphere of nitrogen or argon with rigid
exclusion of moisture from reagents and glassware. Tetra-
hydrofuran was distilled from a blue solution of sodium
benzophenone ketyl. Triethylsilane, triisopropylsilane, and
tert-butyldimethylsilane were purchased from Aldrich
Chemical Co. and were saturated with nitrogen before use.
Benzaldehyde was purchased from Aldrich Chemical Co.
and was distilled before use. All aliphatic aldehydes were
distilled over magnesium sulfate under argon before use.
was kept below ꢁ50 C with rigorous stirring. After the
addition was complete the reaction mixture was stirred for
ꢀ
30 min at ꢁ78 C. The dry ice/acetone bath was removed
and the reaction was allowed to warm to room temperature
and stirred for 3 h. The reaction mixture was poured into an
aqueous NH Cl solution (10 g NH Cl, 100 mL). The mixture
4
4
was extracted with 200 mL pentane. The aqueous layer was
extracted again with 100 mL pentane. The combined pentane
solution was washed repeatedly with water and finally with
brine. The solution was dried with MgSO and pentane was
4
Bis(cyclo-octadienyl)nickel(0) (Ni(cod) ) and tricyclopen-
2
removed in rotovap. Purification via flash chromatography
on silica followed by distillation afforded 1a as a colorless
oil (7.9 g, 65% yield). H NMR (500 MHz, CDCl , d): 5.10
3
tylphosphine were purchased from Strem Chemicals, Inc.,
stored under nitrogen atmosphere, and used without fur-
ther purification. 1,3-Bis-(2,6-di-isopropylphenyl)imidazol-
1
(q, J¼6.4 Hz, 1H), 4.69 (dd, J¼6.7, 3.4 Hz, 2H), 1.99 (m,
1
3
2-ylidene (NHC-IPr) was prepared according to literature
procedure.
1H), 1.80–1.02 (m, 11H); C NMR (125 MHz, CDCl , d):
3
1
5
207.6, 96.3, 75.6, 36.8, 33.2, 26.4, 26.2. IR (NaCl, thin
film): 2925, 2852, 2662, 1955, 1445, 839.
Analytical thin layer chromatography (TLC) was performed
using EM Science silica gel 60 F254 plates. The developed
chromatogram was analyzed by UV lamp (254 nm), etha-
nolic phosphomolybdic acid (PMA) or potassium permanga-
5.2.2. Propa-1,2-dienyl-benzene (1b). Prepared accord-
1
7
ing to the method of Myers. Triphenylphosphine (5 g,
15 mmol) was dissolved in THF (20 mL). The solution
was cooled in a MeOH/ice bath, and diethylazodicarboxy-
late (DEAD) (2.4 mL, 15 mmol) was added to the solution
over 1 min. The solution was stirred for 10 min below
nate (KMnO ). Liquid chromatography was performed
4
using a forced flow (flash chromatography) of the indicated
solvent system on Silicycle silica gel (230–400 mesh). H
1
13
ꢀ
and C NMR spectra were recorded on Varian 300 MHz,
Varian 500 MHz or Bruker 400 MHz spectrometer in
ꢁ10 C. 1-Phenyl-2-propyn-1-ol (1.22 mL, 10 mmol) in
THF (10 mL) was added. THF (5 mL) was used to rinse
the rest of the alcohol into the reaction mixture. The mixture
was stirred for 10 min, and o-nitrobenzenesulfonylhydra-
1
CDCl , unless otherwise noted. Chemical shifts in
H
NMR spectra are reported in parts per million (ppm) on
3
1
7b
the d scale from an internal standard of residual chloroform
(
zine
(3.3 g, 15 mmol in 20 mL THF) was added. The
ꢀ
7.27 ppm). Data are reported as follows: chemical shift,
multiplicity (s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼
mixture was kept below 0 C for 2 h and was allowed to
warm to room temperature and stirred for 16 h. The reaction
was diluted with pentane (300 mL) and washed five times
with ice cold water to remove THF. The mixture was dried
quartet, m ¼ multiplet, br ¼ broad), coupling constant in
1
3
Hertz (Hz), and integration. Chemical shifts of C NMR
spectra are reported in parts per million from the central
peak of CDCl (77.23 ppm) on the d scale. Infrared (IR)
with MgSO . Column chromatography in pentane afforded
4
1
1b as a colorless oil (250 mg, 21% yield). H NMR
(400 MHz, CDCl , d): 7.40–7.28 (m, 4H), 7.25–7.16 (m,
3
spectra were recorded on a Perkin–Elmer 2000 FTIR.
High-resolution mass spectra (HRMS) were obtained on a
Bruker Daltonics APEXII 3 Tesla Fourier Transform Mass
Spectrometer by Dr. Li Li of the Massachusetts Institute of
Technology, Department of Chemistry Instrumentation
3
1H), 6.18 (t, J¼6.8 Hz, 1H), 5.16 (d, J¼6.8 Hz, 2H).
5.2.3. 6-Vinylidene-undecane (1c). 2-Octyn-1-ol (4.3 mL,
30 mmol) and triethylamine (17 mL, 120 mmol) were

11356
S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
dissolvedinanhydrousdichloromethane (35 mL)ina100 mL
round bottom flask. The reaction mixture was stirred
8 h. The reaction was stirred at room temperature for another
12 h. THF and other volatiles were removed under reduced
pressure. The crude mixture was diluted in hexane.
Purification via flash chromatography on silica afforded
the allylic alcohol coupling product.
ꢀ
0 mmol) was added dropwise. After the addition was com-
for 10 min at ꢁ78 C. Methanesulfonyl chloride (7 mL,
9
ꢀ
plete the reaction was stirred for 2 h at ꢁ78 C. The dry ice/
acetone bath was replaced by a sodium chloride/ice
slush bath. The reaction mixture was stirred for 90 min
5.3.2. Standard procedure B. A 10 mL round bottom flask
and a stir bar were oven-dried and brought into a glove box.
Ni(cod) (7 mg, 0.025 mmol, 10 mol %) and tricyclopentyl-
2
ꢀ
at ꢁ10 C. The reaction mixture was poured into water
(
50 mL). The organic layer was separated. The aqueous layer
was extracted with dichloromethane. The combined di-
chloromethane solution was washed with water and dried
with MgSO . Purification via flash chromatography on silica
afforded methanesulfonic acid oct-2-ynyl ester. In an oven-
dried 50 mL round bottom flask magnesium turning
phosphine (7 mL, 0.025 mmol, 10 mol %) were added to the
flask. The flask was sealed with a septum and electrical tape.
The sealed flask was brought out of the glove box and
connected to an argon line. The catalyst mixture was dis-
solved in THF or toluene (0.5 mL) at room temperature under
argon and stirred for 10 min at room temperature. Silane
(0.75 mmol, 300 mol %) was added in one portion. Aldehyde
(0.75 mmol, 300 mol %) was added in one portion. Finally
allene (0.25 mmol, 100 mol %) in THF or toluene (2 mL)
was added into the reaction mixture at room temperature
via a syringe pump over 3.5 h. The reaction was stirred at
room temperature for another 12 h. THF and other volatiles
were removed under reduced pressure. The crude mixture
was diluted in hexane. Purification via flash chromatography
on silica afforded the allylic alcohol coupling product.
4
(0.56 g) was stirred in anhydrous THF (4 mL). A few drops
of 1,2-dibromoethane were added. Gentle heating was ap-
plied to initiate the reaction. n-Pentylbromide (2.84 mL,
2
3 mmol) was added slowly at a rate that caused and main-
tained a gentle reflux. When most of the magnesium vanished
more n-pentylbromide (1 mL) was added. The solution
was cooled down to slightly warm (pentylmagnesium
bromidewas not soluble in cold THF). Meanwhile anhydrous
CuBr (3.44 g, 24 mmol) and anhydrous LiBr (2.08 g,
2
4 mmol) were dissolved in anhydrous THF (40 mL) in an
ice bath and stirred vigorously. Once the mixture became
homogeneous, the warm pentylmagnesium bromide solution
was added via a syringe with a thick needle. The reaction
5.3.3. Standard procedure C. A 10 mL round bottom flask
and a stir bar were oven-dried and brought into a glove box.
Ni(cod) (10 mg, 0.036 mmol, 15 mol %) and tricyclopen-
2
ꢀ
mixture was stirred rigorously for 20 min at 0 C. The reac-
ꢀ
tion mixture was cooled to ꢁ78 C. Methanesulfonic acid
tylphosphine (10 mL, 0.036 mmol, 15 mol %) were added
to the flask. The flask was sealed with a septum and electrical
tape. The sealed flask was brought out of the glove box
and connected to an argon line. The catalyst mixture was
dissolved in THF (0.5 mL) at room temperature under
argon and stirred for 10 min at room temperature. Silane
(0.75 mmol, 300 mol %) was added in one portion. Alde-
hyde (0.75 mmol, 300 mol %) was added in one portion.
Finally allene (0.25 mmol, 100 mol %) in THF or toluene
(3 mL) was added into the reaction mixture at room temper-
ature via a syringe pump over 5 h. The reaction was stirred at
room temperature for another 12 h. THF and other volatiles
were removed under reduced pressure. The crude mixture
was diluted in hexane. Purification via flash chromatography
on silica afforded the allylic alcohol coupling product.
oct-2-ynyl ester in anhydrous THF (30 mL) was added to
the reaction mixture dropwise via a syringe pump over
3
0 min. Once the addition was complete, the dry ice/acetone
bath was allowed to warm back to room temperature and
stirred for 12 h. The reaction mixture was quenched with ice
cold saturated NH Cl (80 mL) and extracted with 250 mL
4
hexane. The aqueous layer was extracted again with hexane
until the aqueous layer became blue. The combined hexane
solution was then washed two times with saturated NH Cl,
4
once with water (50 mL), and finally with brine (50 mL).
Purification via flash column chromatography on silica
afforded 6-vinylidene-undecane 1c (2.54 g, 47% from
1
2
-octyn-1-ol). H NMR (500 MHz, CDCl , d): 4.64 (p,
3
J¼3.0 Hz, 2H), 1.96–1.90 (m, 4H), 1.46–1.39 (m, 4H),
1
3
1
(
.35–1.26 (m, 8H), 0.94–0.87 (t, J¼7.0 Hz, 6H); C NMR
125 MHz, CDCl , d): 205.9, 103.6, 75.4, 32.3, 31.8, 27.5,
3
5.3.4. (1-Cyclohexylmethyl-1-isopropyl-allyloxy)-tri-
ethylsilane (3a). The reaction of propa-1,2-dienyl-cyclo-
hexane (1a) (148 mL, 1 mmol) and isobutyraldehyde (272 mL,
2
1
2.8, 14.3. IR (thin film NaCl): 2957, 2929, 2873, 2859,
958, 843.
3
ethylsilane (480 mL, 3 mmol) in THF following the standard
mmol) with Ni(cod) , tricyclopentylphosphine, and tri-
2
5
5
.3. Nickel-catalyzed couplings of allenes and aldehydes
procedure A described above afforded 3a in 52% yield as
a colorless oil. H NMR (500 MHz, CDCl , d): 4.98 (m,
1
.3.1. Standard procedure A. A 25 mL round bottom flask
3
and a stir bar were oven-dried and brought into a glove box.
Ni(cod) (28 mg, 0.1 mmol, 10 mol %) and tricyclopentyl-
1H), 4.80 (m, 1H), 3.72 (d, J¼6.1 Hz, 1H), 2.00–1.00 (m,
14H), 0.96 (t, J¼8.0 Hz, 9H), 0.85 (t, J¼6.32 Hz, 6H), 0.59
2
1
3
phosphine (28 mL, 0.1 mmol, 10 mol %) were added to the
flask. The flask was sealed with a septum and electrical
tape. The sealed flask was brought out of the glove box
and connected to an argon line. The catalyst mixture was dis-
solved in THF (2 mL) at room temperature under argon and
stirred for 10 min at room temperature. Silane (3 mmol,
(q, J¼7.98 Hz, 6H); C NMR (125 MHz, CDCl , d):
3
149.0, 111.0, 82.0, 39.4, 35.9, 34.1, 33.7, 31.8, 26.9, 26.7,
26.6, 20.1, 17.6, 7.3, 5.2; IR (NaCl, thin film): 3077, 2955,
2923, 2877, 2853, 1811, 1646, 1459, 1449, 1414, 1063,
1007, 904, 834, 740, 725; HRMS-ESI (m/z): [M+Na] calcd
for C H OSi, 333.2584; found, 333.2593.
+
1
9 38
3
3
00 mol %) was added in one portion. Aldehyde (3 mmol,
00 mol %) was added in one portion. Finally allene
5.3.5. tert-Butyl-(2-cyclohexylmethyl-1-isopropyl-allyl-
oxy)-dimethylsilane (3b). The reaction of propa-1,2-dienyl-
cyclohexane (1a) (148 mL, 1 mmol) and isobutyraldehyde
(1 mmol, 100 mol %) in THF (8 mL) was added into the re-
action mixture at room temperature via a syringe pump over

S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
11357
(272 mL, 3 mmol) with Ni(cod) , tricyclopentylphosphine,
and tert-butyldimethylsilane (498 mL, 3 mmol) in THF fol-
5.3.9. tert-Butyl-(2-cyclohexylmethyl-1-phenyl-allyloxy)-
dimethylsilane (3f). A 7 mL vial and a stir bar were oven-
dried and brought into a glove box. Ni(cod) (7 mg, 0.025
mmol, 10 mol %) and IPr (19 mg, 0.05 mmol, 20 mol %)
were added to the flask. The vial was sealed with a septum
and electrical tape. The sealed vial was brought out of the
glove box and connected to an argon line. The catalyst
mixture was dissolved in THF (3 mL) at room temperature
2
lowing the standard procedure A described above afforded
3
2
1
b in 71% yield as a colorless oil. H NMR (500 MHz,
CDCl , d): 4.98 (m, 1H), 4.80 (m, 1H), 3.70 (d, J¼5.8 Hz,
3
1
4
H), 1.98–1.60 (m, 9H), 1.58–1.40 (m, 1H), 1.38–1.10 (m,
H), 0.92 (s, 9H), 0.843 (dd, J¼6.9, 6.6 Hz, 6H), 0.04
1
3
(
1
2
s, 3H), ꢁ0.02 (s, 3H); C NMR (125 MHz, CDCl , d):
3
48.8, 111.1, 81.5, 39.7, 35.7, 34.2, 33.6, 31.7, 26.9, 26.7,
6.6, 26.2, 20.3, 18.5, 17.3, ꢁ4.1, ꢁ4.8; IR (NaCl, thin
under argon and stirred for 10 min at room temperature.
ꢀ
The mixture was cooled to ꢁ78 C. t-BuMe SiH (125 mL,
2
film): 3077, 2957, 2927, 2855, 1647, 1463, 1251, 1057,
863, 838, 774; HRMS-ESI (m/z): [M+Na] calcd for
C H OSi, 333.2584; found, 333.2590.
0.75 mmol, 300 mol %) was added in one portion. Benzalde-
hyde (76 mL, 0.75 mmol, 300 mol %) was added in one
portion. Finally allene (37 mL, 0.25 mmol, 100 mol %) was
+
1
9 38
ꢀ
added. The reaction was stirred for 2 h at ꢁ78 C. The dry
5
.3.6. (1-Cyclohexyl-2-cyclohexylmethyl-allyloxy)-tri-
ice/acetone bath was then covered with aluminum foil and
the temperature was slowly raised to room temperature.
The reaction was stirred for a total of 15 h. THF and
other volatiles were removed under reduced pressure.
Purification via flash chromatography on silica afforded 3f
ethylsilane (3c). The reaction of propa-1,2-dienyl-cyclohex-
ane (1a) (148 mL, 1 mmol) and cyclohexanecarboxaldehyde
(361 mL, 3 mmol) with Ni(cod) , tricyclopentylphosphine,
2
and triethylsilane (480 mL, 3 mmol) in THF following the
1
standard procedure A described above afforded 3c in 46%
yield as a colorless oil. H NMR (500 MHz, CDCl , d):
in 86% yield as a colorless oil. H NMR (400 MHz,
CDCl , d): 7.35–7.20 (m, 5H), 5.24 (s, 1H), 5.10 (s, 1H),
1
3
3
4
0
6
4
2
2
8
.93 (m, 1H), 4.79 (m, 1H), 3.72 (d, J¼6.7 Hz, 1H), 2.00–
4.83 (s, 1H), 1.80 (m, 1H), 1.70 (m, 6H), 1.45 (m, 1H),
1.15 (m, 3H), 0.92 (s, 9H), 0.75 (m, 2H), 0.07 (s, 3H),
.80 (m, 24H), 0.96 (t, J¼7.6 Hz, 9H), 0.59 (q, 7.9 Hz,
1
3
13
H); C NMR (125 MHz, CDCl , d): 148.6, 111.1, 81.8,
3
ꢁ0.04 (s, 3H); C NMR (100 MHz, CDCl , d): 150.0,
3
1.5, 39.0, 35.6, 34.1, 33.7, 30.4, 28.4, 26.9, 26.9,
6.7, 26.7, 26.6, 26.5, 7.3, 5.2; IR (NaCl, thin film): 3076,
923, 2876, 2852, 1809, 1644, 1449, 1239, 1063, 1008,
143.7, 128.1, 127.1, 126.7, 110.9, 78.4, 39.5, 35.8, 33.7,
33.480, 26.8, 26.6, 26.5, 26.1, 18.5, ꢁ4.7, ꢁ4.7; IR (NaCl,
thin film): 2926, 2854, 1472, 1449, 1252, 1090, 1065, 867,
+
+
98, 827, 740; HRMS-ESI (m/z): [M+Na] calcd for
835, 776, 699. HRMS-ESI (m/z): [M+Na] calcd for
C H OSi, 367.2428; found, 367.2431.
C H OSi, 373.2897; found, 373.2892.
2
2
42
22 38
5
.3.7. tert-Butyl-(1-cyclohexyl-2-cyclohexylmethyl-allyl-
5.3.10. tert-Butyl-(1-isopropyl-2-methylene-3-pentyl-oc-
tyloxy)-dimethylsilane (3g). The reaction of 6-vinylidene-
undecane (1c) (57 mL, 0.25 mmol) and isobutyraldehyde
oxy)-dimethylsilane (3d). The reaction of propa-1,2-dienyl-
cyclohexane (1a) (148 mL, 1 mmol) and cyclohexane-
carboxaldehyde (361 mL, 3 mmol) with Ni(cod) , tricyclo-
(68 mL, 0.75 mmol) with Ni(cod) , tricyclopentylphosphine,
2
2
pentylphosphine, and tert-butyldimethylsilane (498 mL,
3 mmol) in THF following the standard procedure A
described above afforded 3d in 73% yield as a colorless
and tert-butyldimethylsilane (125 mL, 0.75 mmol) in THF
following the standard procedure C described above
1
afforded 3g in 75% yield as a colorless oil. H NMR
(500 MHz, CDCl , d): 5.10 (m, 1H), 4.83 (m, 1H), 3.79
1
oil. H NMR (500 MHz, CDCl , d): 4.94 (m, 1H), 4.80
3
3
(
(
m, 1H), 3.70 (d, J¼6.1 Hz, 1H), 2.00–0.80 (m, 24H), 0.91
(br s, 1H), 1.80–1.68 (m, 2H), 1.46–1.18 (m, 22H), 0.97
(d, J¼6.7 Hz, 3H), 0.94 (s, 9H), 0.93–0.85 (m, 6H), 0.76
1
3
s, 9H), 0.03 (s, 3H), ꢁ0.02 (s, 3H); C NMR (125 MHz,
1
3
CDCl , d): 148.4, 111.2, 81.4, 41.5, 39.3, 35.6, 34.2,
3
(d, J¼6.7 Hz, 3H); C NMR (125 MHz, CDCl , d): 154.7,
3
3
1
1
(
3
3.7, 30.7, 28.1, 26.9, 26.9, 26.7, 26.7, 26.6, 26.6, 26.2,
8.5, ꢁ4.1, ꢁ4.7; IR (NaCl, thin film): 3076, 2926,
108.3, 79.7, 41.4, 36.2, 34.0, 32.5, 32.5, 30.9, 27.5, 26.7,
26.2, 22.9, 22.9, 21.4, 18.5, 14.9, 14.4, 14.3, ꢁ3.9, ꢁ4.8;
IR (NaCl, thin film): 2958, 2929, 2858, 1647, 1463, 1250,
645, 1450, 1251, 1061, 900, 837, 774; HRMS-ESI
+
+
m/z): [M+Na] calcd for C H OSi, 373.2897; found,
2
1056, 902, 865, 839, 774. HRMS-ESI (m/z): [M+Na] calcd
for C H OSi, 391.3367; found, 391.3365.
2 42
73.2893.
2
3 48
5
.3.8. (1-Cyclohexyl-2-cyclohexylmethyl-allyloxy)-triiso-
5.3.11. tert-Butyl-(1-cyclohexyl-2-methylene-3-pentyl-oc-
tyloxy)-dimethylsilane (3h). The reaction of 6-vinylidene-
undecane (1c) (57 mL, 0.25 mmol) and cyclohexanecar-
propylsilane (3e). The reaction of propa-1,2-dienyl-cyclo-
hexane (1a) (37 mL, 0.25 mmol) and cyclohexanecarbox-
aldehyde (90 mL, 0.75 mmol) with Ni(cod) , tricyclopentyl-
boxaldehyde (90 mL, 0.75 mmol) with Ni(cod) , tricyclo-
2
2
phosphine, and triisopropylsilane (154 mL, 0.75 mmol) in
toluene following the standard procedure B described
above (except that 1 mL toluene was used to dissolve
pentylphosphine, and tert-butyldimethylsilane (125 mL,
0.75 mmol) in THF following the standard procedure B
described above afforded 3h in 68% yield as a colorless
oil. H NMR (500 MHz, CDCl , d): 5.06 (m, 1H), 4.83 (m,
1
Ni(cod) and tricyclopentylphosphine) afforded 3e in 24%
2
3
1
yield as a colorless oil. H NMR (500 MHz, CDCl , d):
3
1H), 3.76 (br s, 1H), 1.90–1.00 (m, 28H), 0.94 (s, 9H),
0.90 (m, 6H), 0.03 (s, 3H), 0.03 (s, 3H); C NMR
1
3
4
0
.96 (m, 1H), 4.82 (m, 1H), 3.95 (d, J¼5.8 Hz, 1H), 2.00–
1
3
.80 (m, 25H), 1.10 (s, 18H); C NMR (100 MHz,
(125 MHz, CDCl , d): 154.2, 108.4, 79.8, 41.2, 41.1, 36.2,
3
CDCl , d): 148.6, 110.9, 81.9, 42.8, 39.5, 35.6, 34.2, 33.8,
3
34.2, 32.5, 32.5, 32.1, 27.4, 27.1, 27.0, 26.8, 26.6, 26.3,
25.5, 22.9, 22.925, 18.5, 14.4, 14.3, ꢁ3.9, ꢁ4.7; IR (NaCl,
thin film): 2929, 2856, 1647, 1463, 1251, 1103, 902, 835,
3
(
0.2, 28.6, 26.9, 26.8, 26.8, 26.7, 26.6, 18.5, 13.1; IR
NaCl, thin film): 3079, 2924, 2865, 2852, 1645.71, 1449,
+
+
1086, 1062, 883; HRMS-ESI (m/z): [M+Na] calcd for
C H OSi, 415.3367; found, 415.3366.
774. HRMS-ESI (m/z): [M+Na] calcd for C H OSi,
2
6 52
431.3680; found, 431.3700.
2
5 48

11358
S.-S. Ng, T. F. Jamison / Tetrahedron 62 (2006) 11350–11359
5
.3.12. tert-Butyl-dimethyl-(2-methylene-3-pentyl-1-pro-
Chem. Soc. 2003, 125, 8076–8077; (f) Patel, S. J.; Jamison,
T. F. Angew. Chem., Int. Ed. 2003, 42, 1364–1367; (g)
Mahandru, G. M.; Liu, G.; Montgomery, J. J. Am. Chem.
Soc. 2004, 126, 3698–3699; (h) Patel, S. J.; Jamison, T. F.
Angew. Chem., Int. Ed. 2004, 43, 3941–3944; (i) Kimura, M.;
Ezoe, A.; Mori, M.; Tamaru, Y. J. Am. Chem. Soc. 2005,
127, 201–209; (j) Knapp-Reed, B.; Mahandru, G. M.;
Montgomery, J. J. Am. Chem. Soc. 2005, 127, 13156–13157;
(k) Luanphaisarnnont, T.; Ndubaku, C. O.; Jamison, T. F.
Org. Lett. 2005, 7, 2937–2940; Enyne: (l) Miller, K. M.;
Jamison, T. F. J. Am. Chem. Soc. 2004, 126, 15342–15343;
(m) Miller, K. M.; Luanphaisarnnont, T.; Molinaro, C.;
Jamison, T. F. J. Am. Chem. Soc. 2004, 126, 4130–4131; (n)
Miller, K. M.; Colby, E. A.; Woodin, K. S.; Jamison, T. F.
Adv. Synth. Catal. 2005, 347, 1533–1536; (o) Miller, K. M.;
Jamison, T. F. Org. Lett. 2005, 7, 3077–3080; (p) Moslin,
R. M.; Jamison, T. F. Org. Lett. 2006, 8, 455–458; Allene: (q)
Takimoto, M.; Kawamura, M.; Mori, M.; Sato, Y. Synlett
2005, 2019–2022; (r) Ng, S.-S.; Jamison, T. F. J. Am. Chem.
Soc. 2005, 127, 7320–7321; (s) Ng, S.-S.; Jamison, T. F.
Tetrahedron 2005, 61, 11405–11417; (t) Song, M.;
Montgomery, J. Tetrahedron 2005, 61, 11440–11448; Alkene:
(u) Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127,
14194–14195; Diene: (v) Kimura, M.; Ezoe, A.; Shibata, K.;
Tamaru, Y. J. Am. Chem. Soc. 1998, 120, 4033–4034; (w)
Kimura, M.; Fujimatsu, H.; Ezoe, A.; Shibata, K.; Shimizu,
M.; Matsumoto, S.; Tamaru, Y. Angew. Chem., Int. Ed. 1999,
38, 397–400; (x) Sato, Y.; Sawaki, R.; Saito, N.; Mori, M.
J. Org. Chem. 2002, 67, 656–662; (y) Sato, Y.; Takanashi, T.;
Hoshiba, M.; Mori, M. J. Organomet. Chem. 2003, 688, 36–
48; (z) Takimoto, M.; Nakamura, Y.; Kimura, K.; Mori, M.
J. Am. Chem. Soc. 2004, 126, 5956–5957; (aa) Sawaki, R.;
Sato, Y.; Mori, M. Org. Lett. 2004, 6, 1131–1133; (bb)
Takimoto, M.; Kajima, Y.; Sato, Y.; Mori, M. J. Org. Chem.
2005, 70, 8605–8606; Nickel-catalyzed reductive coupling
review: (cc) Montgomery, J. Angew. Chem., Int. Ed. 2004, 43,
pyl-octyloxy)-silane (3i). The reaction of 6-vinylidene-
undecane (1c) (57 mL, 0.25 mmol) and n-butyraldehyde
(68 mL, 0.75 mmol) with Ni(cod) , tricyclopentylphosphine,
2
and tert-butyldimethylsilane (125 mL, 0.75 mmol) in THF
following the standard procedure C described above
afforded 3i in 35% yield as a colorless oil. H NMR
1
(
500 MHz, CDCl , d): 5.09 (br s, 1H), 4.76 (br s, 1H),
3
3
2
3
4
1
2
.97 (t, J¼4.9 Hz, 1H), 1.90–1.82 (m, 1H), 1.55–1.20 (m,
3H), 0.92 (s, 9H), 0.88 (m, 6H), 0.05 (s, 3H), 0.01 (s,
H); C NMR (125 MHz, CDCl , d): 156.0, 107.6, 75.8,
1
3
3
0.7, 39.1, 35.9, 34.7, 32.5, 27.4, 26.9, 26.2, 22.9, 18.8,
8.5, 14.4, 14.3, ꢁ4.2, ꢁ4.7. IR (NaCl, thin film): 2958,
930, 2858, 1646, 1463, 1255, 1085, 902, 836, 774.
+
HRMS-ESI (m/z): [M+Na] calcd for C H OSi,
3 48
3
2
91.3367; found, 391.3350.
5
.3.13. (2-Benzyl-1-phenyl-allyloxy)-tert-butyldimethyl-
silane (3j). The reaction of phenylallene (1b) (121 mL,
mmol) and benzaldehyde (305 mL, 3 mmol) with
Ni(cod) , IPr (78 mg, 0.2 mmol), and tert-butyldimethyl-
1
2
silane (498 mL, 3 mmol) in THF following the standard
procedure A (described above except that tricyclopentyl-
phosphine was replaced by IPr) afforded 3j in 56% yield
as a colorless oil. H NMR (400 MHz, CDCl , d): 7.43–
7
1
4
1
3
.33 (m, 4H), 7.30 (t, J¼7.4 Hz, 3H), 7.22 (t, J¼7.3 Hz,
H), 7.10 (d, J¼7.0 Hz, 2H), 5.35 (s, 1H), 5.19 (s, 1H),
.71 (d, J¼1.4 Hz, 1H), 3.39 (d, J¼16.1 Hz, 1H), 3.05 (d,
J¼16.1 Hz, 1H), 0.97 (s, 9H), 0.09 (s, 3H), ꢁ0.02 (s, 3H);
1
3
C NMR (100 MHz, CDCl , d): 151.8, 143.3, 139.7,
3
1
2
2
8
29.6, 128.4, 128.2, 127.3, 126.6, 126.1, 112.1, 77.8, 37.6,
6.1, 18.5, ꢁ4.7, ꢁ4.8; IR (NaCl, thin film): 3028, 2956,
929, 2857, 1648, 1602, 1494, 1251, 1091, 1067, 868,
+
35, 776, 699. HRMS-ESI (m/z): [M+Na] calcd for
C H OSi, 361.1958; found, 361.1959.
22 30
3
890–3908.
3. (a) Jin, H.; Uenishi, J.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc.
986, 108, 5644–5646; (b) Takai, K.; Tagashira, M.; Kuroda,
Acknowledgements
1
Support for this work was provided by the National Insti-
tute of General Medical Sciences (GM-063755). We also
thank the NIGMS (GM-072566), NSF (CAREER CHE-
T.; Oshima, K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc.
1986, 108, 6048–6050; (c) F u¨ rstner, A.; Shi, N. J. Am. Chem.
Soc. 1996, 118, 2533–2534; (d) F u¨ rstner, A.; Shi, N. J. Am.
Chem. Soc. 1996, 118, 12349–12357; Review: (e) F u¨ rstner,
A. Chem. Rev. 1999, 99, 991–1045; Recent advance: (f)
Namba, K.; Wang, J.; Cui, S.; Kishi, Y. Org. Lett. 2005, 7,
5421–5424; Asymmetric variants: (g) Choi, H.-W.;
Nakajima, K.; Demeke, D.; Kang, F.-A.; Jun, H.-S.; Wan,
Z.-K.; Kishi, Y. Org. Lett. 2002, 4, 4435–4438; (h) Berkessel,
A.; Menche, D.; Sklorz, C. A.; Schr o¨ der, M.; Paterson, I.
Angew. Chem., Int. Ed. 2003, 42, 1032–1035; (i) Namba, K.;
Kishi, Y. Org. Lett. 2004, 6, 5031–5033; (j) Namba, K.; Cui,
S.; Wang, J.; Kishi, Y. Org. Lett. 2005, 7, 5417–5419.
0
134704), Amgen, Boehringer-Ingelheim, Bristol Myers-
Squibb, GlaxoSmithKline, Johnson & Johnson, Merck
Research Laboratories, Pfizer, the Sloan Foundation, Wyeth,
and the Deshpande Center (MIT) for generous financial
support. We are grateful to Dr. Li Li for obtaining mass
spectrometric data for all compounds (MIT Department of
Chemistry Instrumentation Facility, which is supported in
part by the NSF (CHE-9809061 and DBI-9729592) and
the NIH (1S10RR13886-01)).
4
. Recent review of catalytic asymmetric organozinc addition to
carbonyl compounds: (a) Pu, L.; Yu, H.-B. Chem. Rev. 2001,
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