Regio- and stereoselective synthesis of tri- and tetrasubstituted enamides via palladium-catalyzed silaboration of ynamides

Article abstract of DOI:10.1002/adsc.201201111

The palladium-catalyzed silaboration of ynamides is demonstrated. The silaboration proceeds in a highly regioselective manner to give the corresponding tri- and tetrasubstituted enamide derivatives having both a silyl group and a boryl group on the alkene. Furthermore, the silaborated enamide could be utilized as a coupling partner in Suzuki-Miyaura coupling with aryl iodides to give the corresponding cross-coupling product in good yield. Copyright

Full text of DOI:10.1002/adsc.201201111

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DOI: 10.1002/adsc.201201111
Regio- and Stereoselective Synthesis of Tri- and Tetrasubstituted
Enamides via Palladium-Catalyzed Silaboration of Ynamides
Nozomi Saito,a,* Keiichi Saito,a Hiroyasu Sato,b and Yoshihiro Satoa,*
a
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Fax : (+81)-11-706-4982; e-mail: nozomi-s@pharm.hokudai.ac.jp or biyo@pharm.hokudai.ac.jp
Rigaku Corporation, Akishima, Tokyo 196-8666, Japan
b
Received: December 19, 2012; Published online: March 15, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201201111.
Abstract: The palladium-catalyzed silaboration of
ynamides is demonstrated. The silaboration pro-
ceeds in a highly regioselective manner to give the
corresponding tri- and tetrasubstituted enamide de-
rivatives having both a silyl group and a boryl
group on the alkene. Furthermore, the silaborated
enamide could be utilized as a coupling partner in
Suzuki–Miyaura coupling with aryl iodides to give
the corresponding cross-coupling product in good
yield.
Scheme 1. Transition metal-catalyzed bismetallation of
Keywords: boron; metallation; palladium; silicon;
carbon-carbon unsaturated bonds.
ynamides
tuted enamides having two metal components, and
palladium-catalyzed silastannylation and bisstannyla-
tion of ynamides have been reported to date.[6,7] How-
The transition metal-catalyzed addition of an ele- ever, only a terminal alkyne has been employed in
À
ment-element s-bond of a bimetallic reagent (X Y) those studies, and no examples of the bismetallation
to carbon-carbon unsaturated compounds (i.e., bisme- of an ynamide having an internal alkyne structure
tallation) is one of the most important methods for have been reported so far. In this context, we planned
the synthesis of 1,n-dimetallo compounds, which are the silaboration[8–11] of an ynamide as shown in
expected to be useful building blocks for further or- Scheme 2. Thus, if silaboration of ynamide 1 with si-
ganic transformations. Group 10 metals are widely lylborane (Si-B, 2) proceeds in the presence of a tran-
employed for bismetallation reactions.[1] The generally sition metal catalyst, the silaborated enamide 3 and/or
accepted mechanism of bismetallation is shown in 3’ would be formed. Here, we report the palladium-
Scheme 1. First, oxidative addition of a bimetallic re- catalyzed regioselective silaboration of ynamides
agent to a low-valent transition metal (M) proceeds using commercially available (dimethylphenylsilyl)pi-
À À
to give the the X M Y complex I. Insertion of a mul- nacolatoboron [PhMe2SiB
(pin), 4][12,13] that led to the
À
tiple bond in the substrate into either the M X or the formation of a multi-substituted enamide derivative
À
M Y s-bond in I occurs to produce intermediate II bearing vinyl silicon and vinyl boron moieties.
or II’, from which reductive elimination affords bis-
metallated product III.
The N-alkynylamide (ynamide) moiety has been
recognized as a versatile building block in recent syn-
thetic organic chemistry,[2–4] and we have already re-
ported a new transformation of ynamides by virtue of
the use of transition metal catalysis.[5] The aforemen-
tioned bismetallation of ynamides is expected to be
an attractive strategy for the synthesis of multi-substi- tuted enamides.
Scheme 2. Bismetallation of ynamide leading to multi-substi-
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853

Nozomi Saito et al.
Table 1. Silaboration of tosylamide-derived ynamides.[a]
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[a]
[b]
Reaction conditions: PhMe2SiB
ACHTUNGTREN(NUGN pin) (4, 1 equiv.),
Pd(OAc)2 (3 mol%), t-BuCH2CMe2NC (6, 30 mol%), tol-
AHCTUNGTRENNUNG
uene, reflux.
The ratio was determined by 1H NMR analysis
Scheme 3. Pd-catalyzed silaboration of ynamide 5a.
(400 MHz) of the mixture of 7c and 8c.
Referring to the previously reported procedure,[8a] terminal alkyne 5h with 4 also proceeded smoothly to
ynamide 5a was reacted with PhMe2SiBi(pin) (4) in give tri-substituted enamide 7h in 81% yield as a sole
the presence of Pd(OAc)2 and isonitrile ligand 6 in product (run 7).
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
toluene under reflux conditions. As a result, silaborat-
ed enamide 7a was obtained as a single regio- and ste-
reoisomer in 89% yield (Scheme 3). The structure of
7a was unambiguously determined by X-ray crystallo-
graphic analysis.[14] It is known that Pd(0)-catalyzed si-
laboration of alkyne proceeds through insertion of
Next, silaboration of oxazolidinone-derived ynam-
AHCTUNGTRENNUNG
À
a triple bond into the Pd B s-bond of IV formed by
oxidative addition of 4 to Pd(0).[1h,15] Therefore, this
result indicates that regioselective insertion of ynam-
À
G
intermediate V, from which reductive elimination
took place stereoselectively to afford the enamide de-
rivative 7a.
Encouraged by this result, we studied the scope
and limitations of silaboration of ynamides (Table 1).
When ynamide having a 4-methoxyphenyl group on
the alkyne part 5b was reacted with silylborane 4, the
expected silaborated enamide 7b and its regioisomer
8b were produced in 71% yield and 12% yield, re-
spectively (run 1). On the other hand, silaboration of
ynamide 5c bearing an ester group on the aromatic
ring afforded 7c and 8c in totally 63% yield (ratio of
2 to 1). Alkyl-substituted ynamide 5d is also applica-
ble to the silaboration, and the corresponding enam-
ide 7d was obtained in high yield as a single isomer
(run 3). Siloxy, acetoxy and alkenyl groups in substitu-
ents on the alkyne part (5e–g) were tolerated under
the reaction conditions, giving enamide derivatives
7e–g in good yields in a highly regio- and stereoselec-
tive manner (runs 4–6). Furthermore, the reaction of
[a]
Reaction conditions: PhMe2SiB
Pd(OAc)2 (3 mol%), t-BuCH2CMe2NC (6, 30 mol%), tol-
uene, reflux
ACHTUNGTREN(NUGN pin) (4, 1 equiv.),
AHCTUNGTRENNUNG
854
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Adv. Synth. Catal. 2013, 355, 853 – 856

Regio- and Stereoselective Synthesis of Tri- and Tetrasubstituted Enamides
matography on silica gel to give the corresponding silaborat-
ed enamide.
Acknowledgements
This work was partly supported by a Grant-in-Aid for Young
Scientist (B) (No. 24790002) and by a Grant-in-Aid for Sci-
entific Research (B) (No. 23390001) from JSPS and by
a Grant-in-Aid for Scientific Research on Innovative Areas
“Molecular Activation Directed toward Straightforward Syn-
thesis” (No. 23105501) from MEXT, Japan. N.S. acknowledg-
es Takeda Science Foundation for financial support.
Scheme 4. Suzuki–Miyaura coupling of enamide 9d with aryl
iodides
c having an aryl group on the alkyne part were sub-
jected to the optimal conditions, giving the corre-
sponding silaborated enamides 10a–c in high yields
(runs 1–3). The silaboration of ynamide 9d bearing an
alkyl group on the alkyne part gave the desired enam-
ide 10d in 89% yield (run 4). On the other hand,
TMS group-substituted ynamide also reacted with 4
in the presence of a palladium catalyst to give expect-
ed 10e in 55% yield and its regioisomer 11e in 26%
yield (run 5). Terminal alkyne 9f was also applicable
to the silaboration, giving 10f in 74% yield as a single
isomer (run 6).[16]
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General Procedure for Pd-Catalyzed Silaboration of
Ynamides
A solution of an ynamide, PhMe2SiB
ACHTUNGERTN(NUNG pin) (4, 1 equiv. to the
ynamide), Pd(OAc)2 (3 mol% to the ynamide) and 1,1,3,3-
ACHTUNGTRENNUNG
tetramethylbutylisocyanide 6 (30 mol% to the ynamide) in
toluene was stirred at 1108C. The reaction mixture was
cooled to room temperature and concentrated under
vacuum, and the residue was purified by flash column chro-
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À
of the triple bond into the Pd B s-bond.
856
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Adv. Synth. Catal. 2013, 355, 853 – 856