Nickel-catalyzed hydrocarboxylation of ynamides with CO2 and H2O: Observation of unexpected regioselectivity

Article abstract of DOI:10.1039/c7cc03127k

We describe the nickel-catalyzed hydrocarboxylation of ynamides with CO₂ and H₂O to afford a variety of α-amino-α,β-unsaturated esters with high regioselectivities. The selective α-carboxylation of ynamides with this catalytic protocol is unexpected in view of the electronic bias of ynamides and is in sharp contrast to our previous study in which a stoichiometric amount of Ni(0) was used to form a β-carboxylated product exclusively. We revealed that this unexpected C-C bond formation was induced by the combination of Zn and MgBr₂.

Full text of DOI:10.1039/c7cc03127k

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Nickel-Catalyzed Hydrocarboxylation of Ynamides with CO and
2
H O: Observation of Unexpected Regioselectivity†
2
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
b
,a
Ryohei Doi, Iman Abdullah, Takahisa Taniguchi, Nozomi Saito, and Yoshihiro Sato*
DOI: 10.1039/x0xx00000x
www.rsc.org/
We describe the nickel-catalyzed hydrocarboxylation of ynamides Herein, we report
with CO and H
esters with high regioselectivities. Selective α-carboxylation of electronic bias on the C−C triple bond, by use of H
a
nickel-catalyzed regioselective
2
2
O to afford a variety of α-amino-α,β-unsaturated hydrocarboxylation of ynamide, which is known to have an
6
2
2
O and CO .
ynamide with this catalytic protocol is unexpected in view of the Consequently, we observed an interesting selectivity switching
electronic bias of ynamide and is in sharp contrast to our previous triggered by additives.
study in which a stoichiometric amount of Ni(0) was used to form
R2
R1
a
β-carboxylated product exclusively. We revealed that this
unexpected C−C bond formation was induced by the combination
of Zn and MgBr
cat. Ni(0)
R1
R2
R1
R2
+
+
H
H
H , CO
2
CO2R3
CO2R3
B, Minor
2
.
A, Major
Homogeneous nickel catalysis has emerged in the past few
1
decades as a highly efficient tool for organic synthesis. The
This Work:
R1 = N
Martin (2015): R1 = alkyl
/
/
R2 = aryl or alkyl
R2 = aryl
intrinsic chemical properties of some nickel catalysts to
construct a C−C bond have been applied to incorporation of
3
Scheme 1. Regioselective oxidative cyclization of ynamide and CO
H or Me.
2
with Ni(0). R
=
CO , which is an abundant, non-toxic and renewable carbon
2
2
source. Especially, reactions using compounds bearing a C−C
δ−
δ+
δ−
δ+
double bond or triple bond as a coupling partner of CO enable
2
transformation of these building blocks into carboxylic acid
derivatives without prefunctionalization such as halogenation
3
-5
or metalation. Since all carbons constituting an unsaturated
bond are potentially reactive, controlling the regioselectivity is
a common concern of these promising reactions employing Scheme 2. Our previous work: Nickel-mediated hydrocarboxylation of ynamide
with CO
2
CO . Recently, Martin’s group has developed regioselective
2
hydrocarboxylation of alkyl aryl acetylenes with CO employing
2
We previously described a nickel-mediated regioselective
4
a proton source. They speculated that an
f
alcohol as
synthesis of functionalized β-amino-α,β-unsaturated esters
7
and CO . The selectivity was controlled by a
equilibrium would exist between two possible nickelalactones
from ynamides
1
2
derived from alkyne and CO and that steric repulsion between
2
regioselective oxidative cyclization step in which a negative β-
carbon of an ynamide forms a C−C bond with CO2 on Ni(0)
an alkyl group and alcohol would be a key factor for
preferential formation of carboxylic acid
A behind B (Scheme
(
Scheme 2). The resulting β-carboxylated products were shown
1). Their proposed mechanism let us assume another strategy
to be precursors of enantio-enriched β-amino acid derivatives
by conducting Rh-catalyzed asymmetric hydrogenation. As a
next step, we commenced to develop a regioselective catalytic
hydrocarboxylation of ynamides. Recently, Sakaki and Tsuji et
al. reported a nickel-catalyzed double carboxylation of alkyne
for nickel-catalyzed regioselective hydrocarboxylation of a C−C
triple bond with CO2 in which the selectivity would be
engendered by taking advantage of an electronic factor.
by the use of CO in the presence of Zn/MgBr2 as reducing
2
4
agents. We applied their reaction conditions to catalytic
g
hydrocarboxylation of ynamides with CO2 and H O. In the
2
presence of 10 mol% of Ni(cod) and 2,2’-bipyridyl (bpy) and 3
2
equiv. of Zn/MgBr , hydrocarboxylation of ynamide 1a with
2
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2 2
CO and H O occurred to give a mixture of esters 2a and 3a in totally ineffective (runs 4-7). Next, the reactions were
78% yield with a regioisomer ratio of 83/17 (Table 1, run 1). conducted by using other proton sources. In contrast to
The structure of compound 2a was supported by NOE Martin’s system in which repulsion between an alcohol and an
experiments of the corresponding alcohol that was obtained alkyl group is supposed to be a key factor, the selectivity of the
by DIBAL reduction of 2a (see Supporting Information for hydrocarboxylation of ynamide was not significantly affected
details). The preference for generation of α-carboxylation by the difference in proton source, though some alcohols gave
9
product 2a over β-carboxylation product 3a is an unexpected the desired product in lower yields (runs 8-11).
result since our previous study employing a stoichiometric
Table 2. Reaction condition screening
amount of Ni(0) afforded only a β-carboxylation product.
Actually, treatment of the ynamide 1a with a stoichiometric
2
amount of Ni(cod) and bpy followed by addition of aqueous
HCl gave β-carboxylation product 3a as a sole carboxylation
product along with the formation of a considerable amount of
a hydrogenated product
4
as a mixture of cis/trans isomers
[
a]
[b]
8
run 2). Similar results were obtained in the presence of either
Additive
3 equiv.)
Zn/MgBr
Mg/MgBr
Mn/MgBr
Yield
Selectivity
(2a/3a)
(
Run
Proton Source
(
(%)
c]
2
MgBr or Zn (runs 3 and 4). Contrary to these outcomes,
[
1
2
3
4
5
6
7
2
0.5 equiv.
0.5 equiv.
0.5 equiv.
0.5 equiv.
0.5 equiv.
0.5 equiv.
0.5 equiv.
1.0 equiv.
1.0 equiv.
1.0 equiv.
H
2
O
O
O
O
O
O
O
78
83
63
55
92
23
-
17
37
hydrocarboxylation in the presence of both Zn and MgBr
afforded 2a as a major product even though stoichiometric
amounts of Ni(cod) and bpy were loaded (run 5). This
2
2
H
2
11
29
71
13
2
H
2
45
8
2
Zn/MgCl
2
H
2
observation clearly suggests that the selectivity switching is
induced not by the amount of Ni loading but by the
Zn/LiBr
H
2
77
-
Zn/ZnBr
2
H
2
trace
trace
81
2
combination of Zn and MgBr .
Zn/TBAB
H
2
-
-
[
d]
8
9
Zn/MgBr
Zn/MgBr
Zn/MgBr
Zn/MgBr
2
MeOH
80
83
76
72
20
17
24
28
Table 1. Hydrocarboxylation of ynamide with catalytic and stoichiometric
amounts of Ni(0)
[d]
i
2
PrOH
64
[
[
d]
t
1
0
2
2
BuOH
46
Ni(cod)2
d]
Additives
Bu
11
1.0 equiv. CF
3
CH
2
OH
57
Bu
Bu
Bu
1
atm CO2
N
N
N
1
N
Ts
Ts
H
Ts
CO Me Ts
H
[a] Yields were determined by H NMR using 1,1,2,2-tetrachloroethane as an
DMF, 0 °C, 12 h;
1) HCl aq
2
CO2Me
2a
H
3a
H
4
internal standard. [b] The selectivity refers to the ratio of 2a and 3a that was
1
1
a
2) CH N
determined by the integration ratio of H NMR signals. [c] Isolated yield. [d] The
2
2
reactions were conducted for 36 h.
Yield (%)
a + 3a
Run
Condition
Next, we tested a variety of ynamides for the catalytic
hydrocarboxylation reaction protocol (Table 3). In addition to
an ynamide having a butyl group (1a), an ynamide bearing a
2
4
[a]
1
3
0 mol% Ni(cod)
2
/ bpy
2
, 0.5 equiv. H O
78
1
2
3
4
5
[b]
[b]
11
29
35
32
<5
equiv. Zn / MgBr
2
(83/17)
phenylethyl
group
(
1b
)
afforded
the
desired
[c]
3
1
hydrocarboxylation product in good yield with similar
selectivity. The hydrocarboxylation of ynamides possessing a
secondary or tertiary alkyl chain on the alkynyl carbons
delivered the esters in high yield with excellent
regioselectivity. In contrast to these results, the use of silyl-
substituted ynamide 1f resulted in formation of β-carboxylated
product 3f which contains desilylated product 3f’. Some
ynamides having an aromatic ring such as phenyl (1g) or 4-
methoxyphenyl (1h) were applicable to the reaction, while an
1 equiv. Ni(cod)
2
/ bpy
/ bpy
(
0/100)
[c]
1
3
equiv. Ni(cod)
2
29
[b]
(7/93)
equiv. MgBr
2
[c]
1
3
equiv. Ni(cod)
2
/ bpy
/ bpy
29
[b]
[b]
equiv. Zn
(0/100)
[c]
1
3
equiv. Ni(cod)
2
76
equiv. Zn / MgBr
2
(84/16)
[
a] Isolated Yield. [b] NMR yield with the aid of 1,1,2,2-tetrachloroethane as an ynamide 1i having a methoxycarbonyl group at the 4-position
internal standard. [c] Ratio of 2a and 3a determined by comparison of peak areas
of the benzene ring gave
a
complicated mixture.
1
of H NMR signals.
Hydrocarboxylation of alkyl ynamides carrying a terminal silyl
ether group (1j and 1k) gave desired products in 80% and 73%
yields, respectively, with good regioselectivity. In addition,
methoxymethane (MOM) and benzyl (Bn) protections were
tolerated, and these substituents exerted very little effect on
the selectivity (1l and 1m). However, the reaction of alkyl
ynamides having an acetoxy group gave a very small amount
of the hydrocarboxylated product. Next, we modified
substituents on a nitrogen atom. The reaction of ynamides
We further investigated the effects of reaction conditions
on the yield and selectivity (Table 2). As a result, the reaction
was found to be quite sensitive to the choice of a reductant.
When the reaction was conducted by use of Mg or Mn as a
reductant, both the yield and selectivity were significantly
decreased (runs 2 and 3). Addition of magnesium salt was
indispensable for this catalytic reaction; indeed, MgCl showed
2
an effect similar to that of the bromide counterpart, whereas
bearing a benzyl group (1n) and a cyclohexyl group (1o
)
LiBr, ZnBr and tetrabutyl ammonium bromide (TBAB) were
2
afforded the desired products in high yields. The structure of
2
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the product 2n was confirmed by X-ray diffraction study after product
isolation of 2n from the mixture of hydrocarboxylated presence of a catalytic amount of nickelalactone
products followed by crystallization. Unfortunately, allyl compounds 2a 3a and 3c (Scheme 3). The absence of
6. In addition, hydrocarboxylation of 1a in the
5
produced
,
substituted ynamide 1p gave a complicated mixture with the compound 2c in this reaction mixture implies that
catalytic reaction conditions. Ynamide having a phenyl group nickelalactone only gives a β-carboxylated product and that α-
(
1q) on nitrogen yielded the desired product in moderate carboxylation might involve another pathway(s). We propose
yield. Other electron-withdrawing groups such as mesyl (1r that the reaction proceeds via a nickel hydride species derived
and carbamate (1s) were applicable for ynamide protection in from H
)
1
0,11
2
O under a reductive condition.
Recently, Gosmini
this hydrocarboxylation protocol. Interestingly, we observed and Gillaizeau group reported Co-catalyzed carbozincation of
reverse regioselectivity in the reaction of oxazolidione-derived ynamide, in which regioselectivities similar to those in our
1
2
ynamide 1t
.
reactions were observed in some cases. In addition, Hou’s
group developed Cu-catalyzed alkylative carboxylation of
[
a]
Table 3. Substrate scope
13
ynamide that gives α-carboxylated products. Taking these
1
0 mol% Ni(cod)
2
reports into account, the α-selectivity would be induced by
steric repulsion between a nickel complex and carbon
substitution at the β-position and/or by interaction between a
nickel complex and a substituent of nitrogen at the addition
step of a nickel hydride species to ynamide.
R2
10 mol% bpy
3
1
DMF, 0 °C, 12 h;
1) HCl aq, 2) CH N
R1
N
R2
R1
N
R2
equiv. Zn / MgBr
2
R1
N
EWG
H
EWG
2
CO Me
atm CO , 0.5 equiv. H O
2
2
EWG
1
CO
2
Me
H
3
2
2
2
Figure 1. Structure and stoichiometric reaction of nickelalactone 5.
nBu
nBu
N
N
Ts
Ts
H
2
Ts
Ts
2
CO Me
2
3
0 mol% 5
equiv. Zn / MgBr2
CO Me
H
nBu
2a, 34%
3a, 17%
N
Ts
i
Pr
i
Pr
1
atm CO , 0.5 equiv. H O
2 2
DMF, 0 °C, 12 h;
then, 1) HCl aq, 2) CH N
N
N
H
2
CO Me
1
a
2
2
CO2Me
H
2
c, ND
3c, 53%
Scheme 3. Nickelalactone
5
-catalyzed hydrocarboxylation of ynamide 1a. Yields
were determined by H NMR of a crude product. Yields of 2a and 3a are based
on ynamide 1a, while that of 3c is based on nickelalactone
1
5.
In summary, we have described
regioselective hydrocarboxylation of ynamide with CO
O in the presence of Zn/MgBr under mild conditions (0 °C).
a
nickel-catalyzed
2
and
H
2
2
The selectivity of this catalytic protocol is in sharp contrast to
the reaction using a stoichiometric amount of Ni(0) that
resulted in exclusive formation of β-amino-α,β-unsaturated
esters. The major product is a potential precursor of unnatural
1
4
α-amino acids.
Further investigations of the reaction
[
a] Isolated yields are given. [b] 20 mol% catalyst was loaded. [c] Acidic work-up
mechanism to clarify the origin of the selectivity observed in
this nickel-catalyzed hydrocarboxylation are currently
underway in our laboratory.
was conducted using 10% citric acid solution instead of 10% HCl.
To gain an insight into the origin of the selectivity, we
isolated nickelalactone
the reaction mixture containing Ni(cod)
CO . X-ray crystallography of complex
bond formation between ynamide and CO
negative β-carbon, being in good accordance with our previous
5
as an orange precipitate formed from
, bpy, ynamide 1c and
revealed that C−C
occurred at the
This work was financially supported by a Grant-in-Aid for
Scientific Research (B) (26293001) from JSPS, by a Grant-in-Aid
for Young Scientists (Start-up) (16H06593) from MEXT, and by
JST ACT-C Grant Number JPMJCR12YM. T.T. is grateful for
support as a JSPS Research Fellow.
2
2
5
2
7
report (Figure 1). However, treatment of complex
5 with the
MgBr /Zn/H O system in DMF under a CO atmosphere
2
2
2
followed by HCl quenching only afforded β-carboxylation
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Journal Name
1
3 M. Takimoto, S. S. Gholap, Z. Hou, Chem. Eur. J., 2015, 21
5218.
,
Notes and references
1
1
S. Z. Tasker, E. A. Standley and T. F. Jamison, Nature, 2014, 14 The application of an asymmetric hydrogenation condition
509, 299, and references therein.
Selected reviews for transition metal-catalyzed carboxylation
with CO : (a) D. Yu, S. P. Teong, Y. Zhang, Coord. Chem. Rev.,
2
we developed previously (ref. 7) resulted in formation of the
desired α-amino acid derivative in 25% yield and 25%ee. In
addition, we obtained racemic α-amino acid quantitatively
2
2
2
015, 293, 279; (b) Y. Tsuji, T. Fujihara, Chem. Commun.,
012, 48, 9956; (c) A. Correa, R. Martin, Angew. Chem. Int.
by reduction under H pressure in the presence of Pd/C or
2
Crabtree’s catalyst. Further investigation is ongoing.
Ed., 2009, 48, 6201; (d) M. Bӧrjesson, T. Moragas, D. Gallego,
R. Martin, ACS Catal., 2016, , 6739.
Examples of carboxylation of alkenes with a nickel catalyst:
a) M. L. Lejkowski, R. Lindner, T. Kageyama, G. É. Bódizs, P.
N. Plessow, I. B. Müller, A. Schäfer, F. Rominger, P. Hofmann,
C. Futter, S. A. Schunk, M. Limbach, Chem. Eur. J., 2012, 18
4017; (b) C. Hendriksen, E. A. Pidko, G. Yang, B. Schäffner,
6
3
(
,
1
D. Vogt, Chem. Eur. J., 2014, 20, 12037; (c) N. Huguet, I.
Jevtovikj, A. Gordillo, M. L. Lejkowski, R. Lindner, M. Bru, A.
Y. Khalimon, F. Rominger, S. A. Schunk, P. Hofmann, M.
Limbach, Chem. Eur. J., 2014, 20, 16858; (d) S. Manzini, N.
Huguet, O. Trapp, T. Schaub, Eur. J. Org. Chem., 2015, 7122;
(
2
e) C. M. Williams, J. B. Johnson, T. Rovis, J. Am. Chem. Soc.,
008, 130, 14936.
4
Examples of carboxylation involving an alkyne(s) with a
nickel catalyst: (a) K. Shimizu, M. Takimoto, Y. Sato, M. Mori,
Org. Lett., 2005,
Chem. Int. Ed., 2011, 50, 2578; (c) J. Louie, J. E. Gibby, M. V.
Farnworth, T. N. Tekavec, J. Am. Chem. Soc., 2002, 124
7, 195; (b) S. Li, W. Yuan, S. Ma, Angew.
,
1
2
5188; (d) T. N. Tekavec, A. M. Arif, J. Louie, Tetrahedron,
004, 60, 7431; (e) T. Mizuno, Y. Oonishi, M. Takimoto, Y.
Sato, Eur. J. Org. Chem., 2011, 2606; (f) X. Wang, M.
Nakajima, R. Martin, J. Am. Chem. Soc., 2015, 137, 8924; (g)
T. Fujihara, Y. Horimoto, T. Mizoe, F. B. Sayyed, Y. Tani, J.
Terao, S. Sakaki, Y. Tsuji, Org. Lett., 2014, 16, 4960.
5
6
Selected examples of nickel-catalyzed carboxylation of
allenes: (a) M. Takimoto, M. Kawamura, M. Mori, Y. Sato,
Synlett, 2005, 2019; (b) M. Aoki, S. Izumi, M. Kaneko, K. Ukai,
J. Takaya, N. Iwasawa, Org. Lett., 2007, 9, 1251.
Selected reviews on reactivity of ynamide: (a) G. Evano, N.
Blanchard, G. Compain, A. Coste, C. S. Demmer, W. Gati, C.
Guissart, J. Heimburger, N. Henry, K. Jouvin, G. Karthikeyan,
A. Laouiti, M. Lecomte, A. M.-Mingot, B. Métayer, B.
Michelet, A. Nitelet, C. Theunissen, S. Thibaudeau, J. Wang,
M. Zarca, C. Zhang, Chem. Lett., 2016, 574; (b) C. A. Zificsak,
J. A. Mulder, R. P. Hsung, C. Rameshkumar, L.-L. Wei,
Tetrahedron, 2001, 57, 7575; (c) K. A. DeKorver, H. Li, A. G.
Lohse, R. Hayashi, Z. Lu, Y. Zhang, R. P. Hsung, Chem. Rev.,
2
010, 110, 5064. (d) X.-N. Wang, H.-S. Yeom, L.-C. Fang, S. He,
Z.-X. Ma, B. L. Kedrowski, R. P. Hsung, Acc. Chem. Res., 2014,
, 560; (e) G. Evano, A. Coste, K. Jouvin, Angew. Chem. Int.
4
7
Ed., 2010, 49, 2840.
7
8
N. Saito, I. Abdullah, K. Hayashi, K. Hamada, M. Koyama, Y.
Sato, Org. Biomol. Chem., 2016, 14, 10080.
We speculate that nickelalactone intermediates would
deliver compound 4, because the starting material was fully
recovered in the reaction in the absence of CO2.
We also conducted screening of ligands, including 1,10-
phenanthroline and its derivatives, but the reactions resulted
in lower yields. For the results of full ligand screening, see
Supporting Information.
9
1
0 Generation of an alkenyl nickel species from alkyne in the
presence of a reductant and water was also suggested by
Takai. See: K. Takai, S. Sakamoto, T. Isshiki, Org. Lett., 2003,
53.
5,
6
1
1
1 Recently published review for nickel hydride complexes: N. A.
Eberhardt, H. Guan Chem. Rev. 2016, 116, 8373.
2 R. Sallio, M. Corpet, L. Habert, M. Durandetti, C. Gosmini, I.
Gillaizeau, J. Org. Chem., 2017, 82, 1254.
4
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