Regioselective hydrations of 1-aryl-3-en-1-ynes using gold and platinum catalysts: Selective production of 2-en-1-ones and 3-en-1-ones

Article abstract of DOI:10.1039/c4cc02786h

Regiocontrolled hydrations of 1-aryl-3-en-1-ynes have been accomplished with IPrAuOTf and PtCl₂/CO to yield 3-en-1-ones and 2-en-1-ones efficiently; our experimental data indicates that the sizes of catalysts play an important role. This journa

Full text of DOI:10.1039/c4cc02786h

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Regioselective hydrations of 1-aryl-3-en-1-ynes
using gold and platinum catalysts: selective
production of 2-en-1-ones and 3-en-1-ones†
Cite this: Chem. Commun., 2014,
50, 8966
Received 15th April 2014,
Accepted 18th June 2014
Bhanudas Dattatray Mokar and Rai-Shung Liu*
DOI: 10.1039/c4cc02786h
www.rsc.org/chemcomm
Table 1 Catalyst screening over gold and platinum catalysts
Regiocontrolled hydrations of 1-aryl-3-en-1-ynes have been accom-
plished with IPrAuOTf and PtCl2/CO to yield 3-en-1-ones and 2-en-
1-ones efficiently; our experimental data indicates that the sizes of
catalysts play an important role.
Compositionsb (%)
Metal-catalyzed hydrations of alkynes are powerful tools to
access carbonyl compounds.1 Hydration of non-symmetric
alkynes typically forms two distinct products; the control of
their hydration regioselectivity is an important synthetic issue.
Catalytic hydrations of terminal alkynes are shown to yield
either ketone or aldehyde derivatives, depending on the types of
catalysts (eqn (1)).2–4 Ruthenium catalysts can react with terminal
alkynes to form ruthenium vinylidenes (I) to implement the
C(1)-regioselectivity, thus forming aldehyde derivatives via an
anti-Markovnikov addition.2 Electrophilic metal species includ-
ing Au(I or III),3 Pt(II),3 Pd(II),4 Ag(I),4 Zn(II)4 and Hg(II)4 typically
form p-alkyne species to facilitate the C(2)-regioselectivity to
yield ketone products via the Markovnikov pathway.3,4
Entry Catalyst (mol%)
Solventa
Time (h) 1a
2a
3a
1
2
Zn(OTf)2(10)
AgOTf (10)
Dioxane/H20 24
Dioxane/H20 24
Dioxane/H20 24
Dioxane/H20 16
75
67
82
85
90
—
—
—
—
—
50
85
—
—
—
—
—
87
80
55
64
—
23
—
—
—
—
—
—
—
—
—
—
95
25
—
3
4
AuCl/AgOTf (5)
IPrAuCl/CO (5)
5
6
7
8
Ph3PAuCl/AgOTf (5) Dioxane/H20 16
IPrAuCl/AgOTf (5) Dioxane/H20
IPrAuCl/AgOTf (5) MeCN/H20
IPrAuCl/AgSbF6 (5) Dioxane/H20
4
4
4
9
LAuCl/AgOTf (5)
PtCl2/CO (5)
PtCl2/AgOTf (5)
HNTf2 (5)
Dioxane/H20 10
10
11
12
Dioxane/H20 10
Dioxane/H20 24
Dioxane/H20 10
a
b
[1a] = 0.05 M. Product yields are reported after separation from a
silica column. IPrAuCI = chloro[1,3-bis(2,6-diisopropylphenyl)imidazole-
2-ylidene]gold(I).
we report the control of the hydration regioselectivity of 1-aryl-3-
en-1-ynes (1) with suitable Au(I) and Pt(II), giving 3-en-1-ones (2)
and 2-en-1-ones (3) selectively (eqn (2)). Herein, we also develop
one-pot synthesis of allylic and homoallylic alcohols 4 and 5 from
these 3-en-1-ynes, through in situ reductions of two ketone pro-
ducts. Oxygenated acyclic molecules 2–5 are important building
blocks in the synthesis of complicated bioactive molecules.6,7
Table 1 shows the tests of the hydrations of 3-en-1-yne (1a)
over various Lewis acid catalysts at 5–10 mol% loading. Using
Zn(OTf)2, Ag(OTf), AuCl/AgOTf, IPrAuCl/CO (IPr = 1,3-bis(2,6-
diisopropylphenyl)imidazole-2-ylidene), and PPh3AuCl/AgOTf
as catalysts, we found no activity for the alkyne hydration in
hot and wet 1,4-dioxane (10 equiv. of H2O, 80 1C, 24 h); starting
3-en-1-yne 1a was recovered in 67–90% yield (entries 1–5). We
employed IPrAuCl/AgOTf that was reported to be very active in
the alkyne hydration;3c resulting 3-en-1-one 2a was obtained in
87% and 80% yields, in wet 1,4-dioxane and acetonitrile, respec-
(1)
(2)
As internal alkynes only form p-alkyne species (II) with
electrophilic metal complexes, the hydration regioselectivity relies
heavily on the nature of alkynyl substituents.1,3–5 We are aware of
no instances where the regioselectivity of non-symmetric alkynes
can be modulated efficiently using distinct catalysts. In this work,
National Tsing Hua University, Hsinchu, Taiwan. E-mail: rsliu@mx.nthu.edu.tw
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4cc02786h tively; such a hydration regioselectivity was previously reported
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by us for similar enynes (entries 6 and 7).4e An alternation of the whereas PtCl2/CO afforded 3g–3j predominantly. The same regio-
anion as in IPrAuSbF6 gave a decreased yield (ca. 55%) in wet selectivities were observed for additional 1-aryl-3-en-1-ynes 1k–1m
and hot 1,4-dioxane (entry 8). A commonly used gold catalyst bearing alkenyl substituents R = 2-furyl, 2-thienyl or n-propyl; their
like LAuOTf (L = P(o-biphenyl)(t-Bu)2) gave the same 3-en-1-one corresponding 3-en-1-ones 2k–2m and 2-en-1-ones 3k–3m were
2a in 64% yield (entry 9). Notably, a switch to PtCl2/CO com- obtained in 55–84% and 57–91% yields, respectively, for IPrAuOTf
pletely changed the hydration regioselectivity, affording 2-en- and PtCl2/CO (entries 10–12). The presence of E/Z-isomers for
1-one 3a in 95% yield (entry 10). In contrast, PtCl2/AgOTf was 3-en-1-one 2m indicates a 1,3-allylic shift of the gold-Z1-allyl
found to be less active in this alkyne hydration to give a mixture intermediate.8 For 3-en-1-ynes 1n–1o bearing a 2-thienyl group at
of two ketones 2a (23%) and 3a (25%) together with reacted 1a in the alkynyl end, both IPrAuOTf and PtCl2 gave a mixture of 3-en-
50% recovery (entry 11). HNTf2 was catalytically inactive to give a 1-ones 2n–2o and 2-en-1-ones 3n–3o; the former were the major
complete recovery of starting 1a, affording the compound only in products for the gold catalyst whereas the latter were for PtCl2
85% yield (entry 12).
(entries 13 and 14). We tested the reaction on enyne 1p bearing a
3-Enones and 2-enones are common building blocks in organic cyclopropylalkynyl substituent, its corresponding hydrations gave
reactions.6,7 We prepared various 1-aryl-3-en-1-ynes 1b–1o to exam- 3-en-1-one 2p as the major product, but the gold catalyst gave the
ine the generality of such a catalyst-dependent regioselectivity; the ratio of 2p/3p up to 21 (entry 15).
two substituents of substrates, i.e. R and Ar, were varied to study
Our synthetic approach is also applicable to allylic and
their regioselectivity using IPrAuOTf and PtCl2/CO. The results are homoallylic alcohols 4 and 5 using the preceding 3-en-1-ynes;
summarized in Table 2. For 3-en-1-ones 2, we did not obtain their the reactions were operated by initial alkyne hydrations, followed
conjugated a,b-enone products in tractable amounts because by in situ NaBH4 reductions. Table 3 summarizes several instances
the acidic conditions will preferably generate a carbocation at of highly regioselective hydrations in the presence of two catalysts.
the C(4)–carbon adjacent to the R substituent (R = aryl, hetero- With IPrAuOTf, various homoallylic alcohols 4a–4b, 4f, 4h–4i,
aryl or n-propyl), thus inhibiting a 1,2-olefin shift. Entries 1–5 4k and 4l were produced by such one-pot two-step reactions;
depict the hydration reactions of substrates 1b–1f bearing their yields exceeded 76% in most of the cases except for 4k that
various styryl substituents R = 4-XC6H4 (X = methoxy, methyl, was obtained in 50% yield. Analogously, the same enynes also
tert-butyl, chloro or trifluoromethyl); the same regioselectivity allowed the production of allylic alcohols 5a–5b, 5f, 5h–5i, 5k
was maintained with IPrAuOTf to yield 3-en-1-ones 2b–2f and 5l using the PtCl2 catalyst.
exclusively, and with PtCl2/CO to afford only 2-en-1-ones 3b–3f.
We prepared substituted 3-en-1-ynes 1q and 1r to examine
Electronically, the methoxy substrate 1b should be favorable for the effects of the substituents as depicted in Table 4. In the case of
the production of 2-en-1-one 3b whereas trifluoromethyl deriva- 3-en-1-yne 1q bearing a C(3)-methyl group, IPrAuOTf altered its
tive 1f tends to form 3-en-1-one 2f, but they were not obtained, regioselectivity to give 2-en-1-one 3q predominantly (2q/3q = 1/19),
respectively, in the presence of Au and Pt catalysts (entries 1 and 5). due to the steric effect (vide infra). PtCl2/CO also changed its
We also examined the reactions of substrates 1g–1j bearing varied regioselectivity to yield 1-indanone 2q0 as the major species
alkynyl aryl groups, Ar = 4-XC6H4 (X = methoxy, methyl, bromo or (2q0/3q = 2.3). Herein, 2-indanone 2q0 was obtained from a
trifluoromethyl), as depicted in entries 6–9. As in the preceding secondary reaction of 3-en-1-one 2q.9 In the case of 3-en-1-yne 1r,
cases, IPrAuOTf yielded 3-en-1-ones 2g–2j as major or sole species its 2-tolyl group balances the steric effects of the 3-methylstyryl
Table 2 Selective synthesis of 2-en-1-ones or 3-en-1-ones
Enynea
R
IPrAuOTf
PtCl2
Entry
R0
t (h)
Productsb (%)
t (h)
Products (%)
1
2
3
4
5
6
7
8
4-MeOC6H4
4-MeC6H4
4-t-BuC6H4
4-ClC6H4
4-CF3C6H4
Ph
Ph
Ph
Ph
2-Furyl
2-Thienyl
n-Propyl
Ph
2-Thienyl
Ph
Ph (1b)
Ph (1c)
Ph (1d)
Ph (1e)
8
4
4
4
3
3
3
4
6
5
3
7
4
10
3
2b (78)
2c (90)
2d (90)
2e (90)
2f (91)
2g (87)
2h (92)
2i (82)
4
3
5
2.5
3
2.5
1
3
3
3
2
5
4
7
3b (92)
3c (94)
3d (84)
3e (93)
3f (90)
3g (94)
3h (91)
3i (96)
3j (94)
3k (65)
31 (91)
3m (57)
3n/2n = 2.0 (92%)
3o/2o = 2.1 (94%)
2p/3p = 3.5 (90%)
Ph (1f )
4-MeOC6H4 (1g)
4-MeC6H4 (1h)
4-BrC6H4 (1i)
4-CF3C6H4 (1j)
Ph (1k)
Ph (11)
Ph (1m)
2-Thienyl (1n)
2-Thienyl (1o)
Cyclopropyl (1p)
9
2j (61)
2k (55)
21 (84)
10
11
12
13
14
15
2m (62)c
2n/3n = 2.8 (87%)
2o/3o = 4.1 (85%)
2p/3p = 21 (88%)
4.5
a
b
c
[1] = 0.05 M. Product yields are reported after separation from a silica column. A mixture of E- and Z-isomers (E/Z = 3.1) for product 2m.
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Table 3 Selective synthesis of allylic and homoallylic alcohols
a
b
Scheme 1 Rationales for the hydration regioselectivity.
[1] = 0.05 M. Product yields are reported after separation from a
silica column.
of its p-alkyne species A0 to initiate the C(1)-hydration. Small
PtCl2 facilitates this C(1)-hydration to form intermediate C0,
giving 3-en-1-one 2q as the major product. In contrast, bulky
IPrAuOTf prefers the C(2)-hydration to avoid a steric interaction
with the 3-methylstyryl as in species C00 due to the nonplanar
geometry of the diene moiety, thus giving 2-en-1-one 3q via
intermediate B00. Steric effects of 3-en-1-yne substrates and metal
catalysts rationalize well the hydration regioselectivity.
Table 4 Effects of substituents
Enynesa
Time
(hour) yields (%)
Productsb
Entry Catalysts
R
R0
Before this work, there was no evidence to support that internal
alkynes can be catalytically hydrated by different catalysts to
control their regioselectivity efficiently. We report the control of
the regioselective hydrations of 1-aryl-3-en-1-ynes with IPrAuOTf
and PtCl2.10 The gold catalyst implements the hydration of the
alkynyl C(1)–carbon to form 3-en-1-ones whereas the platinum
catalyst facilitates the C(2)-hydration to yield 2-en-1-ones. The
utility of this synthetic method is manifested by its facile access
to useful oxygenated molecules including 2-en-1-ones, 3-en-1-
ones, allylic and homoallylic alcohols. We also tested the reac-
tions on substituted 1-aryl-3-en-1-ynes that showed reasonable
regioselectivity in their alkyne hydrations, although in some
instances the regioselectivity was reversed. Our product analysis
reveals that the sizes of catalysts significantly affect the regio-
selective hydration of these alkynes.
1
2
3
4
5
IPrAuOTf
PtCl2/CO
IPrAuOTf
PtCl2/CO
H
H
Me (1q)
Me (1q) 3.5
3
2q/3q = 1/19 (90%)
2q0/3q = 2.3/1 (95%)
2r/3r = 6/1 (91%)
3r (87%)
Me Me (1r)
Me Me (1r)
H
3
4
16
L2PtCl2/2AgOTf
H (1a)
2a (23%), 3a (47)
a
b
[1] = 0.05 M. Product yields are reported after separation from a
silica column.
group; consequently, both gold and platinum catalysts regain
their original regioselectivity, as depicted by products in entries
3 and 4. We also tested the reactions of 3-en-1-yne 1a with bulky
L2PtCl2/2AgOTf (L2 = 1,2-bis(diphenylphosphino)ethane, dppe)
that gave both 2-en-1-one 3a and 3-en-1-one 2a in 47% and 23%
yields, respectively. As PtCl2 yielded 2-en-1-one 3a exclusively
(Table 1, entry 8); the presence of 3-en-1-one 2a again manifested
the size effects of catalysts.
Scheme 1 rationalizes the distinct regioselectivity of the
alkyne hydrations for IPrAuOTf and PtCl2/CO, respectively. The
attack of water at the less hindered alkynyl carbon is crucial for
the hydration regioselectivity; once the attack is complete, inter-
mediates B and C proceed to form hydration products immedi-
ately. We speculate that the two alkynyl carbons of enyne 1a have
equally positive characters; water attacks at its Pt(II)-p-alkyne
species A at the less hindered C(2)–carbon to give hydration
intermediate B, further proceeding to give 2-en-1-one 3a rapidly.
For bulky IPrAuOTf, we envisage that its corresponding inter-
mediate B0 suffers a steric interaction between IPrAu and the
C(1)–Ar group; instead, species C is the preferable intermediate
to yield the observed 3-en-1-one 2a. In the case of enyne 1q, its
3-methylstyryl group becomes more bulky than the C(1)-phenyl
group; water prefers the attack at the less hindered C(1)–carbon
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