Gold-catalyzed intermolecular addition of alcohols toward the allenic bond of 4-vinylidene-2-oxazolidinones

Article abstract of DOI:10.1039/b808921c

Gold catalyzed intermolecular addition of alcohols toward the proximal allenic double bond of 4-vinylidene-2-oxazolidinones gives hydroalkoxylation products, which can be easily converted into the corresponding novel spiro dihydrofuran or dihydropyran der

Full text of DOI:10.1039/b808921c

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Gold-catalyzed intermolecular addition of alcohols toward the allenic bond of
4-vinylidene-2-oxazolidinones†
Yoshikazu Horino,*a Yasushi Takata,a Ken Hashimoto,a Shigeyasu Kuroda,a Masanari Kimurab and
Yoshinao Tamarub
Received 28th May 2008, Accepted 29th July 2008
First published as an Advance Article on the web 24th September 2008
DOI: 10.1039/b808921c
Gold catalyzed intermolecular addition of alcohols toward the proximal allenic double bond of
4-vinylidene-2-oxazolidinones gives hydroalkoxylation products, which can be easily converted into
the corresponding novel spiro dihydrofuran or dihydropyran derivatives in high yield.
The activation of unsaturated C–C bonds by gold complexes
has led to a range of attractive and useful strategies for a
variety of organic transformations.1 Gold-catalyzed intramolec-
ular hydro-functionalization, especially hydroamination2 and
hydroalkoxylation,3 both of which involve the addition of
heteroatom-containing nucleophiles to alkenes and alkynes, has
emerged as a powerful method for the construction of heterocyclic
compounds. Although a limited number of methodologies for the
catalytic intramolecular hydroalkoxylation of allenes, alkynes and
alkenes have been reported,4 to date, only Au(I) complexes have
shown promise as catalysts for the asymmetric hydroalkoxylation
of allenes.2b,3a In the most recent work in this field, Toste and co-
workers developed a powerful chiral counter ion strategy, which
combines chiral ligand platforms with chiral counter ions, and
results in a highly enantioselective intramolecular hydroalkoxy-
lation of allenyl alcohols catalyzed by gold.2a However, there are
very few examples of gold-catalyzed intermolecular addition of the
H–X bond of hetero nucleophiles to alkynes, allenes and alkenes.5
Recent developments involving the use of allenylamides in
organic synthesis have had a high impact because their trans-
formation can easily introduce nitrogen functionalities and they
can be used as a tether for the introduction of new stereocenters.6
Moreover, some of these compounds exhibit different reaction
modes to other allenes. For instance, we have already demonstrated
gold complexes catalyze the intermolecular addition of alcohols
to the proximal allenic double bond of N-tosyl-4-vinylidene-2-
oxazolidinone 1a, with the opposite regioselectivity to other gold-
catalyzed intermolecular hydroalkoxylations of allenes.5a
Treatment o◦f 1a and allyl alcohol (5 equiv.) as a nucleophile in
dioxane at 80 C gave the distal addition product 2a as a major
product and the proximal addition product 3a as a minor product
(Scheme 1). To our surprise, in contrast to thermal condition,
the use of 5% (Ph3P)AuSbF6, which was generated in situ from
5% (Ph3P)AuCl and 5% AgSbF6 in dichloromethane, altered
the regioselectivity dramatically, and gave the proximal addition
product 3a as the major product along with minor amounts of
the distal addition product 2a. The stereochemistry of 2a was
determined to be E by NOE experiments.11
=
that the terminal allenic C2¢ C3¢ double bond of N-tosyl-4-
vinylidene-2-oxazolidinone 1a7 acts as an electron acceptor in
a similar manner to the double bond of conjugated enones,
and undergoes a wide variety of unique reactions with olefins,
alkynes and hetero-nucleophiles under strictly thermal activation
conditions.8 Compounds possessing a 2-oxazolidione moiety are
also very important in synthetic chemistry since they form the
basis of some antibacterial agents,9 and play a crucial role as chiral
auxiliaries in asymmetric synthesis.10 In this paper, we report that
Scheme 1 Intermolecular addition of allyl alcohol to 1a.
Varying the counter anion of the silver salt showed that
AgSbF6 was the optimal co-catalyst (entries 1–5, Table 1). A
good regioselectivity and high yield of 3a were obtained when
triphenylphosphine was used as a ligand in place of tris(tert-
butyl)phosphine or other phosphine ligands (entries 1 and 4).11
Furthermore, the use of an excess of allyl alcohol (5 equiv.)
improved the yield of 3a and the regioselectivity (entry 3). Gold(I)
chloride and gold(III) chloride were also found to catalyze the
present reaction, albeit in low yield and with low regioselectivity
(entries 6 and 7). The cationic gold complex generated from AuCl
and AgSbF6 led to decomposition of 1a (entry 8), whereas the
combination of AuCl3 and AgSbF6 (3 equiv. with respect to Au)
as a catalyst provided the desired product 3a in slightly better yield
than with AuCl3 alone (entry 9). No reaction or decomposition of
1a was observed in the presence of (Ph3P)AuCl or AgSbF6 alone
aDepartment of Applied Chemistry, Graduate School of Science and Engi-
neering, University of Toyama, Gofuku 3190, Toyama, 930-8555, Japan.
E-mail: horino@eng.u-toyama.ac.jp; Fax: +81 76 445 6819; Tel: +81 76
445 6820
bDepartment of Applied Chemistry, Faculty of Engineering, Nagasaki
University, 1–14, Bunkyo, Nagasaki, 852-8521, Japan
† Electronic supplementary information (ESI) available: Experimental
procedures and characterizations. CCDC reference number 688562. For
ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/b808921c
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Table 1 Catalyst optimizationa
reaction tolerates substitution of the b- and g-positions of allyl
alcohol with alkyl and aryl groups (entries 4–7). The structure of 3d
was unambiguously confirmed by X-ray crystallography (Fig. 1).
The reaction of 1a with phenethyl alcohol gave 2h and 3h with
only low regioselectivity (entry 8). The use of sterically bulky 1-
buten-3-ol as a secondary alcohol diminished the yield of 3i, and
increased the yield of 2i (entry 9), which is obtained by addition
to the distal allenic double bond of 1a. As expected, the use of
tert-butanol as a nucleophile resulted in no reaction and 1a was
recovered quantitatively.
Entry [Au]
[Ag]
Time/h
2a (%)b
3a (%)b
1
(Ph3P)AuCl
AgSbF6
AgBF4
AgSbF6
AgSbF6
AgBF4
—
1.5
3
1.5
8
17
21
2
11
18
8
16
24
6
19
53
42
70
44
30
17
21
2
(Ph3P)AuCl
(Ph3P)AuCl
(t-Bu3P)AuCl
(t-Bu3P)AuCl
AuCl
AuCl3
AuCl
3c
4
5
6d
7e
8
AgSbF6 16
AgSbF6
decomposed
24
9f
AuCl3
0.5
30
10
—
AgSbF6 20
decomposed
a 1a (0.2 mmol), allyl alcohol (0.48 mmol), [Au] (5 mol%), [Ag] (5 mol%)
in DCM (1 mL) under air. b Isolated yield. c 5 equiv. of allyl alcohol was
used. d 1a was recovered in 53%. e 1a was recovered in 10%. f 3 equiv. of
AgSbF6 with respect to Au was used.
Table 2 Au(I)-catalyzed addition of alcohols to 1aa
Fig. 1 Structure of 3d (CCDC number 688562).† Hydrogen atoms have
been omitted for clarity.
The catalytic cycle involved in the present reaction, although
still speculative, probably involves initial coordination of the
gold complex to the central carbon of the allene bond of 1a,13
as shown in Scheme 2. To exclude the possibility that an allyl
cationic intermediate might be generated from 1a, 1a was treated
with the present catalyst system in the absence of allyl alcohol.
No isomerization of the allene bond of 1a to the 1,3-diene was
observed, and 1a was recovered quantitatively. Furthermore, no
reaction or decomposition of 1a was observed upon treatment
with a Brønsted acid catalyst such as p-TsOH or CF3SO3H.
Entry
1
ROH
Time/h
2
2 (%)b
2a (8)c
3 (%)b
3a (70)
2
3
4d
MeOH
EtOH
4
4
2b (0)
2c (5)c
2d (6)e
3b (65)
3c (64)
1.5
3d (57)
3e (60)
3f (68)
5
2
2e (trace)
2f (trace)
6
3
7
2
2g (0)
3g (58)
8
9
3
2h (21)c
2i (34)c
3h (37)
3.5
3i (trace)
Scheme 2 A plausible mechanism for the hydroalkoxylation of 1a.
10
tert-BuOH
12
no reaction
a 1a (0.2 mmol), alcohol (1.0 mmol), [Au] (5 mol%) and [Ag] (5 mol%) in
DCM (1 mL) under air. b Isolated yield. c Only E isomer. d E : Z = 96 : 4
of crotyl alcohol was used. e E : Z = >96 : 4 mixture of crotyl olefin.
The reaction of 1b with allyl alcohol produced only a trace
amount of 2j, and 1b was recovered in 90%. Nucleophilic attack
of the alcohol therefore appears to be hindered by the steric bulk
of the substituent at the C5 position of the 2-oxazolidinone ring.
Changing the tosyl substituent on the nitrogen of 1c for a benzoyl
group, reversed regioselectivity and only a trace amount of 3k were
obtained (Scheme 3). Furthermore, the use of 1d,14 which possesses
a benzyl group instead of an electron withdrawing group on the
(entry 10). Moreover, other group 10 and 11 complexes were found
not to catalyze the present reaction effectively.12
With the optimized reaction conditions in hand, a variety of
alcohols were examined (Table 2). Primary alcohols such as allyl
alcohol, methanol, and ethanol were found to participate in the
present reaction, by adding to the proximal allenic double bond
of 1a in most cases (entries 1–3, Table 2). In addition, the present
=
nitrogen, led to no reaction. Thus, the enamine C1¢ C2¢ double
bond appears to be activated by both the gold complex and the
strongly electron withdrawing tosyl group, thereby allowing attack
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Scheme 3 Effect of substituents on nitrogen.
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of the alcohol at the C5 position of the 2-oxazolidinone ring to
form vinyl gold intermediate II (Scheme 2).
To gain further insight into the mechanism, the gold(I)-catalyzed
addition of CH3OD to 1a was carried out. Deuterium was found
to be incorporated only in the C2¢ position of 1a as determined by
1H NMR analysis (Scheme 4).
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Scheme 4 Deuterium labeling experiment of 1a with CH3OD.
To illustrate the utility of the present hydroalkoxylation prod-
ucts, ring-closing metathesis (RCM) reactions of 3a and 3l using
Grubbs’ second generation catalyst15 gave the corresponding novel
spiro dihydrofuran 4a and dihydropyrane 4b respectively, in high
yields, as shown in Scheme 5.
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Scheme 5 Ring-closing metathesis of 3a and 3l.
In conclusion, we have developed a cationic gold(I)-catalyzed
intermolecular addition of alcohols toward the proximal allenic
double bond of 1a. The intermolecular addition of an alcohol to
the proximal allenic double bond catalyzed by gold is the first
example. Further study of synthetic applications of the reaction is
currently ongoing in our laboratory.
10 D. J. Ager, I. Prakash and D. R. Schaad, Chem. Rev., 1996, 96, 835.
11 See electronic supplementary information (ESI)†.
Notes and references
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12 No desired product 3a was obtained on treatment of 1a and allyl alcohol
with (PPh3)2PdCl2, CuI, CuOTf, PtCl2 or PtCl2/4COD. On the other
hand, use of (PPh3)2PdCl2/2AgSbF6 gave 2a and 3a as a mixture with
concomitant decomposition of 1a in poor yield (<10%, 2a : 3a = 1.7 : 1).
13 A. Fu¨rstner, M. Alcarazo, R. Goddard and C. W. Lehmann, Angew.
Chem., Int. Ed., 2008, 47, 3210.
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1, 953; (b) R. H. Grubbs and S. Chang, Tetrahedron, 1998, 54, 4413.
2 (a) For intramolecular hydroamination of allene, see: G. L. Hamilton,
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This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 4105–4107 | 4107
©