A practical gold-catalyzed route to 4-substituted oxazolidin-2-ones from N-Boc propargylamines

Article abstract of DOI:10.1002/ejoc.200700210

Au¹-catalyzed cyclization of N-Boc propargylamines into 4-alkylidene oxazolidin-2-ones is described. This modular approach provides access to a variety of nonproteogenic 4-substituted oxazolidinones that are important in asymmetric synthesis an

Full text of DOI:10.1002/ejoc.200700210

FULL PAPER
DOI: 10.1002/ejoc.200700210
A Practical Gold-Catalyzed Route to 4-Substituted Oxazolidin-2-ones from
N-Boc Propargylamines
Eun-Sun Lee,[a] Hyun-Suk Yeom,[a] Ji-Hyun Hwang,[a] and Seunghoon Shin*[a]
Keywords: Gold / Oxazolidinones / 1,3-Allylic interactions / Isomerization
AuI-catalyzed cyclization of N-Boc propargylamines into 4-
alkylidene oxazolidin-2-ones is described. This modular
approach provides access to a variety of nonproteogenic 4-
substituted oxazolidinones that are important in asymmetric
synthesis and biological applications. The current flexible
route is characterized by low catalyst loading, mild condi-
tions, and operational simplicity.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
and C–O bonds,[5] we and others reported that O-Boc
(homo)propargyl alcohols efficiently cyclize into cyclic enol
carbonates under AuI catalysis.[5c,5d] We projected an exten-
sion of this cyclization mode to N-Boc propargylamine as
a simple and efficient protocol for the synthesis of 4-substi-
tuted-5-alkylidene-oxazolidin-2-ones (Scheme 1).[6] During
the preparation of this manuscript, Carretero et al. and
Gagosz et al. independently reported such a transforma-
tion, each working on differently substituted substrates
(Figure 1).[6b,6c] Herein, we report our own study on the
cyclization of N-Boc propargylamines leading to the identi-
fication of factors affecting the rates of cyclization and dis-
cuss the intriguing isomerization mechanism found for in-
ternal alkyne substrates.
Introduction
Oxazolidin-2-ones with substituents at the 4-position are
one of the most versatile and widely used chiral auxiliaries
in organic synthesis, and unabated efforts have been made
to utilize this structural motif in a variety of asymmetric
transformations.[1] Over the recent years, oxazolidinone de-
rivatives have also attracted considerable attention as anti-
bacterial agents, as represented by Linezolid (Pfizer).[2] Par-
ticularly, 4-substituted oxazolidinone derivatives have
promising biological applications, such as cytokine modula-
tor and cholesterol lowering agents, as well as interesting
properties in RNA binding and peptidomimetics.[3] There-
fore, a flexible and modular protocol generating structurally
diverse 4-substituted oxazolidinone analogs is of current
interest in terms of its asymmetric synthesis and biological
applications.
The traditional route towards oxazolidin-2-ones involves
the reaction of 1,2-amino alcohol derivatives with phos-
gene.[4a] A number of approaches toward nonproteogenic
oxazolidinones have also been developed, including epoxide
ring opening, aminohydroxylation of alkenes, and electro-
chemical or Pd-catalyzed reaction of propargylamine with
CO2.[4b–4d] However, these methods often involve several
steps, harsh conditions, or are operationally cumbersome.
In this report, we disclose a AuI-catalyzed route toward 4-
substituted-5-alkylidene-oxazolidin-2-ones from N-Boc
propargylamines, which is characterized by mild conditions,
exceptionally low catalyst loading, and operational sim-
plicity.
Scheme 1. AuI-catalyzed route to 4-substituted-5-alkylidene-oxazo-
lidinone.
In the course of our investigation on gold-catalyzed acti-
vation of C–C multiple bonds for the formation of C–N
[a] Department of Chemistry, Hanyang University,
Seoul, Korea 133-791
Fax: +82-2-2299-0762
E-mail: sshin@hanyang.ac.kr
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Figure 1. Substrates used in this study.
Eur. J. Org. Chem. 2007, 3503–3507
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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E.-S. Lee, H.-S. Yeom, J.-H. Hwang, S. Shin
FULL PAPER
substituent (R1) and the Au-moiety bearing ligand. This
rate reduction can also be aggravated by the population of
the unfavored rotamer in the absence of N-substituents in
2.[6c]
Results and Discussion
We commenced our study with the preparation of N-Boc
protected α-aryl- and alkyl-substituted propargylamines by
the direct addition of the alkyne into imine equivalents.
However, N-Boc imines 2 having an aliphatic R1 group has
only scarce precedents owing to its facile tautomerization
into the corresponding enamine under basic conditions.[7]
Therefore, the one-pot procedure of Petrini, which involves
the addition of 2.2 equiv. of an alkynyl Grignard reagent to
readily available sulfones 1,[8] was best-suited for the
preparation of various N-Boc propargylamines 2a–r
with aromatic as well as aliphatic R1 substituents
(Scheme 2).
Therefore, we undertook an extensive optimization study
by using 2g as the substrate, and the selected data are
shown in Table 1.[9] In terms of the ligand on Au, sterically
demanding ligands seemed to have a detrimental effect,
which is in agreement with allylic strain, and a change in
the electronic nature of ligand did not improve the yields
(Table 1, Entries 3–6). Gratifyingly, the efficiency of the cat-
alyst was highly dependent on the counteranion of gold
–
–
–
(Table 1, Entries 6–10). While BF4 , ClO4 , and NTf2 as
counteranions showed a marginal improvement, the TfO–
complex turned out to be highly effective, giving 3g quanti-
tatively in 30 min at room temp. and 1 mol-% catalyst load-
ing (Table 1, Entry 10). THF, toluene, and DCM were all
appropriate solvents, with toluene giving the highest rate
and a 94% yield of 3g in 3 h with the use of only 0.5 mol-
% of the Au(PPh3)OTf complex at room temp.
With the optimized reaction conditions, we next investi-
gated the scope of the current cyclization by using N-Boc
propargylamines 2a–m and 2s–u having a terminal acetyl-
ene moiety (Table 2). For example, substrates having vari-
ous aromatic and heteroaromatic substituents with varying
electronic demand at R1 underwent clean reactions
(Table 2, Entries 1–8). The aliphatic substrates also under-
went a clean reaction, although they required the use of
1–5 mol-% of catalyst (Table 2, Entries 9–12). There was a
noticeable decrease in the reaction rate with increasing ste-
Scheme 2. One-pot preparation of N-Boc propargylamines; alk-
ynylmagnesium reagents (R2 ϶ H) were prepared by treating the
terminal alkynes with nBuLi, followed by MgBr2·OEt2.
In view of the mechanism for the cyclization of 2, a vi- ric bulk of R1 (Table 2, Entries 9–12). For example, 2l re-
nyl–AuI intermediate such as A can be expected as a result quired 5 mol-% of catalyst at 50 °C for a reasonable conver-
of the trans addition across the triple bond (Scheme 1).[11] sion. However, gem-disubstituted substrates 2s and 2t
Presumably, A would suffer from significant unfavorable al- underwent a rapid reaction with the use of 0.5 mol-% of the
lylic 1,3-interaction that develops between the propargylic catalyst (Table 2, Entries 13 and 14), with the help of
Table 1. Optimization of the cyclization.
Entry
Catalyst (loading)[a]
Solvent
Time
Yield [%][b]
1
2
3
4
5
6
7
8
AuCl (1%)
AuCl3 (1%)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
THF
toluene
DCM
toluene
24 h
24 h
24 h
24 h
13 h
8 h
2 h
2 h
2 h
30 min
5 min
5 min
5 min
1 h
Ͻ5
7
43
Au[P(C6F5)3]SbF6 (1%)
Au[P{(tBu)2biphenyl}]SbF6 (1%)
Au[P(o-tol)3]SbF6 (1%)
Au(PPh3)SbF6 (1%)
Au(PPh3)BF4 (1%)
Au(PPh3)ClO4 (1%)
Au(PPh3)NTf2 (1%)
Au(PPh3)OTf (1%)
Au(PPh3)OTf (1%)
Au(PPh3)OTf (1%)
Au(PPh3)OTf (1%)
Au(PPh3)OTf (0.5%)
59
Ͼ99
Ͼ99
3
10
24
Ͼ99
Ͼ99
Ͼ99
Ͼ99
94
9
10
11
12
13
14
[a] Catalyst was prepared in situ by mixing Au(PR3)Cl and Ag salt. [b] GLC yields.
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A Practical Au-Catalyzed Route to 4-Substituted Oxazolidin-2-ones
FULL PAPER
Thorpe–Ingold effect. Interestingly for proline-derived Table 3. Cyclization of substrates with an internal acetylene unit.
amine 2u, the reaction gave a mixture of 5-exo and 6-endo
products 3ua and 3ub in 53 and 17% yield, respectively
(Table 2, Entry 15), which is in contrast to that reported by
Gagosz.[6c]
Table 2. Cyclization of substrates with terminal acetylene.[a]
Entry Substrate (R1, R2)
Time
Yield [%][a] (Z/E)
1
2
3
4
5
6
2n (Ph, Ph)
2o (Ph, nBu)
2p (iPr, Ph)
2q (Ph, tBu)
2r (pMeO-Ph, Ph)
2v
12 h
4 h
12 h
2 h
3 h
3 h
97 (2.6:1)
93 (8.3:1)
99 (7.3:1)
85 (4.9:1)
93 (3.2:1)
92 (9.3:1)
[a] (Z/E) isomers were cleanly separated by chromatography and
the combined yield is indicated.
Scheme 3. Especially in the case of substrates without an
N-substituent (R = H), cationic vinyl–Au intermediate A
would partly undergo proton shift to form imine form C,
which isomerizes into AЈ to relieve the allylic strain. It is
noteworthy that the (E) geometry of 3 might play an inter-
esting role in defining the steric environment of the 4-sub-
stituted oxazolidinone.
[a] The catalyst was formed in situ from Au(PPh3)OTf (0.5 mol-%)
in toluene (0.2 ) at room temp. unless otherwise noted. [b] Isolated
yields after chromatography. [c] At 1 mol-% catalyst loading. [d] At
50 °C and 5 mol-% catalyst loading. [e] At 5 mol-% catalyst load-
ing.
Next, we tested substrates 2n–r that have an internal
acetylene unit; these substrates underwent a much slower
reaction (Table 3). Unexpectedly, in this case we found that
a mixture of geometric isomers was produced. For instance,
reaction of 2n produced a chromatographically separable
mixture of (Z)-3n and (E)-3n in a ratio of 2.6:1 (Table 3,
Entry 1) in 97% combined yield and other substrates gave
the corresponding oxazolidinones with varying ratios of
(Z/E).[10] When isomers (Z)-3n and (E)-3n were separated
and subjected again to the reaction conditions [Au(PPh3)-
OTf (5 mol-%) in toluene at 50 °C], we recovered only the
respective starting isomers even after 10 h without notice-
able isomerization, indicating that the ratio of (Z/E) iso-
mers is not the result of thermodynamic equilibration of
the products. The formation of (E)-3 was surprising, con-
sidering that the related substrate with N-substitution pro-
duced only the (Z) isomers as a result of the trans addition
to the alkyne that was activated by gold.[6b,11]
Scheme 3. Proposed mechanistic model for the isomerization reac-
tion.
The utility of the 4-substituted-5-methylene-oxazolidon-
2-ones was briefly examined as in Equation (1) and Equa-
tion (2). Diastereoselective hydrogenation of 3g in the pres-
ence of Pd on charcoal gave saturated oxazolidinone 4 in
83% yield (dr 7.6:1) and the hydroboration of 3e underwent
smoothly to give cytoxazone 5 in 72% yield, which is a po-
tent natural cytokine modulator.[12]
With the intent to clarify the mechanism for the pro-
duction of (E)-3, which is the apparent cis addition product,
we prepared N-allyl substrate 2v (Table 3, Entry 6). In this
case, there was a noticeable increase in the (Z/E) ratio (from
7.3:1 for 3p to 9.3:1 for 3v). On the basis of this observation,
we postulate the isomerization mechanism depicted in
(1)
Eur. J. Org. Chem. 2007, 3503–3507
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E.-S. Lee, H.-S. Yeom, J.-H. Hwang, S. Shin
FULL PAPER
1
3a: H NMR (400 MHz, CDCl3): δ = 4.19 (dd, J = 2.2, 3.3 Hz, 1
H), 4.75–4.76 (m, H), 6.17 (br. s, 1 H), 6.38 (br. s, 1 H), 7.41–7.60
(m, 4 H), 7.84–8.00 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 56.8, 88.4, 122.3, 124.8, 125.4, 126.1, 127.0, 129.2, 129.6, 130.4,
133.5, 134.1, 155.1, 156.3 ppm. IR (CH Cl ): ν = 1673, 1777 cm–1.
˜
2
2
(2)
C14H11NO2 (225.24): calcd. C 74.65, H 4.92, N 6.22; found C
73.64, H 5.14, N 5.81.
1
Conclusions
3ua: H NMR (400 MHz, CDCl3): δ = 1.58–1.72 (m, 1 H), 1.96–
2.28 (m, 3 H), 3.23 (ddd, J = 4.4, 6.9, 11.3 Hz, 1 H), 3.61–3.67 (m,
1 H), 4.32 (dd, J = 1.8, 3.3 Hz, 1 H), 4.36–4.44 (m, 1 H), 4.73 (dd,
J = 2.2, 2.9 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.0,
An efficient and general route toward 4-substituted-5-
alkylidene-oxazolidin-2-ones is reported by modular as-
sembly of aldehydes and alkynes through a AuI-catalyzed
cyclization. This procedure allows diverse modification of
oxazolidinones for steric and electronic tuning, which
would find fruitful applications in asymmetric synthesis, es-
31.8, 45.8, 62.3, 86.7, 154.7, 158.6 ppm. IR (CH Cl ): ν = 1678,
˜
2
2
1787 cm–1. C7H9NO2 (139.15): calcd. C 60.42, H 6.52; found C
60.47, H 6.75.
1
3ub: H NMR (400 MHz, CDCl3): δ = 1.58–1.72 (m, 2 H), 1.78–
pecially when coupled with asymmetric preparations.[13]
A
1.92 (m, 2 H), 1.96–2.08 (m, 2 H), 2.11–2.22 (m, 1 H), 3.45 (ddd,
J = 3.0, 9.5, 12.4 Hz, 1 H), 3.72 (td, J = 8.4, 11.8 Hz, 1 H), 4.07–
4.11 (m, 1 H), 5.22 (dd, J = 1.8, 6.2 Hz, 1 H), 6.40 (dd, J = 2.2,
5.9 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.7, 32.9,
45.7, 55.7, 103.6, 139.6, 149.5 ppm. C7H9NO2 (139.15): calcd. C
60.42, H 6.52; found: C 60.16, H 6.83.
very low catalyst loading is a further practical merit of the
current protocol in view of the economical consideration.
Further work aimed at the utilization of (E)-3n–v as chiral
auxiliaries is currently underway in this laboratory.
(Z)-3n: IR (CH Cl ): ν = 1688, 1763 cm–1. 1H NMR (400 MHz,
˜
2
2
Experimental Section
CDCl3): δ = 5.30 (d, J = 1.8 Hz, H, vinyl), 5.53 (s, H, NCH), 5.84
(br. s, H, NH), 7.18–7.28 (m, H), 7.30–7.38 (m, 2 H), 7.38–7.52 (m,
6 H), 7.52–7.64 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
60.6, 104.8, 127.0, 127.0, 128.3, 128.4, 129.21, 129.27, 133.1, 138.7,
148.8, 155.9 ppm. C16H13NO2 (251.28): calcd. C 76.48, H 5.21, N
5.57; found C 76.2, H 5.18, N 4.98. nOe correlation:
General: All reactions were performed in oven-dried glassware un-
der an argon atmosphere with freshly distilled solvents. All other
commercially available reagents (Aldrich) were used without fur-
1
ther purification. H and 13C NMR spectra were acquired with a
Varian 400 MHz (Mercury) spectrometer. Chemical shifts are re-
ported relative to chloroform for 1H NMR (7.26 ppm) and 13C
NMR (77.0 ppm) spectroscopy. Elemental analyses were performed
with a Thermo Flash EA1102 Series instrument at Sogang Univer-
sity, Seoul, Korea. Infrared spectra were recorded with a Jasco
Model FTIR-480 Plus spectrometer.
Representative Procedure for the Preparation of N-Boc Propar-
gylamines (2a–r): To a solution of phenylacetylene (176 mg,
1.73 mmol) in tetrahydrofuran (3.6 mL) cooled to 0 °C was added
nBuLi (2.5  in hexane, 0.69 mL, 1.73 mmol) under an Ar atmo-
sphere. The reaction mixture was stirred at 0 °C for 30 min and
magnesium bromide diethyl ether (446.7 mg, 1.73 mmol) was added
to the solution. Subsequently, 1g (200 mg, 0.57 mmol) in THF
(1 mL) was added to the above mixture at 0 °C, and the mixture
was slowly warmed to room temp. over 2 hr. A saturated solution
of NH4Cl (5 mL) was added, and the aqueous layer was extracted
with diethyl ether (3ϫ10 mL). The organic layers were combined
and dried with MgSO4. After removal of solvent in vacuo, the re-
sulting oil was purified by silica gel chromatography (EtOAc/hex-
ane, 1:10) to provide 165.7 mg (94%) of 2n as a pale yellow solid.
(E)-3n: 1H NMR (400 MHz, CDCl3): δ = 5.25–5.28 (m, 1 H, vinyl),
5.62 (dd, J = 1.8, 3.6 Hz, 1 H, NCH), 5.68 (br. s, 1 H, NH), 7.28–
7.46 (m, 7 H), 7.60–7.74 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 55.8, 98.6, 124.7, 126.6 128.4, 128.7, 129.1, 129.4,
131.4, 141.3, 147.5, 150.1 ppm. nOe correlation:
Preparation and Cyclization of N,N-Allyl-Boc Propargylamine 2v:
To a solution of 2p (100.0 mg, 0.365 mmol) in anhydrous DMF
(1 mL) at 0 °C was added NaH (60% dispersion in mineral oil,
17.6 mg, 0.0.439 mmol). When gas evolution ceased, allyl bromide
(66.4 mg, 0.549 mmol) was added, and the mixture was warmed to
room temperature over 4 h. To the reaction was added water (5 mL)
and the aqueous layer was extracted with Et2O (3ϫ5 mL). The
combined organic layer was dried (MgSO4), filtered, and the sol-
vents evaporated. The residue was purified by chromatography
(EtOAc/Hexane, 1:6) to give 2v (101.4 mg, 89%) as a colorless oil.
To a vial containing Au(PPh3)Cl (5.1 mg, 0.010 mmol) and AgOTf
(2.7 mg, 0.010 mmol) was added a solution of 2v (71.0 mg,
0.210 mmol) in toluene (0.4 mL), and the mixture was allowed to
stir at room temp. for 3 h. The crude 1H NMR spectrum indicated
1
2n: H NMR (400 MHz, CDCl3): δ = 1.46 (s, 9 H), 5.21 (br. s, 1
H), 5.90 (br. d, J = 6.9 Hz, 1 H), 7.27–7.31 (m, 4 H), 7.34–7.38 (m,
2 H), 7.44–7.46 (m, 2 H), 7.56 (d, J = 7.3 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 28.2, 46.7, 80.1, 84.6, 87.4, 122.5, 126.8,
127.9, 128.2, 128.3, 128.5, 131.6, 139.4, 154.7 ppm.
Representative Procedure for the Cyclization of 2a–v: To a solution
of Au(PPh3)Cl (1.3 mg, 0.0025 mmol) and AgOTf (0.65 mg,
0.0025 mmol) in toluene (2.5 mL) was added 2a (140 mg,
0.5 mmol) at room temperature, and the reaction mixture was
stirred at room temp. for 50 min. After removal of solvent in vacuo,
the residue was purified by silica gel chromatography (EtOAc/hex-
ane, 1:3) to provide 102 mg (90%) of 3a as a pale yellow solid. For an isomeric ratio of 90.3:9.7 for Z/E isomers. Chromatographic
other substrates, refer to Tables 2 and 3 for catalyst loading and
conditions.
separation of the crude mixture gave 44.7 mg of (Z)-3v (44.7 mg)
and (E)-3v (4.8 mg) with a combined yield of 92%.
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A Practical Au-Catalyzed Route to 4-Substituted Oxazolidin-2-ones
FULL PAPER
2v: 1H NMR (400 MHz, CDCl3, mixture of rotamers at room
temp.): δ = 0.96 (d, J = 6.6 Hz, 3 H), 1.11 (d, J = 6.6 Hz, 1 H),
1.45 (s, 9 H), 2.01 (m, 1 H), 3.96 (br. s, 2 H), 4.59, 4.89 (two br. s,
each from major and minor rotamers, 1 H, NCH), 5.10 (br. d, J =
10.2 Hz, 1 H), 5.20 (br. d, J = 15.4 Hz, 1 H), 5.97 (br. m, 1 H),
7.27–7.32 (m, 3 H), 7.35–7.41 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 19.1, 19.6, 28.3, 32.8, 47.2, 54.9, 79.9, 84.9, 87.3, 115.9,
123.0, 128.0, 128.2, 131.5, 135.8, 155.4 ppm.
(Z)-3v: 1H NMR (400 MHz, CDCl3): δ = 0.92 (d, J = 6.9 Hz, 3
H), 1.07 (d, J = 6.9 Hz, 3 H), 2.15 (m, 1 H), 3.62 (dd, J = 7.7,
15.7 Hz, 1 H), 4.30 (dd, J = 1.8, 2.9 Hz, 1 H), 4.34 (tdd, J = 1.8,
4.8, 15.7 Hz, 1 H), 5.28 (br. d, J = 11.4 Hz, 1 H), 5.28 (d, J =
16.5 Hz, 1 H), 5.49 (d, J = 1.5 Hz, 1 H), 5.79 (m, 1 H), 7.18–7.24
(m, 1 H), 7.30–7.36 (m, 2 H), 7.56–7.61 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 15.4, 17.4, 44.5, 63.5, 104.4, 119.1, 126.8,
128.4, 131.4, 133.4, 144.8, 155.2 ppm.
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Part of this work was presented at Chirality 2006: a) E.-S. Lee,
S. Shin, “Synthesis of Oxazolidin-2-ones by AuI-Catalyzed In-
tramolecular Functionalization of N-Boc Propargyl Amines:
Chiral Auxiliary beyond Chiral Pool”, Chirality 2006, The 18th
International Symposium on Chirality, June 25–28, 2006 (ab-
stract due date April 30, 2006), Busan, Korea. Two papers on a
AuI-catalyzed route to 5-methylene-oxazolidin-2-ones appeared
while this manuscript was in preparation: b) R. Robles-
Machín, J. Adrio, J. C. Carretero, J. Org. Chem. 2006, 71, 5023–
5026; c) A. Buzas, F. Gagosz, Synlett 2006, 2727–2730.
Hydrogenation of Oxazolidinone 3g: To a solution of 3g (30 mg,
0.17 mmol) in methanol (2 mL) was added Pd/C (10 wt.-%, 36 mg,
0.0034 mmol) and H2 gas was bubbled from a balloon at room
temperature. After 3 h, the reaction mixture was filtered through a
pad of Celite and washed with MeOH (4 mL) and diethyl ether
(4 mL). The combined organic phase was dried with MgSO4. After
removal of the solvent in vacuo, the resulting oil was purified by
silica gel chromatography (EtOAc/hexane, 1:4) to provide 25 mg
(83% yield; syn/anti, 87:13) of 4[14] as a white solid.
[6]
Hydroboration of Oxazolidinone 3e: To a solution of 3e (19 mg,
0.095 mmol) in THF (1 mL) was added BH3·THF (1 , 168 µL,
0.17 mmol) dropwise at 0 °C, and the reaction mixture was stirred
at 50 °C for 1 h followed by oxidation with NaOH (2 , 1 mL) and
H2O2 (30%, 1 mL). The aqueous layer was extracted with diethyl
ether (3ϫ2 mL), and the combined organic layer was dried with
MgSO4. After removal of solvent in vacuo, the resulting oil was
purified by silica gel chromatography (CH2Cl2/MeOH, 6:1) to pro-
vide 14.8 mg (72%) of 5.[12b]
[7]
[8]
a) B. M. Trost, J. Jaratjaroonphong, V. Reutrakul, J. Am.
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a) T. Mecozzi, M. Petrini, J. Org. Chem. 1999, 64, 8970–8972.
For a related one-pot protocol, see: b) X. Guinchard, Y. Vallée,
J.-N. Denis, Org. Lett. 2005, 7, 5147–5150; c) R. Ballini, M.
Petrini, Tetrahedron Lett. 1999, 40, 4449–4452; d) T. Mecozzi,
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Supporting Information (see footnote on the first page of this arti-
cle): Compound characterization data for 2a–r and 3b–t, 1H and
13C NMR spectra for all enlisted new compounds.
Acknowledgments
[9] As control experiments, the reaction of 2g in the presence of
Brønsted acid (HNTf2, 5 mol-%) resulted only in partial de-
composition after 2 d at room temp., recovering starting 2g in
84% yield. The use of AgOTf (5 mol-%) instead resulted in
diminished conversion (22% of 3g for 4 h at room temp.). For
examples of the catalytic activity of both gold and protons, see:
A. S. K. Hashmi, L. Schwarz, P. Rubenbauer, M. C. Blacko,
Adv. Synth. Catal. 2006, 348, 705–708.
This work was supported by the research fund of Hanyang Univer-
sity (HY-2005-S) and Korea Research Foundation Grant funded by
the Korean Government (MOEHRD, Basic Research Promotion
Fund, KRF-2005–003-C00106). E. S. L, H. S. Y, and J. H. H thank
BK21 program for financial support.
[10] The double bond geometry was based on NOE experiments.
See Supporting Information.
[1] Asymmetric protonation: a) L.-L. Huang, M.-H. Xu, G.-Q.
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closely related cyclization of N-carbethoxy N-allyl propar-
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[12] Isolation: a) H. Kakeya, M. Morishita, H. Koshino, T.-L. Mor-
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therein.
[13] For kinetic resolution, see: V. B. Birman, H. Jiang, X. Li, E. W.
Uffman, J. Am. Chem. Soc. 2006, 128, 6536–6537.
[14] A. Zietlow, E. Steckhan, J. Org. Chem. 1994, 59, 5658–5661.
Received: March 8, 2007
[2] Linezolid (Zyvox) as a representative example: a) S. J. Brickner,
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Published Online: May 31, 2007
Eur. J. Org. Chem. 2007, 3503–3507
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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