Rhodium(I)-catalyzed cycloisomerization reaction of yne-allenamides: An approach to cyclic enamides

Article abstract of DOI:10.1055/s-2008-1078169

In this paper, we demonstrate a successful conversion of alkynyl allenamides to triene-containing heterocycles via a rhodium(I)-catalyzed cycloisomerization reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1078169

LETTER
2303
Rhodium(I)-Catalyzed Cycloisomerization Reaction of Yne-Allenamides:
An Approach to Cyclic Enamides
R
hodium(I)-Cataly
a
zed
C
ycloi
y
somerizationReact
M
ionof
Y
ne-Allenamid
.
e
s
Brummond,* Bingli Yan
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Fax +1(412)6248611; E-mail: kbrummon@pitt.edu
Received 24 February 2008
O
O
Abstract: In this paper, we demonstrate a successful conversion of
alkynyl allenamides to triene-containing heterocycles via a rhodi-
um(I)-catalyzed cycloisomerization reaction.
[Rh(CO)2Cl]2
(10 mol%)
•
N
N
O
O
toluene, r.t.
30 min, 79%
Key words: cycloisomerization, cyclocarbonylation, allenamide,
enamide, Diels–Alder
1b
2b
Scheme 1
Transition-metal-catalyzed cycloisomerization reactions
represent a powerful strategy for making carbon–carbon
bonds.1 Our group reported the first example of a rhodi-
um(I)-catalyzed cycloisomerization reaction of an allen-
yne to afford a cross-conjugated triene.2 The synthetic
potential of this structurally interesting triene seems high,
yet it has only seen limited use. In large, because of the
limited methods available for their preparation, and con-
trolling the reacting double bonds of the trienyl unit is
challenging.3 The rhodium(I)-catalyzed allenic Alder-ene
reaction discovered in our lab, addresses both of these
shortcomings. Firstly, the conditions required to generate
the triene are mild and show a high degree of functional-
group compatibility. Secondly, the newly formed triene is
comprised of two structurally unique dienes capable of
undergoing discreet reactions. Recently, we have extend-
ed the scope of the allenic Alder-ene reaction to include
allenamides which cycloisomerize to provide enamide-
containing trienes.4 Enamides are important subunits fre-
quently found in natural products and biologically active
compounds.5 They are also useful intermediates in organ-
ic transformations.6 Herein, the results of this study are re-
ported.
amine using 1 N HCl, then the methyl ester was reduced
to a hydroxyl group. Reaction of the resulting amino alco-
hol with triphosgene8 afforded compounds 8a,b and 9a,b
in 26–70% yield for the four steps. Finally, the terminus
of the alkyne was further functionalized with trimethylsi-
lyl, phenyl, and methoxyphenyl groups to give 8c, 9c, 8d
and 9d, respectively.
Propargylic carbamates were prepared from Garner’s al-
dehyde 10.9 Reacting 10 with dimethyl-1-diazo-2-oxo-
propylphosphonate (Seyferth reagent)10 under basic
conditions gave alkyne 11a in 61% yield.11 Compound
11a was converted to 11b in nearly quantitative yield by
using n-BuLi and methyl iodide. Carbamates 12a and 12b
were obtained by treatment of 11a and 11b with trifluoro-
acetic acid in MeOH followed by ring closure in the pres-
ence of triphosgene. The terminus of the alkyne was
further functionalized with a trimethylsilyl and phenyl
group to give 12c and 12d in 90% and 72% yield, respec-
tively.
With carbamates 8a–d, 9a–d, and 12a–d in hand, the cou-
pling reaction with the allenyl halides was examined.12
After some experimentation, it was determined that a
slight modification to the Hsung protocol [copper
thiophene-2-carboxylate (CuTC), N,N-dimethylethylene-
diamine (DMEDA), Cs2O3, BaO, and allenyl iodide at 50
°C] worked best for the preparation of allenamides.13,14
The results of this study are reported in Tables 1 and 2.
Reaction of the carbamate 12a with allene 13b using the
modified Hsung coupling protocol (BaO was added as an
acid scavenger), afforded none of the allenamide 14a, in-
stead only a trace amount of triene 15a was isolated. The
terminal alkyne was assumed to be a complicating factor
in this reaction and as predicted, the reaction of carbamate
12b (R = Me) under identical conditions gave allenamide
14b in 52% yield (Table 1, entry 2). Interestingly, reaction
of carbamate 12c and 12d with allene 13b gave only
trienes 15c and 15d in 52% and 53% yield, respectively
(entries 3, 4). However, carbamate 12c, possessing a TMS
group on the terminus of the alkyne, underwent the cou-
Initially, we conducted a reaction on allenamide 1b using
the standard conditions developed in our group
{[Rh(CO)2Cl]2 (10 mol%), toluene, r.t., argon atmo-
sphere} and in 30 minutes, enamide 2b was obtained in
79% yield (Scheme 1). Encouraged by the successful cy-
cloisomerization reaction of the allenamide 1b, a variety
of alkynyl allenamides were prepared to further explore
the scope and limitations of this reaction.
A variety of alkyne-substituted carbamates were prepared
using the protocols depicted in Scheme 2 and Scheme 3.
The alkynes were installed by first alkylating the protect-
ed methyl ester of glycine 37 with 4a,b or 5b,c to give 6a,b
and 7b,c. Next the protecting group was removed from the
SYNLETT 2008, No. 15, pp 2303–2308
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5
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9
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0
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Advanced online publication: 28.08.2008
DOI: 10.1055/s-2008-1078169; Art ID: S02008ST
© Georg Thieme Verlag Stuttgart · New York

2304
K. M. Brummond, B. Yyn
LETTER
O
O
Ph
Ph
Ph
N
a
N
MeO
R
+
n
X
MeO
Ph
R
n
3
4a,b
5b,c
6a, n = 1, R = H
6b, n = 1, R = Et
7b, n = 2, R = i-Pr
7c, n = 2, R = TMS
O
LDA
O
TMSCl
NH
1) 1 N HCl, THF, 5 min, r.t.
2) NaBH4, EtOH, 55 °C
O
R1 = H
NH
O
Si
3) triphosgene, THF, 55 °C
n
R1
O
n
8c, n = 1
9c, n = 2
ArI, Et3N
8a, n = 1, R1 = H, 54% for 4 steps
8b, n = 1, R1 = Et, 70% for 4 steps
9a, n = 2, R1 = H, 49% for 4 steps
9b, n = 2, R1 = i-Pr, 26% for 4 steps
NH
Pd(PPh3)4
O
R1 = H
Ar
n
8d, n = 1
9d, n = 2
Ar = Ph, 4-MeOC6H4
a) conditions A: NaH, THF–DMF,
conditions B: KH, 18-C-6,
or
Br
Br
4a
4b
TMS
or
I
OTf
5b
5c
Scheme 2
O
1) TFA, MeOH, 0 °C
2) triphosgene, THF
K2CO3, MeOH
Seyferth reagent
NH
O
NBoc
NBoc
O
O
61%
O
R
10
12a 37% over 2 steps, R = H
12b 38% over 2 steps, R = Me
12c 90% from 11a, R = TMS
12d 72% from 11a, R = Ph
R
12
a
b
BuLi
MeI
11a R = H
11b R = Me
a) LDA, TMSCl; b) PhI, Et3N, Pd(PPh3)4
Scheme 3
pling reaction with the less sterically encumbered allene tively (entries 2 and 4). Allenamide formation with the
13a, to give the allenamide 14e in 56% yield (entry 5). less sterically encumbered allene (13a) gave good yields
These results suggest that complication can be partially at- of allenamide 1f–h (entries 5–8). Also the carbamate 8b
tributed to the reactivity of the intermediate allenamide to- underwent the coupling reaction with the electron-defi-
wards carbocyclization and the instability of the resulting cient allenyl iodide 13c, to form the desired product, albeit
trienes. Triene 15c was not stable enough to obtain a 13C in low yield (entry 9). This is the first example of coupling
NMR spectrum and 15d decomposed upon storage over- reaction between a carbamate and an electron-deficient al-
night in the freezer. A control experiment was performed lenyl iodide partner. The allenamides (1e–i) were isolated
where 14d was isolated and heated in toluene at 40 °C to as a mixture of diastereomers (about 1:1).
give triene 15d, suggesting that triene formation is a ther-
mal process.
The allenamide forming protocol was tested on a series of
carbamates 9a–d possessing two methylene units between
We turned to alkynes possessing one methylene unit be- the alkyne and the carbamate (Table 3). Surprisingly, the
tween the alkyne and the carbamate moiety (Table 2). yield for the silyl-substituted alkynes (entries 2 and 5)
This series of substrates proved to be more tolerant of were typically lower than that for terminal alkyne (entry
these coupling conditions, evidenced by terminal alkynes 3) or alkynes substituted with alkyl (entries 1 and 4).
giving moderate yields of allenamides (entries 1 and 5).
Carbamate 8c, possessing an internal alkyne substituted
Each of the allenamides was subjected to the rhodium(I)-
catalyzed Alder-ene reaction conditions developed in our
with a trimethylsilyl group gave an 88% yield of allen-
lab {[Rh(CO)2Cl]2 (10 mol%) in toluene, under an argon
amide 1c (entry 3). Substitution of the alkyne with an eth-
atmosphere at r.t.}.2 Exposure of allenamide 14b to these
yl group and an aryl group (4-MeOC6H4) gave
conditions gave the triene 15b16 in 72% after 3.5 hours
(Table 4, entry 1). Unfortunately, this triene is not stable
allenamides 1b15 and 1d in 79% and 35% yield, respec-
Synlett 2008, No. 15, 2303–2308 © Thieme Stuttgart · New York

LETTER
Rhodium(I)-Catalyzed Cycloisomerization Reaction of Yne-Allenamides
2305
Table 1 Formation of Allenamides 14b,e and Trienes
O
O
O
(CH2NHMe)2
R1
CuTC, Cs2CO3, BaO
N
N
•
R1
NH
+
O
O
O
•
toluene, 50 °C, 14 h
I
13a, R1 = H
13b, R
R
R
R
1 = Me
15
12
14
Entry
Carbamate
Allene
14
Yield (%)
15
15a
–
Yield (%)
1
2
3
4
5
12a R = H
13b R1 = Me
14a
14b
14c
14d
14e
–
trace
–
12b R = Me
12c R = TMS
12d R = Ph
12c R = TMS
13b R1 = Me
13b R1 = Me
13b R1 = Me
13a R1 = H
52
–
15c
15d
–
52
53
–
–
56
Table 2 Copper-Catalyzed Coupling to Form Allenamides 1a–i
Table 3 Copper-Catalyzed Coupling to Form Allenamides 16a–f
O
O
O
NH
NH
O
R
8
O
9
(CH2NHMe)2
O
CuTC, Cs2CO3, BaO
R
R1
•
(CH2NHMe)2
CuTC, Cs2CO3, BaO
N
O
+
•
toluene, 50 °C, 20 h
+
N
O
R1
R1
toluene, 50 °C, 20 h
•
R
R1
•
I
1
13
I
16
R
13
Entry Carbamate
Allene
1
Yield
(%)
Entry
Carbamate
9b R = i-Pr
9c R = TMS
9a R = H
Allene
16
Yield (%)
13b R1 = Me
13b R1 = Me
13a R1 = H
13a R1 = H
13a R1 = H
13a R1 = H
16a
16b
16c
16d
16e
16f
70
40
59
66
32
30
1
2
3
4
5
6
7
8
9
8a R = H
13b R1 = Me
1a
1b
1c
1d
1e
1f
40
79
88
35
40
59
86
68
13
1
2
3
4
5
6
8b R = Et
8c R = TMS
13b R1 = Me
13b R1 = Me
8d R = 4-MeOC6H4 13b R1 = Me
9b R = i-Pr
9c R = TMS
9d R = Ph
8a R = H
13a R1 = H
13a R1 = H
13a R1 = H
8b R = Et
8c R = TMS
1g
1h
1i
8d R = 4-MeOC6H4 13a R1 = H
8b R = Et
13c R1 = CO2Me
lowed by reductive elimination of a metallo-hydride spe-
cies to give trienes 15 and 2.2a Interestingly, the electron-
deficient alkynoate 1i underwent the Alder-ene reaction
smoothly to give the desired triene 2i in 85% yield
(Table 4, entry 11). The presence of the ester can help to
differentiate the reactivity of the double bonds of the
triene. Furthermore, there is no different cycloisomeriza-
tion rate observed between the diastereosiomers of allen-
amides 1e–i.
and can only be stored at room temperature for 2–3 hours.
Reaction of allenamide 14e under these conditions gave a
mixture of unidentifiable compounds (Table 4, entry 2).
Next, the cycloisomerization reaction of the allenamides
1a–i was investigated. To our delight, each one of these
substrates underwent an allenic Alder-ene reaction to af-
ford the trienes in high yields (Table 4, entries 3–11). The
mechanism for the formation of trienes 15 and 2 involves
coordination of rhodium to the allenamides 14 and 1 to
form the rhodium-metallocycle intermediate. b-Hydride
elimination of the intermediate rhodium metallocycle fol-
Cycloisomerization of allenamides 16a–f was examined
(Table 5). Attempts to effect the cycloisomerization on
trisubstitued allenamides 16a and 16b afforded trace
quantities of a product resulting from an isomerization of
the allene to a 1,3-diene along with small amount of cy-
cloisomerization product 17 and cyclocarbonylation prod-
Synlett 2008, No. 15, 2303–2308 © Thieme Stuttgart · New York

2306
K. M. Brummond, B. Yyn
LETTER
Table 4 Rhodium(I)-Catalyzed Alder-Ene Reaction of Allenamides
Table 5 Rhodium(I)-Catalyzed Cyclizations of 16a–f to Form
to Form Five- and Six-Membered Trienes
Seven-Membered Rings
O
O
[Rh(CO)2Cl]2 (10 mol%)
toluene, r.t.,
O
R1
•
R1
N
R1
O
O
O
N
N
30 min to 3.5 h
O
R
n
n
O
R
R
[Rh(CO)2Cl]2 (10 mol%)
toluene, 85 °C, 50 min
17
•
R1
14b,e, n = 0
1a–i, n = 1
N
O
15b,e, n = 0
2a–i, n = 1
+
R1
Entry Allenamide
Triene Yield
(%)
R
16
O
N
O
1
2
14b R = Me, R1 = Me, n = 0
14e R = TMS, R1 = Me, n = 0
15b
15e
2a
2b
2c
72
–
R
18
Entry Allenamide
Atmo- Product Yield dr
3
1a R = H, R1 = Me, n = 1
79
79
95
87
68
71
90
73
85
sphere
(%)
4
1b R = Et, R1 = Me, n = 1
1c R = TMS, R1 = Me, n = 1
1d R = 4-MeOC6H4, R1 = Me, n = 1
1e R = H, R1 = H, n = 1
a
a
1
2
3
4
5
6
7
16a R = i-Pr, R1 = Me
Ar
–
–
–
–
5
16b R = TMS, R1 = Me Ar
–
–
6
2d
2e
16c R = H, R1 = H
16d R = i-Pr, R1 = H
16d R = i-Pr, R1 = H
16e R = TMS, R1 = H
16f R = Ph, R1 = H
Ar
17a
18a
18a
18b
18c
12
35
75
89
75
–
7
Ar
–
8
1f R = Et, R1 = H, n = 1
2f
CO
CO
CO
3:1
3:1
9
1g R = TMS, R1 = H, n = 1
1h R = 4-MeOC6H4, R1 = H, n = 1
1i R = Et, R1 = CO2Me, n = 1
2g
2h
2i
10
11
3.6:1
a Isomerization of allene to 1,3-diene observed by crude 1H NMR.
uct 18 (Table 5, entries 1 and 2). For the disubstituted
allenamide 16c, possessing a terminal alkyne, Alder-ene
product 17a17 formed under cycloisomerization condi-
tions, albeit in 12% yield (Table 5, entry 3). However,
subjecting allenamide 16d to the Alder-ene conditions af-
forded cyclocarbonylation product 18a in 35% yield, but
no Alder-ene product was observed (Table 5, entry 4).
Changing the atmosphere from argon to carbon monoxide
gave 18a in 75% yield18 (Table 5, entry 5). This Pauson–
Khand-type reaction of allenamides to form bicy-
clo[4.3.0]nonadecadienones has also been reported by
Hsung and co-workers.19 Replacement of isopropyl group
on the terminus of alkyne with trimethylsilyl or phenyl
group gave 18b and 18c in 89% and 75% yield, respec-
tively, as a mixture of diastereomers (Table 5, entries 6
and 7). The cyclocarbonylation products 18a–c have dias-
tereomeric ratios ranging from 3:1 to 3.6:1 and the starting
allenamides 16d–f have diastereomeric ratios ranging
from 1:1 to 1.5:1. It is not known at this time whether the
epimerization occurs during the cyclocarbonylation pro-
cess or after the formation of products. It seems that the
substitution pattern on the alkyne moiety of the disubsti-
tuted allenamide plays an important role. For the substi-
tuted alkyne, CO insertion is faster than b-H elimination
affording the cyclocarbonylation products 18a–c. Howev-
er, for the terminal alkyne, b-H elimination is faster than
CO insertion affording enamide triene 17a as the only
product.
Reactions involving the trienes were briefly examined.
Triene 2b underwent Diels–Alder reaction with N-phe-
nylmaleimide to give the tetracyclic compound 1920 as a
single diastereomer (Scheme 4). The stereochemistry was
confirmed by X-ray crystallographic analysis.
In summary, a series of alkyne allenamides were prepared
via a copper-catalyzed coupling reaction between carbam-
ates and allenyl iodides. Allenic cycloisomerization reac-
tions of the corresponding alkyne allenamides proceeded
smoothly to give triene-containing enamides when em-
bedded in a six-membered ring. Cycloisomerization reac-
tions producing trienes as part of a five-membered ring
were too reactive and decomposed upon short-term stor-
age. For cycloisomerization reactions involving the for-
mation of enamides embedded in a seven-membered ring,
competing isomerization and cyclocarbonylation process-
Ph
O
N
O
O
N-phenylmaleimide
toluene, 75 °C, 75%
O
N
H
O
N
H
O
2b
19
Scheme 4
Synlett 2008, No. 15, 2303–2308 © Thieme Stuttgart · New York

LETTER
Rhodium(I)-Catalyzed Cycloisomerization Reaction of Yne-Allenamides
2307
(0.643 g, 4.20 mmol), and Cs2CO3 (1.367 g, 4.20 mmol).
After flushing with nitrogen, toluene (15 mL) was added,
followed by DMEDA (45 mL, 0.42 mmol), then 1-iodo-3-
methylbuta-1,2-diene (500 mL, 4.20 mmol). The flask was
covered with aluminum foil and heated at 50 °C for 20 h.
The reaction was then cooled to r.t., filtered through a short
pad of Celite, and concentrated in vacuo. The residue was
purified by column chromatography [SiO2, eluting with 95%
to hexanes–EtOAc (1:1), 5% Et3N] to afford the allenamide
1b (0.363 g, 79%) as a pale yellow oil.
es were observed. The synthetic utility of these enamide-
containing trienes has briefly been investigated and pre-
liminary studies demonstrated chemo- and stereoselectiv-
ity in a Diels–Alder reaction.
References and Notes
(1) For a recent review, see: Brummond, K. M.; Loyer-Drew, J.
A. C–C Bond Formation (Part 1) by Addition Reactions:
Alder-Ene Reaction, In Comprehensive Organometallic
Chemistry III, Vol. 10; Crabtree, R. H.; Mingos, M. P.;
Ojima, I., Eds.; Elsevier: Oxford, 2007, Chap. 10.12.
(2) (a) Brummond, K. M.; Chen, H.; Sill, P.; You, L. J. Am.
Chem. Soc. 2002, 124, 15186. (b) Brummond, K. M.;
Mitasev, B. Org. Lett. 2004, 6, 2245. (c) Subsequently a
similar finding was reported: Shibata, T.; Takesue, Y.;
Kadowaki, S.; Takagi, K. Synlett 2003, 268.
(3) For example, see: (a) Brummond, K. M.; You, L.
Tetrahedron 2005, 61, 6180. (b) Mitasev, B.; Yan, B.;
Brummond, K. M. Heterocycles 2006, 70, 367; and
references cited therein.
(4) For an enamide cycloisomerization, see: (a) Trost, B. M.;
Pedregal, C. J. Am. Chem. Soc. 1992, 114, 7292.
(b) Arisawa, M.; Terada, Y.; Theeraladanon, C.; Takahashi,
K.; Nakagawa, M.; Nishida, A. J. Organomet. Chem. 2005,
690, 5398.
(5) For preparation of cyclic enamides and natural products
containing cyclic enamides, see: (a) Kinderman, S. S.;
Maarseveen, J. H. V.; Schoemaker, H. E.; Hiemstra, H.;
Rutjes, F. P. J. T. Org. Lett. 2001, 3, 2045. (b) Klapars, A.;
Campos, K. R.; Chen, C.-Y.; Volante, R. P. Org. Lett. 2005,
7, 1185. (c) Zhang, X.; Zhang, Y.; Huang, J.; Hsung, R. P.;
Kurtz, K. C. M.; Oppenheimer, J.; Petersen, M. E.;
Sagamanova, I. K.; Shen, L.; Tracey, M. R. J. Org. Chem.
2006, 71, 4170. (d) Toumi, M.; Couty, F.; Evano, G. Angew.
Chem Int. Ed. 2007, 46, 572. (e) Yet, L. Chem. Rev. 2003,
103, 4283; and references cited therein.
1H NMR (300 MHz, CDCl3): d = 6.57 (sept, J = 2.6 Hz, 1 H),
4.43 (app t, J = 8.7 Hz, 1 H), 4.32 (dd, J = 8.8, 4.3 Hz, 1 H),
3.97–3.90 (m, 1 H), 2.54–2.47 (m, 2 H), 2.20–2.11 (m, 2 H),
1.83 (d, J = 2.6 Hz, 3 H), 1.80 (d, J = 2.6 Hz, 3 H), 1.12 (t,
J = 7.5 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 191.5,
155.5, 108.9, 93.0, 85.3, 72.8, 67.1, 53.8, 22.3, 22.0, 21.8,
14.2, 12.5. IR (neat): 1968, 1757 cm–1. MS: m/z (%) = 220
(10), 219 (50), 204 (31), 190 (68), 152 (88), 108 (87), 81
(100), 67 (92). HRMS (EI): m/z calcd for C13H17NO2 [M+]:
219.1259; found: 219.1259.
(16) General Procedure for the Alder-ene Reaction –
Preparation of (7Z)-7-Ethylidene-7,7a-dihydro-6-(prop-
1-en-2-yl)pyrrolo[1,2-c]oxazol-3(1H)-one (15b)
To a flame-dried test tube equipped with a magnetic stirring
bar was added allenamide 14b (0.022 g, 0.12 mmol). The
test tube was evacuated and charged with nitrogen (3×).
Then, toluene (4.4 mL) was added followed by addition of
[Rh(CO)2Cl]2 (0.002 g, 0.01 mmol). The reaction mixture
was stirred at r.t. for 3.5 h and upon completion, the light
yellow-brown solution was chromatographed [SiO2,
hexanes–EtOAc (4:1)] to give the desired cross-conjugated
triene 15b (0.016 g, 72% yield). 1H NMR (300 MHz,
CDCl3): d = 6.67 (s, 1 H), 5.76 (qd, J = 7.2, 3.1 Hz, 1 H),
5.21–5.11 (m, 3 H), 4.84 (app t, J = 8.5 Hz, 1 H), 4.24 (app
t, J = 8.7 Hz, 1 H), 1.93 (s, 3 H), 1.68 (dd, J = 7.1, 1.8 Hz, 3
H). 13C NMR (75 MHz, CDCl3): d = 157.4, 140.1, 135.8,
130.3 130.0, 116.5, 115.0, 70.7, 61.6, 23.3, 16.0. IR (neat):
1772 cm–1. MS: m/z (%) = 191 (30), 146 (46), 132 (61), 117
(47), 91 (36), 86 (64), 84 (100). HRMS (EI): m/z calcd for
C11H13NO2 [M+]: 191.0946; found: 191.0952.
(6) For an example, see: Zhang, W.; Zhang, X. Angew. Chem.
Int. Ed. 2006, 45, 5515.
(17) (Z)-7,8,9,9a-Tetrahydro-7-methylene-6-vinyl-
oxazolo[3,4-a]azepin-3-(1H)-one (17a)
(7) O’Donnell, M. J.; Plot, R. L. J. Org. Chem. 1982, 47, 2663.
(8) Ni, Y.; Amarasinghe, K. K. D.; Ksebati, B.; Montgomery, J.
Org. Lett. 2003, 5, 3771.
(9) (a) Garner, P.; Park, J. M. J. Org. Chem. 1987, 52, 2361.
(b) Koskinen, A. M. P.; Otsomaa, L. A. Tetrahedron 1997,
53, 6473. (c) Roush, W. R.; Hunt, J. A. J. Org. Chem. 1995,
60, 798.
(10) (a) Seyferth, D.; Marbor, R. S.; Hilbert, P. J. Org. Chem.
1971, 36, 1379. (b) Ohira, S. Synth. Commun. 1989, 19, 561.
(11) (a) Crisp, G. T.; Jiang, Y.-L.; Pullman, P. J.; Savi, C. D.
Tetrahedron 1997, 53, 17489. (b) Meffre, P.; Gauzy, L.;
Branquet, E.; Durand, P.; Goffic, F. L. Tetrahedron 1996,
52, 11215. (c) Meffre, P.; Gauzy, L.; Perdigues, C.;
Desanges-Levecque, F.; Branquet, E.; Durand, P.; Goffic, F.
L. Tetrahedron Lett. 1995, 36, 877.
Following the general procedure for the Alder-ene reaction,
17a was obtained in 12% yield. 1H NMR (300 MHz, CDCl3):
d = 6.62 (s, 1 H), 6.32 (dd, J = 17.1, 10.6 Hz, 1 H), 5.33 (dd,
J = 17.1, 1.4 Hz, 1 H), 5.24 (br s, 1 H), 5.06 (dd, J = 10.6, 1.4
Hz, 1 H), 5.06 (s, 1 H), 5.05 (s, 1 H), 4.50 (app t, J = 8.4 Hz,
1 H), 4.20–4.10 (m, 1 H), 3.94 (app t, J = 8.4 Hz, 1 H), 2.71–
2.65 (m, 1 H), 2.38–2.29 (m, 1 H), 2.16–2.08 (m, 1 H), 1.88–
1.77 (m, 1 H). 13C NMR (75 MHz, CDCl3): d = 156.4, 142.0,
136.5, 126.3, 123.7, 117.9, 114.4, 68.4, 56.9, 35.1, 34.1. IR
(neat): 1755, 1640 cm–1. MS: m/z (%) = 191 (87), 176 (46),
158 (54), 157 (30), 129 (45), 105 (100), 104 (42). HRMS
(EI): m/z calcd for C11H13NO2 [M+]: 191.0946; found:
191.0947.
(18) General Procedure for the Pauson–Khand Reaction –
Preparation of Enone 18a
(12) Trost, B. M.; Stiles, D. T. Org. Lett. 2005, 7, 2117.
(13) Shen, L.; Hsung, R. P.; Zhang, Y.; Antoline, J. E.; Zhang, X.
Org. Lett. 2005, 7, 3081.
(14) For a recent review, see: Wei, L.-L.; Xiong, H.; Hsung, R. P.
Acc. Chem. Res. 2003, 36, 773; and references cited therein.
(15) General Procedure for the Copper-Catalyzed Coupling
Protocol to Prepare an Allenamide – Preparation of 3-(3-
Methylbuta-1,2-dienyl)-4-(pent-2-ynyl)oxazolidin-2-one
(1b)
To a flame-dried test tube equipped with a magnetic stirring
bar was added allenamide 16d (0.009 g, 0.04 mmol). The
test tube was evacuated and charged with carbon monoxide
(3×), then toluene (5.2 mL) was added followed by
[Rh(CO)2Cl]2 (0.002 g, 0.004 mmol). The reaction mixture
was heated at 85 °C for 1 h. Upon completion of the reaction
(TLC), the mixture was cooled to r.t. and chromatographed
[SiO2, hexanes–EtOAc (1:1)] to give 18a as an oil (dr, 3:1,
0.008 g, 75% yield).
A flame-dried 25 mL round-bottom flask was charged with
oxazolidinone 8b (0.321 g, 2.10 mmol), copper(I)
thiophene-2-carboxylate (CuTC, 0.040 g, 0.21 mmol), BaO
Major diastereomer: 1H NMR (300 MHz, CDCl3): d = 6.68
Synlett 2008, No. 15, 2303–2308 © Thieme Stuttgart · New York

2308
K. M. Brummond, B. Yyn
LETTER
then, after cooling to r.t. was chromatographed [SiO2,
(s, 1 H), 4.60 (app t, J = 8.3 Hz, 1 H), 4.19–4.09 (m, 1 H),
3.96 (dd, J = 10.0, 8.5 Hz, 1 H), 3.25 (dt, J = 18.4, 3.2 Hz, 1
H), 2.86–2.76 (m, 2 H), 2.61 (ddd, J = 17.1, 12.8, 3.5 Hz, 1
H), 2.09 (dt, J = 14.1, 4.0 Hz, 1 H), 2.00–1.86 (m, 1 H), 1.24
(d, J = 7.2 Hz, 6 H), 1.20 (d, J = 6.9 Hz, 3 H). 13C NMR (75
MHz, CDCl3): d = 206.6, 159.8, 155.2, 146.5, 123.0, 117.8,
67.6, 58.6, 44.6, 29.2, 28.4, 25.7, 20.3, 20.1, 16.0. IR (neat):
1760, 1682, 1651 cm–1. MS: m/z (%) = 261 (62), 246 (100),
232 (16), 218 (47), 174 (6). HRMS (EI): m/z calcd for
C15H19NO3 [M+]: 261.1365; found: 261.1361.
hexanes–EtOAc, (1:1)] to give the product 19 as a white
solid (0.008 g, 75% yield). 1H NMR (300 MHz, CDCl3): d =
7.46–7.34 (m, 3 H), 7.11–7.08 (m, 2 H), 5.49 (t, J = 7.5 Hz,
1 H), 4.60 (dd, J = 9.0, 5.8 Hz, 1 H), 4.40 (t, J = 7.4 Hz, 1 H),
4.35–4.34 (m, 1 H), 4.11 (dd, J = 11.5, 7.8 Hz, 1 H), 3.95–
3.84 (m, 1 H), 3.27 (ddd, J = 8.9, 7.1, 1.7 Hz, 1 H), 2.77 (dd,
J = 14.5, 1.7 Hz, 1 H), 2.69 (dd, J = 12.7, 3.2 Hz, 1 H), 2.40–
2.32 (m, 1 H), 2.17–2.07 (m, 2 H), 2.02 (s, 3 H), 1.87 (t,
J = 12.3 Hz, 1 H), 1.00 (t, J = 7.5 Hz, 3 H). 13C NMR (75
MHz, CD2Cl2): d = 178.5, 176.7, 157.4, 134.8, 132.5, 130.4,
130.2, 129.3, 128.9, 128.6, 127.1, 69.6, 57.0, 52.8, 40.1,
39.3, 32.3, 28.9, 22.6, 21.7, 14.3. IR (neat): 1746, 1706 cm–1.
MS: m/z (%) = 393 (40), 392 (100), 377 (10), 333 (17), 219
(31), 190 (90), 91 (45). HRMS (EI): m/z calcd for
(19) Xiong, H.; Hsung, R. P.; Wei, L.-L.; Berry, C. R.; Mulder, J.
A.; Stockwell, B. Org. Lett. 2000, 2, 2869.
(20) Diels–Alder Reaction – Preparation of Tetracyclic
Compound 19
To a solution of triene 2b (0.006 g, 0.03 mmol) in toluene
(0.5 mL) was added N-phenylmaleimide (0.005 g, 0.03
mmol). The reaction mixture was heated at 75 °C for 5 h
C23H24N2O4 [M+]: 392.1736; found: 392.1719.
Synlett 2008, No. 15, 2303–2308 © Thieme Stuttgart · New York

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