Rhodium-catalyzed regio-, diastereo-, and enantioselective intermolecular [4+2] carbocyclization of 4-alkynals with electron-deficient alkenes

Article abstract of DOI:10.1002/ejoc.200600383

We established that a cationic rhodium(I)/dppf or dppb complex catalyzes a regio- and diastereoselective intermolecular [4+2] carbocyclization of 5-trimethylsilyl-4-pentynals with electron-deficient alkenes leading to cyclohexanones. We also established that a cationic rhodium(I)/(R,R)-Warphos complex catalyzes a regio- and enantioselective intermolecular [4+2] carbocyclization of 5-substituted 4-pentynals and 2-alkynylbenzaldehydes with N,N-dialkylacrylamides leading to enantio-enriched cyclohexanones and tetralones, respectively. A single olefin isomer was produced in every carbocyclization. Regioselectivities of the alkene insertion depend on the alkenes used. Mechanistic study suggested that a key intermediate in this intermolecular [4+2] carbocyclization is a five-membered acylrhodium intermediate, formed by cis addition of the rhodium hydride to the metal-bound alkyne. This method serves as an attractive new route to highly functionalized cyclohexanones in view of the one-step access to 5-substituted 4-pentynals and 2-alkynylbenzaldehydes starting from readily available terminal alkynes. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600383

FULL PAPER
DOI: 10.1002/ejoc.200600383
Rhodium-Catalyzed Regio-, Diastereo-, and Enantioselective Intermolecular
[4+2] Carbocyclization of 4-Alkynals with Electron-Deficient Alkenes
[a]
[a]
[a]
Ken Tanaka,* Yuji Hagiwara, and Masao Hirano
Keywords: Alkenes / Alkynes / Aldehydes / Asymmetric catalysis / Carbocyclization / Rhodium
We established that a cationic rhodium(I)/dppf or dppb com-
plex catalyzes a regio- and diastereoselective intermolecular
depend on the alkenes used. Mechanistic study suggested
that a key intermediate in this intermolecular [4+2] carbocy-
clization is a five-membered acylrhodium intermediate,
formed by cis addition of the rhodium hydride to the metal-
bound alkyne. This method serves as an attractive new route
to highly functionalized cyclohexanones in view of the one-
step access to 5-substituted 4-pentynals and 2-alkynylben-
zaldehydes starting from readily available terminal alkynes.
[
4+2] carbocyclization of 5-trimethylsilyl-4-pentynals with
electron-deficient alkenes leading to cyclohexanones. We
also established that a cationic rhodium(I)/(R,R)-Walphos
complex catalyzes a regio- and enantioselective intermo-
lecular [4+2] carbocyclization of 5-substituted 4-pentynals
and 2-alkynylbenzaldehydes with N,N-dialkylacrylamides
leading to enantio-enriched cyclohexanones and tetralones,
respectively. A single olefin isomer was produced in every
carbocyclization. Regioselectivities of the alkene insertion
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
intermolecularly with alkenes.[7] A successful generation of
such five-membered acylrhodium intermediates A was real-
ized by the intramolecular cis addition of the rhodium hy-
dride to the metal-bound triple bond of 4-alkynals. This
intermediates A reacts with alkynes leading to substituted
Introduction
Transition-metal-catalyzed carbocyclization is one of the
most valuable tools for the rapid construction of car-
[
1]
bocycles. Among them, [4+2] carbocyclization of dienes
or enynes with alkynes or alkenes is widely used for the
[8]
cyclohexenones in high yield (Scheme 1).
[
2–5]
construction of six-membered ring carbon skeletons.
For the synthesis of six-membered carbonyl compounds,
the [4+2] carbocyclization of cyclic acylmetal intermediates
with alkynes or alkenes is a highly attractive method, how-
[
6–8]
ever, only a few examples have been reported to date.
Furthermore, although some transition-metal-catalyzed
enantioselective intramolecular [4+2] carbocyclizations have
[
4]
been reported, an enantioselective intermolecular [4+2]
[
5]
carbocyclization has been achieved in a limited success.
Scheme 1. Rhodium-catalyzed intermolecular [4+2] carbocycli-
Liebeskind et al. reported that maleoylcobalt and zation of 4-alkynals with alkynes leading to cyclohexenones.
phthaloylcobalt complexes react with alkynes leading to
This result prompted our investigation of intercepting
metalacycle A with alkenes, instead of alkynes. In this arti-
cle, we describe that cationic rhodium(I) complexes catalyze
a regio-, diastereo-, and enantioselective intermolecular
quinones and naphthoquinones, respectively, although stoi-
chiometric metal reagents are required.[6] A catalytic car-
bocyclization involving cyclic acylmetal intermediates was
reported by Murakami et al. Five-membered acylrhodium
intermediates, formed catalytically by the oxidative addition
of rhodium between the carbonyl carbon and the α-carbon
of cyclobutanones, react intramolecularly with alkenes lead-
ing to bicyclic cyclohexanones, although those fail to react
[4+2] carbocyclization of 4-alkynals with electron-deficient
[
a] Department of Applied Chemistry, Graduate School of Engi-
neering, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Fax: +81-42-388-7037
E-mail: tanaka-k@cc.tuat.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Scheme 2. Rhodium-catalyzed intermolecular [4+2] carbocycli-
zation of 4-alkynals with alkenes leading to cyclohexanones.
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Rh-Catalyzed [4+2] Carbocyclization of Alkynals
FULL PAPER
alkenes leading to cyclohexanones, presumably via the com- Table 1. Screening of reaction conditions for rhodium-catalyzed
mon intermediates A (Scheme 2).[
9]
[4+2] carbocyclization of 5-trimethylsilyl-4-pentynal with butyl ac-
rylate.
Results and Discussion
Regio- and Diastereoselective [4+2] Carbocyclization of 5-
Substituted 4-Pentynals with Electron-Deficient Alkenes: We
first examined the [4+2] carbocyclization of 5-butyl-3-
methyl-4-pentynal (1a) with various alkenes in the presence
of catalytic amount of [Rh(dppe)]BF , which was used for
4
[
8]
the [4+2] carbocyclization of 4-alkynals with alkynes. We
found that the use of electron-deficient alkenes such as bu-
tyl acrylate (2a) furnished the cyclohexanone 3aa in low
yield along with the diene 4a. However, the reaction of 3-
methyl-5-phenyl-4-pentynal (1b) furnished the cyclohexan-
one 3ba in a trace amount (Ͻ2% yield); it furnished the
[
10]
cyclopentenone 5b as a major product (Scheme 3).
[a] GC yields. [b] Isolated yield. [c] 2a: 5 equiv. [d] 2a: 10 equiv.
A series of electron-deficient alkenes were subjected to
the above optimal reaction conditions (Table 2, Entries 1–
). Primary (2a,b: Entries 1 and 2), secondary (2c: Entry 3),
6
and tertiary (2d: Entry 4) alkyl acrylates cleanly afforded
the corresponding cyclohexanones. Not only acrylates, but
also n-hexyl vinyl ketone (2e: Entry 5) and N,N-dimethyl-
acrylamide (2f: Entry 6) afforded the corresponding cyclo-
hexanones. With respect to regiochemistry, the electron-
withdrawing group of the alkene is preferentially incorpo-
rated α to the ring carbonyl (product 3) when primary and
secondary alkyl acrylates were used (Entries 1–3). Interest-
ingly, the opposite regioselectivity (product 6) was observed
when tert-butyl acrylate (2d), n-hexyl vinyl ketone (2e), and
N,N-dimethylacrylamide (2f) were used (Entries 4–6). We
have also explored the scope of this process with respect
Scheme 3. Rhodium-catalyzed [4+2] carbocyclization of 5-alkyl-
and 5-phenyl-4-pentynals with butyl acrylate.
Fortunately, the reaction of 3-methyl-5-trimethylsilyl-4- to 5-trimethylsilyl-4-pentynals (Entries 7–10). The reaction
pentynal (1c) furnished the desired cyclohexanones 3ca and tolerates a range of substituents at the 3 position such as
6
(
ca, and the former being obtained as a major isomer butyl (1d: Entries 7 and 8) and phenyl (1e: Entries 9 and
Table 1, Entry 1). Screening of phosphane ligands revealed 10) substituents.[12] In these reactions, the use of tert-butyl
that although the use of dppp (Entry 2), dppb (Entry 3), acrylate (2d) increased the yield of product 6. A single ole-
BINAP (Entry 4), and dppf (Entry 5) increased the yield of fin isomer was produced in each cycloaddition shown in
cyclohexanones, but accompanied with various byproducts Table 2. The product 3 consists of a mixture of keto and
[
11]
(
dppp, dppb: complex mixture; BINAP, dppf: dienal 7c). enol isomers, but product 6 could have two possible dia-
Increasing the amount of 2a is effective for dppf to decrease stereomers. Importantly, these reactions are highly dia-
the generation of the dienal 7c and increases the yield of stereoselective and afforded product 6 as a single dia-
[
13]
cyclohexanones to 74% (5 equiv., Entry 6) and 81% stereomer.
10 equiv., Entry 7). On the contrary, the amount of 2a did methacrylate and methyl crotonate) and other electron-de-
not affect the yield of the cyclohexanones in the case of ficient alkenes (acrylonitrile and phenyl vinyl sulfone) could
Unfortunately, substituted acrylates (methyl
(
dppb as a ligand (Entry 8).
not participate in this carbocyclization.
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FULL PAPER
Table 2. Rhodium-catalyzed regio- and diastereoselective [4+2] car-
bocyclization of 5-trimethylsilyl-4-pentynals with electron-deficient
alkenes.
In the case of the alkynal 1g bearing substituents at both
and 3 positions, one diastereomer preferentially reacted
with 2d to afford the cyclohexanone 6gd in 26% yield as a
single diastereomer; the unreacted alkynal 1g was recovered
in 41% yield with cis/trans = 88:12 (Scheme 5).
2
The reactions of 5-butyl-3-methyl-4-pentynal (1a) and 3-
methyl-5-phenyl-4-pentynal (1b) with N,N-dimethylacryl-
amide (2f) also proceeded to give the corresponding cyclo-
hexanones 6af and 6bf in 37% and 20% yield, respectively,
as a single diastereomer by using [Rh(dppb)]BF as a cata-
4
[
14]
lyst (Scheme 6).
Scheme 6. Rhodium-catalyzed regio- and diastereoselective [4+2]
carbocyclization of 5-butyl- and 5-phenyl-3-methyl-4-pentynals
with N,N-dimethylacrylamide.
[
[
8
a] Yields of isolated products. [b] Catalyst: 20% [Rh(dppf)]BF
c] Catalyst: 20% [Rh(dppb)]BF . Solvent: (CH Cl) . Temperature:
0 °C. [d] Temperature: 8 °C. [e] Yield of 6ce. Product 3ce could
not be isolated due to its low yield.
4
.
4
2
2
Regio- and Enantioselective [4+2] Carbocyclization of 4-
Alkynals with Electron-Deficient Alkenes: Next, we investi-
gated the reaction of 5-substituted 4-pentynals having no
substituent at both 2 and 3 positions with electron-deficient
The reaction of the 2-substituted alkynal 1f with tert- alkenes to develop an enantioselective variant of this [4+2]
butyl acrylate (2d) also proceeded to give the corresponding carbocyclization. After screening various 5-substituted 4-
cyclohexanone 6fd
with high diastereoselectivity pentynals, alkenes, and rhodium(I) complexes, we found
(Scheme 4).
that the reaction of 5-phenyl-4-pentynal (1h) with N,N-di-
methylacrylamide (2f) in the presence of catalytic amount
of [Rh(dppb)]BF furnished the cyclohexanone 6hf in low
4
yield along with the alkynyl ketone 8hf (Scheme 7).
Scheme 4. Rhodium-catalyzed regio- and diastereoselective [4+2]
carbocyclization of 2-methyl-5-trimethylsilyl-4-pentynal with tert-
butyl acrylate.
Scheme 7. Rhodium-catalyzed regioselective [4+2] carbocyclization
of 5-phenyl-4-pentynal with N,N-dimethylacrylamide.
The enantioselective [4+2] carbocyclization of 1h with 2f
was examined using various chiral bidentate phosphane li-
gands (Figure 1), which have the large P–M–P natural bite
angles to facilitate the reductive elimination step (Table 3).
The study revealed that the use of (S,S)-DIOP, (R)-Tol-BI-
NAP, and (R)-(S)-9 furnished the cyclohexanone 6hf, but
both yield and ee were low (Entries 1–3). The use of (R)-
(S)-10, which has the coordinating dimethylamino group,
completely shut down the reaction (Entry 4). We were ple-
ased to find that the use of (R)-(R)-Walphos [(R)-(R)-11][
dramatically increased both yield and ee of 6hf (Entry 5).
The reaction could be carried out using 5–10% catalyst,
although lower yield and ee were observed (Entries 6 and 7).
15]
Scheme 5. Rhodium-catalyzed diastereoselective kinetic resolution
of 2,3-dimethyl-5-trimethylsilyl-4-pentynal.
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Rh-Catalyzed [4+2] Carbocyclization of Alkynals
FULL PAPER
Table 4. Rhodium-catalyzed regio- and enantioselective [4+2] car-
bocyclization of 5-substituted 4-pentynals with N,N-dialkylacryl-
amides.
Figure 1. Structures of chiral bidentate phosphane ligands.
Table 3. Screening of ligands for rhodium-catalyzed regio- and
enantioselective [4+2] carbocyclization of 5-phenyl-4-pentynal with
N,N-dimethylacrylamide.
[
4
a] Yields of isolated products. [b] Catalyst: 20%. [c] Temperature:
0 °C.
[a] NMR yield. [b] Yields of isolated products.
A series of the 5-substituted 4-pentynals 1h–n were sub-
jected to the above optimal reaction conditions (Table 4).
The reactions of aryl (1h–k, Entries 1–4), alkenyl (1l, Entry
6), and alkyl (1m, Entry 7) substituted 4-pentynals with 2f
afforded the corresponding cyclohexanones in good yield
with high enantioselectivity. Not only N,N-dimethylacryl-
amide (2f), but also N-acryloylpyrrolidine (2g) can be em-
ployed (Entry 5). However, the use of substituted acryl-
amides (N,N-dimethylmethacrylamide, 1-pyrrolidin-1-yl-
Figure 2. ORTEP diagram of (S)-(+)-6kf. Ellipsoids drawn at the
5
0% probability level.
Not only N,N-dialkylacrylamides but also tert-butyl ac-
but-2-en-1-one, and N-methylmaleimide) did not afford the rylate (2d) could be used for this regio- and enantioselective
desired carbocyclization products. Although the enantio- [4+2] carbocyclization, and the corresponding enantio-en-
selectivity was very high, the reaction of 5-trimethylsilyl-4- riched cyclohexanone was obtained in 32% yield with 97%
pentynal (1n) proceeded in low yield (Entry 8). Importantly, ee (Scheme 8).
these [4+2] carbocyclizations of 1h–n with 2f,g are highly
We anticipated that enantioselective kinetic resolution of
regioselective and no regioisomer was detected in the crude a 3-substituted 4-alkynal would proceed through the reac-
[
16]
reaction mixtures. The absolute configuration of (+)-6kf tion with N,N-dimethylacrylamide (2f) by using [Rh((R,R)-
was determined to be S by an anomalous dispersion 11)]BF as a catalyst. Indeed, the kinetic resolution of (±)-
4
method (Figure 2).
1a proceeded to give enantio-enriched alkynal (S)-(+)-1a in
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K. Tanaka, Y. Hagiwara, M. Hirano
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served (Entry 7). As demonstrated in Table 4, no re-
[
16]
gioisomer was detected in these reactions. In general, the
reactions of the 2-alkynylbenzaldehydes 1o–t are more facile
than those of the 5-substituted 4-pentynals 1h–n, which al-
low lower catalyst loading. Because the [4+2] carbocycli-
zation of 2-alkynylbenzaldehydes with alkynes did not pro-
ceed at all, this successful [4+2] carbocyclization of 2-alkyn-
ylbenzaldehydes with N,N-dialkylacrylamides is note-
worthy.
Scheme 8. Rhodium-catalyzed regio- and enantioselective [4+2]
carbocyclization of 5-phenyl-4-pentynal with tert-butyl acrylate.
Table 5. Rhodium-catalyzed regio- and enantioselective [4+2] car-
4
4% isolated yield with 93% ee, although another enantio- bocyclization of 2-alkynylbenzaldehydes with N,N-dialkylacryl-
mer (R)-(–)-1a was decomposed to give a complex mixture amides.
of products (Scheme 9).
Scheme 9. Rhodium-catalyzed enantioselective kinetic resolution of
3-methyl-4-nonynal.
Regio- and Enantioselective [4+2] Carbocyclization of 2-
Alkynylbenzaldehydes with N,N-Dialkylacrylamides: Ben-
zene-linked 4-alkynals, 2-alkynylbenzaldehydes, are versatile
substrates due to their facile preparation starting from 2-
bromobenzaldehyde and terminal alkynes through Sonoga-
[
17–18]
shira coupling.
Therefore, the intermolecular [4+2]
[a] Yields of isolated products.
carbocyclization of 2-alkynylbenzaldehydes with 2f leading
to functionalized tetralone derivatives was investigated.
Fortunately, the reaction of 2-alkynylbenzaldehydes 1o and
The enantioselective [4+2] carbocyclization of heterocy-
clic 4-alkynals with 2f was also investigated. The reaction
of the pyridine-linked 4-alkynal 1u with 2f proceeded to
give the corresponding bycyclic pyridine derivative 6uf in
1% yield with 97% ee. However, no reaction was observed
in the case of the furan- or thiophene-linked 4-alkynal 1v
or 1w (Scheme 11).
1
p with 2f in the presence of [Rh(dppb)]BF as a catalyst
4
proceeded to give the corresponding tetralone derivatives in
high yield with good regioselectivity (Scheme 10).
4
Scheme 10. Rhodium-catalyzed regioselective [4+2] carbocycli-
zation of 2-alkynylbenzaldehydes with N,N-dimethylacrylamide.
Next, the enantioselective [4+2] carbocyclization of 2-al-
kynylbenzaldehydes 1o–t with the N,N-dialkylacrylamides
Scheme 11. Rhodium-catalyzed regio- and enantioselective [4+2]
carbocyclization of heterocyclic 4-alkynals with N,N-dimethylacryl-
amide.
2f,g was investigated (Table 5). Aryl- (Entries 1–3), alkenyl-
(Entry 4), and alkyl-substituted (Entries 5 and 6) 2-ethynyl-
benzaldehydes afforded the corresponding cyclohexanones
in good yield with high enantioselectivity. The reaction of
Mechanistic Consideration for Rhodium-Catalyzed Inter-
the trimethylsilyl-substituted 2-ethynylbenzaldehyde 1p pro- molecular [4+2] Carbocyclization of 4-Alkynals with Elec-
ceeded in low yield, but high enantioselectivity was ob- tron-Deficient Alkenes: Scheme 12 shows a possible mecha-
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Rh-Catalyzed [4+2] Carbocyclization of Alkynals
FULL PAPER
Scheme 12. Possible mechanism for rhodium-catalyzed intermolecular [4+2] carbocyclization of 4-alkynals with electron-deficient alkenes.
nism for this carbocyclization.[19] We infer that an oxidative
addition of the aldehyde C–H bond to rhodium(I) affords
the acylrhodium hydride B. The cis addition of the rhodium
hydride to the metal-bound alkyne then provides the five-
membered acylrhodium intermediate A.[ Complexation
of the alkene 2, followed by insertion affords the metall-
acycles C and D. Reductive elimination furnishes cyclohexa-
nones 3 and 6, respectively, and regenerates the Rh catalyst.
The diene 4 is generated through β-hydride elimination
from the metallacycle C followed by reductive elimination.
20]
The dienal 7 is generated through carbonyl migration of the
Scheme 13. Deuterium labeling study.
acylrhodium intermediate A followed by β-hydride elimi-
[
11]
nation. On the other hand, trans addition of the rhodium
hydride to the metal-bound alkyne then provides the six-
membered acylrhodium intermediate E. Reductive elimi-
The formation of the alkynyl ketone 8hf is possible
nation furnishes cyclopentenone 5 and regenerates the Rh through both β hydride elimination from the metallacycle
[
10]
catalyst.
D and carbometallation of the intermediate B with alkene
[
21]
Consistent with these pathways, the reaction of the deu- 2f prior to hydrometallation (Scheme 12). If the latter re-
terium-labeled 4-alkynal 1c-d with 2a led to stereospecific action is the major pathway, the reaction of 5-phenyl-4-pen-
incorporation of deuterium in the α position of the trimeth- tynal (1h) with excess 2f by using [Rh(dppb)]BF as a cata-
4
ylsilyl group of cyclohexanones (Scheme 13).
lyst should increased the yield of 8hf. Indeed, the yield of
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K. Tanaka, Y. Hagiwara, M. Hirano
FULL PAPER
8hf was significantly increased, which supports the car- serves as an attractive new route to highly functionalized
bometallation of intermediate B with 2f leading to 8hf cyclohexanones in view of the one-step access to 5-substi-
(Scheme 14).
tuted 4-pentynals (1,4-addition of terminal alkynes to α,β-
unsaturated aldehydes) and 2-alkynylbenzaldehydes (Sono-
gashira coupling of terminal alkynes with 2-bromobenzal-
dehyde).
Experimental Section
1
General Methods: H NMR spectra were recorded with JEOL AL
1
3
3
00 (300 MHz) or JEOL AL 400 (400 MHz). C NMR spectra
were obtained with complete proton decoupling with JEOL AL
00 (75 MHz) or JOEL AL 400 (100 MHz). HRMS data were ob-
Scheme 14. Rhodium-catalyzed reaction of 5-phenyl-4-pentynal
3
with excess N,N-dimethylacrylamide.
tained with JEOL JMS-700. Infrared spectra were obtained with a
JASCO A-302. The chiral ligands 9, 10, and 11 were obtained from
Solvias AG under their University Ligand Kit program. Anhydrous
A possible mechanism of the selective formation of (S)-
6kf is depicted in Scheme 15. Regio- and enantioselectivity
2 2 2 2
CH Cl (Aldrich, No. 27,099–7) and anhydrous (CH Cl) (Aldrich,
are determined by preferential formation of the intermedi-
ate F followed by the insertion of 2f to form the intermedi-
ate G, in order to avoid the steric repulsion between NMe2
No. 28,450–5) were used as received. Solvents for the synthesis of
substrates were dried with molecular sieves (4 Å, Wako) prior to
use. All reagents were obtained from commercial sources and used
as received, unless otherwise indicated. All reactions were carried
out under argon or nitrogen in oven-dried glassware, unless other-
wise indicated.
group of 2f and PPh group of (R,R)-11. Reductive elimi-
2
nation of rhodium gives (S)-6kf and regenerates the rho-
dium catalyst.
Starting Materials: The 4-alkynals 1a–n were synthesized through
1
,4-addition of the corresponding terminal alkynes and α,β-unsatu-
[22]
rated aldehydes according to the literature procedure. 4-Alkynals
o–w were synthesized through Sonogashira coupling of the corre-
1
sponding terminal alkynes and bromides according to the literature
procedure.[ The 4-alkynal 1c-d was synthesized through the fol-
lowing sequences: 1) Jones oxidation of 1c, 2) reduction with Li-
23]
[
10a]
AlD
4
, 3) Swern oxidation, according to the literature procedure.
[24]
[10a]
1e, 1f, 1h, 1j, 1m, 1n, 1o,[17]
[11]
[25]
[26]
[27]
[28]
[29]
4
1
-Alkynals 1a, 1b,
p, 1r, 1s,[31] 1u, 1v, and 1w were reported in the litera-
[30]
[24]
[32]
[33]
[34]
[35]
[36]
tures. The ketone 2e
and the amide 2g
were reported in the
literatures.
Aldehyde 1c: Colorless oil. IR (neat): ν˜ = 2910, 2180, 1725, 1250,
–
1
1
8
45, 760 cm . H NMR (CDCl
3
, 300 MHz): δ = 9.79 (t, J =
2.1 Hz, 1 H), 3.00 (sext, J = 6.9 Hz, 1 H), 2.54 (ddd, J = 16.8, 6.9,
Scheme 15. Possible mechanism of the selective formation of (S)-
2.1 Hz, 1 H), 2.49 (ddd, J = 16.8, 6.9, 2.1 Hz, 1 H), 1.22 (d, J =
6.9 Hz, 3 H), 0.14 (s, 9 H) ppm. C NMR (CDCl , 75 MHz): δ =
3
1
3
6kf.
2
C H
9
01.0, 109.1, 85.7, 49.8, 21.6, 20.9, 0.0 ppm. HRMS (EI): calcd. for
16OSi [M–H]+ 167.0892; found: 167.0839.
Aldehyde 1d: Colorless oil. IR (neat): ν˜ = 2930, 2180, 1725, 1250,
Conclusions
–
1
1
8
2
6
3
45, 760 cm . H NMR (CDCl , 300 MHz): δ = 9.80 (t, J =
.1 Hz, 1 H), 2.87 (quint, J = 6.9 Hz, 1 H), 2.57 (ddd, J = 16.5,
.9, 2.1 Hz, 1 H), 2.49 (ddd, J = 16.5, 6.9, 2.1 Hz, 1 H), 1.26–1.54
In conclusion, we established that a cationic rhodium(I)/
dppf or dppb complex catalyzes a regio- and diastereoselec-
tive intermolecular [4+2] carbocyclization of 5-trimethyl-
silyl-4-pentynals with electron-deficient alkenes leading to
cyclohexanones. We also established that a cationic rhodi-
um(I)/(R,R)-Walphos complex catalyzes a regio- and enan-
tioselective intermolecular [4+2] carbocyclization of 5-sub-
stituted 4-pentynals and 2-alkynylbenzaldehydes with N,N-
dialkylacrylamides leading to enantio-enriched cyclohexa-
nones and tetralones, respectively. A single olefin isomer
was produced in every carbocyclization. Regioselectivities
1
3
(
(
m, 6 H), 0.91 (t, J = 6.9 Hz, 3 H), 0.14 (s, 9 H) ppm. C NMR
CDCl , 75 MHz): δ = 201.4, 108.1, 86.7, 48.3, 34.4, 29.2, 27.0,
3
+
2
2
2.3, 13.9, 0.1 ppm. HRMS (EI): calcd. for C12
10.1440; found: 210.1380.
H22OSi [M]
Aldehyde 1g: Pale yellow oil. IR (neat): ν˜ = 2960, 2180, 1725, 1250,
–
1
1
8
45, 760 cm . H NMR (CDCl
stereomers, cis:trans = 59:41): δ = 9.76 (d, J = 2.1 Hz, 1 H, trans),
.70 (d, J = 1.8 Hz, 1 H, cis), 2.87–3.01 (m, 1 H, cis), 2.74–2.85
m, 1 H, trans), 2.30–2.46 (m, 2 H, cis and trans), 1.14–1.24 (m, 12
3
, 300 MHz, mixture of dia-
9
(
13
H, cis and trans), 0.15 (s, 9 H, trans), 0.14 (s, 9 H, cis) ppm.
C
of the alkene insertion depend on the alkenes used. Mech- NMR (CDCl , 75 MHz): δ = 204.2, 203.9, 108.0, 107.5, 86.9, 86.8,
3
anistic study suggested that a key intermediate in this inter- 50.5, 50.2, 28.1, 27.5, 18.6, 18.1, 11.2, 10.4, 0.0 ppm. HRMS (EI):
molecular [4+2] carbocyclization is a five-membered calcd. for C10H
18OSi [M]+ 182.1127; found: 182.1064.
acylrhodium intermediate, formed by the cis addition of the Aldehyde 1i: Pale orange oil. IR (neat): ν˜ = 3350, 2875, 2800, 2680,
–
1
1
rhodium hydride to the metal-bound alkyne. This method 1708, 1590, 1492, 1275, 1230, 1163, 1020, 820 cm . H NMR
3588
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3582–3595

Rh-Catalyzed [4+2] Carbocyclization of Alkynals
FULL PAPER
(
6
(
5
CDCl
.87 (m, 2 H), 3.80 (s, 3 H), 2.67–2.79 (m, 4 H) ppm. C NMR
CDCl , 75 MHz): δ = 200.7, 159.2, 132.9, 115.4, 113.8, 86.1, 81.2,
3 28 3
, 300 MHz): δ = 9.85 (s, 1 H), 7.27–7.35 (m, 2 H), 6.75– 30.6, 19.2, 13.7, 0.2 ppm. HRMS (EI): calcd. for C16H O Si [M–
1
3
+
2 4 9
CO C H ] 195.1205; found 195.1144.
3
Ester 6ca: Colorless oil. IR (neat): ν˜ = 2940, 1717, 1242, 1170,
+
5.2, 42.7, 12.6 ppm. HRMS (EI): calcd. for C12
88.0837; found: 188.0814.
H
12
O
2
[M]
–1 1
8
40 cm . H NMR (CDCl
H), 4.02–4.28 (m, 2 H), 3.69 (ddd, J = 12.0, 5.2, 1.6 Hz, 1 H), 3.08–
.23 (m, 1 H), 2.80 (dd, J = 15.2, 12.0 Hz, 1 H), 2.64 (dd, J = 14.4,
6.4 Hz, 1 H), 2.53 (ddd, J = 15.2, 5.2, 2.4 Hz, 1 H), 2.32 (dt, J =
4.4, 2.4 Hz, 1 H), 1.58–1.71 (m, 2 H), 1.39 (sext, J = 7.2 Hz, 2 H),
1.15 (d, J = 7.2 Hz, 3 H), 0.94 (t, J = 7.6 Hz, 3 H), 0.14 (s, 9
3
, 400 MHz): δ = 5.28 (d, J = 1.6 Hz, 1
1
3
Aldehyde 1k: Pale brown solid; m.p. 40–41 °C. IR (neat): ν˜ = 2870,
2
–1
1
780, 2680, 1700, 1472, 1370, 1340, 1083, 820 cm . H NMR
1
(CDCl , 300 MHz): δ = 9.84–9.86 (m, 1 H), 7.21–7.33 (m, 4 H),
3
.68–2.81 (m, 4 H) ppm. 1 C NMR (CDCl
3
2
1
3
, 75 MHz): δ = 200.2,
33.8, 132.8, 128.5, 121.8, 88.8, 80.3, 42.5, 12.6 ppm. HRMS (EI):
1
3
H) ppm. C NMR (CDCl
3
, 75 MHz): δ = 208.9, 172.4, 154.2,
+
125.1, 64.9, 47.7, 47.4, 43.5, 37.5, 30.6, 20.5, 19.1, 13.6, 0.0 ppm.
calcd. for C11
9
H ClO [M – Cl] 157.0653; found:157.0634.
+
HRMS (EI): calcd. for
96.1793.
Ester 3cb: (Table 2, Entry 2) Procedure 1 was followed using 1c and
b. Reaction time: 45 h. Yield 64% (76 mg). Colorless oil. IR (neat):
ν˜ = 2945, 1660, 1620, 1405, 1350, 1270, 1225, 1202, 1082, 1050,
16 28 3
C H O Si [M] 296.1808; found:
Aldehyde 1l: Pale yellow oil. IR (neat): ν˜ = 2910, 1720, 1342, 920,
8
H), 5.96–6.08 (m, 1 H), 2.57–2.72 (m, 4 H), 1.98–2.16 (m, 4 H),
1
1
2
–
1 1
40 cm . H NMR (CDCl
3
, 300 MHz): δ = 9.81 (t, J = 1.2 Hz, 1
2
.48–1.68 (m, 4 H) ppm. 13C NMR (CDCl
34.0, 120.5, 84.7, 83.3, 42.8, 29.3, 25.5, 22.3, 21.5, 12.6 ppm.
3
, 75 MHz): δ = 200.7,
–
1 1
8
3
40 cm . H NMR (CDCl , 300 MHz): δ = 12.16 (s, 1 H), 5.31 (d,
+
HRMS (EI): calcd. for C11
H14O [M] 162.1045; found: 162.0967.
J = 1.8 Hz, 1 H), 3.82–4.04 (m, 2 H), 3.21 (dt, J = 18.1, 2.4 Hz, 1
H), 2.87 (d, J = 18.1 Hz, 1 H), 2.79–2.97 (m, 1 H), 2.45–2.63 (m,
Aldehyde 1q: Pale yellow solid; m.p. 65–67 °C. IR (neat): ν˜ = 2795,
–1
1
1
(
7
(
1
9
680, 1565, 1470, 1455, 1415, 1250, 1185, 740 cm . H NMR 1 H), 2.19 (dd, J = 18.0, 1.3 Hz, 1 H), 2.01 (sept, J = 6.6 Hz, 1 H),
CDCl
, 400 MHz): δ = 10.72 (s, 1 H), 7.93–8.00 (m, 1 H), 7.65– 1.22 (d, J = 7.0 Hz, 3 H), 0.97 (d, J = 6.8 Hz, 6 H), 0.11 (s, 9
.71 (m, 1 H), 7.54–7.63 (m, 2 H), 7.40–7.50 (m, 2 H), 7.22–7.35
H) ppm; vinyl proton of keto isomer: δ = 5.44 (d, J = 1.8 Hz, 1
, 100 MHz): δ = 191.7, 136.1, H) ppm. C NMR (CDCl
35.9, 133.7, 133.2, 129.9, 129.4, 128.9, 127.1, 126.5, 126.3, 122.3,
123.2, 96.1, 70.3, 37.3, 34.1, 31.4, 27.7, 19.2, 189.1, 0.2 ppm.
3
m, 2 H) ppm. 13C NMR (CDCl
13
3
, 75 MHz): δ = 172.0, 169.7, 156.2,
3
+
+
2.9, 89.9 ppm. HRMS (EI): calcd. for C15
H
9
ClO [M] 240.0342;
HRMS (EI): calcd. for C16
found: 195.1165.
H
28
O
3
Si [M–CO
2
C
4
H
9
]
195.1205;
found: 240.0386.
Ester 6cb: (Table 2, Entry 2) Yield 12% (14 mg). Pale yellow solid;
m.p. 38–40 °C. IR (neat): ν˜ = 2940, 1720, 1608, 1245, 1170,
Aldehyde 1t: Pale yellow oil. IR (neat): ν˜ = 2800, 1675, 1580, 1420,
–1 1
1260, 1230, 1183, 750 cm . H NMR (CDCl
3
, 300 MHz): δ = 10.51
–
1 1
3
840 cm . H NMR (CDCl , 300 MHz): δ = 5.30 (d, J = 1.7 Hz, 1
(d, J = 0.9 Hz, 1 H), 7.87–7.92 (m, 1 H), 7.49–7.58 (m, 2 H), 7.37–
H), 3.82–4.04 (m, 2 H), 3.70 (ddd, J = 11.5, 5.3, 1.7 Hz, 1 H), 3.14–
3.24 (m, 1 H), 2.80 (dd, J = 15.0, 11.5 Hz, 1 H), 2.65 (dd, J = 14.5,
7
2
.44 (m, 1 H), 3.73 (t, J = 6.6 Hz, 2 H), 2.71 (t, J = 6.6 Hz, 2 H),
.11 (quint, J = 6.6 Hz, 2 H) ppm. 1 C NMR (CDCl
3
3
, 100 MHz):
6.1 Hz, 1 H), 2.54 (ddd, J = 15.0, 5.3, 2.2 Hz, 1 H), 2.32 (dt, J =
δ = 191.6, 135.9, 133.6, 133.3, 128.1, 127.09, 127.05, 95.6, 77.3,
11ClO [M]+
H
14.5, 2.2 Hz, 1 H), 1.97 (sept, J = 6.8 Hz, 1 H), 1.15 (d, J = 7.1 Hz,
4
2
3.6, 31.2, 17.1 ppm. HRMS (EI): calcd. for C12
06.0498; found: 206.0486.
1
3
3
(
4
H), 0.94 (d, J = 6.6 Hz, 6 H), 0.14 (s, 9 H) ppm. C NMR
CDCl , 100 MHz): δ = 208.7, 172.3, 154.1, 125.1, 71.2, 47.7, 47.6,
3.5, 37.5, 27.7, 20.7, 19.2, 0.1 ppm. HRMS (EI): calcd. for
Si [M]+ 296.1808; found: 296.1782.
3
1
Aldehyde 1c-d: Colorless oil. H NMR (CDCl
3
, 300 MHz): δ = 3.00
(sext, J = 6.9 Hz, 1 H), 2.59 (dd, J = 16.8, 6.9 Hz, 1 H), 2.49 (dd,
16 28 3
C H O
J = 16.8, 6.9 Hz, 1 H), 1.24 (d, J = 6.9 Hz, 3 H), 0.14 (s, 9 H) ppm.
Ester 3cc: (Table 2, Entry 3) Procedure 1 was followed using 1c and
c. Reaction time: 45 h. Yield 61% (68 mg). Pale yellow oil. IR
(neat): ν˜ = 2940, 1650, 1618, 1350, 1265, 1223, 1204, 1048,
2
3
H NMR (CDCl , 61 MHz): δ = 9.83 (s) ppm.
2
General Procedure 1 for Regio- and Diastereoselective [4+2] Car-
bocyclization of 4-Alkynals with Alkenes: (Table 2, Entry 1) Under
–
1 1
3
840 cm . H NMR (CDCl , 300 MHz): δ = 12.24 (s, 1 H), 5.31 (d,
Ar, CH
added to CH
2 2
Cl
(1.0 mL) solution of dppf (22.2 mg, 0.040 mmol) was J = 2.2 Hz, 1 H), 4.83–4.93 (m, 1 H), 3.19 (dt, J = 18.1 and 2.4 Hz,
2
Cl
.040 mmol) and the mixture was stirred at room temperature for
min. H was introduced to the resulting solution in Schlenk tube.
2
(1.0 mL) solution of [Rh(cod)
2
]BF
4
(16.2 mg,
1 H), 2.86 (d, J = 18.1 Hz, 1 H), 2.76–2.95 (m, 1 H), 2.46–2.62 (m,
1 H), 2.18 (d, J = 17.8 Hz, 1 H), 1.63–1.91 (m, 4 H), 1.20–1.58 (m,
6 H), 1.12 (d, J = 7.0 Hz, 3 H), 0.11 (s, 9 H) ppm; vinyl proton of
0
5
2
1
3
After stirring for 0.5 h at room temperature, the resulting solution
was concentrated to dryness. A CH Cl solution (2 mL) of the alde-
hyde 1c (67.3 mg, 0.400 mmol) and butyl acrylate (2a, 513 mg,
keto isomer: δ = 5.42 (s, 1 H) ppm. C NMR (CDCl
δ = 171.5, 169.4, 156.3, 123.0, 96.3, 72.2, 37.3, 34.1, 31.51, 31.47,
25.4, 23.4, 19.2, 0.2 ppm. HRMS (EI): calcd. for C18 Si [M–
3
, 75 MHz):
2
2
30 3
H O
+
4
2
.00 mmol) was added to the residue. The mixture was stirred at
5 °C for 45 h. The resulting solution was concentrated and puri-
2 6 11
CO C H ] 195.1205; found: 195.1156.
Ester 6cc: (Table 2, Entry 3) Yield 18% (25 mg). Colorless solid;
m.p. 40–42 °C. IR (neat): ν˜ = 1930, 1720, 1608, 1243, 1180, 1025,
fied by preparative TLC (hexane/EtOAc, 25:1), which furnished the
ester 3ca (73.3 mg, 0.247 mmol, 62%) and the ester 6ca (17.1 mg,
–1 1
8
40 cm . H NMR (CDCl
H), 4.79–4.92 (m, 1 H), 3.65 (ddd, J = 11.4, 5.4, 1.8 Hz, 1 H), 3.10–
.22 (m, 1 H), 2.79 (dd, J = 15.0, 11.4 Hz, 1 H), 2.65 (dd, J = 14.4,
6.0 Hz, 1 H), 2.52 (ddd, J = 15.0, 5.4, 2.1 Hz, 1 H), 2.31 (dt, J =
4.4, 2.1 Hz, 1 H), 1.64–1.93 (m, 4 H), 1.19–1.60 (m, 6 H), 1.15 (d,
3
, 300 MHz): δ = 5.34 (d, J = 1.8 Hz, 1
0.058 mmol, 14%, Ͼ99% de).
3
Ester 3ca: Colorless oil. IR (neat): ν˜ = 2945, 1653, 1618, 1402,
–1 1
1350, 1265, 1223, 1202, 1080, 1045, 840 cm . H NMR (CDCl
3
,
1
300 MHz): δ = 12.17 (s, 1 H), 5.30 (d, J = 2.0 Hz, 1 H), 4.07–4.25
1
3
J = 7.2 Hz, 3 H), 0.14 (s, 9 H) ppm. C NMR (CDCl
δ = 209.0, 171.8, 154.3, 125.1, 73.3, 47.6, 47.4, 43.4, 37.5, 31.5,
1.4, 25.3, 23.6, 20.7, 0.0 ppm. HRMS (EI): calcd. for C18 Si
3
, 75 MHz):
(m, 2 H), 3.19 (dt, J = 18.1, 2.6 Hz, 1 H), 2.86 (d, J = 18.1 Hz, 1
H), 2.77–2.96 (m, 1 H), 2.50–2.62 (m, 1 H), 2.19 (dd, J = 17.8,
3
[
30 3
H O
1
7
.3 Hz, 1 H), 1.58–1.72 (m, 2 H), 1.35–1.48 (m, 2 H), 1.12 (d, J =
.0 Hz, 3 H), 0.96 (t, J = 7.5 Hz, 3 H), 0.11 (s, 9 H) ppm; vinyl
+
M] 322.1964; found: 322.1927.
13
proton of keto isomer: δ = 5.43 (s, 1 H) ppm. C NMR (CDCl
3
,
Ester 3cd: (Table 2, Entry 4) Procedure 1 was followed using 1c and
2d. Reaction time: 45 h. Yield 24% (29 mg). Colorless oil. IR
75 MHz): δ = 172.0, 169.6, 156.2, 123.1, 96.0, 64.1, 37.2, 34.1, 31.4,
Eur. J. Org. Chem. 2006, 3582–3595
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3589

K. Tanaka, Y. Hagiwara, M. Hirano
FULL PAPER
–
1 1
(neat): ν˜ = 2925, 1650, 1618, 1358, 1288, 1230, 1152, 840 cm . H
(CDCl
3
, 300 MHz): δ = 5.28 (d, J = 1.5 Hz, 1 H), 4.02–4.28 (m, 2
NMR (CDCl
3
, 300 MHz): δ = 12.34 (s, 1 H), 5.30 (d, J = 2.0 Hz,
H), 3.60 (ddd, J = 12.3, 5.4, 1.5 Hz, 1 H), 2.85–3.00 (m, 1 H), 2.79
(dd, J = 15.0, 12.3 Hz, 1 H), 2.35–2.66 (m, 3 H), 1.53–1.76 (m, 2
1
2
1
H), 3.14 (dt, J = 18.2, 2.4 Hz, 1 H), 2.80 (d, J = 18.2 Hz, 1 H),
.68–2.96 (m, 1 H), 2.42–2.66 (m, 1 H), 2.16 (d, J = 17.8 Hz, 1 H), H), 1.05–1.51 (m, 8 H), 0.94 (t, J = 7.5 Hz, 3 H), 0.89 (t, J =
.51 (s, 9 H), 1.11 (d, J = 7.0 Hz, 3 H), 0.11 (s, 9 H) ppm; vinyl
1
3
3
7.2 Hz, 3 H), 0.15 (s, 9 H) ppm. C NMR (CDCl , 75 MHz): δ =
13
proton of keto isomer: δ = 5.42–5.44 (m, 1 H) ppm. C NMR
CDCl , 75 MHz): δ = 171.7, 168.8, 156.5, 122.6, 96.9, 80.8, 37.1,
5.8, 34.0, 28.1, 19.1, 0.0 ppm. HRMS (EI): calcd. for C16 Si
208.7, 172.2, 153.8, 125.1, 64.6, 47.2, 46.1, 43.8, 42.8, 33.3, 30.4,
29.2, 22.5, 18.9, 13.7, 13.4, 0.0 ppm. HRMS (EI): calcd. for
(
3
19 34 3
C H O
Si [M]+ 338.2277; found: 338.2233.
3
H
28
O
3
+
2 4 9
[M–CO C H ] 195.1205; found: 195.1149.
Ester 3dd: (Table 2, Entry 8) Procedure 1 was followed using 1d
and 2d. Reaction time: 23 h. Yield 25% (33 mg). Colorless oil. IR
Ester 6cd: (Table 2, Entry 4) Yield 62% (74 mg). Relative configu-
ration was determined by NOESY experiment (see supporting in-
formation; for supp. inf. see also the footnote on the first page of
this article). Pale brown solid; m.p. 46–47 °C. IR (neat): ν˜ = 2950,
–
1 1
(neat): ν˜ = 2940, 1650, 1620, 1355, 1285, 1240, 1150, 840 cm . H
NMR (CDCl , 300 MHz): δ = 12.32 (s, 1 H), 5.34 (d, J = 1.7 Hz,
3
1 H), 3.03 (dt, J = 17.8, 2.4 Hz, 1 H), 2.77 (d, J = 1.78 Hz, 1 H),
2.64 (q, J = 6.8 Hz, 1 H), 2.38–2.55 (m, 1 H), 2.25 (d, J = 18.0 Hz,
1 H), 1.50 (s, 9 H), 1.15–1.49 (m, 6 H), 0.89 (t, J = 6.8 Hz, 3 H),
0.11 (s, 9 H) ppm; vinyl proton of keto isomer: δ = 5.45–5.48 (m,
–1
1
1
3
5
1
5
1
1
3
2
3
720, 1610, 1365, 1250, 1155, 840 cm . H NMR (CDCl ,
00 MHz): δ = 5.41 (d, J = 1.8 Hz, 1 H, Ha), 3.56 (ddd, J = 11.4,
.5, 1.8 Hz, 1 H, Hb), 3.05–3.23 (m, 1 H, Hc), 2.74 (dd, J = 15.2,
1.4 Hz, 1 H), 2.64 (dd, J = 14.7, 6.1 Hz, 1 H), 2.50 (ddd, J = 15.2,
.5, 2.0 Hz, 1 H), 2.30 (dt, J = 14.7, 2.2 Hz, 1 H), 1.48 (s, 9 H),
1
3
1 H) ppm. C NMR (CDCl
3
, 75 MHz): δ = 171.9, 169.4, 155.8,
123.9, 97.4, 81.0, 39.7, 36.0, 32.54, 32.51, 29.9, 28.3, 23.0, 14.1,
.14 (d, J = 7.3 Hz, 3 H), 0.15 (s, 9 H) ppm. 13C NMR (CDCl
,
0.5 ppm. HRMS (EI): calcd. for C19
237.1674; found: 237.1639.
+
3
34 3 2 4 9
H O Si [M–CO C H ]
00 MHz): δ = 209.0, 171.5, 154.5, 124.8, 81.4, 48.0, 47.5, 43.4,
7.5, 28.1 20.8, 0.1 ppm. HRMS (EI): calcd. for C16
96.1808; found: 296.1732.
28 3
H O
Si [M]+
Ester 6dd: (Table 2, Entry 8) Yield 52% (71 mg). Pale yellow oil.
–1
1
IR (neat): ν˜ = 2940, 1720, 1368, 1250, 1155, 840 cm . H NMR
(CDCl , 300 MHz): δ = 5.40 (d, J = 1.7 Hz, 1 H), 3.48 (ddd, J =
Ketone 6ce: (Table 2, Entry 5) Procedure 1 was followed using 1c,
e (2.0 equiv.), and 20% [Rh(cod) ]BF /dppf. Reaction time: 43 h.
Yield 69% (82 mg). Pale brown solid; m.p. 39–41 °C. IR (neat): ν˜ =
3
2
2
4
12.1, 5.1, 1.7 Hz, 1 H), 2.81–2.95 (m, 1 H), 2.72 (dd, J = 14.5,
12.1 Hz, 1 H), 2.36–2.59 (m, 3 H), 1.48 (s, 9 H), 1.10–1.43 (m, 6
–1
1
13
2
3
1
1
1
0
1
1
925, 1702, 1610, 1405, 1375, 1245, 1045, 845 cm . NMR (C
00 MHz): δ = 5.31 (d, J = 1.2 Hz, 1 H), 3.45 (ddd, J = 11.4, 4.8, 75 MHz): δ = 209.1, 171.5, 154.5, 125.0, 81.2, 47.8, 46.1, 43.9, 43.0,
6
D
6
,
3
H), 0.89 (t, J = 6.6 Hz, 3 H), 0.15 (s, 9 H) ppm. C NMR (CDCl ,
.2 Hz, 1 H), 2.83–3.00 (m, 2 H), 2.29–2.52 (m, 3 H), 2.18 (dt, J =
4.4, 2.1 Hz, 1 H), 1.94–2.08 (m, 1 H), 1.55–1.73 (m, 2 H), 1.16–
.38 (m, 6 H), 0.98 (t, J = 6.9 Hz, 3 H), 0.96 (t, J = 6.9 Hz, 3 H),
33.5, 29.3, 27.9, 22.7, 13.9, 0.1 ppm. HRMS (EI): calcd. for
Si [M]+ 338.2277; found: 338.2242.
19 34 3
C H O
Ester 3ea: (Table 2, Entry 9) Procedure 1 was followed using 1e and
a at 8 °C. Reaction time: 44 h. Yield 66% (94 mg). Colorless oil.
IR (neat): ν˜ = 2920, 1650, 1615, 1400, 1350, 1272, 1240, 1213, 1065,
.13 (s, 9 H) ppm. 13C NMR (C
D
6
, 75 MHz): δ = 208.5, 207.2,
6
2
57.9, 125.2, 52.7, 47.7, 43.2, 42.7, 38.3, 32.0, 29.2, 23.7, 22.8, 20.6,
4.2, –0.1 ppm. HRMS (EI): calcd. for C18
+
H
32
O
2
Si [M] 308.2172;
–1 1
8
40, 735, 698 cm . H NMR (CDCl
H), 7.14–7.36 (m, 5 H), 5.51 (s, 1 H), 3.92–4.20 (m, 3 H), 2.97 (d,
Amide 3cf and 6cf: (Table 2, Entry 6) Procedure 1 was followed J = 18.3 Hz, 1 H), 2.71–2.85 (m, 3 H), 1.50–1.66 (m, 2 H), 1.34
using 1c, 2f (1.0 equiv.), and 20% [Rh(cod) ]BF /dppb at 80 °C in (sext, J = 7.8 Hz, 2 H), 0.90 (t, J = 7.5 Hz, 3 H), 0.20 (s, 9 H) ppm;
CH Cl) . Reaction time: 45 h. Yield 7% (7.4 mg). Pale yellow so-
lid; m.p. 107–109 °C (mixture of isomers). IR (neat): ν˜ = 3340,
3
, 300 MHz): δ = 12.24 (s, 1
found: 308.2169.
2
4
1
3
(
2
2
vinyl proton of keto isomer: δ = 5.66–5.69 (m, 1 H) ppm. C NMR
(CDCl , 75 MHz): δ = 171.8, 169.6, 154.3, 140.7, 128.4, 126.6,
126.4, 125.5, 97.0, 64.1, 43.1, 33.9, 32.3, 30.5, 19.1, 13.7, 0.4 ppm.
3
–1 1
2
1
1
3
5
7
5
3
910, 1620, 1238, 835 cm . H NMR (CDCl , 400 MHz, 3cf/6cf =
+
1:89): δ = 5.21 (d, J = 1.2 Hz, 1 H), 3.80 (ddd, J = 13.2, 5.2,
.2 Hz, 1 H), 3.18–3.28 (m, 1 H), 3.03 (s, 3 H), 2.92 (s, 3 H), 2.88–
.08 (m, 1 H), 2.63 (dd, J = 14.0, 6.4 Hz, 1 H), 2.42 (ddd, J = 14.8,
.2, 2.4 Hz, 1 H), 2.32 (dt, J = 14.0, 2.8 Hz, 1 H), 1.17 (d, J =
.2 Hz, 3 H), 0.15 (s, 9 H) ppm; vinyl proton of minor isomer: δ =
.42 (d, J = 1.6 Hz, 1 H, keto isomer), 5.27–5.29 (m, 1 H, enol
HRMS (EI): calcd. for C21
found: 257.1376.
H
30
O
3
Si [M–CO
2
C
4
H
9
]
257.1361;
Ester 6ea: (Table 2, Entry 9) Yield 6% (9.3 mg). Pale brown oil. IR
–1
1
(
neat): ν˜ = 2920, 1720, 1598, 1245, 1175, 840, 750, 700 cm . H
NMR (CDCl , 300 MHz): δ = 7.18–7.42 (m, 5 H), 5.64 (d, J =
.5 Hz, 1 H), 4.26–4.38 (m, 1 H), 4.01–4.24 (m, 2 H), 3.44 (ddd, J
3
1
13
isomer) ppm. C NMR (CDCl
3
, 75 MHz): δ = 210.1, 171.0, 154.4,
=
10.5, 5.4, 1.5 Hz, 1 H), 3.16 (dt, J = 15.9, 1.8 Hz, 1 H), 2.83 (dd,
124.4, 48.3, 44.9, 44.1, 38.0, 36.8, 35.6, 19.6, –0.1 ppm. HRMS
J = 15.9, 6.0 Hz, 1 H), 2.73 (dd, J = 15.9, 10.5 Hz, 1 H), 2.43 (ddd,
J = 15.9, 5.4, 1.8 Hz, 1 H), 1.52–1.70 (m, 2 H), 1.37 (sext, J =
+
2
(EI): calcd. for C14H25NO Si [M] 267.1655; found: 267.1633.
1
3
Ester 3da: (Table 2, Entry 7) Procedure 1 was followed using 1d
and 2a. Reaction time: 45 h. Yield 56% (60 mg). Colorless oil. IR
7.5 Hz, 2 H), 0.94 (t, J = 7.2 Hz, 3 H), 0.17 (s, 9 H) ppm. C NMR
(CDCl , 75 MHz): δ = 208.3, 172.3, 152.5, 140.4, 128.9, 127.9,
3
(
neat): ν˜ = 2940, 1655, 1620, 1400, 1350, 1275, 1230, 1205, 1075, 127.0, 126.9, 64.8, 47.2, 45.5, 44.8, 43.3, 30.5, 19.1, 13.6, 0.0 ppm.
40 cm . H NMR (CDCl , 300 MHz): δ = 12.17 (s, 1 H), 5.35 (s, HRMS (EI): calcd. for C H O Si [M] 358.1964; found:
3 21 30 3
–1
1
+
8
1
1
H), 4.00–4.28 (m, 2 H), 3.10 (d, J = 17.5 Hz, 1 H), 2.83 (d, J = 358.1981.
7.5 Hz, 1 H), 2.37–2.73 (m, 2 H), 2.28 (d, J = 18.0 Hz, 1 H), 1.66
Ester 3ed: (Table 2, Entry 10) Procedure 1 was followed using 1e
and 2d at 8 °C. Reaction time: 70 h. Yield 38% (54 mg). Colorless
solid; m.p. 83–84 °C. IR (neat): ν˜ = 2925, 1648, 1617, 1390, 1355,
(
quint, J = 6.9 Hz, 2 H), 1.09–1.53 (m, 8 H), 0.95 (t, J = 7.5 Hz, 3
H), 0.89 (t, J = 6.0 Hz, 3 H), 0.14 (s, 9 H) ppm; vinyl proton of
keto isomer: δ = 5.47 (s, 1 H) ppm. 13C NMR (CDCl
, 75 MHz):
δ = 172.0, 170.1, 155.3, 124.2, 96.4, 64.1, 39.6, 35.9, 32.4, 32.1,
0,7, 29.9, 23.0, 19.2, 14.0, 13.7, 0.4 ppm. HRMS (EI): calcd. for
3
–1
1
1285, 1243, 1218, 1158, 1060, 840, 750, 698 cm . H NMR
(
CDCl , 300 MHz): δ = 12.41 (s, 1 H), 7.13–7.39 (m, 5 H), 5.50 (s,
3
3
C
1
2
H), 4.02 (d, J = 5.7 Hz, 1 H), 2.94 (d, J = 18.0 Hz, 1 H), 2.69–
+
19
H
34
O
3
Si [M–CO
2 4 9
C H ] 237.1674; found: 237.1618.
.85 (m, 3 H), 1.43 (s, 9 H), 0.20 (s, 9 H) ppm; vinyl proton of keto
1
3
Ester 6da: (Table 2, Entry 7) Yield 65% (15 mg). Pale yellow oil.
IR (neat): ν˜ = 2925, 1720, 1608, 1245, 1175, 840 cm . H NMR
isomer: δ = 5.66 (s, 1 H) ppm. C NMR (CDCl
171.6, 169.0, 154.7, 140.9, 128.4, 126.7, 126.4, 125.3, 98.0, 81.1,
3
, 75 MHz): δ =
–1 1
3590
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3582–3595

Rh-Catalyzed [4+2] Carbocyclization of Alkynals
3.2, 33.9, 32.7, 28.2, 0.4 ppm. HRMS (EI): calcd. for C21
FULL PAPER
4
H
30
O
3
Si
ture, the resulting solution was concentrated to dryness. A CH
solution (2 mL) of the aldehyde 1g (72.9 mg, 0.400 mmol, cis/trans
59:41) and tert-butyl acrylate (2d, 513 mg, 4.00 mmol) was added
2 2
Cl
+
2 4 9
[M–CO C H ] 257.1361; found: 257.1376.
=
Ester 6ed: (Table 2, Entry 10) Yield 35% (50 mg). Pale yellow solid;
m.p. 80–82 °C. IR (neat): ν˜ = 2900, 1705, 1600, 1365, 1250, 1203,
to the residue. The mixture was stirred at 25 °C for 27 h. The re-
sulting solution was purified by silica gel column chromatography
O, 40:1), which furnished the aldehyde 1g (29.6 mg,
.162 mmol, 41%, cis/trans = 88:12) and the ester 6gd (32.1 mg,
.103 mmol, 26%, cis/trans Ϸ 1:99). Relative configuration was de-
–
1 1
1
7
3
2
2
3
145, 838, 768, 702 cm . H NMR (CDCl , 300 MHz): δ = 7.13–
(
hexane/Et
2
.42 (m, 5 H), 5.79 (d, J = 1.5 Hz, 1 H), 4.29 (d, J = 3.9 Hz, 1 H),
.37 (ddd, J = 9.3, 5.7, 1.5 Hz, 1 H), 3.14 (d, J = 15.9 Hz, 1 H),
.83 (dd, J = 15.9, 5.7 Hz, 1 H), 2.64 (dd, J = 15.9, 9.3 Hz, 1 H),
.37 (ddd, J = 15.9, 5.7, 1.2 Hz, 1 H), 1.45 (s, 9 H), 0.16 (s, 9
0
0
termined by NOESY experiment (see supporting information).
Colorless oil. IR (neat): ν˜ = 2950, 1715, 1605, 1360, 1243, 1145,
13
H) ppm. C NMR (CDCl
3
, 75 MHz): δ = 208.6, 171.5, 152.5,
–
1 1
838 cm . H NMR (C
6
D
6
, 300 MHz): δ = 5.66 (s, 1 H, H
), 2.96–3.11 (m, 1 H, H ), 2.29–
), 2.11–2.23 (m, 1 H, H ), 1.39 (s, 9 H),
.95 (d, J = 7.2 Hz, 3 H), 0.90 (d, J = 6.9 Hz, 3 H), 0.07 (s, 9
a
), 3.50
1
–
3
40.6, 128.8, 128.0, 126.9, 126.7, 81.3, 47.9, 45.2, 44.5, 42.8, 27.9,
(ddd, J = 12.9, 5.4, 1.8 Hz, 1 H, H
b
d
+
0.1 ppm. HRMS (EI): calcd. for C21
01.1259; found: 301.1288.
30 3 4 9
H O Si [M – C H ]
2
0
.50 (m, 2 H, H
c
and H
f
e
1
3
Ester 3aa: (Scheme 3) Procedure 1 was followed using 1a, 2a
2.0 equiv.), and 20% [Rh(nbd) ]BF /dppe at 50 °C in (CH Cl)
Reaction time: 20 h. Yield 9% (10 mg). Colorless oil. IR (neat): ν˜
6 6
H) ppm. C NMR (C D , 75 MHz): δ = 210.2, 171.3, 154.6, 125.4,
80.7, 51.7, 48.1, 44.8, 40.7, 28.0, 20.6, 17.4, 0.3 ppm. HRMS (EI):
calcd. for C H O Si [M] 310.1965; found: 310.1986.
(
2
4
2
2
.
+
1
8
30
3
–1 1
=
3
2920, 1650, 1615, 1270, 1220, 1080, 820 cm . H NMR (CDCl ,
Amide 6af: (Scheme 6) Procedure 1 was followed using 1a, 2f
1.0 equiv.), and 20% [Rh(cod) ]BF /dppb at 80 °C in (CH Cl)
Reaction time: 25 h. Yield 37% (37 mg). Pale yellow oil. IR (neat):
3
4
2
00 MHz): δ = 12.17 (s, 1 H), 5.24 (dt, J = 7.5, 2.1 Hz, 1 H), 4.07–
.25 (m, 2 H), 2.93–3.11 (m, 2 H), 2.77 (d, J = 18.0 Hz, 1 H), 2.43–
.55 (m, 1 H), 1.92–2.18 (m, 3 H), 1.58–1.72 (m, 2 H), 1.23–1.49
(
2
4
2
2
.
–
1
ν˜ = 2850, 1702, 1620, 1390, 1250, 1218, 1130, 1050, 702, 470 cm .
(
(
m, 6 H), 1.67 (d, J = 7.2 Hz, 3 H), 0.96 (t, J = 7.5 Hz, 3 H), 0.89
t, J = 7.2 Hz, 3 H) ppm; vinyl proton of keto isomer: δ = 5.33 (t,
1
H NMR (CDCl
3
, 300 MHz): δ = 5.11 (t, J = 7.2 Hz, 1 H), 3.72
13
(dd, J = 12.6, 3.9 Hz, 1 H), 3.35 (d-quint, J = 6.6, 2.7 Hz, 1 H),
J = 7.5 Hz, 1 H) ppm. C NMR (CDCl
3
, 75 MHz): δ = 172.2,
70.1, 136.4, 123.7, 96.5, 64.1, 37.1, 32.2, 30.7, 28.6, 28.0, 26.6,
2.3, 19.2, 18.9, 14.0, 13.7 ppm. HRMS (EI): calcd. for C17
3
6
.02 (s, 3 H), 2.95 (s, 3 H), 2.85–2.97 (m, 1 H), 2.59 (dd, J = 14.1,
.6 Hz, 1 H), 2.40 (ddd, J = 14.7, 4.8, 2.1 Hz, 1 H), 2.29 (dt, J =
1
2
28 3
H O
+
14.1, 2.1 Hz, 1 H), 2.11 (q, J = 7.2 Hz, 2 H), 1.24–1.42 (m, 4 H),
[M–CO
2 4 9
C H ] 179.1435; found: 179.1411.
1
3
1
(
3
.13 (d, J = 6.9 Hz, 3 H), 0.90 (t, J = 6.9 Hz, 3 H) ppm. C NMR
CDCl , 75 MHz): δ = 210.9, 171.2, 136.2, 125.1, 48.1, 44.9, 42.3,
6.8, 35.5, 31.7, 31.5, 27.1, 22.3, 19.5, 13.8 ppm. HRMS (EI): calcd.
Ester 4a: (Scheme 3) Yield 21% (24 mg). Colorless oil. IR (neat): ν˜
=
3
–1 1
2925, 1710, 1615, 1270, 1165 cm . H NMR (CDCl
δ = 9.69 (t, J = 1.8 Hz, 1 H), 7.20 (d, J = 15.9 Hz, 1 H), 5.97 (d, J
15.9 Hz, 1 H), 5.89 (t, J = 7.2 Hz, 1 H), 4.15 (t, J = 6.6 Hz, 2
H), 3.43 (sext, J = 7.2 Hz, 1 H), 2.55–2.72 (m, 2 H), 2.16–2.28 (m, Amide 6bf: (Scheme 6) Procedure 1 was followed using 1b, 2f
3
, 300 MHz):
+
2
for C15H25NO [M] 251.1885; found: 251.1858.
=
2
3
H), 1.55–1.72 (m, 2 H), 1.27–1.49 (m, 6 H), 1.19 (d, J = 7.2 Hz, (1.0 equiv.), and 20% [Rh(cod) ]BF /dppb at 80 °C in (CH Cl) .
2 4 2 2
1
3
H), 0.95 (t, J = 7.2 Hz, 3 H), 0.92 (t, J = 7.2 Hz, 3 H) ppm.
C
Reaction time: 46 h. Yield 20% (22 mg). Pale yellow solid; m.p.
NMR (CDCl
3
, 75 MHz): δ = 201.2, 167.3, 146.0, 139.5, 139.0,
105–107 °C. IR (neat): ν˜ = 2880, 1700, 1622, 1478, 1396, 1195,
–
1 1
1
1
2
17.1, 64.3, 48.8, 31.4, 30.7, 28.3, 27.2, 22.4, 19.3, 19.2, 13.9,
3.7 ppm. HRMS (EI): calcd. for C17
80.2047.
1112, 1042, 698, 465 cm . H NMR (CDCl , 300 MHz): δ = 7.13–
3
+
H
28
O
3
[M] 280.2038; found:
7.42 (m, 5 H), 6.28 (s, 1 H), 3.90 (ddd, J = 12.9, 4.5, 2.1 Hz, 1 H),
3.58 (d-quint, J = 6.6, 2.1 Hz, 1 H), 3.06 (s, 3 H), 3.03 (s, 3 H),
2
=
.95–3.14 (m, 1 H), 2.58 (dd, J = 14.1, 6.6 Hz, 1 H), 2.50 (ddd, J
Ketone 5b: (Scheme 3)[10a] Procedure 1 was followed using 1b, 2a
2.0 equiv.), and 20% [Rh(nbd) ]BF /dppe at 50 °C in (CH Cl)
Reaction time: 20 h. Yield 44% (30 mg). Colorless oil. H NMR
CDCl , 300 MHz): δ = 7.66–7.72 (m, 3 H), 7.28–7.43 (m, 3 H),
.01 (d-quint, J = 7.2, 2.4 Hz, 1 H), 2.82 (dd, J = 18.9, 6.6 Hz, 1
H), 2.17 (dd, J = 18.9, 2.4 Hz, 1 H), 1.26 (d, J = 6.9 Hz, 3 H) ppm.
14.7, 4.8, 2.4 Hz, 1 H), 2.23 (dt, J = 14.1, 2.4 Hz, 1 H), 1.25 (d,
(
2
4
2
2
.
1
3
J = 6.9 Hz, 3 H) ppm. C NMR (CDCl
3
, 75 MHz): δ = 210.4,
1
1
3
2
70.9, 139.7, 136.7, 128.6, 128.4, 127.1, 125.0, 48.2, 45.1, 42.7, 37.0,
5.7, 32.3, 19.6 ppm. HRMS (EI): calcd. for C17
71.1572; found: 271.1592.
(
3
3
+
2
H21NO [M]
1
3
C NMR (CDCl
3
, 75 MHz): δ = 207.3, 163.9, 142.3, 131.4, 128.36,
Ester 4c: (Table 1, Entry 1) Yield 7% (8.3 mg). Colorless oil. IR
128.34, 127.1, 44.4, 32.9, 20.2 ppm.
–1
1
(
(
1
neat): ν˜ = 2940, 1710, 1620, 1248, 1165, 843 cm . H NMR
CDCl , 300 MHz): δ = 9.72 (t, J = 1.8 Hz, 1 H), 7.24 (d, J =
5.6 Hz, 1 H), 6.11 (d, J = 15.6 Hz, 1 H), 6.00 (s, 1 H), 4.16 (t, J
Ester 6fd: (Scheme 4) Procedure 1 was followed using 1f and 2d.
Reaction time: 45 h. Yield 57% (68 mg). Relative configuration was
determined by NOESY experiment (see Supporting Information).
Pale yellow oil. IR (neat): ν˜ = 2925, 1720, 1610, 1360, 1245, 1150,
3
=
1
6.6 Hz, 2 H), 3.21–3.34 (m, 1 H), 2.62 (ddd, J = 16.8, 8.1, 1.8 Hz,
H), 2.54 (ddd, J = 16.8, 6.9, 1.8 Hz, 1 H), 1.60–1.71 (m, 2 H),
–
1
1
1.35–1.47 (m, 2 H), 1.18 (d, J = 6.9 Hz, 3 H), 0.95 (t, J = 6.9 Hz,
3
8
3
1
(
(
3
40 cm . H NMR (CDCl , 300 MHz): δ = 5.61 (s, 1 H, Ha), 3.43–
1
3
H), 0.14 (s, 9 H) ppm. C NMR (CDCl
3
, 75 MHz): δ = 200.8,
.56 (m, 1 H, Hb), 2.63–2.75 (m, 2 H, Hc and Hf), 2.49 (ddd, J =
5.0, 6.6, 0.9 Hz, 1 H, Hd), 2.28–2.43 (m, 2 H, He and Hg), 1.42
166.9, 155.0, 144.5, 135.2, 120.4, 64.4, 48.9, 33.7, 30.7, 19.7, 19.2,
+
1
3
16 28 3
13.7, –0.1 ppm. HRMS (EI): calcd. for C H O Si [M] 296.1808;
found: 296.1805.
s, 9 H), 1.11 (d, J = 6.3 Hz, 3 H), 0.16 (s, 9 H) ppm. C NMR
CDCl , 75 MHz): δ = 209.5, 171.6, 149.8, 129.5, 81.4, 55.6, 44.7,
2.9, 37.9, 27.8, 15.1, –0.1 ppm. HRMS (EI): calcd. for C16 Si
3
4
[
28 3
H O
Aldehyde 7c: (Table 1, Entry 4) Yield 30% (20 mg). Colorless oil.
IR (neat): ν˜ = 2800, 1660, 1220, 815 cm . H NMR (CDCl
+
M] 296.1808; found: 296.1769.
Ester 6gd: (Scheme 5). Under Ar, CH
22.2 mg, 0.040 mmol) was added to CH
Rh(cod) ]BF (16.2 mg, 0.040 mmol) and the mixture was stirred
at room temperature for 5 min. H was introduced to the resulting
solution in a Schlenk tube. After stirring for 0.5 h at room tempera-
–
1
1
3
,
2
Cl
2
(1.0 mL) solution of dppf
Cl (1.0 mL) solution of 4.77–4.81 (m, 1 H), 1.85–1.89 (m, 3 H), 0.19 (s, 9 H) ppm.
NMR (CDCl , 75 MHz): δ = 194.7, 159.0, 154.0, 141.9, 116.7,
300 MHz): δ = 9.41 (s, 1 H), 6.68 (s, 1 H), 5.08–5.12 (m, 1 H),
1
3
(
[
2
2
C
2
4
3
2
9
22.7, –0.6 ppm. HRMS (EI): calcd. for C H
16OSi [M]+ 168.0970;
found: 168.0898.
Eur. J. Org. Chem. 2006, 3582–3595
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3591

K. Tanaka, Y. Hagiwara, M. Hirano
FULL PAPER
General Procedure 2 for Regio- and Enantioselective [4+2] Carbocy-
291.1026; found: 291.0974. CHIRALCEL OD-H, hexane/iPrOH,
clization of 4-Alkynals with Alkenes: (Table 4, Entry 1) Under Ar,
70:30, 0.8 mL/min, retention times: 12.6 min (major isomer) and
2 2
a CH Cl (1.0 mL) solution of (R,R)-11 (19.8 mg, 0.030 mmol) was 15.4 min (minor isomer). The absolute configuration was deter-
added to a CH
2
Cl
.030 mmol) and the mixture was stirred at room temperature for
min. H was introduced to the resulting solution in a Schlenk
2
(1.0 mL) solution of [Rh(cod)
2
]BF
4
(12.2 mg,
mined to be S configuration by the anomalous dispersion method.
0
5
Amide (+)-6kg: (Table 4, Entry 5) Procedure 2 was followed using
2
1
k and 2g. Reaction time: 16 h. Yield 77% (73 mg, Ͼ99% ee). Pale
tube. After stirring at room temperature for 0.5 h, the resulting
solution was concentrated to dryness. A CH Cl solution (1.5 mL)
25
brown solid; m.p. 126–128 °C. [α]
D
= +74.9 (c = 1.102, acetone,
2
2
Ͼ99% ee). IR (neat): ν˜ = 3400, 2950, 2895, 1705, 1623, 1435, 1090,
of the aldehyde 1h (47.6 mg, 0.300 mmol) and N,N-dimethylacryl-
amide (2f, 29.7 mg, 0.300 mmol) was added to the residue. The mix-
ture was stirred at 80 °C for 16 h. The resulting solution was con-
centrated and purified by preparative TLC (hexane/EtOAc, 1:4),
which furnished the amide (+)-6hf (43.8 mg, 0.170 mmol, 57%
yield, Ͼ99% ee) as a pale brown solid.
–1 1
8
7
3
3
30 cm . H NMR (CDCl , 300 MHz): δ = 7.29–7.37 (m, 2 H),
.11–7.20 (m, 2 H), 6.49 (s, 1 H), 3.74 (t, J = 5.4 Hz, 1 H), 3.40–
.62 (m, 4 H), 2.70–2.90 (m, 3 H), 2.42–2.62 (m, 2 H), 2.24–2.40
m, 1 H), 1.76–2.08 (m, 4 H) ppm. C NMR (CDCl , 75 MHz): δ
3
13
(
=
208.0, 169.6, 136.4, 134.9, 132.9, 130.1, 128.5, 126.4, 50.2, 46.6,
4
C
6.1, 44.2, 40.3, 26.2, 25.2, 24.2 ppm. HRMS (EI): calcd. for
Amide (+)-6hf: Pale brown solid; m.p. 126–127 °C. [α]2
5
= +125.9
+
D
18
H
20ClNO
ane/iPrOH, 70:30, 1.5 mL/min, retention times: 12.4 min (major
, 300 MHz): δ = 7.32–7.42 isomer) and 17.2 min (minor isomer).
2
[M] 317.1183; found: 317.1192. Chiralpak AS, hex-
(c = 1.348, acetone, Ͼ99% ee). IR (neat): ν˜ = 2900, 1693, 1630,
–1 1
1395, 1130, 705 cm . H NMR (CDCl
3
(
m, 2 H), 7.20–7.32 (m, 3 H), 6.55 (s, 1 H), 3.91 (t, J = 5.4 Hz, 1
H), 3.12 (s, 3 H), 3.01 (s, 3 H), 2.67–2.90 (m, 3 H), 2.53–2.61 (m,
H), 2.49 (ddd, J = 15.0, 5.4 and 1.2 Hz, 1 H), 2.25–2.39 (m, 1
Amide (+)-6lf: (Table 4, Entry 6) Procedure 2 was followed using
1
9
1
1
5
3
2
7
4
l, 2f and 20% catalyst. Reaction time: 20 h. Yield 50% (39 mg,
1
25
D
7% ee). Pale yellow solid; m.p. 99–100 °C. [α] = +134.7 (c =
13
H) ppm. C NMR (CDCl
1
2
3
, 75 MHz): δ = 208.4, 171.4, 136.5,
.680, acetone, 97% ee). IR (neat): ν˜ = 3400, 2900, 1700, 1620,
35.7, 128.7, 128.3, 127.8, 127.1, 48.4, 44.7, 40.5, 37.4, 35.9,
–1 1
3
398, 1122 cm . H NMR (CDCl , 300 MHz): δ = 5.80 (s, 1 H),
+
2
5.2 ppm. HRMS (EI): calcd. for C16H19NO [M] 257.1416;
.54–5.67 (m, 1 H), 3.71 (t, J = 5.4 Hz, 1 H), 3.04 (s, 3 H), 2.97 (s,
found: 257.1436. CHIRALCEL OD-H, hexane/iPrOH, 70:30,
.8 mL/min, retention times: 11.6 min (major isomer) and 16.9 min
minor isomer).
H), 2.70–2.87 (m, 2 H), 2.46–2.70 (m, 2 H), 2.23–2.43 (m, 2 H),
0
(
13
3
.00–2.18 (m, 4 H), 1.52–1.70 (m, 4 H) ppm. C NMR (CDCl ,
5 MHz): δ = 208.9, 171.7, 134.3, 132.3, 130.8, 127.7, 48.7, 45.0,
1.1, 37.3, 35.9, 29.1, 25.45, 25.42, 22.7, 21.9 ppm. HRMS (EI):
Amide (+)-6if: (Table 4, Entry 2) Procedure 2 was followed using
1
orange oil. [α] = +110.8 (c = 0.352, acetone, Ͼ99% ee). IR (neat):
D
ν˜ = 3430, 2925, 1705, 1625, 1500, 1400, 1243, 1178, 1128, 1030,
8
6
3
2
2
4
+
calcd. for C20
H23NO
2
[M] 309.1729; found: 309.1739. CHI-
i and 2f. Reaction time: 23 h. Yield 58% (50 mg, Ͼ99% ee). Pale
25
RALCEL OD-H, hexane/iPrOH, 85:15, 1.0 mL/min, retention
times: 12.3 min (major isomer) and 17.0 min (minor isomer).
–1 1
3
35 cm . H NMR (CDCl , 300 MHz): δ = 7.13–7.21 (m, 2 H),
Amide (+)-6mf: (Table 4, Entry 7) Procedure 2 was followed using
.84–6.95 (m, 2 H), 6.48 (s, 1 H), 3.88 (t, J = 5.4 Hz, 1 H), 3.82 (s,
H), 3.10 (s, 3 H), 3.00 (s, 3 H), 2.66–2.90 (m, 3 H), 2.41–2.62 (m,
1
m, 2f, and 20% catalyst at 40 °C. Yield 77% (55 mg, Ͼ99% ee).
25
Reaction time: 16 h. Pale yellow oil. [α]
D
= +134.0 (c = 0.804,
H), 2.23–2.39 (m, 1 H) ppm. 13C NMR (CDCl
, 100 MHz): δ =
08.4, 171.4, 158.5, 134.2, 129.9, 128.9, 127.3, 113.7, 55.3, 48.5,
4.8, 40.6, 37.5, 36.0, 25.2 ppm. HRMS (EI): calcd. for C17
3
acetone, Ͼ99% ee). IR (neat): ν˜ = 2910, 1708, 1628, 1398,
–1
1
1
130 cm . H NMR (CDCl
3
, 300 MHz): δ = 5.40 (t, J = 7.2 Hz,
H21NO
3
1
H), 3.69 (t, J = 5.4 Hz, 1 H), 3.02 (s, 3 H), 2.96 (s, 3 H), 2.74
+
[M–CO
2
NMe
2
]
215.1072; found: 215.1028. CHIRALCEL OJ,
(ddd, J = 15.3, 5.7 and 1.5 Hz, 1 H), 2.44–2.59 (m, 3 H), 2.25–2.40
hexane/iPrOH, 70:30, 1.2 mL/min, retention times: 18.5 min (major
isomer) and 22.1 min (minor isomer).
(
m, 2 H), 2.02–2.18 (m, 2 H), 1.24–1.43 (m, 4 H), 0.91 (t, J =
.2 Hz, 3 H) ppm. C NMR (CDCl , 75 MHz): δ = 209.1, 171.7,
3
13
7
1
1
32.6, 128.2, 48.0, 45.0, 40.8, 37.3, 35.8, 31.9, 27.5, 24.4, 22.3,
Amide (+)-6jf: (Table 4, Entry 3) Procedure 2 was followed using
1
yellow solid; m.p. 122–124 °C. [α]
9
+
2
3.9 ppm. HRMS (EI): calcd. for C14H23NO [M] 237.1729;
j and 2f. Reaction time: 36 h. Yield 51% (50 mg, 94% ee). Pale
25
found: 237.1686. Chiraldex B-DM column, 130 °C isothermal, re-
tention times: 65.8 min (major isomer) and 66.1 min (minor iso-
mer).
D
= +111.3 (c = 0.464, acetone,
4% ee). IR (neat): ν˜ = 2920, 1705, 1628, 1400, 1320, 1115, 1070,
–1 1
8
3
30 cm . H NMR (CDCl , 300 MHz): δ = 7.62 (d, J = 8.1 Hz, 2
H), 7.35 (d, J = 8.1 Hz, 2 H), 6.56 (s, 1 H), 3.94 (t, J = 5.4 Hz, 1 Amide (+)-6nf: (Table 4, Entry 8) Procedure 2 was followed using
H), 3.13 (s, 3 H), 3.02 (s, 3 H), 2.68–2.92 (m, 3 H), 2.44–2.62 (m, 1n, 2f and 20% catalyst. Reaction time: 25 h. Yield 25% (19 mg,
H), 2.26–2.41 (m, 1 H) ppm. 13C NMR (CDCl
07.6, 170.9, 139.99, 139.98, 137.9, 128.9, 126.3, 125.17 (q), 125.15,
, 100 MHz): δ = Ͼ99% ee). Colorless oil. [α]D = +112.7 (c = 0.262, acetone, Ͼ99%
25
2
2
4
3
ee). IR (neat): ν˜ = 2890, 1702, 1600, 1390, 1240, 1108, 830,
470 cm . H NMR (CDCl , 300 MHz): δ = 5.49 (s, 1 H), 3.75 (t,
3
[M] 325.1290; found: 325.1284. CHIRALCEL OD- J = 5.4 Hz, 1 H), 3.02 (s, 3 H), 2.98 (s, 3 H), 2.27–2.84 (m, 6 H),
–
1 1
8.2, 44.6, 40.3, 37.4, 36.0, 25.3 ppm. HRMS (EI): calcd. for
+
C
17
H
18
F
3
NO
2
1
3
H, hexane/iPrOH, 70:30, 0.8 mL/min, retention times: 10.0 min
0.16 (s, 9 H) ppm. C NMR (CDCl , 75 MHz): δ = 208.1, 171.2,
3
(
major isomer) and 12.6 min (minor isomer).
150.6, 127.9, 51.0, 45.0, 41.3, 37.5, 36.0, 30.1, 0.14 ppm. HRMS
+
(
EI): calcd. for C13
H23NO
2
Si [M] 253.1498; found: 253.1484. Chi-
Amide (S)-(+)-6kf: (Table 4, Entry 4) Procedure 2 was followed
raldex G-TA column, 130 °C isothermal, retention times: 77.5 min
(major isomer) and 78.1 min (minor isomer).
using 1k and 2f. Reaction time: 16 h. Yield 68% (59 mg, Ͼ99% ee).
Yellow solid; m.p. 159–161 °C. [α]2
5
D
= +121.4 (c = 0.702, acetone,
Ͼ99% ee). IR (neat): ν˜ = 3360, 2910, 1698, 1620, 1478, 1390, 1090, Amide (+)-6of: (Table 5, Entry 1) Procedure 2 was followed using
–
1 1
8
7
3
2
1
3
20 cm . H NMR (CDCl
.17 (d, J = 8.7 Hz, 2 H), 6.49 (s, 1 H), 3.91 (t, J = 5.4 Hz, 1 H), 97% ee). Orange solid; m.p. 56–58 °C. [α]
.12 (s, 3 H), 3.00 (s, 3 H), 2.66–2.90 (m, 3 H), 2.42–2.61 (m, 2 H), acetone, 97% ee). IR (neat): ν˜ = 2930, 1680, 1630, 1600, 1445,
3
, 300 MHz): δ = 7.30–7.40 (m, 2 H), 1o, 2f, and 5% catalyst. Reaction time: 20 h. Yield 80% (73 mg,
2
5
D
= +201.0 (c = 1.534,
.24–2.39 (m, 1 H) ppm. 13C NMR (CDCl
71.2, 136.6, 134.9, 133.0, 130.1, 128.5, 126.6, 48.3, 44.7, 40.4, 37.4,
6.0, 25.2 ppm. HRMS (EI): calcd. for C16
, 75 MHz): δ = 208.1, 1400, 1282, 1240, 1142, 772, 758, 730, 700 cm . H NMR (CDCl
300 MHz): δ = 8.02–8.12 (m, 1 H), 7.28–7.37 (m, 1 H), 7.07–7.26
(m, 7 H), 6.67 (s, 1 H), 4.04 (dd, J = 6.9 and 4.5 Hz, 1 H), 3.25
–1 1
3
3
,
+
2
H18ClNO [M]
3592 www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3582–3595

Rh-Catalyzed [4+2] Carbocyclization of Alkynals
FULL PAPER
(
dd, J = 17.4 and 6.9 Hz, 1 H), 3.20 (s, 3 H), 2.94 (s, 3 H), 2.87
H), 3.07 (s, 3 H), 2.89 (s, 3 H), 2.75 (dd, J = 17.4, 4.5 Hz, 1 H),
2.38 (q, J = 7.2 Hz, 2 H), 1.40–1.52 (m, 2 H), 1.34 (sext, J = 7.2 Hz,
2 H), 0.89 (t, J = 7.2 Hz, 3 H) ppm. C NMR (CDCl , 100 MHz):
3
13
3
(dd, J = 17.4 and 4.5 Hz, 1 H) ppm. C NMR (CDCl , 75 MHz):
1
3
δ = 196.2, 170.2, 137.5, 136.1, 134.1, 133.2, 132.2, 129.1, 128.9,
1
28.7, 128.5, 128.3, 127.5, 126.7, 48.7, 43.1, 37.6, 36.0 ppm. HRMS δ = 196.2, 170.5, 137.8, 132.7, 132.4, 132.1, 131.1, 127.9, 126.6,
+
(EI): calcd. for C20
H19NO
2
[M–CONMe
2
]
233.0967; found:
48.6, 43.6, 37.4, 35.8, 32.2, 28.8, 22.3, 13.9 ppm. HRMS (EI): calcd.
+
2
33.0984. Chiralpak AD, hexane/iPrOH, 90:10, 1.0 mL/min, reten-
2
for C18H23NO [M] 285.1729; found: 285.1708. Chiralpak AD,
tion times: 18.3 min (major isomer) and 22.7 min (minor isomer).
hexane/iPrOH, 95:5, 1.0 mL/min, retention times: 18.1 min (major
isomer) and 23.8 min (minor isomer).
Amide (+)-6og: (Table 5, Entry 2) Procedure 2 was followed using
1
9
o, 2g, and 5% catalyst. Reaction time: 20 h. Yield 80% (79 mg,
Amide (+)-6tf: (Table 5, Entry 6) Procedure 2 was followed using
1t, 2f, and 5% catalyst. Reaction time: 20 h. Yield 81% (74 mg,
7% ee). Orange solid; m.p. 205–206 °C. [α]2
5
= +199.6 (c = 1.392,
D
2
5
acetone, 97% ee). IR (neat): ν˜ = 2960, 2880, 1678, 1615, 1598, 1430,
1
3
D
97% ee). Yellow solid; m.p. 82–84 °C. [α] = +107.9 (c = 1.922,
–1
1
330, 1278, 1222, 1178, 780, 760, 692 cm . H NMR (CDCl
3
,
acetone, 97% ee). IR (neat): ν˜ = 3400, 2920, 1675, 1625, 1598, 1445,
–
1 1
00 MHz): δ = 8.03–8.10 (m, 1 H), 7.27–7.36 (m, 1 H), 7.10–7.25 1390, 1280, 1242, 1140, 770 cm . H NMR (CDCl
3
, 400 MHz): δ
(
m, 7 H), 6.68 (s, 1 H), 3.89 (t, J = 5.4 Hz, 1 H), 3.70 (dt, J = 9.9, = 8.03–8.13 (m, 1 H), 7.53 (dt, J = 5.7 and 1.2 Hz, 1 H), 7.31–7.45
.9 Hz, 1 H), 3.58 (dt, J = 9.9, 6.9 Hz, 1 H), 3.50 (dt, J = 12.0, (m, 2 H), 5.65 (t, J = 5.4 Hz, 1 H), 3.93 (m, 1 H), 3.55 (t, J =
.9 Hz, 1 H), 3.37 (dt, J = 12.0, 6.9 Hz, 1 H), 3.27 (dd, J = 17.4, 4.8 Hz, 2 H), 3.12 (dd, J = 12.9, 4.8 Hz, 1 H), 3.07 (s, 3 H), 2.90
.3 Hz, 1 H), 2.87 (dd, J = 17.4, 4.2 Hz, 1 H), 2.03 (quint, J = (s, 3 H), 2.75 (dd, J = 12.9, 3.9 Hz, 1 H), 2.56 (dq, J = 5.7 and
.9 Hz, 2 H), 1.86 (quint, J = 6.9 Hz, 2 H) ppm. 13C NMR (CDCl
6
6
6
6
7
1
2
2
1
13
3
,
3
2.1 Hz, 2 H), 1.84–2.02 (m, 2 H) ppm. C NMR (CDCl ,
5 MHz): δ = 196.2, 168.7, 137.5, 136.2, 133.7, 133.2, 132.1, 129.0,
100 MHz): δ = 196.0, 170.3, 137.5, 133.7, 132.8, 132.5, 128.5, 128.3,
28.8, 128.6, 128.5, 128.3, 127.5, 126.7, 50.4, 46.8, 46.2, 42.7, 26.3,
127.8, 126.7, 48.5, 44.3, 43.5, 37.4, 35.9, 32.7, 26.5 ppm. HRMS
+
+
4.1 ppm. HRMS (EI): calcd. for C22
H21NO
2
[M–CON(CH
2
)
4
]
(EI): calcd. for C17
H20ClNO
2
[M – Cl] 270.1494; found: 270.1499.
33.0966; found: 233.0928. Chiralpak AD, hexane/iPrOH, 90:10,
Chiralpak AD, hexane/iPrOH, 85:15, 1.0 mL/min, retention times:
.0 mL/min, retention times: 21.5 min (major isomer) and 25.5 min
11.4 min (major isomer) and 14.5 min (minor isomer).
(
minor isomer).
Amide (+)-6pf: (Table 5, Entry 7) Procedure 2 was followed using
1p, 2f, and 5% catalyst. Reaction time: 42 h. Yield 26% (24 mg,
Amide (+)-6qf: (Table 5, Entry 3) Procedure 2 was followed using
1
9
ee). IR (neat): ν˜ = 2900, 1680, 1630, 1398, 1280, 1238, 1140, 1055,
7
and 1.2 Hz, 1 H), 7.38–7.45 (m, 1 H), 7.33 (dt, J = 7.5, 1.2 Hz, 1
H), 7.12–7.24 (m, 2 H), 6.91–7.06 (m, 3 H), 6.70 (s, 1 H), 4.10 (dd,
J = 6.9, 4.5 Hz, 1 H), 3.28 (dd, J = 17.4, 6.9 Hz, 1 H), 3.25 (s, 3
H), 2.96 (s, 3 H), 2.89 (dd, J = 17.4, 4.5 Hz, 1 H) ppm. 1 C NMR
2
5
q, 2f, and 5% catalyst. Reaction time: 20 h. Yield 94% (96 mg,
D
Ͼ99% ee). Pale yellow solid; m.p. 151–152 °C. [α] = +150.2 (c =
0% ee). Pale yellow oil. [α]2
5
= +185.5 (c = 1.040, acetone, 90%
1.115, acetone, Ͼ99% ee). IR (neat): ν˜ = 2880, 1672, 1602, 1580,
D
–
1 1
3
1478, 1230, 1175, 830, 750, 468 cm . H NMR (CDCl , 300 MHz):
–1 1
58, 690 cm . H NMR (CDCl
3
, 300 MHz): δ = 8.07 (dd, J = 7.5
δ = 8.00–8.07 (m, 1 H), 7.46–7.55 (m, 3 H), 5.78 (d, J = 0.9 Hz, 1
H), 3.97–4.04 (m, 1 H), 3.15 (dd, J = 17.1, 6.3 Hz, 1 H), 3.07 (s, 3
H), 2.89 (s, 3 H), 2.78 (dd, J = 17.1, 4.5 Hz, 1 H), 0.08 (s, 9 H) ppm.
1
3
C NMR (CDCl
3
, 75 MHz): δ = 196.1, 170.2, 149.7, 139.8, 132.6,
3
132.4, 130.8, 129.1, 127.5, 126.3, 51.9, 43.4, 37.5, 35.8, 0.32 ppm.
+
3 2 3
(CDCl , 100 MHz): δ = 195.9, 169.9, 136.8, 135.4, 135.0, 133.7, HRMS (EI): calcd. for C17H23NO Si [M – CH ] 286.1263; found:
1
4
33.0, 132.2, 131.0, 129.3, 128.9, 128.8, 128.6, 126.7, 126.5, 125.9,
8.5, 42.9, 37.6, 36.1 ppm. HRMS (EI): calcd. for C20 18ClNO
286.1221. CHIRALCEL OD-H, hexane/iPrOH, 85:15, 1.0 mL/
min, retention times: 9.8 min (major isomer) and 14.5 min (minor
isomer).
H
2
+
[M] 339.1026; found: 339.0956. Chiralpak AD, hexane/iPrOH,
9
2
0:10, 1.0 mL/min, retention times: 21.1 min (major isomer) and
6.8 min (minor isomer).
Ester (+)-6hd: (Scheme 8) Procedure 2 was followed using 1h and
2
d (10 equiv.). Reaction time: 25 h. Yield 32% (28 mg, 97% ee).
2
5
Amide (+)-6rf: (Table 5, Entry 4) Procedure 2 was followed using
1
9
D
Pale yellow solid; m.p. 82–83 °C. [α] = +85.5 (c = 1.465, acetone,
97% ee). IR (neat): ν˜ = 2920, 1704, 1138, 695, 470 cm . H NMR
(CDCl , 300 MHz): δ = 7.31–7.42 (m, 2 H), 7.20–7.31 (m, 3 H),
–
1 1
r, 2f, and 5% catalyst. Reaction time: 44 h. Yield 56% (52 mg,
9% ee). Orange solid; m.p. 129–131 °C. [α]2
5
= +230.9 (c = 1.189,
D
3
acetone, 99% ee). IR (neat): ν˜ = 3300, 2910, 1680, 1630, 1445, 1395,
6.66 (s, 1 H), 3.57–3.65 (m, 1 H), 2.96 (dt, J = 15.0, 6.0 Hz, 1 H),
–1 1
1
8
7
3
3
2
1
1
2
283, 1240, 1142, 778 cm . H NMR (CDCl
.08 (m, 1 H), 7.46–7.54 (m, 1 H), 7.42 (dt, J = 7.2, 1.5 Hz, 1 H), 1 H), 2.27–2.41 (m, 1 H), 1.47 (s, 9 H) ppm. C NMR (CDCl
.34 (dt, J = 7.2, 1.5 Hz, 1 H), 6.12 (s, 1 H), 5.64–5.75 (m, 1 H), 75 MHz): δ = 208.7, 171.7, 136.8, 134.5, 128.8, 128.7, 128.3, 127.0,
3
, 300 MHz): δ = 7.98– 2.66–2.84 (m, 2 H), 2.57 (dd, J = 15.0, 6.0 Hz, 1 H), 2.42–2.57 (m,
1
3
3
,
.89 (dd, J = 6.9, 4.5 Hz, 1 H), 3.15 (dd, J = 17.4, 6.9 Hz, 1 H),
.10 (s, 3 H), 2.90 (s, 3 H), 2.76 (dd, J = 17.4, 4.5 Hz, 1 H), 1.84–
81.7, 51.1, 42.7, 39.7, 27.9, 24.9 ppm. HRMS (EI): calcd. for
+
C
18
H
22
O
3
[M–CO
2
tBu]
185.0966; found: 185.0922. CHI-
.12 (m, 4 H), 1.50–1.65 (m, 4 H) ppm. 13C NMR (CDCl
,
RALCEL OD-H, hexane/iPrOH, 90:10, 1.0 mL/min, retention
times: 7.4 min (major isomer) and 17.9 min (minor isomer).
3
00 MHz): δ = 196.5, 170.4, 138.7, 134.0, 132.6, 132.0, 131.9, 131.1,
30.1, 128.7, 128.1, 126.2, 48.6, 43.3, 37.5, 35.9, 28.4, 25.7, 22.7,
Aldehyde (S)-(+)-1a: (Scheme 9) Under Ar, CH
tion of (R,R)-11 (39.5 mg, 0.060 mmol) was added to a CH
1.0 mL) solution of [Rh(cod) ]BF (24.4 mg, 0.060 mmol) and the
mixture was stirred at room temperature for 5 min. H was intro-
2
Cl
2
(1.0 mL) solu-
+
2.0 ppm. HRMS (EI): calcd. for C20
H23NO
2
[M] 309.1729;
2
Cl
2
found: 309.1702. Chiralpak AD, hexane/iPrOH, 95:5, 1.0 mL/min,
retention times: 23.3 min (major isomer) and 29.0 min (minor iso-
mer).
(
2
4
2
duced to the resulting solution in a Schlenk tube. After stirring at
room temperature for 0.5 h, the resulting solution was concentrated
Amide (+)-6sf: (Table 5, Entry 5) Procedure 2 was followed using
1
s, 2f, and 5% catalyst. Reaction time: 28 h. Yield 56% (48 mg,
2 2
to dryness. A CH Cl solution (1.5 mL) of 3-methylnon-4-ynal (1a,
25
Ͼ99% ee). Yellow solid; m.p. 82–83 °C. [α]
acetone, Ͼ99% ee). IR (neat): ν˜ = 2900, 1678, 1630, 1390, 1280,
D
= +151.0 (c = 1.038,
91.3 mg, 0.600 mmol) and N,N-dimethylacrylamide (2f, 59.5 mg,
0.600 mmol) was added to the residue. The mixture was stirred at
80 °C for 11 h. The resulting solution was concentrated [NMR
yield of (S)-(+)-1a is 46% determined by dimethyl terephthalate as
an internal standard] and purified by silica gel column chromatog-
–1 1
3
1140, 770 cm . H NMR (CDCl , 300 MHz): δ = 8.02–8.14 (m, 1
H), 7.45–7.56 (m, 1 H), 7.32–7.42 (m, 2 H), 5.69 (t, J = 7.2 Hz, 1
H), 3.91 (dd, J = 6.3, 4.5 Hz, 1 H), 3.13 (dd, J = 17.4, 6.3 Hz, 1
Eur. J. Org. Chem. 2006, 3582–3595
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3593

K. Tanaka, Y. Hagiwara, M. Hirano
FULL PAPER
raphy (pentane/Et
.267 mmol, 44% isolated yield, 93% ee) as a colorless oil. [α]
16.7 (c = 1.825, CHCl , 93% ee). Chiraldex B-DM column, 85 °C
isothermal, retention times: 26.7 min (minor isomer) and 27.0 min
major isomer).
2
O, 50:1), which furnished (S)-(+)-1a[37] (40.6 mg,
2 H), 2.67–2.71 (m, 2 H), 2.61–2.66 (m, 2 H) ppm. 13C NMR
2
5
0
+
D
=
(CDCl
3
, 100 MHz): δ = 207.9, 171.3, 131.5, 128.1, 127.6, 123.6,
3
88.7, 80.8, 41.9, 37.3, 37.1, 35.5, 27.3, 14.0 ppm. HRMS (EI): calcd.
+
for C16
X-ray Crystallographic Studies of Amide 6kf: A crystal suitable for
X-ray analysis was obtained by recrystallization from CH Cl /n-
2
H19NO [M] 257.1416; found: 257.1377.
(
Amide 3of: (Scheme 10) Procedure 1 was followed using 1o, 2f
1.0 equiv.), and 5% [Rh(cod) ]BF /dppb at 80 °C. Reaction time:
2 h. Yield 7% (6.4 mg). Pale yellow oil. IR (neat): ν˜ = 2920, 1658,
2
2
(
2
4
pentane. CCDC-277585 contains the supplementary crystallo-
graphic data for compound 4g. These data can be obtained free
4
1
–
1
630, 1582, 1480, 1440, 1390, 1238, 1130, 1048, 730, 698, 472 cm . of charge from The Cambridge Crystallographic Data Centre via
1
H NMR (CDCl
3
, 300 MHz): δ = 8.00–8.06 (m, 1 H), 7.17–7.35 www.ccdc.cam.ac.uk/data_request/cif.
(
m, 8 H), 6.77 (d, J = 1.8 Hz, 1 H), 4.06 (dd, J = 12.3, 4.5 Hz, 1
Supporting Information (see also the footnote on the first page of
this article): H NMR spectra of 3, 4, 6, 7, and 8, and NOESY
spectra of 6cd, 6fd, and 6gd.
H), 3.39 (dt, J = 12.9, 1.8 Hz, 1 H), 3.18 (s, 3 H), 3.08 (s, 3 H), 2.78
(
=
1
1
1
3
dd, J = 12.9 and 4.5 Hz, 1 H) ppm. C NMR (CDCl
194.2, 169.3, 140.3, 136.9, 134.0, 132.7, 132.0, 129.0, 128.5, 128.4,
28.3, 128.1, 127.7, 127.4, 53.1, 39.1, 37.8, 35.9 ppm. HRMS (EI):
3
, 75 MHz): δ
+
calcd. for C20
Amide 3pf: (Scheme 10) Procedure 1 was followed using 1p, 2f
1.0 equiv.), and 5% [Rh(cod) ]BF /dppb at 80 °C. Reaction time:
2 h. Yield 11% (9.9 mg). Pale yellow solid; m.p. 121–123 °C. IR
neat): ν˜ = 2890, 1658, 1624, 1582, 1478, 1436, 1382, 1235, 1126,
H19NO
2
[M–CONMe
2
]
233.0967; found: 233.0964. Acknowledgments
We thank Solvias AG for the gift of chiral ligands 9, 10, and 11
under their University Ligand Kit program. We also thank Prof.
K. Noguchi (Instrumentation Analysis Center, Tokyo University of
Agriculture and Technology) for his X-ray crystallographic analysis
and Prof. Gregory C. Fu (Massachusetts Institute of Technology)
for his helpful encouragement.
(
4
(
1
8
=
1
1
1
4
2
4
–
1 1
045, 830, 755, 470 cm . H NMR (CDCl
.05 (m, 1 H), 7.48–7.59 (m, 2 H), 7.37–7.46 (m, 1 H), 5.86 (d, J
1.5 Hz, 1 H), 3.97 (dd, J = 12.6, 4.5 Hz, 1 H), 3.47 (dt, J = 12.6,
.5 Hz, 1 H), 3.15 (s, 3 H), 3.06 (s, 3 H), 2.76 (dd, J = 12.6, 4.8 Hz,
H), 0.13 (s, 9 H) ppm. 13C NMR (CDCl
, 75 MHz): δ = 194.3,
69.3, 150.2, 142.1, 133.1, 131.5, 130.1, 128.8, 127.54, 127.48, 53.5,
2.4, 37.8, 35.8, 0.4 ppm. HRMS (EI): calcd. for C17 Si [M–
3
, 300 MHz): δ = 7.97–
3
[1] For reviews of transition-metal-catalyzed carbocyclizations,
see: a) I. Ojima, M. Tzamarioudaki, Z. Li, R. J. Donovan,
Chem. Rev. 1996, 96, 635–662; b) M. Lautens, W. Klute, W.
Tam, Chem. Rev. 1996, 96, 49–92; c) P. A. Wender, J. A. Love,
in: Advances in Cycloaddition, JAI Press: Greenwich, 1999, vol.
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Organic Reactions (Ed.: P. A. Evans), Wiley-VCH, 2005, p. 241.
[2] For transition-metal-catalyzed intramolecular [4+2] carbocycli-
zations. For Rh, see: a) D. Motoda, H. Kinoshita, H. Shino-
kubo, K. Oshima, Angew. Chem. 2004, 116, 1896–1898; Angew.
Chem. Int. Ed. 2004, 43, 1860–1862; b) B. Wang, P. Cao, X.
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P. A. Wender, T. E. Jenkins, S. Suzuki, J. Am. Chem. Soc. 1995,
H23NO
2
+
CONMe
2
] 229.1049; found: 229.1026.
Amide (+)-6uf: (Scheme 11) Procedure 2 was followed using 1u and
2
oil. [α]
f. Reaction time: 43 h. Yield 41% (38 mg, 97% ee). Pale yellow
25
D
= +214.3 (c = 1.115, acetone, 97% ee). IR (neat): ν˜ =
–
1 1
2
905, 1680, 1620, 1572, 1480, 1390, 1108, 722, 690, 470 cm . H
NMR (CDCl , 300 MHz): δ = 8.46 (dd, J = 4.5 and 2.1 Hz, 1 H),
.34 (dd, J = 8.1, 2.1 Hz, 1 H), 7.30 (dd, J = 8.1, 4.5 Hz, 1 H),
.10–7.25 (m, 5 H), 6.86 (s, 1 H), 4.18 (t, J = 4.5 Hz, 1 H), 3.26
3
8
7
(dd, J = 17.4, 4.5 Hz, 1 H), 3.24 (s, 3 H), 2.89 (dd, J = 17.4, 4.5 Hz,
1
1
1
H), 2.88 (s, 3 H) ppm. 13C NMR (CDCl
3
, 75 MHz): δ = 195.3,
1
17, 1843–1844; e) D. J. R. O’Mahony, D. B. Belanger, T. Liv-
70.1, 155.1, 152.6, 135.6, 134.2, 133.0, 132.7, 129.3, 128.9, 127.83,
inghouse, Org. Biomol. Chem. 2003, 1, 2038–2040; f) R. S. Jolly,
G. Luedtke, D. Sheehan, T. Livinghouse, J. Am. Chem. Soc.
1990, 112, 4965–4966; g) M. Murakami, M. Ubukata, K. It-
ami, Y. Ito, Angew. Chem. 1998, 110, 2362–2364; Angew. Chem.
Int. Ed. 1998, 37, 2248–2250; h) B. Witulski, J. Lumtscher, U.
Bergsträßer, Synlett 2003, 708–710. For Ni, see; i) P. A. Wender,
T. E. Smith, Tetrahedron 1998, 54, 1255–1275; j) P. A. Wender,
T. E. Smith, J. Org. Chem. 1996, 61, 824–825; k) P. A. Wender,
T. E. Smith, J. Org. Chem. 1995, 60, 2962–2963; l) P. A.
Wender, T. E. Jenkins, J. Am. Chem. Soc. 1989, 111, 6432–6434.
For Pd, see; m) J. R. Dunetz, R. L. Danheiser, J. Am. Chem.
Soc. 2005, 127, 5776–5777; n) L. J. van Boxtel, S. Körbe, M.
Noltemeyer, A. de Meijere, Eur. J. Org. Chem. 2001, 2283–
27.77, 124.0, 48.4, 43.2, 37.8, 36.1 ppm. HRMS (EI): calcd. for
+
C
19
H
18
N
2
O
2
[M–CONMe
2
]
234.0919; found: 234.0922. Chi-
ralpak AD, hexane/iPrOH, 90:10, 1.0 mL/min, retention times:
1.4 min (major isomer) and 25.8 min (minor isomer).
2
Ester 3ca-d: (Scheme 13) Procedure 1 was followed using 1c-d and
2
1
a. Reaction time: 45 h. Yield 60% (71 mg). Colorless oil. H NMR
(
(
(
CDCl , 300 MHz): δ = 12.18 (s, 1 H), 4.08–4.25 (m, 2 H), 3.19
dd, J = 18.3, 2.7 Hz, 1 H), 2.86 (d, J = 18.0, Hz, 1 H), 2.76–2.96
m, 1 H), 2.45–2.62 (m, 1 H), 2.19 (dd, J = 17.7, 1.2 Hz, 1 H),
3
1
0
6
.58–1.72 (m, 2 H), 13.5–1.48 (m, 2 H), 1.12 (d, J = 6.9 Hz, 3 H),
2
.96 (t, J = 7.5 Hz, 3 H), 0.11 (s, 9 H) ppm. H NMR (CDCl
1 MHz): δ = 5.33 (s) ppm.
3
,
2
292; o) M. Murakami, K. Itami, Y. Ito, J. Am. Chem. Soc.
1997, 119, 7163–7164; p) K. Kumar, R. Jolly, Tetrahedron Lett.
Ester 6ca-d: (Scheme 13) Yield 12% (14 mg). Colorless oil. 1
NMR (CDCl , 300 MHz): δ = 4.03–4.27 (m, 2 H), 3.69 (dd, J =
3
1998, 39, 3047–3048; q) T. Mandai, S. Suzuki, A. Ikawa, T.
Murakami, M. Kawada, J. Tsuji, Tetrahedron Lett. 1991, 32,
H
7
687–7688. For Co, see; r) G. Hilt, S. Lüers, K. I. Smolko, Org.
12.0, 5.4 Hz, 1 H), 3.11–3.24 (m, 1 H), 2.80 (dd, J = 14.7, 12.0 Hz,
1 H), 2.64 (dd, J = 14.4, 6.3 Hz, 1 H), 2.53 (ddd, J = 14.7, 5.4,
2.1 Hz, 1 H), 2.27–2.37 (m, 1 H), 1.54–1.71 (m, 2 H), 1.39 (sext, J
Lett. 2005, 7, 251–253; s) G. Hilt, S. Lüers, K. Harms, J. Org.
Chem. 2004, 69, 624–630; t) G. Hilt, K. I. Smolko, Angew.
Chem. 2003, 115, 2901–2903; Angew. Chem. Int. Ed. 2003, 42,
2795–2797; u) G. Hilt, L. Steffen, Synthesis 2002, 686–692; v)
G. Hilt, S. Lüers, Synthesis 2003, 1784–1786; w) G. Hilt, K. I.
Smolko, B. V. Lotsch, Synlett 2002, 1081–1084; x) G. Hilt, T. J.
Korn, Tetrahedron Lett. 2001, 42, 2783–2785; y) G. Hilt, F.
du Mesnil, Tetrahedron Lett. 2000, 41, 6757–6761. For Au, see;
z) C. Nietro-Oberhuber, S. López, A. M. Echavarren, J. Am.
Chem. Soc. 2005, 127, 6178–6179.
=
7.5 Hz, 2 H), 1.15 (d, J = 7.2 Hz, 3 H), 0.95 (t, J = 7.2 Hz, 3 H),
2
0.15 (s, 9 H) ppm. H NMR (CDCl
3
, 61 MHz): δ = 5. 34 (s) ppm.
Amide 8hf: (Scheme 14) Yield 40% (41 mg). Colorless oil. IR
–
1 1
(
neat): ν˜ = 3400, 2900, 1705, 1630, 1395, 1095, 758, 695 cm . H
NMR (CDCl , 400 MHz): δ = 7.33–7.39 (m, 2 H), 7.24–7.28 (m, 3
H), 3.03 (s, 3 H), 2.93 (s, 3 H), 2.83–2.88 (m, 2 H), 2.75–2.81 (m,
3
3594
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3582–3595

Rh-Catalyzed [4+2] Carbocyclization of Alkynals
FULL PAPER
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[
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of dienal.
13] For these cycloadditions in Table 2, the regioisomers have been
easily separated by silica gel chromatography except Entry 6.
14] Cyclopentenone 5b was isolated in 29% yield as a major by-
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Received: May 2, 2006
[
[
[
[
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2
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I+
16] In the case of the reactions of 1h–u using Rh /(R,R)-11, no
vinyl proton other than those of the desired cyclohexanones
6
was observed by 1H NMR analyses of the crude reaction
mixtures.
Published Online: June 7, 2006
Eur. J. Org. Chem. 2006, 3582–3595
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3595