Studies on the diastereoselective intramolecular Pauson-Khand reaction on regioisomeric chiral perhydrobenzoxazines derived from (-)-8-aminomenthol

Article abstract of DOI:10.1002/ejoc.201101462

Chiral perhydrobenzoxazines derived from (-)-8-aminomenthol and containing a 1,6-enyne moiety participate in intramolecular diastereoselective Pauson-Khand reactions with diastereoselection that depends on the nature of the starting compounds. 3-Propargyl-2-vinyl-substituted perhydrobenzoxazines yielded the cyclization products with low diastereoselectivity except for compounds where the double bond was 1,2-disubstituted. Regioisomeric perhydrobenzoxazines with the acetylenic bond at C-2 and an allyl substituent at the nitrogen atom gave much better stereochemical discrimination. Chiral perhydrobenzoxazines derived from (-)-8-aminomenthol and containing a 1,6-enyne moiety participate in intramolecular diastereoselective Pauson-Khand reactions leading to cyclization products with moderate to good diastereoselectivity. The diastereoselection depends on both the substitution pattern of the double bond and the regiochemistry of the starting perhydrobenzoxazines Copyright

Full text of DOI:10.1002/ejoc.201101462

FULL PAPER
DOI: 10.1002/ejoc.201101462
Studies on the Diastereoselective Intramolecular Pauson–Khand Reaction on
Regioisomeric Chiral Perhydrobenzoxazines Derived from (–)-8-Aminomenthol
Alicia Maestro,[a] Rafael Pedrosa,*[a] Alfonso Pérez-Encabo,[a] and Juan J. Pérez-Rueda[a]
Keywords: Asymmetric synthesis / Cyclization / Enynes / Stereoselective synthesis
Chiral perhydrobenzoxazines derived from (–)-8-aminomen-
thol and containing a 1,6-enyne moiety participate in intra-
molecular diastereoselective Pauson–Khand reactions with
diastereoselection that depends on the nature of the starting
selectivity except for compounds where the double bond was
1,2-disubstituted. Regioisomeric perhydrobenzoxazines with
the acetylenic bond at C-2 and an allyl substituent at the
nitrogen atom gave much better stereochemical discrimi-
compounds. 3-Propargyl-2-vinyl-substituted perhydrobenz- nation.
oxazines yielded the cyclization products with low diastereo-
clizations,[8] and now we reasoned that this structure could
Introduction
act as a chiral template in diastereoselective intramolecular
PKRs. The attachment of a vinyl substituent at C-2 and a
propargyl group at the nitrogen atom of the perhydrobenz-
oxazine nucleus allows the construction of chiral 1,6-en-
ynes, which could lead to pirrolyl cyclopentenone deriva-
tives diastereoselectively. To this end, we have prepared a
series of 1,6-enynes tethered by the nitrogen atom to form
part of a chiral structure derived from (–)-8-aminomenthol
and then studied the diastereoselective PKR.
Cyclization of an alkene, an alkyne, and carbon mono-
xide in the presence of dicobalt octacarbonyl, named the
Pauson–Khand reaction (PKR), is one of the most power-
ful and flexible methods available to construct polysubsti-
tuted cyclopentenone derivatives.[1] Other metal carbonyls
have been also used for similar carbocyclizations leading to
cyclopentenones.[2] The intermolecular version of the PKR
presents some problems associated with the poor reactivity
of common alkenes and, in some cases, the low regioselec-
tivity of the process when a combination of unsymmetri-
cally substituted alkenes and alkynes are used.
Results and Discussion
More interesting is the intramolecular version of the
PKR, because it is regioselective, thermodynamically more
favored, and allows the synthesis of polycyclic cyclo-
pentenone derivatives. The development of the stereoselec-
tive intramolecular PKR is especially important. One of the
most studied methods uses chiral auxiliaries attached to
both the alkene or alkyne components of the reaction,[3] but
it has been demonstrated that the presence of substituents
at the tether chain, making the C-3 and C-5 atoms stereo-
genic centers, also promotes diastereoselective PKRs. Both
approaches have been widely employed in the synthesis of
natural products.[4]
Enantiopure 2-vinyl-3-propargyl-substituted perhydro-
benzoxazines 2a–i were prepared, in two steps, from (–)-
8-aminomenthol by condensation with the corresponding
aldehyde followed by alkylation with propargyl bromides or
by reaction with propargyl bromides and condensation with
acrolein or methacrolein for 2a and 2f (Scheme 1).
Perhydrobenzoxazines derived from (–)-8-aminomenthol
have been shown to be excellent chiral templates in a series
of intramolecular reactions such as radical cyclizations,[5]
Diels–Alder[6] and dipolar cycloadditions,[7] or anionic cy-
[a] Instituto CINQUIMA (Centro de Innovación en Química y
Materiales Avanzados) and Departamento de Química
Orgánica, Facultad de Ciencias, Universidad de Valladolid
Dr. Mergelina s/n, 47011 Valladolid. Spain
Scheme 1. Reagents and conditions: (i) propargyl bromide, K2CO3,
MeCN, r.t.; (ii) aldehyde, DCM, r.t.; (iii) acrolein or methacrolein,
sealed tube, 120 °C; (iv) propargyl bromides, K2CO3, MeCN, re-
flux.
Fax: +34-983-186324
E-mail: pedrosa@qo.uva.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101462.
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Eur. J. Org. Chem. 2012, 1202–1208

Diastereoselective Intramolecular Pauson–Khand Reactions
Initially, parent compound 2a was selected to study the
The influence of the substitution pattern at both the ole-
reaction, and it was subjected to cyclization with dicobalt finic and acetylenic components in the diastereoselection
octacarbonyl under different conditions (Scheme 2 and was studied in compounds 2b–i by using the described stoi-
Table 1).
chiometric and catalytic reaction conditions, and the results
are summarized in Table 2. The reaction of perhydrobenz-
oxazines 2b–d with a substituent at the outer position of the
vinyl group led to equimolar mixtures of diastereoisomers
independent of the size of the substituents (Table 2, En-
tries 1–6). Only a very low diastereoselection was observed
for monosubstituted vinyl derivatives when an additional
bulky group (TMS) was attached to the acetylenic bond
(i.e., 2e; Table 2, Entries 6 & 7).
Scheme 2. Pauson–Khand reaction of 2-vinyl-3-propargylperhy-
drobenzoxazines.
Table 2. Stoichiometric and catalytic Pauson–Khand reactions of
perhydrobenzoxazines 2b–i.
Table 1. Pauson–Khand reaction for 2a under different conditions.
Entry Compd.
R1/R2/R3
Cond.[a]
Yield[b]
[%]
dr
(3/epi-3)
Entry
Solvent
Additive
T
[°C]
Time
[h]
Yield[a]
[%]
dr
(3a/epi-3a)
1
2
3
4
5
6
7
8
2b
2b
2c
2c
2d
2d
2e
2e
2f
H/Me/H
H/Me/H
H/Ph/H
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
74
85
68
50:50
50:50
50:50
50:50
50:50
50:50
60:40
55:45
62:38
55:45
75:25
67:33
90:10
80:20
90:10
80:20
1
2
3
4
5
6
7
toluene
DCM
–
110
25
2
24
24
4
10
9
28
45
50
84
60
20
85
40:60
48:52
47:53
48:52
50:50
50:50
50:50
NMO[b]
H/Ph/H
88
DCM TMANO[b] 25
H/TMS/H
H/TMS/H
H/Ph/TMS
H/Ph/TMS
Me/H/H
Me/H/H
Me/Ph/H
36[c]
55[d]
77
DCM TMANO[c]
DCM TMANO[c]
DME
DME
25
0
60
60
CyNH2
CyNH2
30
40
75
56
73
75
70
68
4
9
[a] Isolated yield. [b] 6 equiv. of amine oxide. [c] 8 equiv. of
TMANO and 8 equiv. of 3 Å MS.
10
11
12
13
14
15
16
2f
2g
2g
2h
2h
2i
Me/Ph/H
–(CH2)4–/H
–(CH2)4–/H
–(CH2)4–/Me
–(CH2)4–/Me
Complete disappearance of the starting compound was
observed when an equimolar mixture of 2a and Co2(CO)8
was heated in refluxing toluene for 2 h, but a lot of decom-
position products were formed and only 28% of cyclization
diastereoisomers 3a and epi-3a was isolated as a 2:3 mixture
(Table 1, Entry 1). The yield was improved to 45–50% when
an equimolar mixture of 2a and Co2(CO)8 in DCM and
NMO or trimethylamine N-oxide (TMANO, 6 equiv.) was
allowed to stand at room temperature for 24 h, but the dia-
2i
40
[a] Conditions A: Stoichiometric reaction. Conditions B: catalytic
reaction. [b] Isolated yield. [c] 30% of desilylation products 3a and
epi-3a were isolated. [d] 17% of desilylation products 3a and epi-3a
were isolated.
Interestingly, the substitution at the endo position of the
stereoisomers were isolated as a near equimolar mixture double bond made the reaction more diastereoselective, es-
(Table 1, Entries 2 & 3). A much better yield, although pecially for the stoichiometric reaction (Table 2, Entry 9 vs.
without an improvement in the diastereoselectivity, was ob- 10). Much better diastereoselection was obtained for the
served for the reaction in which 8 equiv. of TMANO and reaction of 2g with two substituents at the double bond
8 equiv. of 3 Å molecular sieves was used (Table 1, Entry 4). (Table 2, Entries 11 & 12), and the best stereochemical re-
Under the same reaction conditions, 60% of an equimolar sults were obtained in the cyclization of cyclohexene car-
mixture of diastereoisomers was obtained when the reaction boxaldehyde derivatives 2h (Table 2, Entries 13 & 14) and
was carried out at 0 °C, but the reaction time had to be 2i (Table 2, Entries 15 & 16).
increased to 10 h (Table 1, Entry 5).
All the diastereoisomers obtained were separated by
The catalytic version of the reaction was also tested by flash chromatography except compounds 3c and 3d, which
heating a 0.1 m solution of 2a and a catalytic amount of could not be totally purified, and their stereochemistry was
dicobalt octacarbonyl in DME with 20% of cyclohex- established on the basis of the chemical shifts of the proton
ylamine under atmospheric carbon monoxide pressure (bal- at the N,O-acetal carbon atom and the coupling constants
loon of CO) at 60 °C. The reaction took place only if the of that proton with the angular one.[9] NOESY experiments
solution was saturated with CO previous to the addition of allowed the assignation of the stereochemistry for diastereo-
the catalyst, and the yield was highly dependent on the cata- isomers 3g and epi-3g[10] (Figure 1). As expected, the sub-
lyst loading. In the presence of 5 mol-% of Co2(CO)8, a stituents at the double bond retained the stereochemistry in
mixture of diastereoisomers was obtained in only 20% the cyclic system, and both diastereoisomers differed in the
yield, but the yield increased to 85% when using 10 mol-% relative stereochemistry of that substituent with respect to
of the catalyst, although no diastereoselection was observed the hydrogen at the N,O-acetal carbon atom, being cis for
in any case (Table 1, Entries 6 & 7).
3a–i and trans for epi-3a–i.
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A. Maestro, R. Pedrosa, A. Pérez-Encabo, J. J. Pérez-Rueda
FULL PAPER
Table 3, Entries 1–8 vs. 9–11). Third, the same mixtures of
diastereoisomeric PKR products (7/epi-7) were obtained in-
dependent of the stereochemical composition of the starting
perhydrobenzoxazines 5a–d (Table 3, Entry 1 vs. En-
tries 2 & 3, Entry 4 vs. Entries 5 & 6, and Entry 9 vs. En-
tries 10 & 11). Moreover, cyclization diastereoisomers 7 and
epi-7 have the S configuration at the N,O-acetal carbon
atom. This can be explained by accepting that the transfor-
mation of 5a–d into 7a–d and epi-7a–d occurs by a tandem
intramolecular Nicholas reaction and PKR.[12] In fact, the
coordination of Co2(CO)8 to compounds 5a–d leads to co-
balt complexes derived from a propargylic alcohol, which
evolve into cobalt carbonyl stabilized propargylic cations.
Those complexes can be intramolecularly captured to form
stable intermediate 6 with the S configuration at C-2 in a
Nicholas-like transformation.[13] Subsequent PKRs on
complexes 6 give cyclization adducts 7a–d and epi-7a–d
(Scheme 4). Compounds 7 and epi-7 were purified by flash
chromatography, and the stereochemistry of 7c was as-
signed by X-ray diffraction analysis[10] and extended by
analogy to all the diastereoisomers.
Figure 1. NOE contacts for compounds 3g and epi-3g.
We have previously demonstrated that the diastereoselec-
tivity for radical cyclizations in related systems is highly de-
pendent on the regioisomers of the starting perhydrobenz-
oxazine derivative.[11] The low selectivity observed for the
intramolecular PKR of compounds 2 led us to study the
reaction on regioisomeric perhydrobenzoxazines 5 with the
acetylenic bond at C-2 and the olefinic component on the
nitrogen atom.
The synthesis of compounds 5 was achieved, in two steps,
by condensation of (–)-8-aminomenthol with acetylenic al-
dehydes followed by alkylation of 4 with the corresponding
allyl bromides (Scheme 3). The condensation of the alde-
hydes with aminomenthol is totally diastereoselective, lead-
ing to compounds 4a–c as single diastereoisomers with S
configuration at C-2, but surprisingly the alkylation process
led to a mixture (19:1) of epimers of 5a–d after 10 d at room
temperature or an equimolar mixture after 72 h in boiling
acetonitrile. In addition, the mixtures of epimers could not
be separated by flash chromatography because of the
stereochemical lability at C-2 of these compounds.
Scheme 4. Isomerization and Pauson–Khand reaction of perhy-
drobenzoxazines 5a–d.
Table 3. Stoichiometric and catalytic Pauson–Khand reactions of
perhydrobenzoxazines 5a–d.
Entry Compd. Epimers
R1/R2
Cond.[a] Yield[b]
[%]
dr
at C-2
(7/epi-7)[c]
(S/R)
Scheme 3. Reagents and conditions: (i) aldehydes, DCM, r.t.; (ii)
allyl bromide, acetonitrile, r.t., 10 d (19:1dr) or allyl bromides,
acetonitrile, reflux, 72 h. (1:1dr).
1
2
3
4
5
6
7
8
5a
5a
5a
5b
5b
5b
5c
5c
5d
5d
5d
97:3
50:50
50:50
95:5
50:50
50:50
50:50
50:50
92:8
Me/H
Me/H
Me/H
Ph/H
Ph/H
Ph/H
TMS/H
TMS/H
Me/Ph
Me/Ph
Me/Ph
A
A
B
A
A
B
A
B
A
A
B
73
70
30
80
85
40
61
20
61
67
40
75:25
75:25
75:25
80:20
80:20
80:20
80:20
80:20
60:40
60:40
60:40
Compounds 5a–d (as a mixture of diastereoisomers) were
subjected to intramolecular PKRs under both stoichiomet-
ric and catalytic conditions, and the results are summarized
in Scheme 4 and Table 3. Three important facts can be gen-
eralized from these data. First, the chemical yields for the
stoichiometric reactions (conditions A) are much better
than those for the catalytic ones (conditions B) but the dia-
stereoselectivities are not affected by the reaction condi-
tions. Second, the diastereoselection for the intramolecular
PKR of perhydrobenzoxazines 5a–d, with the acetylenic
bond at C-2 and the olefinic bond on the nitrogen atom, is
9
10
11
50:50
50:50
[a] Conditions A: Stoichiometric reaction. Conditions B: Catalytic
reaction. [b] Isolated yield. [c] Determined by 1H NMR spectro-
scopic analysis of the reaction mixture.
The elimination of the aminomenthol appendage in the
better than that for their regioisomers 2a–i, and reactions adducts is very well established[5] and allows the synthesis
of compounds 5a–c, with unsubstituted double bonds, are of enantiopure polycyclic keto pirrolidines; we tested this
more diastereoselective than the same reaction performed transformation with compound 3h. The cyclization product
with a substrate with a substituted double bond (i.e., 5d; was first hydrogenated to saturated compound 8, and its
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Eur. J. Org. Chem. 2012, 1202–1208

Diastereoselective Intramolecular Pauson–Khand Reactions
digital polarimeter by using a 5-mL cell with a 1-dm path length
and a sodium lamp. Infrared spectra were recorded with a Perkin–
Elmer FTIR spectrometer. Melting points were obtained with open
capillary tubes. Flash chromatography was carried out by using
silica gel (230–240 mesh). Chemical yields refer to pure isolated
substances. TLC analysis was performed on glass-backed plates
coated with silica gel 60 and an F254 indicator and were visualized
by either UV irradiation or by staining with a phosphomolybdic
acid solution. Organic compounds were purchased from Aldrich
and used as received. Solvents were dried and stored over micro-
wave-activated 4 Å molecular sieves.
absolute stereochemistry was determined by X-ray diffrac-
tion analysis,[10] which confirmed that previously assigned
for 3h. Reductive ring opening of 8 with aluminum hydride
gave diol 9 as a mixture of diastereoisomers that was con-
verted into diketone 10 by oxidation with PCC. This ketone,
without isolation, was subjected to a retro-Michael reaction
by treatment with a solution of KOH in ethanol. The tricy-
clic keto pyrrolidine was isolated as tosylate 11 by reaction
with tosyl chloride (Scheme 5).
General Procedure for the Stoichiometric Pauson–Khand Reactions
(Method A): A 25-mL flask was charged with perhydrobenzoxazine
(1.3 mmol) in dry DCM (10 mL), 3 Å molecular sieves (8-fold in
weight), and Co2(CO)8 (1.4 mmol) under an argon atmosphere, and
the mixture was stirred for 2 h at room temperature. Then,
TMANO (10.4 mmol) was added and stirring was continued at
room temperature until the reaction was complete (TLC). The reac-
tion mixture was filtered, the solids were washed with DCM (2 or
3ϫ), and the solvent was evaporated under vacuum. The residues
were purified by flash chromatography (EtOAc/hexanes).
General Procedure for the Catalytic Pauson–Khand Reactions
(Method B): A two-necked flask equipped with septum inlets and
a magnetic stirring bar was charged with the corresponding perhy-
drobenzoxazine (0.8 mmol) in dimethoxyethane (8 mL), and the
solution was flushed with carbon monoxide for 2 min. Then,
Co2(CO)8 (0.08 mmol) was added, the solution was flushed with
carbon monoxide again, and cyclohexylamine (0.16 mmol) was
added. The mixture was heated to 60 °C under a CO atmosphere
(CO balloon) until the reaction was complete (TLC). After cooling
to room temperature, the mixture was filtered, the solids were
washed with dimethoxyethane, and the solvent was evaporated un-
der reduced pressure. The residue was purified by flash chromatog-
raphy on silica gel (EtOAc/hexanes).
Adduct 3a: Yellowish oil. [α]2D5 = –213.30 (c = 1.12, CHCl3). 1H
NMR: δ = 0.90 (d, J = 6.6 Hz, 3 H), 0.93–1.12 (m, 2 H), 1.18 (s,
3 H), 1.24 (s, 3 H), 1.29–1.45 (m, 2 H), 1.57–1.79 (m, 4 H), 2.38
(dd, J = 6.3, 17.3 Hz, 1 H), 2.50 (dd, J = 4.1, 17.2 Hz, 1 H), 3.25
(m, 1 H), 3.43 (dt, J = 4.2, 10.5 Hz, 1 H), 3.82 (d, J = 17.1 Hz, 1
H), 3.91 (d, J = 17.1 Hz, 1 H), 4.88 (d, J = 4.0 Hz, 1 H), 5.93 (s, 1
H) ppm. 13C NMR: δ = 22.1 (CH3), 22.2 (CH3), 24.6 (CH2), 26.4
(CH3), 31.2 (CH), 34.9 (CH2), 36.8 (CH2), 41.0 (CH2), 42.7 (CH),
45.6 (CH2), 50.9 (CH), 53.5 (C), 74.0 (CH), 83.4 (CH), 124.5
Scheme 5. Reagents and conditions: (i) H2, 1 atm, 10% Pd/C,
EtOH, r.t.. (ii) AlH3, THF, 0 °C. (iii) PCC, 4 Å MS, DCM, r.t.
(iv) 1. KOH, MeOH/THF; 2. TsCl, DIPEA EtOAc, r.t.
Conclusions
Chiral perhydrobenzoxazines derived from (–)-8-amino-
menthol with acetylenic and olefinic substituents at the 2-
and 3-positions have been shown to be good chiral tem-
plates for diastereoselective intramolecular PKRs. The dia-
stereoselectivity of the reaction is dependent on both the
substitution pattern of the double bond and the nature of
the starting regioisomer.
For 2-vinyl-3-propargyl-substituted substrates, the dia-
stereoselection was very low except when the olefinic com-
ponent had two substituents at the endo and exo positions.
Much better stereochemical discrimination was observed
for regioisomers bearing the acetylenic bond at C-2 and the
allyl substituent at the nitrogen atom. In that case, the dia-
stereoselection improved with the size of the substituent at
the triple bond.
(CH=), 184.7 (C=), 210.5 (C=O) ppm. IR (thin layer): ν = 3078,
˜
2924, 1710, 1643 cm–1.
Adduct epi-3a: White solid, m.p. 87.7–88.9 °C (hexane). [α]2D5
=
+57.90 (c = 0.92, CHCl3). 1H NMR (CDCl3): δ = 0.91 (s, 3 H),
0.94 (d, J = 6.5 Hz, 3 H), 0.98–1.13 (m, 2 H), 1.18 (s, 3 H), 1.26–
1.73 (m, 5 H), 1.98 (m, 1 H), 2.27 (dd, J = 3.5, 17.9 Hz, 1 H), 2.66
(dd, J = 6.3, 17.9 Hz, 1 H), 3.21 (m, 1 H), 3.39 (dt, J = 4.1, 10.6 Hz,
1 H), 3.60 (d, J = 16.9 Hz, 1 H), 4.05–4.11 (m, 2 H), 5.97–5.99 (m,
1 H) ppm. 13C NMR (CDCl3): δ = 11.1 (CH3), 22.0 (CH3), 24.6
(CH2), 26.5 (CH3), 31.3 (CH), 34.5 (CH2), 39.3 (CH2), 41.1 (CH2),
44.5 (CH2), 50.2 (CH), 50.7 (CH), 54.7 (C), 76.2 (CH), 90.2 (CH),
Interestingly, the same stereochemical results were ob-
tained starting from perhydrobenzoxazines 5a–d as an equi-
molar mixture of epimers at C-2 than from stereochemically
pure ones, indicating that a Nicholas-like reaction occurred
on these compounds prior to the intramolecular PKR.
Experimental Section
126.0 (CH=), 180.7 (C=), 209.0 (C=O) ppm. IR (KBr): ν = 3078,
˜
2931, 1706, 1606 cm–1.
General Methods: 1H NMR (300 MHz) and 13C NMR (75 MHz)
spectra were recorded with a Bruker AC–300 spectrometer in
CDCl3. Chemical shifts for protons are reported in ppm from tet-
ramethylsilane with the residual CHCl3 resonance as internal refer-
ence. Chemical shifts for carbon atoms are reported in ppm from
tetramethylsilane and are referenced to the carbon resonance of
the solvent. Specific rotations were measured with a Perkin–Elmer
Adduct 3b: White solid, m.p. 113.6–115.0 °C (hexane). [α]2D5
=
–167.25 (c = 0.8, CHCl3). 1H NMR (CDCl3): δ = 0.89 (d, J =
6.5 Hz, 3 H), 0.94–1.06 (m, 2 H), 1.18 (s, 3 H), 1.20 (d, J = 7.3 Hz,
3 H), 1.25 (s, 3 H), 1.27–1.45 (m, 2 H), 1.58–1.80 (m, 5 H), 2.54
(dq, J = 4.0,J2 = 7.2 Hz, 1 H), 2.87 (m, 1 H), 3.44 (dt, J = 4.1,
10.5 Hz, 1 H), 3.78–3.92 (m, 2 H), 4.93 (d, J = 4.0 Hz, 1 H), 5.9
Eur. J. Org. Chem. 2012, 1202–1208
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A. Maestro, R. Pedrosa, A. Pérez-Encabo, J. J. Pérez-Rueda
FULL PAPER
(d, J = 1.8 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 13.1 (CH3), 22.2 13C NMR (CDCl3): δ = –1.4 (3 CH3), 11.2 (CH3), 22.1 (CH3), 24.6
(CH3), 22.3 (CH3), 24.7 (CH2), 26.5 (CH3), 31.2 (CH), 35.0 (CH2), (CH2), 26.7 (CH3), 31.3 (CH), 34.6 (CH2), 41.2 (CH2), 45.6 (CH2),
41.0 (CH2), 42.6 (CH), 42.7 (CH), 45.6 (CH2), 53.6 (C), 59.2 (CH),
50.0 (CH), 54.7 (C), 57.5 (CH), 58.9 (CH), 76.0 (CH), 90.1 (CH),
74.1 (CH), 83.0 (CH), 123.5 (CH=), 182.1 (C=), 212.4 (C=O) ppm. 126.6 (CH=), 128.3 (2 CH=), 128.4 (2 CH=), 135.8 (C=), 137.4
IR (Nujol): ν = 3072, 2920, 1706, 1643 cm–1. C H NO (289.41):
calcd. C 74.70, H 9.40, N 4.84; found C 74.59, H 8.17, N 4.20.
(C=), 185.3 (C=), 210.8 (C=O) ppm. IR (thin layer): ν = 3017,
˜
˜
18 27
2
2930, 1700, 1620 cm–1.
Adduct epi-3b: Colorless oil. [α]2D5 = +130.77 (c = 0.52, CHCl3). 1H
NMR (CDCl3): δ = 0.92 (s, 3 H), 0.94 (d, J = 6.5 Hz, 3 H), 0.97–
Adduct 3f: Colorless oil. [α]2D5 = –185.96 (c = 1.14, CHCl3). 1H
NMR (CDCl3): δ = 0.81–1.11 (m, 4 H), 0.89 (d, J = 6.5 Hz, 3 H),
1.14 (m, 2 H), 1.17 (s, 3 H), 1.25 (d, J = 7.3 Hz, 3 H), 1.28–1.58 1.16 (s, 3 H), 1.21 (s, 3 H), 1.28 (s, 3 H), 1.57–1.79 (m, 3 H), 2.07
(m, 3 H), 1.70–1.73 (m, 2 H), 1.98 (m, 1 H), 2.31 (dq, J = 3.6,
7.2 Hz, 1 H), 2.85 (m, 1 H), 3.38 (dt, J = 4.1, 10.6 Hz, 1 H), 3.58
(d, J = 17.0 Hz, 1 H), 4.05 (dt, J = 1.9, 17.0 Hz, 1 H), 4.12 (d, J =
(d, J = 16.6 Hz, 1 H), 2.79 (d, J = 16.6 Hz, 1 H), 3.41 (dt, J = 4.1,
10.4 Hz, 1 H), 3.80 (d, J = 17.5 Hz, 1 H), 3.89 (d, J = 17.5 Hz, 1
H), 4.57 (s, 1 H), 5.80 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 22.2
7.6 Hz, 1 H), 5.96 (dd, J = 1.9, 3.7 Hz, 1 H) ppm. 13C NMR (CH3), 22.3 (CH3), 24.7 (CH2), 24.9 (CH3), 26.4 (CH3), 31.2 (CH),
(CDCl3): δ = 11.3 (CH3), 13.6 (CH3), 22.1 (CH3), 24.6 (CH2), 26.6
(CH3), 31.4 (CH), 34.6 (CH2), 41.2 (CH2), 44.4 (CH2), 46.5 (CH), (C), 55.0 (C), 74.1 (CH), 88.1 (CH), 123.0 (CH=), 189.0 (C=), 210.7
50.0 (CH), 54.7 (C), 58.7 (CH), 58.3 (CH), 76.1 (CH), 90.2 (CH), (C=O) ppm. IR (thin layer): ν = 3072, 2926, 1708, 1640 cm–1.
35.0 (CH2), 41.1 (CH2), 42.9 (CH), 44.7 (CH2), 45.2 (CH2), 53.2
˜
124.9 (CH=), 178.5 (C=), 211.2 (C=O) ppm. IR (thin layer): ν =
˜
Adduct epi-3f: Colorless oil. [α]2D5 = +72.50 (c = 0.40, CHCl3). H
1
3076, 2926, 1709, 1642 cm–1.
NMR (CDCl3): δ = 0.88–1.32 (m, 4 H), 0.88 (s, 3 H), 0.94 (d, J =
6.5 Hz, 3 H), 1.14 (s, 3 H), 1.27 (s, 3 H), 1.44 (m, 1 H), 1.69 (d, J
= 7.1 Hz, 2 H), 1.97 (m, 1 H), 2.34 (d, J = 2.6 Hz, 1 H), 3.37 (dt,
J = 4.1, 10.5 Hz, 1 H), 3.57 (d, J = 17.1 Hz, 1 H), 4.01 (dd, J =
Adduct epi-3c: White solid. m.p. 175.6–177.1 °C (hexane). [α]2D5
=
+114.05 (c = 1.11, CHCl3). 1H NMR (CDCl3): δ = 0.91 (d, J =
6.5 Hz, 3 H), 0.96 (s, 3 H), 0.98–1.12 (m, 2 H), 1.19 (s, 3 H), 1.21–
1.43 (m, 3 H), 1.69–1.71 (m, 2 H), 1.92 (m, 1 H), 3.34–3.50 (m, 3 1.7, 17.5 Hz, 1 H), 4.09 (s, 1 H), 5.85 (s, 1 H) ppm. 13C NMR
H), 3.66 (d, J = 16.8 Hz, 1 H), 4.12 (dt, J = 1.8, 16.9 Hz, 1 H),
4.28 (d, J = 7.1 Hz, 1 H), 6.06 (m, 1 H), 7.22–7.33 (m, 5 H) ppm.
13C NMR (CDCl3): δ = 11.6 (CH3), 22.0 (CH3), 24.6 (CH2), 26.6
(CDCl3): δ = 10.7 (CH3), 20.5 (CH3), 22.1 (CH3), 24.5 (CH2), 26.7
(CH3), 31.3 (CH), 34.5 (CH2), 41.1 (CH2), 43.3 (CH2), 48.3 (CH2),
50.4 (CH), 52.5 (C), 54.3 (C), 75.8 (CH), 91.3 (CH), 124.5 (CH=),
(CH3), 31.3 (CH), 34.6 (CH2), 41.1 (CH2), 44.5 (CH2), 49.8 (CH), 186.0 (C=), 209.3 (C=O) ppm. IR (thin layer): ν = 3078, 2933,
˜
54.8 (C), 56.9 (CH), 58.3 (CH), 76.1 (CH), 90.2 (CH), 124.7 (CH=), 1708, 1642 cm–1.
126.9 (CH=), 128.3 (2 CH=), 128.5 (2 CH=), 137.3 (C=), 178.7
Adduct 3g: White solid, m.p. 192.9–194.7 °C (hexane). [α]2D5
=
(C=), 208.0 (C=O) ppm. IR (KBr): ν = 3028, 2934, 1705,
˜
1
–108.15 (c = 0.92, CHCl3). H NMR (CDCl3): δ = 0.89 (s, 3 H),
0.93 (d, J = 6.5 Hz, 3 H), 0.82–1.13 (m, 3 H), 1.17 (s, 3 H), 1.19
(s, 3 H), 1.34 (m, 1 H), 1.47 (m, 1 H), 1.61 (m, 1 H), 1.71 (m, 1
H), 1.89 (m, 1 H), 3.51 (dt, J = 4.1, 10.4 Hz, 1 H), 3.91 (s, 2 H),
4.32 (s, 1 H), 4.54 (s, 1 H), 5.96 (s, 1 H), 7.18–7.35 (m, 5 H) ppm.
13C NMR (CDCl3): δ = 22.2 (CH3), 22.3 (CH3), 23.0 (CH3), 24.8
(CH2), 26.4 (CH3), 31.3 (CH), 35.0 (CH2), 41.2 (CH2), 43.1 (CH),
1646 cm–1. C23H29NO2 (351.58): calcd. C 78.59, H 8.32, N 3.99;
found C 79.17, H 8.35, N 4.19.
Adduct epi-3d: Yellowish oil. [α]2D5 = +121.33 (c = 0.30, CHCl3). 1H
NMR (CDCl3): δ = 0.11 (s, 9 H), 0.87 (s, 3 H), 0.80–1.11 (m, 3 H),
0.92 (d, J = 6.5 Hz, 3 H), 1.16 (s, 3 H), 1.19–1.43 (m, 2 H), 1.67–
1.70 (m, 2 H), 1.92 (m, 1 H), 2.01 (d, J = 2.1 Hz, 1 H), 3.06 (m, 1
H), 3.31 (dt, J = 4.0, 10.6 Hz, 1 H), 3.54 (dd, J = 0.9, 16.4 Hz, 1 45.2 (CH2), 53.3 (C), 58.5 (CH), 60.0 (C), 74.4 (CH), 87.7 (CH),
H), 3.96 (d, J = 7.9 Hz, 1 H), 4.05 (dt, J = 1.8, 16.4 Hz, 1 H), 5.90
122.7 (CH=), 126.6 (CH=), 128.2 (2 CH=), 129.9 (2 CH=), 136.6
(s,1 H) ppm. 13C NMR (CDCl3): δ = –2.6 (3CH3), 11.0 (CH3), 22.1
(C=), 186.3 (C=), 209.0 (C=O) ppm. IR (KBr): ν = 3051, 2908,
˜
(CH3), 24.6 (CH2), 26.6 (CH3), 31.3 (CH), 34.6 (CH2), 41.1 (CH2), 1702, 1639 cm–1. C24H31NO2 (365.51): calcd. C 78.87, H 8.55, N
42.9 (CH), 44.4 (CH2), 50.5 (CH), 53.8 (CH), 54.9 (C), 76.2 (CH), 3.83; found C 77.56, H 8.28, N 3.94.
90.6 (CH), 127.0 (CH=), 179.1 (C=), 210.8 (C=O) ppm. IR (thin
Adduct epi-3g: White solid, m.p. 185.8–187.1 °C (hexane). [α]2D5
–46.82 (c = 0.44, CHCl3). H NMR (CDCl3): δ = 0.88–1.09 (m, 3
H), 0.88 (s, 3 H), 0.94 (s, 3 H), 0.95 (d, J = 6.5 Hz, 3 H), 1.15 (s,
3 H), 1.23 (m, 1 H), 1.48 (m, 1 H), 1.70 (d, J = 8.3 Hz, 2 H), 1.96
=
layer): ν = 2925, 1690, 1647 cm–1. C H NO Si (347.57): calcd. C
˜
1
20 32
2
69.11, H 9.57, N 4.03; found C 67.55, H 9.62, N 3.99.
Adduct 3e: Colorless oil. [α]2D5 = –306.06 (c = 1.04, CHCl3). 1H
NMR (CDCl3): δ = 0.24 (s, 9 H), 0.85–1.17 (m, 3 H), 0.93 (d, J = (m, 1 H), 3.44 (dt, J = 4.2, 10.5 Hz, 1 H), 3.63 (d, J = 18.8 Hz, 1
6.5 Hz, 3 H), 1.22 (s, 3 H), 1.24 (s, 3 H), 1.27–1.43 (m, 2 H), 1.62 H), 3.66 (s, 1 H), 4.03 (d, J = 18.8 Hz, 1 H), 4.31 (s, 1 H), 6.03 (s,
(m, 1 H), 1.73 (m, 1 H), 1.85 (m, 1 H), 3.41–3.48 (m, 2 H), 3.72 1 H), 7.24–7.35 (m, 5 H) ppm. 13C NMR (CDCl3): δ = 10.8 (CH3),
(d, J = 5.1 Hz, 1 H), 3.87 (dd, J = 2.6, 17.4 Hz, 1 H), 3.97 (dd, J
= 2.0, 17.4 Hz, 1 H), 4.94 (d, J = 4.1 Hz, 1 H), 7.18–7.27 (m, 3 H),
7.32–7.37 (m, 2 H) ppm. 13C NMR (CDCl3): δ = –1.4 (3 CH3),
18.7 (CH3), 22.1 (CH3), 24.6 (CH2), 26.7 (CH3), 31.3 (CH), 34.6
(CH2), 41.3 (CH2), 43.3 (CH2), 50.3 (CH), 54.4 (C), 56.9 (C), 63.6
(CH), 75.8 (CH), 92.8 (CH), 124.3 (CH=), 126.7 (CH=), 128.0 (2
22.2 (CH3), 22.3 (CH3), 24.7 (CH2), 26.5 (CH3), 31.2 (CH), 35.0 CH=), 130.0 (2 CH=), 135.8 (CH=), 184.1 (C=), 208.2 (C=O) ppm.
(CH2), 41.1 (CH2), 46.7 (CH2), 53.6 (C), 54.6 (CH), 60.0 (CH),
74.3 (CH), 82.9 (CH), 126.6 (CH=), 128.4 (2 CH=), 128.5 (2 CH=),
133.8 (C=), 138.3 (C=), 189.3 (C=), 212.1 (C=O) ppm. IR (thin
IR (KBr): ν = 3030, 2920, 1699, 1641 cm–1.
˜
Adduct 3h: Colorless oil. [α]2D5 = –162.31 (c = 0.32, CHCl3). 1H
NMR (CDCl3): δ = 0.89 (d, J = 6.6 Hz, 3 H), 0.91–1.15 (m, 4 H),
1.17 (s, 3 H), 1.23 (s, 3 H), 1.25–1.48 (m, 4 H), 1.52–1.63 (m, 4 H),
1.70 (m, 1 H), 1.78 (m, 1 H), 2.13–2.27 (m, 2 H), 2.74 (d, J =
6.7 Hz, 1 H), 3.44 (dt, J = 4.1, 10.5 Hz, 1 H), 3.84 (s, 2 H), 4.63 (s,
layer): ν = 3023, 2926, 1698, 1623 cm–1. C H NO Si (423.66):
˜
26 37
2
calcd. C 73.71, H 8.80, N 3.31; found C 77.3, H 8.24, N 3.17.
Adduct epi-3e: Colorless oil. [α]2D5 = +181.52 (c = 0.66, CHCl3). 1H
NMR (CDCl3): δ = 0.23 (s, 9 H), 0.84–1.17 (m, 3 H), 0.92 (d, J = 1 H), 5.82 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 21.6 (CH2), 22.2
6.5 Hz, 3 H), 0.96 (s, 3 H), 1.21 (s, 3 H), 1.26–1.44 (m, 2 H), 1.70–
(CH3), 22.4 (CH3), 22.5 (CH2), 22.7 (CH2), 24.8 (CH2), 26.5 (CH3),
1.73 (m, 2 H), 1.94 (m, 1 H), 3.38 (dt, J = 4.2, 10.5 Hz, 1 H), 3.45– 31.2 (CH), 35.0 (CH2), 35.5 (CH2), 41.1 (CH2), 42.9 (CH), 45.2
3.54 (m, 2 H), 3.62 (dd, J = 2.2, 17.2 Hz, 1 H), 4.13 (dd, J = 1.5,
17.2 Hz, 1 H), 4.23 (d, J = 7.2 Hz, 1 H), 7.20–7.41 (m, 5 H) ppm.
(CH2), 48.9 (CH), 53.2 (C), 58.3 (C), 74.3 (CH), 86.3 (CH), 121.1
(CH=), 188.3 (C=), 211.2 (C=O) ppm. IR (thin layer): ν = 3051,
˜
1206
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1202–1208

Diastereoselective Intramolecular Pauson–Khand Reactions
1
2928, 1708, 1642 cm–1. C21H31NO2 (329.24): calcd. C 76.55, H 9.48,
N 4.25; found C 74.98, H 10.53, N 4.29.
Adduct epi-7c: Colorless oil. [α]2D5 = +82.14 (c = 0.56, CHCl3). H
NMR (CDCl3): δ = 0.20 (s, 9 H), 0.83–1.05 (m, 3 H), 0.91 (d, J =
6.5 Hz, 3 H), 1.18 (s, 3 H), 1.23 (s, 3 H), 1.30 (m, 1 H), 1.45 (m, 1
H), 1.59–1.72 (m, 2 H), 1.82 (m, 1 H), 2.21 (dd, J = 4.3, 17.2 Hz,
1 H), 2.54 (dd, J = 6.5, 17.1 Hz, 1 H), 2.70 (dd, J = 7.2, 9.5 Hz, 1
H), 3.02 (m, 1 H), 3.24 (t, J = 7.2 Hz, 1 H), 3.56 (dt, J = 4.3,
10.4 Hz, 1 H), 5.54 (s, 1 H) ppm. 13C NMR (CDCl3): δ = –1.5 (3
CH3), 21.2 (CH3), 22.2 (CH3), 24.9 (CH2), 26.7 (CH3), 31.2 (CH),
34.9 (CH2), 41.3 (CH2), 41.7 (CH2), 44.6 (CH), 46.4 (CH), 48.4
(CH2), 53.5 (C), 74.6 (CH), 82.2 (CH), 138.9 (C=), 193.9 (C=),
Adduct 3i: Colorless oil. [α]2D5 = –151.76 (c = 1.48, CHCl3). 1H
NMR (CDCl3): δ = 0.81–1.16 (m, 5 H), 0.88 (d, J = 6.6 Hz, 3 H),
1.18 (s, 3 H), 1.23 (s, 3 H), 1.25–1.62 (m, 6 H), 1.69 (s, 3 H), 1.72–
2.04 (m, 3 H), 2.11 (d, J = 18.3 Hz, 1 H), 2.25 (d, J = 15.6 Hz, 1
H), 2.66 (d, J = 6.7 Hz, 1 H), 3.43 (dt, J = 4.1, 10.4 Hz, 1 H), 3.76
(s, 2 H), 4.61 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 8.9 (CH3), 21.8
(CH2), 22.2 (CH3), 22.4 (CH2, CH3), 22.7 (CH2), 24.8 (CH2), 26.5
(CH3), 31.2 (CH), 35.0 (CH2), 35.4 (CH2), 41.2 (CH2), 42.9 (CH),
44.3 (CH2), 48.2 (CH), 53.2 (C), 56.3 (C), 74.2 (CH), 86.6 (CH),
213.7 (C=O) ppm. IR (thin layer): ν = 2929, 1702, 1628 cm–1.
˜
128.4 (C=), 180.2 (C=), 211.2 (C=O) ppm. IR (thin layer): ν =
˜
Adduct 7d: Yellow oil. [α]2D5 = –160.00 (c = 1.10, CHCl3). 1H NMR
(CDCl3): δ = 0.93 (d, J = 6.5 Hz, 3 H), 0.97–1.11 (m, 2 H), 1.16
(s, 3 H), 1.25 (s, 3 H), 1.48–1.56 (m, 3 H), 1.63 (m, 1 H), 1.74 (m,
1 H), 1.87 (d, J = 2.3 Hz, 3 H), 1.92 (m, 1 H), 2.95 (dd, J = 3.8,
8.0 Hz, 1 H), 3.39 (d, J = 3.9 Hz, 2 H), 3.48–3.55 (m, 2 H), 3.64
(dt, J = 4.2, 10.4 Hz, 1 H), 5.53 (s, 1 H), 7.16–7.19 (m, 2 H), 7.23–
7.36 (m, 3 H) ppm. 13C NMR (CDCl3): δ = 9.1 (CH3), 20.2 (CH3),
22.2 (CH3), 25.0 (CH2), 26.7 (CH3), 31.3 (CH), 35.0 (CH2), 41.5
(CH2), 45.6 (CH), 48.3 (CH2), 51.3 (CH), 53.7 (C), 58.5 (CH), 74.8
(CH), 82.3 (CH), 126.9 (CH=), 128.3 (2 CH=), 128.6 (2 CH=),
133.3 (C=), 138.4 (C=), 174.7 (C=), 209.3 (C=O) ppm. IR (thin
2922, 1708, 1680 cm–1.
Adduct 7a: Yellowish oil. [α]2D5 = –171.50 (c = 0.92, CHCl3). 1H
NMR (CDCl3): δ = 0.93 (d, J = 6.7 Hz, 3 H), 0.98–1.13 (m, 2 H),
1.16 (s, 3 H), 1.22 (s, 3 H), 1.49–1.57 (m, 2 H), 1.65 (m, 1 H), 1.72–
1.76 (m, 2 H), 1.79 (d, J = 2.4 Hz, 3 H), 1.91 (m, 1 H), 2.20 (dd, J
= 3.4, 17.5 Hz, 1 H), 2.69–2.77 (m, 2 H), 3.42–3.52 (m, 2 H), 3.62
(dt, J = 4.2, 10.4 Hz, 1 H), 5.45 (s, 1 H) ppm. 13C NMR (CDCl3):
δ = 9.0 (CH3), 20.8 (CH3), 22.2 (CH3), 24.7 (CH2), 25.8 (CH3),
31.2 (CH), 34.9 (CH2), 38.7 (CH), 41.3 (CH2), 42.9 (CH2), 44.3
(CH), 48.8 (CH2), 53.7 (C), 74.6 (CH), 81.0 (CH), 131.7 (C=), 173.3
layer): ν = 3027, 2922, 1719, 1690 cm–1. C H NO (365.51): calcd.
(C=), 210.6 (C=O) ppm. IR (thin layer): ν = 2923, 1714, 1691 cm–1.
˜
˜
24 31
2
C 78.87, H 8.55, N 3.83; found C 77.68, H 8.30, N 3.94.
C18H27NO2 (289.41): calcd. C 74.70, H 9.40, N 4.84; found C
73.62, H 8.08, N 4.10.
Adduct epi-7d: White solid, m.p. 135.3–137.2 °C (hexane). [α]2D5
=
Adduct epi-7a: White solid, m.p. 131.7–133.7 °C (hexane). [α]2D5
=
+211.50 (c = 1.06, CHCl3). 1H NMR (CDCl3): δ = 0.93 (d, J =
6.5 Hz, 3 H), 0.95–1.14 (m, 2 H), 1.16 (s, 3 H), 1.20 (s, 3 H), 1.27–
1.49 (m, 2 H), 1.61–1.73 (m, 3 H), 1.87 (m, 1 H), 1.92 (m, 1 H),
2.94 (dd, J = 8.8, 7.2 Hz, 1 H), 3.14–3.22 (m, 1 H), 3.31 (dd, J =
7.1, 7.1 Hz, 1 H), 3.43 (d, J = 4.0 Hz, 1 H), 3.56–3.65 (td, J = 4.3,
10.5 Hz, 1 H), 5.67 (s, 1 H), 7.16–7.20 (m, 2 H), 7.25 (m, 1 H),
7.30–7.36 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 9.1 (CH3), 20.2
(CH3), 22.2 (CH3), 24.9 (CH2), 26.6 (CH3), 31.3 (CH), 35.0 (CH2),
41.4 (CH2), 45.5 (CH), 48.3 (CH2), 51.3 (CH), 53.7 (C), 58.5 (CH),
74.7 (CH), 82.2 (CH), 126.9 (CH=), 128.3 (2 CH=), 128.6 (2 CH=),
133.2 (C=), 138.4 (C=), 174.7 (C=), 209.3 (C=O) ppm. IR (KBr):
1
+68.20 (c = 0.78, CHCl3). H NMR (CDCl3): δ = 0.85–1.13 (m, 3
H), 0.90 (d, J = 6.5 Hz, 3 H), 1.17 (s, 3 H), 1.20 (s, 3 H), 1.30 (m,
1 H), 1.42 (m, 1 H), 1.60–1.71 (m, 2 H), 1.79 (d, J = 2.5 Hz, 1 H),
1.84 (m, 1 H), 2.21 (dd, J = 3.6, 7.4 Hz, 1 H), 2.58 (dd, J = 6.2,
17.4 Hz, 1 H), 2.73 (dd, J = 7.4, 9.2 Hz, 1 H), 2.96 (m, 1 H), 3.24
(t, J = 7.2 Hz, 1 H), 3.56 (dt, J = 4.3, 10.4 Hz, 1 H), 5.62 (s, 1 H)
ppm. 13C NMR (CDCl3): δ = 8.7 (CH3), 20.2 (CH3), 22.2 (CH3),
24.9 (CH2), 26.6 (CH3), 31.2 (CH), 34.9 (CH2), 40.3 (CH2), 41.4
(CH2), 42.3 (CH), 45.6 (CH), 48.7 (CH2), 53.6 (C), 74.6 (CH), 82.2
(CH), 134.5 (C=), 177.6 (C=), 210.6 (C=O) ppm. IR (KBr): ν =
˜
2924, 1709, 1678 cm–1.
ν = 3018, 2936, 1719, 1682 cm–1.
˜
Adduct 7b: Yellowish solid, m.p. 148.4–150.2 °C (hexane). [α]2D5
=
Adduct 8: White solid, m.p. 64.7–66.3 °C (hexane). [α]2D5 = +11.46
1
–122.21 (c = 1.04, CHCl3). H NMR (CDCl3): δ = 0.83–1.08 (m,
3 H), 0.96 (d, J = 6.5 Hz, 3 H), 1.13 (s, 3 H), 1.17 (s, 3 H), 1.53–
1.77 (m, 4 H), 2.02 (m, 1 H), 2.42 (dd, J = 10.3, 14.0 Hz, 1 H),
2.92 (dd, J = 6.3, 17.3 Hz, 1 H), 3.49–3.58 (m, 2 H), 3.66 (dt, J =
4.0, 10.0 Hz, 1 H), 5.43 (s, 1 H), 7.31–7.59 (m, 3 H), 7.60–7.63 (m,
2 H) ppm. 13C NMR (CDCl3): δ = 20.4 (CH3), 22.2 (CH3), 24.8
(CH2), 26.0 (CH3), 31.4 (CH), 35.0 (CH2), 39.2 (CH), 41.5 (CH2),
44.5 (CH2), 44.7 (CH), 48.3 (CH2), 53.8 (C), 75.0 (CH), 82.6 (CH),
128.4 (3 CH=), 128.8 (2 CH=), 130.8 (C=), 175.0 (C=), 208.3
1
(c = 0.89, CHCl3). H NMR (CDCl3): δ = 0.90 (d, J = 6.5 Hz, 3
H), 0.94–1.04 (m, 2 H), 1.07 (s, 3 H), 1.08 (s, 3 H), 1.14–1.48 (m,
8 H), 1.56–1.61 (m, 3 H), 1.64–1.69 (m, 2 H), 1.84 (m, 1 H), 2.12–
2.25 (m, 2 H), 2.48 (m, 1 H), 2.74–2.78 (m, 2 H), 3.13 (t, J = 8.4 Hz,
1 H), 3.36 (dt, J = 4.2, 10.4 Hz, 1 H), 4.35 (s, 1 H) ppm. 13C NMR
(CDCl3): δ = 18.0 (CH3), 22.2 (CH3), 22.6 (CH2), 22.9 (CH2), 23.1
(CH2), 24.7 (CH2), 26.8 (CH3), 31.2 (CH), 34.2 (CH2), 35.0 (CH2),
39.3 (CH), 41.3 (CH2), 41.7 (CH2), 45.7 (CH), 48.5 (CH), 50.5
(CH2), 51.4 (C), 53.3 (C), 74.7 (CH), 92.2 (CH), 219.7 (C=O) ppm.
(C=O) ppm. IR (KBr):
ν =
˜
3022, 2922, 1707, 1668 cm–1.
IR (Nujol): ν = 2928, 1741 cm–1. C H NO (331.49): calcd. C
˜
21 33
2
C23H29NO2 (351.48): calcd. C 78.59, H 8.32, N 3.99; found C
77.09, H 8.13, N 4.06.
76.09, H 10.03, N 4.23; found C 76.86, H 9.71, N 4.36.
Adduct 7c: Yellowish solid. m.p. 99.5–101.5 °C (hexane). [α]2D5
–173.30 (c = 0.94, CHCl3). H NMR (CDCl3): δ = 0.21 (s, 9 H),
0.86–1.12 (m, 3 H), 0.92 (d, J = 6.5 Hz, 3 H), 1.15 (s, 3 H), 1.18 –8.42 (c = 1.52, CHCl3). H NMR (CDCl3, 333 K): δ = 0.86 (d, J
=
(3aR,5aS)-2-{2-[(1S,2R,4R)-2-Hydroxy-4-methylcyclohexyl]propan-
1
2-yl}decahydro-1H-indeno[1-c]pyrrol-5-ol (9): Colorless oil. [α]2D5
=
1
(s, 3 H), 1.45–1.55 (m, 2 H), 1.62 (m, 1 H), 1.70 (m, 1 H), 1.91 (m,
1 H), 2.17 (dd, J = 3.6, 17.2 Hz, 1 H), 2.62–2.75 (m, 2 H), 3.39–
3.49 (m, 2 H), 3.57 (dt, J = 4.1, 10.6 Hz, 1 H), 5.39 (s, 1 H) ppm.
13C NMR (CDCl3): δ = –1.4 (3 CH3), 20.4 (CH3), 22.2 (CH3), 24.7
= 6.5 Hz, 3 H), 0.89 (s, 3 H), 0.79–1.09 (m, 4 H), 1.12 (s, 3 H),
1.18–1.64 (m, 12 H), 1.77 (m, 1 H), 1.81–1.88 (m, 3 H), 2.23–2.37
(m, 2 H), 2.60–2.74 (m, 3 H), 3.58 (dt, J = 4.0, 10.2 Hz, 1 H), 3.91
(dd, J = 9.2, 17.0 Hz, 1 H), 8.28 (s, 1 H) ppm. 13C NMR (CDCl3,
(CH2), 25.8 (CH3), 31.3 (CH), 34.9 (CH2), 41.4 (CH2), 42.4 (CH), 333 K): δ = 17.1 (CH3), 21.5 (CH2), 21.9 (2 CH3), 22.6 (CH2), 24.0
44.3 (CH2), 44.5 (CH), 48.3 (CH2), 53.7 (C), 74.9 (CH), 82.3 (CH),
(CH2), 25.6 (CH2), 30.9 (CH), 35.1 (CH2), 36.1 (CH2), 39.7 (CH2),
44.4 (CH2), 45.3 (CH), 47.5 (C), 48.0 (CH), 50.7 (CH), 52.1 (CH2),
136.0 (C=), 187.9 (C=), 214.1 (C=O) ppm. IR (KBr): ν = 2921,
˜
1698, 1643 cm–1. C20H33NO2Si (347.57): calcd. C 69.11, H 9.57, N
4.03; found C 66.04, H 10.01, N 3.93.
57.3 (CH ), 58.7 (C), 72.9 (CH), 73.7 (CH) ppm. IR (thin layer): ν
˜
2
= 3372, 2921 cm–1.
Eur. J. Org. Chem. 2012, 1202–1208
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1207

A. Maestro, R. Pedrosa, A. Pérez-Encabo, J. J. Pérez-Rueda
FULL PAPER
(3aR,5aS,91R)-2-Tosyloctahydro-1H-indeno[1-c]pyrrol-5(5aH)-one
(11): Yellowish oil. [α]2D5 = +64.17 (c = 0.60, CHCl3). 1H NMR
(CDCl3): δ = 1.19–1.50 (m, 3 H), 1.58–1.80 (m, 4 H), 1.93 (m, 1
H), 2.05 (m, 1 H), 2.22 (m, 1 H), 2.49–2.55 (m, 2 H), 2.56 (s, 3 H),
3.12 (dd, J = 7.5, 10.4 Hz, 1 H), 3.20 (d, J = 10.1 Hz, 1 H), 3.71
(d, J = 10.1 Hz, 1 H), 3.77 (dd, J = 8.7, 10.4 Hz, 1 H), 7.46 (d, J
= 8.0 Hz, 1 H), 7.84 (d, J = 8.3 Hz, 1 H) ppm. 13C NMR (CDCl3):
δ = 20.9 (CH2), 21.5 (CH3), 22.6 (CH2), 23.0 (CH2), 32.7 (CH2),
39.3 (CH2), 41.6 (CH), 49.4 (C), 50.5 (CH), 52.6 (CH2), 57.2 (CH2),
127.3 (2 CH=), 129.7 (2 CH=), 133.2 (CH=), 143.8 (C=), 216.1
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˜
[4]
Supporting Information (see footnote on the first page of this arti-
cle): Synthesis and characterization of compounds 1a, 1d, 1g, 2a–
i, 4a–c, and 5a–d; copies of the 1H NMR and 13C NMR spectra
for all new compounds; ORTEP representation of the X-ray struc-
tures for compounds 7c and 8.
Acknowledgments
We acknowledge the financial support of the Spanish Ministerio
de Ciencia e Innovacion (MICINN) (Projects CTQ2005-01191/
BQU and CTQ2008-03960/BQU) and Junta de Castilla y León
(Project GR 168). J. J. P.-R. also thanks the Ministerio de Educa-
ción y Ciencia (MEC) for a predoctoral fellowship (FPU program).
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Received: October 7, 2011
Published Online: December 27, 2011
1208
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1202–1208