Synthesis of substituted 1,4,5,6-tetrahydrocyclopenta[ b ]pyrroles by platinum-cata yzed cascade cyclization/ring expansion of 2-alkynyl-1-azaspiro[2. 3]hexanes

Article abstract of DOI:10.1021/jo201000f

The reaction of 2-alkynyl-1-azaspiro[2.3]hexanes with a platinum catalyst is described. 1,4,5,6-Tetrahydrocyclopenta[b]pyrroles having a variety of substituents were conveniently synthesized via a cascade cyclization/ring- expansion process.

Full text of DOI:10.1021/jo201000f

ARTICLE
pubs.acs.org/joc
Synthesis of Substituted 1,4,5,6-Tetrahydrocyclopenta[b]pyrroles by
Platinum-Catalyzed Cascade Cyclization/Ring Expansion of 2-Alkynyl-
1-azaspiro[2.3]hexanes
Masahiro Yoshida,* Yohei Maeyama, Mohammad Al-Amin, and Kozo Shishido
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
S Supporting Information
b
ABSTRACT: The reaction of 2-alkynyl-1-azaspiro[2.3]hexanes with a plati-
num catalyst is described. 1,4,5,6-Tetrahydrocyclopenta[b]pyrroles having a
variety of substituents were conveniently synthesized via a cascade cyclization/
ring-expansion process.
Scheme 1. Platinum-Catalyzed Cycloisomerization of Pro-
pargylic Aziridines
’ INTRODUCTION
Cyclopenta[b]pyrroles (1,4,5,6-tetrahydrocyclopenta[b]pyrroles)
are an important class of heteroaromatic molecules which are
components of the phorbine chromophore present in all types of
chlorophylls.1 They are also utilized as synthetic intermediates for
biologically active molecules having a 2-azabicyclo[3.3.0]octane
skeletone.2 Consequently, considerable effort has been devoted
toward the development of an efficient methodology for the synthesis
of cyclopenta[b]pyrroles.3 However, few appropriate general meth-
ods for their synthesis exist.
Transition-metal-catalyzed cycloisomerization of propargylic
aziridines is a useful methodology for the synthesis of substituted
pyrroles.4,5 Recently, some examples of a gold-catalyzed synthesis
of pyrroles has been reported.4 We have also found that platinum
acts as a catalyst6 for the conversion of propargylic aziridines to 2,
5-disubstituted pyrroles(Scheme 1).5a,b As an application of this
cycloisomerization reaction, we report herein a novel methodology
for the synthesis of cyclopenta[b]pyrroles by platinum-catalyzed
cascade cyclization/ring expansion of 2-alkynyl-1-azaspiro[2.3]
hexanes 1, in which various 1,4,5,6-tetrahydrocyclopenta[b]
pyrroles 2 were synthesized with high efficiency.
The initial reactions for the synthesis of cyclopenta[b]pyrroles
were attempted using the 2-pentynyl-1-azaspiro[2.3]hexane 1a
(Scheme 3). When 1a was subjected to the reaction with 10 mol %
of PtCl2 in dioxane/H2O (2/1) at 100 °C following our pro-
cedure for the synthesis of pyrroles,5a the cyclopenta[b]pyrrole
2a was produced in 84% yield. After several attempts, we found
that the yield of 2a could be increased to 97% when the reaction
was carried out in dioxane.
The reactions of the various substituted 2-alkynyl-1-azaspiro-
[2.3]hexanes 1bꢀl under the optimized conditions are summar-
ized in Table 1. When the reactions of the substrates 1b and 1c
containing an allyl and a 4-pentenyl group at the alkynyl position
were carried out, the cyclopenta[b]pyrroles 2b and 2c were
obtained in 91% and 90% yield, respectively (entries 1 and 2).
The reactions of 1d and 1e having an alkynyl and a siloxy group
also afforded the corresponding products 2d and 2e in good
yields (entries 3 and 4). The substrate 1f containing a free
hydroxyl group was uneventfully transformed to the cyclopenta-
[b]pyrrole 2f in 82% yield (entry 5). The substrate 1g, which has
a substituent on the cyclobutane ring, was successfully trans-
formed to the product 2g in 75% yield (entry 6). The reactions of
1h and 1i having 2-heptyl- and 2-phenethylcyclobutane moieties
also afforded the products 2h and 2i in 71% and 75% yield,
respectively (entries 7 and 8). The resulting 2h and 2i were
obtained as the sole products, which indicates the predominant
migration of a secondary carbon atom. When the reaction of the
’ RESULTS AND DISCUSSION
The substrates 1 for the cyclization reactions were synthesized as
follows (Scheme 2). After the reaction of cyclobutanone (3a) with
benzylamine, the resulting imine was treated with the allenylzinc
reagent to give the TMS-substituted propargylic aziridine 4a.7
Compound 4a was subjected to the reaction with K2CO3 in MeOH
to afford the desilylated compound 5a, and then various substitu-
ents at the terminal position of the alkyne 5a were introduced to
give 1aꢀe by the reactions with BuLi and the corresponding alkyl
bromides. Compound 1f containing a free hydroxyl group was
obtained from the reaction of 1e with TBAF. The 2-alkynyl-1-
azaspiro[2.3]hexanes 1gꢀl were also prepared from the corre-
sponding cyclobutanones 3gꢀl by following the same procedure.
Received: May 18, 2011
Published: June 08, 2011
r
2011 American Chemical Society
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Scheme 2. Synthesis of 2-Alkynyl-1-azaspiro[2.3]hexanes 1
Scheme 3. Platinum-Catalyzed Cycloisomerization of Pro-
pargylic Aziridines
To further highlight the potential of this process, we next
constructed 4,5,6,7-tetrahydro-1H-indoles by the reaction of
2-alkynyl-1-azaspiro[2.4]heptanes (Scheme 5). The 2-alkynyl-
1-azaspiro[2.4]heptanes 1m and 1n were prepared from cyclo-
pentanone (3m) by following the same procedure described for
1a and 1e. When the substrate 1m was treated with 10 mol % of
PtCl2 in dioxane at 100 °C, the desired product 2m was produced
in 91% yield. Similarly, the reactions of 1n having a siloxy group
afforded the corresponding product 2n in 84% yield.
’ CONCLUSION
In conclusion, we have developed a methodology for the syn-
thesis of cyclopenta[b]pyrroles by platinum-catalyzed cascade cycli-
zation/ring expansion of 2-alkynyl-1-azaspiro[2.3]hexanes. The
reactions afford a variety of substituted cyclopenta[b]pyrroles, and
the process is an efficient and convenient protocol for the prepara-
tion of these derivatives.
propargylic aziridine 1j having an oxabicyclo[3.2.0]heptane ring
was carried out, the tricyclic pyrrole 2j was produced in 80% yield
(entry 9). Similarly, the corresponding products 2k and 2l were
obtained from the reactions of 1k and 1l containing a bicyclo-
[3.2.0]heptane and a bicyclo[4.2.0]octane moiety (entries 10
and 11).
A plausible mechanism for the cascade reaction of 2-alkynyl-1-
azaspiro[2.3]hexanes is summarized in Scheme 4. It is presumed
that the cyclopenta[b]pyrroles can be formed by two different
pathways. The first possible one (a) involves the coordination of
the platinum to the carbonꢀcarbon triple bond as in 6, followed
by attack of the aziridine nitrogen on the alkyne, to produce the
cyclized intermediate 7. Then a regioselective 1,2-migration/ring
expansion would proceed,8 leading to the pyrrolylplatinum
species 8, which would undergo proto-demetalation to afford
the cyclopenta[b]pyrrole 2. As an alternative pathway (b), a ring
expansion of the four-membered ring could be initially triggered
by the coordination of the platinum to the aziridine nitrogen as
shown in 9, resulting in the formation of the cyclopentane imine
10. Finally, the platinum-catalyzed cycloisomerization of 10
would take place3d to give the product 2.
’ EXPERIMENTAL SECTION
General Procedures. All nonaqueous reactions were carried out
under a positive atmosphere of argon in dried glassware unless otherwise
indicated. Materials were obtained from commercial suppliers and used
without further purification except when otherwise noted. Solvents were
dried and distilled according to standard protocol. The phrase “residue
upon workup” refers to the residue obtained when the organic layer was
separated and dried over anhydrous MgSO4 and the solvent was
evaporated under reduced pressure. Cyclobutanones 3g,9 3h,10 3i,11
3j,12 3k,13 and 3l,13 were prepared according to the procedures
described in the literature.
General Procedure for the Synthesis of TMS-Substituted
Propargylic Aziridines 4. Synthesis of 4a. To a stirred solution of
cyclobutanone (3a) (2.00 mL, 26.8 mmol) and 4 Å MS in CH2Cl2 was
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Table 1. Reactions Using Various Substrates 1bꢀl
Scheme 4. Proposed Reaction Mechanisms
Scheme 5. Synthesis of 4,5,6,7-Tetrahydro-1H-indoles
a All reactions were carried out in the presence of 10 mol % of
PtCl2 in dioxane at 100 °C for 10ꢀ60 min.
and stirring was continued at the same temperature for 1 h to produce
allenylzinc compound. N-Cyclobutanbenzylimine in THF (20 mL) was
then added dropwise to the resulting solution of allenylzinc compound
at ꢀ78 °C. The mixture was allowed to rt slowly, and further stirring was
continued for 1 h at the same temperature. The resulting mixture was
quenched with saturated aqueous NH4Cl and extracted with Et2O. The
combined organic extracts were washed with saturated aqueous NaCl.
The residue upon workup was chromatographed on silica gel with
hexaneꢀAcOEt (95:5, v/v) as eluent to give the TMS-substituted
propargylic aziridine 4a (5.66 g, 78%, two steps) as a yellow oil.
added N-benzylamine (2.90 mL, 26.8 mmol) at rt under argon atomo-
sphere. After stirring was continued overnight at the same temperature,
the resulting solution was filtered through a Celite pad. The filtrate was
evaporated under reduced pressure to give N-cyclobutanbenzylimine.
This crude product was used in the next steps without purification. To a
stirred solution of (3-chloro-1-propynyl)trimethylsilane (4.70 g, 32.1
mmol) in THF (50 mL) was added ZnBr2 (12.0 g, 53.5 mmol) at
ꢀ78 °C. A freshly prepared solution of lithium diisopropylamide (1.0 M,
2.0 equiv) was slowly added dropwise to the resulting white suspension,
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1-Benzyl-2-(trimethylsilylethynyl)-1-azaspiro[2.3]hexane (4a): yield
78% (two steps); yellow oil; 1:1 mixture of two invertomers; IR (neat)
2959, 1497, 1354, 1250, 1090 cmꢀ1; 1H NMR (400 MHz, CDCl3) for the
1:1 mixture of two invertomers: δ 7.41ꢀ7.38 (m, 2H), 7.35ꢀ7.31 (m,
2H), 7.27ꢀ7.23 (m, 1H), 3.58ꢀ3.55 (m, 2H), 2.57ꢀ1.85 (m, 7H), 0.18
(s, 4.5H), 0.10 (s, 4.5H); 13C NMR (100 MHz, CDCl3) for the 1:1
mixture of two invertomers: δ 139.5, 139.0, 128.23, 128.20, 128.1, 127.4,
126.7, 126.6, 103.6, 101.4, 90.8, 87.0, 57.6, 51.9, 50.2, 49.3, 38.2, 35.6, 31.4,
28.9, 25.9, 24.2, 14.6, 14.3, 0.0; HRMS (ESI) m/z calcd for C17H24NSi
[M + H]+ 270.1678, found 270.1677.
1.75 (dd, J = 4.8, 13.6 Hz, 1 H), 1.66ꢀ1.62 (m, 1H), 1.56ꢀ1.26 (m, 4H),
0.18 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 139.6, 128.5, 128.1, 126.7,
101.6, 90.9, 52.2, 48.9, 46.4, 36.7, 33.2, 32.6, 28.0, 27.9, 24.4, 0.0; HRMS
(ESI) m/z calcd for C20H28NSi [M + H]+ 310.1991, found 310.1989.
1-Benzyl-3-(trimethylsilylethynyl)spiro(aziridine-2,70-bicyclo[4.2.0]-
octane) (4l): yield 64% (two steps); colorless oil; 85:15 mixture of two
invertomers; IR (neat) 2931, 2854, 2165, 1452, 1250, 1068 cmꢀ1; 1H
NMR (400 MHz, CDCl3) for 85:15 mixture of two invertomers: δ
7.42ꢀ7.37 (m, 2H), 7.32 (t, J = 7.2 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 4.18
(d, J = 14.4 Hz, 0.15H), 3.58 (d, J = 13.6 Hz, 0.85H), 3.50 (d, J = 13.6 Hz,
0.85H), 3.08 (d, J = 14.4 Hz, 0.15H), 2.58 (s, 0.85H), 2.52ꢀ2.41 (m,
1H), 2.31 (t, J = 9.2 Hz, 0.85H), 2.23ꢀ2.15 (m, 1.7H), 1.75ꢀ1.61 (m,
1.6H), 1.55ꢀ1.43 (m, 4H), 1.40ꢀ1.26 (m, 2H), 1.08ꢀ1.02 (m, 1H),
0.17 (s, 7.65H), 0.15 (s, 1.35H); 13C NMR (100 MHz, CDCl3) δ 139.5,
128.7, 128.1, 126.7, 101.9, 90.7, 52.9, 52.0, 39.5, 35.2, 27.0, 26.1, 26.0,
23.9, 22.4, 21.4, 0.0; HRMS (ESI) m/z calcd for C21H30NSi [M + H]+
324.2148, found 324.2151.
1-Benzyl-2-(trimethylsilylethynyl)-1-azaspiro[2.4]heptane (4m): yield
60% (two steps); yellow oil; 1:1 mixture of two invertomers; IR (neat)
2959, 1497, 1354, 1250, 1090 cmꢀ1. 1H NMR (400 MHz, CDCl3) for the
1:1 mixture of two invertomers: δ 7.39ꢀ7.36 (m, 2H), 7.33ꢀ7.29 (m,
2H), 7.23 (t, J = 7.2 Hz, 1H), 3.84ꢀ3.51 (m, 2H), 2.60 (s, 0.5H), 2.02 (s,
0.5H), 1.86ꢀ1.61 (m, 8H), 0.18 (s, 4.5H), 0.17 (s, 4.5H); 13C NMR (100
MHz, CDCl3) for the 1:1 mixture of two invertomers: δ 139.8, 139.3,
128.2, 128.0, 127.2, 126.5, 104.1, 101.8, 91.1, 87.4, 58.0, 54.4, 53.6, 52.1,
39.9, 37.1, 36.2, 32.7, 26.5, 25.9, 25.6, 24.9, 24.6, 24.0, 0.0; HRMS (ESI)
m/z calcd for C18H25NNaSi [M + Na]+ 306.1654, found 306.1655.
1-Benzyl-5-(but-3-enyl)-2-(trimethylsilylethynyl)-1-azaspiro[2.3]hexane
(4g). Yield 46% (two steps); yellow oil; 1:1 mixture of two invertomers;
1
IR (neat) 2959, 2922, 2151, 1454, 1250, 1092 cmꢀ1; H NMR (400
MHz, CDCl3) for the 1:1 mixture of two invertomers: δ 7.40ꢀ7.37 (m,
2H), 7.35ꢀ7.31 (m, 2H), 7.27ꢀ7.23 (m, 1H), 5.85ꢀ5.74 (m, 1H), 4.99
(d, J = 17.2 Hz, 1H), 4.94 (d, J = 10.4 Hz, 1H), 3.58ꢀ3.49 (m, 2H), 2.57
(s, 0.5H), 2.45ꢀ2.19 (m, 3H), 2.07ꢀ1.88 (m, 4.5H), 1.55ꢀ1.50 (m, 2H),
0.17 (s, 4.5H), 0.16 (s, 4.5H); 13C NMR (100 MHz, CDCl3) for the 1:1
mixture of two invertomers: δ 139.5, 138.9, 138.4, 128.2, 128.2, 128.1,
127.4, 126.7, 126.6, 114.5, 103.6, 101.4, 90.9, 87.0, 57.8, 52.0, 47.6, 46.6,
38.0, 37.4, 36.2, 36.1, 35.5, 34.9, 32.2, 31.6, 30.4, 28.1, 27.8, 0.0; HRMS
(ESI) m/z calcd for C21H30NSi [M + H]+ 324.2148, found 324.2143.
1-Benzyl-4-heptyl-2-(trimethylsilylethynyl)-1-azaspiro[2.3]hexane (4h):
yield 60% (two steps); yellow oil; IR (neat) 2926, 2854, 2166, 1455,
1250, 843 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.2 Hz,
2H), 7.32 (t, J = 7.2 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 3.60 (d, J = 13.6 Hz,
1H), 3.45 (d, J = 13.6 Hz, 1H), 2.48 (s, 1H), 2.38ꢀ2.22 (m, 3H), 2.08
(quint, J = 8.8 Hz, 1H), 1.53ꢀ1.44 (m, 2H), 1.31ꢀ1.14 (m, 11H), 0.87
(t, J = 7.2 Hz, 3H), 0.18 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 139.6,
128.5, 128.1, 126.6, 101.7, 90.5, 52.3, 52.3, 42.4, 35.5, 31.8, 31.4, 29.6,
29.2, 26.9, 22.6, 21.8, 20.7, 14.0, 0.0; HRMS (ESI) m/z calcd for
C24H37NNaSi [M + Na]+ 390.2593, found 390.2594.
General Procedure for the Synthesis of Terminal Alkyne
5. Synthesis of 5a. To a stirred solution of the TMS-substituted
propargylic aziridine 4a (661 mg, 2.45 mmol) in MeOH (12 mL) was
added K2CO3 (678 mg, 4.91 mmol) at rt, and the stirring was continued
for 0.5 h at the same temperature. The reaction mixture was then poured
into Et2O/H2O (1/1). The aqueous layer was extracted with Et2O, and
the combined organic extracts were washed with saturated aqueous
NaCl. The residue upon workup was chromatographed on silica gel with
hexaneꢀAcOEt (90:10, v/v) as eluent to give the terminal alkyne 5a
(477 mg, 98%) as yellow oil.
1-Benzyl-4-phenethyl-2-(trimethylsilylethynyl)-1-azaspiro[2.3]hexane
(4i): yield 52% (two steps); yellow oil; 9:1 mixture of two invertomers;
1
IR (neat) 2958, 2165, 1496, 1454, 1250 cmꢀ1; H NMR (400 MHz,
CDCl3) for the 9:1 mixture of two invertomers: δ 7.42 (d, J = 7.2 Hz,
2H), 7.31 (t, J = 7.2 Hz, 2H), 7.24 (t, J = 7.6 Hz, 3H), 7.15 (t, J = 7.2 Hz,
1H), 7.10 (d, J = 7.6 Hz, 2H), 3.72 (d, J = 14.0 Hz, 0.1H), 3.59 (d, J =
13.6 Hz, 0.9H), 3.48 (d, J = 13.6 Hz, 0.9H), 3.33 (d, J = 14.0 Hz, 0.1 H),
2.55 (t, J = 8.0 Hz, 2H), 2.48 (s, 1H), 2.42ꢀ2.25 (m, 3H), 2.12 (quint, J =
8.0 Hz, 1H), 1.92ꢀ1.82 (m, 1H), 1.66ꢀ1.50 (m, 2H), 0.17 (s, 8.1H),
0.14 (s, 0.9H); 13C NMR (100 MHz, CDCl3) δ 142.4, 139.6, 128.5,
128.3, 128.2, 128.1, 126.7, 125.5, 101.6, 90.6, 52.3, 52.1, 41.7, 35.4, 33.4,
33.3, 21.8, 20.7, 0.0; HRMS (ESI) m/z calcd for C25H31NNaSi
[M + Na]+ 396.2123, found 396.2122. The stereochemistry of 4i was
determined unambiguously by NOE correlation.
1-Benzyl-3-(trimethylsilylethynyl)-30-oxaspiro(aziridine-2,60-bicyclo-
[3.2.0]heptane) (4j): yield 47% (two steps); colorless needles; mp
69.2ꢀ70.6 °C [AcOEtꢀhexane (2:1)]; IR (neat) 2959, 2847, 2170,
1250, 1078 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.2 Hz,
2H), 7.33 (t, J = 7.2 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 4.22 (d, J = 9.6 Hz,
1H), 3.90 (d, J = 9.6 Hz, 1H), 3.65 (d, J = 13.6 Hz, 1H), 3.50ꢀ3.42 (m,
2H), 3.41 (d, J = 13.6 Hz, 1H), 2.99ꢀ2.92 (m, 1H), 2.89ꢀ2.86 (m, 1H),
2.57 (s, 1H), 2.51 (dd, J = 8.4, 13.6 Hz, 1H), 2.08 (dd, J = 5.2, 13.6 Hz, 1H),
0.18 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 139.4, 128.6, 128.3, 126.8,
101.0, 91.7, 73.8, 69.8, 52.0, 48.0, 47.2, 36.7, 33.5, 28.1, 0.0; HRMS (ESI)
m/z calcd for C19H26NOSi [M + H]+ 312.1784, found 312.1781. The
stereochemistry of 4j was determined unambiguously by NOE correlation.
1-Benzyl-3-(trimethylsilylethynyl)spiro(aziridine-2,60-bicyclo[3.2.0]
heptane) (4k): yield 49% (two steps); yellow oil; IR (neat) 2955, 2360,
2173, 1250, 1075, 843 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J =
7.2 Hz, 2H), 7.34 (t, J = 7.2 Hz, 2H), 7.25 (t, J = 7.2 Hz, 1H), 3.55 (d, J =
13.6 Hz, 1H), 3.45 (d, J = 13.6 Hz, 1H), 2.77ꢀ2.67 (m, 2H), 2.51 (s,
1H), 2.47 (ddd, J = 2.0, 8.6, 13.6 Hz, 1H), 1.82 (dd, J = 4.8, 12.0 Hz, 1H),
1-Benzyl-2-ethynyl-1-azaspiro[2,3]hexane (5a): yield 98%; yellow
oil; 1:1 mixture of two invertomers; IR (neat) 3292, 3087, 3062, 3029,
2985, 2931, 2846, 2119, 1645, 1605, 1584, 1496, 1454, 1426, 1398,
1
1355 cmꢀ1. H NMR (400 MHz, CDCl3) for the 1:1 mixture of two
invertomers: δ 7.40ꢀ7.38 (m, 2H), 7.35ꢀ7.32 (m, 2H), 7.27ꢀ7.23 (m,
1H), 3.65 (d, J = 14.4 Hz, 0.5H), 3.61 (d, J = 14.4 Hz, 0.5H), 3.54 (d, J =
14.4 Hz, 0.5H), 3.50 (d, J = 14.4 Hz, 0.5H), 2.59 (d, J = 1.6 Hz, 0.5H),
2.51ꢀ2.10 (m, 4.5H), 2.05ꢀ1.88 (m, 3H); 13C NMR (100 MHz,
CDCl3) for the 1:1 mixture of two invertomers: δ 139.2, 138.6,
128.04, 128.03, 127.5, 127.1, 126.5, 126.4, 81.5, 78.9, 73.5, 69.9, 57.3,
51.7, 49.6, 48.6, 36.8, 34.4, 31.0, 28.7, 25.5, 24.0, 14.3, 14.0; HRMS (ESI)
m/z calcd for C14H15NNa [M + Na]+ 220.1102, found 220.1106.
1-Benzyl-5-(but-3-enyl)-2-ethynyl-1-azaspiro[2.3]hexane (5g): yield
86%; yellow oil; 1:1 mixture of two invertomers; IR (neat) 3310, 2925,
2853, 1415cmꢀ1; 1H NMR (400 MHz, CDCl3) for the 1:1mixture oftwo
invertomers: δ 7.39ꢀ7.37 (m, 2H), 7.34 (t, J = 7.2 Hz, 2H), 7.26ꢀ7.22
(m, 1H), 5.84ꢀ5.74 (m, 1H), 4.99 (d, J = 17.2 Hz, 1H), 4.94 (d, J = 10.0
Hz, 1H), 3.65ꢀ3.44 (m, 2H), 2.59 (s, 0.5H), 2.47ꢀ2.17 (m, 4H),
2.09ꢀ1.86(m, 4.5H), 1.55ꢀ1.50 (m, 2H);13C NMR (100 MHz, CDCl3)
for the 1:1 mixture of two invertomers: δ 139.4, 138.8, 138.4, 128.3, 127.9,
127.4, 126.8, 126.7, 114.5, 81.8, 79.3, 73.7, 70.1, 57.7, 52.0, 47.3, 46.2, 37.4,
37.0, 36.14, 36.10, 34.9, 34.6, 32.1, 31.5, 30.4, 28.1, 27.8; HRMS (ESI)
m/z calcd for C18H21NNa [M + Na]+ 274.1572, found 274.1567.
1-Benzyl-2-ethynyl-4-heptyl-1-azaspiro[2.3]hexane (5h): yield 97%;
yellow oil; IR (neat) 3310, 2925, 2853, 1415 cmꢀ1; 1H NMR (400 MHz,
CDCl3) δ 7.42 (d, J = 7.6 Hz, 2H), 7.33 (t, J = 7.6 Hz, 2H), 7.25 (t, J = 7.6
Hz, 1H), 3.67 (d, J = 14.0 Hz, 1H), 3.45 (d, J = 14.0 Hz, 1H), 2.50 (d,
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J = 2.0 Hz, 1H), 2.38ꢀ2.24 (m, 4H), 2.08 (quint, J = 8.4 Hz, 1H),
1.52ꢀ1.43 (m, 2H), 1.31ꢀ1.14 (m, 11H), 0.87 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 139.6, 128.4, 128.2, 126.7, 79.6, 73.3, 52.3,
52.0, 42.3, 35.5, 31.9, 31.4, 29.7, 29.2, 27.0, 22.7, 21.8, 20.9, 14.1; HRMS
(ESI) m/z calcd for C21H29NNa [M + Na]+ 318.2198, found 318.2197.
1-Benzyl-2-ethynyl-4-phenethyl-1-azaspiro[2.3]hexane (5i): yield
98%; colorless oil; IR (neat) 3291, 2930, 1496, 1454 cmꢀ1; 1H NMR
(400 MHz, CDCl3) δ 7.42 (d, J = 7.2 Hz, 2H), 7.32 (t, J = 7.2 Hz, 2H),
7.24 (t, J = 7.6 Hz, 3H), 7.15 (t, J = 7.2 Hz, 1H), 7.09 (d, J = 7.6 Hz, 2H),
3.66 (d, J = 14.0 Hz, 1H), 3.47 (d, J = 14.0 Hz, 1H), 2.55 (t, J = 8.0 Hz,
2H), 2.50 (d, J = 1.6 Hz, 1H), 2.42ꢀ2.26 (m, 4H), 2.11 (quint, J = 8.0
Hz, 1H), 1.90ꢀ1.81 (m, 1H), 1.64ꢀ1.48 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 142.5, 139.5, 128.43, 128.40, 128.2, 128.1, 126.8, 125.6,
79.5, 73.4, 52.3, 51.9, 41.6, 34.5, 33.4, 33.3, 21.8, 20.8; HRMS (ESI) m/z
calcd for C22H24N [M + H]+ 302.1909, found 302.1909.
bromide (2.70 mL, 30.4 mmol) and HMPA (3.50 mL, 30.4 mmol) in
THF (5 mL) was then added dropwise to the stirred solution at the same
temperature, and then the mixture was allowed gradually to rt. After
being stirred for 1 h at rt, the reaction mixture was quenched with
saturated aqueous NH4Cl solution and extracted with Et2O. The
combined organic extracts were washed with saturated aqueous NaCl.
The residue upon workup was chromatographed on silica gel with
hexaneꢀAcOEt (90:10, v/v) as eluent to give the 2-pentynyl-1-azaspiro-
[2.3]hexane 1a (1.07 g, 88%) as colorless oil.
1-Benzyl-2-pent-1-ynyl-1-azaspiro[2,3]hexane (1a): yield 88%; col-
orless oil; 1:1 mixture of two invertomers; IR (neat) 3087, 3062, 3028,
2961, 2931, 2872, 2842, 2233, 1605, 1584, 1496, 1454, 1427, 1380,
1354 cmꢀ1 1H NMR (400 MHz, CDCl3) for the mixture of two
;
invertomers: δ 7.40 (d, J = 7.6 Hz, 2H), 7.35ꢀ7.29 (m, 2H), 7.24 (d, J =
7.6 Hz, 1H), 3.62 (d, J = 14.4 Hz, 0.5H), 3.58 (d, J = 14.4 Hz, 0.5H), 3.55
(d, J = 14.4 Hz, 0.5H), 3.52 (d, J = 14.4 Hz, 0.5H), 2.58 (s, 0.5H),
2.51ꢀ2.16 (m, 5.5H), 2.14ꢀ1.84 (m, 3H), 1.53 (dsext, J = 2.8, 7.6 Hz,
2H), 0.96 (t, J = 7.6 Hz, 3H); 3C NMR (100 MHz, CDCl3) for the 1:1
mixture of two invertomers: δ 139.9, 139.2, 128.1, 127.8, 127.3, 126.5,
126.4, 86.2, 82.7, 77.6, 75.0, 57.6, 51.8, 49.5, 48.4, 38.1, 35.6, 31.6, 28.9,
25.8, 24.2, 22.3, 22.1, 20.8, 20.8, 14.6, 14.3, 13.4, 13.3; HRMS (ESI): m/z
calcd for C17H21NNa [M + Na]+ 262.1572, found 262.1570.
1-Benzyl-2-pent-4-en-1-ynyl-1-azaspiro[2.3]hexane (1b): yield 67%;
colorless oil; 1:1 mixture of two invertomers; IR (neat) 3086, 3062, 3028,
2982, 2929, 2846, 2195, 1641, 1605, 1496, 1453, 1418, 1355 cmꢀ1; 1H
NMR (400 MHz, CDCl3) for the 1:1 mixture of two invertomers: δ 7.39
(d, J = 7.2 Hz, 2H), 7.33 (t, J = 7.2 Hz, 2H), 7.25ꢀ7.21 (m, 1H),
5.85ꢀ5.77 (m, 1H), 5.34ꢀ5.26 (m, 1H), 5.13ꢀ5.08 (m, 1H) 3.63 (d, J =
14.4 Hz, 0.5H), 3.57 (d, J = 14.4 Hz, 0.5H), 3.54 (d, J = 14.4 Hz, 0.5H),
3.50 (d, J = 14.4 Hz, 0.5H), 3.04 (t, J = 7.6 Hz, 1H), 2.99 (t, J = 7.6 Hz,
1H), 2.62 (s, 0.5H), 2.48ꢀ2.31 (m, 3H), 2.20ꢀ2.10 (m, 1H), 2.01ꢀ1.87
(m, 2.5H); 13C NMR (100 MHz, CDCl3) for the 1:1 mixture of two
invertomers: δ 139.8, 139.1, 132.6, 132.5, 128.2, 127.8, 127.4, 126.6,
126.5, 116.0, 115.9, 82.6, 79.9, 79.2, 77.5, 57.6, 51.9, 49.7, 48.6, 37.9, 35.5,
31.4, 29.0, 25.9, 24.3, 23.3, 23.1, 14.6, 14.3; HRMS (ESI): m/z calcd for
C17H19NNa [M + Na]+ 260.1415, found 260.1413.
1-Benzyl-3-ethynyl-30-oxaspiro(aziridine-2,60-bicyclo[3.2.0]heptane)
(5j): yield 98%; colorless needles; mp 64.2ꢀ65.3 °C [AcOEtꢀhexane
1
(2:1)]; IR (neat) 3287, 2849, 1354, 1076, 906 cmꢀ1; H NMR (400
MHz, CDCl3) δ 7.41 (d, J = 7.2 Hz, 2H), 7.33 (t, J = 7.2 Hz, 2H), 7.25 (t,
J = 7.2 Hz, 1H), 4.20 (d, J = 9.2 Hz, 1H), 3.90 (d, J = 8.8 Hz, 1H), 3.65
(d, J = 13.6 Hz, 1H), 3.50ꢀ3.42 (m, 2H), 3.45 (d, J = 13.6 Hz, 1H),
2.99ꢀ2.93 (m, 1H), 2.91ꢀ2.87 (m, 1H), 2.59 (s, 1H), 2.53 (ddd, J = 2.0,
8.8, 13.4 Hz, 1H), 2.35 (d, J = 2.0 Hz, 1H), 2.10 (dd, J = 5.2, 13.4 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 139.2, 128.3, 128.2, 126.8, 78.8, 74.4,
73.7, 69.7, 51.9, 47.6, 47.1, 35.8, 33.4, 28.0; HRMS (ESI) m/z calcd for
C16H18NO [M + H]+ 240.1388, found 240.1386.
1-Benzyl-3-ethynylspiro(aziridine-2,60-bicyclo[3.2.0]heptane) (5k):
yield 89%; yellow oil; IR (neat) 3300, 2949, 2853, 2117, 1496, 1454,
1355, 1092 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.2 Hz,
2H), 7.33 (t, J = 7.2 Hz, 2H), 7.25 (t, J = 7.2 Hz, 1H), 3.60 (d, J = 14.0 Hz,
1H), 3.43 (d, J = 14.0 Hz, 1H), 2.76ꢀ2.66 (m, 2H), 2.52 (d, J = 1.6 Hz,
1H), 2.49 (ddd, J = 1.6, 8.4, 13.6 Hz, 1H), 2.31 (d, J = 1.6 Hz, 1H),
1.84ꢀ1.73 (m, 2H), 1.64ꢀ1.52 (m, 2H), 1.48ꢀ1.26 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 139.6, 128.4, 128.2, 126.8, 79.4, 73.7, 52.3, 48.6,
46.4, 35.9, 33.2, 32.6, 28.0, 27.9, 24.3; HRMS (ESI) m/z calcd for
C17H20N [M + H]+ 238.1596, found 238.1597.
1-Benzyl-3-ethynylspiro(aziridine-2,70-bicyclo[4.2.0]octane) (5l): yield
87%; colorless oil; 4:1 mixture of two invertomers; IR (neat) 3296, 2930,
2854, 1496, 1451, 1356 cmꢀ1; 1H NMR (400 MHz, CDCl3) for 4:1 mixture
of two invertomers: δ 7.42ꢀ7.37 (m, 2H), 7.35ꢀ7.31 (m, 2H), 7.26ꢀ7.23
(m, 1H), 4.19 (d, J = 14.4 Hz, 0.2H), 3.62 (d, J = 13.6 Hz, 0.8H), 3.50 (d, J =
13.6 Hz, 0.8H), 3.07 (d, J = 14.4 Hz, 0.2H), 2.60 (d, J = 1.6 Hz, 1H),
2.53ꢀ2.41 (m, 1.4H), 2.35ꢀ2.29 (m, 1.6H), 2.35ꢀ2.29 (m, 2H), 2.12ꢀ1.94
(m, 0.8H), 1.78ꢀ1.60 (m, 2H), 1.56ꢀ1.43 (m, 2.2H), 1.37ꢀ1.24 (m, 2H),
1.09ꢀ0.99 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 139.4, 128.5, 128.2,
126.8, 79.7, 73.5, 52.9, 51.6, 39.4, 34.2, 27.0, 26.1, 26.1, 23.8, 22.4, 21.4;
HRMS (ESI) m/z calcd for C18H22N [M + H]+ 252.1752, found 252.1750.
1-Benzyl-2-ethynyl-1-azaspiro[2.4]heptane (5m): yield 79%; yellow-
ish oil; 1:1 mixture of two invertomers; IR (neat): 3293, 3062, 3029, 2957,
2868, 2118, 1605, 1496, 1453, 1356 cmꢀ1; 1H NMR (400 MHz, CDCl3)
for the 1:1 mixture of two invertomers: δ 7.39 (2H, d, J = 7.2 Hz), 7.34
(2H, t, J = 7.2 Hz), 7.25ꢀ7.21 (1H, m), 3.77 (0.5H, d, J = 14.4 Hz), 3.76
(0.5H, d, J = 14.4 Hz), 3.60 (0.5H, d, J = 14.4 Hz), 3.57 (0.5H, d, J = 14.4
Hz), 2.62 (1H, d, J = 1.6 Hz), 2.35 (1H, d, J = 2.0 Hz), 2.21(1H, d, J = 2.0
Hz), 2.01ꢀ1.94 (1H, m), 1.85ꢀ1.63 (6H, m); 13C NMR (100 MHz,
CDCl3) for the 1:1 mixture of two invertomers: δ 139.6, 139.1, 128.1,
127.6, 127.1, 126.5, 126.4, 82.0, 79.4, 73.9, 70.5, 57.8, 53.9, 53.0, 52.0, 38.7,
36.09, 36.04, 32.5, 26.4, 25.7, 25.5, 24.7, 24.4, 23.9; HRMS (ESI): m/z
calcd for C15H17NNa [M + Na]+ 234.1259; found 234.1254.
1-Benzyl-2-hept-6-en-1-ynyl-1-azaspiro[2.3]hexane (1c): yield 62%;
yellow oil; 1:1 mixture of two invertomers; IR (neat) 3063, 3029, 2930,
2857, 2232, 1640, 1605, 1496, 1453, 1354 cmꢀ1; 1H NMR (400 MHz,
CDCl3) for the 1:1 mixture of two invertomers:δ 7.39 (d, J = 7.2 Hz, 2H),
7.32 (t, J = 7.2 Hz, 2H), 7.25ꢀ7.21 (m, 1H), 5.84ꢀ5.73 (m, 1H),
5.05ꢀ4.96 (m, 2H), 3.60 (d, J = 14.4 Hz, 0.5H), 3.57 (d, J = 14.4 Hz,
0.5H), 3.52 (d, J = 14.4 Hz, 0.5H), 3.50 (d, J = 14.4 Hz, 0.5H), 2.58 (s,
0.5H), 2.51ꢀ2.08 (m, 8H), 2.06ꢀ1.84 (m, 2.5H), 1.60 (quint, J = 7.6 Hz,
2H); 13C NMR (100 MHz, CDCl3) for the 1:1 mixture of two
invertomers: δ 139.8, 139.2, 137.8, 137.6, 128.2, 127.8, 127.3, 126.6,
126.5, 115.1, 114.9, 86.0, 82.5, 77.8, 75.2, 57.6, 51.8, 49.6, 48.4, 38.0, 35.6,
32.7, 32.6, 31.3, 28.9, 28.0, 27.9, 25.8, 24.2, 18.3, 18.1, 14.6, 14.3; HRMS
(ESI) m/z calcd for C19H23NNa [M + Na]+ 288.1728, found 288.1722.
1-Benzyl-2-(7-phenylhepta-1,6-diynyl)-1-azaspiro[2.3]hexane (1d):
yield 68%; colorless oil; 1:1 mixture of two invertomers; IR (neat) 2933,
1490 cmꢀ1 1H NMR (400 MHz, CDCl3) for 1:1 mixture of two
;
invertomers: δ 7.41ꢀ7.23 (m, 10H), 3.63ꢀ3.50 (m, 2H), 2.59ꢀ1.77
(m, 13H); 13C NMR (100 MHz, CDCl3) for 1:1 mixture of two
invertomers: δ 139.8, 139.2, 131.5, 128.25, 128.17, 128.14, 127.8,
127.6, 127.5, 127.4, 126.7, 126.5, 123.8, 123.8, 89.2, 88.9, 85.3, 81.8,
81.3, 81.1, 78.3, 75.8, 57.7, 51.9, 49.7, 48.6, 38.0, 35.6, 31.4, 29.0, 28.0,
25.9, 24.3, 18.6, 18.5, 18.2, 18.1, 14.7, 14.4; HRMS (ESI) m/z calcd for
C25H24N [M ꢀ H]+ 338.1909, found 338.1907.
General Procedure for the Synthesis of 2-Alkynyl-1-
azaspiro[2.3]hexanes 1. Synthesis of 1a. To a stirred solution of
propargylic aziridine 5a (1.00 g, 5.07 mmol) in THF (25 mL) was added
slowly a 2.7 M hexane solution of n-BuLi (5.60 mL, 15.2 mmol) at
ꢀ78 °C. After stirring was continued for 1 h, a solution of n-propyl
1-Benzyl-2-[5-(tert-butyldiphenylsilanyloxy)pent-1-ynyl]-1-azaspiro-
[2.3]hexane (1e): yield 55%; colorless oil; 1:1 mixture of two inverto-
mers; IR (neat) 3069, 3028, 2980, 2930, 2856, 2234, 1656, 1605, 1589,
1567, 1496, 1471, 1427, 1390, 1359 cmꢀ1; 1H NMR (400 MHz, CDCl3)
for the 1:1 mixture of two invertomers: δ 7.71ꢀ7.65 (m, 4H),
5817
dx.doi.org/10.1021/jo201000f |J. Org. Chem. 2011, 76, 5813–5820

The Journal of Organic Chemistry
ARTICLE
7.42ꢀ7.24 (m, 10H), 7.22 (t, J = 7.2 Hz, 1H), 3.73 (t, J = 6.4 Hz, 2H),
3.55 (d, J = 14.4 Hz, 1H), 3.45 (d, J = 14.4 Hz, 1H), 2.55 (s, 0.5H),
2.50ꢀ2.31 (m, 3.5H), 2.30ꢀ2.19 (m, 2H), 2.17ꢀ1.83 (m, 3H),
1.77ꢀ1.72 (m, 2H), 1.05 (s, 4.5H), 1.04 (s, 4.5H); 13C NMR (100
MHz, CDCl3) for the 1:1 mixture of two invertomers: δ 139.8, 139.2,
135.5, 135.5, 134.7, 133.8, 133.8, 129.5, 129.5, 129.5, 128.2, 128.2, 127.8,
127.6, 127.5, 127.5, 127.4, 126.6, 126.5, 85.9, 82.5, 77.6, 75.1, 62.5, 62.3,
57.6, 51.8, 49.6, 48.4, 38.0, 35.6, 31.84, 31.79, 31.36, 29.00, 26.82, 26.55,
25.88, 24.29, 19.20, 15.54, 15.37, 14.65, 14.33; HRMS (ESI) m/z calcd
for C33H39NNaOSi [M + Na]+ 516.2699, found 516.2698.
1-Benzyl-5-(but-3-enyl)-2-(pent-1-ynyl)-1-azaspiro[2.3]hexane (1g):
yield 91%; colorless oil; 1:1 mixture of two invertomers; IR (neat) 2961,
2928, 1639, 1497, 1454, 1354 cmꢀ1; 1H NMR (400 MHz, CDCl3) for the
1:1 mixture of two invertomers: δ 7.40ꢀ7.38 (m, 2H), 7.34ꢀ7.31 (m,
2H), 7.26ꢀ7.20 (m, 1H), 5.85ꢀ5.74 (m, 1H), 5.02ꢀ4.93 (m, 2H),
3.61ꢀ3.46 (m, 2H), 2.58 (s, 0.5H), 2.44ꢀ2.16 (m, 5H), 2.06ꢀ1.86 (m,
4.5H), 1.56ꢀ1.48 (m, 4H), 0.97 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) for the 1:1 mixture of two invertomers: δ 139.9, 139.2, 138.5,
128.2, 127.9, 127.4, 126.6, 126.5, 114.4, 86.4, 82.9, 77.7, 75.1, 57.7, 51.9,
46.9, 45.8, 38.0, 37.5, 36.3, 36.2, 35.5, 35.0, 32.1, 31.6, 30.5, 28.2, 27.8, 22.3,
22.2, 20.9, 20.8, 13.4; HRMS (ESI) m/z calcd for C21H26N [M ꢀ H]+
292.2065, found 292.2060.
1-Benzyl-4-heptyl-2-(pent-1-ynyl)-1-azaspiro[2.3]hexane (1h): yield
81%; colorless oil; IR (neat) 2959, 2926, 1455, 729 cmꢀ1; 1H NMR (400
MHz, CDCl3) δ 7.41 (d, J = 7.2 Hz, 2H), 7.32 (t, J = 7.2 Hz, 2H), 7.23 (t,
J = 7.2 Hz, 1H), 3.62 (d, J = 14.4 Hz, 1H), 3.41 (d, J = 14.4 Hz, 1H), 2.49
(s, 1H), 2.34ꢀ2.21 (m, 5H), 2.11ꢀ2.02 (m, 1H), 1.58ꢀ1.42 (m, 5H),
1.38ꢀ1.12 (m, 10H), 0.98 (t, J = 7.6 Hz, 3H), 0.87 (t, J = 7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 140.0, 128.4, 128.1, 126.6, 86.0, 75.4, 52.2,
51.6, 42.3, 35.47, 31.9, 31.4, 29.7, 29.2, 27.0, 22.7, 22.4, 21.9, 20.9, 20.8,
14.1, 13.4; HRMS (ESI) m/z calcd for C24H36N [M + H]+ 338.2848,
found 338.2849.
27.9, 24.4, 22.4, 20.9, 13.4; HRMS (ESI) m/z calcd for C20H26N [M +
H]+ 280.2065, found 280.2065.
1-Benzyl-3-(pent-1-ynyl)spiro(aziridine-2,70-bicyclo[4.2.0]octane) (1l):
yield 82%; colorless oil; 85:15 mixture of two invertomers; IR (neat)
2930, 2854, 1496, 1452, 1355 cmꢀ1; 1H NMR (400 MHz, CDCl3) for
85:15 mixture of two invertomers: δ 7.41ꢀ7.38 (m, 2H), 7.34ꢀ7.30
(m, 2H), 7.25ꢀ7.21 (m, 1H), 4.17 (d, J = 14.4 Hz, 0.15H), 3.58 (d, J =
13.6 Hz, 0.85H), 3.46 (d, J = 13.6 Hz, 0.85H), 3.08 (d, J = 14.4 Hz,
0.15H), 2.59 (s, 0.85H), 2.53ꢀ2.40 (m, 1.3H), 2.32ꢀ2.14 (m, 4.85H),
1.76ꢀ1.62 (m, 1H), 1.58ꢀ1.48 (m, 7H), 1.38ꢀ1.28 (m, 2H), 0.97
(t, J = 7.6 Hz, 2.55H), 0.97 (t, J = 7.2 Hz, 0.45H); 13C NMR (100 MHz,
CDCl3) δ 139.9, 128.6, 128.2, 126.6, 86.2, 75.6, 52.8, 51.2, 39.4, 35.2,
27.0, 26.1, 26.1, 23.9, 22.5, 22.4, 21.5, 20.9, 13.4; HRMS (ESI) m/z calcd
for C21H27NNa [M + Na]+ 316.2041, found 316.2040.
1-Benzyl-2-(pent-1-ynyl)-1-azaspiro[2.4]heptane (1m): yield 80%;
colorless oil; 1:1 mixture of two invertomers; IR (neat) 3086, 3063,
3029, 2968, 2932, 2872, 2233, 1605, 1587, 1496, 1451, 1429, 1382,
1
1354 cmꢀ1; H NMR (400 MHz, CDCl3) for the 1:1 mixture of two
invertomers: δ 7.37 (2H, d, J = 7.2 Hz), 7.30 (2H, t, J = 7.2 Hz), 7.21
(1H, t, J = 7.2 Hz), 3.78 (0.5H, d, J = 14.4 Hz), 3.74 (0.5H, d, J = 14.4
Hz), 3.54 (0.5H, d, J = 14.4 Hz), 3.53 (0.5H, d, J = 14.4 Hz), 2.61 (0.5H,
t, J = 2.0 Hz), 2.24ꢀ2.17 (2H, m), 1.99ꢀ1.81 (1H, m), 1.79ꢀ1.70 (2H,
m), 1.67ꢀ1.66 (5.5H, m), 1.56ꢀ1.50 (2H, m), 0.98 (3H, t, J = 7.2 Hz);
13C NMR (100 MHz, CDCl3) for the 1:1 mixture of two invertomers: δ
140.1, 139.6, 128.1, 128.1, 127.8, 127.2, 126.4, 126.4, 86.6, 83.2, 77.9,
75.4, 57.9, 53.7, 52.6, 52.0, 39.8, 37.1, 36.2, 32.6, 26.6, 25.9, 25.6, 24.9,
24.6, 24.0, 22.3, 22.1, 20.9, 20.8, 13.4, 13.3; HRMS (ESI): m/z calcd for
C18H23NNa [M + Na]+ 276.1728, found 276.1726.
1-Benzyl-2-[5-(tert-butyldiphenylsilyloxy)pent-1-ynyl]-1-azaspiro-
[2.4]heptane (1n): yield 50%; colorless oil; 1:1 mixture of two inverto-
mers; IR (neat) 3069, 3028, 2980, 2955, 2856, 2234, 1605, 1589, 1496,
1471, 1453, 1428, 1390, 1359 cmꢀ1; 1H NMR (400 MHz, CDCl3) for
the 1:1 mixture of two invertomers: δ 7.58 (4H, d, J = 7.2 Hz),
7.35ꢀ7.10 (11H, m), 3.71 (0.5H, d, J = 14.4 Hz), 3.67 (2H, t, J = 6.4
Hz), 3.60 (0.5H, d, J = 14.4 Hz), 3.44 (0.5H, d, J = 16.4 Hz), 3.40 (0.5H,
d, J = 14.8 Hz), 2.51 (0.5H, s), 2.36ꢀ2.27 (2H, m), 1.89ꢀ1.82 (1H, m),
1.71ꢀ1.63 (4H, m), 1.61ꢀ1.55 (5.5H, m), 0.97 (4.5H, s), 0.96 (4.5H,
s); 13C NMR (100 MHz, CDCl3) for the 1:1 mixture of two inverto-
mers: δ 140.1, 139.6, 135.5, 135.5, 133.9, 133.8, 129.5, 129.5, 128.1,
127.8, 127.6, 127.5, 127.2, 126.5, 126.4, 86.2, 82.9, 78.0, 77.2, 75.5, 62.5,
62.4, 58.0, 53.7, 52.7, 52.0, 39.8, 37.1, 36.2, 32.7, 31.8, 31.8, 26.8, 26.6,
25.9, 25.7, 24.9, 24.6, 24.1, 19.2, 15.5, 15.4, 14.1, 14.0; HRMS (ESI) m/z
calcd for C34H41NNaOSi [M + Na]+ 530.2855, found 530.2851.
5-(1-Benzyl-1-azaspiro[2.3]hex-2-yl)pent-4-yn-1-ol (1f). To a stir-
red solution of propargylic aziridine 1e (85.0 mg, 0.172 mmol) in THF
(5.0 mL) was added 1.0 M THF solution of TBAF (0.7 mL, 0.699
mmol) at 0 °C, and after that the reaction mixture was allowed to warm
rt with stirring. After being stirred for 1.5 h at the same temperature, the
reaction mixture was poured into aq satd NH4Cl solution. The aqueous
layer was extracted with AcOEt (3 ꢁ 15 mL). The combined organic
extracts were washed with brine (2 ꢁ 15 mL) and dried over MgSO4.
After solvent evaporation at reduced pressure, the residue was chroma-
tographed on silica gel with hexaneꢀAcOEt (65:35) as eluent to give the
propargylic aziridine 1f (38.7 mg, 88%) as a colorless oil as a 1:1 mixture
of two invertomers: IR (neat): 3317, 3088, 3062, 3029, 2929, 2850,
2235, 1605, 1497, 1453, 1428, 1355 cmꢀ1; 1H NMR (400 MHz, CDCl3)
for the 1:1 mixture of two invertomers: δ 7.39ꢀ7.37 (2H, m),
7.34ꢀ7.31 (2H, m), 7.26ꢀ7.23 (1H, m), 3.71ꢀ3.65 (2H, m), 3.61
(0.5H, d, J = 14.4 Hz), 3.59 (0.5H, d, J = 14.4 Hz), 3.53 (0.5H, d, J = 14.4
Hz), 3.49 (0.5H, d, J = 14.4 Hz), 2.58 (0.5H, s), 2.49ꢀ2.25 (5H, m),
2.22ꢀ2.10 (2H, m), 2.03ꢀ1.89 (2.5H, m), 1.75ꢀ1.67 (2H, m); 13C
NMR (100 MHz, CDCl3) for the 1:1 mixture of two invertomers: δ
139.7, 139.0, 134.7, 128.2, 128.2, 127.7, 127.3, 126.7, 126.5, 85.6, 82.1,
78.0, 75.3, 61.3, 61.3, 57.5, 51.8, 49.7, 48.5, 38.0, 35.5, 31.5, 31.3, 31.2,
1-Benzyl-2-(pent-1-ynyl)-4-phenethyl-1-azaspiro[2.3]hexane (1i):
1
yield 92%; colorless oil; IR (neat) 2931, 1496, 1454, 733 cmꢀ1; H
NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.2 Hz, 2H), 7.31 (t, J = 7.2 Hz,
2H), 7.26ꢀ7.22 (m, 3H), 7.15 (t, J = 7.2 Hz, 1H), 7.09 (d, J = 7.2 Hz,
2H), 3.61 (d, J = 14.0 Hz, 1H), 3.44 (d, J = 14.0 Hz, 1H), 2.55 (t, J = 8.0
Hz, 2H), 2.49 (s, 1H), 2.38ꢀ2.21 (m, 5H), 2.15ꢀ2.04 (m, 1H),
1.91ꢀ1.82 (m, 1H), 1.64ꢀ1.45 (m, 4H), 0.98 (t, J = 7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 142.6, 140.0, 128.4, 128.4, 128.2, 128.1,
126.6, 125.5, 86.1, 75.3, 52.2, 51.4, 41.7, 35.4, 33.5, 33.4, 22.4, 21.9, 20.9,
20.8, 13.4; HRMS (ESI) m/z calcd for C25H29NNa [M + Na]+
366.2198, found 366.2201.
1-Benzyl-3-(pent-1-ynyl)-30-oxaspiro(aziridine-2,60-bicyclo[3.2.0]-
heptane) (1j): yield 64%; yellow oil; IR (neat) 2962, 2846, 1497,1454,
1354, 1266, 1075 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 7.2
Hz, 2H), 7.32 (t, J = 7.2 Hz, 2H), 7.23 (t, J = 7.2 Hz, 1H), 4.21 (d, J = 9.6
Hz, 1H), 3.89 (d, J = 8.8 Hz, 1H), 3.60 (d, J = 13.6 Hz, 1H), 3.50ꢀ3.42
(m, 2H), 3.45 (d, J = 13.6 Hz, 1H), 2.97ꢀ2.91 (m, 1H), 2.88ꢀ2.85 (m,
1H), 2.58 (t, J = 1.6 Hz, 1H), 2.49 (ddd, J = 1.6, 8.8, 13.0 Hz, 1H), 2.23
(dt, J = 1.6, 7.2 Hz, 2H), 2.06 (dd, J = 4.8, 13.0 Hz, 1H), 1.53 (sext, J = 7.2
Hz, 2H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 139.7,
128.4, 128.2, 126.7, 87.1, 74.7, 73.8, 69.7, 51.8, 47.2, 47.1, 36.7, 33.5,
28.1, 22.3, 20.8, 13.4; HRMS (ESI) m/z calcd for C19H24NO [M + H]+
282.1858, found 282.1862.
1-Benzyl-3-(pent-1-ynyl)spiro(aziridine-2,60-bicyclo[3.2.0]heptane)
(1k): yield 93%; yellow oil; IR (neat) 2957, 1496, 1454, 1354,
1090 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 6.8 Hz, 2H),
7.32 (t, J = 6.8 Hz, 2H), 7.23 (t, J = 6.8 Hz, 1H), 3.56 (d, J = 14.0 Hz, 1H),
3.40 (d, J = 14.0 Hz, 1H), 2.74ꢀ2.65 (m, 2H), 2.50 (d, J = 1.6 Hz, 1H),
2.49 (ddd, J = 2.4, 8.4, 13.4 Hz, 1H), 2.23 (dt, J = 1.6, 7.2 Hz, 2H), 1.80
(dd, J = 4.4, 11.8 Hz, 1H), 1.71 (dd, J = 4.4, 13.4 Hz, 1H), 1.63ꢀ1.24 (m,
7H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 140.0,
128.5, 128.2, 126.7, 86.5, 75.3, 52.1, 48.1, 46.4, 36.8, 33.2, 32.6, 28.1,
5818
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ARTICLE
29.6, 28.9, 25.8, 24.2, 15.4, 15.3, 14.6, 14.3; HRMS (ESI) m/z calcd for
C17H21NONa [M + Na]+ 278.1521; found 278.1526.
(s, 2H), 3.64 (t, J = 6.4 Hz, 2H), 2.63 (t, J = 6.8 Hz, 2H), 2.57ꢀ2.52
(m, 4H), 2.39ꢀ2.32 (m, 2H), 1.78 (quint, J = 7.2 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 138.6, 137.8, 135.3, 128.6, 127.1, 126.2, 124.5,
100.9, 62.4, 48.4, 32.1, 28.6, 25.7, 24.8, 23.2; HRMS (ESI) m/z calcd for
C17H21NNaO [M + Na]+ 278.1521, found 278.1520.
General Procedure for the Synthesis of Pyrroles from
Propargylic Aziridines Using Platinum Catalyst. Synthesis of
2a. To a stirred solution of propargylic aziridine 1a (90.0 mg, 0.376
mmol) in dioxane was added PtCl2 (10.0 mg, 0.0380 mmol) at rt. After
stirring was continued for 40 min at 100 °C, the resulting mixture was
cooled to rt and diluted with a minimum amount of Et2O. The solution
was then filtered through a small amount of silica gel. Concentration at
reduced pressure gave the residue, which was chromatographed on silica
gel with hexaneꢀAcOEt (98:2) as eluent to give the pyrrole 2a (87.3 mg,
97%) as a yellow oil.
1-Benzyl-2-propyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole (2a): yield
97%; yellow oil; IR (neat) 3066, 3028, 2929, 2851, 1605, 1597, 1496,
1453, 1425, 1376, 1352 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.31ꢀ7.21
(m, 3H), 6.98(d, J =7.2 Hz, 2H), 5.76 (s, 1H), 4.94(s, 2H), 2.63 (t, J =6.8
Hz, 2H), 2.52 (t, J = 7.2 Hz, 2H), 2.42 (t, J = 7.2 Hz, 2H), 2.38ꢀ2.31 (m,
2H), 1.56 (sext, J = 7.2 Hz, 2H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 138.7, 137.3, 136.4, 128.6, 127.0, 126.2, 124.4, 100.7,
48.4, 29.1, 28.6, 25.7, 24.8, 22.5, 14.0; HRMS (ESI) m/z calcd for
C17H21NNa [M + Na]+ 262.1572, found 262.1571.
1-Benzyl-2-pent-4-enyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole (2b):
yield 91%; yellow oil; IR (neat) 2843, 1640, 1605, 1584, 1496, 1453,
1354 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.29 (t, J = 7.2 Hz, 2H), 7.23
(t, J = 7.2 Hz, 1H), 6.98 (d, J = 7.2 Hz, 2H), 5.93ꢀ5.83 (m, 1H), 5.76 (s,
1H), 5.06ꢀ4.99 (m, 2H), 4.95(s, 2H), 3.22 (d, J = 6.4 Hz, 2H), 2.63 (t, J =
6.8 Hz, 2H), 2.53 (t, J = 6.8 Hz, 2H), 2.35 (quint, J = 6.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 138.6, 138.1, 136.2, 133.4, 128.6, 127.1,
126.3, 124.6, 115.6, 101.9, 48.5, 31.9, 28.6, 25.7, 24.9; HRMS (ESI) m/z
calcd for C17H19NNa [M + Na]+ 260.1415, found 260.1413.
1-Benzyl-2-pent-4-enyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole (2c):
yield 90%; yellow oil; IR (neat) 2851, 1639, 1605, 1497, 1478, 1452,
1388, 1354cmꢀ1; 1H NMR (400 MHz, CDCl3) δ7.29 (t, J = 7.2Hz, 2H),
7.22 (t, J = 7.2 Hz, 1H), 6.98 (d, J = 7.2 Hz, 2H), 5.80ꢀ5.70 (m, 1H), 5.76
(s, 1H), 4.99ꢀ4.91 (m, 4H), 2.63 (t, J = 6.8 Hz, 2H), 2.52 (t, J = 6.8 Hz,
2H), 2.43 (t, J = 6.8 Hz, 2H), 2.39ꢀ2.32 (m, 2H), 2.07 (q, J = 7.2Hz, 2H),
1.62 (quint, J = 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 138.7,
138.4, 137.4, 136.0, 128.6, 127.0, 126.2, 124.5, 114.6, 100.8, 48.4, 33.3,
28.6, 28.4, 26.3, 25.7, 24.8; HRMS (ESI): m/z calcd for C19H23NNa
[M + Na]+ 288.1728, found 288.1726.
1-Benzyl-5-(but-3-enyl)-2-propyl-1,4,5,6-tetrahydrocyclopenta[b]-
1
pyrrole (2g): yield 75%; yellow oil; IR (neat) 2925, 1454 cmꢀ1; H
NMR (400 MHz, CDCl3) δ 7.30 (t, J = 7.2 Hz, 2H), 7.23 (t, J = 7.2 Hz,
1H), 6.97 (d, J = 7.2 Hz, 2H), 5.87ꢀ5.77 (m, 1H), 5.73 (s, 1H),
5.02ꢀ4.91 (m, 2H), 4.93 (s, 2H), 2.86ꢀ2.77 (m, 2H), 2.69 (dd, J = 7.6,
14.0 Hz, 1H), 2.41 (t, J = 7.2 Hz, 2H), 2.35ꢀ2.28 (m, 1H), 2.22 (dd, J =
6.4, 14.0 Hz, 1H), 2.08 (q, J = 7.2 Hz, 2H), 1.68ꢀ1.51 (m, 4H), 0.92 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 139.0, 138.8, 136.1,
136.0, 128.6, 127.1, 126.2, 123.2, 114.2, 100.8, 48.3, 43.8, 36.0, 32.7, 32.4,
31.6, 29.1, 22.5, 14.1; HRMS (ESI) m/z calcd for C21H28N [M + H]+
294.2222, found 294.2224.
1-Benzyl-4-heptyl-2-propyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole
(2h): yield 81%; yellow oil; IR (neat) 2926, 1672, 1455 cmꢀ1; 1H NMR
(400 MHz, CDCl3) δ 7.31ꢀ7.21 (m, 3H), 6.97 (d, J = 7.2 Hz, 2H), 5.77
(s, 1H), 4.93 (s, 2H), 2.99ꢀ2.90 (m, 1H), 2.57ꢀ2.39 (m, 5H),
1.94ꢀ1.87 (m, 1H), 1.61ꢀ1.52 (m, 2H), 1.48ꢀ1.17 (m, 12H), 0.92
(t, J = 7.2 Hz, 3H), 0.89 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 138.8, 136.6, 135.9, 128.9, 128.6, 127.0, 126.2, 100.6, 48.3,
39.4, 37.5, 36.1, 31.9, 29.9, 29.4, 29.2, 28.2, 24.4, 22.7, 22.3, 14.1; HRMS
(ESI) m/z calcd for C24H36N [M + H]+ 338.2848, found 338.2850. The
regiochemistryof2hwas determinedunambiguously byNOE correlation.
1-Benzyl-4-phenethyl-2-propyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole
(2i): yield 75%; yellow oil; IR (neat) 2929, 1671, 1455 cmꢀ1; 1H NMR
(400 MHz, CDCl3) δ 7.31ꢀ7.22 (m, 7H), 7.16 (t, J = 6.8 Hz, 1H), 6.97
(d, J = 6.8 Hz, 2H), 5.82 (s, 1H), 4.94 (s, 2H), 3.01 (quint, J = 6.8 Hz,
1H), 2.84ꢀ2.69 (m, 2H), 2.59ꢀ2.40 (m, 5H), 1.98ꢀ1.72 (m, 3H), 1.57
(sext, J = 7.6 Hz, 2H), 0.93 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 143.1, 138.8, 136.7, 136.1, 128.6, 128.5, 128.4, 128.2, 127.0,
126.2, 125.5, 100.7, 48.3, 39.3, 39.0, 36.0, 34.5, 29.2, 24.4, 22.3, 14.1;
HRMS (ESI) m/z calcd for C25H30N [M + H]+ 344.2378, found
344.2376.
1-Benzyl-2-propyl-3b,4,5,6,6a,7-hexahydro-1H-pentalenofuran-[2,1b]
pyrrole (2j): yield 81%; yellow oil; IR (neat) 2956, 2846, 1454, 923 cmꢀ1
;
1H NMR (400 MHz, CDCl3) δ 7.32ꢀ7.22 (m, 3H), 6.96 (d, J = 6.8 Hz,
2H), 5.72 (s, 1H), 4.91 (s, 2H), 3.95ꢀ3.90 (m, 2H), 3.72 (dd, J = 4.0, 8.6
Hz, 1H), 3.66ꢀ3.61 (m, 1H), 3.49 (dd, J = 5.6, 8.6 Hz, 1H), 3.37ꢀ3.29
(m, 1H), 2.76 (dd, J = 8.6, 15.0 Hz, 1H), 2.40 (t, J = 7.6 Hz, 2H), 2.34 (d,
J = 15.0 Hz, 1H), 1.55 (sext, J = 7.6 Hz, 2H), 0.92 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 138.5, 137.5, 135.4, 128.7, 127.2, 126.2,
126.0, 100.0, 75.1, 74.0, 48.5, 48.3, 45.0, 30.2, 29.2, 22.3, 14.0; HRMS
(ESI) m/z calcd for C19H24NO [M + H]+ 282.1858, found 282.1857.
1-Benzyl-2-propyl-3b,4,5,6,6a,7-hexahydro-1H-pentaleno[2,1b]pyrrole
(2k): yield 80%; yellow oil; IR (neat) 2938, 2859, 1497, 1451, 1391,
1354 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.31ꢀ7.21 (m, 3H), 6.94
(d, J = 7.6 Hz, 2H), 5.69 (s, 1H), 4.90 (s, 2H), 3.42ꢀ3.36 (m, 1H),
3.19ꢀ3.11 (m, 1H), 2.81 (dd, J = 8.4, 14.6 Hz, 1H), 2.39 (t, J = 7.6 Hz,
2H), 2.19 (d, J = 14.6 Hz, 1H), 1.83ꢀ1.71 (m, 2H), 1.61ꢀ1.34 (m, 5H),
1.41ꢀ1.34 (m, 1H), 0.91 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 138.9, 136.8, 135.6, 128.6, 128.4, 127.0, 126.1, 99.9, 48.2, 47.8,
43.8, 35.4, 33.5, 32.7, 29.2, 26.3, 22.3, 14.1; HRMS (ESI) m/z calcd for
C20H26N [M + H]+ 280.2065, found 280.2065.
1-Benzyl-2-(5-phenylpent-4-ynyl)-1,4,5,6-tetrahydrocyclopenta[b]-
pyrrole (2d): yield 79%; yellow oil; IR (neat) 2934, 2850, 1490, 1452,
1388, 1353 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.34ꢀ7.20 (m, 8H),
6.98 (d, J = 6.8 Hz, 2H), 5.81 (s, 1H), 4.98 (s, 2H), 2.64 (t, J = 7.2 Hz,
4H), 2.55 (t, J = 6.8 Hz, 2H), 2.43 (t, J = 6.8 Hz, 2H), 2.39ꢀ2.32 (m,
2H), 1.82 (quint, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
138.7, 137.7, 135.2, 131.5, 128.6, 128.2, 127.5, 127.1, 126.2, 124.6, 123.9
101.2, 89.8, 81.1, 48.5, 28.7, 28.3, 26.0, 25.8, 24.9, 19.0; HRMS (ESI)
m/z calcd for C25H25NNa [M + Na]+ 362.1885, found 362.1881.
1-Benzyl-2-[3-(tert-butyldiphenylsilanyloxy)propyl]-1,4,5,6-tetrahy-
drocyclopenta[b]pyrrole (2e): yield 89%; yellow oil; IR (neat) 2926,
1
1589, 1517, 1471, 1453, 1359 cmꢀ1; H NMR (400 MHz, CDCl3) δ
7.63ꢀ7.61 (m, 4H), 7.40ꢀ7.38 (m, 2H), 7.36ꢀ7.32 (m, 4H),
7.27ꢀ7.23 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 5.72 (s, 1H), 4.92 (s,
2H), 3.68 (t, J = 6.4 Hz, 2H), 2.63 (t, J = 6.8 Hz, 2H), 2.57ꢀ2.51 (m,
4H), 2.38ꢀ2.31 (m, 2H), 1.83ꢀ1.76 (m, 2H), 1.01 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 138.6, 137.4, 135.9, 135.5, 133.9, 129.5, 128.6,
127.5, 127.0, 126.2, 124.4, 100.6, 63.3, 48.4, 32.2, 28.6, 26.8, 25.7, 24.8,
23.3, 19.1; HRMS (ESI) m/z calcd for C33H39NNaOSi [M + Na]+
516.2699, found 516.2694.
1-Benzyl-2-(3-hydroxypropyl)-1,4,5,6-tetrahydrocyclopenta[b]pyr-
role (2f): yield 82%; yellow oil; IR (neat) 3365, 3094, 3063, 2929, 2854,
1605, 1454 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.30 (t, J = 7.2 Hz,
2H), 7.21 (t, J = 7.2 Hz, 1H), 6.99 (d, J = 7.2 Hz, 2H), 5.78 (s, 1H), 4.96
1-Benzyl-2-propyl-1,3b,4,5,6,7,7a,8-octahydroindeno[2,1b]pyrrole (2l):
yield 62%; yellow oil; IR (neat) 2922, 2848, 1496, 1452, 1390, 1354 cmꢀ1
;
1H NMR (400 MHz, CDCl3) δ 7.31ꢀ7.21 (m, 3H), 6.95 (d, J = 7.6 Hz,
2H), 5.74 (s, 1H), 4.94 (s, 2H), 2.87 (q, J = 6.4 Hz, 1H), 2.70 (sext, J =
6.4 Hz, 1H), 2.49 (dd, J = 7.2, 14.0 Hz, 1H), 2.40 (t, J = 7.6 Hz, 2H), 2.25
(dd, J = 6.4, 14.0 Hz, 1H), 1.82ꢀ1.71 (m, 1H), 1.61ꢀ1.26 (m, 9H), 0.92
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 139.0, 136.1, 135.1,
129.3, 128.6, 127.0, 126.1, 99.9, 48.3, 43.3, 38.8, 30.3, 30.1, 29.1, 28.8, 23.2,
5819
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ARTICLE
23.1, 22.3, 14.1; HRMS (ESI) m/z calcd for C21H28N [M + H]+ 294.2222,
found 294.2224.
(4) (a) Davies, P. W.; Martin, N. Org. Lett. 2009, 11, 2293. (b) Chen,
D.-D.; Hou, X-.L.; Dai, L.-X. Tetrahedron Lett. 2009, 50, 6944. (c) Du,
X.; Xie, X.; Liu, Y. J. Org. Chem. 2010, 75, 510. (d) Blanc, A.; Alix, A.;
Weibel, J.-M.; Pale, P. Eur. J. Org. Chem. 2010, 1644. (e) Davies, P. W.;
Martin, N. J. Organomet. Chem. 2011, 696, 159.
(5) (a) Yoshida, M.; Al-Amin, M.; Shishido, K. Synthesis 2009, 2454.
(b) Yoshida, M.; Easmin, S.; Al-Amin, M.; Hirai, Y.; Shishido, K.
Tetrahedron 2011, 67, 3194. (c) Motamed, M.; Bunnelle, E. M.;
Singaram, S. W.; Sarpong, R. Org. Lett. 2007, 9, 2167.
(6) For selected reviews of platinum-catalyzed reactions, see:
(a) Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348,
2271. (b) F€urstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007,
46, 3410. (c) Chianese, A. R.; Lee, S. J.; Gagnꢀe, M. R. Angew. Chem., Int.
Ed. 2007, 46, 4042. (d) F€urstner, A. Chem. Soc. Rev. 2009, 38, 3208 and
references therein.
1-Benzyl-2-propyl-4,5,6,7-tetrahydro-1H-indole (2m): yield 91%;
yellow oil; IR (neat) 2928, 2854, 1605, 1597, 1496, 1428, 1372 cmꢀ1
;
1H NMR (400 MHz, CDCl3) δ 7.28 (t, J = 7.6 Hz, 2H), 7.21 (t, J = 7.6
Hz, 1H), 6.90 (d, J = 7.6 Hz, 2H), 5.76 (s, 1H), 4.95 (s, 2H), 2.52 (t, J =
6.0 Hz, 2H), 2.40 (t, J = 7.6 Hz, 2H), 2.38 (t, J = 7.6 Hz, 2H), 1.80ꢀ1.69
(m, 4H), 1.56 (sext, J = 7.6 Hz, 2H), 0.92 (t, J = 7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 139.0, 131.9, 128.5, 126.9, 126.8, 125.7, 116.2,
103.9, 46.2, 28.5, 23.8, 23.4, 23.1, 22.2, 21.9, 14.1; HRMS (ESI) m/z
calcd for C18H23NNa [M + Na]+ 276.1728, found 276.1724.
1-Benzyl-2-[3-(tert-butyldiphenylsilyloxy)propyl]-4,5,6,7-tetrahydro-
1H-indole (2n): yield 84%; yellow oil; IR (neat) 2928, 1605, 1589, 1516,
1496, 1471, 1454, 1440, 1428, 1411, 1357 cmꢀ1; 1H NMR (400 MHz,
CDCl3) δ 7.65ꢀ7.56 (4H, m), 7.41ꢀ7.39 (2H, m), 7.38ꢀ7.31 (4H, m),
7.27ꢀ7.18 (3H, m), 6.88 (2H, d, J = 7.2 Hz), 5.72 (1H, s), 4.93 (2H, s),
3.68 (2H, t, J = 6.0 Hz), 2.55ꢀ2.49 (4H, m), 2.39 (2H, t, J = 6.0 Hz),
1.84ꢀ1.70 (6H, m), 1.00 (9H, s); 13C NMR (100 MHz, CDCl3) δ 138.8,
135.5, 134.0, 131.5, 129.4, 128.6, 127.5, 127.1, 126.8, 125.7, 116.2, 103.9,
63.4, 46.2, 31.9, 26.8, 23.8, 23.4, 23.1, 22.7, 21.9, 19.1; HRMS (ESI) m/z
calcd for C34H41NNaOSi [M + Na]+ 530.2855, found 530.2851.
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’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra of all
S
b
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) Petit, F.; Furstoss, R. Tetrahedron: Asymmetry 1993, 4, 1341.
(13) Salaun, J. Sci. Synth. 2004, 26, 557.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: yoshida@ph.tokushima-u.ac.jp.
’ ACKNOWLEDGMENT
This study was supported in part by a Grant-in-Aid for the
Encouragement of Young Scientists (B) from the Japan Society
for the Promotion of Science (JSPS), the Takeda Science
Foundation, the Uehara Memorial Foundation, and the Program
for the Promotion of Basic and Applied Research for Innovations
in the Bio-oriented Industry (BRAIN).
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