Copper(I) halide promoted diastereoselective synthesis of chiral propargylamines and chiral allenes using 2-dialkylaminomethylpyrrolidine, aldehydes, and 1-alkynes

Article abstract of DOI:10.1021/jo302534f

Copper bromide promoted reactions of aldehydes, 1-alkynes, and chiral 2-dialkylaminomethylpyrrolidine at 25 C give the corresponding chiral propargylamine derivatives in up to 96% yield and 99:1 dr that are readily converted to the corresponding disubstit

Full text of DOI:10.1021/jo302534f

Article
pubs.acs.org/joc
Copper(I) Halide Promoted Diastereoselective Synthesis
of Chiral Propargylamines and Chiral Allenes using
2‑Dialkylaminomethylpyrrolidine, Aldehydes, and 1‑Alkynes
Ramani Gurubrahamam and Mariappan Periasamy*
School of Chemistry, University of Hyderabad, Central University P.O., Hyderabad 500046, India
S
* Supporting Information
ABSTRACT: Copper bromide promoted reactions of aldehydes, 1-alkynes, and chiral 2-dialkylaminomethylpyrrolidine at 25 °C
give the corresponding chiral propargylamine derivatives in up to 96% yield and 99:1 dr that are readily converted to the
corresponding disubstitued chiral allenes in up to 81% yield and 99% ee upon reaction with CuI in dioxane at 100 °C.
INTRODUCTION
■
Chiral propargylamines are useful synthons for synthesis of
biological active skeletons, natural products, and polyfunctional
amino derivatives.1−4 Copper−chiral ligand catalyzed enantio-
selective propargylamines have been accessed using the chiral
auxiliaries quinap,5−8 pinap,9−11 pybox,12−15 and binam
diimine.16,17 Also, chiral amino acid promoted enantioselective
synthesis of propargylamines has been reported.18−20 Recently,
Che et al. reported the chiral prolinol derived propargylamines
using gold(III) salen complexes.21,22 The chiral allene structural
motifs are also present in several biologically active natural
products and pharmaceuticals.23−25 Also, chiral allenes are versatile
synthons with the potential to provide excellent axis-to-center
chirality transfer in organic synthesis.23,26,27
Over the years, several synthetic methods were developed to
access allenes.28−35 Recently, zinc halide promoted conversion
of 1-alkynes, aldehydes, and morpholine to racemic 1,3-di-
substituted allenes36 and to enantiopure allenes using certain
chiral cyclic secondary amines were reported.37 Also, a two-step
synthesis involving preparation of chiral propargylamines and
conversion to chiral allenes in a ZnI2-promoted reaction was
reported.38 Copper(I) bromide promoted reactions of 1-alkynes,
paraformaldehyde, or substituted aldehydes and diisopropylamine
or N,N-dicyclohexylamine were reported to give 1-substituted
allenes39−41 or racemic 1,3-disubstituted allenes.42,43 Herein, we
report the results of detailed studies on the CuBr-promoted
diastereoselective synthesis of chiral propargylamines (4−6)
using 1-alkynes, aldehydes, and 2-dialkylaminomethylpyrrolidines
(1−3) and their conversion to chiral allenes 7 in a CuI-promoted
reaction (Figure 1).
Figure 1. Chiral 2-dialkylaminomethylpyrrolidine derivatives, prop-
argylamines, and allenes.
RESULTS AND DISCUSSION
■
Recently, we have reported that the chiral (2S)-phenylpyrro-
lidine (10) and (S)-diphenypyrrolidinemethanol (11; (S)-DPP)
gave the chiral (R)-allene 7 in 66% and 98% ee, respectively, in a
ZnX2-promoted one-pot, three-component allene transformation
(Scheme 1).37
Presumably, better selectivity is observed in the case of
(S)-DPP (11) due to coordination of the hydroxyl group with
the ZnBr2 during the formation of the chiral propargylamine
intermediate and also during the conversion of the propargyl-
amine into the chiral allene.37 It was of interest to us to examine
the use of the readily accessible and commercially available
(S)-2-(1-pyrrolidinylmethyl)pyrrolidine (1) in this one-pot, three-
component chiral allene transformation using ZnI2. We have
observed that in this reaction the (R)-allene 7aa was obtained with
94% ee but only in 4% yield in addition to the corresponding
propargylamine intermediate 4aa (88% yield, 96:4 dr).
Received: November 20, 2012
Published: January 15, 2013
© 2013 American Chemical Society
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A mechanism outlined in Scheme 3 can be considered for this
transformation on the basis of previous reports on reactions of
CuBr amine phosphine complexes.6 Probably, the chiral diamine 1
would initially form the dimeric copper complex 13 on reaction
with CuBr,5,45 which would then react with 1-alkyne to give the in-
termediate complex 14. This could react with the intermediate
aminal 15, formed in situ by the reaction of chiral diamine and alde-
hyde. The intermediate 16 formed in this way would then deliver
the alkynyl group from the bottom face of the iminium group,
leading to an S stereogenic center at the propargylamine product 4.
We then turned our attention toward conversion of the chiral
propargylamines obtained this way into the chiral allene 7 using
various metal salts in different solvents. We have observed that
the reaction of the propargylamine derivative 4aa with ZnI2
gave the (R)-allene 7aa in 98% ee but only in 8% yield. The
unreacted propargylamine 4aa was recovered in 70% yield after
the reaction (Table 2, entry 1). The same reaction in dioxane
gave the (R)-allene in only 10% yield but with 86% ee. We have
examined the use of AgNO3 in this conversion, as it was reported
to give the chiral allenes with high enantioselectivities using
the corresponding propargylamine derivatives prepared with
(S)-prolinol.46 However, in this run also the (R)-allene 7aa was
obtained only in 14% yield and 99% ee (Table 2, entry 3).
The use of CuI (0.5 equiv) gave better results. Whereas (R)-
allene in 76−92% ee with 18−35% yield was observed in reac-
tions in toluene, when the reaction was carried out in dioxane at
100 °C for 18 h using CuI (0.25 equiv), the (R)-allene was ob-
tained in 33% yield with 99% ee (Table 2, entry 6). When the
same reaction reaction was carried out using more CuI (0.5 equiv),
the yield was improved to 62% with 99% ee (Table 2, entry 7).
Further increases in the amount of CuI did not improve yields
(Table 2, entries 9 and 10). We have also observed that the use of
other copper halides, CuCl and CuBr, led to lower yields (22−
30%) and enantioselectivities (90−92% ee) (Table 2, entries 11
and 12). The reason for the higher yields and selectivity obtained
using the CuI−dioxane system is not clear. However, such
observations have been observed in other transformations using
the CuI−dioxane system by previous workers.42,43,47
Scheme 1. Chiral Allene Transformation Using 1-Decyne,
Benzaldehyde, and Pyrrolidine Derivatives Promoted by
ZnX2
We have also examined the other proline diamines (S)-2-
(piperidinomethyl)pyrrolidine (2) and (S)-2-(diethylaminomethyl)-
pyrrolidine (3) in this reaction. Whereas the chiral diamine 2
gave the (R)-allene 7aa in 7% yield with 94% ee in addition to
the corresponding propargylamine derivative 5 with 82% yield
and 96:4 dr, the chiral diamine 3 gave the chiral allene 7aa in
11% yield with 90% ee along with the propargylamine deriva-
tive 6 in 50% yield and 90:10 dr (Scheme 2).
This ZnI2-promoted three-component coupling gave the
corresponding chiral propargylamine derivatives in reasonable
yields and diastereoselectivity but requires refluxing toluene.
Fortunately, the relatively inexpensive CuBr catalyzes this
reaction and various chiral propargylamines (4aa−4fh) are
readily accessed using different substrates of aldehydes and
alkynes at 25 °C (Table 1). The chiral propargylamines were
obtained with good yields (75−96%) and diastereoselectiv-
ities (96:4−99:1 dr).
To study the structural effects of the diamine derivatives in
this transformation, we have used the diamines 2 and 3, contain-
ing piperidine and diethylamine moieties. The corresponding
propargylamines 5 and 6 were prepared using CuBr (20 mol %),
benzaldehyde (8a) and 1-decyne (9a) with up to 84% yield (99:1
dr) and 68% yield (98:2 dr), respectively. The absolute con-
figurations of propargylamines 4−6 were assigned by com-
parison with the data reported for the propargylamine 6ba.22
We have observed that the reaction of the chiral diamine 1 with
ethyl propiolate gave the Michael adduct 12 in 88% yield in
15 min at 25 °C.44 When the reaction was carried out with the
propargyl alcohol under these conditions, only a complex mix-
ture of unidentified products was obtained. The corresponding
benzoyl ester leads to the formation of the N-benzoyl derivative
of the diamine 1. However, when the reaction was carried out
with propargyl benzyl ether, the corresponding chiral propargyl-
amines (4fa−fh) were obtained (Table 1).
The propargylamines 5 and 6 gave the chiral (R)-allene 7aa
in 54% yield and 99% ee and 42% yield and 96% ee, respec-
tively, under these conditions (Table 2, entries 13 and 14).
Clearly, the chiral diamine containing pyrrolidine moiety 4aa
gave better results in comparison to the propargylamine con-
taining diethylamine and piperidine amine moieties.
We then carried out the reaction of other propargylamine
derivatives 4ab−fh using CuI (0.5 equiv) at 100 °C, which gave
optimum results using 7aa (Table 2, entry 7). The propargyl-
amines 4ab−af were converted to the corresponding chiral
allenes 7ab−af in 59−68% yields with good enantioselectivities
(94−98% ee, Table 3). The propargylamine (4ba) prepared
Scheme 2. Chiral Allene Transformation Using 1-Decyne, Benzaldehyde, and (S)-2-Dialkylaminomethylpyrrolidine Promoted
by ZnI2
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Table 1. Diastereoselective Synthesis of Propargylamines Using Chiral Amine, Aldehyde, and 1-Alkyne and Copper
a c
−
Bromide
a
The reactions were carried out by taking amine 1−3 (2.0 mmol), 1-alkyne (2.2 mmol), and aldehyde (2.0 mmol) in toluene (3 mL) with CuBr (0.4
b
c
1
́
mmol) and MS (1.0 g, 4 Å) at 25 °C for 36 h. dr ratio based on crude H NMR. Isolated yield.
Scheme 3. Tentative Mechanism for Copper-Catalyzed Propargylamine Formation
from phenylacetylene (9b) and benzaldehyde (8a) gave the
chiral allene 7ba in 56% yield and 85% ee. The other propargyl-
amines 4ca−fh prepared from different alkynes and aldehydes
afforded the corresponding chiral allenes 7ca−fh in 58−81%
yields with good enantioselectivities (94−99%, Table 3).
The mechanism outlined in Scheme 4 may be considered for
this transformation.43,48 The triple bond of propargylamine 4
would complex with CuI to give the intermediate 18, which could
undergo a 1,5-hydride shift to give the alkenyl copper species 19.
Antiperiplanar elimination of the CuI and the imine would then
give the chiral allene (R)-7. A similar mechanism was previously
proposed for the Ag(I)-catalyzed conversion of a chiral propargyl-
amino alcohol to chiral allenes (Scheme 4). The optimum results
obtained using dioxane may be due to its interaction with CuI in
the transition states for the formation of the intermediate 18, 19,
and allene (R)-7.
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a
Table 2. Reaction of Propargylamines 4aa, 5, and 6 with ZnI2, AgNO3, and CuX
b
c
entry
diamine
solvent
temp (°C)
MX
ZnI2
amt of MX (equiv)
time (h)
yield (%)
ee (%)
1
4aa
4aa
4aa
4aa
4aa
4aa
4aa
4aa
4aa
4aa
4aa
4aa
5
toluene
dioxane
CH3CN
toluene
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
120
100
50
0.5
0.5
0.5
0.5
0.5
0.25
0.5
0.5
0.75
1.0
0.5
0.5
0.5
0.5
24
18
24
2
8
10
14
18
35
33
62
68
65
70
22
30
54
42
98
86
99
92
76
99
99
98
99
98
92
90
99
96
2
ZnI2
AgNO3
CuI
3
4
120
120
100
100
100
100
100
100
100
100
100
5
CuI
5
6
CuI
18
18
24
18
18
18
18
18
18
7
CuI
8
CuI
9
CuI
10
11
12
13
14
CuI
CuCl
CuBr
CuI
6
CuI
a
b
c
The reactions were carried out by taking up amines 4aa, 5, and 6 (0.5 mmol) in solvent (2 mL). Isolated yields. The % ee was confirmed by
HPLC analysis on Chiralcel OD-H.
a c
−
Table 3. Copper Iodide Promoted Chiral Allene Transformation Using Corresponding Propargylamines
a
b
c
The reactions were carried out by taking up amines 4 (0.5 mmol) and CuI (0.25 mmol) in dioxane (2 mL). Isolated yield. The % ee was
confirmed by HPLC analysis on Chiralcel OD-H, OB-H and OJ-H columns.
Scheme 4. Tentative Mechanism for Copper(I)-Catalyzed Allene Formation
We have made efforts to isolate the imine byproduct 17 but
were not successful. However, we have observed that the imine
intermediate 17 formed during the reaction could be readily con-
verted back to the starting (S)-2-(1-pyrrolidinylmethyl)pyrrolidine
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(400 MHz, CDCl3): δ 7.47−7.41 (m, 4H), 5.18 (s, 1H), 3.07−3.03
(m, 1H), 2.68 (dd, J = 11.9, 5.2 Hz, 1H), 2.58−2.46 (m, 6H), 2.31 (t,
J = 6.7 Hz, 2H), 1.99−1.93 (m, 2H), 1.77 (s, 4H), 1.68−1.53 (m, 5H),
1.46−1.44 (m, 2H), 1.29 (s, 8H), 0.88 (t, J = 6.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 139.8, 130.9, 129.9, 120.7, 88.1, 75.6, 62.3, 59.4,
55.9, 54.9, 47.4, 31.8, 30.6, 29.3, 29.1, 28.9, 23.5, 22.7, 22.6, 18.7, 14.1.
[α]D25 = −64.6° (c = 0.85, CHCl3). LCMS (m/z): 461 (M + 2). Anal.
Calcd for C26H39BrN2: C, 67.96; H, 8.55; N, 6.10. Found: C, 67.85; H,
8.51; N, 6.15.
1 by reduction in situ using NaBH4/MeOH in 61% yield
without loss of its optical purity (eq 1).
Cul (0.5 equiv)
NaBH4/MeOH
4aa ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→ (R)‐7aa + [17] ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→
1
dioxane,18 h
0−25 °C, 2 h
61% y, 99% ee
100 °C
(1)
We have also examined the utility of chiral diamine 1 in a
one-pot chiral allene transformation using CuBr for the pre-
paration of a propargylamine derivative followed by addition of
CuI (in dioxane) for chiral (R)-allene formation. In this case,
we have obtained the chiral (R)-allene 7aa with 48% yield and
90% ee.
(S)-1-((S)-1-(3-Methoxyphenyl)-3-phenylprop-2-yn-1-yl)-2-(pyrro-
lidin-1-ylmethyl)pyrrolidine (4ad). Yellow oil. Yield: 0.62 g (75%). IR
(neat): 2925, 2448, 2777, 1599, 1484, 1314, 1424, 1045, 755, 689
cm−1. 1H NMR (400 MHz, CDCl3): δ 7.23 (d, J = 8.0 Hz, 1H), 7.18−
7.17 (m, 2H), 6.78 (d, J = 8.1 Hz, 1H), 5.18 (s, 1H), 3.82 (s, 3H),
3.08−3.04 (m, 1H), 2.68 (dd, J = 12.0, 5.3 Hz, 1H), 2.62−2.47 (m,
6H), 2.31 (t, J = 6.8 Hz, 2H), 1.99−1.97 (m, 1H), 1.77 (s, 4H), 1.68−
1.53 (m, 6H), 1.45−1.44 (m, 2H), 1.29 (bs, 8H), 0.89 (t, J = 7.1 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ 159.4, 142.4, 128.9, 120.7,
114.0, 112.1, 87.5, 76.2, 62.4, 59.5, 56.4, 55.1, 55.0, 47.6, 31.9, 30.6,
29.3, 29.2, 28.9, 23.5, 22.8, 22.7, 18.8, 14.1. [α]D25 = −82.1° (c = 1.03,
CHCl3). LCMS (m/z): 409 (M − 1). Anal. Calcd for C25H42N2O: C,
78.97; H, 10.31; N, 6.82. Found: C, 78.85; H, 10.38; N, 6.73.
(S)-2-(Pyrrolidin-1-ylmethyl)-1-((S)-1-(p-tolyl)undec-2-yn-1-yl)-
pyrrolidine (4ae). Light yellow oil. Yield: 0.71 g (90%). IR (neat):
CONCLUSION
■
We have developed a CuBr-promoted method for diastereo-
selective synthesis of chiral propargylamine derivatives using
(2S)-dialkylaminomethylpyrrolidine and transformed them into
chiral (R)-allenes using copper iodide. Since the chiral propargyl-
amines were obtained in good yields and excellent diaster-
eoselectivities and the chiral allenes synthesized were in high
enantiomeric purities, the methods described here have con-
siderable potential for further exploitations in synthesis.
1
2928, 2858, 2791, 1510, 1460, 1350, 1141, 831, 765 cm−1. H NMR
(400 MHz, CDCl3): δ 7.47 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 7.8 Hz,
2H), 5.17 (s, 1H), 3.09−3.06 (m, 1H), 2.70 (dd, J = 11.9, 5.0 Hz, 1H),
2.62−2.46 (m, 7H), 2.34−2.30 (m, 5H), 2.02−1.96 (m, 1H), 1.78 (s,
4H), 1.69−1.55 (m, 5H), 1.49−1.48 (m, 2H), 1.31 (s, 8H), 0.91 (t, J =
6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 137.7, 136.5, 128.6,
128.1, 87.4, 76.4, 62.3, 59.5, 56.2, 54.9, 47.6, 31.9, 30.7, 29.3, 29.2,
29.1, 28.9, 23.5, 22.8, 22.7, 21.1, 18.8, 14.1. [α]D25 = −81.9° (c = 1.19,
CHCl3). LCMS (m/z): 395 (M + 1). Anal. Calcd for C27H42N2: C,
82.17; H, 10.73; N, 7.10. Found: C, 82.21; H, 10.81; N, 7.03.
(S)-2-(Pyrrolidin-1-ylmethyl)-1-((S)-1-(m-tolyl)undec-2-yn-1-yl)-
pyrrolidine (4af). Light yellow oil. Yield: 0.65 g (82%). IR (neat):
EXPERIMENTAL SECTION
■
General Information. Chiral proline diamine derivatives 1−3
were synthesized by following the literature reports.49 CuBr and CuI
were purchased from Sigma Aldrich and used without any further
purification. Toluene and dioxane were dried on sodium benzophe-
none ketyl and stored on sodium wire.
General Procedure for Synthesis of (2S)-Dialkylaminome-
thylpyrrolidine-Derived Chiral Propargylamines. In an oven-
dried 10 mL flask, copper(I) bromide (57 mg, 20 mol %) and chiral
diamine 1−3 (2 mmol) in dry toluene (3 mL) were added. Freshly
1
2926, 2858, 2785, 1608, 1460, 1143, 754 cm−1. H NMR (400 MHz,
́
CDCl3): δ 7.39−7.37 (m, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.05 (d, J =
7.3 Hz, 1H), 5.15 (s, 1H), 3.08−3.05 (m, 1H), 2.69 (dd, J = 11.9, 4.9 Hz,
1H), 2.63−2.46 (m, 7H), 2.39−2.30 (m, 5H), 2.02−1.97 (m, 1H), 1.78 (s,
4H), 1.70−1.54 (m, 5H), 1.49−1.47 (m, 2H), 1.31−1.30 (m, 8H), 0.89 (t,
J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 140.5, 137.5, 128.9,
127.9, 127.7, 125.3, 87.5, 76.3, 62.3, 59.6, 56.5, 55.0, 47.6, 31.9, 30.7, 29.3,
distilled aldehyde 8 (2 mmol), 4 Å MS (1.0 g), and 1-alkyne 9 (2.2
mmol) were added, and the mixture was stirred at 25 °C for 36 h. The
́
4 Å MS was removed by filtration and washed with Et2O. The crude
product was concentrated in vacuo and purified by chromatography on
basic alumina. The product was eluted in a 98/2 mixture of hexane and
ethyl acetate.
25
29.2, 28.9, 23.5, 22.73, 22.70, 21.5, 18.8, 14.1. [α]D = −80.2° (c = 0.7,
(S)-1-((S)-1-Phenylundec-2-yn-1-yl)-2-(pyrrolidin-1-ylmethyl)-
CHCl3). LCMS (m/z): 395 (M + 1). Anal. Calcd for C27H42N2: C, 82.17;
H, 10.73; N, 7.10. Found: C, 82.06; H, 10.65; N, 7.18.
pyrrolidine (4aa). Light yellow oil. Yield: 0.70 g (92%). IR (neat):
1
3061, 3028, 2928, 1601, 1493, 1450, 700 cm−1. H NMR (400 MHz,
(S)-1-((S)-1,3-Diphenylprop-2-yn-1-yl)-2-(pyrrolidin-1-ylmethyl)-
CDCl3): δ 7.58 (d, J = 7.6 Hz, 2H), 7.31−7.23 (m, 3H), 5.20 (s, 1H),
3.10−3.03 (m, 1H), 2.69 (dd, J = 11.9, 5.0 Hz, 1H), 2.62−2.44 (m,
6H), 2.34−2.30 (m, 2H), 2.01−1.94 (m, 1H), 1.81−1.77 (m, 5H),
1.69−1.54 (m, 5H), 1.48−1.44 (m, 2H), 1.31−1.29 (m, 8H), 0.89 (t,
J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 140.6, 128.2, 127.9,
126.9, 87.6, 76.1, 62.3, 59.5, 56.5, 54.9, 47.5, 31.8, 30.6, 29.3, 29.1,
pyrrolidine (4ba).22 Yellow oil. Yield: 0.65 g (94%). IR (neat): 3437,
1
3061, 3030, 1599, 1489, 1448, 756, 692 cm−1. H NMR (400 MHz,
CDCl3): δ 7.66 (d, J = 7.6 Hz, 2H), 7.54−7.52 (m, 2H), 7.38−7.28
(m, 6H), 5.57 (s, 1H), 3.23−3.18 (m, 1H), 2.79 (dd, J = 12.0, 5.6 Hz,
1H), 2.73 (t, J = 8.6 Hz, 1H), 2.65−2.52 (m, 6H), 2.05−2.0 (m, 1H),
1.79 (s, 4H), 1.74−1.62 (m, 3H). 13C NMR (100 MHz, CDCl3): δ
140.0, 131.9, 128.4, 128.25, 128.20, 128.1, 127.3, 123.5, 87.6, 86.5,
62.3, 59.5, 57.0, 54.9, 47.9, 30.8, 23.6, 22.9. [α]D25 = −120.8° (c = 0.91,
CHCl3). LCMS (m/z): 346 (M + 1). Anal. Calcd for C24H28N2: C,
83.68; H, 8.19; N, 8.13. Found: C, 83.56; H, 8.12; N, 8.25.
(S)-1-((S)-1,5-Diphenylpent-2-yn-1-yl)-2-(pyrrolidin-1-ylmethyl)-
pyrrolidine (4ca). Yellow oil. Yield: 0.66 g (89%). IR (neat): 3057,
3030, 2964, 1600, 1490, 1441, 695 cm−1. 1H NMR (400 MHz,
CDCl3): δ 7.52 (d, J = 7.3 Hz, 2H), 7.35−7.24 (m, 8H), 5.21 (s, 1H),
3.04−2.97 (m, 1H), 2.93 (t, J = 7.3 Hz, 2H), 2.71−2.66 (m, 3H),
2.58−2.42 (m, 8H), 1.98−1.91 (m, 1H), 1.79 (bs, 4H), 1.67−1.57 (m,
2H). 13C NMR (100 MHz, CDCl3): δ 140.8, 140.5, 128.6, 128.4,
128.2, 128.0, 127.0, 126.2, 86.7, 62.4, 59.5, 56.4, 55.0, 47.5, 35.4, 30.6,
23.5, 22.7, 20.8. [α]D25 = −87.7° (c = 0.12, CHCl3). LCMS (m/z): 373
(M + 1). Anal. Calcd for C26H32N2: C, 83.82; H, 8.66; N, 7.52. Found:
C, 83.91; H, 8.72; N, 7.45.
25
28.9, 23.5, 22.7, 22.7, 18.8, 14.1. [α]D = −89.3° (c = 0.68, CHCl3).
LCMS (m/z): 381 (M + 1). Anal. Calcd for C26H40N2: C, 82.05; H,
10.59; N, 7.36. Found: C, 82.15; H, 10.59; N, 7.31.
(S)-1-((S)-1-(4-Chlorophenyl)undec-2-yn-1-yl)-2-(pyrrolidin-1-
ylmethyl)pyrrolidine (4ab). Light yellow oil. Yield: 0.70 g (84%). IR
1
(neat): 2928, 2785, 1487, 1460, 1089, 1016 cm−1. H NMR (400 MHz,
CDCl3): δ 7.52 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.3 Hz, 2H), 5.21 (s,
1H), 3.10−3.05 (m, 1H), 2.70 (dd, J = 11.9, 5.4 Hz, 1H), 2.60−2.47 (m,
7H), 2.32 (t, J = 6.8 Hz, 2H), 1.99−1.94 (m, 1H), 1.77 (bs, 4H), 1.68−
1.53 (m, 5H), 1.47−1.45 (m, 2H), 1.29 (s, 8H), 0.89 (t, J = 6.8 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 139.3, 132.6, 129.5, 128.0, 88.0, 75.8,
62.4, 59.4, 55.9, 54.9, 47.5, 31.9, 30.6, 29.3, 29.1, 28.9, 23.5, 22.7, 22.6,
18.8, 14.1. [α]D25 = −79.5° (c = 0.75, CHCl3). LCMS (m/z): 415 (M + 1).
Anal. Calcd for C26H39ClN2: C, 75.24; H, 9.47; N, 6.75. Found: C, 75.11;
H, 9.56; N, 6.68.
(S)-1-((S)-1-(4-Bromophenyl)undec-2-yn-1-yl)-2-(pyrrolidin-1-
ylmethyl)pyrrolidine (4ac). Yellow oil. Yield: 0.79 g (86%). IR (neat):
(S)-1-((S)-1-(4-Bromophenyl)-5-phenylpent-2-yn-1-yl)-2-(pyrroli-
din-1-ylmethyl)pyrrolidine (4cc). Yellow oil. Yield: 0.70 g (78%). IR
1
3435, 2926, 2858, 1658, 1587, 1483, 1012, 856, 723 cm−1. H NMR
1467
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Article
(neat): 3030, 2962, 2868, 2789, 1604, 1485, 1010, 744, 698 cm−1. H
NMR (400 MHz, CDCl3): δ 7.41−7.22 (m, 9H), 5.16 (s, 1H), 2.98−
2.95 (m, 1H), 2.90 (t, J = 7.2 Hz, 2H), 2.69−2.64 (m, 3H), 2.58−2.43
(m, 6H), 2.39−2.34 (m, 1H), 1.94−1.89 (m, 1H), 1.79−1.75 (m, 4H),
1.63−1.55 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 140.6, 139.6,
130.1, 129.9, 128.6, 128.4, 126.3, 120.7, 87.1, 76.6, 62.4, 59.3, 55.9,
55.0, 47.4, 35.3, 30.5, 23.5, 22.7, 20.7. [α]D = −56.6° (c = 0.1,
CHCl3). LCMS (m/z): 451(M + 1). Anal. Calcd for C26H31BrN2: C,
69.17; H, 6.92; N, 6.21. Found: C, 69.05; H, 6.87; N, 6.28.
(S)-1-((R)-1-Cyclohexyl-5-phenylpent-2-yn-1-yl)-2-(pyrrolidin-1-
ylmethyl)pyrrolidine (4cg). Yellow oil. Yield: 0.73 g (96%). IR (neat):
3063, 3028, 2922, 2851, 2785, 1670, 1604, 1496, 1450, 744, 698 cm−1.
1H NMR (400 MHz, CDCl3): δ 7.32−7.20 (m, 5H), 3.30 (d, J = 10.0
Hz, 1H), 2.85−2.80 (m, 3H), 2.70−2.66 (m, 1H), 2.57−2.48 (m, 7H),
2.43−2.32 (m, 2H), 1.97−1.96 (m, 2H), 1.89−1.85 (m, 1H), 1.76−
1.55 (m, 10H), 1.34−1.14 (m, 4H), 0.93−0.85 (m, 2H). 13C NMR
(100 MHz, CDCl3): δ 140.9, 128.5, 128.2, 126.1, 84.4, 78.8, 62.1, 59.9,
58.6, 54.9, 46.8, 41.3, 35.7, 31.4, 30.5, 30.4, 26.9, 26.2, 26.0, 23.5, 23.3,
20.8. [α]D25 = −94.0° (c = 1.02, CHCl3). LCMS (m/z): 380 (M + 1).
Anal. Calcd for C26H38N2: C, 82.48; H, 10.12; N, 7.40. Found: C,
82.36; H, 10.18; N, 7.31.
3.46 (d, J = 9.9 Hz, 1H), 2.93−2.90 (m, 1H), 2.79−2.74 (m, 1H),
2.64−2.62 (m, 1H), 2.51−2.34 (m, 6H), 2.06−1.88 (m, 2H), 1.75−
1.59 (m, 12H), 1.31−1.20 (m, 5H). 13C NMR (100 MHz, CDCl3): δ
1
137.7, 128.4, 128.1, 127.8, 85.2, 80.9, 71.0, 62.1, 60.1, 58.6, 57.5, 55.0,
25
47.1, 41.1, 31.4, 30.5, 30.4, 26.8, 26.1, 25.9, 23.5, 23.3. [α]D
=
−101.9° (c = 0.71, CHCl3). LCMS (m/z): 395 (M + 1). Anal. Calcd
for C26H38N2O: C, 79.14; H, 9.71; N, 7.10. Found: C, 79.25; H, 9.63;
N, 7.18.
25
(S)-1-((S)-1-(Benzyloxy)dodec-2-yn-4-yl)-2-(pyrrolidin-1-
ylmethyl)pyrrolidine (4fh). Yellow oil. Yield: 0.74 g (87%). IR (neat):
1
3027, 2925, 2854, 1455, 1350, 1073, 734, 697 cm−1. H NMR (400
MHz, CDCl3): δ 7.36−7.30 (m, 5H), 4.62 (s, 2H), 4.23 (s, 2H), 3.88
(t, J = 7.4 Hz, 1H), 2.95−2.86 (m, 2H), 2.64 (q, J = 8.6 Hz, 1H), 2.51
(s, 5H), 2.43−2.38 (m, 1H), 1.98−1.93 (m, 1H), 1.75 (s, 6H), 1.65−
1.60 (m, 3H), 1.50−1.41 (m, 2H), 1.29−1.27 (m, 10H), 0.88 (t, J =
6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 137.6, 128.4, 128.1,
127.8, 85.8, 80.4, 71.1, 62.1, 60.0, 57.5, 55.0, 52.8, 47.4, 35.2, 31.9,
30.5, 29.5, 29.3, 26.8, 23.5, 22.9, 22.7, 14.2. [α]D25 = −66.5° (c = 1.22,
CHCl3). LCMS (m/z): 425 (M + 1). Anal. Calcd for C28H44N2O: C,
79.19; H, 10.44; N, 6.60. Found: C, 79.32; H, 10.38; N, 6.75.
1-(((S)-1-((S)-1-Phenylundec-2-yn-1-yl)pyrrolidin-2-yl)methyl)-
piperidine (5). Light yellow oil. Yield: 0.66 g (84%). IR (neat): 3061,
3028, 1726, 1602, 1493, 1450, 1124, 725, 700 cm−1. 1H NMR: (400 MHz,
CDCl3) δ 7.58 (d, J = 7.4 Hz, 2H), 7.33−7.21 (m, 3H), 5.42 (s, 1H),
3.13−3.08 (m, 1H), 2.62 (dd, J = 17.2, 8.6 Hz, 1H), 2.65−2.30 (m, 8H),
2.17 (s, 1H), 1.94−1.88 (m, 1H), 1.65−1.43 (m, 13H), 1.30 (s, 8H),
0.89−0.88 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 140.9, 128.2, 127.9,
126.9, 87.4, 76.4, 65.8, 57.4, 56.6, 55.4, 47.7, 31.9, 30.6, 29.3, 29.2, 29.1,
28.9, 26.2, 24.6, 22.73, 22.7, 18.8, 14.1. [α]D25 = −76.0° (c = 0.81, CHCl3).
LCMS (m/z): 396 (M + 1). Anal. Calcd for C27H42N2: C, 82.17; H,
10.73; N, 7.10. Found: C, 82.35; H, 10.62; N, 7.18.
(S)-1-((R)-1-Cyclohexyl-3-phenylprop-2-yn-1-yl)-2-(pyrrolidin-1-
ylmethyl)pyrrolidine (4bg). Yellow oil. Yield: 0.67 g (96%). IR (neat):
1
3435, 2924, 2787, 1599, 1489, 1446, 754, 690 cm−1. H NMR (400
MHz, CDCl3): δ 7.43−7.41 (m, 2H), 7.31−7.27 (m, 3H), 3.61 (d, J =
10.0 Hz, 1H), 3.03−2.96 (m, 1H), 2.84−2.79 (m, 1H), 2.72 (q, J = 8.4 Hz,
1H), 2.53−2.37 (m, 6H), 2.12−1.92 (m, 3H), 1.76−1.48 (m, 13H), 1.30−
1.19 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 131.7, 128.2, 127.6, 123.9,
88.5, 85.6, 62.1, 60.2, 59.1, 55.0, 47.2, 41.3, 31.5, 30.6, 30.5, 26.9, 26.2,
26.0, 23.6, 23.5. [α]D25 = −142.1° (c = 0.83, CHCl3). LCMS (m/z): 352
(M + 1). Anal. Calcd for C24H34N2: C, 82.23; H, 9.78; N, 7.99. Found: C,
82.15; H, 9.86; N, 7.91.
N-Ethyl-N-((S)-1-((S)-1-phenylundec-2-yn-1-yl)pyrrolidin-2-yl)-
methyl)ethanamine (6). Yellow oil. Yield: 0.52 g (68%). IR (neat):
3061, 2959, 2928, 1493, 1450, 1383, 1327, 698 cm−1. 1H NMR (400 MHz,
CDCl3): δ 7.58 (d, J = 7.4 Hz, 2H), 7.33−7.23 (m, 3H), 5.33 (s, 1H),
3.08−3.06 (m, 1H), 2.61−2.41 (m, 8H), 2.33−2.30 (m, 2H), 1.98−1.91
(m, 1H), 1.66−1.54 (m, 5H), 1.47−1.46 (m, 2H), 1.29 (s, 8H), 1.06 (t, J =
6.9 Hz, 6H), 0.89 (t, J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ
140.8, 128.2, 127.9, 126.9, 87.5, 76.3, 59.5, 58.4, 56.6, 48.0, 47.9, 31.9, 30.6,
(S)-1-((S)-3-(Cyclohex-1-en-1-yl)-1-phenylprop-2-yn-1-yl)-2-(pyr-
rolidin-1-ylmethyl)pyrrolidine (4da). Light yellow oil. Yield: 0.61 g
(88%). IR (neat): 3061, 3028, 2930, 2785, 1491, 1448, 1136, 702
cm−1. 1H NMR (400 MHz, CDCl3): δ 7.58 (d, J = 7.5 Hz, 2H), 7.34−
7.21 (m, 4H), 6.16−6.14 (m, 1H), 5.37 (s, 1H), 3.12−3.07 (m, 1H),
2.72 (dd, J = 12.0, 5.4 Hz, 1H), 2.65−2.47 (m, 6H), 2.22−2.11 (m,
4H), 2.01−1.96 (m, 1H), 1.77−1.58 (m, 11H). 13C NMR (100 MHz,
25
29.4, 29.3, 29.0, 22.8, 22.6, 18.8, 14.2, 12.1. [α]D = −89.3° (c = 1.15,
CDCl3): δ 140.4, 134.0, 128.2, 128.0, 127.0, 120.8, 89.4, 83.3, 62.4,
25
CHCl3). LCMS (m/z): 383 (M + 1). Anal. Calcd for C26H42N2: C, 81.61;
H, 11.06; N, 7.32. Found: C, 81.49; H, 11.15; N, 7.21.
59.6, 56.9, 55.0, 47.7, 30.6, 29.8, 25.6, 23.6, 22.8, 22.4, 21.6. [α]D
=
−115.6° (c = 1.18, CHCl3). LCMS (m/z): 350 (M + 1). Anal. Calcd
for C24H32N2: C, 82.71; H, 9.25; N, 8.04. Found: C, 82.65; H, 9.21; N,
8.12.
General Procedure for Synthesis of Chiral Allenes from
Chiral Proline Derived Propargylamines. The chiral propargyl-
amine (0.5 mmol) was added to a stirred suspension of CuI (48 mg,
0.25 mmol) in dry dioxane (2 mL), and the contents were refluxed for
18 h at 100 °C under a nitrogen atmosphere. Dioxane was removed
under reduced pressure, and the crude product was purified on silica
gel (100−200) using hexane as eluent to isolate the chiral allene 7.
Characterization data of the chiral allenes 7aa−ea were identical with
our previously reported data.40
(S)-7-Phenyl-7-((S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)hept-
5-ynenitrile (4ea). Yellow oil. Yield: 0.61 g (91%). IR (neat): 3059,
1
3030, 2922, 2868, 2797, 2247, 1493, 1450, 702, 665 cm−1. H NMR
(400 MHz, CDCl3): δ 7.54 (d, J = 7.4 Hz, 2H), 7.35−7.31 (m, 2H),
7.25−7.23 (m, 1H), 5.27 (s, 1H), 3.04−2.99 (m, 1H), 2.71 (dd, J =
12.0, 5.4 Hz, 1H), 2.57−2.48 (m, 11H), 1.98−1.90 (m, 3H), 1.77 (s,
4H), 1.68−1.61 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 140.1,
128.1, 128.0, 127.2, 119.1, 84.4, 78.6, 62.3, 59.6, 56.4, 55.0, 47.8, 30.6,
(R)-(4-(Benzyloxy)buta-1,2-dien-1-yl)benzene (7fa). Colorless
25
liquid. Yield: 0.076 g (64%). IR (neat): 3063, 3032, 1952, 1726,
25.0, 23.5, 22.8, 18.0, 16.2. [α]D = −104.2° (c = 0.96, CHCl3).
1
1599, 1494, 1454 cm−1. H NMR (400 MHz, CDCl3): δ 7.36−7.20
LCMS (m/z): 336 (M + 1). Anal. Calcd for C22H29N3: C, 78.76; H,
8.71; N, 12.53. Found: C, 78.85; H, 8.65; N, 12.45.
(m, 10H), 6.29−6.26 (m, 1H), 5.73 (q, J = 6.6 Hz, 1H), 4.63−4.56
(m, 2H), 4.19 (dd, J = 6.7, 2.3 Hz, 2H). 13C NMR (100 MHz,
CDCl3): δ 206.1, 138.1, 133.9, 128.7, 128.4, 127.9, 127.7, 127.1, 126.9,
(S)-1-((S)-4-(Benzyloxy)-1-phenylbut-2-yn-1-yl)-2-(pyrrolidin-1-
ylmethyl)pyrrolidine (4fa). Yellow oil. Yield: 0.64 g (82%). IR (neat):
3061, 3030, 2962, 1602, 1493, 1452, 1201 cm−1. 1H NMR (400 MHz,
CDCl3): δ 7.61 (d, J = 7.4 Hz, 2H), 7.41−7.28 (m, 8H), 5.42 (s, 1H),
4.70 (s, 2H), 4.37 (s, 2H), 3.14−3.11 (m, 1H), 2.75 (dd, J = 5.5, 5.5
Hz, 1H), 2.67−2.51 (m, 7H), 2.03−1.99 (m, 1H), 1.79−1.62 (m, 7H).
13C NMR (100 MHz, CDCl3): δ 139.9, 137.7, 128.5, 128.2, 127.9,
25
95.6, 92.6, 72.0, 67.9. [α]D = −116.5° (c = 0.55, CHCl3). LCMS
(m/z): 237 (M + 1). Anal. Calcd for C17H16O: C, 86.40; H, 6.82.
Found: C, 86.18; H, 6.91. HPLC: 94% ee (Daicel Chiralcel OJ-H,
hexane/iPrOH 99/1, flow rate 1.0 mL/min, 254 nm, tR(R) = 31.9 min,
tR(S) = 34.7 min).
(R)-(((4-Cyclohexylbuta-2,3-dien-1-yl)oxy)methyl)benzene (7fg).
127.3, 83.5, 83.2, 71.3, 62.5, 59.5, 57.6, 56.6, 55.0, 47.9, 30.6, 23.6,
25
Colorless liquid. Yield: 0.082 g (68%). IR (neat): 3030, 2926, 2851,
22.8. [α]D = −86.2° (c = 0.6, CHCl3). LCMS (m/z): 389 (M + 1).
Anal. Calcd for C26H32N2O: C, 80.37; H, 8.30; N, 7.21. Found: C,
80.25; H, 8.36; N, 7.13.
1
1961, 1450, 1095 cm−1. H NMR (400 MHz, CDCl3): δ 7.37−7.30
(m, 5H), 5.32−5.23 (m, 2H), 4.56 (s, 2H), 4.07 (dd, J = 6.8, 2.2 Hz,
2H), 2.04−2.00 (m, 1H), 1.79−1.64 (m, 6H), 1.35−1.11 (m, 4H). 13C
NMR (100 MHz, CDCl3): δ 204.0, 138.3, 128.4, 127.8, 127.6, 98.0,
(S)-1-((S)-4-(Benzyloxy)-1-cyclohexylbut-2-yn-1-yl)-2-(pyrrolidin-
1-ylmethyl)pyrrolidine (4fg). Yellow oil. Yield: 0.72 g (91%). IR
1
25
(neat): 3065, 3030, 2928, 1450, 1352 cm−1. H NMR (400 MHz,
89.3, 71.6, 68.8, 37.0, 33.07, 33.03, 26.1, 25.9. [α]D = −39.7° (c =
CDCl3): δ 7.36−7.29 (m, 5H), 4.62 (s, 2H), 4.24 (d, J = 1.6 Hz, 2H),
0.58, CHCl3). LCMS (m/z): 243 (M + 1). HPLC: 94% ee (Daicel
1468
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Article
Chiralcel OB-H, hexane/iPrOH 99/1, flow rate 0.5 mL/min, 215 nm,
tR(R) = 10.2 min, tR(S) = 11.2 min). Anal. Calcd for C17H22O: C,
84.25; H, 9.15. Found: C, 84.15; H, 9.21.
(3) Kauffman, G. S.; Harris, G. D.; Dorow, R. L.; Stone, B. R. P.;
Parsons, R. L.; Pesti, J. A., Jr.; Magnus, N. A.; Fortunak, J. M.;
Confalone, P. N.; Nugent, W. A. Org. Lett. 2000, 2, 3119.
(4) Trost, B. M.; Chung, C. K.; Pinkerton, A. B. Angew. Chem., Int.
Ed. 2004, 43, 4327.
(R)-((Dodeca-2,3-dien-1-yloxy)methyl)benzene (7fh). Colorless
liquid. Yield: 0.090 g (66%). IR (neat): 3058, 3032, 2925, 2856,
1
1961, 1453, 1096, 734, 687 cm−1. H NMR (400 MHz, CDCl3): δ
(5) Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed.
7.38−7.28 (m, 5H), 5.25−5.20 (m, 2H), 4.55 (s, 2H), 4.06 (dd, J =
6.6, 2.4 Hz, 2H), 2.04−2.0 (m, 2H), 1.44−1.27 (m, 12H), 0.89 (t, J =
7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 205.1, 138.3, 128.4,
127.9, 127.6, 92.0, 88.3, 71.6, 68.7, 31.9, 29.4, 29.3, 29.15, 29.10, 28.6,
22.7, 14.1. [α]D25 = −15.3° (c = 0.4, CHCl3). LCMS (m/z): 273 (M + 1).
HPLC: 96% ee (Daicel Chiralcel OB-H, hexane/iPrOH 100/0, flow rate
0.5 mL/min, 215 nm, tR(R)= 15.2 min, tR(S)= 17.0 min). Anal. Calcd for
C19H28O: C, 83.77; H, 10.36. Found: C, 83.65; H, 10.26.
2002, 41, 2535.
(6) Gommermann, N.; Koradin, C.; Polborn, K.; Knochel, P. Angew.
Chem., Int. Ed. 2003, 42, 5763.
(7) Koradin, C.; Gommermann, N.; Polborn, K.; Knochel, P. Chem.
Eur. J. 2003, 9, 2797.
(8) Gommermann, N.; Knochel, P. Chem. Eur. J. 2006, 12, 4380.
(9) Knopfel, T. F.; Aschwanden, P.; Ichikawa, T.; Watanabe, T.;
̈
Carreira, E. M. Angew. Chem., Int. Ed. 2004, 43, 5971.
(10) Aschwanden, P.; Stephenson, C. R. J.; Carreira, E. M. Org. Lett.
2006, 8, 2437.
Reduction of the Imine Intermediate 17 Present in the
Product Mixture. The procedure for the synthesis of chiral allenes
from chiral propargylamine (0.5 mmol, 0.190 g was followed, and this
crude mixture was cooled to 0 °C. Methanol (3 mL) and NaBH4 (0.6
mmol, 0.023 g) were added, and the mixture was stirred further for 2 h
at 25 °C. The mixture was then chromatographed on a silica gel (100−
200 mesh) column to isolate the allene (R)-7 using n-hexane as eluent
(yield 0.07 g, 62% y, 99% ee). The chiral diamine 1 was recovered
using CHCl3/MeOH (90/10) as eluent without change in its enantio-
(11) Zarotti, P.; Knopfel, T. F.; Aschwanden, P.; Carreira, E. M. ACS
Catal. 2012, 2, 1232.
(12) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002, 124, 5638.
(13) Singh, V. K.; Bisai, A. Org. Lett. 2006, 8, 2405.
(14) Panera, M.; Diez, J.; Merino, I.; Rubio, E.; Gamasa, M. P. Inorg.
Chem. 2009, 48, 11147.
(15) Nakamura, S.; Ohara, M.; Makamura, Y.; Shinbata, N.; Toru, T.
Chem. Eur. J. 2010, 16, 2360.
(16) Benadlia, M.; Negri, D.; Anna, G. D. Tetrahedron Lett. 2004, 45,
8705.
(17) Colombo, F.; Benaglia, M.; Orlandi, S.; Usuelli, F.; Celentano,
G. J. Org. Chem. 2006, 71, 2064.
(18) Akullian, L. C.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem.,
Int. Ed. 2003, 42, 4244.
(19) Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L. Org. Lett. 2003,
5, 3273.
(20) Lu, Y.; Johnstone, T. C.; Arndtsen, B. A. J. Am. Chem. Soc. 2009,
131, 11284.
(21) Lo, V. K.-Y.; Liu, Y.; Wong, M.-K.; Che, C.-M. Org. Lett. 2006,
̈
25
meric purity. Yield: 0.047 g (61%). [α]D = +8.4° (c = 0.94, EtOH)
(lit.50 [α]D = +8.5° (c = 2.4, EtOH)).
25
Procedure for the Synthesis of (S,E)-Ethyl 3-(2-(Pyrrolidin-1-
ylmethyl)pyrrolidin-1-yl)acrylate (12). To the chiral diamine 1
(0.31 g, 2.0 mmol) in dry toluene (3 mL) was added ethyl propiolate
(0.2 g, 2.0 mmol) at 25 °C slowly, and the mixture was stirred further
for 15 min. Toluene was removed under reduced pressure, and the crude
product was purified on basic alumina. The enamine adduct 8 was eluted
using hexane/ethyl acetate (80/20).
Yield: 0.44 g (88%). IR (neat): 3503, 2972, 2791, 1685, 1608, 1460,
1
787, 733 cm−1. H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 12.0 Hz,
1H), 4.47 (d, J = 12.8 Hz, 1H), 4.09 (q, J = 8.0 Hz, 2H), 3.64−3.62
(m, 1H), 3.18−3.11 (m, 2H), 2.53−2.42 (m, 6H), 1.96−1.74 (m, 8H),
1.23 (t, J = 8.0 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 169.7, 148.6,
84.9, 60.6, 58.7, 54.6, 29.6, 23.5, 23.2, 14.7. [α]D25 = −43.9° (c = 0.58,
CHCl3). LCMS (m/z): 253 (M + 1). Anal. Calcd for C14H24N2O2: C,
66.63; H, 9.59; N, 11.10. Found: C, 66.51; H, 9.52; N, 11.21.
8, 1529.
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Wiley-VCH: Weinheim, Germany, 2004.
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43, 1196.
(25) Yu, S.; Ma, S. Angew. Chem., Int. Ed. 2012, 51, 2.
(26) Bates, R. W.; Satcharoen, V. Chem. Soc. Rev. 2002, 31, 12.
(27) Ma, S. Chem. Rev. 2005, 105, 2829.
̈
ASSOCIATED CONTENT
■
S
* Supporting Information
Text giving a representative procedure for the preparation of
racemic allenes and figures giving H and 13C NMR spectra of
1
the products and HPLC analysis profiles. This material is
available free of charge via the Internet at http://pubs.acs.org.
́
(28) Rona, P.; Crabbe, P. J. Am. Chem. Soc. 1969, 91, 3289.
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̈
AUTHOR INFORMATION
Corresponding Author
*E-mail: mpsc@uohyd.ernet.in.
■
(31) Karunakar, G. V.; Periasamy, M. J. Org. Chem. 2006, 71, 7463.
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Notes
The authors declare no competing financial interest.
(35) Yu, S.; Ma, S. Chem. Commun. 2011, 47, 5384.
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2012, 14, 1346.
ACKNOWLEDGMENTS
■
We are grateful to the DST (New Delhi) for a J. C. Bose
National Fellowship grant to M.P. and for the FIST and IRPHA
programs. Support of the UGC under UPE and CAS programs
is also gratefully acknowledged. R.G. is grateful to the CSIR
(New Delhi) for a research fellowship.
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Chem. Commun. 1979, 859.
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