Diastereoselective synthesis of tetrasubstituted propargylamines via hydroamination and metalation of 1-alkynes and their enantioselective conversion to trisubstituted chiral allenes

Article abstract of DOI:10.1021/acs.joc.5b02554

Reaction of cyclic secondary amines with 1-alkynes and copper(I) chloride at 110-120 °C gives the corresponding alkynylcopper complex, which adds to the iminium ion intermediate formed in situ by hydroamination of 1-alkynes to give the corresponding propargylamine derivatives in up to 94% yield and 99% regioselectivity. The diastereomerically pure chiral propargylamines were obtained in 23-89% yield using optically active 2-benzyl morpholine and N-methyl camphanyl piperazine. These chiral propargylamines are readily converted to the corresponding trisubstitued chiral allenes in 71-89% yields with up to 99% ee upon reaction with ZnBr₂ at 120 °C. The results are discussed considering mechanisms involving diastereoselective addition of alkynylcopper complex formed in situ to iminium ions formed in situ regioselectively to produce the corresponding propargylamines, which in turn give the chiral allenes with very high enantioselectivity via an intramolecular 1,5-hydrogen shift in the presence of zinc bromide.

Full text of DOI:10.1021/acs.joc.5b02554

Article
pubs.acs.org/joc
Diastereoselective Synthesis of Tetrasubstituted Propargylamines
via Hydroamination and Metalation of 1‑Alkynes and Their
Enantioselective Conversion to Trisubstituted Chiral Allenes
Mariappan Periasamy,* Polimera Obula Reddy, Iddum Satyanarayana, Lakavathu Mohan,
and Athukuri Edukondalu
School of Chemistry, University of Hyderabad, Central University P.O., Hyderabad 500046, India
S
* Supporting Information
ABSTRACT: Reaction of cyclic secondary amines with 1-
alkynes and copper(I) chloride at 110−120 °C gives the
corresponding alkynylcopper complex, which adds to the
iminium ion intermediate formed in situ by hydroamination of
1-alkynes to give the corresponding propargylamine derivatives
in up to 94% yield and 99% regioselectivity. The
diastereomerically pure chiral propargylamines were obtained
in 23−89% yield using optically active 2-benzyl morpholine
and N-methyl camphanyl piperazine. These chiral propargyl-
amines are readily converted to the corresponding trisub-
stitued chiral allenes in 71−89% yields with up to 99% ee upon reaction with ZnBr2 at 120 °C. The results are discussed
considering mechanisms involving diastereoselective addition of alkynylcopper complex formed in situ to iminium ions formed in
situ regioselectively to produce the corresponding propargylamines, which in turn give the chiral allenes with very high
enantioselectivity via an intramolecular 1,5-hydrogen shift in the presence of zinc bromide.
1). Propargylamine 7aa was also obtained in similar yields using
other copper halides like CuBr and CuI under this reaction
condition along with allene byproduct (entry 11, Table 1). The
reaction temperature was also found to be crucial for this
transformation. Elevating the temperature above 110 °C led to
formation of more amounts of the trisubstituted allene 8a
(entry 9, Table 1), whereas lowering the temperature to 100 °C
resulted in lower yields of the propargylamine product 7aa
(entry 12, Table 1). However, experiments carried out at
different temperatures and time interval conditions to obtain
the trisubstituted allene 8a as major product in a single-pot
operation were not successful. The copper(II) salts CuX2 (Cl
or Br) are not effective, but Cu(OTf)2 affords product 7aa in
92% yield within 0.5 h at 100 °C (entry 12 and 13, Table 1).
Although the use Cu(OTf)2 gave better results, we have
explored the scope of the reaction using CuCl (Table 1, entries
6 and 8) as it is less expensive. The results are summarized in
Table 2.
INTRODUCTION
■
In recent years, there have been several reports on the
hydroamination of alkynes.1 For example, it has been reported
that Zn(OTf)2 promotes hydroamination of 1-alkynes using
amines to give ketimine or keteminium intermediates, which
upon reduction, give trisubstituted amines.2 Metal salts like
ZnX2 and CuX also promote metalation of 1-alkynes to
produce alkynyl metal intermediates, which could add to the
keteiminium intermediates.3 Accordingly, we have envisaged
the generation of iminium ions and alkynylmetal intermediates4
in situ for the synthesis of chiral propargylamines, which in turn
could be converted to trisubstituted chiral allenes. Herein, we
describe the results of detailed studies on the synthesis of
tetrasubstituted chiral propargylamines and trisubstituted chiral
allenes from 1-alkynes (Scheme 1).
RESULTS AND DISCUSSION
■
Initially, we carried out experiments using 1-decyne and
morpholine for the reaction with ZnCl2 or ZnBr2 at 120 °C.
Propargylamine 7aa was not formed under these conditions
(entries 1 and 2, Table 1), but it was formed in 15% yield in 24
h (entry 3, Table 1) when ZnI2 was used and in 27% yield
when Zn(OTf)2 was used (entry 4, Table 1)
Interestingly, when the reaction was carried out using
Zn(OTf)2 without using toluene at 120 °C, propargylamine
7aa was formed in 69% yield within 2 h (entry 5, Table 1).
Further screening led to the observation that the cheaper CuCl
plays the same role, affording 7aa in 83% yield (entry 8, Table
The reaction of morpholine and other 1-alkynes like 1-
octyne 2b and 1-heptyne 2c gave the corresponding
tetrasubstituted propargylamines 7ab and 7ac in 73−79%
yields. The 1-alkynes, such as 3-cyclohexyl-1-propyne (2d), 2-
cyclohexyl-1-acetylene (2e), and 4-phenyl-1-butyne (2g),
furnished the corresponding products in up to 85% yield.
The functionalized alkynes like 6-cyano-1-hexyne (2j), 1-
Received: November 6, 2015
© XXXX American Chemical Society
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Scheme 1. Synthesis of Tetrasubstituted Chiral Propargylamines and Trisubstituted Chiral Allenes
Table 1. Reaction of Morpholine 1a and 1-Decyne 2a with Different Metal Salts to Produce Tetrasubstituted Propargylamine
a
7aa
s. no
solvent
temp. (°C)
MXn
ZnCl2
mol (%)
time (h)
7aa yield (%)
1
2
3
4
5
6
7
8
toluene
toluene
toluene
toluene
120
120
120
120
120
120
110
110
120
110
110
100
100
5
5
24
24
24
24
2
ZnBr2
ZnI2
5
15
27
69
80
68
83
71
79
77
69
92
Zn(OTf)2
Zn(OTf)2
CuCl
5
5
toluene
20
5
6
CuCl
0.5
0.5
0.5
0.5
0.5
0.5
0.5
CuCl
10
10
10
10
10
5
b
9
CuCl
b
10
CuBr
b
11
CuI
12
13
CuCl
Cu(OTf)2
a
b
The reactions were carried out using morpholine 1a (1.0 mmol) and 1-decyne 2a (2.2 mmol). Allene 8a was formed in 7−12% yields as
1
determined by H NMR spectral analysis of the crude reaction mixture.
methoxy-10-decyne (2k), and 1-tert-butyldimethylsilyloxy-5-
hexyne (2l) afforded the corresponding propargylamines in
74−81% (7aj), 69−73% (7ak), and 62−69% (7al) yields,
respectively.
When the reaction was carried out with phenylacetylene 2f
and morpholine 1a in solvent-free conditions at 110 °C,
tetrasubstituted propargylamine 7af was obtained in 29% along
with some unidentified products, but the reaction in toluene
solvent resulted in only a mixture of unidentified products
being formed, and amine 7af was not obtained. We have also
observed that the reaction of 1-decyne 2a with different cyclic
amine derivatives (1b−1f) led to the corresponding tetrasub-
stituted propargylamines 7ba−7fa in 72−83% yields.
It was of interest to us to examine whether the hydro-
amination reaction under these conditions would give the
corresponding chiral propargylamines with diastereoselectivity
if enantiomerically pure chiral amines are used. Accordingly, we
have examined the use of different readily accessible optically
active chiral secondary amines 1g−1l (Figure 1).5
The chiral amines 1g, 1h, and 1k failed to give the
corresponding propargylamines under these conditions, pre-
sumably due to the sterically crowded nature of these amines.
The relatively less hindered chiral amine 1i did give the
corresponding tetrasubstituted propargylamine 7ia in 45% yield
along with the trisubstituted propargylamine 9ia in 37% yield in
the reaction using CuCl in toluene at 120 °C (Scheme 2).
When the reaction was carried out without using toluene, better
selectivity was realized as the tetrasubstituted propargylamine
7ia was obtained in 79% yield along with the trisubstituted
propargylamine 9ia (11% yield) (Scheme 2, eq-1). The
reaction using the chiral morpholine derivative 1j in toluene
gave the diastereomerically pure tetrasubstituted propargyl-
amine 7ja in 76% yield, and the other diastereomer was not
obtained (Scheme 2, eq-2). Slightly higher yield (87%) was
realized in the experiment without using toluene. Whereas the
optically active N-methyl camphanyl piperazine 1l gave an
unidentified mixture of products in toluene, the diastereomeri-
cally pure chiral propargylamine 7la was obtained in 68% yield
under solvent-free conditions. The presence of the other
1
diastereomers in the product could not be detected by H and
13C NMR spectral analysis, but in this experiment, ketone 10a
was obtained as a side product in 14% yield (Scheme 2, eq-3).
We have carried out several experiments using the chiral
morpholine 1j with different alkynes, and the results are
summarized in Table 3. The reactions using 1-alkyne 2b and 2c
gave the corresponding propargylamines in 64−86% yield. The
reaction is also applicable to substituted aliphatic 1-alkynes as
illustrated by reactions using the alkynes 2d, 2e, 2g, 2h, and 2i.
B
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Table 2. Synthesis of Propargylamine 7 Using Cyclic Amines 1 and 1-Alkyne 2
a
b
The reactions were carried out by using amine (1.0 mmol) and 1-alkyne (2.2 mmol) in toluene (3 mL) at 120 °C for 6 h. The reactions were
carried out by using amine (1.0 mmol) and 1-alkyne (2.2 mmol) at 110 °C for 0.5 h.
Figure 1. Chiral amines (1g−1l) used in CuCl-catalyzed chiral propargylamine synthesis.
The corresponding propargylamines were obtained in 59−83%
yields in these experiments. Similarly, the 1-alkynes 2j, 2k, and
2l also gave the corresponding diastereomerically pure
propargylamines with reasonable to good yields.
The configurations at the newly formed stereogenic centers
were assigned as (S) on the basis of X-ray single crystal
structure analysis of propargylamine 7jf (Figure S2).
We have observed that the chiral propargylamines 7ja−7jk
react with ZnBr2 at 120 °C to give the corresponding allenes
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Scheme 2. Synthesis of Chiral Propargylamines from 1-Alkynes Using Chiral Amines (1i−1l)
Table 3. Synthesis of Chiral Propargylamine 7 Using 1-Alkyne 2 and the Chiral Amine 1j Using CuCl
a
b
The reactions were carried out using amines (1.0 mmol) and 1-alkyne (2.2 mmol) in toluene (3 mL) at 120 °C for 6 h. The reactions were carried
c
out using amines (1.0 mmol) and 1-alkyne (2.2 mmol) at 110 °C for 0.5 h. In all reactions, the propargylamine derivatives 7 were obtained in
diastereomerically pure form, and the other diastereomer could not be detected by H NMR or 13C NMR spectral data.
1
D
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a
Table 4. ZnBr2-Promoted Conversion of Chiral Propargylamines to Chiral Allenes
a
The reactions were carried out using propargylamine (1 mmol), which was obtained from chiral morpholine 1j in toluene (3 mL) with ZnBr2 (0.5
mmol) at 120 °C. Yield of allenes. The ee was determined by chiral HPLC analysis.
8a−8k in 68−89% yields (Table 4). The propargylamines
having functionalized groups also afforded the chiral allenes 8j
and 8k in 68−71% yields with up to 99% ee. All propargyl-
amines are converted to the corresponding chiral allenes 8
within 1−3 h under these reaction conditions (Table 4). All of
the optically active allenes obtained using chiral amines 1j are
levorotatory. Hence, the absolute configurations of the major
enantiomer of the chiral allenes are assigned as R based on the
Lowe−Brewster rule6a,b and the Taft6c and Runge6d,e polar-
izabilty parameters expected for the substituents in these
allenes.6f
In recent years, several enantiomerically enriched chiral
trisubstituted allenes were reported, but their configurations
were assigned based only on reaction mechanisms without even
considering the Lowe−Brewster rule. Hence, it is desirable to
briefly discuss the assignment of configuration for the
enantiomerically enriched trisubstituted allenes considering
the Lowe−Brewster rule. The chiral allenes may be considered
to have the structures with substituents A and B at one allene
Figure 2. Configuration of allenes and sign of [α]D values based on
Brewster−Lowe−Taft−Runge polarizability order and Cahn−Ingold−
Prelog (CIP) priority rules.
end and groups X and Y at the other allene end, as depicted in
Figure 2. In the Lowe model,6a the group with highest polarity
(R) configuration. Therefore, the (R)-(+) configuration
A is placed at the top [Figure 2, structure (a)] and the other
group B is also placed above the plane with the X and Y groups
placed in the sides below the plane. The Lowe rule predicts the
allene to be levorotatory with (−)[α]D if the polarizability of
the group X > Y and the allene to be dextrorotatory with
(+)[α]D if the polarizability is Y > X. For disubstitued chiral
allenes, the Cahn−Ingold−Prelog (CIP) priority rules will be in
the order A > B (BH), X > Y (YH). Hence, the
disubstitued allene with (R) configuration will have (−)[α]D,
and the corresponding enantiomer will have (+)[α]D value with
(S) configuration. This will also be the case for enantiomerically
enriched trisubstituted allenes 8a−8k [A (APh or alkyl) > B
(BCH3), X (X Ph or alkyl) > Y (YH) reported here,
where the expected Lowe−Brewster polarizability order and the
CIP priority order are the same as in disubstituted allenes.
Hence, the enantiomerically enriched trisubstituted allene
derivatives 8a−8k with (−)[α]D values are assigned to the
reported for the enantiomerically enriched chiral allene with
same substituents as in 8f (Ph, CH3 and Ph, H) but with [α]D
+122.4 should be corrected as (S)-(+).6h Presumably, the (R)-
(+) configuration was assigned erroneously in the earlier
report6h by comparison with incorrect drawing of the allene
structure (substituents Ph, n-Bu and Ph, H) with [α]D +251 for
which the original authors did not assign the configuration.6g
An interesting possibility is that a group may have higher
priority as per the CIP rules but may not have the highest
polarizability [Figure 2, structure (b)]. In such cases, the allene
with (R) configuration will give (+)[α]D and its (S) enantiomer
will give (−)[α]D values as per the Lowe−Brewster rule. There
are several reports assigning (R)-(+) and (S)-(−) config-
urations for trisubstituted allenes based on reaction mecha-
nisms,7a−d but in these reports, the Lowe−Brewster and Taft−
Runge polarizability and the CIP priority order for the
substituents were not considered while assigning configura-
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Scheme 3. Tentative Mechanism for the Formation of Chiral Propargylamines Using Chiral Amine 7j and Their Conversion to
Chiral Allenes
tions, and the assigned configurations were also not confirmed
by X-ray structure analysis or NMR spectral analysis with chiral
solvating agents as was done in some other cases.7e,f Such
ambiguity is also expected in assigning configurations for
tetrasubstituted chiral allenes.7g Needless to say, because the
Lowe−Brewster rule is based on the sign of optical rotation,
this method of assigning configuration may not be reliable if the
magnitude of the [α]D value is small. In this regard, it may be of
interest to note that an interesting spontaneous resolution of
tetrasubstituted allenic phosphinate derivatives was reported
recently, and the enantiomers were characterized by X-ray
structure analysis but the samples did not have significant
[α]D.7h Presumably, the differences in polarizability of
substituents are small in these cases.
The CuCl-catalyzed formation of propargylamines 7la−7ll
and their conversion to chiral allenes by ZnBr2-promoted
transformation can be explained by the tentative mechanism
and intermediates outlined in Scheme 3. Initially, chiral amine 1
would react with CuCl to form complex 15.8 Then, its reaction
with 1-alkyne would give intermediate complex 17, which could
react with the intermediate 14a formed in situ via hydro-
amination of alkyne through the intermediates 11, 12a, and 16
(Scheme 3).4 Delivery of the alkynyl group from the bottom
face of the ketiminium ion species would lead to the new (S)-
stereogenic center at propargylamine product 19 (Figure S1)
that could complex with ZnBr2 to give intermediate 20, which
after an intramolecular hydride shift and addition of H and
ZnBr group across the triple bond would give intermediate 21
that after elimination of ZnBr2 and imine 22 would afford chiral
allene (R)-8 (Scheme 3).5,9 An important aspect of this
tentative mechanism for the ZnBr2-promoted conversion of
propargylamine 19 to allene (R)-8 is the interaction of the
morpholine oxygen with the ZnBr2 moiety during the
transformation (Scheme 3). Although there is no direct
evidence for this mechanism, previously only poor selectivity
was realized in the chiral disubstituted allene synthesis from
enantiomerically pure propargylamines obtained using 1-alkyne,
benzaldehyde, and simple chiral 2-phenyl pyrrolidine system
where there is no additional oxygen or nitrogen coordination
site available.5a
Enantiomerically pure chiral camphanyl propargylamine
derivatives of 7l are also readily prepared in 68−89% yields
from the corresponding camphanyl amine 1l under solvent-free
conditions (Table 5).
Unfortunately, these propargylamine derivatives 7la−7ll
failed to crystallize, but the configurations of the newly formed
stereocenters were assigned as (S) based on their conversion to
the chiral (R) allenes as the mechanism of formation of
enantiomerically enriched trisubstituted chiral allenes (Scheme
4) is expected to be same as the mechanism for conversion of
tetrasubstituted morpholinyl propargylamine derivatives
(Scheme 3). The chiral propargylamines 7la−7ll react with
ZnBr2 at 120 °C to give the corresponding allenes 8a−8l in
68−90% yield at 120 °C (Table 6). The propargylamines
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a
Table 5. Synthesis of Chiral Propargylamine 7 Using 1-Alkyne 2 and the Chiral Amine 1l Using CuCl
a
The reactions were carried out using amines (1.0 mmol) and 1-alkyne (2.2 mmol) at 110 °C for 0.5 h. In all reactions, the propargylamine
derivatives 7 were obtained in diastereomerically pure forms, and the other diastereomer could not be detected by H NMR or 13C NMR spectral
data. Yield of propargylamines.
1
b
Solvent Conditions. To a stirred suspension of amines 1 (1 mmol)
were added CuCl (0.020 g, 0.2 mmol) and 1-alkyne 2 (2.2 mmol) in
toluene (3 mL) at 25 °C under N2 atmosphere. The contents were
stirred at 120 °C for 6 h. The reaction mixture was cooled to room
temperature. Toluene was removed using reduced pressure. Water (5
mL) and DCM (15 mL) were added. The DCM layer was washed
with saturated NaCl solution, dried (Na2SO4), and concentrated. The
residue was subjected to column chromatography using hexane and
ethyl acetate (90:10) as eluent to isolate propargyl amines 7.
General Procedure for the Synthesis of Tetrasubstituted
Propargylamines 7 from 1-Alkyne and Amine 1 with CuCl in
Solvent-Free Conditions. To a stirred suspension of amines 1 (1
mmol) were added CuCl (0.010 g, 0.1 mmol) and 1-alkyne 2 (2.2
mmol) in sealed tube at 25 °C under N2 atmosphere. The contents
were stirred at 110 °C for 0.5 h. The reaction mixture was cooled to
room temperature. Water (5 mL) and DCM (15 mL) were added.
The DCM layer was washed with saturated NaCl solution, dried
(Na2SO4), and concentrated. The residue was subjected to column
chromatography using hexane and ethyl acetate (90:10) as eluent to
isolate propargylamines 7.
4-(9-Methylnonadec-10-yn-9-yl)morpholine (7aa). Using toluene
as solvent (Table 2): 0.290 g, 80% yield. Under solvent-free conditions
(Table 2): 0.301 g, 83% yield. Colorless oil; Rf = 0.6 (silica gel, 90:10
hexane/EtOAc); IR (neat) 3029, 2947, 2854, 1599, 1495, 1451, 1391,
1352, 1128 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.70 (t, J = 4.0 Hz,
4H), 2.59−2.57 (m, 4H), 2.17 (t, J = 8.0 Hz, 2H), 1.48−1.39 (m, 4H),
1.38−1.23 (m, 25H), 0.87 (t, J = 8.0 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 84.5, 81.6, 67.4, 57.5, 47.0, 39.3, 31.8, 30.0, 29.5, 29.3,
29.2, 29.1, 29.0, 28.8, 24.0, 23.7, 22.6, 18.6, 14.0; LCMS m/z 364 [M +
1]; anal. calcd for C24H45NO C 79.27, H 12.47, N 3.85; found C
79.35, H 12.41, N 3.91.
having functionalized groups also afforded the chiral allenes
8a−8l and in 68−90% yields with up to 99% ee. It was also
found that all propargylamines are converted to the
corresponding chiral allenes 8 within 1−3 h under these
reaction conditions (Table 6). All the optically active allenes
obtained using chiral amines 1l are levorotatory from which the
absolute configurations of the major enantiomers of the chiral
allenes are assigned as R by the Lowe−Brewster rule
considering the Taft−Runge polarizability order expected for
the substituents in these allene derivatives (Figure 2).6
We have also found that the imine byproducts 22 and 34
could be easily reduced before workup to the starting chiral
secondary amines 1j or 1l in 62−72% yields by adding sodium
borohydride in methanol at −20 °C and bringing the contents
to 25 °C and stirring for 2 h.
CONCLUSIONS
■
We have developed a convenient method for the synthesis of
tetrasubstituted propargylamine derivatives via the CuCl-
catalyzed hydroamination of 1-alkynes using the achiral amine
derivatives. In addition, we have devised a method for the
diastereoselective synthesis of chiral propargylamine derivatives
using chiral amines. Furthermore, we have converted these
chiral propargylamine derivatives to trisubstituted chiral allenes
in high enantiomeric purities using zinc bromide. Therefore,
the methods described herein have considerable potential for
further synthetic applications.
4-(7-Methylpentadec-8-yn-7-yl)morpholine (7ab). Using toluene
as solvent (Table 2): 0.224 g, 73% yield. Under solvent-free conditions
(Table 2): 0.230 g, 75% yield. Colorless oil; Rf = 0.6 (silica gel, 90:10
hexane/EtOAc); IR (neat) 2953, 2916, 2845, 2820, 1435, 1118, 945,
EXPERIMENTAL SECTION
General Procedure for the Synthesis of Tetrasubstituted
Propargylamines 7 from 1-Alkyne and Amines 1 with CuCl in
■
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Scheme 4. Tentative Mechanism for the Formation of Chiral Propargylamines Using Chiral Amines 7l and Their Conversion to
Chiral Allenes
cm−1; 1H NMR (400 MHz, CDCl3) δ 3.02 (t, J = 8.0 Hz, 4H), 2.48 (t,
J = 8.0 Hz, 2H), 2.22−2.15 (m, 4H), 1.66−1.55 (m, 6H), 1.39 (s, 3H),
1.26−1.17 (m, 5H), 1.09−0.98 (m, 3H), 0.90−0.88 (m, 7H), 0.79−
0.77 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 84.4, 81.5, 67.4,
57.4, 47.0, 39.3, 31.8, 31.3, 29.0, 28.5, 23.9, 23.7, 22.6, 22.5, 18.5, 14.0;
LCMS m/z 307 [M + 1]; anal. calcd for C20H37NO C 78.11, H 12.13,
N 4.55; found C 78.23, H 12.06, N 4.48.
4-(6-Methyltridec-7-yn-6-yl)morpholine (7ac). Using toluene as
solvent (Table 2): 0.214 g, 77% yield. Under solvent-free conditions
(Table 2): 0.220 g, 79% yield. Yellow oil; Rf = 0.7 (silica gel, 90:10
hexane/EtOAc); IR (neat) 2953, 2926, 2854, 1698, 1600, 1501, 1452,
1323, 1156, 838 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.75−3.73 (m,
4H), 2.67−2.58 (m, 4H), 2.20 (t, J = 8.0 Hz, 2H), 1.61−1.28 (m,
14H), 1.27 (s, 3H), 1.00−0.83 (m, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 84.4, 81.5, 67.4, 57.4, 47.0, 39.3, 32.2, 31.0, 28.8, 23.7, 23.6,
22.5, 22.1, 18.5, 14.0, 13.9; LCMS m/z 280 [M + 1]; anal. calcd for
C18H33NO C 77.36, H 11.90, N 5.01; found C 77.23, H 11.82, N 5.12.
4-(1,5-Dicyclohexyl-2-methylpent-3-yn-2-yl)morpholine (7ad).
Using toluene as solvent (Table 2): 0.261 g, 79% yield. Under
solvent-free conditions (Table 2): 0.271 g, 82% yield. Brown liquid; Rf
= 0.6 (silica gel, 90:10 hexane/EtOAc); IR (neat) 2949, 2855, 2357,
2341, 1452, 1359, 1326, 1274, 1119, 1071, 1032 cm−1; 1H NMR (400
MHz, CDCl3) δ 3.74 (t, J = 4.0 Hz, 4H), 2.66−2.61 (m, 4H), 2.22 (d,
J = 4.0 Hz, 2H), 2.06−1.99 (m, 3H), 1.89−1.77 (m, 6H), 1.72−1.68
(m, 3H), 1.66−1.58 (m, 8H), 1.57−1.51 (m, 5H), 1.31 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 84.0, 81.8, 67.5, 57.6, 47.2, 45.2,
39.3, 36.3, 34.6, 34.4, 32.0, 25.3, 24.9, 24.5; LCMS m/z 332 [M + 1];
anal. calcd for C22H37NO C 79.70, H 11.2, N 4.22; found C 79.58, H
11.31, N 4.28.
4-(2,4-Dicyclohexylbut-3-yn-2-yl)morpholine (7ae). Using toluene
as solvent (Table 2): 0.221 g, 73% yield. Under solvent-free conditions
(Table 2): 0.239 g, 79% yield. Brown liquid; Rf = 0.6 (silica gel, 90:10
hexane/EtOAc); IR (neat) 2934, 2853, 2354, 2333, 1440, 1268, 1251,
1
1004, 792 cm−1; H NMR (400 MHz, CDCl3) δ 3.72 (t, J = 4.0 Hz,
4H), 2.59 (q, J = 4.0 Hz, 2H), 2.17 (t, J = 8.0 Hz, 4H), 1.57−1.47 (m,
7H), 1.26−1.21 (m, 11H), 0.89−0.86 (m, 5H); 13C{1H} NMR (100
MHz, CDCl3) δ 84.5, 81.5, 67.4, 57.4, 47.0, 39.3, 31.9, 30.0, 29.6, 29.3,
29.1, 28.8, 24.0, 23.7, 22.7, 18.6, 14.1; LCMS m/z 304 [M + 1]; anal.
calcd for C20H33NO C 79.15, H 10.96, N 4.62; found C 79.23, H
10.85, N 4.56.
4-(2,4-Diphenylbut-3-yn-2-yl)morpholine (7af). Under solvent-
free conditions (Table 2): 0.084 g, 29% yield. Brown liquid; Rf = 0.6
(silica gel, 95:5 hexane/EtOAc); IR (neat) 3068, 3024, 2954, 2870,
2810, 1498, 1456, 1396, 1254, 1122 1100, 1073, 1023 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.86−7.82 (m,2H), 7.62−7.59 (m,2H), 7.42−
7.32 (m, 6H), 3.80−3.77 (m, 4H), 2.88−2.75 (m, 2H), 2.64−2.50 (m,
2H), 1.73 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.8, 131.8,
128.3, 128.2, 128.1, 127.2, 126.6, 123.1, 88.2, 67.4, 63.4, 48.0, 30.5;
H
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a
Table 6. ZnBr2-Promoted Conversion of Chiral Propargylamines to Chiral Allenes
a
The reactions were carried out by using propargylamine (1 mmol) which obtained from chiral amine 1l in toluene (3 mL) with ZnBr2 (0.5 mmol)
b
c
at 120 °C. Yield of allenes. The ee was determined by chiral HPLC analysis. The ee could not be determined by chiral HPLC as the AD-H, AS-H,
OB-H, OD-H, and OJ-H columns available to us failed to separate the enantiomers of 8l.
LCMS m/z 292 [M + 1]; anal. calcd for C20H21NO C 82.44, H 7.26,
N 4.81; found C 82.28, H 7.31, N 4.73.
hexane/EtOAc); IR (neat) 2942, 2857, 2363, 2242, 1714, 1666, 1454,
1425, 1283, 1115 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.73−3.71 (m,
4H), 2.58−2.57 (m, 4H), 2.51−2.47 (m, 2H), 2.43−2.37 (m, 4H),
1.89−1.84 (m, 2H), 1.80−1.76 (m, 4H), 1.29 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 119.6, 119.1, 82.8, 82.2, 67.2, 60.3, 56.9, 47.0,
38.0, 24.7, 23.6, 21.0, 20.1, 17.1, 16.2, 14.1; LCMS m/z 274 [M + 1];
anal. calcd for C16H23N3O C 70.30, H 8.48, N 15.37; found C 70.21, H
8.41, N 15.26.
4-(3-Methyl-1,7-diphenylhept-4-yn-3-yl)morpholine (7ag). Using
toluene as solvent (Table 2): 0.284 g, 82% yield. Under solvent-free
conditions (Table 2): 0.295 g, 85% yield. Brown liquid; Rf = 0.6 (silica
gel, 90:10 hexane/EtOAc); IR (neat) 3084, 3057, 3030, 2958, 2931,
2860, 1715, 1649, 1600, 1490, 1452, 1260, 1128, 1013 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.33−7.18 (m, 10H), 3.74 (t, J = 4.0 Hz, 4H),
2.87 (t, J = 8.0 Hz, 2H), 2.73 (t, J = 8.0 Hz, 2H), 2.64−2.55 (m, 6H),
1.92−1.88 (m, 2H), 1.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 142.5, 140.7, 128.5, 128.3, 126.2, 125.7, 84.1, 82.2, 67.4, 57.4, 46.9,
41.1, 35.4, 30.5, 23.4, 20.7; LCMS m/z 349 [M + 1]; anal. calcd for
C24H29NO C 82.95, H 8.41, N 4.03; found C 82.84, H 8.47, N 4.07.
4-(4-Methyl-1,9-diphenylnon-5-yn-4-yl)morpholine (7ah). Using
toluene as solvent (Table 2): 0.316 g, 84% yield. Under solvent-free
conditions (Table 2): 0.307 g, 82% yield. Brown liquid; Rf = 0.6 (silica
gel, 90:10 hexane/EtOAc); IR (neat) 2944, 2845, 1733, 1623, 1485,
1435, 1271, 935, cm−1; 1H NMR (400 MHz, CDCl3) δ 7.32−7.28 (m,
5H), 7.22−7.19 (m, 5H), 3.73 (t, J = 4.0 Hz 4H), 2.66−2.62 (m, 6H),
2.25 (t, J = 8.0 Hz, 2H), 1.80−1.73 (m, 3H), 1.64−1.56 (m, 5H), 1.27
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.6, 142.4, 128.3,
128.2, 125.7, 125.6, 84.2, 81.7, 67.4, 57.4, 47.0, 39.1, 35.8, 35.3, 31.8,
30.5, 28.6, 23.8, 23.6, 18.4; LCMS m/z 376 [M + 1]; anal. calcd for
C26H33NO C 83.15, H 8.86, N 3.73; found C 83.05, H 8.81, N 3.68.
4-(5-Methyl-1,11-diphenylundec-6-yn-5-yl)morpholine (7ai).
Using toluene as solvent (Table 2): 0.326 g, 81% yield. Under
solvent-free conditions (Table 2): 0.313 g, 83% yield. Brown liquid; Rf
= 0.6 (silica gel, 90:10 hexane/EtOAc); IR (neat) 3057, 3024, 2926,
4-(1,19-Dimethoxy-9-methylnonadec-10-yn-9-yl)morpholine
(7ak). Using toluene as solvent (Table 2): 0.291 g, 69% yield. Under
solvent-free conditions (Table 2): 0.308 g, 73% yield. Brown liquid; Rf
= 0.6 (silica gel, 85:15 hexane/EtOAc); IR (neat) 2926, 2853, 2363,
1
1708, 1456, 1383, 1273, 1118, 964, 863, 724 cm−1; H NMR (400
MHz, CDCl3) δ 371 (t, J = 4.0 Hz 4H), 3.35 (t, J = 8.0 Hz, 4H), 3.31
(s, 6H), 2.58−2.57 (m, 4H), 2.1 (t,J = 8.0 Hz, 2H), 1.59−1.53 (m,
10H), 1.38−1.29 (m, 16H), 1.23 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 84.4, 81.5, 72.9, 67.4, 58.5, 57.4, 47.0, 39.3, 29.9, 29.6, 29.5,
29.4, 29.1, 29.0, 28.7, 26.1, 26.0, 23.9, 23.8,18.5; LCMS m/z 424 [M +
1]; anal. calcd for C26H49NO3 C 73.71, H 11.66, N 3.31; found C
73.65, H 11.61, N 3.36.
4-(2,2,3,3,9,17,17,18,18-Nonamethyl-4,16-dioxa-3,17-disilanona-
dec-10-yn-9-yl)morpholine (7al). Using toluene as solvent (Table 2):
0.316 g, 62% yield. Under solvent-free conditions (Table 2): 0.352 g,
69% yield. Brown liquid; Rf = 0.6 (silica gel, 95:5 hexane/EtOAc); IR
(neat) 2920, 2854, 2356, 1720, 1643, 1457, 1172 cm−1; 1H NMR (400
MHz, CDCl3) δ 3.69 (t, J = 4.0 Hz, 4H), 3.61 (t, J = 8.0 Hz, 4H),
2.60−2.56 (m, 4H), 2.19 (t, J = 8.0 Hz, 2H), 1.63−1.47 (m, 10H),
1.24 (s, 3H), 0.89 (s, 18H), 0.03 (s, 12H); 13C{1H} NMR (100 MHz,
CDCl3) δ 84.3, 81.6, 67.4, 63.0, 62.7, 57.3, 47.0, 39.1, 33.1, 32.0, 25.9,
25.6, 23.8, 20.2, 18.4, 18.3, −5.2; LCMS m/z 512 [M + 1]; anal. calcd
for C28H57NO3Si2 C 65.69, H 11.22, N 2.74; found C 65.58, H 11.06,
N 2.81.
1
2854, 1484, 1441, 1380, 1326, 1254, 1123, 1024, 964 cm−1; H NMR
(400 MHz, CDCl3) δ 7.32−7.28 (m, 5H), 7.22−7.19 (m, 5H), 3.73 (t,
J = 4.0 Hz, 4H), 2.67−2.57 (m, 8H), 2.25 (t, J = 8.0 Hz, 2H), 1.76 (q,
J = 8.0 Hz, 4H), 1.66−1.53 (m, 6H), 1.27 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 142.6, 142.4, 128.3, 128.2, 125.7, 125.6, 84.2,
81.7, 67.4, 57.4, 47.0, 39.1, 35.8, 35.3, 31.8, 30.5, 28.6, 23.8, 23.6, 18.4;
LCMS m/z 402 [M-1]; anal. calcd for C28H37NO C 83.33, H 9.24, N
3.47; found C 83.15, H 9.32, N 3.41.
1-(9-Methylnonadec-10-yn-9-yl)piperidine (7ba). Using toluene
as solvent (Table 2): 0.277 g, 77% yield. Under solvent-free conditions
(Table 2): 0.292 g, 81% yield. Yellow oil; Rf = 0.6 (silica gel, 90:10
hexane/EtOAc); IR (neat) 3040, 2958, 2931, 2860, 1709, 1687, 1605,
1
1452, 1216, 1172 1024, 854 cm−1; H NMR (400 MHz, CDCl3) δ
7-Methyl-7-morpholinoundec-5-ynedinitrile (7aj). Using toluene
as solvent (Table 2): 0.202 g, 74% yield. Under solvent-free conditions
(Table 2): 0.221 g, 81% yield. Brown liquid; Rf = 0.5 (silica gel, 70:30
2.70−2.59 (m, 4H), 2.20 (t, J = 8.0 Hz, 2H), 1.78−1.58 (m, 6H),
1.49−1.29 (m, 29H), 0.90 (t, J = 8.0 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 83.6, 82.7, 57.8, 47.5, 39.7, 31.9, 31.8, 30.1, 29.5, 29.3,
I
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1
29.2, 29.1, 29.0, 28.8, 26.6, 24.8, 24.2, 24.0, 22.6, 18.6, 14.0; LCMS m/
z 362 [M + 1]; anal. calcd for C25H47N C 83.03, H 13.10, N 3.87;
found C 82.91, H 13.15, N 3.81.
1120, 1079, 949, 894, 739 cm−1; H NMR (400 MHz, CDCl3) δ
7.32−7.28 (m, 3H), 7.25−7.21 (m, 2H), 3.93 (d, J = 8.0 Hz 2H), 3.63
(t, J = 8.0 Hz 2H), 3.40−3.10 (m, 2H), 2.59 (d, J = 12.0 Hz, 2H),
2.22−2.19 (m, 1H), 1.66−1.53 (m, 6H), 1.50 (s, 3H), 1.42−1.30 (m,
10H), 0.95−0.88 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ
141.0, 129.4, 128.3, 125.6, 84.9, 83.8, 68.4, 68.0, 57.0, 55.9, 41.0, 40.1,
31.9, 31.8, 30.3, 30.1, 29.6, 29.3, 29.2, 29.1, 29.0, 28.9, 27.0, 24.2, 22.6,
18.7, 14.1, 14.0; LCMS m/z 454 [M + 1]; anal. calcd for C31H51NO C
82.06, H 11.33, N 3.09; found C 82.16, H 11.26, N 3.15.
1-Methyl-4-(9-methylnonadec-10-yn-9-yl)piperazine (7ca). Using
toluene as solvent (Table 2): 0.274 g, 73% yield. Under solvent-free
conditions (Table 2): 0.300 g, 80% yield. Yellow oil; Rf = 0.7 (silica
gel, 85:15 hexane/EtOAc); IR (neat) 3063, 2926, 2854, 2800, 2756,
1
1495, 1245, 1391, 1205, 1128, 1030, 745 cm−1; H NMR (400 MHz,
CDCl3) δ 2.79−2.42 (m, 8H), 2.29 (s, 3H), 2.18 (t, J = 8.0 Hz, 3H),
1.58−1.39 (m, 9H), 1.35−1.28 (m, 19H), 0.90 (s, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 84.2, 81.9, 57.2, 55.7, 46.3, 45.9, 39.6,
31.9, 31.8, 30.0, 29.5, 29.3, 29.2, 29.1, 29.0, 28.8, 24.1, 23.9, 22.6, 18.6,
14.0; LCMS m/z 377 [M + 1]; anal. calcd for C25H48N2 C 79.72, H
12.84, N 7.44; found C 79.62, H 12.76, N 7.51.
1-(9-Methylnonadec-10-yn-9-yl)-4-phenylpiperazine (7da). Using
toluene as solvent (Table 2): 0.315 g, 72% yield. Under solvent-free
conditions (Table 2): 0.337 g, 77% yield. Yellow oil; Rf = 0.6 (silica
gel, 90:10 hexane/EtOAc); IR (neat) 3062, 3013, 2953, 2925, 2876,
2837, 1665, 1626, 1478, 1391, 1369, 1237, 1117, 1034, 1056 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.31−7.27 (m, 2H), 6.98−6.87 (m, 3H),
3.24 (t, J = 8.0 Hz, 4H), 2.84−2.79 (m, 4H), 2.22 (t, J = 8.0 Hz, 4H),
1.67−1.65 (m, 3H), 1.54−1.38 (m, 9H), 1.34−1.29 (m, 15H), 0.93−
0.90; 13C{1H} NMR (100 MHz, CDCl3) δ151.4, 129.0, 119.4, 115.8,
84.4, 81.8, 57.3, 49.5, 46.5, 43.8, 39.6, 31.9, 31.8, 30.1, 29.6, 29.3, 29.2,
29.1, 28.8, 24.1, 24.0, 23.8, 22.6, 18.6, 14.1; LCMS m/z 439 [M + 1];
anal. calcd for C30H50N2 C 82.13, H 11.49, N 6.39; found C 82.21, H
11.36, N 6.45.
(S)-3-Benzyl-4-((S)-7-methylpentadec-8-yn-7-yl)morpholine (7jb).
Using toluene as solvent (Table 3): 0.321 g, 81% yield. Under solvent-
free conditions (Table 3): 0.341 g, 86% yield. Brown liquid; Rf = 0.8
25
(silica gel, 90:10 hexane/EtOAc); [α]D −41.5 (c 0.69, CHCl3); IR
(neat) 3020, 2953, 2927, 2853, 2033, 1606, 1495, 1364, 1276, 1120,
1077, 955, 843, 739 cm−1; H NMR (400 MHz, CDCl3) δ 7.31−7.17
1
(m, 5H), 3.95−3.37 (m, 2H), 3.23−3.10 (m, 2H), 2.65−2.42 (m, 3H),
2.22 (t, J = 8.0 Hz, 2H), 1.52−1.39 (m, 8H), 1.37−1.30 (m, 2H),
0.91−0.86 (m, 6H), 1.48 (s, 3H), 1.31−1.28 (m, 13H), 0.92−0.88 (m,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.9, 129.4, 128.4, 125.7,
84.6, 84.1, 68.5, 68.0, 56.8, 55.3, 41.7, 41.4, 31.9, 31.3, 30.0, 29.6, 29.0,
28.6, 24.5, 23.7, 22.7, 22.6, 18.7, 14.1, 14.0; LCMS m/z 398 [M − 1];
anal. calcd for C27H43NO C 81.55, H 10.90, N 3.52; found C 81.46, H
10.82, N 3.48.
(S)-3-Benzyl-4-((S)-6-methyltridec-7-yn-6-yl)morpholine (7jc).
Using toluene as solvent (Table 3): Yield: 0.287g, 78% Under
solvent-free conditions (Table 3): 0.313 g, 85% yield. Brown liquid; Rf
= 0.8 (silica gel, 90:10 hexane/EtOAc); [α]D25 −39.5(c 0.36, CHCl3);
IR (neat) 3023, 2955, 2928, 2854, 2150,1601, 1455, 1366, 1273, 1120,
1-Benzyl-4-(9-methylnonadec-10-yn-9-yl)piperazine (7ea). Using
toluene as solvent (Table 2): 0.357 g, 79% yield. Under solvent-free
conditions (Table 2): 0.339 g, 75% yield. Yellow oil; Rf = 0.7 (silica
gel, 95:5 hexane/EtOAc); IR (neat) 3024, 2953, 2854, 1604, 1583,
1
1079, 1029, 949, 802, 739 cm−1; H NMR (400 MHz, CDCl3) δ
7.33−7.21 (m, 5H), 3.96−3.60 (m, 3H), 3.41−3.09 (m, 5H), 2.60−
2.20 (m, 3H), 1.69−1.55 (m, 4H), 1.50 (s,H), 1.46−1.29 (m, 10H),
0.95−0.88 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.9,
129.4, 128.4, 125.7, 84.7, 84.1, 68.5, 68.0, 56.8, 55.3, 41.7, 41.4, 32.1,
31.1, 30.0, 28.7, 24.5, 23.5, 22.7, 22.2, 18.7, 14.1, 14.0; LCMS m/z 368
[M − 1]; anal. calcd for C25H39NO C 81.24, H 10.64, N 3.79; found C
81.14, H 10.56, N 3.86.
1
1489, 1451, 1325, 1259, 1128, 1051, 728 cm−1; H NMR (400 MHz,
CDCl3) δ 7.35−7.28 (m, 5H), 3.5 (s, 2H), 2.70−2.53 (m, 8H), 2.19 (t,
J = 8.0 Hz, 2H), 1.58−1.52 (m, 2H), 1.51−1.49 (m, 3H), 1.43−1.41
(m, 5H), 1.40−1.30 (m, 16H), 1.28 (s, 3H), 0.90 (t, J = 8.0 Hz, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 138.2, 129.2, 128.1, 126.9, 84.1,
(S)-3-Benzyl-4-((S)-2,4-dicyclohexylbut-3-yn-2-yl)morpholine
(7je). Using toluene as solvent (Table 3): 0.282 g, 72% yield. Under
solvent-free conditions (Table 3): 0.310 g, 79% yield. Brown liquid; Rf
= 0.8 (silica gel, 90:10 hexane/EtOAc); [α]D25 −37.1 (c 0.56, CHCl3);
IR (neat) 2925, 2864, 1995, 1655, 1495, 1344, 1276, 1120, 1078, 1022,
82.2, 63.0, 57.3, 53.6, 46.4, 39.6, 31.9, 31.8, 30.0, 29.5, 29.3, 29.2, 29.1,
28.8, 24.2, 23.9, 22.6. 18.6, 14.0; LCMS m/z 451 [M − 1]; anal. calcd
for C31H52N2 C 82.24, H 11.58, N 6.19; found C 82.15, H 11.48, N
6.27.
1-(9-Methylnonadec-10-yn-9-yl)piperidin-3-ol (7fa). Using tol-
uene as solvent (Table 2): 0.294 g, 78% yield. Under solvent-free
conditions (Table 2): 0.312 g, 83% yield. Yellow oil; Rf = 0.7 (silica
gel, 70:30 hexane/EtOAc); IR (neat) 3342, 2953, 2926, 2854, 1704,
1676, 1621, 1320, 1172, 1128, 1063, cm−1; 1H NMR (400 MHz,
CDCl3) δ 3.81(brs, 1H), 2.73−2.35 (m, 6H), 2.16 (t, J = 8.0 Hz, 2H),
1.77−1.75 (m, 1H), 1.57−1.55 (m, 5H), 1.49−1.45 (m, 2H) 1.41−
1.37 (m, 4H), 1.33−1.23 (m, 20H), 0.87 (t, J = 8.0 Hz, 6H) ; 13C{1H}
NMR (100 MHz, CDCl3) δ 83.8, 82.3, 66.5, 57.3, 57.1, 54.0, 53.8,
47.2, 46.8, 39.8, 39.7, 32.0, 31.8, 30.0, 29.0, 28.8, 24.2, 24.0, 23.9, 22.6,
22.0, 18.5, 14.0; LCMS m/z 378 [M + 1]; anal. calcd for C25H47NO C
79.51, H 12.54, N 3.71; found C 79.45, H 12.48, N 3.78.
1-(((S)-1-((S)-9-methylnonadec-10-yn-9-yl)pyrrolidin-2-yl)-
methyl)piperidine (7ia). Using toluene as solvent: 0.199 g, 45% yield.
Under solvent-free conditions (Table 2): 0.350 g, 79% yield. Brown
oil; Rf = 0.6 (silica gel, 90:10 hexane/EtOAc); IR (neat) 2931, 2849,
2213, 1704, 1665, 1457, 1369, 1326, 1205, 1150, 1101, 1063, 991, 904,
734 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.30−3.25 (m, 2H), 2.94−
2.92 (m, 2H), 2.72−2.54 (m,6H), 2.29−2.16 (m, 12H), 1.88 (d, J =
8.0 Hz, 2H), 1.75−1.70 (m,4H), 1.63−1.54 (m, 8H), 1.49−1.46 (m,
4H), 1.41−1.36 (m, 7H), 1.29 (s, 3H), 0.91−0.86 (m, 6H); 13C-
{1H}NMR (100 MHz, CDCl3) δ 82.7, 82.6, 66.6, 58.8, 56.7, 55.3,
50.0, 41.4, 31.8, 31.3, 29.7, 29.5, 29.1, 28.4, 27.1, 25.8, 24.4, 24.1, 22.6,
18.6; LCMS m/z 445 [M + 1]; anal. calcd for C30H56NO C 81.01, H
12.0, N 6.30; found C 81.12, H 12.61, N 6.21.
1
974, 801, 740 cm−1; H NMR (400 MHz, CDCl3) δ 7.30−7.28 (m,
2H), 7.25−7.20 (m, 3H) 3.94 (d, J = 8.0 Hz, 2H), 3.61 (t, J = 12.0 Hz,
2H), 3.42−3.13 (m, 2H), 2.60 (d, J = 8.0 Hz, 2H), 2.37−2.36 (m,
1H), 2.28−2.26 (m, 1H), 2.11−2.10 (m, 4H), 1.81−1.79 (m, 7H),
1.69−1.65 (m, 5H), 1.53 (s, 3H), 1.29−1.26 (m, 5H); 13C{1H} NMR
(100 MHz, CDCl3) δ 141.2, 129.4, 128.4, 125.6, 89.3, 83.6, 68.6, 68.1,
58.6, 56.8, 45.0, 40.9, 33.1, 33.0, 29.3, 29.1, 27.4, 27.1, 26.3, 25.9,
24.8,19.4; LCMS m/z 394 [M + 1]; anal. calcd for C27H39NO C 82.39,
H 9.99, N 3.56; found C 82.45, H 9.91, N 3.61.
(S)-3-Benzyl-4-((S)-2,4-diphenylbut-3-yn-2-yl)morpholine (7jf).
Under solvent-free conditions (Table 3): Yield: 0.087g, 23%. Brown
liquid; Rf = 0.8 (silica gel, 90:10 hexane/EtOAc); [α]D25 −35.8 (c 0.74,
CHCl3); IR (neat) 3023, 2954, 2850, 2055, 1683, 1597, 1488, 1370,
1277, 1171, 1069, 975, 841, 755 cm−1; 1H NMR (400 MHz, CDCl3) δ
7.89−7.87 (m, 3H), 7.56−7.54 (m, 2H), 7.39−7.32 (m, 10H), 3.82−
3.76 (m, 2H), 3.65−3.62 (m, 2H), 3.41−3.35 (m, 2H), 2.64−2.52 (m,
1H), 2.21 (d, J = 8 Hz, 2H), 1.85 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 146.8, 140.6, 131.5, 129.5, 128.5, 128.3, 128.2, 128.1, 127.1,
126.3, 125.9, 123.2, 91.6, 87.9, 68.7, 67.8, 61.5, 56.8, 42.9, 30.5, 30.3;
LCMS m/z 380 [M − 1]; anal. calcd for C27H27NO C 85.00, H 7.13,
N 3.67; found C 85.12, H 7.18, N 3.75.
(S)-3-Benzyl-4-((S)-4-methyl-1,9-diphenylnon-5-yn-4-yl)-
morpholine (7jh). Using toluene as solvent (Table 3): 0.330 g, 71%
yield. Under solvent-free conditions (Table 3): 0.385 g, 83% yield.
Brown liquid; Rf = 0.8 (silica gel, 90:10 hexane/EtOAc); [α]D25 −41.3
(c 0.59, CHCl3); IR (neat) 3024, 2944, 2852, 1954, 1663, 1495, 1370,
1274, 1119,1080, 950, 834, 741 cm−1; 1H NMR (400 MHz, CDCl3) δ
7.36−7.30 (m, 7H), 7.28−7.24 (m, 8H), 3.95 (d, J = 4.0 Hz 2H), 3.65
(d, J = 4.0 Hz 2H), 3.43−3.39 (m, 2H), 2.79−2.75 (m, 2H), 2.71−
(S)-3-Benzyl-4-((S)-9-methylnonadec-10-yn-9-yl)morpholine
(7ja). Using toluene as solvent (Table 3): 0.344 g, 76% yield. Under
solvent-free conditions (Table 3): 0.394 g, 87% yield. Brown liquid; Rf
= 0.8 (silica gel, 90:10 hexane/EtOAc); [α]D25 −45.5 (c 0.62, CHCl3);
IR (neat) 3023, 2953, 2928, 2853, 2195,1601, 1495, 1455, 1366, 1274,
J
DOI: 10.1021/acs.joc.5b02554
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The Journal of Organic Chemistry
Article
2.66 (m, 2H), 2.54−2.51 (m, 2H), 2.29−2.25 (m, 3H), 1.90−1.79 (m,
6H), 1.55 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.5, 141.7,
140.8, 129.4, 128.5, 128.4, 128.3, 125.8,125.7, 84.6, 84.2, 68.5, 67.9,
56.8, 55.2, 41.4, 41.1, 36.0, 34.9, 30.7, 30.1, 25.6, 24.6, 18.2; LCMS m/
z 466 [M + 1]; anal. calcd for C33H39NO C 85.11, H 8.44, N 3.01;
found C 85.03, H 8.49, N 3.18.
50.0, 48.3, 47.4, 47.1, 41.8, 37.7, 37.4, 37.3, 34.2, 33.4, 33.2, 32.6, 31.2,
26.7, 26.5, 26.3, 26.2, 25.9, 22.1, 20.8, 14.6; LCMS m/z 452 [M + 2];
anal. calcd for C31H52N2 C 82.24, H 11.58, N 6.19; found C 82.15, H
11.51, N 6.23.
(4aS,5R,8S,8aR)-1-((S)-2,4-Dicyclohexylbut-3-yn-2-yl)-4,5,9,9-tet-
ramethyldecahydro-5,8-methanoquinoxaline (7le). Under solvent-
free conditions (Table 5): 0.250 g, 59% yield. Yellow liquid; Rf = 0.6
(S)-7-((S)-3-Benzylmorpholino)-7-methylundec-5-ynedinitrile
(7jj). Using toluene as solvent (Table 3): 0.250 g, 69% yield. Under
solvent-free conditions (Table 3): 0.261 g, 72% yield. Brown liquid; Rf
= 0.6 (silica gel, 60:40 hexane/EtOAc); [α]D25 −37.9 (c 0.51, CHCl3);
IR (neat) 2956, 2854, 2244, 1601, 1454, 1274, 1173, 1081, 1029, 950,
25
(silica gel, 90:10 hexane/EtOAc); [α]D −39.3 (c 0.52, CHCl3); IR
(neat) 2922, 2850, 1447, 1388, 1366, 1341, 1314, 1259, 1117, 1021,
1
965, 889, 804, 766 cm−1; H NMR (400 MHz, CDCl3) δ 3.04−3.00
(m, 2H), 2.20 (s, 5H), 2.12 (s, 1H), 1.92−1.86 (m, 3H), 1.80−1.64
(m, 2H), 1.59−1.55 (m, 2H), 1.48−1.42 (m, 6H), 1.16 (s, 4H), 1.11
(s, 5H), 1.09 (s, 2H), 0.97 (s, 3H), 0.76 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 85.6, 84.4, 77.4, 63.9, 61.8, 55.5, 55.2, 51.4, 49.2, 49.1,
46.3, 45.8, 43.7, 37.0, 33.2, 32.5, 29.6, 28.9, 28.4, 27.4, 27.1, 26.4, 26.0,
25.5, 24.7, 22.3, 22.0, 20.3, 14.4; LCMS m/z 425 [M + 1]; anal. calcd
for C29H48N2 C 82.01, H 11.39, N 6.60; found C 82.15, H 11.31, N
6.73.
1
866, 735 cm−1; H NMR (400 MHz, CDCl3) δ 7.33−7.29 (m, 2H),
7.28−7.23 (m, 3H), 3.94 (d, J = 8.0 Hz 2H), 3.61 (t, J = 12.0 Hz, 2H),
3.25−3.21 (m, 2H), 2.55−2.50 (m, 7H), 2.19−2.11 (m, 2H), 1.94−
1.87 (m, 6H), 1.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
140.1, 129.3, 128.5, 126.0, 119.6, 118.9, 85.2, 82.4, 68.4, 67.7, 56.7,
54.8, 41.4, 40.3, 29.9, 24.7, 24.3, 20.0, 17.9, 17.3, 16.3; LCMS m/z 364
[M + 1]; anal. calcd for C23H29N3O C 76.00, H 8.04, N 11.56; found
C 76.15, H 8.12, N 11.65.
(4aS,5R,8S,8aR)-4,5,9,9-Tetramethyl-1-((S)-3-methyl-1,7-diphe-
nylhept-4-yn-3-yl)decahydro-5,8-methanoquinoxaline (7lg). Under
solvent-free conditions (Table 5): 0.355 g, 76% yield. Yellow liquid; Rf
= 0.6 (silica gel, 90:10 hexane/EtOAc); [α]D25 −35.1 (c 0.39, CHCl3);
IR (neat) 3024, 2950, 2931, 2849, 1457, 1265, 1213, 1117, 1050, 915,
(S)-3-Benzyl-4-((S)-1,19-dimethoxy-9-methylnonadec-10-yn-9-
yl)morpholine (7jk). Using toluene as solvent (Table 3): 0.425 g, 83%
yield. Under solvent-free conditions (Table 3): 0.456 g, 89% yield.
Brown liquid; Rf = 0.8 (silica gel, 90:10 hexane/EtOAc); [α]D25 −29.3
(c 0.47, CHCl3); IR (neat) 2925, 2852, 2201, 1718, 1658, 1455, 1356,
1274, 1173, 1029, 973, 843, 741 cm−1; 1H NMR (400 MHz, CDCl3) δ
7.30−7.17 (m, 5H), 3.92 (d, J = 4.0 Hz, 2H), 3.59 (t, J = 8.0, 2H),
3.38−3.35 (m, 2H), 3.33 (s, 3H), 3.32 (s, 3H), 3.21−3.05 (m, 4H),
2.55 (d, J = 12.0 Hz, 2H), 2.43−2.39 (m, 1H), 2.18 (t, J = 8.0, 2H),
1.58−1.50 (m, 10H), 1.46 (s, 3H), 1.30−1.27 (m, 16H); 13C{1H}
NMR (100 MHz, CDCl3) δ 140.9, 129.3, 128.3, 125.7, 84.6, 84.1, 72.9,
72.8, 68.5, 68.0, 58.5, 56.8, 55.2, 43.7, 41.7, 41.3, 29.9, 29.8, 29.6, 29.5,
29.4, 29.3, 29.2, 29.0, 28.9, 28.8, 26.1, 26.0, 24.5, 23.8, 18.6; LCMS m/
z 514 [M + 1]; anal. calcd for C33H55NO3 C 77.14, H 10.79, N 2.73;
found C 77.26, H 10.72, N 2.71.
1
739, 701 cm−1; H NMR (400 MHz, CDCl3) δ 7.34−7.28 (m, 6H),
7.24−7.19 (m, 4H), 3.16−3.10 (t, J = 8.0 Hz, 3H), 3.06−2.91 (m,
2H), 2.88−2.77 (m, 2H), 2.74−2.61 (m, 2H), 2.56−2.46 (m, 3H),
2.27−2.18 (m, 4H), 2.14−1.76 (m, 4H),1.65−1.58 (m, 2H), 1.39 (s,
3H), 1.24 (s, 3H), 1.19−1.09 (m, 2H) 1.03 (s, 3H), 0.82 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 143.0, 140.8, 128.5, 128.4, 128.3,
126.2, 125.5, 85.5, 80.7, 62.0, 60.1, 55.4, 55.0, 49.3, 49.0, 46.4, 44.1,
43.4, 36.9, 35.4, 30.4, 29.3, 27.1, 25.6, 22.0, 20.7, 20.4, 14.4; LCMS m/
z 469 [M + 1]; anal. calcd for C33H44N2 C 84.56, H 9.46, N 5.98;
found C 84.48, H 9.36, N 5.91.
(4aS,5R,8S,8aR)-4,5,9,9-Tetramethyl-1-((S)-4-methyl-1,9-diphe-
nylnon-5-yn-4-yl)decahydro-5,8-methanoquinoxaline (7lh). Under
solvent-free conditions (Table 5): 0.372 g, 75% yield. Yellow liquid; Rf
= 0.6 (silica gel, 90:10 hexane/EtOAc); [α]D25 −41.8 (c 0.53, CHCl3);
IR (neat) 3057, 3018, 2953, 2962, 2832, 1665, 1621, 1473, 1445, 1385,
1232, 1160, 760 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.34−7.27 (m,
5H), 7.24−7.19 (m, 5H), 2.90−2.88 (m, 3H), 2.77 (t, J = 8.0 Hz, 2H),
2.62 (t, J = 8.0 Hz, 2H), 2.29−2.16 (m, 6H), 1.85−1.46 (m, 13H),
1.29 (s, 3H), 1.03 (s, 3H), 0.93 (s, 3H), 0.81 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 142.6, 141.8, 128.5, 128.5, 128.3, 128.2, 125.8,
125.6, 85.5, 80.8, 77.2, 62.1, 60.1, 55.3, 55.1, 49.2, 49.0, 46.3, 44.1,
40.9, 36.9, 36.1, 34.8, 30.7, 27.2, 25.7, 25.5, 22.0, 20.3, 18.1, 14.4;
LCMS m/z 498 [M + 2]; anal. calcd for C35H48N2 C 84.62, H 9.74, N
5.64; found C 84.56, H 9.71, N 5.58.
(4aS,5R,8S,8aR)-4,5,9,9-Tetramethyl-1-((S)-9-methylnonadec-10-
yn-9-yl)decahydro-5,8-methanoquinoxaline (7la). Under solvent-
free conditions (Table 5): 0.329 g, 68% yield. Yellow liquid; Rf = 0.6
25
(silica gel, 90:10 hexane/EtOAc); [α]D −32.1 (c 0.42, CHCl3); IR
(neat) 2953, 2925, 2854, 2794, 1462, 1385, 1259, 1150, 1084, 1023,
1
855, 799, 710 cm−1; H NMR (400 MHz, CDCl3) δ 3.09−2.95 (m,
2H), 2.49−2.40 (m, 4H), 2.27−2.21 (m, 4H), 2.14 (s, 3H), 1.64−1.51
(m, 8H), 1.31−1.24 (m, 20H), 1.19 (s, 3H), 0.99 (s, 3H), 0.90−0.87
(m, 10H), 0.79 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 85.2,
81.1, 62.1, 60.1, 55.4, 55.1, 49.2, 49.0, 46.3, 44.1, 41.4, 36.9, 31.9, 31.8,
30.0, 29.6, 29.3, 29.1, 28.8, 27.2, 25.7, 23.8, 22.6, 22.0, 20.3, 18.6, 14.4,
14.1; LCMS m/z 486 [M + 2]; anal. calcd for C33H60N2 C 81.75, H
12.47, N 5.78; found C 81.62, H 12.36, N 5.71.
(4aS,5R,8S,8aR)-4,5,9,9-Tetramethyl-1-((S)-4-methyl-1,10-diphe-
nyldec-5-yn-4-yl)decahydro-5,8-methanoquinoxaline (7li). Under
solvent-free conditions (Table 5): 0.413 g, 79% yield. Yellow liquid;
Rf = 0.6 (silica gel, 90:10 hexane/EtOAc); [α]D −47.6 (c 0.56,
CHCl3); IR (neat) 3056, 3016, 2956, 2849, 1664, 1625, 1473, 1384,
1236, 1150, 739 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.32−7.21 (m,
10H), 2.92−2.81 (m, 4H), 2.66−2.52 (m, 5H), 2.34−2.26 (m, 8H),
1.79−1.70 (m, 7H), 1.36−1.29 (m, 12H), 1.04 (s, 3H), 0.81 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 142.4, 128.4, 128.3, 125.7, 84.8,
78.2, 75.1, 65.3, 54.5, 50.1, 47.7, 47.5, 47.1, 46.5, 43.5, 37.3, 35.4, 30.4,
29.7, 28.6, 26.3, 22.2, 20.5, 18.5, 14.9; LCMS m/z 525 [M + 1]; anal.
calcd for C37H52N2 C 84.68, H 9.99, N 5.34; found C 84.49, H 9.91, N
5.26.
(4aS,5R,8S,8aR)-4,5,9,9-Tetramethyl-1-((S)-7-methylpentadec-8-
yn-7-yl)decahydro-5,8-methanoquinoxaline (7lb). Under solvent-
free conditions (Table 5): 0.273 g, 64% yield. Yellow liquid; Rf = 0.6
25
25
(silica gel, 90:10 hexane/EtOAc); [α]D −48.8 (c 0.13, CHCl3); IR
(neat) 2964, 2926, 2854, 2810, 1457, 1375, 1271, 1128, 958, 931, 860,
1
830, 750, 706 cm−1; H NMR (400 MHz, CDCl3) δ 3.08−2.99 (m,
2H), 2.52−2.47 (d, J = 4.0 Hz, 1H), 2.25−2.16 (m, 7H), 1.73−1.49
(m, 8H), 1.30−1.26 (m, 17H), 1.17 (s, 3H), 1.12−1.07 (m, 1H), 0.99
(s, 3H), 0.90−0.88 (m, 7H), 0.78 (s, 3H); 13C{1H}NMR (100 MHz,
CDCl3) δ 85.2, 81.1, 77.3, 62.1, 60.2, 55.4, 55.1, 49.2, 49.0, 46.3, 44.1,
41.4, 36.9, 31.8, 31.4, 29.6, 29.0, 28.5, 27.2, 25.7, 23.7, 22.6, 22.1, 20.3,
18.7, 14.4, 14.1; LCMS m/z 428 [M+]; anal. calcd for C29H52N2 C
81.24, H 12.22, N 6.53; found C 81.06, H 12.15, N 6.45.
(4aS,5R,8S,8aR)-1-((S)-1,5-Dicyclohexyl-2-methylpent-3-yn-2-yl)-
4,5,9,9-tetramethyldecahydro-5,8-methanoquinoxaline (7ld).
Under solvent-free conditions (Table 5): 0.275 g, 61% yield. Yellow
liquid; Rf = 0.6 (silica gel, 90:10 hexane/EtOAc); [α]D25 −42.3 (c 0.39,
CHCl3); IR (neat) 2914, 2844, 2363, 1669, 1432, 1368, 1277, 1258,
(4aS,5R,8S,8aR)-1-((S)-1,19-Dimethoxy-9-methylnonadec-10-yn-
9-yl)-4,5,9,9-tetramethyldecahydro-5,8-methanoquinoxaline (7lk).
Under solvent-free conditions (Table 5): 0.424 g, 78% yield. Yellow
liquid; Rf = 0.6 (silica gel, 90:10 hexane/EtOAc); [α]D25 −48.6 (c 0.61,
CHCl3); IR (neat) 2925, 2951, 2854, 1451, 1391, 1265, 1122, 1030,
1
1
1156, 745 cm−1; H NMR (400 MHz, CDCl3) δ 3.45 (t, J = 8.0 Hz,
910, 854, 730, 701 cm−1; H NMR (400 MHz, CDCl3) δ 3.39−3.36
1H), 2.89−2.82 (m, 2H), 2.75−2.70 (m, 1H), 2.58−2.53 (m, 1H),
2.26 (s, 3H), 2.12−2.08 (m, 5H), 1.80−1.64 (m, 15H), 1.54−1.40 (m,
5H), 1.25 (s, 3H), 1.18−1.04 (m, 10H), 0.99 (s, 3H), 0.77 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 82.9, 80.1, 78.7, 64.8, 54.7, 53.9,
(m, 4H), 3.34 (s, 6H), 3.08−3.00 (m, 3H), 2.23 (s, 4H), 2.20−2.15
(m, 3H), 1.59−1.55 (m, 7H), 1.51−1.46 (m, 4H), 1.34−1.27 (m,
22H), 1.18 (s, 3H), 1.12−1.08 (m, 2H), 0.99 (s, 3H), 0.79 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 85.2, 81.0, 77.1, 72.9, 62.1, 60.1,
K
DOI: 10.1021/acs.joc.5b02554
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The Journal of Organic Chemistry
Article
58.5, 55.4, 55.1, 49.2, 49.0, 46.3, 44.1, 41.3, 36.9, 29.9, 29.6, 29.5, 29.4,
29.3, 29.1, 29.0, 28.8, 27.2, 26.1, 25.6, 23.7, 22.0, 20.3, 18.6, 14.4;
LCMS m/z 546 [M + 2]; anal. calcd for C35H64N2O2 C 77.15, H
11.84, N 5.14; found C 77.31, H 11.76, N 5.23.
100:0 hexane/EtOAc). The enantioselectivity was determined by
HPLC using chiral column, chiralcel OJ-H, 95:5 hexanes/i-PrOH; flow
rate, 0.5 mL/min, 190 nm; retention times, 6.4 min (major) and 8.2
min (minor); IR (neat) 2936, 2841, 2239, 1964, 1448, 1416, 1280,
1
(4aS,5R,8S,8aR)-4,5,9,9-Tetramethyl-1-((S)-2,2,3,3,9,17,17,18,18-
nonamethyl-4,16-dioxa-3,17-disilanonadec-10-yn-9-yl)decahydro-
5,8-methanoquinoxaline (7ll). Under solvent-free conditions (Table
5): 0.391 g, 62% yield. Yellow liquid; Rf = 0.6 (silica gel, 85:15 hexane/
1232, 840 cm−1; H NMR (400 MHz, CDCl3) δ 5.02 (s, 1H), 1.90−
1.67 (m, 12H), 1.26−1.22 (m, 9H), 1.14−1.00 (m, 4H); 13C{1H}
NMR (100 MHz, CDCl3) δ 199.2, 105.3, 96.9, 41.6, 37.7, 33.3, 32.1,
32.0, 26.5, 26.4, 26.3, 26.1, 17.8; LCMS m/z 219 [M + 1]; anal. calcd
for C16H26 C 88.00, H 12.0; found C 87.91, H 12.06.
25
EtOAc); [α]D −31.9 (c 0.73, CHCl3) IR (neat) 2947, 2931, 2851,
1
2859, 2788, 1467, 1396, 1254, 1106, 832, 782 cm−1; H NMR (400
(R)-Buta-1,2-diene-1,3-diyldibenzene (8f). From chiral propargyl-
amine 7jf: 0.146 g, 71% yield, 94% ee; [α]D25 −962.3 (c 0.47, CHCl3).
Colorless liquid, Rf = 0.6 (silica gel, 97:3 hexane/EtOAc). The
enantioselectivity was determined by HPLC using chiral column,
chiralcel OB-H, 98:2 hexanes/i-PrOH; flow rate, 1.0 mL/min, 220 nm;
retention times, 6.15 min (minor) and 7.05 min (major); IR (neat)
MHz, CDCl3) δ 3.64−3.61 (m, 4H), 3.08−2.96 (m, 2H), 2.53−2.45
(m, 1H), 2.23−2.14 (m, 6H), 1.73−1.46 (m, 11H), 1.43−1.34 (m,
2H), 1.28 (s, 5H), 1.18 (s, 3H), 1.12−1.07 (m, 2H), 0.99 (s, 3H), 0.90
(s, 18H), 0.78 (s, 3H), 0.06 (s, 12H); 13C{1H}NMR (100 MHz,
CDCl3) δ 85.2, 81.0, 63.3, 62.7, 62.1, 60.1, 55.4, 55.1, 49.2, 49.0, 46.3,
44.0, 41.3, 36.9, 33.2, 32.0, 29.6, 27.2, 25.9, 25.6, 25.5, 22.0, 20.3, 20.2,
18.5, 18.3, 14.4, −5.2; LCMS m/z 634 [M + 2]; anal. calcd for
C37H72N2O2Si2 C 70.09, H 11.46, N 4.42; found C 70.27, H 11.37, N
4.36.
General Procedure for the Preparation of Chiral Allenes
from Propargylamines. The chiral propargylamines 7 (1 mmol)
were added to a stirred suspension of ZnBr2 (0.113 g, 50 mol %) in
dry toluene (3 mL), and the contents were refluxed for 1−3 h at 120
°C under a nitrogen atmosphere. Toluene was removed under reduced
pressure, and the crude product was purified with silica gel (100−200
mesh) column chromatography using hexane/ethyl acetate as eluent to
isolate the chiral allenes 8.
(R)-9-Methylnonadeca-9,10-diene (8a). From chiral propargyl-
amine 7ja: 0.239 g, 86% yield, 96% ee; [α]D25 −99.9 (c 0.51, CHCl32)5.
From chiral propargylamine 7la: 0.247 g, 89% yield, 97% ee; [α]D
−101.5 (c 0.72, CHCl3). Colorless liquid, Rf = 0.8 (silica gel, 100:0
hexane/EtOAc). The enantioselectivity was determined by HPLC
using chiral column, chiralcel Phenomenex cellulose-1, 100:0 hexanes/
i-PrOH; flow rate, 1.5 mL/min, 190 nm; retention times, 2.3 min
(minor) and 3.5 min (major); IR (neat) 2958, 2926, 2854, 1961, 1468,
1380, 723 cm−1; 1H NMR (400 MHz, CDCl3) δ 5.00 (s, 1H), 2.36 (s,
1H), 1.95−1.92 (m, 4H), 1.67−1.66 (t, J = 4.0 Hz, 3H), 1.40- 1.36 (m,
21H), 0.90−0.89 (m, 8H); 13C{1H} NMR (100 MHz, CDCl3) δ
201.1, 99.1, 90.0, 34.1, 31.8, 31.7, 29.4, 29.3, 29.0, 28.8, 27.5, 22.7,
19.3, 14.1; LCMS m/z 279 [M + 1]; anal. calcd for C20H38 C 86.25, H
13.75; found C 86.42, H 13.71.
(−)-7-Methylpentadeca-7,8-diene (8b). From chiral propargyl-
amine 7jb: 0.197 g, 89% yield, 90% ee; [α]D25 −98.8 (c 0.42, CHCl32)5.
From chiral propargylamine 7lb: 0.200 g, 90% yield, 96% ee; [α]D
−121.8 (c 0.56, CHCl3). Colorless liquid, Rf = 0.8 (silica gel, 100:1
hexane/EtOAc). The enantioselectivity was determined by HPLC
using chiral column, chiralcel OB-H, 90:10 hexanes/i-PrOH; flow rate,
0.3 mL/min, 190 nm; retention times, 10.3 min (major) and 13.3 min
(minor); IR (neat) 2958, 2926, 2854, 1961, 1498, 1380, 723 cm−1; 1H
NMR (400 MHz, CDCl3) δ 5.00−4.97 (m, 1H), 1.99−1.91 (m, 4H),
1.68−1.58 (m, 3H), 1.44- 1.31 (m, 16H), 0.93−0.89 (m, 6H);
13C{1H}NMR (100 MHz, CDCl3) δ 201.1, 99.1, 90.0, 34.1, 31.8, 31.7,
1
3060, 3027, 2955, 1936, 1597, 1493, 1452, 758 cm−1; H NMR (400
MHz, CDCl3) δ 7.59−7.55 (m, 2H), 7.44−7.33 (m, 8H), 6.57 (s, 1H),
2.32 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 206.8, 136.3,
134.5, 128.7, 128.4, 127.0, 126.9, 125.8, 104.5, 96.5, 16.7. The 13C
NMR data showed 1:1 correspondence with the reported data.
(R)-(3-Methylhepta-3,4-diene-1,7-diyl)dibenzene (8g). From chi-
25
ral propargylamine 7lg: 0.233 g, 89% yield, 99% ee; [α]D −109.3 (c
0.45, CHCl3). Colorless liquid, Rf = 0.9 (silica gel, 100:0 hexane/
EtOAc). The enantioselectivity was determined by HPLC using chiral
column, chiralcel chiralcel OJ-H, 100:0 hexanes/i-PrOH; flow rate, 0.5
mL/min, 214 nm; retention times, 11.8 min (major) and 16.1 min
(minor); IR (neat) 3084, 3068, 3024, 2854, 1961, 1600, 1495, 1452,
1265, 1035, 745 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.31 (t, J = 8.0
Hz, 5H), 7.21 (d, J = 4.0 Hz, 5H), 5.14−5.10 (m, 1H), 2.69 (t, J = 8.0
Hz, 4H), 2.31−2.22 (m, 4H), 1.70 (s, 3H); 13C{1H}NMR (100 MHz,
CDCl3) δ 201.4, 142.2, 142.0, 128.4, 128.3, 128.1, 125.6, 99.4, 90.2,
35.6, 35.4, 33.8, 30.8, 19.3; LCMS m/z 263 [M + 1]; anal. calcd for
C20H22 C 91.55, H 8.45; found C 91.45, H 8.53.
(R)-(4-Methylnona-4,5-diene-1,9-diyl)dibenzene(8h). From chiral
propargylamine 7jh: 0.243 g, 84% yield, 99% ee; [α]D25 −85.9 (c 0.46,
CHCl3). From chiral propargylamine 7lh: 0.251 g, 86% yield, 99% ee;
25
[α]D −85.5 (c 0.63, CHCl3). Colorless liquid, Rf = 0.6 (silica gel,
100:0 hexane/EtOAc). The enantioselectivity was determined by
HPLC using chiral column, chiralcel Phenomenex amylose-2, 100:0
hexanes/i-PrOH; flow rate, 0.5 mL/min, 190 nm; retention times, 8.1
min (major) and 11.7 min (minor); IR (neat) 2958, 2849, 1960, 1447,
1347, 1258, 986, 962, 889, 842 cm−1; 1H NMR (400 MHz, CDCl3) δ
7.34−7.29 (m, 5H), 7.24−7.20 (m, 5H), 5.10 (s, 1H), 2.74 (t, J = 8.0
Hz, 2H), 2.68−2.64 (m, 3H), 2.23 (d of t J1 = 8.0 Hz, J2 = 2.6 Hz,
2H), 2.08−1.99 (m, 4H), 1.80−1.72 (m, 4H), 1.28 (t, J = 8.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 201.3, 142.6, 128.4, 128.2, 125.6,
99.1, 90.1, 35.4, 35.3, 33.5, 31.0, 29.3, 28.8, 19.4; LCMS m/z 291 [M +
1]; anal. calcd for C22H26 C 90.98, H 9.02; found C 90.82, H 9.08.
(R)-(5-Methylundeca-5,6-diene-1,11-diyl)dibenzene(8i). From chi-
25
ral propargylamine 7li: 0.263 g, 83% yield, 94% ee; [α]D −97.2 (c
0.49, CHCl3). Colorless liquid, Rf = 0.9 (silica gel, 100:0 hexane/
EtOAc). The enantioselectivity was determined by HPLC using chiral
column, chiralcel Phenomenex amylose-2, 100:0 hexanes/i-PrOH;
flow rate, 1.0 mL/min, 190 nm; retention times, 3.7 min (major) and
5.2 min (minor); IR (neat) 2923, 2850, 1962, 1727, 1599, 1489, 1448,
1089, 1019, 810 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.30−7.27 (m,
5H), 7.26−7.18 (m, 5H), 5.06−4.96 (m, 1H), 2.65−2.58 (m, 5H),
2.23−2.19 (m, 2H), 1.97 (t, J = 8.0 Hz, 4H), 1.66−1.63 (m, 4H), 1.46
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 201.2, 142.8, 128.4,
128.2, 125.6, 99.1, 90.0, 35.8, 33.9, 31.1, 29.2, 29.0, 28.8, 27.2, 19.3;
LCMS m/z 319 [M + 1]; anal. calcd for C24H30 C 90.51, H 9.49;
found C 90.65, H 9.39.
29.7, 29.4, 29.3, 29.0, 28.8, 27.5, 22.7, 19.3, 14.1; LCMS m/z 223 [M +
1]; anal. calcd for C16H30 C 86.40, H 13.60,; found C 86.28, H 13.51.
(R)-(2-Methylpenta-2,3-diene-1,5-diyl)dicyclohexane (8d). From
chiral propargylamine 7ld: 0.209 g, 85% yield, 99% ee; [α]D25 −91.1 (c
0.39, CHCl3). Colorless liquid, Rf = 0.9 (silica gel, 100:0 hexane/
EtOAc). The enantioselectivity was determined by HPLC using chiral
column, chiralcel OJ-H, 95:5 hexanes/i-PrOH; flow rate, 0.5 mL/min,
190 nm; retention times, 6.4 min (minor) and 8.1 min (major); IR
(neat) 3059, 3030, 2923, 2853, 1965, 1605, 1495, 1454, 1263, 1074,
1
1019 cm−1; H NMR (400 MHz, CDCl3) δ 4.90 (s, 1H), 1.86−1.80
(m, 3H), 1.71−1.63 (m, 10H), 1.4−1.18 (m, 10H), 0.89 (m, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 202.3, 96.5, 87.6, 42.3, 38.1,
37.5, 35.7, 33.4, 33.3, 33.1, 26.6, 26.3, 19.4; LCMS m/z 247 [M + 1];
anal. calcd for C18H30 C 87.73, H 12.27; found C 87.63, H 12.21.
(R)-Buta-1,2-diene-1,3-diyldicyclohexane (8e). From chiral prop-
(R)-5-Methylundeca-5,6-dienedinitrile(8j). From chiral propargyl-
25
amine 7jj: 0.133 g, 71% yield, 99% ee; [α]D −56.2 (c 0.35, CHCl3).
Colorless liquid, Rf = 0.6 (silica gel, 95:5 hexane/EtOAc). The
enantioselectivity was determined by HPLC using chiral column,
chiralcel AS-H, 100:0 hexanes/i-PrOH; flow rate, 0.3 mL/min, 190
nm; retention times, 13.0 min (minor) and 17.2 min (major); IR
(neat) 3298, 2931, 2854, 2246, 1956, 1446, 1424, 1375, 1238 cm−1;
1H NMR (400 MHz, CDCl3) δ 5.04 (m, 1H), 2.37 (q, J = 8.0 Hz,
25
argylamine 7je: 0.189 g, 87% yield, 99% ee; [α]D −77.9 (c 0.42,
CHCl3). From chiral propargylamine 7le: 0.187 g, 85% yield, 99% ee;
25
[α]D −76.8 (c 0.59, CHCl3). Colorless liquid, Rf = 0.8 (silica gel,
L
DOI: 10.1021/acs.joc.5b02554
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
4H), 2.14−2.06 (m, 4H), 1.80−1.72 (m, 4H), 1.68 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 201.5, 119.5, 98.6, 89.2, 32.5, 27.9, 24.7,
23.2, 19.1, 16.5, 16.4; LCMS m/z 188 [M + 1]; anal. calcd for
C12H16N2 C 76.55, H 8.57, N 14.88; found C 76.63, H 8.51, N 14.72.
(R)-1,19-Dimethoxy-9-methylnonadeca-9,10-diene(8k). From
(c) Biyikal, M.; Porta, M.; Roesky, P. W.; Blechert, S. Adv. Synth. Catal.
2010, 352, 1870.
(4) (a) Zhou, L.; Jiang, H.-f.; Li, C.-J. Adv. Synth. Catal. 2008, 350,
2226. (b) Zhou, L.; Shuai, Q.; Jiang, H.-f.; Li, C.-J. Chem. - Eur. J. 2009,
15, 11668. (c) Zhou, L.; Bohle, D.; Jiang, H.-f.; Li, C.-J. Synlett 2009,
2009, 937. (d) Han, J.-B.; Xu, B.; Hammond, G. B. J. Am. Chem. Soc.
2010, 132, 916. (e) Pierce, C. J.; Yoo, H.; Larsen, C. H. Adv. Synth.
Catal. 2013, 355, 3586. (f) Palchak, Z.; Lussier, D. J.; Pierce, C. J.;
Yoo, H.; Larsen, C. H. Adv. Synth. Catal. 2015, 357, 539.
(5) (a) Periasamy, M.; Sanjeevakumar, N.; Dalai, M.;
Gurubrahamam, R.; Reddy, P. O. Org. Lett. 2012, 14, 2932.
(b) Gurubrahamam, R.; Periasamy, M. J. Org. Chem. 2013, 78, 1463.
(c) Periasamy, M.; Reddy, P. O.; Sanjeevakumar, N. Eur. J. Org. Chem.
2013, 2013, 3866. (d) Periasamy, M.; Reddy, P. O.; Edukondalu, A.;
Dalai, M.; Alakonda, L. M.; Udaykumar, B. Eur. J. Org. Chem. 2014,
2014, 6067. (e) Periasamy, M.; Reddy, P. O.; Sanjeevakumar, N.
Tetrahedron: Asymmetry 2014, 25, 1634.
(6) (a) Lowe, G. Chem. Commun. 1965, 411. (b) Brewster, J. H. Top.
Stereochem. 1967, 2, 1. (c) Taft, R. W.; Taagepera, M.; Abboud, J. L.
M.; Wolf, J. F.; DeFrees, D. J.; Hehre, W. J.; Bartmess, J. E.; Mclver, R.
T. J. Am. Chem. Soc. 1978, 100, 7767. (d) Runge, W.; Kresze, G. J. Am.
Chem. Soc. 1977, 99, 5597. (e) Elsevier, C. J.; Vermeer, P.; Gedanken,
A.; Runge, W. J. Org. Chem. 1985, 50, 364. (f) Stereochemistry of
Organic Compounds; Eliel, E. L., Wilen, S. H., Mander, L. N., Eds.; John
Wiley and sons: New York, 2008. (g) Jansen, A.; Krause, N. Inorg.
Chim. Acta 2006, 359, 1761. (h) Ruano, J. L. G.; Marzo, L.; Marcos,
V.; Alvarado, C.; Aleman, J. Chem. - Eur. J. 2012, 18, 9775.
(7) (a) Uehling, M. R.; Marionni, S. T.; Lalic, G. Org. Lett. 2012, 14,
25
chiral propargylamine 7jk: 0.229 g, 68% yield, 99% ee; [α]D −92.3
(c 0.55, CHCl3). From chiral propargylamine 7lk: 0.246 g, 73% yield,
90% ee; [α]D25 −79.1 (c 0.62, CHCl3). Yellow oil, Rf = 0.7 (silica gel,
98:2 hexane/EtOAc). The enantioselectivity was determined by
HPLC using chiral column, chiralcel OD-H, 100:0 hexanes/i-PrOH;
flow rate, 1.0 mL/min, 190 nm; retention times, 6.0 min (major) and
9.2 min (minor); IR (neat) 2920, 2860, 1967, 1714, 1457, 1368, 1261,
1
1172, 745 cm−1; H NMR (400 MHz, CDCl3) δ 4.97 (s, 1H), 3.41−
3.32 (m, 10H), 1.95−1.88 (m, 3H), 1.65−1.64 (m, 3H), 1.61−1.52
(m, 4H), 1.42−1.30 (m, 20H); 13C{1H} NMR (100 MHz, CDCl3) δ
201.1, 99.1, 90.0, 72.9, 58.5, 34.1, 29.6, 29.5, 29.3, 29.2, 29.0, 27.5,
26.1, 19.3; LCMS m/z 339 [M + 1]; anal. calcd for C22H42O2 C 78.05,
H 12.5; found C 78.23, H 12.41.
(R)-2,2,3,3,13,25,25,26,26-Nonamethyl-4,24-dioxa-3,25-disila-
heptacosa-13,14-diene (8l). From chiral propargylamine 7ll: 0.289 g,
25
68% yield; [α]D −66.3 (c 0.41, CHCl3). Colorless liquid, Rf = 0.6
(silica gel, 97:3 hexane/EtOAc); IR (neat) 2958, 2936, 2806, 1715,
1
1473, 1260, 1095 cm−1; H NMR (400 MHz, CDCl3) δ 5.0 (s, 1H),
3.63−3.59 (m, 4H), 2.21 (s, 3H), 1.98−1.95 (m, 4H), 1.66−1.52 (m,
4H), 1.46−1.26 (m, 4H), 0.89 (s, 18H), 0.05 (s, 12H); 13C{1H} NMR
(100 MHz, CDCl3) δ 201.2, 99.2, 90.1, 84.5, 68.2, 63.1, 62.5, 33.8,
32.4, 32.3, 31.8, 31.5, 29.1, 25.9, 25.5, 24.9, 23.8,19.2, 18.3, 18.2,
−5.20; LCMS m/z 427 [M + 1]; anal. calcd for C24H50O2Si2 C 67.54,
H 11.81; found C 67.41, H 11.76.
́ ́
362. (b) Li, H.; Muller, D.; Guenee, L.; Alexakis, A. Org. Lett. 2012, 14,
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5880. (c) Yang, M.; Yokokawa, N.; Ohmiya, H.; Sawamura, M. Org.
Lett. 2012, 14, 816. (d) Wang, Y.; Zhang, W.; Ma, S. J. Am. Chem. Soc.
2013, 135, 11517. (e) Wang, M.; Liu, Z-Li.; Zhang, X.; Tian, P.-P.; Xu,
Y.-H.; Loh, T.-P. J. Am. Chem. Soc. 2015, 137, 14830. (f) Uccello-
Barretta, G.; Balzano, F.; Caporusso, A. M.; Iodice, A.; Salvadori, P. J.
Org. Chem. 1995, 60, 2227. (g) Hammel, M.; Deska, J. Synthesis 2012,
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02554.
1
Copies of the H and 13C NMR spectra of the products,
HPLC analysis profiles, X-ray data, and ORTEP diagram
(PDF)
(8) (a) Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed.
2002, 41, 2535. (b) Beck, W.; Schmidt, C.; Wienold, R.; Steimann, M.;
Wagner, B. Angew. Chem., Int. Ed. Engl. 1989, 28, 1529.
AUTHOR INFORMATION
Corresponding Author
*E-mail: mpsc@uohyd.ernet.in.
Notes
■
(9) (a) Crabbe,
Chem. Commun. 1979, 859. (b) Searles, S.; Li, Y.; Nassim, B.; Lopes,
M.-T. R.; Tran, P. T.; Crabbe, P. J. Chem. Soc., Perkin Trans. 1 1984,
́ ́
P.; Fillion, H.; Andre, D.; Luche, J.-L. J. Chem. Soc.,
́
747. (c) Lo, V. K.-Y.; Wong, M.-K.; Che, C.-M. Org. Lett. 2008, 10,
517. (d) Lo, V. K.-Y.; Zhou, C.-Y.; Wong, M.-K.; Che, C. M. Chem.
Commun. 2010, 46, 213. (e) Tang, X.; Zhu, C.; Cao, T.; Kuang, J.; Lin,
W.; Ni, S.; Ma, S. Nat. Commun. 2013, 4, 2450. (f) Tang, X.; Han, Y.;
Ma, S. Org. Lett. 2015, 17, 1176.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are thankful to the DST-SERB (New Delhi) for a J. C. Bose
National Fellowship grant (SR/S2/JCB-33/2005) and CSIR
(New Delhi) research grant (02(0176/14/EMR-II) to M.P.
and also for the FIST and IRPHA programs. Support of the
UGC under UPE and CAS programs is also gratefully
acknowledged. Research fellowships to P.O.R. and A.E. by
CSIR (New Delhi) and to I.S. and L.M. by UGC (New Delhi)
are gratefully acknowledged.
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DOI: 10.1021/acs.joc.5b02554
J. Org. Chem. XXXX, XXX, XXX−XXX