Enantioselective synthesis of both enantiomers of chiral allenes using chiral N-methylcamphanyl piperazine templates

Article abstract of DOI:10.1002/ejoc.201300231

The reaction of unsubstitued camphanyl-piperazine 4 with ZnCl₂, phenylacetylene, and benzaldehyde in toluene gave the corresponding dipropargylamine (i.e., 15) with opposite configurations at the newly formed stereogenic centres, which, upon re

Full text of DOI:10.1002/ejoc.201300231

FULL PAPER
DOI: 10.1002/ejoc.201300231
Enantioselective Synthesis of Both Enantiomers of Chiral Allenes Using Chiral
N-Methylcamphanyl Piperazine Templates
Mariappan Periasamy,*[a] Polimera Obula Reddy,[a] and Nalluri Sanjeevakumar[a]
Keywords: Allenes / Alkynes / Chirality / Zinc / Enantioselectivity
The reaction of unsubstitued camphanyl-piperazine 4 with
ZnCl2, phenylacetylene, and benzaldehyde in toluene gave
the corresponding dipropargylamine (i.e., 15) with opposite
configurations at the newly formed stereogenic centres,
which, upon reaction with ZnI2 resulted in the formation of
a racemic mixture of 1,3-diphenyl allene in 45% yield. N-
tion of N-methylcamphanyl-piperazine isomer 5 with several
1-alkynes and aldehydes in the presence of ZnBr2 gave the
corresponding (R)-allenes in 40–75% yield and 79–99% ee.
In contrast, regioisomeric N-methylcamphanyl-piperazine 6
reacted with ZnBr2 to give the corresponding (S)-allenes in
38–71% yield and with 79–99% ee. The opposite chiral dis-
Methylcamphanyl-piperazine regioisomer 5, prepared by se- criminating abilities of the two NH moieties in camphanyl-
lective N-methylation of the NH moiety attached to the
stereogenic centre with (S)-configuration, upon reaction with
ZnCl2, phenylacetylene, and benzaldehyde in toluene, gave
the corresponding propargylamine in 90% yield, with an (S)-
configuration at the newly formed stereogenic centre, and
upon subsequent reaction with ZnI2, this intermediate gave
(R)-1,3-diphenyl allene in 52% yield and with 96% ee. Reac-
piperazines was confirmed by single-crystal X-ray analysis
of the propargylamines formed. The results are discussed
considering mechanisms involving the in situ formation of
alkynylzinc halides, followed by diastereoselective addition
to chiral iminium ion derivatives to give the corresponding
propargylamines, and subsequent conversion to chiral all-
enes by an intramolecular 1,5-hydrogen shift.
Introduction
Allenes are versatile functional groups that could act as
useful synthons for synthetic manipulations, with the po-
tential for conversion to chiral molecules with asymmetric
centers.[1] Chiral allene structural motifs are also present in
several biologically active natural products and pharmaceu-
ticals.[2] For decades, chiral allenes have been prepared by
the general reaction of propargyl alcohol derivatives with
nucleophiles by SN2 addition. Generally, the methods avail-
able to access enantiomerically enriched allenes require
multi-step synthetic operations.[3] Metal-catalysed enantio-
selective synthesis of chiral allenes from chiral proparg-
ylamines using gold[4a] and silver(I)[4b] complexes and zinc
halides[4c] by a two-step synthetic protocol have been re-
ported. Although the preparation of a monosubstituted all-
ene from CuBr, a 1-alkyne, and formaldehyde was reported
by Crabbe in 1979, the synthesis of racemic 1,3-disubsti-
tuted allenes from terminal alkynes, aldehydes, morpholine,
and ZnX2 was reported only very recently.[5] We have re-
cently reported that zinc halides promote the one-pot enan-
tioselective synthesis of chiral allenes using aldehydes, ter-
minal alkynes, and the chiral amine derivatives (1–3;
Scheme 1).[6]
Scheme 1. Synthesis of chiral allenes.
In this paper, we wish to report details of our investi-
gations into the zinc-halide-mediated enantioselective syn-
thesis of both enantiomers of chiral 1,3-disubstituted all-
enes with up to 99% ee using terminal alkynes, aldehydes,
and readily accessible chiral camphanyl-piperazine deriva-
tives (4–6; Figure 1).
[a] School of Chemistry, University of Hyderabad,
Gachibowli, Hyderabad 500046, India
Fax: +91-40-23012460
E-mail: mpsc@uohyd.ernet.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300231.
Figure 1. Chiral camphanyl-piperazine derivatives 4–6.
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Enantioselective Synthesis of Chiral Allenes
stereogenic centres were assigned as (R,S) in diproparg-
ylamine 15 by X-ray crystal structure analysis (Figure 3).[10]
Interestingly, dipropargylamine 15 reacted with ZnI2
(0.5 mmol) to give only racemic allene 11ba in 45% yield.
Results and Discussion
Chiral piperazine derivative 4 containing a camphanyl
moiety was readily prepared by a recently reported method
(Scheme 2).[7]
Scheme 2. Synthesis of chiral piperazine.
We examined the use of chiral cyclic secondary piperaz-
ine 4 for the preparation of chiral allenes using various
aldehydes, 1-alkynes, and zinc halides. We observed that the
reaction of chiral piperazine 4, 1-decyne (9a), and benzalde-
hyde (10a) using ZnI2 at 120 °C gave (R)-allene 11aa in 75%
yield and with 62% ee (Scheme 3).
Scheme 4. Synthesis of dipropargylamine intermediate 15 using
phenylacetylene (9b), benzaldehyde (10a), and piperazine 4 using
ZnCl2.
Scheme 3. Reaction of 1-decyne (9a) and benzaldehyde (10a) with
chiral piperazine 4, promoted by zinc iodide.
We performed several experiments to understand the
probable reason for the relatively low enantioselectivity ob-
served using chiral piperazine 4, compared to the previously
reported method using chiral piperazine derivative 3 (Fig-
ure 1). The different chiral discrimination abilities of the
two secondary amine moieties present in chiral camphanyl-
piperazine 4 could lead to the formation of a mixture of
chiral propargylamine intermediates 12, 13, and 14 (Fig-
ure 2), leading to the formation (R)-allene 11aa with only
in 62% ee.
Figure 3. ORTEP representation of dipropargylamine 15 (hydrogen
atoms are removed for clarity, and thermal ellipsoids are drawn
with 30% probability).
It occurred to us that blocking of one of the secondary
amine moieties in chiral piperazine 4 would give better op-
tical purities in this allene transformation. To examine this
theory, we developed methods for the synthesis of N-
Figure 2. Possible propargylamine intermediates in the reaction of
1-decyne (9a) and benzaldehyde (10a) with chiral piperazine 4, pro-
moted by zinc iodide.
To examine this theory, we carried out the reaction of methyl-substituted camphanyl-piperazine derivatives 5 and
phenylacetylene (9b), benzaldehyde (10a) and piperazine 4 6 from chiral camphanyl-piperazine 4. Boc-protection fol-
using ZnCl2 (0.1 mmol) at 120 °C, to stop the reaction at lowed by methylation and Boc deprotection gave N-methyl
the propargylamine stage (Scheme 4). In this experiment, piperazine 5 in 93% yield. Direct methylation using tBuOK
dipropargylamine intermediate 15 was obtained in 93% followed by reaction with methyl iodide at –78 °C gave N-
yield. The relative configurations at the newly formed methyl camphanyl-piperazine 6 in 85% yield (Scheme 5).
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(0.6 mmol) for 4 h at 120 °C led to the formation of (R)-
allene 11aa in 61% yield with 96% ee (Scheme 7).
Scheme 7. Reaction of 1-decyne (9a) and benzaldehyde (10a) with
piperazine 5, promoted by zinc iodide.
Scheme 5. Synthesis of mono-protected piperazine derivatives 5
and 6.
We carried out this chiral allene transformation under
various reaction conditions using different zinc halides with
1-decyne (9a), benzaldehyde (10a), and piperazine 5. It is
evident that ZnBr2 (0.6 mmol; Table 1, entry 5) gave the
best results. Under these optimized conditions, we then per-
formed the reaction using various aldehydes and 1-alkynes
(Table 2). A broad range of aldehydes and 1-alkynes were
converted into the corresponding chiral allenes in high
yields and with high enantiomeric purities (Table 2).
We observed that the reaction of phenylacetylene (9b),
benzaldehyde (10a), N-methylcamphanyl-piperazine 5, and
ZnCl2 (10 mol-%) at 120 °C for 4 h gave propargylamine
intermediate 18 in 90% yield and with 99:1 dr (Scheme 6).
Indeed, as shown in the structure of dipropargylamine 15,
the configuration of the newly formed stereogenic centre in
chiral propargylamine 18 has an (S)-configuration, as re-
vealed by X-ray single crystal structure analysis (Fig-
ure 4).[10] Furthermore, upon reaction with ZnI2
(0.5 mmol), chiral propargylamine 18 gave (R)-allene 11ba
in 52% yield with 96% ee.
Table 1. Reaction of 1-decyne (9a) and aldehyde (10a) with piperaz-
ine 5, promoted by zinc halides.[a],
.
Entry Zinc halide mmol
Time [h] Yield [%][b] ee [%][c]
1
2
3
3
4
5
6
7
8
ZnCl2
ZnCl2
ZnCl2
ZnBr2
ZnBr2
ZnBr2
ZnI2
1
4
4
6
4
4
6
4
4
4
28
17
11
71
69
65
54
68
61
99
99
99
91
94
98
87
90
96
0.8
0.6
1
0.8
0.6
1
Scheme 6. Reaction of 1-decyne (9a) and benzaldehyde (10a) with
piperazine 5, promoted by zinc chloride.
ZnI2
ZnI2
0.8
0.6
[a] The reactions were carried out by taking piperazine
5
(1.0 mmol), benzaldehyde (1 mmol), and 1-decyne (1.1 mmol) in
toluene (3 mL) at 25 °C. [b] Isolated yields. [c] The ee was deter-
mined by HPLC analysis.
Substituted benzaldehydes reacted with 1-decyne to give
the corresponding chiral allenes (i.e., 11aa–11ah) in 58–75%
yield, and with up to 90–99% ee (Table 2). The reaction
between benzaldehyde (10a) and phenylacetylene (9b) gave
11ba in 42% yield and with 79% ee (Table 2). 1-Phenylbut-
yne (9c) reacted with benzaldehyde (10a) to give the corre-
sponding allene 11ca in 72% yield, and with 98% ee
(Table 2). The reaction was also applicable to aliphatic alk-
ynes, as illustrated by the reactions of alkynes 9d, 9e, and
9f with benzaldehyde. The corresponding chiral allenes (i.e.,
11da, 11ea, and 11fa) were obtained in 62–68% yield, and
Figure 4. ORTEP representation of propargylamine 18 (hydrogen
atoms are removed for clarity, and thermal elipsoids are drawn with
30% probability).
We also observed that the reaction of 1-decyne (9a), with 79–99% ee (Table 2). We observed that the reaction
benzaldehyde (10a), and chiral piperazine 5 using ZnI2 of simple propargyl alcohol with benzaldehyde under these
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Enantioselective Synthesis of Chiral Allenes
reaction conditions led only to a complex mixture of prod- its p-nitrobenzyl ether derivative 9g, react with aldehydes
ucts, whereas protected forms of propargyl alcohol, such as like 10a and 10k to give the corresponding chiral allenes
(i.e., 11ga and 11gk) in 62–75% yield, and with up to 99%
Table 2. Reaction of terminal alkynes 9 and aldehydes 10 with chi-
ral piperazine 5, promoted by zinc bromide.[a,b,c]
Table 3. Reaction of terminal alkynes 9 and aldehydes 10 with chi-
ral piperazine 6, promoted by zinc bromide.[a,b,c]
[a] The reactions were carried out by taking piperazine
(1.0 mmol), ZnBr2 (0.6 mmol), aldehyde (1 mmol), and 1-alkyne (1.0 mmol), ZnBr2 (0.6 mmol), aldehyde (1 mmol), and 1-alkyne
5
[a] The reactions were carried out by taking piperazine 6
(1.1 mmol) in toluene (3 mL) at 25 °C. [b] Isolated yields. [c] The
ee value was determined by HPLC analysis.
(1.1 mmol) in toluene (3 mL) at 25 °C. [b] Isolated yields. [c] The
ee was determined by HPLC analysis.
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ee (Table 2). Thiophene-2-aldehyde (10i) also reacted with prior to the addition of the alkynlzinc reagent, which is di-
1-alkynes 9a and 9d to give the corresponding allenes (i.e., rected by coordination to the other nitrogen. The corre-
11ai and 11di) in reasonable yields and with reasonable sponding zinc bromide complex of propargylamine inter-
selectivity (Table 2). However, we observed that the reaction mediate 23 would then undergo an intramolecular hydride
of ethyl propiolate with chiral piperazine 5 gave the corre- shift to give alkenylzinc intermediate 24, which would then
sponding Michael addition product (i.e., 19; Scheme 8).
undergo elimination of zinc bromide and the imine by anti-
periplanar cleavage of the C–N bond in intermediate 24 to
give chiral allene (R)-11 and the corresponding chiral cam-
phanyl imine (i.e., 25). Such hydrogen shifts were previously
considered in the gold- and silver-catalysed transformation
of propargylamine derivatives into chiral allenes.[4a,4b]
We found that imine by-product 25 could easily be con-
verted into starting chiral piperazine 5 by simple borohyd-
ride reduction without any change in enantiomeric purity.
We then examined the use of isomeric piperazine 6 in
chiral allene synthesis. We observed that the reaction of 1-
Scheme 8. Formation of Michael addition product 19 in the reac-
tion of ethyl propiolate with chiral piperazine 5.
All the optically active allenes obtained using 5 were le- decyne (9a), benzaldehyde (10a), and piperazine 6 using
vorotatory, from which the absolute configurations of the ZnBr2 (0.6 mmol) led to the (S)-allene in 53% yield, and
major enantiomers of the allenes were assigned as (R) by with 95% ee, with reversed enantioselectivity, as expected
the Lowe–Brewster rule, and also by comparison with re- (Table 3). This transformation is also generally applicable
ported [α]2D5 values.[8] The formation of chiral allenes in this to different aldehydes and 1-alkynes. The corresponding
transformation can be explained by considering the mecha- chiral 1,3-disubstituted allenes were obtained in 38–71%
nism outlined in (Scheme 9). Previously, the formation of yields with high enantioselectivities 79–99% (Table 3).
an alkynylzinc intermediate was reported in the reaction of Again, all the optically active allenes obtained using 6 were
1-alkyne, triethylamine, and zinc triflate.[9a] Also, alk- dextrorotatory, from which the absolute configurations of
ynylzinc addition to iminium ion intermediates has been the major enantiomers of the chiral allenes were assigned
reported.[9b] Accordingly, initially formed alkynylzinc inter- as (S) by the Lowe–Brewster rule, and also by comparison
mediate 20 would react with favoured conformer 21A of the with reported [α]2D5 values.
iminium ion derived from aldehyde 10 and chiral piperazine
5 to selectively give the corresponding propargylamine (i.e., plained by considering
The formation of chiral (S)-allenes using 6 can be ex-
mechanism outlined in
a
22; Scheme 9). Thus, the formation of the single isomer of (Scheme 10). In this case, favoured iminium ion intermedi-
intermediate 22 is mainly due to the exclusive formation of ate 26A would lead to propargylamine intermediate 28,
the favoured conformer of iminium ion intermediate 21A which has an (R) configuration at the newly formed ste-
Scheme 9. Mechanism for the formation of (R)-allenes using piperazine 5.
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Enantioselective Synthesis of Chiral Allenes
Scheme 10. Mechanism for the formation of (S)-allenes using piperazine 6.
(100 MHz) NMR spectra were recorded with Bruker AC 200 and
reogenic centre, in contrast to (S)-propargylamine interme-
diate 18, which was formed using regioisomeric chiral piper-
azine 5. Thus, the corresponding zinc bromide complex of
29 is expected to undergo an intramolecular hydride shift
from the camphanyl skeleton to the acetylinic moiety to
give alkenylzinc intermediate 30, which, after cleavage of
the C–N bond via an antiperiplanar transition state, would
result in the formation of the (S)-allene, along with zinc
bromide and chiral camphanyl imine 31.
Bruker Avance 400 spectrometers, respectively with CDCl3 as sol-
vent and tetramethylsilane (TMS) as reference (δ = 0 ppm). Chemi-
cal shifts are expressed in δ downfield from the signal of TMS.
Liquid chromatography (LC) and mass analysis (LC-MS) were per-
formed with a SHIMADZU-LCMS-2010A instrument. The mass
spectral analyses were carried out using the chemical ionization
(CI) or electrospray ionization (ESI) techniques. Elemental analy-
ses were carried out using a Perkin–Elmer elemental analyser
model-240C or a Thermo Finnigan analyser series Flash EA 1112.
Mass spectral analyses for some of the compounds were carried
out with a VG 7070H mass spectrometer using the EI technique
at 70 eV. Optical rotations were measured with Rudolph Research
Analytical AUTOPOL-II (readability Ϯ0.01°) and AUTOPOL-IV
(readability Ϯ0.001°) automatic polarimeters. The condition of the
polarimeter was checked by measuring the optical rotation of a
standard S-(–)-diphenyl prolinol, 99% ee (DPP), which was pur-
chased from Gerchem Labs (P) Ltd., Hyderabad. Analytical grade
ZnCl2 and ZnBr2 were purchased from E. Merck, India, and Nice
Chemicals Pvt Ltd., India, respectively. ZnI2 was purchased from
Sigma–Aldrich. Powdered zinc halide samples were heated at
120 °C under reduced pressure (0.001 Torr) in a vacuum oven and
stored under dry nitrogen. Toluene supplied by E. Merck, India,
was freshly distilled from sodium benzophenone ketyl before use.
Analytical thin layer chromatography was carried out on glass-
backed plates (3 ϫ 10 cm) coated with 250 μm Acme silica gel-G
and GF254 containing 13% calcium sulfate as binder. The spots
were visualized by short exposure to iodine vapor or UV light.
Column chromatography was carried out using Acme silica gel
(100–200 or 230–400 mesh) or neutral alumina.
Conclusions
In summary, we have developed a versatile and efficient
stereoselective synthesis of both enantiomers of several chi-
ral 1,3-disubstituted allenes with high enantiomeric purities,
exploiting the chiral discrimination abilities of the regioiso-
mers of chiral N-methyl-substituted camphanyl-piperazine
derivatives 5 and 6 in a ZnBr2-promoted transformation.
Since chiral piperazine derivatives 5 and 6 are readily ac-
cessible, and are also easily recoverable for reuse without
loss in optical purity, the method described here has con-
siderable potential for further synthetic exploitation.
Experimental Section
General Information: Melting points were determined using a Su-
perfit capillary melting point apparatus. IR (KBr) spectra were re-
corded with a JASCO FTIR spectrophotometer Model 5300. Neat
IR spectra were recorded with a JASCO FTIR spectrophotometer
Model 5300 or a SHIMADZU FTIR spectrophotometer Model
8300, with polystyrene as reference. 1H (400 MHz) and 13C
tert-Butyl 5,9,9-Trimethyloctahydro-5,8-methanoquinzoline-1-carb-
oxylate (16): (Boc)2O (1.090 g, 5 mmol) in dry CH2Cl2 (10 mL) was
added carefully over a period of 0.5 h to a stirred solution of piper-
azine 4 (1.940 g, 10 mmol) in dry CH2Cl2 (20 mL) at 0 °C, and the
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resulting mixture was stirred for a further 12 h at 25 °C. The
CH2Cl2 was removed under reduced pressure, and amide 16
(2.513 g, 85%) was isolated by column chromatography on silica
gel 100–200 (hexane/ethyl acetate, 1:1 as eluent). [α]2D5 = –68.2 (c =
0.55, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 3.56–3.53 (d, 1
H), 3.44–3.41 (d, 1 H), 3.18–3.17 (t, 1 H), 3.03–2.96 (m, 2 H), 2.67–
2.63 (m, 1 H), 2.06 (s, 1 H), 1.67–1.65 (m, 1 H), 1.53–1.52 (m, 1
H), 1.47 (s, 9 H), 1.15 (s, 3 H), 1.13 (s, 3 H), 1.12 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 156.2, 79.3, 66.1, 58.7, 48.4,
H), 2.54–2.52 (d, J = 8.0 Hz, 1 H), 2.17 (s, 3 H), 1.90–1.89 (d, J =
4.0 Hz, 1 H), 1.75–1.65 (m, 4 H), 1.54–1.47 (m, 2 H), 1.36 (s, 3 H),
1.19–1.11 (m, 3 H), 0.95 (s, 3 H), 0.81 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 74.5, 67.1, 52.6, 47.7, 46.9, 46.5, 43.0, 41.8,
36.5, 26.5, 22.6, 20.3, 12.0 ppm. IR (neat): ν = 3281, 3076, 2934,
˜
1554, 1485, 1415, 1379, 1147 cm–1. HRMS (ESI): calcd. for
C13H25N2 [M + H]+ 209.2118; found 209.2131.
1,4-Bis(1,3-diphenylprop-2-ynyl)-5,9,9-trimethyldecahydro-5,8-meth-
anoquinazoline (15): A stirred suspension of piperazine 4 (0.194 g,
1 mmol), ZnCl2 (0.010 g 0.1 mmol), and phenylacetylene 9b
(0.102 g, 1 mmol) in toluene (3 mL) was heated to 120 °C for
15 min. Freshly distilled benzaldehyde 10a (0.110 g, 1 mmol) was
added at 25 °C, and then the resulting mixture was heated at reflux
at 120 °C under a nitrogen atmosphere. The reaction mixture was
brought to room temperature after 4 h. The toluene was removed,
water (5 mL) was added, and the mixture was extracted with
CH2Cl2 (25 mL). The CH2Cl2 phase was separated, dried with an-
hydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. The crude product was purified by column chromatography
on silica gel 100–200 (hexane/ethyl acetate, 95:5 as eluent) to give
optically pure amine 15 (0.533 g, 93%). [α]2D5 = +43 (c = 1.62,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.79–7.74 (t, J =
20.0 Hz, 4 H), 7.52–7.48 (t, J = 16.0 Hz, 4 H), 7.40–7.26 (m, 10
H), 7.21–7.17 (t, J = 16 Hz, 2 H), 5.24 (s, 1 H), 5.04 (s, 1 H), 3.46–
3.38 (m, 2 H), 2.93–2.85 (m, 1 H), 2.70–2.64 (m, 2 H), 2.33–2.28
(m, 2 H), 1.89–1.82 (m, 1 H), 1.59 (s, 3 H), 1.38–1.28 (m, 2 H),
1.15 (s, 3 H), 0.98 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 139.6, 139.4, 131.9, 131.8, 128.3, 128.3, 128.2, 128.1, 128.0, 127.9,
127.3, 123.3, 123.2, 88.9, 88.5, 85.2, 85.0, 68.6, 67.3, 62.4, 58.4,
51.2, 48.1, 47.1, 45.8, 44.0, 36.1, 26.6, 22.2, 20.8, 13.6 ppm. IR
45.5, 43.0, 35.5, 28.5, 26.6, 22.0, 21.3, 11.6 ppm. IR (neat): ν =
˜
3335, 2953, 1689, 1369, 1172, 1032, 777 cm–1. LCMS: m/z = 295
[M + 1]. C17H30N2O2 (294.44): calcd. C 69.35, H 10.27, N 9.51;
found C 69.21, H 10.35, N 9.45.
tert-Butyl
4,5,9,9-Trimethyloctahydro-5,8-methanoquinzoline-1-
carboxylate (17): CH3I (2.100 g, 15 mmol) in dry THF (10 mL) was
added carefully to a stirred solution of amide 16 (2.941 g, 10 mmol)
and NaH (0.360 g, 15 mmol) in dry THF (20 mL) at 0 °C, and the
resulting solution was stirred for a further 2 h at 25 °C. Water
(5 mL) was added, followed by diethyl ether (30 mL). The diethyl
ether layer was separated, washed with NaCl (saturated aq.), dried
(Na2SO4), and concentrated. Amine 17 (2.799 g, 90%) was isolated
by column chromatography on silica gel 100–200 (hexane/ethyl
1
acetate, 9:1 as eluent). [α]2D5 = –61.2 (c = 0.52, CHCl3). H NMR
(400 MHz, CDCl3): δ = 3.69–3.60 (m, 2 H), 3.35–3.32 (m, 1 H),
2.67–2.65 (m, 1 H), 2.24 (s, 3 H), 1.87 (s, 1 H), 1.67 (s, 1 H), 1.45
(s, 9 H), 1.04 (s, 5 H), 0.99 (s, 3 H), 0.77 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 156.0, 79.4, 74.8, 59.0, 54.5, 53.3, 49.8,
48.5, 45.6, 41.8, 36.2, 28.5, 26.6, 22.1, 20.4, 14.6 ppm. IR (neat): ν
˜
= 2953, 1695, 1454, 1367, 1170, 869, 775 cm–1. LCMS: m/z = 309
[M + 1]. C18H32N2O2 (308.46): calcd. C 70.09, H 10.46, N 9.08;
found C 70.21, H 10.35, N 9.16.
(neat): ν = 3076, 2934, 1554, 1485, 1415, 1379, 1147 cm–1. LCMS:
˜
m/z = 575 [M + 1]. C42H42N2 (574.81): calcd. C 87.76, H 7.36, N
4.87; found C 87.58, H 7.41, N 4.79.
1,8,9,9-Tetramethyldecahydro-5,8-methanoquinazoline
(5):
CF3COOH (5 mL) was added carefully to a stirred solution of
amide 17 (3.900 g, 10 mmol) in dry CH2Cl2 (10 mL) at 0 °C, and
the resulting solution was stirred for a further 12 h at 25 °C. The
CF3COOH (5 mL) was removed under reduced pressure, and
NaHCO3 (saturated aq.; 10 mL) and CH2Cl2 (25 mL) were added.
The CH2Cl2 layer was separated, washed with NaCl (saturated aq.),
dried (Na2SO4), and concentrated. Piperazine 5 (1.943 g, 93%) was
isolated by column chromatography on silica gel 100–200 (chloro-
1-(1,3-Diphenylprop-2-ynyl)-4,5,9,9-Tetramethyldecahydro-5,8-meth-
anoquinazoline (18): A stirred suspension of piperazine 5 (0.208 g,
1 mmol), ZnCl2 (0.010 g, 0.1 mmol), and phenylacetylene 9b
(0.102 g, 1 mmol) in toluene (3 mL) was heated to 120 °C for
15 min. Freshly distilled benzaldehyde 10a (0.110 g, 1 mmol) was
added at 25 °C, and the resulting mixture was heated at reflux at
120 °C under a nitrogen atmosphere. The reaction mixture was
brought to room temperature after 4 h. The toluene was removed,
water (5 mL) was added, and the mixture was extracted with
CH2Cl2 (25 mL). The CH2Cl2 phase was separated, dried with an-
hydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. The crude product was purified by column chromatography
on silica gel 100–200 (hexane/ethyl acetate, 95:5 as eluent) to give
optically pure piperazine 18 (0.358 g, 90%). [α]2D5 = –74.7 (c = 0.52,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.70–7.68 (d, J = 8 Hz,
2 H), 7.56–7.54 (d, J = 8 Hz, 2 H), 7.38–7.26 (m, 6 H), 5.25 (s, 1
H), 3.15–3.12 (d, J = 12 Hz, 1 H), 2.59–2.57 (m, 1 H), 2.49–2.48
(m, 1 H), 2.26–1.23 (m, 5 H), 1.99–1.63 (m, 1 H), 1.52 (s, 3 H),
1.30–1.25 (m, 3 H), 1.06 (s, 3 H), 0.83 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 138.9, 132.0, 128.3, 128.2, 127.2, 123.3,
87.8, 86.0, 78.1, 65.6, 58.2, 54.2, 50.3, 48.2, 47.5, 47.4, 42.9, 37.2,
1
form/methanol, 9:1 as eluent). [α]2D5 = +22.7 (c = 0.53, CHCl3). H
NMR (400 MHz, CDCl3): δ = 3.12–3.09 (m, 1 H), 2.77–2.73 (m, 2
H), 2.64–2.58 (m, 1 H), 2.25 (s, 3 H), 1.91–1.63 (m, 6 H), 1.41 (s,
3 H), 1.25–1.11 (m, 3 H), 1.06 (s, 3 H), 0.83 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 79.8, 61.6, 54.9, 50.3, 50.0, 47.2,
46.1, 41.9, 37.4, 27.2, 22.2, 21.0, 15.8 ppm. IR (neat): ν = 3281,
˜
3076, 2934, 1554, 1485, 1415, 1379, 1147, 1055, 808, 692 cm–1.
LCMS: m/z = 209 [M + 1]. C13H24N2 (208.34): calcd. C 74.94, H
11.61, N 13.45; found C 74.85, H 11.56, N 13.56.
1,8,9,9-Tetramethyldecahydro-5,8-methanoquinazoine (6):
An oven-dried 100 mL reaction flask was flushed with dry nitro-
gen, and tBuOK (1.940 g, 10 mmol) and dry THF (20 mL) were
added. The mixture was cooled to –78 °C, and then piperazine 4
(1.94 g, 10 mmol) in dry THF (10 mL) was added. The resulting
mixture was stirred for 0.5 h at –78 °C. MeI (0.66 mL, 10 mmol) in
dry THF (5 mL) was then added to this reaction mixture. After
about 15 min, the reaction was quenched with water, and diethyl
ether was added. The separated organic phase was washed with
NaCl solution and dried with Na2SO4. Purification by column
chromatography (basic alumina) in hexane gave optically pure
piperazine 6 (1.773 g, 85%). [α]2D5 = –24.6 (c = 0.45, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 3.13–3.08 (m, 1 H), 2.68–2.61 (m, 2
26.3, 22.2, 21.2, 14.7 ppm. IR (neat): ν = 3061, 3026, 2951, 2870,
˜
2831, 2756, 1599, 1489, 1488, 1388, 1365, 1064 842, 694 cm–1.
LCMS: m/z = 399 [M + 1]. C28H34N2 (398.58): calcd. C 84.31, H
8.60, N 7.03; found C 84.21, H 8.51, N 7.12.
Reaction of Terminal Alkyne, Aldehyde, and Amine with ZnBr2:
Amine (5 or 6; 0.209 g, 1 mmol) was dissolved in toluene (3 mL)
in a flame-dried 25 mL reaction flask, and ZnBr2 (0.135 g,
0.6 mmol) and alkyne 9 (1.1 mmol) were added. The mixture was
3872
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 3866–3875

Enantioselective Synthesis of Chiral Allenes
stirred in a pre-heated oil bath at 120 °C for 10 min. The reaction
flask was then removed from the oil bath and cooled to room tem-
perature under nitrogen. Freshly distilled aldehyde 10 (1 mmol) was
added to the reaction mixture at 25 °C. The resulting mixture was
gradually heated to 120 °C over about 45 min, and was stirred for
the time given in Table 2 or 3. The mixture was brought to 25 °C,
the toluene was evaporated, the residue was purified by column
chromatography on silica gel (100–200 mesh) using hexane as elu-
ent to give the chiral allene.
1-(4-Trifluoromethyl)phenylundeca-1,2-diene (11ae): Data for (R)-
11ae: Yield 0.210 g (70%); 99% ee. [α]2D5 = –175.6 (c = 0.60, CHCl3).
Data for (S)-11ae: Yield 0.201 g (67%); 96% ee. [α]2D5 = +169.2 (c
= 0.60, CHCl3). HPLC using chiral column, chiralcel OD-H; hex-
anes/iPrOH, 100:0; flow rate 1.5 mL/min; 254 nm; retention times:
1
15.4 min (S) and 17.0 min (R). H NMR (400 MHz, CDCl3): δ =
7.55–7.52 (d, J = 12 Hz, 2 H), 7.38–7.36 (d, J = 8 Hz, 2 H), 6.16–
6.13 (m, 1 H), 5.66–5.62 (m, 1 H), 2.18–2.12 (m, 2 H), 1.54–1.45
(m, 2 H), 1.38–1.27 (m, 10 H), 0.89–0.88 (t, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 206.1, 139.1, 131.6, 126.6, 125.6, 125.4,
125.4, 95.6, 93.8, 31.8, 29.3, 29.2, 29.1, 29.0, 28.5, 22.6, 14.0 ppm.
The 13C NMR spectroscopic data was in agreement with the re-
1-Phenylundeca-1,2-diene (11aa): Data for (R)-11aa: Yield 0.155 g
(68%); 98% ee. [α]2D5 = –225.2 (c = 0.50, CHCl3). Data for (S)-11aa:
Yield 0.120 g (53%); 95% ee. [α]2D5 = +215.7 (c = 0.50, CHCl3).
HPLC using chiral column, chiralcel OD-H; hexanes/iPrOH, 100:0;
flow rate 1.5 mL/min; 254 nm; retention times: 4.7 min (R) and
ported data, see ref.[6] IR (neat): ν = 2928, 2856, 1950, 1616, 1325,
˜
844 cm–1.
1
1-(3-Methoxyphenyl)undeca-1,2-diene (11af): Data for (R)-11af:
Yield 0.167 g (65%); 97% ee. [α]2D5 = –201.7 (c = 0.50, CHCl3).
Data for (S)-11af: Yield 0.157 g (61%); 97% ee. [α]2D5 = +201.2 (c
= 0.50, CHCl3). HPLC using chiral column, chiralcel OJ-H; hex-
anes/iPrOH, 100:0; flow rate 1.0 mL/min; 254 nm; retention times:
7.3 min (R) and 9.5 min (S). 1H NMR (400 MHz, CDCl3): δ =
7.24–7.20 (m, 1 H), 6.90–6.86 (m, 2 H), 6.76–6.74 (m, 1 H), 6.12–
6.10 (m, 1 H), 5.58–5.57 (m, 1 H), 3.81 (s, 3 H), 2.17–2.12 (m, 2
H), 1.53–1.46 (m, 2 H), 1.39–1.28 (m, 10 H), 0.91–0.87 (t, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 205.2, 159.8, 136.7, 129.4,
119.3, 112.4, 111.7, 95.2, 94.5, 55.1, 31.8, 29.4, 29.3, 29.2, 28.7,
22.6, 14.1 ppm. The 13C NMR spectroscopic data was in agreement
5.2 min (S). H NMR (400 MHz, CDCl3): δ = 7.34–7.28 (m, 4 H),
7.24–7.20 (m, 1 H), 6.19–6.14 (m, 1 H), 5.64–5.58 (m, 1 H), 2.19–
2.15 (m, 2 H), 1.56–1.51 (m, 2 H), 1.41–1.32 (m, 12 H), 0.95–0.91
(t, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.1, 22.6, 28.7,
29.1, 29.3, 29.4, 31.8, 94.5, 95.5, 126.5, 128.5, 135.1, 205.1 ppm.
The 13C NMR spectroscopic data was in agreement with the re-
ported data, see ref.[6] IR (neat): ν = 2926, 2854, 1950, 1599, 1460,
˜
773 cm–1.
1-(4-Bromophenyl)undeca-1,2-diene (11ab): Data for (R)-11ab: Yield
0.220 g (72%); 97% ee. [α]2D5 = –148.4 (c = 0.50, CHCl3). Data for
(S)-11ab: Yield 0.196 g (64%); 99% ee. [α]2D5 = +154.7 (c = 0.50,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/
iPrOH, 100:0; flow rate 1.5 mL/min; 254 nm; retention times:
3.5 min (S) and 4.6 min (R). 1H NMR (400 MHz, CDCl3): δ =
7.44–7.41 (d, 2 H), 7.18–7.15 (d, 2 H), 6.10–6.07 (m, 1 H), 5.61–
5.56 (m, 1 H), 2.17–2.11 (m, 2 H), 1.51–1.46 (m, 2 H), 1.39–1.28
(m, 10 H), 0.92–0.89 (t, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 205.2, 134.2, 131.6, 128.0, 120.1, 95.5 93.7, 31.8, 29.3, 29.3,
29.1, 29.1, 28.6, 22.6, 14.1 ppm. The 13C NMR spectroscopic data
with the reported data, see ref.[6] IR (neat): ν = 3055, 2926, 2854,
˜
1946, 1508, 1325, 817, 746 cm–1.
1-(3-Methylphenyl)undeca-1,2-diene (11ag): Data for (R)-11ag:
Yield 0.163 g (67%); 90% ee. [α]2D5 = –125.5 (c = 0.55, CHCl3).
Data for (S)-11ag: Yield 0.140 g (58%); 90% ee. [α]2D5 = +125.1 (c
= 0.55, CHCl3). HPLC using chiral column, chiralcel OJ-H; hex-
anes/iPrOH, 100:0; flow rate 1.0 mL/min; 254 nm; retention times:
5.8 min (R) and 8.3 min (S). 1H NMR (400 MHz, CDCl3): δ =
7.28–7.22 (m, 1 H), 7.16–7.14 (d, J = 8 Hz, 2 H), 7.05–7.04 (d, J
= 4.0 Hz, 1 H), 6.16–6.13 (m, 1 H), 5.62–5.57 (m, 1 H), 2.38 (s, 3
H), 2.20–2.15 (m, 2 H), 1.56–1.52 (m, 2 H), 1.43–1.32 (m, 10 H),
0.94–0.92 (t, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 205.1,
138.1, 135.0, 128.4, 127.4, 127.2, 123.7, 94.9, 94.5, 31.9, 29.4, 29.3,
29.2, 28.8, 22.7, 21.4, 14.1 ppm. The 13C NMR spectroscopic data
was in agreement with the reported data, see ref.[6] IR (neat): ν =
˜
2926, 2858, 1950, 1599, 1487, 829 cm–1.
1-(4-Chlorophenyl)undeca-1,2-diene (11ac): Data for (R)-11ac: Yield
0.190 g (71%); 92% ee. [α]2D5 = –163.6 (c = 0.50, CHCl3). Data for
(S)-11ac: Yield 0.162 g (60%); 98% ee. [α]2D5 = +172.9 (c = 0.50,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/
iPrOH, 100:0; flow rate 1.5 mL/min; 254 nm; retention times:
3.3 min (S) and 4.2 min (R). 1H NMR (400 MHz, CDCl3): δ =
7.27–7.20 (m, 4 H), 6.09–6.06 (m, 1 H), 5.60–5.55 (m, 1 H), 2.16–
2.09 (m, 2 H), 1.51–1.44 (m, 2 H), 1.37–1.26 (m, 10 H), 0.92–0.87
(t, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 205.2, 133.7,
132.1, 128.6, 127.7, 95.5, 93.7, 31.8, 29.3, 29.3, 29.1, 28.6, 22.6,
14.1 ppm. The 13C NMR spectroscopic data was in agreement with
was in agreement with the reported data, see ref.[6] IR (neat): ν =
˜
2957, 2926, 1950, 1599, 1494, 690 cm–1.
1-(4-Methylphenyl)undeca-1,2-diene (11ah): Data for (R)-11ah:
Yield 0.152 g (63%); 99% ee. [α]2D5 = –172.2 (c = 0.55, CHCl3).
Data for (S)-11ah: Yield 0.150 g (62%); 95% ee. [α]2D5 = +164.9 (c
= 0.55, CHCl3). HPLC using chiral column, chiralcel OJ-H; hept-
ane/iPrOH, 100:0; flow rate 1.5 mL/min; 254 nm; retention times
4.9 min (R) and 5.5 min (S). 1H NMR (400 MHz, CDCl3): δ =
7.20–7.18 (d, J = 8 Hz, 2 H), 7.12–7.10 (d, J = 8 Hz, 2 H), 6.12–
6.09 (m, 1 H), 5.55–5.54 (m, 1 H), 2.36 (s, 3 H), 2.15–2.10 (m, 2
H), 1.50–1.44 (m, 2 H), 1.38–1.27 (m, 10 H), 0.94–0.90 (t, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 204.8, 136.3, 132.1, 129.2,
126.4, 95.0, 94.3, 31.8, 29.4, 29.3, 29.2, 28.8, 22.7, 21.1, 14.1 ppm.
The 13C NMR spectroscopic data was in agreement with the re-
the reported data, see ref.[6] IR (neat): ν = 2926, 2854, 1950, 1491,
˜
831 cm–1.
1-(4-Fluorophenyl)undeca-1,2-diene (11ad): Data for (R)-11ad: Yield
0.175 g (75%); 98% ee. [α]2D5 = –162.7 (c = 0.45, CHCl3). Data for
(S)-11ad: Yield 0.150 g (65%); 96% ee. [α]2D5 = +157.3 (c = 0.45,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/iP-
rOH, 100:0; flow rate 1.5 mL/min; 254 nm; retention times: 4.4 min
ported data, see ref.[6] IR (neat): ν = 2924, 2854, 1948, 1512, 1464,
˜
1
(S) and 4.8 min (R). H NMR (400 MHz, CDCl3): δ = 7.26–7.22
821 cm–1.
(m, 2 H), 7.01–6.96 (m, 2 H), 6.11–6.08 (m, 1 H), 5.57–5.56 (m, 1
H), 2.15–2.09 (m, 2 H), 1.50–1.44 (m, 2 H), 1.37–1.28 (m, 10 H),
1,5-Diphenylpenta-1,2-diene (11ca): Data for (R)-11ca: Yield
0.98–0.89 (t, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 204.9, 0.159 g (72%); 98% ee. [α]2D5 = –210.1 (c = 0.45, CHCl3). Data for
162.9, 160.5, 131.1, 127.9, 127.8, 115.5, 115.3, 95.3, 93.9, 31.8, 29.4,
29.3, 29.2, 29.1, 28.7, 22.6, 14.1 ppm. The 13C NMR spectroscopic
data was in agreement with the reported data, see ref.[6] IR (neat):
(S)-11ca: Yield 0.143 g (64%); 96% ee. [α]2D5 = +206.9 (c = 0.45,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/
iPrOH, 100:0; flow rate 1.5 mL/min; 254 nm; retention times:
9.6 min (R) and 11.1 min (S). 1H NMR (400 MHz, CDCl3): δ =
ν = 2926, 2854, 1950, 1602, 1508, 1228, 837 cm–1.
˜
Eur. J. Org. Chem. 2013, 3866–3875
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3873

M. Periasamy, P. O. Reddy, N. Sanjeevakumar
FULL PAPER
7.31–7.28 (m, 4 H), 7.25–7.16 (m, 6 H), 6.14–6.11 (d, J = 8 Hz, 1
CHCl3). HPLC using chiral column, chiralcel OB-H; heptane/iP-
H), 5.62–5.57 (m, 1 H), 2.84–2.79 (m, 2 H), 2.51–2.43 (m, 2 H) rOH, 100:0; flow rate 0.3 mL/min; 254 nm; retention times:
1
ppm. 13C NMR (100 MHz, CDCl3): δ = 205.3, 141.5, 134.8, 128.6,
128.5, 128.4, 126.7, 126.6, 125.9, 95.0, 94.3, 35.4, 30.6 ppm. The
13C NMR spectroscopic data was in agreement with the reported
16.3 min (S) and 18.0 min (R). H NMR (400 MHz, CDCl3): δ =
7.19–7.14 (m, 1 H), 6.96–6.88 (m, 2 H), 6.36–6.34 (m, 1 H), 5.58–
5.56 (dd, 1 H), 2.37 (s, 1 H), 2.14–2.09 (m, 2 H), 1.57–1.52 (m, 2 H),
1.43–1.32 (m, 10 H), 0.94–0.92 (t, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 204.5, 139.8, 127.4, 124.1, 124.0, 95.5, 88.9, 31.8, 29.7,
29.3, 29.2, 28.8, 22.6, 21.4, 14.1 ppm. The 13C NMR spectroscopic
data was in agreement with the reported data, see ref.[6] IR (neat):
data, see ref.[6] IR (neat): ν = 2928, 2856, 1945, 1698, 1325,
˜
844 cm–1.
1-Phenyl-6-chlorohexa-1,2-diene (11da): Data for (R)-11da: Yield
0.142 g (68%); 98% ee. [α]2D5 = –152.3 (c = 0.65, CHCl3). Data for
(S)-11da: Yield 0.126 g (59%); 98% ee. [α]2D5 = +152.5 (c = 0.65,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/
iPrOH, 100:0; flow rate 1 mL/min; 254 nm; retention times:
ν = 3068, 2925, 2848, 1950, 1456, 1374, 1265, 1034 854 cm–1.
˜
1-(2-Thiophenyl)-6-chlorohexa-1,2-diene (11di): Data for (R)-11di:
Yield 0.130 g (66%); 99% ee. [α]2D5 = –182.1 (c = 0.55, CHCl3).
Data for (S)-11di: Yield 0.126 g (64%); 99% ee. [α]2D5 = +184.7 (c
= 0.55, CHCl3). HPLC using chiral column, chiralcel OB-H; hex-
anes/iPrOH, 95:5; flow rate 0.5 mL/min; 254 nm; retention times:
1
9.78 min (S) and 11.5 min (R). H NMR (400 MHz, CDCl3): δ =
7.34–7.32 (m, 1 H), 7.23–7.20 (m, 2 H), 6.21–6.19 (d, J = 8.0 Hz,
1 H), 5.62–5.57 (d, J = 8.0 Hz, 1 H), 3.64–3.61 (t, J = 12 Hz, 2 H),
2.34–2.30 (m, 2 H), 2.0–1.96 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 205.2, 134.6, 128.6, 126.9, 126.6, 95.4, 93.6, 44.4, 30.2,
25.8 ppm. The 13C NMR spectroscopic data was in agreement with
1
13.6 min (S) and 14.2 min (R). H NMR (400 MHz, CDCl3): δ =
7.17–7.15 (d, J = 8.0 Hz, 1 H), 6.96–6.90 (m, 2 H), 6.42–6.40 (m,
1 H), 5.62–5.57 (m, 1 H), 3.64–3.61 (m, 2 H), 2.36–2.24 (m, 2 H),
2.05–1.94 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 204.7,
the reported data, see ref.[6] IR (neat): ν = 3063, 3030, 2957, 1950,
˜
1599, 1494, 1275, 1078, 877 cm–1.
139.1, 127.4, 124.6, 124.4, 94.0, 89.9, 44.3, 31.5, 25.9 ppm. The 13
C
NMR spectroscopic data was in agreement with the reported data,
7-Phenyl-1-cyanohepta-5,6-diene (11ea): Data for (R)-11ea: Yield
0.113 g (62%); 99% ee. [α]2D5 = –140.2 (c = 0.60, CHCl3). Data for
(S)-11ea: Yield 0.107 g (58%); 97% ee. [α]2D5 = +135.2 (c = 0.60,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/
iPrOH, 100:0; flow rate 1 mL/min; 254 nm; retention times:
see ref.[6] IR (neat): ν = 2955, 2926, 2854, 1950, 1738, 1442, 1261,
˜
1039, 875 cm–1.
1-(2-Furanyl)undeca-1,2-diene (11aj): Data for (R)-11aj: Yield
0.087 g (40%); 86% ee. [α]2D5 = –94.7 (c = 0.60, CHCl3). Data for
(S)-11aj: Yield 0.083 g (38%); 85% ee. [α]2D5 = +93.2 (c = 0.60,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/
iPrOH, 100:0; flow rate 0.5 mL/min; 254 nm; retention times:
1
19.6 min (S) and 22.1 min (R). H NMR (400 MHz, CDCl3): δ =
7.34–7.32 (m, 1 H), 7.23–7.20 (m, 2 H), 6.23–6.20 (m, 1 H), 5.61–
5.56 (d, J = 8.0 Hz, 1 H), 2.53–2.39 (m, 2 H), 2.0–1.96 (m, 2 H),
1.92–1.87 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 205.3,
1
11.1 min (R) and 12.5 min (S). H NMR (400 MHz, CDCl3): δ =
134.3, 128.7, 127.1, 126.5, 95.8, 93.0, 27.3, 24.5, 17.5 ppm. The 13
C
7.35 (s, 1 H), 6.38–6.37 (s, 1 H), 6.19 (s, 1 H), 6.14–6.11 (m, 1 H),
5.62–5.58 (d, 1 H), 4.64 (s, 2 H), 2.15–2.11 (m, 3 H), 1.54–1.09 (m,
13 H), 0.90–0.87 (m, 7 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 204.4, 149.0, 141.7, 111.3, 106.6, 95.7, 85.4, 31.9, 31.8, 29.4, 29.3,
29.0, 28.8, 27.1, 22.7, 14.1 ppm. The 13C NMR spectroscopic data
NMR spectroscopic data was in agreement with the reported data,
see ref.[6] IR (neat): ν = 3296, 2941, 2247, 1950, 1597, 1494, 1263,
˜
1074, 881 cm–1.
1- (4-Nitrobenzyloxy)-4-phenylbuta-2,3-diene (11ga): Data for (R)-
11ga: Yield 0.174 g (62%); 99% ee. [α]2D5 = –196.1 (c = 0.50,
was in agreement with the reported data, see ref.[6] IR (neat): ν =
˜
3115, 2926, 2824, 1952, 1585, 1464, 1344, 1079, 925 cm–1.
CHCl3). Data for (S)-11ga: Yield 0.162 g (58%); 97% ee. [α]2D5
=
+192.8 (c = 0.50, CHCl3). HPLC using chiral column, chiralcel
OB-H; hexanes/iPrOH, 85:15; flow rate 0.3 mL/min; 254 nm; reten-
tion times: 73.3 min (R) and 76.7 min (S). 1H NMR (400 MHz,
CDCl3): δ = 8.20–8.18 (d, J = 8.0 Hz, 2 H), 7.51–7.49 (d, J =
8.0 Hz, 2 H), 7.35–7.22 (m, 4 H), 6.31–6.29 (m, 1 H), 5.75–5.70 (m,
1 H), 4.66 (s, 2 H), 4.22–4.12 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 206.2, 145.8, 133.6, 128.7, 127.8, 126.9, 123.6, 95.9,
92.1, 70.6, 68.5 ppm. The 13C NMR spectroscopic data was in
1-(4-Nitrobenzyloxy)octan-2,3-diene (11gk): Data for (R)-11gk:
Yield 0.195 g (75%); 99% ee. [α]2D5 = –48.8 (c = 0.60, CHCl3). Data
for (S)-11gk: Yield 0.176 g (68%); 98% ee. [α]2D5 = +48.1 (c = 0.60,
CHCl3). HPLC using chiral column, chiralcel AD-H; hexanes/
iPrOH, 100:0; flow rate 1.5 mL/min; 254 nm; retention times:
1
29.8 min (R) and 34.1 min (S). H NMR (400 MHz, CDCl3): δ =
8.20–8.18 (d, J = 8.0 Hz, 2 H), 7.59–7.49 (d, J = 8.0 Hz, 2 H),
5.25–5.20 (m, 2 H), 4.62 (s, 2 H), 4.09–4.07 (m, 2 H), 2.05–1.99 (m,
2 H), 1.43–1.32 (m, 4 H), 0.90–0.89 (t, J = 12.0 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 205.2, 147.3, 146.1, 127.7, 123.5,
92.2, 87.8, 70.4, 69.3, 31.2, 28.2, 22.1, 13.9 ppm. The 13C NMR
spectroscopic data was in agreement with the reported data, see
agreement with the reported data, see ref.[6] IR (neat): ν = 2922,
˜
2858, 2362, 1952, 1605, 1520, 1087, 775 cm–1.
3-(Cyclohex-1-enyl)-1-phenylpropa-1,2-diene (11fa): Data for (R)-
11fa: Yield 0.125 g (64%); 79% ee. [α]2D5 = –143.6 (c = 0.50, CHCl3).
Data for (S)-11fa: Yield 0.113 g (58%); 80% ee. [α]2D5 = +145.1 (c
= 0.50, CHCl3). HPLC using chiral column, chiralcel OD-H; hex-
anes/iPrOH, 99:1; flow rate 0.3 mL/min; 215 nm; retention times:
ref.[6] IR (neat): ν = 2957, 2928, 2859, 2362, 2336, 1969, 1605 cm–1.
˜
5-(Cyclohexyl)-1-phenylpenta-3,4-diene (11cl): Data for (R)-11cl:
Yield 0.157 g (70%); 99% ee. [α]2D5 = –197.3 (c = 0.70, CHCl3).
Data for (S)-11cl: Yield 0.153 g (68%); 97% ee. [α]2D5 = +194.2 (c
= 0.70, CHCl3). HPLC using chiral column, chiralcel OJ-H; hex-
anes/iPrOH, 100:0; flow rate 0.3 mL/min; 215 nm; retention times:
1
14.0 min (S) and 16.6 min (R). H NMR (400 MHz, CDCl3,): δ =
7.39–7.28 (m, 4 H), 7.23–7.18 (m, 1 H), 6.41–6.40 (d, J = 4 Hz, 1
H), 6.27–6.26 (d, J = 4 Hz, 1 H), 5.78 (s, 1 H), 2.15–2.00 (m, 4 H),
1.66–1.54 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 206.4,
142.0, 128.5, 128.4, 128.2, 125.8, 97.6, 91.7, 37.2, 35.5, 33.0, 32.9,
30.8, 29.7, 26.2, 26.0 ppm. The 13C NMR spectroscopic data was
1
18.8 min (S) and 19.8 min (R). H NMR (400 MHz, CDCl3): δ =
7.32–7.20 (m, 5 H), 5.19–5.17 (m, 1 H), 5.12–5.10 (m, 1 H), 2.76–
2.72 (m, 2 H), 2.34–2.32 (m, 2 H), 1.92–1.84 (m, 1 H), 1.73–1.63
(m, 6 H), 1.38–1.26 (m, 8 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 202.8, 142.0, 128.5, 128.4, 128.2, 125.8, 97.6, 91.7, 37.2, 35.5,
33.0, 32.9, 30.8, 29.7, 26.2, 26.0 ppm. The 13C NMR spectroscopic
data was in agreement with the reported data, see ref.[6] IR (neat):
in agreement with the reported data, see ref.[6] IR (neat): ν = 3028,
˜
2924, 2858, 2858, 1930, 1599, 1493, 1074 cm–1.
1-(2-Thienyl)undeca-1,2-diene (11ai): Data for (R)-11ai: Yield
0.173 g (74%); 91% ee. [α]2D5 = –198.3 (c = 0.45, CHCl3). Data for
(S)-11ai: Yield 0.164 g (71%); 99% ee. [α]2D5 = +215.1 (c = 0.45,
ν = 3026, 2924, 2851, 1959, 1728, 1450, 1057 cm–1.
˜
3874
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 3866–3875

Enantioselective Synthesis of Chiral Allenes
H. U. Reissig, R. Zimmer, Acc. Chem. Res. 2009, 42, 45; c) B.
Alcaide, P. Almendros, T. M. del Campo, Chem. Eur. J. 2010,
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2012, 51, 3074.
1,3-Diphenylpropan-1,2-diene (11ba): Data for (R)-11ba: Yield
0.081 g (42%); 79% ee. [α]2D5 = –723.1 (c = 0.65, CHCl3). Data for
(S)-11ba: Yield 0.073 g (38%); 79% ee. [α]2D5 = +726.7 (c = 0.65,
CHCl3). HPLC using chiral column, chiralcel OD-H; hexanes/
iPrOH, 99:1; flow rate 0.5 mL/min; 254 nm; retention times:
1
11.0 min (R) and 14.4 min (S). H NMR (500 MHz, CDCl3): δ =
7.36–7.30 (m, 8 H), 7.25–7.21 (m, 2 H), 6.60 (s, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 207.8, 133.6, 128.7, 127.3, 127.0,
98.4 ppm. The 13C NMR spectroscopic data was in agreement with
[2]
[3]
a) . A. G. Myers, B. Zheng, J. Am. Chem. Soc. 1996, 118, 4492;
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the reported data, see ref.[6] IR (KBr): ν = 3061, 3028, 1936, 1597,
˜
1493, 1450, 758 cm–1.
3-Cyclohexyl-1-phenyl-1,2-propadiene (11bl): Data for (R)-11ba:
Yield 0.134 g (68%); 83% ee. [α]2D5 = –135.1 (c = 0.70, CHCl3).
Data for (S)-11ba: Yield 0.122 g (62%); 91% ee. [α]2D5 = +152.1 (c
= 0.70, CHCl3). HPLC using chiral column, chiralcel OD-H; hept-
ane/iPrOH, 100:0; flow rate 1 mL/min; 214 nm; retention times:
5.4 min (R), and 7.2 min (S). 1H NMR (400 MHz, CDCl3): δ =
7.31–7.24 (m, 4 H), 7.23–7.17 (m, 1 H), 6.21–6.11 (m, 1 H), 5.62–
5.52 (m, 1 H), 2.22–2.04 (m, 1 H), 1.93–1.57 (m, 5 H), 1.41–1.09
(m, 5 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 204.0, 135.2,
128.5, 126.6, 126.4, 101.0, 95.4, 37.6, 33.2, 33.1, 26.1, 26.0 ppm.
The 13C NMR spectroscopic data was in agreement with the re-
[4]
ported data, see ref.[6] IR (KBr): ν = 3061, 3028, 1936, 1597, 1493,
˜
1450, 758 cm–1.
Supporting Information (see footnote on the first page of this arti-
[5]
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Chem. Commun. 1979, 859; b) J. Kuang, S. Ma, J. Am. Chem.
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1
cle): Chiral HPLC analysis data and H and 13C NMR spectra for
all new compounds.
M. Periasamy, N. Sanjeevakumar, M. Dalai, R. Gurubrah-
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Acknowledgments
[7] M. Periasamy, N. Sanjeevakumar, P. O. Reddy, Synthesis 2012,
44, 3185.
The authors are thankful to the Department of Science and Tech-
nology (DST) for support of a J. C. Bose National Fellowship grant
to M. P., and for the FIST and IRPHA programs. The support of
the University Grants Commission (UGC) under the UPE and
CAS programs is also gratefully acknowledged. N. S. K. and
P. O. R are grateful to the Council of Scientific and Industrial Re-
search (CSIR), New Delhi for research fellowships.
[8] G. Lowe, J. Chem. Soc., Chem. Commun. 1965, 411.
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[10] X-ray crystallography: CCDC-914858 (for 15) and CCDC-
914859 (for 18) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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Received: February 13, 2013
Published Online: May 5, 2013
Eur. J. Org. Chem. 2013, 3866–3875
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3875