Stereoselective synthesis of (2E,4Z)-dienamides employing (triphenylphosphoranylidene)ketene

Article abstract of DOI:10.1002/ejoc.200900176

The three-component reaction between ylide Ph₃PCCO, amines and aldehydes is known to afford selectively (￡)-a,ssunsaturated amides. We applied a variant of this methodology to the preparation of (2B,4Z)-dienamides 11 utilizing the phosphonium s

Full text of DOI:10.1002/ejoc.200900176

FULL PAPER
DOI: 10.1002/ejoc.200900176
Stereoselective Synthesis of (2E,4Z)-Dienamides Employing
(Triphenylphosphoranylidene)ketene
Steffen Pachali,[a][‡] Christine Hofmann,[a][‡] Georg Rapp,[b] Rainer Schobert,[b]
Angelika Baro,[a] Wolfgang Frey,[a] and Sabine Laschat*[a]
Keywords: Aldehydes / C–C coupling / Synthetic methods / Wittig reactions / Ylides
The three-component reaction between ylide Ph3PCCO,
amines and aldehydes is known to afford selectively (E)-α,β-
unsaturated amides. We applied a variant of this methodol-
ogy to the preparation of (2E,4Z)-dienamides 11 utilizing the
phosphonium salt formation from ethyl 5-aminopentanoate
hydrochloride and Ph3PCCO followed by deprotonation with
DBU and a Wittig olefination of the corresponding ylide with
various (Z)-α,β-unsaturated aldehydes 10. The (2E,4Z)-dien-
amides 11 were isolated in yields of up to 80%. The (Z)-con-
figuration of the starting aldehydes 10 remained untouched
during the reaction.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
(2E,4Z)-Dienamides are constituents of a variety of
pharmacological relevant natural products such as immun-
omodulatory, phototoxic antimicrobial and taste active N-
alkylamides 1a,b from Echinacea purpurea,[1–3] cis-pellitor-
ine (2a) from Artemisia dracunculus,[4] pipericine (2b) from
Piper nigrum,[5] mitochondrial complex I inhibiting myxal-
amide analogues like 4,[6] cytotoxic (4Z)-onnamide A 5
from a marine Theonella sponge,[7] cylindramide (6) from
the marine sponge Halichondria cylindrata[8,9] or aburatu-
bolactam A (7) produced by a Streptomyces species of a
marine mollusc[10] as well as non-natural insecticides 3[11]
(Scheme 1).
Synthetic efforts towards these (2E,4Z)-dienamides relied
mainly on Wittig reactions employing amide-derived phos-
phonium salts or olefination followed by introduction of
the amide moiety via acid chloride as the final step.[12,13]
Other known synthetic routes involved photoisomerization
of the corresponding (2E,4E)-dienamides[11a] or proceeded
via metal exchange starting from N-isobutyl-5-telluro-
(2E,4Z)-pentadienamide,[14] or via solid-phase Wittig and
Stille reactions of amino acid derivatives.[15]
The E,Z-dienamide structure in cylindramide 6 was built
up by Lindlar reduction of the coupling enyne fragment
from the propynyl-substituted pentalene and a hydroxyorni-
Scheme 1. Some natural products with (2E,4Z)-dienamide struc-
tural motif.
[a] Institut für Organische Chemie der Universität Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: +49-711-68564285
thine-derived subunit,[16,17] which is also present in related
natural products such as 7. However, the Lindlar reduction
suffered from overreduction of the (Z)-configured double
bond. Thus, in order to find a more general way to this
type of macrocyclic tetramic acid lactams, we developed a
procedure allowing the combined preparation of the
(2E,4Z)-diene subunit and the hydroxyornithine-derived
E-mail: sabine.laschat@oc.uni-stuttgart.de
[b] Lehrstuhl für Organische Chemie, Universität Bayreuth,
Universitätsstrasse 30, 95440 Bayreuth, Germany
E-mail: Rainer.Schobert@uni-bayreuth.de
[‡] Both S. P. and C. H. contributed equally to this manuscript.
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Eur. J. Org. Chem. 2009, 2828–2835

(2E,4Z)-Dienamides from (Triphenylphosphoranylidene)ketene
amide function. For this purpose, we intended to use the
Bestmann ylide (triphenylphosphoranylidene)ketene[18]
(Ph3P=C=C=O, 9) for preparing (2E,4Z)-dienamides 11 on
the basis of our previous syntheses of (E)-α,β-unsaturated
amides from aldehydes and amines (Scheme 2).[19,20] The re-
sults are reported below.
Scheme 3. Preparation of (2Z)-alkenals (Z)-10a–e. Yields of iso-
lated (Z)-isomers after chromatography.
Scheme 2. Amide formation by intermolecular three-component
synthesis.
ship to the original hydroxyornithine subunit[16] we chose
5-aminopentanoic acid as the amine component, which was
treated with SOCl2 in EtOH to give ethyl 5-aminopentano-
ate hydrochloride 8a.[31]
Results and Discussion
In order to explore the scope and limitations of the envi-
sioned synthetic concept we employed as model compounds
the easily available (Z)-α,β-unsaturated aldehydes 10a,b as
well as the 1,2-difunctionalized cyclopentane derivatives
10c–e (Scheme 3). The starting trans-configured cyclopen-
tanecarbaldehydes 12c and 12d were prepared in optical pu-
rities of 96% ee and 80% ee, respectively,[21] by conjugate
1,4-addition of Grignard reagents to the chiral α,β-unsatu-
rated aldimine from cyclopentenecarbaldehyde and tert-leu-
cine tert-butyl ester according to the method by Koga[22]
(see Supporting Information). Selective defunctionaliz-
ation[23,24] of the commercially available Weiss diketone fol-
lowed by a reaction sequence of Baeyer Villiger oxi-
dation,[25] reduction, ring opening and final DMP oxidation
gave the cis-configured cyclopentanecarbaldehyde 12e (see
Supporting Information).
Synthesis of (Z)-α,β-Unsaturated Aldehydes (Z)-10a–e
Following a procedure developed by Ando[26] the (Z)-
acrylates (Z)-13a, 13b[27] and 13c–e were obtained in Z/E-
ratios of ca. 70:30 from the corresponding aldehydes 12a–e
by Horner–Wadsworth–Emmons olefination employing
ethyl (di-o-tolylphosphono)acetate (Scheme 3). Subsequent
reduction to the respective allyl alcohol with DIBAL in
THF at –78 °C, followed by oxidation with MnO2 in hexane
at room temperature gave the target (2Z)-alkenals (Z)-
10a,[28] (Z)-10b,[29] and (Z)-10c–e.
Scheme 4. Preparation of ethyl 5-[N-(penta-2,4-dienoyl)amino]
pentanoates 11a–e. Atom numbering for assignment of NMR sig-
nals.
Synthesis of (2E,4Z)-Dienamides 11a–e
Next, we set out to prepare an amide-functionalized
With hydrochloride 8a in hand we started our systematic
phosphonium salt from an amine precursor and investigation of the olefination reaction using the commer-
Ph3PCCO[30] (Scheme 4). Because of its structural relation- cially available (E)-cinnamaldehyde (E)-10a. The reaction
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S. Laschat et al.
FULL PAPER
Table 1. Synthesis of 5-substituted ethyl 5-[(penta-2,4-dienoyl)amino]pentanoates 11a–e under various conditions.[a]
Entry Enals 10
Solvent
Method
T [°C]
Time
Yield [%]
Ratio
Products 11
[c]
1
2
3
4
5
6
7
8
(E)-10a
(E)-10a
(E)-10a
(E)-10a
(E)-10a
(E)-10a
(Z)-10a
(Z)-10a
(Z)-10b
(Z)-10b
(Z)-10b
(Z)-10c
(Z)-10d
(Z)-10e
THF
THF
THF
one pot
80
20 h
19
15
Ͻ1
51
55
39
48
63
66
81
44
80
77
58
80:20
–
–
(2E,4E)-11a/(2Z,4E)-11a
(2E,4E)-11a/(2Z,4E)-11a
(2E,4E)-11a/(2Z,4E)-11a
(2E,4E)-11a/(2Z,4E)-11a
(2E,4E)-11a/(2Z,4E)-11a
(2E,4E)-11a/(2Z,4E)-11a
(2E,4Z)-11a/(2Z,4Z)-11a
(2E,4Z)-11a/(2Z,4Z)-11a
(2E,4Z)-11b/(2Z,4Z)-11b
(2E,4Z)-11b/(2Z,4Z)-11b
(2E,4Z)-11b/(2Z,4Z)-11b
(2E,4Z)-11c/(2Z,4Z)-11c
(2E,4Z)-11d/(2Z,4Z)-11d
(2E,4Z)-11e[e]
one pot, mw[b]
one pot, mw[d]
110
110
170
170
170
120
160
120
170
190
170
170
170
20 min
20 min
20 min
20 min
20 min
3 d
20 min
3 d
20 min
20 min
20 min
20 min
20 min
toluene/CH2Cl2 (9:1) 2 steps, mw
toluene/CH2Cl2 (9:1) 2 steps, mw[d]
toluene/CH2Cl2 (9:1) 2 steps, mw[d]
toluene/CH2Cl2 (9:1) 2 steps
toluene/CH2Cl2 (9:1) 2 steps, mw
toluene/CH2Cl2 (9:1) 2 steps
toluene/CH2Cl2 (9:1) 2 steps, mw
toluene/CH2Cl2 (9:1) 2 steps, mw
toluene/CH2Cl2 (9:1) 2 steps, mw
toluene/CH2Cl2 (9:1) 2 steps, mw
toluene/CH2Cl2 (9:1) 2 steps, mw
74:26
66:34
74:26
86:14
75:25
77:23
71:29
77:23
80:20
78:22
100:0
9
10
11
12
13
14
[a] See Scheme 4. [b] For microwave (mw) conditions see Experimental. [c] Yields refer to isolated yields, and product ratios were deter-
mined from isolated yields after chromatographic separation. [d] With additive LiCl (1 equiv.) (entries 3, 5) or LiBr (1 equiv.) (entry 6).
[e] The (2Z,4Z)-isomer was not detected.
was initially carried out in a one-pot fashion starting from were assigned by the vicinal coupling constants of the olefinic
hydrochloride 8a with Ph3PCCO (2 equiv.) serving also as 2-H and 3-H signals in 1H NMR spectra, being J2,3
=
the base as shown in Scheme 2. However, a mixture of 14.9 Hz (for 2E) and J2,3 = 11.2 Hz (for 2Z). The assign-
(2E,4E)- and (2Z,4E)-11a in only poor yield of 19% was ments were further supported by an X-ray crystal structure
obtained (Table 1, entry 1). The low yield was assumed to analysis of compound (2E,4E)-11a (Figure 1).[32]
arise from incomplete deprotonation of the phosphonium
Next, (Z)-cinnamaldehyde (Z)-10a was treated with
salt 14 by Ph3PCCO. Therefore, instead of Ph3PCCO the phosphonium salt 14 at 120 °C. After 3 d reaction time, the
external base DBU was applied to deprotonate 14.[19a] In desired (2E,4Z)-dienamide (2E,4Z)-11a was isolated in 48%
order to exclude an excess of base we performed the reac- yield together with its minor (2Z,4Z)-isomer (2Z,4Z)-11a
tion in two steps, isolating phosphonium salt 14, which was in a ratio of 86:14 (entry 7). Again the isomers were sepa-
prepared from 8a and Ph3PCCO in dioxane at 60 °C, prior rated by simple column chromatography on silica gel, and
to deprotonation with DBU and reaction with aldehydes the ratio was determined from isolated yields. Performing
(Scheme 4). Furthermore, due to this modification the sol- the reaction at 160 °C under microwave irradiation for
vent THF could be replaced with a mixture of toluene/ 20 min further increased the yield to 63%, however, at the
CH2Cl2 (9:1) to improve the solubility of 14 and to allow a expense of the E/Z-ratio (75:25) (entry 8).
high temperature in microwave reactions. Indeed, (2E,4E)-
Similar results were found for (Z)-3-cyclopentylacrylal-
and (2Z,4E)-11a were isolated in yields of up to 55% by dehyde (Z)-10b (entries 9–11). At 120 °C a mixture of
microwave-irradiated two-step reaction (Table 1, entries 4–6). (2E,4Z)-11b and (2Z,4Z)-11b was isolated in 66% yield
The attempts to enhance the (E)-selectivity of the olefination with a product ratio of 77:23 in favour of the desired
by addition of lithium salts failed. In all cases, the product (2E,4Z)-isomer (entry 9). By using microwave irradiation at
was obtained with similar (2E,4E):(2Z,4E) ratios. Therefore, 170 °C a further increase to 81% yield was observed, while
all further experiments with (Z)-aldehydes were carried out the (E)-selectivity of the olefination slightly decreased (en-
without any external additive. The isomers could be sepa- try 10). An increase of the temperature to 190 °C neither
rated readily by column chromatography on silica gel and improved the yield nor the (E)-selectivity (entry 11).
Figure 1. Structure of ethyl 5-{[(2E,4E)-5-phenylpenta-2,4-dienoyl]amino}pentanoate (2E,4E)-11a in the solid state. Double bond lengths
C2=C3 1.31(1) Å and C4=C5 1.31(1) Å.
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(2E,4Z)-Dienamides from (Triphenylphosphoranylidene)ketene
tions were measured on a Perkin–Elmer 241 polarimeter. Micro-
wave: CEM Explorer, 170 °C for 20 min (300 W, isothermic).
When 3-(2-vinylcyclopentyl)acrylaldehyde (Z)-10c and 3-
(2-phenylcyclopentyl)acrylaldehyde (Z)-10d were employed
at 170 °C under microwave conditions, the corresponding
ethyl [(penta-2,4-dienoyl)amino]pentanoates 11c and 11d
were isolated in 80% and 77% yield with (2E,4Z):(2Z,4Z)
ratios of 80:20 and 78:22, respectively (entries 12, 13). Un-
der the same conditions 3-(2-allylcyclopentyl)acrylaldehyde
(Z)-10e reacted cleanly to pentanoate (2E,4Z)-11e. Its iso-
mer (2Z,4Z)-11e could not be detected (entry 14). These
results indicate that even substituted enals were suitable
starting materials for this olefination reaction.
General Procedure for the Synthesis of (Z)-Acrylates 13: To a sus-
pension of NaH (248 mg, 10.34 mmol) in THF (40 mL) in a flame-
dried Schlenk flask at 0 °C was slowly added a solution of ethyl
(di-o-tolylphosphono)acetate (3.60 g, 10.34 mmol) in THF
(10 mL). After completion of the gas formation, the reaction mix-
ture was cooled to –78 °C, and a solution of the respective aldehyde
12 (9.4 mmol) in THF (10 mL) was added. The reaction mixture
was stirred for 1.5 h, warmed to room temperature and after ad-
dition of dest. H2O (50 mL), the layers were separated and the
aqueous layer was extracted with Et2O. The combined organic lay-
ers were dried (MgSO4) and concentrated under vacuum. The (Z)-
and (E)-isomers of 13 were separated by chromatography on silica
gel with hexanes/EtOAc (10:1) and obtained in all cases in a ratio
(Z):(E) = 70:30.
Despite the harsh reaction conditions the stereochemical
integrity of the C=C bond of the starting (E)- or (Z)-prope-
nals 10 was maintained during the reaction sequence. As
already described for the (E)-cinnamaldehyde derived prod-
ucts 11a, this was proved by distinctive vicinal coupling con-
Ethyl 3-[(1S,2S)-2-Vinylcyclopentyl]acrylate (13c): Yield 1.22 g
(67%). Rf = 0.90 (hexanes/EtOAc, 10:1). [α]2D0 = +40.1 (c = 1.00,
1
stants of the olefinic signals in the H NMR spectra as ex-
1
emplified for (2E,4Z)-11b and (2Z,4Z)-11b. Both isomers
CH2Cl2). H NMR (500 MHz, CDCl3): δ = 1.27 (t, J = 7.1 Hz, 3
can clearly be differentiated by the coupling constants be- H, CO2CH2CH3), 1.37 (ddt, J = 12.6, 9.7, 8.9 Hz, 1 H, 5-Ha), 1.47–
1.56 (m, 1 H, 3-Ha), 1.68–1.79 (m, 2 H, 4-H), 1.92 (ddt, J = 12.5,
7.9, 4.5 Hz, 1 H, 3-Hb), 1.99 (ddt, J = 12.6, 7.7, 4.8 Hz, 1 H, 5-
Hb), 2.12–2.21 (m, 1 H, 2-H), 3.57 (dddd, J = 20.1, 9.7, 7.7, 1.0 Hz,
1 H, 1-H), 4.15 (dq, J = 7.1, 1.0 Hz, 2 H, CO2CH2CH3), 4.89 (ddd,
J = 10.2, 2.0, 0.9 Hz, 1 H, 2Ј-Hcis), 4.95 (ddd, J = 17.1, 2.0, 1.1 Hz,
1 H, 2Ј-Htrans), 5.73 (ddd, J = 17.1, 10.2, 7.9 Hz, 1 H, 1Ј-H), 5.75
(dd, J = 11.5, 1.0 Hz, 1 H, CH=CHCO2Et), 6.03 (dd, J = 11.5,
10.0 Hz, 1 H, CH=CHCO2Et) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.3 (CO2CH2CH3), 23.9 (C-4), 32.6, 32.7 (C-3, C-5), 45.0 (C-
1), 52.5 (C-2), 59.8 (CO2CH2CH3), 113.7 (C-2Ј), 119.5 (C-1Ј), 141.1
(CHCHCO2Et), 153.3 (CHCHCO2Et), 166.5 (CO2Et) ppm. FT-IR
tween 2-H and 3-H, which were determined to be J2,3
=
14.9 Hz and 11.5 Hz in (2E,4Z)-11b and (2Z,4Z)-11b,
respectively, while the coupling constants of the other ole-
finic 4-H, 5-H, and 6-H protons are comparable.
Conclusions
This study demonstrates the potential of the cumulated
phosphorus ylide Ph3PCCO 9 in the synthesis of (2E,4Z)-
dienamides 11a–e from 5-aminovaleric acid and (Z)-α,β-un-
saturated aldehydes 10a–e. The three-component reaction
was performed in two steps involving formation of phos-
phonium salt 14 from hydrochloride 8a and ylide 9 followed
by deprotonation of isolated 14 with DBU to give the corre-
sponding acyl ylide and finally its reaction with aldehydes
10. Noteworthy, (2E,4Z)-dienamide (2E,4Z)-11e was de-
tected exclusively as product, whereas the E,Z-selectivity in
the reaction of the other propenals 10a–d remained com-
parable regardless of the conditions, resulting in isomeric
ratios of about 80:20 in favour of (2E,4Z)-11a–d. However,
in all cases, the (Z)-configuration of the starting aldehyde
10 was left untouched. This is particularly remarkable be-
cause phosphanes are known to catalyze the isomerization
of electron-withdrawing (Z)-alkenes.[33] The desired
(2E,4Z)-products were easily separated from their minor
(2Z,4Z)-isomers by simple column chromatography with
hexanes/EtOAc as eluent.
(ATR): ν = 2954 (w), 2868 (w), 1719 (vs), 1641 (m), 1418 (w), 1185
˜
(vs), 1031 (m), 908 (m), 821 (m) cm–1. GC-MS (EI): m/z (%) = 194
(30), 165 (50), 149 (28), 121 (100), 114 (28), 97 (34), 91 (38), 79
(42), 67 (40), 55 (36), 41 (24). HRMS (ESI): calcd. for C12H19O2
[M + H]: 194.1380; found 194.1382.
Ethyl 3-[(1S,2R)-2-Phenylcyclopentyl]acrylate (13d): Yield 1.90 g
(83%). Rf = 0.85 (hexanes/EtOAc, 10:1). [α]2D0 = +37.2 (c = 1.00,
1
CH2Cl2). H NMR (500 MHz, CDCl3): δ = 1.19 (t, J = 7.1 Hz, 3
H, CO2CH2CH3), 1.45–1.54 (m, 1 H, 5-Ha), 1.73–1.94 (m, 3 H, 3-
Ha, 4-H), 2.11–2.74 (m, 2 H, 3-Hb, 5-Hb), 2.73 (dt, J = 10.3, 7.8 Hz,
1 H, 2-H), 3.95–4.04 (m, 1 H, 1-H), 4.02 (q, J = 7.1 Hz, 2 H,
CO2CH2CH3), 5.64 (dd, J = 11.5, 0.9 Hz, 1 H, CH=CHCO2Et),
6.07 (dd, J = 11.5, 10.0 Hz, 1 H, CH=CHCO2Et), 7.13–7.26 (m, 5
H, Ar) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.2
(CO2CH2CH3), 24.1 (C-4), 32.9 (C-5), 35.4 (C-3), 45.0 (C-1), 53.9
(C-2), 59.7 (CO2CH2CH3), 119.7 (CHCHCO2Et), 126.1, 127.4,
128.2, 143.5 (Ar), 152.9 (CHCHCO2Et), 166.3 (CO2Et) ppm. FT-
IR (ATR): ν = 2953 (m), 2870 (w), 1715 (vs), 1644 (m), 1418 (w),
˜
1183 (vs), 1146 (s), 1029 (m), 823 (m), 755 (s), 698 (s) cm–1. MS
(ESI): m/z = 267, 245, 199, 181, 155, 146, 129, 121, 103. HRMS
(ESI): calcd. for C16H20NaO2 [M + Na]: 267.1356; found 267.1355.
Ethyl 3-(2-Allylcyclopentyl)acrylate (13e): According to the GP,
from 12e (183 mg, 1.33 mmol), NaH (343 mg, 1.43 mmol), and
ethyl (di-o-tolylphosphono)acetate (0.50 g, 1.43 mmol); yield
Experimental Section
Materials and Methods: Melting points were determined on a Büchi
SMP 20 and are uncorrected. NMR spectra were recorded on a
Bruker Avance 300 and Avance 500 with TMS as an internal stan-
dard. TLC: Silica gel 60 F254 (Merck). Column chromatography:
Kieselgel 60, grain size 40–63 µm (Fluka). IR spectra were recorded
on a Bruker Vector 22. Mass spectra were recorded on a Bruker
Daltonics micrOTOF_Q. GC-MS: GC HP 5890 series II, HP-5 col-
umn (Hewlett–Packard) with helium as carrier gas. Specific rota-
218 mg (79%). Rf
=
0.59 (pentane/Et2O, 50:1). 1H NMR
(500 MHz, CDCl3): δ = 1.29 (t, J = 7.1 Hz, 3 H, CO2CH2CH3),
1.35–1.42 (m, 1 H, 5-Ha), 1.42–1.50 (m, 1 H, 3-Ha), 1.60–1.67 (m,
1 H, 4-Ha), 1.71–1.85 (m, 2 H, 4-Hb, 5-Hb), 1.85–1.95 (m, 2 H, 1Ј-
Ha, 3-Hb), 2.07–2.20 (m, 2 H, 1Ј-Hb, 1-H), 3.86–3.96 (m, 1 H, 2-
H), 4.17 (q, J = 7.1 Hz, 2 H, CO2CH2CH3), 4.92 (ddd, J = 10.1,
2.2, 1.4 Hz, 1 H, 3Ј-Hcis), 4.97 (ddd, J = 17.1, 2.2, 1.4 Hz, 1 H, 3Ј-
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Htrans), 5.71–5.81 (m, 1 H, 2Ј-H), 5.77 (dd, J = 11.5, 1.0 Hz, 1 H, 1.66–1.77 (m, 2 H, 3-Hb, 4-Hb), 1.81–1.90 (m, 2 H, 1Ј-Ha, 5-Hb),
CH=CHCO2Et), 6.15 (dd, J = 11.5, 11.5 Hz, 1 H, CH=CHCO2Et) 2.07–2.20 (m, 2 H, 1Ј-Hb, 1-H), 3.86–3.96 (m, 1 H, 2-H), 4.80 (ddd,
ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2 (CO2CH2CH3), 23.3
J = 11.2, 2.7, 1.4 Hz, 1 H, 3Ј-Hcis), 4.85 (ddd, J = 17.0, 3.8, 1.4 Hz,
(C-4), 30.4 (C-5), 32.2 (C-3), 35.5 (C-1Ј), 41.2 (C-2), 43.8 (C-1), 1 H, 3Ј-Htrans), 5.61–5.69 (m, 1 H, 2Ј-H), 5.77 (dd, J = 11.7, 8.0 Hz,
59.7 (CO2CH2CH3), 114.9 (C-3Ј), 119.1 (CHCO2Et), 138.3 (C-2Ј), H, CH=CHCHO), 6.52 (dd, 11.7, 11.7 Hz,
151.8 (CHCHCO Et), 166.4 (CO Et) ppm. FT-IR (ATR): ν = 3073 CH=CHCHO), 9.99 (d, J = 8.0 Hz, 1 H, CHO) ppm. 13C NMR
1
J
=
1 H
˜
2
2
(w), 2942 (s), 2868 (m), 1717 (vs), 1640 (m), 1454 (w), 1423 (w), (125 MHz, acetone): δ = 23.8 (C-4), 31.0 (C-5), 33.1 (C-3), 36.1 (C-
1382 (w), 1292 (w), 1182 (vs), 1101 (m), 997 (w), 907 (vs), 822 (m), 1Ј), 41.1 (C-2), 45.1 (C-1), 115.8 (C-3Ј), 130.4 (CHCHCHO), 138.8
729 (vs) cm–1. MS (ESI): m/z (%) = 209 (32) [M+ + H], 181 (6),
163 (100), 149 (6), 145 (12), 135 (46), 107 (4). HRMS (ESI): calcd.
for C13H20NaO2 [M + Na]: 231.1356; found 231.1354.
(C-2Ј), 154.7 (CHCHCHO), 191.4 (CHO) ppm. FT-IR (ATR): ν =
˜
2953 (vs), 2869 (m), 1678 (vs), 1640 (m), 1438 (w), 1085 (m), 994
(m), 912 (vs), 772 (s) cm–1. MS (ESI): m/z (%) = 164 (5), 146 (10),
135 (11), 124 (8), 123 (100), 120 (60), 110 (5), 107 (11), 105 (20),
95 (74), 83 (24), 81 (59), 79 (57), 77 (22), 70 (7), 67 (53), 57 (5), 55
(19), 53 (17), 41 (40), 39 (19). HRMS (EI): calcd. for C11H16O
[M+]: 164.1201; found 164.1214.
General Procedure for the Synthesis of Acrylaldehydes 10: To a solu-
tion of the respective 13 (11.9 mmol) in THF (150 mL) at –78 °C
was slowly added dropwise a 1  solution of diisobutylalumini-
umhydride in hexane (29.8 mL, 29.8 mmol) and the reaction mix-
ture stirred for 2 h. After addition of a satd. sodium/potassium
tartrate solution (100 mL), the reaction mixture was stirred at room
temperature for 30 min. The organic layer was separated and
washed with brine (200 mL). The aqueous layers were extracted
with Et2O (300 mL). The combined organic layers were dried
(MgSO4), the solvent was removed under vacuum and the crude
resulted alcohol reacted without further purification.
Ethyl 5-({[Chloro(triphenyl)phosphoranyl]acetyl}amino)pentanoate
(14): To a solution of 8a (182 mg, 1 mmol) in dioxane (10 mL) was
added Ph3PCCO (302 mg, 1 mmol) and the cloudy reaction mix-
ture was heated at 60 °C for 4 h. The solvent was removed under
vacuum to give 14 (483 mg, 1 mmol, 100%) as a colorless foam.
1H NMR (CDCl3, 500 MHz): δ = 1.24 (t, J = 7.1 Hz, 3 H,
CH2CH3), 1.37–1.44 (m, 2 H, 4-H), 1.47–1.56 (m, 2 H, 3-H), 2.21
(t, J = 7.4 Hz, 2 H, 2-H), 3.09 (dd, J = 13.2, 6.6 Hz, 2 H, 5-H),
4.09 (q, J = 7.1 Hz, 2 H, CH2CH3), 5.06 (d, JP-H = 14.4 Hz, 2 H,
7-H), 7.58–7.91 (m, 15 H, Ar-H) 9.93 (br., 1 H, NH) ppm. 13C
NMR (CDCl3, 125 MHz): δ = 14.1 (CH2CH3), 22.1 (C-3), 28.1
(C-4), 31.9 (d, JP-C = 55.2 Hz, C-7), 33.6 (C-2), 39.4 (C-5), 60.0
(CH2CH3), 118.3 (d, JP-C = 88.7 Hz, i-C), 129.9 (d, JP-C = 13.0 Hz,
m-C), 133.9 (d, JP-C = 10.6 Hz, o-C), 134.8 (d, JP-C = 2.9 Hz, p-C),
162.2 (d, JP-C = 5.0 Hz, C-6), 173.2 (C-1) ppm. 31P NMR (CDCl3,
The alcohol (11.9 mmol) was dissolved in hexane (200 mL) and
freshly precipitated MnO2 (5 g) was added. The suspension was
stirred for 16 h, then filtered through Celite (10 g) and the residue
washed with Et2O (200 mL). The combined filtrates were concen-
trated under vacuum and the crude product chromatographed on
silica gel with hexanes/EtOAc (100:1).
3-[(1S,2S)-2-Vinylcyclopentyl]acrylaldehyde (10c): Yield 607 mg
(34%). Rf = 0.85 (hexanes/EtOAc, 10:1). [α]2D0 = +107.2 (c = 1.00,
202 MHz): δ = 22.1 (m) ppm. FT-IR (ATR): ν = 3056 (w), 2938
˜
1
CHCl3). H NMR (500 MHz, CDCl3): δ = 1.47–1.64 (m, 2 H, 3-
(w), 2868 (w), 2362 (w), 2192 (w), 1730 (m), 1666 (s), 1557 (m),
1438 (s), 1163 (m), 1110 (vs), 1096 (s), 910 (s), 790 (vs) cm–1. MS
(ESI): m/z = 448, 420, 303, 279, 219, 201, 129, 101. HRMS (ESI):
calcd. for C27H31NO3P 448.2036; found 448.2041.
Ha, 5-Ha), 1.75–1.85 (m, 2 H, 4-H), 1.93–2.09 (m, 2 H, 3-Hb, 5-
Hb), 2.18–2.31 (m, 1 H, 2-H), 3.09–3.22 (m, 1 H, 1-H), 5.01 (m, 2
H, 2Ј-H), 5.67 (ddd, J = 17.7, 9.6, 8.1 Hz, 1 H, 1Ј-H), 5.95 (ddd, J
= 11.0, 8.2, 1.0 Hz, 1 H, CH=CHCHO), 6.44 (t, J = 11.0 Hz, 1 H,
CH=CHCHO), 9.96 (dd, J = 8.2, 0.5 Hz, 1 H, CHO) ppm. 13C
NMR (125 MHz, CDCl3): δ = 24.1 (C-4), 32.5, 33.6 (C-3, C-5),
45.0 (C-1), 52.0 (C-2), 115.5 (C-2Ј), 130.0 (CHCHCHO), 139.7 (C-
General Procedure for the Synthesis of (2E,4Z)-Dienamides 11: To
a solution of freshly prepared 14 (483 mg, 1 mmol) in toluene/
CH2Cl2 (9:1) at –30 °C was added DBU (0.16 mL, 168 mg,
1.1 mmol) and the reaction mixture stirred for 2 h. Then the respec-
tive aldehyde 10a–d (0.7 mmol) was added and the reaction mixture
was heated at 170 °C for 20 min in a sealed vessel in a microwave
oven. After removal of the solvent, the crude product was chro-
matographed on silica gel with hexanes/EtOAc (2:1) to separate
the isomers. 11e was prepared from 14 (345 mg, 0.71 mmol), DBU
(0.11 mL, 120 mg, 0.79 mmol), and 10e (82 mg, 0.5 mmol).
1Ј), 156.2 (CHCHCHO), 191.5 (CHO) ppm. FT-IR (ATR): ν =
˜
2955 (m), 2868 (w), 1676 (vs), 1639 (m), 1419 (w), 1172 (m), 995
(m), 911 (s), 761 (s) cm–1. MS (APCI): m/z = 151, 133, 107, 105,
91. HRMS (ESI): calcd. for C10H14NaO [M + Na]: 173.0937; found
173.0934.
3-[(1S,2R)-2-Phenylcyclopentyl]acrylaldehyde (10d): Yield 634 mg
(27%). Rf = 0.74 (hexanes/EtOAc, 10:1). [α]2D0 = +90.7 (c = 1.00,
Ethyl
5-{[(2E,4E)-5-Phenylpenta-2,4-dienoyl]amino}pentanoate
1
CH2Cl2). H NMR (500 MHz, CDCl3): δ = 1.60–1.74 (m, 1 H, 5-
[(2E,4E)-11a]: Yield 78 mg (57%). Rf = 0.31 (hexanes/EtOAc, 3:1);
Ha), 1.85–1.98 (m, 3 H, 3-Ha, 4-H), 2.14–2.27 (m, 2 H, 3-Hb, 5-
Hb), 2.75–2.86 (m, 1 H, 2-H), 3.39–3.48 (m, 1 H, 1-H), 5.83 (ddd,
J = 11.0, 8.2, 1.0 Hz, 1 H, CH=CHCHO), 6.49 (dd, J = 11.0,
11.0 Hz, 1 H, CH=CHCHO), 7.09–7.32 (m, 5 H, Ar), 9.49 (d, J =
8.2 Hz, 1 H, CHO) ppm. 13C NMR (125 MHz, CDCl3): δ = 24.6
(C-4), 33.9 (C-5), 34.4 (C-3), 47.5 (C-1), 53.7 (C-2), 126.7, 127.3,
128.6 (Ar), 130.3 (CHCHCHO), 155.8 (CHCHCHO), 190.9 (CHO)
1
m.p. 83 °C. H NMR (500 MHz, CDCl3): δ = 1.26 (t, J = 7.1 Hz,
3 H, CH2CH3), 1.56–1.64 (m, 2 H, 4Ј-H), 1.65–1.73 (m, 2 H, 3Ј-
H), 2.35 (t, J = 7.2 Hz, 2 H, 2Ј-H), 3.37 (td, J = 6.9, 5.8 Hz, 2 H,
5Ј-H), 4.13 (q, J = 7.1 Hz, 2 H, CH2CH3), 5.72 (br., 1 H, NH),
5.96 (d, J = 14.9 Hz, 1 H, 2-H), 6.84–6.87 (m, 2 H, 4-H, 5-H),
7.23–7.45 (m, 5 H, Ar), 7.39 (ddd, J = 14.9, 7.6, 2.6 Hz, 1 H, 3-H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2 (CH2CH3), 22.1 (C-
3Ј), 29.0 (C-4Ј), 33.7 (C-2Ј), 39.2 (C-5Ј), 60.4 (CH2CH3), 123.9 (C-
2), 126.3 (C-4), 127.0 (m-C), 128.7 (p-C), 128.8 (o-C), 136.3 (i-C),
139.1 (C-5), 140.9 (C-3), 166.0 (C-1), 173.6 (C-1Ј) ppm. FT-IR
ppm. FT-IR (ATR): ν = 2953 (m), 2870 (m), 1728 (m), 1684 (vs),
˜
1493 (w), 1451 (w), 1151 (m), 976 (m), 755 (s), 699 (vs) cm–1. MS
(APCI): m/z = 201, 199, 183, 155, 145, 141, 129, 117, 91. HRMS
(APCI): calcd. for C14H17O [M + H]: 201.1274; found 201.1262.
(ATR): ν = 3305 (m), 2950 (m), 2866 (w), 1727 (vs), 1643 (s), 1604
˜
3-(2-Allylcyclopentyl)acrylaldehyde (10e): According to the GP,
(s), 1523 (s), 1486 (w), 1375 (w), 1262 (m), 1164 (m), 1096 (w), 1035
from 13e (218 mg, 1.05 mmol), DIBAL (2.6 mL, 2.6 mmol), and (w), 993 (vs), 983 (s), 836 (m), 689 (s), 623 (s) cm–1. MS (ESI): m/z
MnO2 (0.5 g); yield 109 mg (63%). Rf = 0.56 (pentane/Et2O, 25:1).
Z/E ratio Ͼ9:1. H NMR (500 MHz, acetone): δ = 1.30–1.39 (m, H]: 302.1756; found 302.1753. C18H23NO3 (301.39): calcd. C 71.73,
1 H, 3-Ha), 1.42–1.51 (m, 1 H, 5-Ha), 1.51–1.60 (m, 1 H, 4-Ha), H 7.69, N 4.65; found: C 71.68, H 7.61, N 4.59.
= 302, 256, 157, 129. HRMS (ESI): calcd. for C18H24NO3 [M +
1
2832
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2828–2835

(2E,4Z)-Dienamides from (Triphenylphosphoranylidene)ketene
Compound (2Z,4E)-11a: Yield 38 mg (18%). Rf = 0.38 (hexanes/
(C-3), 166.4 (C-1), 173.6 (C-1Ј) ppm. FT-IR (ATR): ν = 3270 (w),
˜
EtOAc, 3:1). 1H NMR (500 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, 2944 (s), 2868 (s), 1730 (vs), 1650 (s), 1542 (s), 1447 (w), 1324 (w),
3 H, CH2CH3), 1.57–1.64 (m, 2 H, 4Ј-H), 1.65–1.73 (m, 2 H, 3Ј- 1163 (vs), 1096 (s), 1029 (s), 981 (s), 724 (w) cm–1. MS (ESI): m/z
H), 2.34 (t, J = 7.2 Hz, 2 H, 2Ј-H), 3.35 (td, J = 6.9, 5.8 Hz, 2 H,
= 294, 149, 131, 121, 100. HRMS (ESI): calcd. for C17H28NO3 [M
5Ј-H), 4.13 (q, J = 7.1 Hz, 2 H, CH2CH3), 5.61 (ddd, J = 11.2, 1.1, + H]: 294.2064; found 294.2065.
0.8 Hz, 1 H, 2-H), 5.72 (br., 1 H, NH), 6.57 (td, J = 11.2, 0.9 Hz,
Compound (2Z,4Z)-11b: Yield 46 mg (22%). Rf = 0.47 (hexanes/
EtOAc, 2:1). H NMR (500 MHz, CDCl3): δ = 1.21–1.34 (m, 2 H,
1 H, 3-H), 6.73 (d, J = 15.8 Hz, 1 H, 5-H), 7.25–7.34 (m, 3 H, Ar),
7.50–7.54 (m, 2 H, Ar), 8.30 (ddd, J = 15.8, 11.2, 1.1 Hz, 1 H, 4-
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2 (CH2CH3), 22.1
(C-3Ј), 29.0 (C-4Ј), 33.8 (C-2Ј), 39.0 (C-5Ј), 60.4 (CH2CH3), 120.1
(C-2), 125.3 (C-4), 127.4 (m-C), 128.6 (p-C), 128.7 (o-C), 136.6 (i-
C), 139.7 (C-5), 141.4 (C-3), 166.4 (C-1), 173.6 (C-1Ј) ppm. FT-IR
1
7-Ha, 10-Ha), 1.26 (t, J = 7.1 Hz, 3 H, CH3CH2O), 1.54–1.73 (m,
8 H, 3Ј-H, 4Ј-H, 8-H, 9-H), 1.78–1.86 (m, 2 H, 7-Hb, 10-Hb), 2.33
(t, J = 7.3 Hz, 2 H, 2Ј-H), 2.90–3.41 (m, 1 H, 6-H), 3.31 (td, J =
6.9, 5.7 Hz, 2 H, 5Ј-H), 4.13 (q, J = 7.1 Hz, 2 H, CH3CH2O), 5.56
(dt, J = 11.5, 1.4 Hz, 1 H, 2-H), 5.59–5.68 (m, 1 H, NH), 5.72 (ddt,
J = 11.0, 9.7, 1.4 Hz, 1 H, 5-H), 6.78 (td, J = 11.5, 1.4 Hz, 1 H, 3-
H), 7.17–7.22 (m, 1 H, 4-H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.2 (CH3CH2O), 22.1 (C-3Ј), 25.5 (C-8, C-9), 29.0 (C-4Ј), 33.7
(C-2Ј), 33.8 (C-7, C-10), 38.1 (C-6), 38.6 (C-5Ј), 60.4 (CH3CH2O),
120.2 (C-2), 122.9 (C-5), 135.5 (C-3), 145.1 (C-4), 166.6 (C-1), 173.6
(ATR): ν = 3249 (m), 2934 (m), 2868 (w), 2182 (w), 1730 (vs), 1649
˜
(s), 1615 (s), 1538 (s), 1449 (m), 1371 (m), 1242 (s), 1170 (vs), 1100
(m), 1029 (m), 1001 (m), 966 (m), 747 (m), 692 (s) cm–1. MS (ESI):
m/z = 302, 157, 145, 129, 115. HRMS (ESI): calcd. for C18H24NO3
[M + H]: 302.1756; found 302.1758.
Compound (2E,4Z)-11a: Yield 99 mg (47%). Rf = 0.34 (hexanes/
(C-1Ј) ppm. FT-IR (ATR): ν = 3293 (w), 2949 (s), 2867 (s), 1732
˜
EtOAc, 3:1). 1H NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, (vs), 1645 (s), 1535 (s), 1447 (m), 1372 (m), 1243 (s), 1162 (vs), 1096
3 H, CH2CH3), 1.50–1.74 (m, 4 H, 3Ј-H, 4Ј-H), 2.33 (t, J = 7.2 Hz,
(m), 1030 (m), 710 (w) cm–1. MS (ESI): m/z = 316, 294, 149, 131,
2 H, 2Ј-H), 3.34 (td, J = 6.8, 5.8 Hz, 2 H, 5Ј-H), 4.13 (q, J = 7.1 Hz, 121, 93. HRMS (ESI): calcd. for C17H28NO3 [M + H]: 294.2064;
2 H, CH2CH3), 5.70 (br., 1 H, NH), 5.99 (dt, J = 14.9, 0.9 Hz, 1 found 294.2043.
H, 2-H), 6.32 (td, J = 11.6, 0.9 Hz, 1 H, 4-H), 6.72–6.77 (m, 1 H,
Ethyl 5-({(2E,4Z)-5-[(1S,2S)-2-Vinylcyclopentyl]penta-2,4-dienoyl}-
5-H), 7.26–7.45 (m, 5 H, Ar), 7.72 (ddd, J = 14.9, 11.6, 0.9 Hz, 1
amino)pentanoate [(2E,4Z)-11c]: Yield 145 mg (65%). Rf = 0.52
H, 3-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2 (CH2CH3),
22.1 (C-3Ј), 29.0 (C-4Ј), 33.8 (C-2Ј), 39.1 (C-5Ј), 60.4 (CH2CH3),
126.4 (C-2), 127.5 (C-4), 127.9, 128.5, 129.2 (Ar), 136.5 (Ar), 136.5,
1
(hexanes/EtOAc, 1:1). [α]2D0 = +94.1 (c = 1.00, CH2Cl2). H NMR
(500 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, 3 H, CH3CH2O), 1.35–
1.54 (m, 2 H, 8-Ha, 10-Ha), 1.54–1.61 (m, 2 H, 4Ј-H), 1.64–1.73
136.6 (C-3, C-5), 166.1 (C-1), 173.6 (C-1Ј) ppm. FT-IR (ATR): ν
˜
(m, 4 H, 3Ј-H, 9-H), 1.87–1.95 (m, 2 H, 8-Hb, 10-Hb), 2.13–2.20
(m, 1 H, 7-H), 2.33 (t, J = 7.2 Hz, 2 H, 2Ј-H), 2.79 (dddd, J = 19.9,
10.0, 7.7, 0.9 Hz, 1 H, 6-H), 3.34 (tdd, J = 6.8, 5.9, 1.0 Hz, 2 H,
5Ј-H), 4.13 (q, J = 7.1 Hz, 2 H, CH3CH2O), 4.90 (ddd, J = 10.2,
2.0, 0.9 Hz, 1 H, cis-CH2=), 4.93 (ddd, J = 17.1, 2.0, 1.1 Hz, 1 H,
trans-CH2=), 5.59–5.64 (m, 1 H, 5-H), 5.69 (ddd, J = 17.1, 10.2,
7.8 Hz, 1 H, CH=), 5.80 (dt, J = 14.8, 0.8 Hz, 1 H, 2-H), 6.09 (ddt,
= 3281 (m), 2935 (m), 2869 (w), 2175 (m), 1730 (vs), 1650 (s), 1614
(s), 1540 (s), 1486 (w), 1273 (m), 1177 (s), 1100 (w), 1029 (w), 997
(m), 869 (m), 696 (s) cm–1. MS (ESI): m/z = 324, 302, 279, 157,
145, 129, 115. HRMS (ESI): calcd. for C18H23NO3Na [M + Na]:
324.1570; found 324.1562.
Compound (2Z,4Z)-11a: Yield 34 mg (16%). Rf = 0.37 (hexanes/
1
EtOAc, 3:1). H NMR (500 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, J = 11.6, 10.7, 0.9 Hz, 1 H, 4-H), 7.49 (ddd, J = 14.8, 11.6, 1.1 Hz,
3 H, CH2CH3), 1.56–1.63 (m, 2 H, 4Ј-H), 1.66–1.73 (m, 2 H, 3Ј-
H), 2.34 (t, J = 7.2 Hz, 2 H, 2Ј-H), 3.37 (td, J = 6.9, 5.8 Hz, 2 H,
5Ј-H), 4.13 (q, J = 7.1 Hz, 2 H, CH2CH3), 5.72 (br., 1 H, NH),
5.69 (dt, J = 11.5, 1.3 Hz, 1 H, 2-H), 6.87 (td, J = 11.5, 1.3 Hz, 1
1 δ = 14.2
H, 3-H) ppm. 13C NMR (125 MHz, CDCl3):
(CH3CH2O), 22.1, 23.8 (C-3Ј, C-9), 29.0 (C-4Ј), 32.3 (C-8), 33.4
(C-10), 33.7 (C-2Ј), 39.1 (C-5Ј), 45.4 (C-6), 51.9 (C-12), 60.4
(CH3CH2O), 114.1 (CH2=), 123.8 (C-2), 126.4 (C-4), 136.5 (C-3),
H, 3-H), 6.79–6.82 (m, 1 H, 5-H), 7.57 (td, J = 11.5, 1.3 Hz, 1 H, 141.0 (CH=), 143.5 (C-5), 166.4 (C-1), 173.6 (C-1Ј) ppm. FT-IR
4-H), 7.24–7.37 (m, 5 H, Ar) ppm. 13C NMR (125 MHz, CDCl3):
(ATR): ν = 3273 (w), 2941 (m), 2867 (m), 1733 (vs), 1652 (s), 1619
δ = 14.3 (CH2CH3), 22.2 (C-3Ј), 29.1 (C-4Ј), 33.9 (C-2Ј), 38.8 (C- (s), 1542 (s), 1447 (w), 1321 (m), 1272 (m), 1163 (vs), 1097 (s), 1030
5Ј), 60.4 (CH2CH3), 122.5 (C-2), 126.0 (C-4), 127.7 (m-C), 128.3
(m), 992 (s), 908 (m), 867 (m), 668 (m) cm–1. MS (ESI): m/z = 320,
(p-C), 129.4 (o-C), 136.2 (C-5), 136.5 (C-3), 136.6 (i-C), 166.3 (C- 175, 157, 147, 133, 119, 105, 91. HRMS (ESI): calcd. for
˜
1), 173.6 (C-1Ј) ppm. FT-IR (ATR): ν = 3296 (m), 2934 (m), 2869
C19H29NO3Na [M + Na]: 342.2040; found 342.2037.
˜
(w), 1730 (vs), 1638 (s), 1532 (s), 1436 (w), 1371 (w), 1243 (m),
Compound (2Z,4Z)-11c: Yield 34 mg (15%). Rf = 0.60 (hexanes/
EtOAc, 1:1). [α]2D0 = +37.2 (c = 1.00, CH2Cl2). 1H NMR (500 MHz,
CDCl3): δ = 1.25 (t, J = 7.1 Hz, 3 H, CH3CH2O), 1.38–1.75 (m, 8
H, 3Ј-H, 4Ј-H, 8-Ha, 9-H, 10-Ha), 1.82–1.99 (m, 2 H, 8-Hb, 10-Hb),
2.11–2.25 (m, 1 H, 7-H), 2.33 (t, J = 7.1 Hz, 2 H, 2Ј-H), 2.61–2.76
(m, 1 H, 6-H), 3.31 (td, J = 6.8, 5.8 Hz, 2 H, 5Ј-H), 4.12 (q, J =
7.1 Hz, 2 H, CH3CH2O), 4.90 (ddd, J = 10.3, 1.9, 1.0 Hz, 1 H, cis-
CH2=), 4.96 (ddd, J = 17.2, 1.9, 1.1 Hz, 1 H, trans-CH2=), 5.55
1164 (s), 1096 (m), 1028 (m), 813 (m), 697 (s) cm–1. MS (ESI): m/z
=
324, 302, 157, 145, 129, 115. HRMS (ESI): calcd. for
C18H23NO3Na [M + Na]: 324.1570; found 324.1564.
Ethyl 5-{[(2E,4Z)-5-Cyclopentylpenta-2,4-dienoyl]amino}pentanoate
[(2E,4Z)-11b]: Yield 120 mg (58%). Rf = 0.42 (hexanes/EtOAc,
2:1). 1H NMR (500 MHz, CDCl3): δ = 1.22–1.29 (m, 2 H, 7-Ha,
10-Ha), 1.25 (t, J = 7.1 Hz, 3 H, CH3CH2O), 1.54–1.72 (m, 8 H,
3Ј-H, 4Ј-H, 8-H, 9-H), 1.77–1.88 (m, 2 H, 7-Hb, 10-Hb), 2.33 (t, J (dt, J = 11.7, 1.1 Hz, 1 H, 2-H), 5.58–5.78 (m, 3 H, CH=, 5-H,
= 7.2 Hz, 2 H, 2Ј-H), 2.98–3.01 (m, 1 H, 6-H), 3.35 (td, J = 6.9, NH), 6.69 (td, J = 11.7, 1.2 Hz, 1 H, 3-H), 7.27 (ddt, J = 11.7,
5.8 Hz, 2 H, 5Ј-H), 4.13 (q, J = 7.1 Hz, 2 H, CH3CH2O), 5.69 (ddt, 10.9, 1.1 Hz, 1 H, 4-H) ppm. 13C NMR (125 MHz, CDCl3): δ =
J = 10.7, 9.8, 1.0 Hz, 1 H, 5-H), 5.75–5.80 (m, 1 H, NH), 5.82 (dd,
J = 14.9, 0.9 Hz, 1 H, 2-H), 6.00 (ddt, J = 11.6, 10.7, 0.9 Hz, 1 H,
14.2 (CH3CH2O), 22.2, 23.9 (C-3Ј, C-9), 29.1 (C-4Ј), 32.2 (C-8),
33.4 (C-10), 33.8 (C-2Ј), 38.9 (C-5Ј), 44.6 (C-6), 51.6 (C-7), 60.4
4-H), 7.57 (ddd, J = 14.9, 11.6, 1.0 Hz, 1 H, 3-H) ppm. 13C NMR (CH3CH2O), 114.1 (CH2=), 120.7 (C-2), 124.3 (C-4), 135.6 (C-3),
(125 MHz, CDCl3): δ = 14.2 (CH3CH2O), 22.1 (C-3Ј), 25.5 (C-8,
C-9), 29.0 (C-4Ј), 33.7 (C-2Ј), 33.8 (C-7, C-10), 39.0 (C-6), 39.1 (C-
5Ј), 60.4 (CH3CH2O), 123.4 (C-5), 124.9 (C-2), 136.4 (C-4), 145.5
141.0 (CH=), 143.1 (C-5), 166.4 (C-1), 173.5 (C-1Ј) ppm. FT-IR
(ATR): ν = 3294 (w), 2937 (m), 2868 (m), 1732 (vs), 1640 (s), 1535
˜
(s), 1446 (w), 1372 (m), 1241 (s), 1162 (vs), 1096 (s), 1030 (m), 996
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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S. Laschat et al.
FULL PAPER
(m), 908 (m), 798 (m), 710 (w), 669 (w) cm–1. MS (ESI): m/z = 320,
3), 138.2 (CH=), 141.5 (C-5), 166.4 (C-1), 173.6 (C-1Ј) ppm. FT-
175, 157, 147, 133, 119, 105, 91. HRMS (ESI): calcd. for IR (ATR): ν = 3279 (w), 2942 (m), 2869 (m), 1733 (vs), 1652 (s),
˜
C19H30NO3 [M + H]: 320.2220; found 320.2211.
1618 (s), 1542 (s), 1442 (m), 1372 (m), 1326 (m), 1273 (s), 1163 (vs),
1097 (m), 1031 (m), 993 (s), 962 (m), 910 (m), 869 (m), 786 (w),
732 (w), 674 (w) cm–1. MS (ESI): m/z (%) = 334 (47) [M+ + H],
189 (28), 171 (30), 161 (100), 133 (19). HRMS (ESI): calcd. for
C20H31NNaO3 [M + Na]: 356.2196; found 356.2202.
Ethyl 5-({(2E,4Z)-5-[(1S,2R)-2-Phenylcyclopentyl]penta-2,4-dienoyl}-
amino)pentanoate [(2E,4Z)-11d]: Yield 155 mg (60%). Rf = 0.45
(hexanes/EtOAc, 1:1). [α]2D0 = +8.6 (c = 1.00, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3 H, CH3CH2O), 1.47–
1.60 (m, 3 H, 4Ј-H, 10-Ha), 1.62–1.70 (m, 2 H, 3Ј-H), 1.76–1.92
(m, 3 H, 8-Ha, 9-H), 2.02–2.10 (m, 1 H, 10-Hb), 2.12–2.20 (m, 1
H, 8-Hb), 2.33 (t, J = 7.2 Hz, 2 H, 2Ј-H), 2.73 (td, J = 10.0, 7.9 Hz,
1 H, 7-H), 3.10–3.13 (m, 1 H, 6-H), 3.23–3.31 (m, 2 H, 5Ј-H), 4.13
(q, J = 7.1 Hz, 2 H, CH3CH2O), 5.51 (br., 1 H, NH), 5.64–5.71
(m, 2 H, 2-H, 5-H), 5.97 (dddd, J = 11.6, 10.6, 0.9, 0.9 Hz, 1 H, 4-
H), 7.11–7.15 (m, 1 H, 3-H), 7.17–7.21 (m, 1 H, p-H), 7.23–7.28
(m, 4 H, o-H, m-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2
(CH3CH2O), 22.1 (C-3Ј), 24.3 (C-8), 29.0 (C-4Ј), 33.8 (C-2Ј), 33.9
(C-7), 34.8 (C-9), 39.1 (C-5Ј), 47.2 (C-6), 53.5 (C-10), 60.4
(CH3CH2O), 123.9 (C-2), 126.1 (p-C), 126.7 (C-3), 128.3 (o-C),
128.5 (m-C), 135.7 (C-4), 143.0 (C-5), 143.7 (i-C), 166.3 (C-1), 173.6
Supporting Information (see also the footnote on the first page of
this article): Detailed procedures, 1H and 13C NMR spectra, analyt-
ical data of precursors. GC separations of the enantiomers of deriv-
atives 12c,d.
Acknowledgments
Generous financial support by the Deutsche Forschungsgemein-
schaft (DFG), the Ministerium für Wissenschaft, Forschung und
Kunst des Landes Baden-Württemberg (“Landesgraduierten Sti-
pendium” to C. H.) and the Fonds der Chemischen Industrie are
gratefully acknowledged.
(C-1Ј) ppm. FT-IR (ATR): ν = 3278 (w), 2941 (m), 2861 (m), 1731
˜
(vs), 1652 (s), 1620 (s), 1542 (s), 1452 (m), 1372 (w), 1163 (vs), 1097
(m), 1030 (m), 992 (m), 960 (w), 905 (m), 868 (m), 699 (vs) cm–1.
MS (ESI): m/z = 370, 255, 197, 183, 169, 141, 117, 105. HRMS
(ESI): calcd. for C23H31NNaO3 [M + Na]: 392.2196; found
392.2190.
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Compound (2Z,4Z)-11d: Yield 44 mg (17%). Rf = 0.56 (hexanes/
EtOAc, 1:1). [α]2D0 = –0.5 (c = 1.00, CHCl3). H NMR (500 MHz,
1
CDCl3): δ = 1.23 (t, J = 7.3 Hz, 3 H, CH3CH2O), 1.49–1.58 (m, 3
H, 4Ј-H, 10-Ha), 1.59–1.67 (m, 2 H, 3Ј-H), 1.79–1.89 (m, 3 H, 8-
Ha, 9-H), 1.98–2.08 (m, 1 H, 10-Hb), 2.11–2.21 (m, 1 H, 8-Hb),
2.33 (t, J = 7.3 Hz, 2 H, 2Ј-H), 2.73 (td, J = 9.8, 7.6 Hz, 1 H, 7-
H), 3.01–3.12 (m, 1 H, 6-H), 3.19–3.28 (m, 2 H, 5Ј-H), 4.13 (q, J
= 7.3 Hz, 2 H, CH3CH2O), 5.34 (dt, J = 11.3, 1.3 Hz, 1 H, 2-H),
5.50 (br., 1 H, NH), 5.70 (ddt, J = 11.1, 9.8, 1.3 Hz, 1 H, 5-H),
6.30 (td, J = 11.3, 1.3 Hz, 1 H, 3-H), 7.12–7.21 (m, 4 H, 4-H, o-H,
p-H), 7.21–7.27 (m, 2 H, m-H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.2 (CH3CH2O), 22.1 (C-3Ј), 24.6 (C-8), 29.0 (C-4Ј), 33.8 (C-
2Ј), 33.9 (C-7), 34.6 (C-9), 38.8 (C-5Ј), 46.8 (C-6), 53.5 (C-10), 60.4
(CH3CH2O), 120.4 (C-2), 124.4 (C-4), 126.0 (p-C), 127.4 (o-C),
128.3 (m-C), 135.3 (C-3), 141.3 (C-5), 142.7 (i-C), 166.5 (C-1), 173.5
(C-1Ј) ppm. FT-IR (ATR): ν = 3295 (w), 2947 (m), 2868 (m), 1730
˜
(vs), 1632 (s), 1531 (s), 1452 (m), 1368 (w), 1166 (vs), 1095 (m),
1032 (m), 939 (m), 897 (m), 750 (m), 700 (vs) cm–1. MS (ESI): m/z
= 370, 255, 197, 183, 169, 141, 117, 105. HRMS (ESI): calcd. for
C23H31NNaO3 [M + Na]: 392.2196; found 392.2190.
Ethyl 5-({(2E,4Z)-5-[2-Allylcyclopentyl]penta-2,4-dienoyl}amino)-
pentanoate [(2E,4Z)-11e]: Yield 96 mg (58%). Rf = 0.36 (hexanes/
EtOAc, 1:1). 1H NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz,
3 H, CO2CH2CH3), 1.31–1.40 (m, 1 H, 8-Ha), 1.40–1.49 (m, 1 H,
10-Ha), 1.54–1.64 (m, 3 H, 4Ј-H, 9-Ha), 1.64–1.71 (m, 2 H, 3Ј-H),
1.70–1.89 (m, 4 H, =CHCHaHb, 8-Hb, 9-Hb, 10-Hb), 1.99–2.05 (m,
1 H, 7-H), 2.06–2.13 (m, 1 H, =CHCHaHb), 2.33 (t, J = 7.2 Hz, 2
H, 2Ј-H), 3.15–3.28 (m, 1 H, 6-H), 3.35 (td, J = 6.7, 5.7 Hz, 2 H,
5Ј-H), 4.12 (q, J = 7.1 Hz, 2 H, CO2CH2CH3), 4.92 (ddt, J = 10.2,
2.4, 1.1 Hz, 1 H, cis-CH2=), 4.95 (ddt, J = 17.0, 2.4, 1.3 Hz, 1 H,
trans-CH2=), 5.68–5.77 (m, 2 H, CH=CH2, 5-H), 5.86 (dt, J = 14.9,
0.8 Hz, 1 H, 2-H), 5.96–6.00 (m, 1 H, NH), 6.09 (ddt, J = 11.7,
10.7, 0.9 Hz, 1 H, 4-H), 7.57 (ddd, J = 14.9, 11.7, 1.2 Hz, 1 H, 3-
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2 (CO2CH2CH3),
22.1 (C-3Ј), 23.2 (C-9), 29.0 (C-4Ј), 30.4 (C-8), 32.5 (C-10), 33.8
(C-2Ј), 35.5 (CHCH2), 39.1 (C-5Ј), 41.1 (C-6), 44.0 (C-7), 60.4
(CO2CH2CH3), 115.1 (CH2=), 124.0 (C-2), 126.1 (C-4), 136.0 (C-
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812.
Received: February 19, 2009
Published Online: April 21, 2009
Eur. J. Org. Chem. 2009, 2828–2835
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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