5-Aminocyclopentadienes by intramolecular addition of enolether to aminoallene functionalities

Article abstract of DOI:10.1016/S0040-4020(02)01427-8

3-(1-Alkoxyvinyl)-1-aminoallenes 6 were generated by conjugate addition of acyclic and cyclic (1-alkoxyvinyl)cuprates with the semicyclic propyne iminium salt 4. They isomerized smoothly into spiroannellated cyclopentadienes 7 through a 1,5-cyclization that in some cases occurred already at ≤20°C. (1-Methoxyallenyl)cuprates reacted with salt 4 in a 2:1 ratio to give the 5,5-dimethoxy-4-methylenepentalene-1-spiro-2′-dihydroindole derivative 10. The thermal isomerization of morpholinoallene 12 into cyclopentadiene 13 indicates that the novel 1,5-cyclization can be extended to other 3-(1-alkoxyvinyl)-1-aminoallenes as well.

Full text of DOI:10.1016/S0040-4020(02)01427-8

Tetrahedron 58 (2002) 10329–10334
5-Aminocyclopentadienes by intramolecular addition of enolether
to aminoallene functionalities
*
Robert Reinhard, Jens Schlegel and Gerhard Maas
Divison of Organic Chemistry I, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany
Received 24 July 2002; revised 8 October 2002; accepted 31 October 2002
Abstract—3-(1-Alkoxyvinyl)-1-aminoallenes 6 were generated by conjugate addition of acyclic and cyclic (1-alkoxyvinyl)cuprates with the
semicyclic propyne iminium salt 4. They isomerized smoothly into spiroannellated cyclopentadienes 7 through a 1,5-cyclization that in some
cases occurred already at #208C. (1-Methoxyallenyl)cuprates reacted with salt 4 in a 2:1 ratio to give the 5,5-dimethoxy-4-
methylenepentalene-1-spiro-20-dihydroindole derivative 10. The thermal isomerization of morpholinoallene 12 into cyclopentadiene 13
indicates that the novel 1,5-cyclization can be extended to other 3-(1-alkoxyvinyl)-1-aminoallenes as well. q 2002 Elsevier Science Ltd. All
rights reserved.
1. Introduction
tion of the resulting a,b,g,d-unsaturated azomethine ylide.
As the concomitant formation of 3 as well as other
examples6 show, the 1,7-electrocyclization also takes
place when the vinylic double bond is replaced by a
(hetero)aromatic p bond.
Vinylallenes are useful building blocks for the synthesis of
polyenes and carbocycles of biological significance.1 Many
of these syntheses are based on the ability of vinylallenes to
get involved in several pericyclic reactions, such as [1,5]-
sigmatropic H shifts,2 electrocyclic ring closure to form
methylenecyclobutene derivatives,3 and intra-1 as well as
intermolecular4 [4þ2] cycloaddition reactions.
We report now that the thermal isomerization pathway
changes when the aminoallenes are decorated with a
1-alkoxyvinyl rather than a simple vinyl substituent at the
allenic C-3 position.
Vinylallenes featuring a more electron-rich allene moiety,
such as 1-morpholino-3-vinylallene 1, rearrange thermally
into [1,4]oxazino[4,3-a]azepine derivatives 2 (Scheme 1).5
This isomerization is likely to proceed via a [1,4]-H shift in
the CvC–NCH moiety and subsequent 1,7-electrocycliza-
2. Results and discussion
We have shown in previous work5–7 that highly substituted
aminoallenes can be prepared conveniently from propyne
iminium salts and organocuprates. In an extension of these
studies, we decided to use (1-alkoxyvinyl)cuprates because
they would allow the introduction of additional function-
ality into the resulting aminoallenes and their thermal
isomerization products (see Section 1).8 In this paper, we
focus on (alkoxyvinyl)allenes derived from the semicyclic
propyne iminium salt 49 because their thermal isomerization
reactions cover a remarkably wide temperature range,
depending on the enolether function. Salt 4 was allowed
to react with (1-ethoxyvinyl)cuprate 5a between 260 and
2408C (Scheme 2). To our surprise, the product that was
obtained, after bringing the reaction mixture to room
temperature followed by extraction into pentane, was not
the expected vinylallene 6a but rather, the spiroannellated
cyclopentadiene 7a. This product is likely to result from a
1,5-cyclization that includes nucleophilic attack of the
enolether function’s b-carbon at the amino-substituted
allenic carbon atom, and subsequent 1,4-migration of a
Scheme 1.
Keywords: allenes; copper and compounds; cyclization; cyclopentadienes;
iminium salts; spiro compounds.
*
Corresponding author. Tel.: þ49-731-50-22790; fax: þ49-731-50-22803;
e-mail: gerhard.maas@chemie.uni-ulm.de
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01427-8

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R. Reinhard et al. / Tetrahedron 58 (2002) 10329–10334
in the case of 6a, dihydropyran-2-yl-substituted amino-
allene 6b was not observed due to its rapid isomerization
into cyclopenta[b]pyran derivative 7b, the constitution of
which was confirmed by XRD analysis. In contrast, allenes
bearing 1,4-dioxen-2-yl (6c) and dihydrofuran-2-yl (6d)
groups, respectively, could be isolated and fully character-
ized. When 6c was heated in toluene (808C, 12 h), it also
underwent 1,5-cyclization yielding spiroannellated cyclo-
penta-1,4-dioxin derivative 7c. Allene 6d did not react
analogously but rather rearranged into 1,3,5-triene 8 which
was obtained as a 12:1 mixture of diastereomers. Based on
the inspection of 1H chemical shifts, we assume the
presence of the Z and E isomers with respect to the enamine
double bond. The phenyl ring at C-3 is expected to be in an
almost perpendicular position with respect to the 1,3-diene
system, and should therefore cause magnetic shielding of
neighboring methyl groups at the dihydroindole ring. In
agreement with this, we observed a shielding of the NMe
protons in the major (Z) isomer by 20.49 ppm relative to the
minor isomer and, conversely, a high-field shift of the CMe2
protons in the E isomer (Dd¼20.34 ppm). The configur-
ation at the C-3–C-4 double bond in 8 could not be
assigned; nOe experiments were not applicable because of
the very similar chemical shifts of 2-H and the allylic
protons in the dihydrofuran ring which prevented selective
irradiation at the 2-H resonance. The mechanism of the
isomerization 6d!8 deserves some comment: what looks
like a simple [1,5]-H shift, can hardly be a concerted
sigmatropic reaction since the configuration of the endo-
cyclic enolether double bond prevents the formation of an
unstrained cyclic transition structure. We propose that this
Scheme 2.
proton. The description of the cyclization step as A!B
(Scheme 2), where A represents a resonance structure of the
enamine function in 6a, illustrates that it may also be called
a 5-exo-trig iminium cyclization.
When iminium salt 4 was combined with Gilman–Lipshutz
cuprates derived from cyclic enolethers,10 the thermal
stability and isomerization pathway was found to depend
on the exact nature of the enolether function (Scheme 3). As
Scheme 3. (a) THF, 2608C, then 1 h at 2408C, then 2408C!rt during 2 h. (b) Toluene, 808C, 12 h. (c) Toluene, 1008C, 2.5 h. (d) Conditions as for (a), 1 or
2 equiv. of 5e.

R. Reinhard et al. / Tetrahedron 58 (2002) 10329–10334
10331
Figure 1. Molecular structure of 10 in the solid state (ORTEP plot). Only
one of two molecules not related by space group symmetry is shown.
˚
Distances (A): C12–C13 1.334(6), C14–C19 1.345(6), C15–C16 1.325(7),
C17–C18 1.546(7).
Scheme 4. (a) THF/CH2Cl2, 3 h at 2408C, then 2408C!rt. (b) Toluene,
1358C, 4 h; or CHCl3, rt, 2 h.
thermal rearrangement begins with the formation of an
azomethine ylide by a [1,4]-H shift from the NMe group to
the central allenic carbon. Instead of following the 1,7-
electrocyclization pathway discussed in Section 1 (see also
Scheme 1), this intermediate is flexible enough to allow an
allylic hydrogen atom in the dihydrofuran ring to undergo a
concerted [1,8]-migration.
of C-2(ring) from sp2 to sp3. On the other hand, the
readiness of allenes 6 to undergo the cyclization depends on
the nucleophilicity of the enolether moieties, and in this
respect, the dihydrodioxin substituent in 6c is clearly
disfavored. In the case of 6d, it can be argued that the
distance between the b-C atom of the enolether function and
the amino-substituted allenic carbon atom is larger than in
all other cases due to the larger exocyclic bond angle at C-2
(dihydrofuran). This geometric factor may push the
activation energy for 1,5-cyclization to a value that is
higher than the barrier for the [1,4]-H shift generating an
azomethine ylide intermediate.
Iminium salt 4 reacted with 1 equiv. of (1-methoxy-
allenyl)cuprate 5e to form the 5,5-dimethoxy-4-methylene-
pentalene-1-spiro-20-dihydroindole derivative 10 in 47%
isolated yield (Scheme 3). Its constitution was established
beyond doubt by XRD analysis (Fig. 1). Evidently, two
methoxyallene moieties are incorporated into 10. This fact
led us to repeat the reaction by applying 2 equiv. of the
cuprate, since it is known that cuprates of the type R2CuLi in
general deliver only one organic residue.11 However, no
yield improvement was achieved. Furthermore, several
variations of reaction parameters (Et2O instead of THF
as the solvent, reaction time; modification of the
cuprate, e.g. RCu(CN)Li, RCuLi, R(2-thienyl)CuLi·LiCN
(R¼1-methoxyallenyl)) were probed, but in no case the
yield could be improved.
The cases of 7a–c and 10 illustrate that this novel synthesis
of aminocyclopentadienes covers a range of useful enol-
ether building blocks. The reaction shown in Scheme 4
indicates that there is also flexibility in the choice of the
amino component, i.e. in the propyne iminium salt serving
as starting material. Propynylidene-morpholinium salt 11
reacted with cuprate 5b to give the expected morpholino-
allene 12 which, in contrast to its relative 6b, could be
isolated. The low yield of 12 is caused by extensive homo-
coupling of the cuprate to give 2,20-bis(5,6-dihydro-4H-
pyran).12 Efforts to suppress this side reaction, which was
not a problem for the combination of 5b with 4, by variation
of the reaction temperature were not successful so far.
Allene 12 did not undergo the thermal isomerization shown
for the vinylallene analogue 1 in Scheme 1, but could rather
Although further experimental investigations of this inter-
esting transformation are required, the currently available
results suggest that 4 reacts with alkoxyallenyl cuprates in
two addition steps, the addition of the second allene moiety
to a precursor of 10 being faster than the formation of the
latter. In line with the formation of cyclopentadienes 7a–c,
it may be assumed that the initially formed bis(allene)
undergoes a spontaneous 1,5-cyclization leading to the
dipolar intermediate 9. Due to the absence of a transferable
proton, the latter cannot tautomerize to give a neutral
cyclopentadiene, as in the cases of 7a–c. Rapid addition of
another organocopper species [a second molecule of
excess R2CuLi or, in the case of a 1:1 stoichiometry,
(allenyl)copper(I)] followed by ring-closure and OMe
migration would finally yield the tricylic compound 10.
be rearranged into
a
cyclopentadiene, like the
(alkoxyvinyl)allenes 6a–c. Transformation of 12 into
morpholino-substituted cyclopenta[b]pyran 13 required
heating in toluene at 1358C (pressure vial), but was also
achieved when 12 was kept in CHCl3 solution at rt. In the
latter case, the isomerization is obviously proton-catalyzed
and proceeds via an iminium ion resulting from protonation
of the enamine function.13
Unfortunately, our efforts to obtain further (alkoxyvinyl)-
allenes from iminium salt 11 and other enolether cuprates 5
have not been successful so far since only product mixtures
were obtained which could not be separated and identified.
However, work with other acyclic propyne iminium salts
reacting in the desired way is in progress.
The widely differing reaction temperatures for the thermal
isomerization of (alkoxyvinyl)allenes 6a–d and 12 deserve
some comments. Obviously, the indoline-derived allenes 6
are better suited for the cyclization reaction than the acyclic
morpholinoallene 12 (6b isomerizes at #208C, while 12
requires heating at 1358C), because the angle strain of the
indoline ring in 7 is smaller than in 6 due to rehybridization
In conclusion, a previously unknown thermal isomerization
of l-amino-3-(1-alkoxyvinyl)allenes has allowed us to
develop a novel synthesis of 5-amino-cyclopentadienes of

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R. Reinhard et al. / Tetrahedron 58 (2002) 10329–10334
various structural types. This methodology is complemen-
tary, in terms of substituents and substitution patterns, to the
recently reported cyclopentadiene synthesis by a formal
[3þ2] cycloaddition of b-(dialkylamino)alkenylidene
chromium complexes with terminal alkynes.14
THF (15 mL) cooled at 2608C. After the addition was
completed, the mixture was brought to 08C within 5 min and
after a homogeneous yellowish solution had formed (ca.
15 min), it was cooled to 2608C for further use.
3.2.4. (4,5-Dihydrofuran-2-yl)2CuLi·LiCN (5d). A sol-
ution of freshly distilled 4,5-dihydrofuran (0.47 mL,
6.0 mmol) in THF (5 mL) was cooled at 08C and a 1.6 M
solution of n-butyl lithium in hexane (3.75 mL, 6.0 mmol)
was added dropwise. After 30 min, this solution was added
to a suspension of copper(I) cyanide (0.269 g, 3.0 mmol) in
THF (15 mL) cooled at 2608C. After the addition was
completed, the mixture was brought to 2108C and kept at
this temperature for 15 min to form a homogeneous
solution. It was then cooled to 2608C for further use.
3. Experimental
3.1. General
NMR spectra: Bruker AC 200 (1H: 200.13 MHz, 13C:
50.32 MHz) and Bruker AM 400 (1H. 400.13 MHz, 13C:
100.61 MHz). Unless stated otherwise, the spectra were
recorded with the latter instrument. TMS was applied as the
internal standard. IR spectra: Perkin–Elmer IR-Spectro-
photometers 1310 and 883, wavenumbers (cm21) are given.
Elemental analyses: Perkin–Elmer EA 2240. Mass spectra:
Varian MAT 711. Flash column chromatography was
performed on silica gel Si60 (Macherey-Nagel, 0.063–
0.2 mm).
3.2.5. (1-Methoxy-1,2-propadienyl)2CuLi·LiBr (5e). THF
(5 mL) was cooled at 2308C and a 1.6 M solution of n-butyl
lithium in hexane (3.75 mL, 6.0 mmol) in hexane was
added. After dropwise addition of methoxypropa-1,2-diene
(0.51 mL, 6 mmol) and stirring for another 15 min at
2308C, the solution was added dropwise to a suspension
of copper(I) bromide dimethyl sulfide complex
(CuBr·SMe2) (0.62 g, 3.0 mmol) in THF (15 mL) kept at
2608C. The mixture was brought to 2408C and after
formation of a clear orange-colored solution cooled again at
2608C for further use.
All reactions were carried out in rigorously dried glassware
under an argon atmosphere. Solvents were dried according
to standard methods and stored under an argon atmosphere.
Compounds 49 and 1115 were prepared by published
procedures.
3.3. Aminoallenes 6 and their isomerization products
3.2. Preparation of cuprates 5a–e
3.3.1. 2,3-Dihydro-2-[2-(5,6-dihydro-1,4-dioxin-2-yl)-2-
phenylvinylidene]-1,3,3-trimethyl-1H-indole (6c). To a
solution of cuprate 5c (3 mmol) in THF, kept at 2608C, was
added dropwise a suspension of iminium salt 4 (1.23 g,
3.0 mmol) in THF (15 mL). The reaction mixture was then
stirred for 1 h at 2408C and was finally allowed to assume rt
within 2 h. The solvent was evaporated (0.01 mbar), and the
dark residue was extracted with pentane (3£70 mL).
Concentration of the combined pentane extracts gave a
yellow oil which could be crystallized when dissolved in
pentane and cooled at 2308C. Yield: 0.48 g (46%); light-
brown powder, mp 688C. IR (KBr): n 1920 (s, br,
All cuprates were prepared by variation of procedures
reported in the literature.
3.2.1. (1-Ethoxyvinyl)2CuLi·LiBr (5a). A solution of
freshly distilled ethyl vinyl ether (0.57 mL, 6.0 mmol) in
THF (5 mL) was cooled at 2308C, and a 1.7 M solution of
tert-butyl lithium in hexane (3.53 mL, 6.0 mmol) was
added. The yellow solution was brought to 08C and stirred
for 15 min whereupon the color faded, then slowly added to
a suspension of CuBr·Me2S (0.62 g, 3.0 mmol) in THF
(15 mL) that was kept at 2608C. The suspension was
warmed at 2308C to form a clear red solution which was
cooled again at 2608C for further use.
1
CvCvC), 1625 (s), 1590 (vs) cm21. H NMR (CDCl3,
200 MHz): d 1.34/1.43 (2s, CMe2), 2.96 (s, NMe), 4.10 (m,
4H, OCH2CH2O), 6.16 (s, 1H, OCHv), 6.49 (d, J¼7.7 Hz,
1H), 6.72 (t, J¼7.4 Hz, 1H), 7.05–7.47 (m, 7Harom). 13C
NMR (CDCl3): d 29.0/29.1 (CMe2), 30.3 (NMe), 44.7
(CMe2), 64.1/64.2 (OCH2CH2O), 105.0 (CH), 117.5
(NCvCvC), 117.7 (CH), 121.6 (CH), 127.2 (CH), 127.5
(CH), 127.6 (OCHv), 127.9 (2CH), 128.4 (2CH), 134.8,
137.0, 137.5, 146.5 (NCvCvC), 191.3 (NCvCvC).
Anal. calcd for C23H23NO2: C 79.97, H 6.71, N 4.06;
found C 80.0, H 6.9, N 4.1.
3.2.2. (5,6-Dihydro-4H-pyran-2-yl)2CuLi·LiCN (5b). A
solution of freshly distilled 5,6-dihydro-4H-pyran (0.56 mL,
6.0 mmol) in THF (5 mL) was cooled at 08C and a 1.7 M
solution of tert-butyl lithium in hexane (3.53 mL, 6.0 mmol)
was added dropwise. The yellow solution was stirred until
the color had disappeared (ca. 1 h), then it was gradually
added to a suspension of copper(I) cyanide (0.269 g,
3.0 mmol) in THF (15 mL) kept at 2608C. The suspension
was warmed to 2208C in order to form a homogeneous
solution. This solution was cooled to 2608C for further use.
3.3.2. 2,3-Dihydro-2-[2-(4,5-dihydrofuran-2-yl)-2-
phenylvinylidene]-1,3,3-trimethyl-1H-indole (6d). Pre-
pared from cuprate 5d (3 mmol) and iminium salt 4
(1.23 g, 3.0 mmol) as described for 6c. Yield: 0.67 g
(68%), colorless powder, mp 628C. IR (KBr): n 1920 (m,
3.2.3. (5,6-Dihydro-1,4-dioxin-2-yl)2CuLi·LiCN (5c). A
solution of freshly distilled 5,6-dihydro-1,4-dioxin
(0.48 mL, 6.0 mmol) in THF (5 mL) was cooled at 2408C
and a 1.7 M solution of tert-butyl lithium in hexane
(3.53 mL, 6.0 mmol) was added dropwise. The yellow
solution was brought to 08C and stirred for 10 min
whereupon the color faded. It was then added gradually to
a suspension of copper(I) cyanide (0.269 g, 3.0 mmol) in
br, CvCvC), 1700 (m), 1595 (vs) cm21 1H NMR
.
(400 MHz): d 1.34/1.44 (2s, CMe2), 2.68 (dt, J¼9.3,
9.4 Hz, 2H, OCH2CH2), 2.91 (s, NMe), 4.35 (mc, 2H,
OCH2), 4.95 (mc, 1H, OCHv), 6.43 (d, J¼7.7 Hz, 1H),

R. Reinhard et al. / Tetrahedron 58 (2002) 10329–10334
10333
6.67 (t, J¼7.4 Hz, 1H), 6.99–7.09 (m, 2H), 7.18 (mc, 1HPh),
7.24–7.28 (m, 2HPh), 7.49 (mc, 2HPh). 13C NMR: d 29.0
(CMe2), 30.3 (CH2), 30.7 (NMe), 44.6 (CMe2), 69.9 (CH2),
100.0 (CH), 105.0 (CH), 115.0 (NCvCvC), 117.7 (CH),
121.5 (CH), 127.1 (CH), 127.5 (CH), 127.8 (2CH), 128.0
(2CH), 135.0, 137.4, 137.7, 146.4 (NCvC), 194.3
(NCvCvC).
J¼7.6, 1.2 Hz, 1H), 7.29 (mc, 1H), 7.33–7.37 (m, 2H),
7.69–7.72 (m, 2H). 13C NMR (CDCl3): d 23.0/27.1 (CMe2),
30.5 (NMe), 46.4 (CMe2), 64.9/65.7 (OCH2CH2O), 82.5
(spiro-C), 107.1 (CH), 117.8 (CH), 120.3 (CH), 120.8 (CH),
126.7 (2CH), 127.5 (CH), 128.1 (CH), 128.4 (2CH), 133.3,
134.5, 137.7, 139.3, 140.7, 151.3. Anal. calcd for
C23H23NO2: C 79.97, H 6.71, N 4.06; found C 80.0, H
6.8, N 3.8.
3.3.3. (2-Ethoxy-3-phenylcyclopenta-1,4-diene)-5-spiro-
20-(20,30-dihydro-1,3,3-trimethyl-1H-indole) (7a). A sus-
pension of iminium salt 4 (1.23 g, 3.0 mmol) in THF
(15 mL) was gradually added at 2608C to the solution of
cuprate 5a (3 mmol). Then, the mixture was warmed at
2408C, stirred for 1 h, and allowed to assume rt during 2 h
The solvent was removed (0.01 mbar), and the residue was
extracted with pentane (3£70 mL). The combined extracts
were concentrated, the remaining oil was purified by flash
chromatography (silica gel), and the product was crystal-
lized from CH2Cl2–pentane at 2308C to give 7a as orange
crystals (0.74 g, 74%), mp 588C. IR (KBr): n 1620 (w), 1590
(s) cm21. 1H NMR (CDCl3): d 1.24/1.27 (2s, CMe2), 1.39 (t,
CH2Me), 2.58 (s, NMe), 3.96 (q, OCH2), 4.93 (d,
3.3.6. 2,3-Dihydro-2-[2-(2,5-dihydrofuran-2-ylidene)-2-
phenylethen-1-ylidene]-1,3,3-trimethyl-1H-indole (8). A
solution of allene 6d (0.66 g, 2.0 mmol) in toluene (3 mL)
was heated at 1008C for 2.5 h. The solvent was evaporated
(0.01 mbar), a few drops of ether were added to the residue,
and pentane was then added until crystallization started.
Yield: 0.54 g (82%); off-white powder, mp 978C. According
to NMR, the product is a 12:1 mixture of E/Z diastereomers
with respect to the NCvC bond. 1H NMR (CDCl3): d
(major/minor isomer) 1.44/1.10 (s, CMe2), 2.64/3.12
(NMe), 5.11/5.05 (mc, 2H, OCH2), 5.15/5.36 (s, br, 1H,
NCvCH), 6.24 (dt, J¼6.0, 2.3 Hz, 1H, 4-Hfuran), 6.38 (d,
J¼8.2 Hz, 1H), 6.56 (dt, J¼6.0, 2.3 Hz, 1H, 3-Hfuran), 6.78
(t, J¼7.4 Hz, 1H), 7.07–7.11 (m, 2H), 7.15–7.19 (m, 1H),
7.23–7.31 (m, 4H). 13C NMR (CDCl3): d (major isomer)
30.3 (CMe2), 33.6 (NMe), 45.8 (CMe2), 77.2 (OCH2), 89.6
(NCvCH), 106.1 (CH), 109.1 (OCvCPh), 118.8 (CH),
121.5 (CH), 124.9 (CH), 125.8 (CH), 127.4 (CH), 128.0
(2CH), 129.1 (2CH), 131.2 (CH), 138.1, 141.3, 148.0, 155.9
(NCvCH), 157.3 (OCvCPh). Anal. calcd for C23H23NO
(329.4): C 83.85, H 7.04, N 4.25; found C 82.8, H 7.1, N 4.1.
5
5J¼2.4 Hz, vCH), 6.34 (d, J¼2.4 Hz, vCH), 6.48 (d,
J¼7.7 Hz, 1H), 6.73 (dt, J¼6.7, 0.8 Hz, 1H), 6.99 (dd,
J¼7.1, 0.8 Hz, 1H), 7.12 (dt, J¼7.7, 1.3 Hz, 1H), 7.25–7.33
(m, 3H), 7.64–7.67 (m, 2H). 13C NMR (CDCl3): d 14.4
(OCH2Me), 23.8/26.0 (CMe2), 30.0 (NMe), 46.4 (CMe2),
65.4 (OCH2), 85.5 (spiro-C), 99.2 (vCHcyclopent), 107.4,
117.7, 121.1, 127.3 (2C), 127.6, 128.1 (2C), 131.6, 133.5,
135.3 (vCHcyclopent), 139.5, 141.5, 151.1, 159.7. Anal.
calcd for C23H25NO (331.5): C 83.34, H 7.60, N 4.23; found
C 82.3, H 7.4, N 4.2.
3.3.7. (1,4,5,6-Tetrahydro-5,5-dimethoxy-4-methylene-
pentalene)-1-spiro-20-(20,30-dihydro-10,30,30-trimethyl-
1H-indole) (10). Prepared from iminium salt 4 (1.23 g,
3.0 mmol) and cuprate 5e (3 mmol) as described for 7a.
Yield: 0.56 g (47%), yellow crystals, mp 968C. IR (KBr): n
3.3.4. (3,4-Dihydro-2H,5H-7-phenylcyclopenta[b]-
pyran)-5-spiro-20-(20,30-dihydro-10,30,30-trimethyl-1H-
indole) (7b). Prepared as described for 7a from iminium salt
4 and cuprate 5b; yield: 0.71 g (69%); colorless crystals, mp
1
1630 (m), 1580 (s) cm21. H NMR (CDCl3): d 1.20/1.31
1
1118C. IR (KBr): n 1650 (m, OCvC), 1595 (s) cm21. H
(2s, CMe2), 2.26/2.33 (AB system, J¼17.6 Hz, 2H), 2.51 (s,
NMe), 3.22/3.24 (2s, 6H, OMe), 5.12 (s, 2H, vCH2), 6.26
(s, 1H, vCHcyclopent.), 6.49 (d, J¼7.7 Hz, 1H), 6.73 (dt,
J¼7.4, 0.9 Hz, 1H), 6.99 (dd, J¼7.3, 0.7 Hz, 1H), 7.10 (dt,
NMR (CDCl3): d 1.21/1.30 (2s, CMe2), 1.61–1.77 (m, 4H,
4-/5-Hpyran), 2.49 (s, NMe), 4.00/4.16 (2mc, 2H, 6-Hpyran),
6.35 (s, 1H, 5-Hcyclopent), 6.44 (d, J¼7.7 Hz, 1H), 6.68 (dt,
J¼7.4, 0.9 Hz, 1H), 6.96 (dd, J¼7.1, 0.9 Hz, 1H), 7.08 (t,
J¼7.6, 1.3 Hz, 1H), 7.25 (d, J¼7.5, 1.3 Hz, 1H), 7.31 (mc,
2H), 7.70 (mc, 2H). 13C NMR (CDCl3): d 21.6/21.9
(OCH2CH2CH2), 22.2/27.2 (CMe2), 30.1 (NMe), 46.4
(CMe2), 67.4 (OCH2), 85.6 (spiro-C), 106.6 (CH), 113.6,
117.3 (CH), 120.8 (CH), 127.1 (2CH), 127.4 (CH), 127.7
(CH), 128.2 (2CH), 130.9 (CH), 133.4, 139.5, 142.2, 151.4,
153.3. Anal. calcd for C24H25NO (343.5): C 83.93, H 7.34,
N 4.08; found C 84.0, H 7.2, N 4.0.
J¼7.6, 1.2 Hz, 1H), 7.31–7.40 (m, 3H), 7.51 (mc, 2H). 13
C
NMR (CDCl3): d 22.8/26.8 (CMe2), 30.8 (NMe), 40.9
(CH2), 46.8 (CMe2), 49.4 (OMe), 49.5 (OMe), 86.8 (spiro-
C), 107.5 (CH), 107.5 (vCH2), 111.1 (C(OMe)2), 118.0
(CH), 121.1 (CH), 127.5 (2CH), 127.6 (CH), 127.8 (CH),
128.1 (2CH), 135.1, 135.4 (CH), 139.1, 142.5, 144.6, 144.7,
150.8, 156.6.
3.3.8. 4-[1,3-Diphenyl-3-(5,6-dihydro-4H-pyran-2-
yl)propadienyl]morpholine (12). To a solution of cuprate
5b (3 mmol, see above) in THF, cooled at 2408C, was
added the solution of iminium salt 11 (1.27 g, 3.0 mmol) in
dichloromethane (15 mL). After the mixture had kept with
stirring at this temperature for 3 h, it was brought to rt and
the solvent was evaporated (0.01 mbar). The brown residue
was extracted with petroleum ether 40–708C (2£70 mL)
and ether (1£5 mL). The combined organic extracts were
concentrated (0.02 mbar) to leave a yellow oil which was
redissolved in a small volume of petroleum ether. Low-
temperature crystallization gave 12 as a yellow powder
which still contained a small amount of 2,20-bis(5,6-
dihydro-4H-pyran). Yield: 0.25 g (ca. 24%). 1H NMR
3.3.5. (2,3-Dihydro-7-phenyl-5H-cyclopenta-1,4-dioxin)-
5-spiro-20-(20,30-dihydro-10,30,30-trimethyl-1H-indole)
(7c). A solution of allene 6c (0.69 g, 2.0 mmol) in toluene
(3 mL) was heated at 808C for 12 h (color change to dark-
green). The solvent was evaporated (0.01 mbar), the residue
was dissolved in dichloromethane, and pentane was added.
At 2308C, orange-colored crystals of 7c were obtained.
Yield: 0.62 g, 90%; mp 1348C. IR (KBr): n 1660 (s,
OCvC), 1590 (s) cm21. 1H NMR (CDCl3): d 1.32/1.33 (2s,
CMe2), 2.60 (s, NMe), 4.06/4.17 (2mc, 4H, OCH2CH2O),
5.92 (s, 1H, CHcyclopent), 6.50 (d, J¼7.7 Hz, 1H), 6.72 (dt,
J¼7.4, 0.9 Hz, 1H), 6.98 (dd, J¼7.2, 1.1 Hz, 1H), 7.10 (dt,

10334
R. Reinhard et al. / Tetrahedron 58 (2002) 10329–10334
(200.13 MHz, CD3CN): d 1.76–1.96 (m, 2H, 5-Hpyran),
2.06–2.16 (m, 2H, 4-Hpyran), 2.80 (mc, 4H, NCH2), 3.79
(pseudo-t, 4H, OCH2-morph.), 4.05 (pseudo-t, 2H, OCH2-
pyran), 4.84 (t, J¼3.8 Hz, 1H, 3-Hpyran), 7.20–7.53 (m,
collected reflections, 6240 independent reflections
(R(int)¼0.037), 3345 observed reflections (I.2s(I)]. Struc-
ture refinement with 6235 data and 551 parameters gave the
following final R indices: R1¼0.0731, wR2¼0.1281
(I.2s(I)); R1¼0.1518, wR2¼0.1784 (all data); residual
10Harom). 13C NMR (50.32 MHz, CD3CN):
d 20.9
23
˚
(5-Cpyran), 22.4 (4-Cpyran), 51.3 (NCH2), 66.4 (6-Cpyran),
67.0 (OCH2-morph.), 96.7 (3-Cpyran), 114.9 (NCvCvC),
116.7, 127.1, 127.3, 127.7, 128.1, 128.2, 128.3, 129.3,
134.7, 136.5, 148.0. 150.0, 200.7 (NCvCvC).
electron between 0.20 and 20.21 e. A
.
Acknowledgements
3.3.9. 3,4-Dihydro-2H,5H-5,7-diphenyl-5-morpholino-
cyclopenta[b]pyran (13). A solution of 12 (0.27 g,
0.75 mmol) in chloroform (5 mL) was stirred for 2 h. The
solvent was evaporated, and the residue was purified by
flash chromatography (silica gel) to give the product as a
yellow powder. Yield: 0.25 g (92%). 1H NMR
(200.13 MHz, CDCl3): d 1.8–2.0 and 2.05–2.20 (2 m,
4H, OCH2CH2CH2), 2.65 (mc, 4H, NCH2), 3.70 (pseudo-t,
4H, OCH2-morph), 3.95–4.10 (m, 2H, 2-H2), 6.75 (s, 1H,
6-H), 7.20–7.80 (m, 10Harom). 13C NMR (50.32 MHz,
CDCl3): d 19.3 (CH2), 22.3 (CH2), 48.4 (NCH2), 67.4
(OCH2-pyran), 67.8 (C-5), 67.9 (OCH2-morph.), 117.0
(C-4a), 127.2, 127.5, 127.8, 128.1, 128.3, 128.5, 129.2,
129.4, 132.7, 133.4, 141.4, 142.1, 151.7. MS (FD, 8 keV):
m/z 359 (100%) [Mþ].
Financial support of this work by the Deutsche Forschungs-
gemeinschaft and the Fonds der Chemischen Industrie is
gratefully acknowledged.
References
1. (a) Okamura, W. H.; Curtin, M. L. Synlett 1990, 1–9.
(b) Okamura, W. H. Acc. Chem. Res. 1983, 16, 81–89.
2. (a) Wu, K-M.; Midland, M. M.; Okamura, W. H. J. Org.
Chem. 1990, 55, 4381–4392. (b) Shen, G.-Y.; Tapia, R.;
Okamura, W. H. J. Am. Chem. Soc. 1987, 109, 7499–7506.
3. (a) Lopez, S.; Rodriguez, J.; Rey, J. G.; de Lera, A. R. J. Am.
Chem. Soc. 1996, 118, 1881–1891. (b) Murakami, M.; Amii,
H.; Itami, K.; Ito, Y. Angew. Chem. 1995, 107, 1649–1650.
4. Koop, U.; Handke, G.; Krause, N. Liebigs Ann. Chem. 1996,
1487–1500.
3.4. X-Ray diffraction analysis of compounds 7b and 10
Data collection on single crystals of 7b and 10 was
performed with a diffractometer CAD4 (Enraf-Nonius),
operating in the omega-2theta scan mode, with mono-
5. Mayer, T.; Maas, G. Tetrahedron Lett. 1992, 33, 205–208.
6. Reinhard, R.; Glaser, M.; Neumann, R.; Maas, G. J. Org.
Chem. 1997, 62, 7744–7751.
˚
chromatized Mo Ka radiation (l¼0.71073 A). The
structures were solved with direct methods and refined
with full-matrix least-squares procedures using F 2 values.
Relevant crystal data and details of the structure determi-
nation are given below. Crystallographic data have been
deposited as CCDC-186967 (for 7b) and 186968 (for 10).
These data can be obtained free of charge via www.ccdc.
cam.ac.uk/conts/retrieving.html (or from the Cambridge
crystallographic data centre, 12, Union road, Cambridge
CB2 1EZ, UK; fax: þ44-1223-336-033).
7. Schlegel, J.; Maas, G. J. Prakt. Chem. 2000, 342, 235–239.
8. In contrast to other organocuprates, (1-alkoxyvinyl)cuprates
have been applied surprisingly little for C–C bond forming
reactions; see, e.g. Friesen, R. W. J. Chem. Soc., Perkin Trans.
1 2001, 1969–2001, review.
9. Reinhard, R.; Maas, G.; Bohrisch, J.; Liebscher, J. Liebigs
Ann. Chem. 1994, 429–432.
10. We found that in the case of cyclic enolethers, cuprates
R2CuLi·LiCN (Gilman–Lipshutz type) gave cleaner reactions
and better yields than cuprates R2CuLi (Gilman type), while
the opposite was true for cuprates derived from ethyl vinyl
ether and methoxyallene, respectively.
3.4.1. Compound 7b. C24H25NO, Mr¼343.5; triclinic,
space group P1 (no. 2), a¼9.926(2), b¼12.028(3), c¼
˚
8.660(3) A, a¼106.31(2), b¼104.99(2), g¼74.77(2)8 V¼
11. Recent reviews on cuprate chemistry (a) Krause, N. Angew.
Chem. 1997, 109, 194–213. (b) Krause, N. Angew. Chem. Int.,
Ed. Engl. 1997, 36, 186–204. (c) Lipshutz, B. H. In
Organometallics in Synthesis. Schlosser, M., Ed.; Wiley:
Chichester, 1994; pp 283–382. (d) In Modern Organocopper
Chemistry. Krause, N., Ed.; Wiley/VCH: Weinheim, 2002.
12. (5,6-Dihydro-4H-pyran-2-yl) lithium undergoes homo-
coupling in high yield under the action of copper(II) chloride:
Ley, S. V.; Leslie, R.; Tiffin, P. D.; Woods, M. Tetrahedron
Lett. 1992, 33, 4767–4770.
3
938.2(8) A , Z¼2; Dcalc¼1.216 mg m23, m¼0.07 mm21
.
˚
Data collection: Crystal size 0.30£0.30£0.75 mm,
T¼293(2) K; theta range for data collection 2.00–24.008;
29#h#9, 210#k#11, 0#l#13; 3088 collected reflec-
tions, 2774 independent reflections (R(int)¼0.053), 1977
observed reflections (I.2s(I)]. Final R indices of the
structure refinement (1977 data with I.2s(I), 310 para-
meters): R1¼0.0576, wR2¼0.0515, residual electron
23
˚
density between 0.17 and 20.09 e. A
.
13. See Ref. 4 for a transformation that appears to include a Lewis
acid mediated vinylallene-to-cyclopentadiene isomerization.
14. (a) Flynn, B. L.; Schirmer, H.; Duetsch, M.; de Meijere, A.
J. Org. Chem. 2001, 66, 1747–1754. (b) Schirmer, H.; Funke,
F. J.; Mu¨ller, S.; Noltemeyer, M.; Flynn, B. L.; de Meijere, A.
Eur. J. Org. Chem. 1999, 2025–2031. (c) Flynn, B. L.; de
Meijere, A. J. Org. Chem. 1999, 64, 400–404.
3.4.2. Compound 10. C27H29NO2, Mr¼399.5; triclinic,
space group P1 (no. 2), a¼8.7098(6), b¼16.354(8), c¼
˚
18.392(12) A, a¼64.69(6), b¼89.48(4), g¼74.91(5)8
3
˚
V¼2270(2) A ,
Z¼4;
Dcalc¼1.169 mg m23
,
m¼
0.073 mm21. Data collection: Crystal size 0.65£0.50£
0.30 mm, T¼293(2) K; theta range for data collection
2.24–22.918; 0#h#9, 216#k#17, 219#l#20; 6472
15. Maas, G.; Rahm, R. Synthesis 1994, 295–299.