Allene-Based Gold-Catalyzed Stereodivergent Synthesis of Azapolycyclic Derivatives of Unusual Structure

Article abstract of DOI:10.1002/adsc.201501145

The present study provides insights into the manner in which the configuration of β-aminoallene precursors affects their gold-catalyzed cyclization reactions. The reactivity can be switched by using indolizidinone-tethered β-aminoallenes bearing the syn- or the anti-disposition of both protons at the α- and β-allenic stereocenters. Fused heterocycles (seven examples, 60-75% yields) are obtained from the syn-precursors, while a dimerization-aminoketalization-spirocyclization sequence to afford benzo[b]pyrrolo[3,2,1-ij][1,7]naphthyridin-1-ones (four examples, 34-48% yields) can be achieved starting from their anti-isomers.

Full text of DOI:10.1002/adsc.201501145

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DOI: 10.1002/adsc.201501145
Allene-Based Gold-Catalyzed Stereodivergent Synthesis of
Azapolycyclic Derivatives of Unusual Structure
Benito Alcaide,a,* Pedro Almendros,b,* Raffll Martín-Montero,a and M. Pilar Ruiza
a
Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgµnica I, Unidad Asociada al CSIC, Facultad
de Química, Universidad Complutense de Madrid, 28040 Madrid, Spain
Fax: (+34)-91-394-4103; e-mail: alcaideb@quim.ucm.es
Instituto de Química Orgµnica General, Consejo Superior de Investigaciones Científicas, IQOG-CSIC, Juan de la Cierva
b
3, 28006 Madrid, Spain
Fax: (+34)-91-564-4853; e-mail: Palmendros@iqog.csic.es
Received: December 15, 2015; Revised: March 8, 2016; Published online: April 27, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201501145.
Abstract: The present study provides insights into the syn-precursors, while a dimerization–aminoketal-
the manner in which the configuration of b-aminoal- ization–spirocyclization sequence to afford benzo[b]-
lene precursors affects their gold-catalyzed cycliza- pyrrolo[3,2,1-ij][1,7]naphthyridin-1-ones (four exam-
tion reactions. The reactivity can be switched by ples, 34–48% yields) can be achieved starting from
using indolizidinone-tethered b-aminoallenes bearing their anti-isomers.
the syn- or the anti-disposition of both protons at the
a- and b-allenic stereocenters. Fused heterocycles Keywords: allenes; gold; heterocyclic compounds;
(seven examples, 60–75% yields) are obtained from selectivity; synthetic methods
Introduction
ed to explore the stereodivergent preparation of poly-
azaheterocycles (Scheme 1).
Gold complexes continue to attract considerable in-
terest within organic synthesis due to their soft Lewis
acidic nature, which allows for selective activation of Results and Discussion
p-systems.[1]
Demands for the efficient generation of diverse Starting materials, new indolizidinone-tethered ami-
drug-like small molecules continue to stimulate the noallenes 3, were obtained from cis-b-lactams 1 after
development of versatile synthetic strategies. The bio- several steps. (2S,3R)-4-Oxoazetidine-2-carbaldehydes
logical properties of a typical organic compound di- 1a–d were prepared in enantiopure form as single
rectly depend on its molecular scaffold.[2] Specifically, trans-diastereoisomers from cis-4-oxoazetidine-2-car-
heterocyclic scaffolds with higher average saturation baldehydes through base-promoted chemoselective C-
factor (higher proportion of sp3 carbons) are more 2 epimerization (Scheme 2).[6] b-Lactam-tethered ami-
likely to progress through the stages of drug develop- noallenes 2 were obtained as mixtures of chromato-
ment than sp2-heterocycles.[3] Besides, the configura- graphically separable syn/anti isomers, taking advant-
tion of an organic molecule is a key feature account- age of the diphenyl hydrogen phosphate-catalyzed
ing for its biological activity.[4] Consequently, a judi- iminoallenylation reaction of trans-carbaldehydes
cious entry to all stereoisomers of a molecule is
1
with
2-[4-(trimethylsilyl)but-2-ynyl]aniline
highly desirable for stereochemistry–activity studies. (Scheme 2). b-Lactam-tethered aminoallenes syn-2a–
Although only as the minor isomer, we have recently d and anti-2a–d were converted into pyrroloquinoli-
described the synthesis of a new spiranic azapolycyclic none-tethered b-aminoallenes syn-3a–d and anti-3a–d
scaffold bearing several sterocenters through the con- by treatment with sodium methoxide in methanol
trollable gold-catalyzed cyclization reaction of indoli- (Scheme 3),[7] through a chemoselective rearrange-
zidinone-tethered b-aminoallenes.[5] Taking into ac- ment reaction. Partial epimerization was observed for
count that efficient synthetic protocols for different minor isomers syn-2b–d. Fortunately, flash chroma-
stereoisomers of a new class of molecular scaffold tography allowed the smooth separation of com-
open the door for further biological studies, we decid-
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Scheme 1. Stereodivergent reactivity of 4-oxoazetidine-2-carbaldehydes.
Scheme 2. Preparation of b-lactam-tethered aminoallenes syn-2a–d and anti-2a–d. Reagents and conditions: i) 200 mol%
Na2CO3, acetonitrile/water (1:1), room temperature, 14 h; ii) 2 mol% (PhO)2P(O)OH, acetonitrile, room temperature, 16–
24 h. PMP=4-MeOC6H4.
pounds syn-3b–d from the epimeric syn-epi-3b–d sub- found influence on the reactivity, several metallic
strates.
complexes were evaluated (Table 1). Our investiga-
Taking into account the sole report available in the tion began with b-aminoallene syn-3a as substrate.
literature on different reaction outcomes of gold-cata- The reaction of syn-3a in the presence of palladium-
lyzed stereoisomers,[5] applying gold catalysis to dia- or platinum-based salts gave rise to poor conversion.
stereomeric indolizidinone-tethered b-aminoallenes Happily, improvements were observed using gold-
syn-3a–d, syn-epi-3b–d, and anti-3a–d represents an based catalytic systems. Under the optimized condi-
attractive challenge in terms of stereochemically con- tions, treatment of b-aminoallene syn-3a with 5 mol%
trolled reactivity. Since the catalyst may have a pro- [IPrAuCl]
[IPr=1,3-bis(2,6-diisopropylphen-
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Allene-Based Gold-Catalyzed Stereodivergant Synthesis
Scheme 3. Preparation of indolizidinone-tethered b-aminoallenes syn-3a–d, syn-epi-3b–d, and anti-3a–d. Reagents and condi-
tions: i) NaOMe, MeOH, room temperature, 14–40 h. PMP=4-MeOC6H4.
Table 1. Selective hydroamination reaction of b-aminoallene
syn-3a under modified metal-catalyzed conditions
With these optimized protocols in hand, we con-
ducted the syntheses of derivatives 4b–d using starting
materials syn-3b–d (Scheme 4). With reaction times
ranging from 12 to 48 h, benzo[b]pyrrolonaphthyri-
din-1-ones could be afforded in reasonable yields (66–
74%). To access more sterochemically diverse com-
pounds, b-aminoallenes syn-epi-3b–d were converted
into their corresponding benzo[b]pyrrolonaphthyri-
din-1-ones epi-4 under the above gold-conditions
Entry Catalyst
Additive t [h]
Yield [%][a] (Scheme 4). Under these circumstances, specific six-
membered ring formation seems to be the exclusive
tendency; with no influence of the opposite configura-
1
2
3
4
5
6
7
8
PtCl2
PdCl2
AuCl3
AuCl
[AuClPPh3]
[AuClPPh3]
[(Ph3P)AuNTf2]
[AuClIPr]
[AuClIPr]
[AuClIPr]
[AuClIPr][b]
[AuClIPr][c]
–
–
–
–
48
14
28
18
16
16
10
14
14
14
16
2
18
21
36
34
42
75
70
72
60
74
AgSbF6
AgOTf
–
AgSbF6
AgOTf
AgBF4
9
10
11
12
[b]
AgSbF6[c] 48
AgSbF6 14
[a]
Yield of pure, isolated product with correct analytical
and spectral data.
1 mol% was used.
[b]
[c]
10 mol% were used.
yl)imidazol-2-ylidene] in the presence of AgSbF6
(5 mol%) gave benzo[b]pyrrolonaphthyridin-1-one 4a
in 75% yield (Table 1, entry 8). A screening of sol-
vents (dichloromethane, tetrahydrofuran, 1,4-dioxane,
toluene) revealed that the reaction is best performed
in DCE (1,2-dichloroethane).
Scheme 4. Synthesis of benzo[b]pyrrolonaphthyridin-1-ones
4 and epi-4 through gold-catalyzed intramolecular hydroami-
nation reaction of b-aminoallenes syn-3 and syn-epi-3.
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tion of the center a to the amino group and g to the
allene moiety in compounds syn-3 and syn-epi-3.
Interestingly, these results indicate that the regiose-
lectivity in the reaction was affected by the relative
It became necessary to examine whether anti-3 iso- configuration of the precursors. It may be inferred
mers would also serve as precursors for 6-endo-dig that targeting the synthesis of dimeric spiro amino
aminocyclizations. At this point, it was interesting to ketals 5, the anti-disposition of both protons at the a-
observe that b-aminoallene anti-3a reacted under the and b-allenic stereocenters is required. Our divergent
above gold-catalyzed conditions without formation of approach hinges on the spatial disposition of both the
benzo[b]pyrrolonaphthyridin-1-one products. Note- stereocenter a to the allene functionality and the b-
worthy, this simple protocol allows unusual tunable amino group. The structure of dimeric compounds 5
selectivity. Indeed, when b-aminoallene anti-3a was was identified by comparison with spectroscopic data
treated with the catalytic system [AuClIPr]/AgSbF6 in from their isomers, previously reported by us.[5] On
DCE at room temperature, spiro[benzo[e]furo- the basis of coupling constant information between
1
[2’,3’:4,5]pyrrolo[4,3,2-hi]indolizine-2,4’-benzo[e]pyr-
the protons in the H NMR spectra of ketones 6, the
rolo[4,3,2-hi]indolizine]-1’,6(2’H,4a1H)-dione 5a was stereochemical assignment was found to be unambig-
isolated in 48% yield, along with the uncyclizated uous (see Figure S1 in the Supporting Information).
ketone 6a (22% yield). The use of AgSbF6 was tested,
The pathway depicted in Scheme 6 is proposed for
but it failed to catalyze the reaction in the absence of the formation of fused tetracyclic products 4 and epi-
the gold salt [AuClIPr], which proved that the silver 4. Complexes syn-3-Au(L) and syn-epi-3-Au(L) were
activator itself is unreactive. Next, we decided to initially formed through coordination of the Au(I)
study how the use of preformed carbene-Au(Sb6) cat- salt to the distal allenic double bond. Next, regioselec-
alyst affected the reactivity. In the event, no apprecia- tive 6-endo aminoauration forms intermediate ammo-
ble differences between formed in situ and preformed nium cation type 7. Loss of proton affords neutral
complexes were found. After these control experi- species 8, which followed by protonolysis of the
ments it was demonstrated that the silver salt alone carbon-gold bond generated diazatetracycles 4 and
does not catalyze the dimerization reaction. The opti- epi-4 with concurrent regeneration of the gold catalyst
mal amount of catalyst was established at 5 mol% (Scheme 6).
with a ratio Au(I) salt/Ag(I) salt of 1:1. Other coun-
It is worth noting that the reaction of b-aminoal-
ter-ions provided the same reactivity but have some lenes anti-3 affords adducts 5 from an allenic amino-
effect,[8] because changing the silver salt delivered the cyclization–dimerization sequence instead of that
dimeric product 5a but in lower yields (AgOTf: 30% from the usually preferred conventional cycloisomeri-
yield, AgBF4: 40% yield, and AgNTf2: 36% yield). zation. In order to see if ketones 6 are able to rear-
On the basis of the chemical structures of compounds range to dimeric adducts 5, reaction of 6a was con-
5a and 6a, it may be presumed that moisture was in- ducted under gold catalysis. The reaction did not pro-
volved in this gold-catalyzed sequence. The scope of ceed. In the event, unaltered 6a was recovered, and
the spirodimerization reaction of various indolizidi- adduct 5a was not formed. Taking into account the
none-tethered b-aminoallenes anti-3 was investigated above experiment, the possible pathway may not in-
and the results are shown in Scheme 5. The reaction volve a ketone intermediate. This experimental result,
occurred to give a mixture of dimeric spiro amino combined with our previous observations for isomeric
ketals 5 and ketones 6 with the dimeric product 5 adducts,[5] led us to propose the following mechanism
being the major one,[9,10] with the exception of b-ami- for the formation of the dimeric products (Scheme 7).
noallene anti-3c which was free of ketone formation. Initially, [IPrAuSbF6] coordinates to the distal allenic
Scheme 5. Synthesis of dimeric spiro amino ketals 5 and ketones 6 through gold-catalyzed reactions of b-aminoallenes anti-3.
Reagents and conditions: i) 5 mol% IPrAuCl, 5 mol% AgSbF6, DCE, room temperature, 14–46 h.
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Allene-Based Gold-Catalyzed Stereodivergant Synthesis
fusion of the hypothetical intermediate of type 9 {(1-
oxohexahydrobenzo[e]pyrrolo[4,3,2-hi]indolizin-3-
ium-4-yl)methyl}gold. The loss of proton in ammoni-
um 9 furnishes neutral species 10. Protonolysis of the
carbon-gold bond of adducts 10 yields tetracyclic in-
termediates 11 and releases the metal catalyst into
the first catalytic cycle (Scheme 7, right catalytic
cycle). Species 11 may evolve to O,N-acetal 12 via
gold-catalyzed nucleophilic addition of water.[11] Sub-
sequent oxidative coupling between endocyclic enam-
ine 11 and O,N-acetal 12 with the concerted elimina-
tion of H2, would generate spirocycles 5, therefore
closing the sequence. Although merely speculative at
this time, the oxidative addition of 12 to 11 under re-
lease of hydrogen should proceed with the help of
molecular oxygen from air.
Conclusions
Scheme 6. Mechanistic explanation for the gold-catalyzed
aminocyclization reaction of indolizidinone-tethered b-ami-
noallenes syn-3 and syn-epi-3 into benzo[b]pyrrolo[3,2,1-ij]
[1,7]naphthyridin-1-ones 4 and epi-4.
In conclusion, the present study provides insights into
the manner in which the configuration of b-aminoal-
lene precursors affects their gold-catalyzed cyclization
reactions. The reactivity can be switched by using in-
double bond of allenes anti-3 to produce anti-3- dolizidinone-tethered b-aminoallenes bearing the syn-
Au(L). The regioselective 5-exo aminocyclization re- or anti-disposition of both protons at the a- and b-al-
action of the thus generated gold complex gives inter- lenic stereocenters. Fused heterocycles are obtained
mediates 9. As experimental results reveals, dimeriza- from the syn-precursors, while a dimerization–amino-
tion via 5-exo aminocyclization falters in indolizidi- ketalization–spirocyclization sequence can be ach-
none-tethered b-aminoallenes syn-3. Probably, the 5- ieved starting from their anti-isomers.
exo aminoauration in syn-3 is restricted by the trans
Scheme 7. Rationalization for the gold-catalyzed heterocyclization-spirodimerization reaction of indolizidinone-tethered b-
aminoallenes anti-3.
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6.99–6.91 (m, 2H, ArH), 6.85 (AA’XX’, 2H, ArH), 5.64 (br
s, 1H, =CH), 4.81 (br s, 1H, H-5), 4.71 (d, J=12.2 Hz, 1H,
OCHH), 4.58 (d, J=12.2 Hz, 1H, OCHH), 4.20 (d, J=
4.1 Hz, H-3), 4.03 (dd, J=16.9, 2.6 Hz, 1H, NCHH), 3.83 (s,
3H, OCH3), 3.83–3.73 (m, 1H, CHH), 3.60–3.48 (m, 2H,
NCHH, CHH), 3.22 (dd, J=8.3, 4.1 Hz, 1H, H-4); 13C NMR
(75 MHz, CDCl3, 258C): d=169.8 (C=O), 156.5 (Ar), 145.6
(Ar), 137.0 (Ar), 135.1 (Ar), 129.2 (Ar), 128.1 (2Ar), 128.0
(2Ar), 127.5 (Ar), 127.1 (Ar), 124.5 (Ar), 123.7 (2Ar), 123.6
(Ar), 119.6 (=CH), 118.5 (2Ar), 114.5 (2Ar), 77.42 (C-3),
71.5 (OCH2), 63.8 (C-4), 57.8 (NCH2), 56.1 (C-5), 55.4
(OCH3), 30.4 (CH2); IR (CHCl3): n=1698 cmÀ1; HR-MS
(ES): m/z=439.2024, calcd. for C28H27N2O3 [M+H]+:
439.2016.
Experimental Section
General Methods
1H NMR and 13C NMR spectra were recorded on a Bruker
DPX-300, Bruker DPX-300 BACS-60 or Bruker AV 500
spectrometers in CDCl3, except otherwise stated. Chemical
shifts are given in ppm relative to TMS (1H, 0.0 ppm) or
CDCl3 (13C, 77.0 ppm). Low and high resolution mass spec-
tra were performed on an AGILENT 6520 Accurate-Mass
QTOF LC/MS spectrometer using the electrospray modes
(ES) unless otherwise stated. Specific rotation [a]D is given
in 10À1 degcm2 gÀ1 at 208C, and the concentration (c) is ex-
pressed in grams per 100 mL. All commercially available
compounds were used without further purification. Flash
chromatography was performed by using silica gel 60 (230–
400 mesh) or neutral alumina. Products were identified by
TLC (Kieselgel 60F-254). UV light (l=254 nm) and a solu-
tion of phosphomolybdic acid in EtOH (1 g of phosphomo-
lybdic acid hydrate, 100 mL EtOH) was used to develop the
plates.
Tetracycle (+)-4c: From 41 mg (0.10 mmol) of b-aminoal-
lene (+)-syn-3c, and after chromatography of the residue
using n-hexane/ethyl acetate (8:2) as eluent gave compound
(+)-4c as a pale green oil; yield: 27 mg (66%); [a]D: +193.1
1
(c 0.5, CHCl3). H NMR (300 MHz, C6D6, 258C): d=9.15 (d,
1H, J=8.2 Hz, ArH), 7.30 (m, 2H, ArH), 7.13–7.07 (m, 1H,
ArH), 7.06–7.00 (m, 2H, ArH), 6.96 (AA’XX’, 2H, ArH),
6.92–6.82 (m, 2H, ArH), 6.75 (t, J=7.3 Hz, 1H, ArH), 6.68
(AA’XX’, 2H, ArH), 5.07 (br s, 1H, =CH), 4.83–4.73 (m,
1H, H-5), 4.80 (d, J=4.1 Hz, 1H, H-3), 3.70–3.62 (m, 1H,
NCHH), 3.32–3.16 (m, 2H, NCHH, CHH), 3.22 (s, 3H,
OCH3), 3.02 (d, J=19.8 Hz, 1H, CHH), 2.70 (dd, J=8.2,
4.1 Hz, 1H, H-4); 13C NMR (75 MHz, C6D6, 258C): d=169.0
(C=O), 159.1 (Ar), 157.2 (Ar), 143.2 (Ar), 135.9 (Ar), 129.6
(2Ar), 129.2 (Ar), 129.0 (Ar), 128.6 (Ar), 127.5 (Ar), 124.8
(2Ar), 123.8 (Ar), 123.7 (Ar), 122.4 (Ar), 119.8 (=CH),
119.2 (Ar), 117.5 (2Ar), 114.7 (2Ar), 79.5 (C-3), 64.6 (C-4),
57.2 (NCH2), 55.7 (C-5), 54.9 (OCH3), 30.8 (CH2); IR
(CHCl3): n=1704 cmÀ1; HR-MS (ES): m/z=425.1867, calcd.
for C27H25N2O3 [M+H]+: 425.1860.
General Procedure for the Gold-Catalyzed Reaction
of Indolizidinone-Tethered b-Aminoallenes syn-3a–d
and syn-epi-3b–d
Preparation of benzo[b]pyrrolonaphthyridin-1-ones 4a–d
and epi-4b–d: AgSbF6 (0.01 mmol, 5 mol%) was added to
a well stirred solution of IPrAuCl (0.01 mmol, 5 mol%) in
1,2-dichloroethane (3 mL), at room temperature, in the
dark. The resulting mixture was stirred for 5 min and, then,
the appropriate b-aminoallene syn-3 or syn-epi-3
(0.20 mmol) was added. The mixture was stirred at the same
temperature until the total disappearances of starting mate-
rial (TLC). The solvent was removed under reduced pres-
sure and the residue was purified by flash silica gel column
chromatography eluting with n-hexane/ethyl acetate mix-
tures to give analytically pure tetracyclic compounds 4.[12]
Tetracycle (+)-4a: From 40 mg (0.11 mmol) of b-aminoal-
lene (À)-syn-3a, and after chromatography of the residue
using n-hexane/ethyl acetate (7:3) as eluent gave compound
(+)-4a as a pale green oil; yield: 30 mg (75%); [a]D: +30.3
Tetracycle (+)-4d: From 80 mg (0.17 mmol) of b-aminoal-
lene (À)-syn-3d, and after chromatography of the residue
using n-hexane/ethyl acetate (8:2) as eluent gave compound
(+)-4d as a pale yellow oil; yield: 59 mg (74%); [a]D:
1
+183.0 (c 0.4, CHCl3). H NMR (300 MHz, CDCl3, 258C):
d=8.60 (d, 1H, J=8.3 Hz, ArH), 7.22 (t, J=6.9 Hz, 2H,
ArH) 7.14–7.08 (m, 5H, ArH), 6.92 (AA’XX’, 2H, ArH),
6.81 (AA’XX’, 2H, ArH), 5.72 (t, J=2.5 Hz, 1H, =CH),
4.94–4.86 (m, 1H, H-5), 4.75 (d, J=4.1 Hz, 1H, H3), 4.00
(dd, J=17.3, 2.1 Hz, 1H, NCHH), 3.84 (d, J=20.1 Hz, 1H,
CHH), 3.76 (s, 3H, OCH3), 3.72–3.54 (m, 2H, NCHH
CHH), 3.35 (dd, J=8.2, 4.1 Hz, 1H, H-4); 13C NMR
(75 MHz, CDCl3, 258C): d=168.4 (C=O), 156.8 (Ar), 156.6
(Ar), 142.3 (Ar), 134.8 (Ar), 129.2 (Ar), 129.1 (2Ar), 128.7
(Ar), 127.2 (Ar), 127.0 (Ar), 124.4 (2Ar), 124.1 (Ar), 123.7
(Ar), 120.0 (=CH), 118.7 (Ar), 118.3 (2Ar), 114.7 (2Ar),
79.2 (C-3), 64.5 (C-4), 57.4 (NCH2), 55.7 (C-5), 55.4 (OCH3),
30.5 (CH2); IR (CHCl3): n=1702 cmÀ1; HR-MS (ES): m/z=
459.1459, calcd. for C27H24ClN2O3 [M+H]+: 459.1470.
Tetracycle (+)-epi-4b: From 25 mg (0.05 mmol) of b-ami-
noallene (À)-syn-epi-3b, and after chromatography of the
residue using n-hexane/ethyl acetate (7:3) as eluent gave
compound (+)-epi-4b as a pale yellow oil; yield: 15 mg
(60%); [a]D: +96.7 (c 0.1, CHCl3). 1H NMR (300 MHz,
CDCl3, 258C): d=8.57 (dd, J=8.3, 1.0 Hz, 1H, ArH), 7.30–
7.10 (m, 7H, ArH), 7.04–6.98 (m, 3H, ArH), 6.76 (AA’XX’,
1
(c 0.3, CHCl3). H NMR (300 MHz, CDCl3, 258C): d=8.62
(d, 1H, J=8.3 Hz, ArH), 7.30–7.15 (m, 4H, ArH), 7.06 (td,
J=8.5, 1.1 Hz, 1H, ArH), 6.90 (AA’XX’, 2H, ArH), 5.64
(m, 1H, =CH), 4.81–4.66 (m, 1H, H-5), 4.11–4.01 (m, 1H,
NCHH), 4.02 (d, J=3.9 Hz, 1H, H-3), 3.85–3.69 (m, 1H,
CHH), 3.81 (s, 3H, OCH3), 3.67–3.47 (m, 2H, NCHH,
CHH), 3.39 (s, 3H, OCH3), 3.21 (dd, J=8.3, 3.9 Hz, 1H, H-
4); 13C NMR (75 MHz, CDCl3, 258C): d=169.6 (C=O),
156.3 (Ar), 135.0 (Ar), 129.2 (Ar), 128.9 (Ar), 127.1 (Ar),
123.8 (Ar), 123.6 (Ar), 123.2 (2Ar), 119.5 (=CH), 118.6
(Ar), 114.5 (2Ar), 80.9 (C-3), 64.1 (C-4), 58.5 (OCH3), 57.3
(NCH2), 55.9 (C-5), 55.4 (OCH3), 30.4 (CH2); IR (CHCl3):
n=1702 cmÀ1
; HR-MS (ES): m/z=363.1702, calcd. for
C22H23N2O3 [M+H]+: 363.1703.
Tetracycle (+)-4b: From 100 mg (0.23 mmol) of b-amino-
allene (+)-syn-3b, and after chromatography of the residue
using n-hexane/ethyl acetate (75:25) as eluent gave com-
pound (+)-4b as a pale green oil; yield: 71 mg (71%); [a]D:
+97.8 (c 0.3, CHCl3). 1H NMR (300 MHz, CDCl3, 258C):
d=8.66 (d, 1H, J=8.2 Hz, ArH), 7.32–7.02 (m, 8H, ArH),
À
2H, ArH), 5.70 (br s, 1H, CH=), 4.98 (d, J=11.0 Hz, 1H,
OCH2), 4.55 (d, J=11.0 Hz, 1H, OCH2), 4.25 (d, J=
1474
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Allene-Based Gold-Catalyzed Stereodivergant Synthesis
11.0 Hz, 1H, H-3), 3.94–3.65 (m, 4H, CHH, H-4, H-5), 3.75
(s, 3H, OCH3), 3.54–3.40 (m, 2H, CHH); 13C NMR
(75 MHz, CDCl3, 258C): d=171.0 (C=O), 156.8 (Ar), 141.3
(Ar), 137.3 (Ar), 134.9 (C=), 129.2 (Ar), 128.6 (Ar), 128.3
(Ar), 128.2 (Ar), 127.8 (Ar), 127.1 (Ar), 125.7 (Ar), 123.6
by flash neutral alumina column chromatography eluting
with n-hexane/ethyl acetate mixtures to give analytically
pure dimeric spiro amino ketals 5 and ketones 6.
Preparation of dimeric spiro amino ketal (+)-5a and
ketone (À)-6a: From 100 mg (0.28 mmol) of b-aminoallene
(+)-anti-3a, and after chromatography of the residue using
hexanes/ethyl acetate (55:45!15:85) as eluent, the less
polar compound (À)-6a (yield: 24 mg, 22%) and the more
polar compound (+)-5a (yield: 50 mg, 48%) were obtained.
Dimeric spiro amino ketal (+)-5a: Pale yellow oil; [a]D:
+31.0 (c 0.1, CHCl3). 1H NMR (500 MHz, CDCl3, 258C):
d=8.12 (d, 1H, J=8.2 Hz, ArH), 7.29 (m, 1H, ArH), 7.24–
7.11 (m, 4H, ArH), 7.06–6.85 (m, 9H, ArH), 6.70 (d, J=8.7,
1H, ArH), 4.77 (m, 2H, H4, H4’), 4.26 (d, J=4.7 Hz, 1H,
H-3) 4.19 (t, J=6.4, 1H, H-5’), 4.10 (d, J=4.6 Hz, 1H, H-
3’), 4.01 (d, J=8.0 Hz, 1H, H-5’’), 3.90 (s, 3H, OCH3), 3.89
(s, 3H, OCH3), 3.51 (s, 3H, OCH3), 3.03 (d, J=15.2 Hz, 1H,
CAr-CHH) 2.97 (s, 3H, OCH3), 2.87 (d, J=18.3 Hz, 1H,
CHH), 2.45 (q, J=6.3 Hz, 1H, CHH), 1.98–1.73 (m, 3H, C-
5’’-CHH, CAr-CHH, H-5’’), 1.11 (m, 1H, C-5’’-CHH), 1.06 (s,
3H, CH3); 13C NMR (125 MHz, CDCl3, 258C): d=170.2
(C=O), 169.6 (C=O), 157.9 (Ar), 152.4 (Ar), 139.7 (Ar),
136.4 (Ar), 135.9 (Ar), 133.6 (Ar), 133.4 (Ar), 128.4 (Ar),
128.1 (Ar), 127.11 (Ar), 127.0 (Ar), 126.4 (Ar), 125.5 (Ar),
124.5 (Ar), 123.5 (Ar), 120.65 (Ar), 117.04 (4Ar), 114.5
(Ar), 113.15 (Ar), 107.12 (O-Cspir-N) 86.5 (O-Cspir), 83.0
(C-3), 80.5 (C-3’), 75.3 (C-Me), 60.6 (C-5’’), 60.3 (OCH3),
60.0 (OCH3), 59.0 (C-5’), 58.2 (C-4’), 56.6 (C-4), 55.7
(OCH3), 55.5 (OCH3) 53.2 (C-5), 36.5 (CH2), 34.9 (CAr-
CH2), 29.5 (C-5’’-CH2), 25.0 (CH3); IR (CHCl3): n=
À
(Ar), 123.2 (Ar), 120.6 ( CH=), 118.4 (Ar), 114.2 (Ar), 79.4
(C-3), 72.6 (OCH2), 67.0 (C-4), 55.4 (OCH3), 55.0 (CH2),
50.8 (C-5), 30.4 (CH2); IR (CHCl3): n=1710 cmÀ1; HR-MS
(ES): m/z=439.2025, calcd. for C28H27N2O3 [M+H]+:
439.2016.
Tetracycle (+)-epi-4c: From 20 mg (0.048 mmol) of b-ami-
noallene (À)-syn-epi-3c, and after chromatography of the
residue using n-hexane/ethyl acetate (7:3) as eluent gave
compound (+)-epi-4c as a pale yellow oil; yield: 13 mg
(65%); [a]D: +71.7 (c 0.1, CHCl3). 1H NMR (300 MHz,
C6D6, 258C): d=9.08 (d, J=8.3 Hz, 1H, ArH), 7.13–7.07
(m, 4H, ArH), 6.97–6.83 (m, 6H, ArH), 6.62 (AA’XX’, 2H,
À
ArH), 5.03 (br s, 1H, CH=), 4.77 (d, J=11.0 Hz, 1H, H-3),
3.65–3.14 (m, 4H, CHH, CHH, H-5), 3.33 (dd, J=11.0,
9.0 Hz, 1H, H-4), 3.26 (s, 3H, OCH3), 2.96 (d, J=20.1 Hz,
1H, CHH); 13C NMR (75 MHz, C6D6, 258C): d=168.9 (C=
O), 159.4 (Ar), 157.4 (Ar), 135.8 (C=), 134.3 (Ar), 134.1
(Ar), 129.4 (Ar), 129.3 (Ar), 129.1 (Ar), 127.6 (Ar), 125.8
À
(Ar), 123.6 (Ar), 123.2 (Ar), 122.2 (Ar), 118.9 ( CH=),
117.3 (Ar), 114.6 (Ar), 80.4 (C-3), 67.2 (C-4), 55.0 (OCH3),
54.5 (CH2), 49.8 (C-5), 30.4 (CH2); IR (CHCl3): n=
1712 cmÀ1
;
HR-MS (ES): m/z=425.1873, calcd. for
C27H25N2O3 [M+H]+: 425.1860.
Tetracycle (À)-epi-4d: From 25 mg (0.054 mmol) of b-
aminoallene (À)-syn-epi-3d, and after chromatography of
the residue using n-hexane/ethyl acetate (8:2) as eluent gave
compound (À)-epi-4d as a pale yellow oil; yield: 15 mg
(61%); [a]D: À198.2 (c 0.1, CHCl3). 1H NMR (300 MHz,
C6D6, 258C): d=9.06 (d, J=8.1 Hz, 1H, ArH), 7.14–7.08
(m, 1H, ArH), 7.03 (AA’XX’, 2H, ArH), 6.92–6.86 (m, 2H,
ArH), 6.88 (AA’XX’, 2H, ArH), 6.81 (AA’XX’, 2H, ArH),
1710 cmÀ1
;
HR-MS (ES): m/z=741.3307, calcd. for
C44H45N4O7 [M+H]+: 741.3283.
Ketone (À)-6a: Colorless oil; [a]D: À7.2 (c 0.1, CHCl3).
1H NMR (300 MHz, CDCl3, 258C): d=8.80 (d, 1H, J=
7.9 Hz, ArH), 7.29–7.24 (m, 1H, ArH), 7.15 (d, J=7.0 Hz,
1H, ArH), 7.06 (t, J=7.2 Hz, 1H, ArH), 6.76 (AA’XX’, 2H,
ArH), 6.58 (AA’XX’, 2H, ArH), 4.44 (ddd, J=8.8, 6.3,
4.6 Hz, 1H, H-4), 4.22 (d, J=6.4 Hz, 1H, H-3), 4.20 (dd, J=
10.5, 4.5 Hz, 1H, H-5), 3.74 (s, 3H, OCH3), 3.63 (d, J=
8.7 Hz, 1H, NH), 3.36 (s, 3H, OCH3), 3.28 (ddd, J=12.7,
10.7, 4.6 Hz, 1H, H-6), 3.12 (dd, J=16.0, 4.6 Hz, CHH), 2.84
(dd, J=15.7, 13.0 Hz, 1H, CHH), 2.08 (s, 3H, CH3CO);
13C NMR (125 MHz, CDCl3, 258C): d=209.6 (C=O), 169.3
(C=O), 153.0 (Ar), 141.4 (Ar), 135.5 (Ar), 128.8 (Ar), 127.7
(Ar), 124.0 (Ar), 123.9 (Ar), 119.2 (Ar), 115.5 (2Ar), 114.9
(2Ar), 79.3 (C-3), 59.7 (C-4), 58.9 (OCH3), 55.7 (OCH3),
52.8 (C-5), 44.9 (C-6), 31.2 (CH2), 29.7 (CH3); IR (CHCl3):
À
6.62 (AA’XX’, 2H, ArH), 5.04 (t, J=2.4 Hz, 1H, CH=),
4.56 (d, J=11.0 Hz, 1H, H-3), 3.59–3.40 (m, 3H, H-5,
CHH), 3.29–3.20 (m, 2H, H-4, CHH), 3.27 (s, 3H, OCH3),
2.97 (d, J=20.2 Hz, 1H, CHH); 13C NMR (75 MHz, C6D6,
258C): d=168.6 (C=O), 157.8 (Ar), 157.5 (Ar), 141.4 (Ar),
135.7 (C=), 129.4 (Ar), 129.3 (Ar), 127.2 (Ar), 126.0 (Ar),
123.8 (Ar), 123.2 (Ar), 120.7 (CH=), 118.8 (Ar), 118.7
(2Ar), 114.6 (Ar), 80.9 (C-3), 67.1 (C-4), 55.0 (OCH3), 54.5
(CH2), 50.4 (C-5), 30.3 (CH2); IR (CHCl3): n=1709 cmÀ1
;
HR-MS (ES): m/z=459.1468, calcd. for C27H24ClN2O3 [M+
H]+: 459.1470.
n=1704 cmÀ1
; HR-MS (ES): m/z=381.1810, calcd. for
C22H25N2O4 [M+H]+: 381.1809.
General Procedure for the Gold-Catalyzed Reaction
of Indolizidinone-Tethered b-Aminoallenes anti-3b–d
Preparation of dimeric spiro amino ketal (+)-5b and
ketone (À)-6b: From 125 mg (0.28 mmol) of b-aminoallene
(+)-anti-3b, and after chromatography of the residue using
hexanes/ethyl acetate (7:3!1:1) as eluent, the less polar
compound (À)-6b (yield: 13 mg, 10%) and the more polar
compound (+)-5b (yield: 41 mg, 34%) were obtained.
Dimeric spiro amino ketal (+)-5b: Pale yellow oil; [a]D:
Preparation of spiro[benzo[e]furo[2’,3’:4,5]pyrrolo[4,3,2-
hi]indolizine-2,4’-benzo[e]pyrrolo[4,3,2-hi]indolizine]-
1’,6(2’H,4a1H)-diones 5a–d and ketones 6a,b and 6d:
AgSbF6 (0.01 mmol, 5% mol) was added to a well stirred so-
lution of IPrAuCl (0.01 mmol, 5% mol) in 1,2-dichloro-
ethane (3 mL), at room temperature, in the dark. The result-
ing mixture was stirred for 5 min and, then, the appropriate
b-aminoallene anti-3 (0.20 mmol) was added. The mixture
was stirred at the same temperature until the total disap-
pearances of starting material (TLC). The solvent was re-
moved under reduced pressure and the residue was purified
1
+4.8 (c 0.1, CHCl3). H NMR (500 MHz, CDCl3, 258C): d=
8.12 (d, 1H, J=8.2 Hz, Ar), 7.30–7.21 (m, 7H, ArH), 7.20–
7.10 (m, 8H, ArH), 7.03 (t, J=7.4 Hz, 1H, ArH), 6.91 (s,
4H, Ar), 6.86–6.82 (m, 4H, ArH), 6.71 (d, J=7.4 Hz, 1H,
ArH), 4.95 (d, J=12.6 Hz, 1H, OCHH’), 4.78–4.74 (m, 3H,
H-4’, H-4, OCHH’), 4.65 (d, J=12.3 Hz, 1H, OCHH), 4.40
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Benito Alcaide et al.
(d, J=4.6, Hz, 1H, H-3’), 4.30 (t, J=6.2 Hz, 2H, H-3,
1714 cmÀ1
;
HR-MS (ES): m/z=865.3636, calcd. for
C54H49N4O7 [M+H]+: 865.3596.
OCHH), 4.17 (dd, J=8.0, 1.3 Hz, 1H, H-5’), 3.97 (d, J=
4.5 Hz, H-5) 3.90 (s, 6H, 2OCH3), 3.03 (d, J=15.2 Hz, 1H,
CHH), 2.83 (d, J=18.4 Hz, 1H, CAr-CHH), 2.45 (ddd, J=
14.1, 8.0, 1.5 Hz, 1H, H-5’’), 2.01 (d, J=15.2 Hz, 1H, CHH),
1.84–1.79 (m, 2H, CAr-CHH, C-5’’-CHH), 1.14–1.09 (m, 4H,
C-5’’-CHH, CH3); 13C NMR (125 MHz, CDCl3, 258C): d=
170.5 (C=O), 170.4 (C=O), 157.8 (Ar), 152.5 (Ar), 139.8
(Ar), 137.7 (Ar), 137.6 (Ar), 136.7 (Ar), 135.8 (Ar), 133.6
(Ar), 133.4 (Ar), 128.5 (Ar), 128.1 (2Ar), 127.8 (2Ar), 127.7
(2Ar), 127.5 (Ar), 127.1 (2Ar), 127.0 (Ar), 126.9 (Ar), 126.3
(Ar), 125.4 (Ar), 124.5 (Ar), 123.4 (Ar), 120.6 (Ar), 117.4
(2Ar), 114.5 (Ar), 113.3 (Ar), 107.2 (O-Cspir-N), 86.4 (O-
Cspir), 79.2 (C-3’), 77.4 (C-3), 75.3 (C-Me), 73.0 (OCH2),
72.8 (OCH2’), 60.6 (C-5), 58.9 (C-4’), 58.2 (C-5’), 56.8 (C-4),
55.7 (OCH3), 55.5 (OCH3), 52.9 (C-5’’), 36.4 (CAr-CH2), 35.0
(CH2), 29.4 (C-5’’-CH2), 25.0 (CH3); IR (CHCl3): n=
Preparation of dimeric spiro amino ketal (+)-5d and
ketone (À)-6d: From 100 mg (0.22 mmol) of b-aminoallene
(+)-anti-3d, and after chromatography of the residue using
hexanes/ethyl acetate (8:2!1:1) as eluent, the less polar
compound (+)-6d (yield: 20 mg, 20%) and the more polar
compound (+)-5d (yield: 40 mg, 42%) were obtained.
Dimeric spiro amino ketal (+)-5d: Pale yellow oil; [a]D:
+30.0 (c 0.1, CHCl3). 1H NMR (500 MHz, CDCl3, 258C):
d=8.13 (d, 1H, J=8.2 Hz, Ar), 7.32 (d, 1H, J=7.6 Hz,
ArH), 7.26–7.18 (m, 3H, ArH), 7.16–7.11 (m, 3H, ArH),
7.04 (t, J=7.5 Hz, 1H, ArH), 7.00 (AA’XX’, 2H, ArH),
6.97–6.91 (m, 1H, ArH), 6.92–6.77 (m, 6H, ArH), 6.71–6.63
(m, 4H, ArH), 6.40 (AA’XX’, 2H, ArH), 5.14 (d, J=4.7 Hz,
1H, H-3), 5.03 (d, J=6.4 Hz, 1H, H-3’), 4.91 (t, J=4.6 Hz,
1H, H-5), 4.88 (t, J=6.4 Hz, 1H, H-4’), 4.28 (t, J=6.6 Hz,
1H, H-5’), 4.11 (d, J=4.4 Hz, 1H, H-5), 3.89 (s, 3H, OCH3),
3.84 (s, 3H, OCH3), 3.04 (d, J=15.2 Hz, 1H, CAr-CHH),
2.84 (d, J=18.3 Hz, 1H, CHH), 2.48 (q, J=5.6 Hz, 1H, H-
5’’), 2.03 (d, J=15.2 Hz, 1H, CAr-CHH) 1.86–1.82 (m, 2H,
C-5’’-CHH, CHH), 1.15 (dd, J=13.4, 6.2 Hz, 1H, C-5’’-
CHH), 1.09 (s, 3H, CH3); 13C NMR (125 MHz, CDCl3,
258C): d=168.5 (C=O), 168.2 (C=O), 159.9 (Ar), 157.2
(Ar), 156.9 (Ar), 152.7 (Ar), 139.5 (Ar), 135.6 (Ar), 135.5
(Ar), 133.4 (Ar), 133.2 (Ar), 129.1 (2Ar), 128.6 (2Ar), 128.5
(Ar), 128.1 (Ar), 127.2 (Ar), 127.1 (Ar), 126.6 (Ar), 126.2
(Ar), 125.3 (Ar), 124.9 (Ar), 123.5 (Ar), 120.7 (Ar), 117.5
(Ar), 117.1 (2Ar), 116.5 (2Ar), 107.1 (O-Cspir-N), 86.6 (O-
Cspir), 79.9 (C-3), 76.9 (C-3’), 75.4 (C-Me), 60.8 (C-5’’), 58.4
(C-5’), 58.3 (C-4’), 56.5 (C-5), 55.7 (OCH3), 55.6 (OCH3),
53.0 (C-5), 36.3 (CH2), 35.0 (CAr-CH2), 29.5 (C5-’’-CH2), 25.0
(CH3); IR (CHCl3): n=1714 cmÀ1; HR-MS (ES): m/z=
933.2796, calcd. for C54H47Cl2N4O7 [M+H]+: 933.2816.
Ketone (+)-6d: Colorless oil; [a]D: +6.1 (c 0.1, CHCl3).
1H NMR (500 MHz, CDCl3, 258C): d=8.84 (d, 1H, J=
8.3 Hz, ArH), 7.19–7.07 (m, 5H, ArH), 6.82 (AA’XX’, 2H,
ArH), 6.66 (AA’XX’, 2H, ArH), 6.51 (AA’XX’, 2H, ArH),
5.05 (d, J=6.4 Hz, 1H, H-3), 4.60 (ddd, J=9.5, 6.5, 4.2 Hz,
1H, H-4), 4.30 (dd, J=10.5, 4.6 Hz, 1H, H-5), 3.71 (s, 3H,
OCH3), 3.59 (d, J=10.5 Hz, 1H, NH), 3.33 (ddd, J=12.8,
10.5, 4.5 Hz, 1H, H-6), 3.15 (dd, J=15.9, 4.5 Hz, CHH), 2.89
(dd, J=15.7, 12.9 Hz, 1H, CHH), 2.12 (s, 3H, CH3CO);
13C NMR (125 MHz, CDCl3, 258C): d=209.2 (C=O), 168.3
(C=O), 156.5 (Ar), 153.2 (Ar), 141.0 (Ar), 135.4 (Ar), 129.3
(2Ar), 129.1 (Ar), 127.8 (Ar), 127.2 (Ar), 124.3 (Ar), 124.0
(Ar), 119.0 (Ar), 117.6 (2Ar), 116.2 (2Ar), 114.7 (2Ar), 77.6
(C-3), 59.5 (C-4), 55.7 (OCH3), 53.8 (C-5), 44.9 (C-6), 31.1
(CH2), 29.7 (CH3); IR (CHCl3): n=1704 cmÀ1; HR-MS
(ES): m/z=477.1579, calcd. for C27H26ClN2O4 [M+H]+:
477.1576.
1710 cmÀ1
;
HR-MS (ES): m/z=893.3895, calcd. for
C56H53N4O7 [M+H]+: 893.3909.
Ketone (À)-6b; Pale yellow oil; [a]D: À4.7 (c 0.1, CHCl3).
1H NMR (300 MHz, CDCl3, 258C): d=8.79 (d, J=8.3 Hz,
1H, ArH), 7.33–7.18 (m, 6H, ArH), 7.14 (d, J=7.1 Hz, 1H,
ArH), 7.05 (t, J=7.4 Hz, 1H, ArH), 6.75 (AA’XX’, 2H,
ArH), 6.56 (AA’XX’, 2H, ArH), 4.6 (s, 2H, OCH2), 4.34 (br
s, 2H, H-3, H-4), 4.15 (dd, J=10.6, 4.1 Hz, 1H, H-5), 3.76 (s,
3H, OCH3), 3.76–3.68 (br s, 1H, NH), 3.27 (ddd, J=13.0,
10.8, 4.3 Hz, 1H, H-6), 3.10 (dd, J=16.0, 4.6 Hz, CHH), 2.83
(dd, J=16.0, 12.9 Hz, 1H, CHH), 2.08 (s, 3H, CH3CO);
13C NMR (125 MHz, CDCl3, 258C): d=209.6 (C=O), 169.7
(C=O), 153.0 (Ar), 141.5 (Ar), 136.6 (Ar), 135.6 (Ar), 128.8
(Ar), 128.4 (2Ar), 128.1 (2Ar), 128.0 (Ar), 127.7 (Ar), 124.0
(Ar), 123.9 (Ar), 119.1 (Ar), 115.8 (2Ar), 114.9 (2Ar), 76.3
(C-3), 72.7 (OCH2), 59.7 (C-4), 55.7 (OCH3), 53.2 (C-5),
45.0 (C-6), 31.3 (CH2), 29.8 (CH3); IR (CHCl3): n=
1699 cmÀ1
;
HR-MS (ES): m/z=457.2124, calcd. for
C28H29N2O4 [M+H]+: 457.2122.
Dimeric spiro amino ketal (+)-5c: From 54 mg
(0.13 mmol) of b-aminoallene (+)-anti-3c, and after chroma-
tography of the residue using n-hexane/ethyl acetate (55:45)
as eluent gave compound (+)-5c as a colorless solid; yield:
23 mg (42%); mp 250–2528C; [a]D: +103.4 (c 0.3, CHCl3).
1H NMR (500 MHz, C6D6, 258C): d=8.65 (d, 1H, J=
8.2 Hz, ArH), 7.65 (d, 1H, J=7.3, ArH), 7.08–7.04 (m, 5H,
ArH), 7.02–6.96 (m, 4H, ArH), 6.92–6.90 (m, 3H, ArH),
6.83–6.76 (m, 8H, ArH), 6.65 (d, 2H, J=7.8 Hz, ArH), 6.50
(d, J=8.7, 2H, ArH), 4.70 (d, J=5.6, 2H, H-3, H-3’), 4.59
(t, J=6.4, 1H, H-5’), 4.38 (t, J=4.6 Hz, 1H, H-4), 4.01 (t,
J=8.0, Hz, 1H, H-4’), 3.68 (d, J=4.4 Hz, 1H, H-5’’), 3.57 (s,
3H, OCH3), 3.41 (s, 3H, OCH3), 2.80 (m, 2H, CHH, CAr-
CHH), 2.30 (q, J=6.3 Hz, 1H, H-5), 1.79 (m, 3H, CAr-CHH,
C-5’’-CHH, CHH), 1.05 (m, 1H, C-5’’-CHH), 0.85 (s, 3H,
CH3); 13C NMR (125 MHz, C6D6, 258C): d=168.8 (C=O),
168.3 (C=O), 159.7 (Ar), 159.5 (Ar), 158.3 (Ar), 153.1 (Ar),
140.0 (Ar), 136.9 (Ar), 136.6 (Ar), 134.4 (Ar), 134.3 (Ar),
129.4 (4Ar), 129.1 (4Ar), 128.8 (Ar), 127.5 (Ar), 127.4 (Ar),
126.5 (Ar), 125.5 (Ar), 124.8 (Ar), 124.1 (Ar), 122.0 (Ar),
121.6 (Ar), 121.1 (Ar), 117.9 (Ar), 116.6 (4Ar), 116.2 (4Ar),
107.4 (O-Cspir-N), 86.6 (O-Cspir), 80.3 (C-3), 77.7 (C-3’),
75.6 (C-Me), 60.9 (C-5’’), 59.0 (C-5’), 58.4 (C-4’), 57.0 (C-4),
55.4 (OCH3), 55.3 (OCH3), 53.4 (C-5), 36.9 (CAr-CH2), 35.1
(CH2), 29.7 (C-5’’-CH2), 24.8 (CH3); IR (CHCl3): n=
Acknowledgements
Support for this work by MINECO and FEDER (Projects
CTQ2012-33664-C02-01, CTQ2012-33664-C02-02, CTQ2015-
65060-C2-1-P, and CTQ2015-65060-C2-2-P) is gratefully ac-
knowledged.
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References
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[11] To shed light on the active participation of water,
a new experiment was carried out. Thus, the reaction
of b-aminoallene anti-3c was run in a strictly anhydrous
environment, under otherwise identical conditions. No-
tably, the spirodimer formation event was cut down be-
cause compound 5c was formed from anti-3c in only
trace amount. Taking into account the almost absence
of product 5c by performing the experiment under
Schlenk conditions, we are confident that the oxygen
atom in spirodimers 5 was coming from ambient water.
[12] Experimental procedures as well as full spectroscopic
and analytical data for compounds not included in this
Experimental Section are described in the Supporting
Information. It contains compound characterization
data, experimental procedures, and copies of NMR
spectra for all new compounds.
[7] The benzo-fused indolizidinone core of pyrroloquinoli-
none-tethered b-aminoallenes 3 is present in the natu-
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