Microwave-assisted competing domino processes in the octaline diol series

Article abstract of DOI:10.1002/ejoc.200900242

A Pb(OAc)₄-mediated, path selective, modular domino transformation using an octaline diol framework as a probe is described. Alteration of the nature of the angular substituent or the length of the tether chain controls the effectiveness of the

Full text of DOI:10.1002/ejoc.200900242

FULL PAPER
DOI: 10.1002/ejoc.200900242
Microwave-Assisted Competing Domino Processes in the Octaline Diol Series
Zobida Elkhayat,[a] Imad Safir,[a] Maurizio Aquino,[a] Manuel Perez,[a] Zoila Gandara,[a]
Pascal Retailleau,[a] and Siméon Arseniyadis*[a]
Keywords: Domino reactions / Lead / Diols / Microwave chemistry
A Pb(OAc)4-mediated, path selective, modular domino trans-
formation using an octaline diol framework as a probe is de-
scribed. Alteration of the nature of the angular substituent or
the length of the tether chain controls the effectiveness of the
“ring-expanded” versus “ring-retained” domino path. The
solvent can modify the behaviour of the transient intermedi-
transformations leading to half-cascade intermediates when
used as the solvent. Irrespective of the nature of the substitu-
ents (alkyl, alkenyl, alkoxy, acyloxy) and the solvent, all diol
substrates react with PhI(OAc)2 to afford exclusively the in-
terrupted cascade as the only domino product.
ates and the reaction time is reduced under microwave heat- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ing, whereas water cleanly promotes oxidative/pericyclic
Germany, 2009)
Introduction
Unsaturated bicyclic vicinal diols can react with Pb(OAc)4
or PhI(OAc)2, which act as domino promoters in several
ways, depending on the reaction conditions.[1] When the
angular position bears a functional substituent, such as an
alkoxy, an ester or a carbonyl group, more than one domino
reaction path could be put into competition.[2] In the hyd-
rindene diol series, the reaction course could be directed
towards either of two distinct pathways, simply by the judi-
cious choice of the angular substituent. As illustrated by
Scheme 1, examples of this process include competition of
two domino processes for diol substrates differing only at
the angular substitution. Ether linkage was a prerequisite
for the oxonium path, whereas its efficiency was shown to
decrease with increasing separation of the oxygen from the
angular position and the bulk of the linking chain.[2b] Con-
versely, any ester or alkyl group at the angular position
completely reversed the tendency to undergo ring expan-
sion.[2c] Moreover, a dramatic increase in rate was observed
in the reactions conducted under microwave activation at
either 60 or 90 °C, which represent an important experi-
mental improvement.
Scheme 1. Scope with respect to the angular substituent.
of this process, as well as the effect of varying the angular
substituent, the solvent and the domino[5] promoter.
Results and Discussion
Access to the requisite octaline diols with varying chain
lengths and steric requirements was readily achieved from
a known bicyclic diol used in our earlier studies,[2a] through
trivial transformations. To probe the path selectivity, com-
petition experiments involving the domino reactions of 1a
and 5a were conducted as a preliminary screen (Scheme 2).
We chose the above octaline diols, as their structures
seemed to lend themselves to a useful test of the methodol-
ogy given the precedents in the lower homologue hydrind-
ene diol series. Thus, investigating the role of tether length
to control the orientation for selective access to either ring-
expanded 8a or ring-retained 3a, we first found that the
solvent played a critical role in the product distribution in
the octaline diol series.[6] A survey of three solvents, PhMe,
H2O and AcOH, revealed that AcOH was the solvent of
This captivating path selectivity prompted us to scope
out the features associated with selective construction of the
[6+7] fused ring system, precursor of elaborated cyclohep-
tanes,[3] and to investigate the regiochemical course in the
presence of a variety of functional groups. We report in this
paper on the feasibility of the microwave-assisted[4] version
[a] Institut de Chimie des Substances Naturelles, CNRS,
91198 Gif-sur-Yvette, France
E-mail: simeon.arseniyadis@icsn.cnrs-gif.fr
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Scheme 2. Scope with respect to the tether length.
choice, increasing the propensity of the diol to undergo oxy-
plumbation (necessary for either the oxonium or ring-ex-
pansion path). A few minutes of microwave irradiation led
to the selective formation of the desired domino product in
satisfactory yield, by using the appropriate solvent, as out-
lined in Scheme 2. Accordingly, when operating in PhMe as
solvent, only half-cascade domino products 2a and 6a were
obtained.[7] Carrying out the same sequence in water[8] af-
forded cleanly 55% of 2a and 50% of 6a, along with reco-
vered starting diols.[9] Switching to AcOH changed the
product distribution leading to either 3a or 8a, depending
upon the length of the linking chain. Hence, treatment of
unsaturated diol 1a with Pb(OAc)4 cleanly afforded tetra-
cyclic trisacetal 3a in 75% yield as a single domino product.
Its higher homologue 5a, under the same reaction condi-
tions gave rise to ring-enlarged domino product 8a in 61%
isolated yield.
Figure 1. Competing domino processes by tuning the tether
length – a mechanistic rationale.
The mechanism of these one-pot multistage transforma-
tions was investigated in our previous studies and it is estab-
lished that, following glycol fission (i, Figure 1), the reac-
tion proceeds through a hetero-[4π+2π] cycloaddition lead- temperature (A) or with conventional heating at 60 °C (C).
ing to cyclic ene–acetal ii and a subsequent oxyplumbation, Methods A, B, and C use AcOH as solvent. Method D,
which sets the final destination on the basis of the geometry which can be also realized with PhI(OAc)2 as the domino
of the transient organolead intermediate (iii or v) along promoter, uses PhMe, and finally method E uses H2O as
with the nature of the angular substituent.[1a,1b,2c] As por- solvent. The scope and efficiency of the presented work are
trayed in Figure 1, the product distribution can be altered illustrated by the results summarized in Tables 1 and 2.
through the magnitude of the connecting chain, thus ensur- With PhMe or H2O as solvent (domino conditions D and
ing a regioselective profile for the oxyplumbation–deplumb- E), only the glycal-type half-cascade products (i.e., 2, 6, 10,
ation sequence. Although the one-pot conversions of 1a 13, 16) were obtained, irrespective of the nature of the
into 3a and 5a into 8a proceed through a similar transient angular substitution. These compounds, whose synthetic
organolead intermediate of type v and iii, respectively, the utility was explored,[12] are also cleanly obtained in PhMe
product distribution is markedly different for each template by using PhI(OAc)2 as the domino promoter. In AcOH,
differing only in tether length. These outstandingly selective treatment of unsaturated diols 1b–h with Pb(OAc)4 under
domino reactions associate entropy as a powerful control all domino conditions (A, B or C) gave no detectable quan-
element in product formation along with orbital alignment tities of ring-expanded structures. The only product isolated
considerations.[10]
from this reaction was 3 (Table 1, Entry 1). The same trend
With a representative range of templates in the octaline was observed with substrates 9 and 12, where correspond-
diol series, the stage was at hand to explore the factors that ing ring-retained domino products 11 and 14 were obtained
govern the path selectivity. The diols were subjected to exclusively (Table 1, Entries 3 and 4).
Pb(OAc)4-mediated oxidative cleavage under five sets of
In the case involving homologated ether linkage, with
conditions (methods A, B, C, D and E).[11] The reliance on OMe and OTMS groups at the angular position (5b,c;
the solvent was examined by using PhMe, AcOH and H2O. Table 1, Entry 2), the reaction proceeds via an intermediate
Three of the methods, B, D and E, employ microwave irra- oxonium with exclusive formation of tetracyclic bis(acetal)
diation at 60 °C, whereas methods A and C operate at room 7. Tuning the length of the connecting chain along with the
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Microwave-Assisted Competing Domino Processes in the Octaline Diol Series
Table 1. Variation of the product distribution by alternating the sufficiently bulky to considerably obstruct cyclic trityloxon-
factors controlling the competition.
ium formation. When subjected to the action of Pb(OAc)4
in AcOH (Methods A, B, C), a bulky ester group (1i–k)
gave rise to a single domino product of type 4 isolated in
high yield (Table 1, Entry 5). Under the same conditions,
the less sterically demanding esters (1b,c), like any ether
linkage, delivered ring-retained domino product 3, unless
additional steric bulk and chain lengthening was introduced
(Table 1, Entry 6). The absence of the ring-expanded dom-
ino product from 1b and 1c could be due to the fact that the
intermediate of type v (Figure 1) did not live long enough to
allow for C9–C5 bond migration. The observed divergent
behaviour in the octaline diol series shows that fused-ring
size is an important regiodeterminant in these reactions.
The oxonium path could be also completely suppressed
by carrying out the domino reactions on substrates having
longer connecting chains (ethylene tethered esters 5e–k;
Table 1, Entry 6). With diol substrates bearing an alkyl[1a]
or an alkenyl substituent at the bridgehead position, exem-
plified by compounds 15a and 15b, the cascade culminating
in a ring-expanding rearrangement proceeded selectively to
give domino products 17a and 17b, respectively (Table 1,
Entry 7). A comparison of the products from Entries 1 vs.
6 and 2 vs. 7 reveals the subtle effect of the angular substitu-
ent; it has a controlling influence on the course of the dom-
ino reaction, the products of which are either type 4, 8 or
17 ring-expanded cis-fused [6+7] bicyclic systems or ring-
retained cis-fused tetrahydrofurans (i.e., 3, 11, 14) and cis-
fused tetrahydropyrans (i.e., 7). The structure of crystalline
domino product 8e first ascertained by the measurement of
spatial proximity effects by using 2D NOESY experiments
was confirmed by a single-crystal X-ray diffraction study
(Figure 2) and served to corroborate the relative configura-
tions of all ring-expanded domino products (i.e., 4, 8, 17).
The structures of 3, 3a and 7 were assigned by analogy to
their lower homologues.[2b,2c] The half-cascade domino
products were obtained exclusively, in either PhMe or
AcOH, when PhI(OAc)2 was used as the domino promoter.
[a] Methods D, E: The substrate (1.0 mmol) and Pb(OAc)4
(1.2 mmol) were heated in a microwave for 5–10 min at 60 °C; in
1 mL of PhMe (D) or in 1 mL of H2O (E). [b] Methods A, B, C:
reactions conducted with Pb(OAc)4 (2.4 mmol) and the diol sub-
strate (1.0 mmol) in AcOH (1 mL). Method A: room temperature
for 12–15 h; method B: microwave irradiation, 10 min at 60 °C;
method C: conventional heating, 10 min at 60 °C.
steric bulk of the angular alkoxy substituent (OPiv group
at the angular position, 5d; Table 1, Entry 6) allowed the
path selectivity to be changed, as the trityl protection was Figure 2. ORTEP view of the molecular structure of 8e.
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Examining the results depicted in Table 1, one can figure haviour in the octaline diol series. The drop in path selectiv-
out that diols of type 1, 5, 9, 12 or 15 can lead to either the ity could be attributed to the fused ring size effect in orbital
half-cascade (i.e., 2, 6, 10, 13, 16), the ring-expanded dom- alignment.
ino (i.e., 4, 8, 17) or the ring-retained domino products (i.e.,
The domino reaction of 1l–o gave a mixture of three
3, 7, 11, 14) through the appropriate choices of solvent, compounds, half-cascade 2l–o (a common intermediate for
oxidant and angular substituent. A partial explanation for both domino paths), ring-retained 3 and ring-expanded
the dominant reaction pathway and product distribution 4l–o in varying yields and ratios (Table 2, Entries 1–4). In
may be found in the relative rates of cyclic oxonium forma- the ether-tethered substrates, the isolation of ring-retained
tion vs. C5–C10 ring-expanding bond migration.
in addition to ring-expanded products was also observed
To further investigate the effect of angular substitution upon homologation (Table 2, Entries 5–8). Thus, exploring
on the ability to orient a domino path, we performed ad- diols 5l–o we found that two domino products, 7 and
ditional experiments on a range of substrates portrayed in 8l–o, were formed in each case investigated along with their
Table 2 and Scheme 3. The experiments listed in Table 2, precursor, tricyclic ene–acetal 6l–o (half-cascade). Even
like those in Table 1, were all performed competitively, with though the oxonium pathway (heteroatom promoted anch-
the same amount of reagent in three different solvents, at imerically assisted deplumbation) leading to 7 was expected
room temperature or at 60 °C (conventional or microwave to be severely compromised as the tether length increases,
heating). The ester-tethered substrates, which in the hydrin- rather mixed results were obtained. Again, the interrupted
dene diol series proceed in a totally selective manner to cascade sequence in water (domino conditions D) under mi-
yield a ring-expanded domino product, displayed dual be- crowave irradiation occurs rapidly to afford cleanly 2l–o
Table 2. Orienting experiments for modular construction of oxygen heterocycles.
[a] Methods D, E: The substrate (1.0 mmol) and Pb(OAc)4 (1.2 mmol) were heated in a microwave for 5–10 min at 60 °C; in 1 mL of
PhMe (D) or in 1 mL of H2O (E). [b] Methods, A, B, C: reactions conducted with Pb(OAc)4 (2.4 mmol) and the diol substrate (1.0 mmol)
in AcOH (1 mL). Method A: room temperature for 12–15 h; method B: microwave irradiation, 10 min at 60 °C; method C: conventional
heating, 10 min at 60 °C.
Scheme 3.
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Microwave-Assisted Competing Domino Processes in the Octaline Diol Series
and 6l–o in good yields (see the Supporting Information for
Of special note is the possibility to use water as solvent
1
the H NMR spectrum of the crude reaction mixture for under microwave irradiation;[15] up to 78% isolated yields
2l).
of half-cascade products 2, 6, 10, 13 and 16 were obtained
We finally examined the path-discriminating ability of (Table 1, Entries 1–7; Table 2, Entries 1–8). Taking into ac-
the C11 configuration on diols 18 and 21 (epimeric mixture count the high level of molecular complexity attained in a
at C11).[13] As in the lower homologue series,[2b] the ox- one-pot transformation, the yields are remarkably high. As
onium path was disadvantaged in one of the two epimers summarized in Figure 3, the process may be used for path-
where the stereocentre at the angular position is of the (R) determined domino reactions starting from the same bicy-
configuration. Thus, diols 18 and 21 reacted by an oxonium clic diol framework 1 or 5 and by switching the reactivity
path for their (C11S)-counterparts to furnish 20 and 23 (61 pattern by varying the nature or the length of the linking R
and 67%, respectively), whereas the contribution of their chain,[16] the solvent and the domino promoter.
(C11R)-counterparts could not be elucidated (Scheme 3).[14]
The (C11S/C11R) ratio was safely measured for half-cas-
cade intermediates 19 and 22 (10:1 and 12:1, respectively)
running the domino reaction in PhMe.
Experimental Section
General: See ref.[2a,2b,2c]
In summary, in the octaline diol series, in addition to the
Representative Examples for Microwave-Assisted Domino Transfor-
mations
importance of the nature of the angular substituent (steric
and entropic factors), solvent plays an important role on
the balance between the competing pathways, whereas mi-
Method B: A microwave tube was charged with a solution of a
crowave acceleration allows cleaner transformations for the bicyclic unsaturated diol (1 mmol) in dry toluene (1 mL) and
Pb(OAc)4 (2.4 mmol), sealed with a septum and inserted inside a
microwave cavity. The reaction mixture was magnetically stirred for
10 min (60 °C at 100 W). The tube was cooled to room tempera-
ture, and the mixture was diluted with Et2O. Brine was added fol-
lowed by NaHCO3, and the organic layer was dried with MgSO4,
domino reactions than does conventional heating.
Conclusions
At the outset of this investigation, our goal was to de- filtered, concentrated and purified by flash chromatography.
velop a modular domino reaction in the octaline diol series,
Method E: A microwave tube was charged with a solution of a
which could provide tuneable access to all the possible dom-
ino products (the half-cascade, ring-expanded and ring-
retained domino products). The examples presented in this
article indicate the wide range of substitution that is com-
patible with the process. The reaction course can be directed
towards either of two distinct pathways or interrupted half-
way through by the appropriate choice of the angular sub-
bicyclic unsaturated diol (0.1 mmol) in water (0.1 mL) and
Pb(OAc)4 (1.2 mmol), sealed with a septum and inserted inside a
microwave cavity. The reaction mixture was magnetically stirred for
5 min (60 °C, at 100 W). The tube was cooled to room temperature,
and the mixture was diluted with Et2O. The above procedure was
then followed.
Microwave-Assisted Domino Transformations in AcOH following the
stituent, the length of the linking chain, the solvent or the Oxonium Path
domino promoter. In all cases investigated, microwave heat-
Domino Product 3: Oxidative cleavage of diols 1e (60 mg,
0.13 mmol) by using method B afforded 3 (30 mg, 86%). White
ing was found to be more desirable, occurring with a tenfold
increase in rate relative to that observed with conventional
heating (and a spectacular increase relative to room-tem-
perature runs).
solid. M.p. 81–82 °C (heptane). IR (film): ν = 2934, 2863, 1738,
˜
1448, 1371, 1236, 1185, 1145, 1057, 945, 936, 845, 748 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 1.26 (m, 1 H), 1.34 (ddd, J = 5.0,
13.9, 17.8 Hz, 1 H), 1.48 (m, 1 H), 1.59 (m, 3 H), 1.90 (d, J =
12.9 Hz, 1 H), 2.09 (s, 3 H), 2.11 (d, J = 3.8 Hz, 2 H), 2.34 (dd, J
= 6.7, 9.2 Hz, 1 H), 3.77 (d, J = 1.3 Hz, 1 H), 3.84 and 3.89 (ABq,
J = 8.7 Hz, 2 H), 5.53 (dd, J = 1.7, 3.7 Hz, 1 H), 6.96 (d, J =
1.3 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.6, 21.3,
21.8, 30.7, 32.0, 47.0, 50.8, 74.9, 82.8, 86.7, 90.8, 98.6, 170.0 ppm.
MS (ESI, MeOH): m/z (%) = 277.1 (100) [M + Na]+. HRMS (ESI):
calcd. for C13H18NaO5 277.1052; found 277.1056. C13H18O5
(254.12): calcd. C 61.40, H 7.14; found C 61.01, H 7.47.
Domino Product 3a: Oxidative cleavage of 1a (60 mg, 0.25 mmol)
by using method B afforded ring-retained domino product 3a
(66.8 mg, 75%) after flash chromatography (SiO2; heptane/EtOAc,
4:1). Colourless oil. IR (film): ν = 2944, 2912, 1739, 1449, 1371,
˜
1277, 1233, 1172, 1110, 1049, 1012, 938, 795, 735, 667 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 1.28 (m, 2 H), 1.48 (m, 1 H), 1.66
(m, 2 H), 1.94 (m, 1 H), 1.96 (dd, J = 1.9, 12.1 Hz, 1 H), 1.98 (m,
1 H), 2.00 (s, 3 H), 2.02 (s, 3 H), 2.30 (m, 2 H), 3.58 (d, J = 3.4 Hz,
1 H), 3.72 (dd, J = 2.9, 14.9 Hz, 1 H), 3.76 (dd, J = 3.2, 12.8 Hz,
1 H), 3.88 (dd, J = 3.6, 12.8 Hz, 1 H), 4.14 (dt, J = 3.4, 11.6 Hz, 1
H), 5.40 (d, J = 5.4 Hz, 1 H), 5.89 (d, J = 3.4 Hz, 1 H), 6.34 (s, 1
Figure 3. Competing domino paths: (a) “ring-expansion”; (b) “ox-
onium”; (c) hetero[4π+2π]. Reaction conditions: Pb(OAc)4, MW
60 °C, 10 min in AcOH (for a, b), in PhMe or H2O (for c).
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H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.9, 22.6, 28.9, 31.6,
ppm. 13C NMR (125 MHz, CDCl3): δ = 20.8, 21.5, 22.6, 24.6, 27.1
31.8, 34.5, 46.1, 48.7, 69.3, 70.2, 85.3, 86.2, 92.6, 97.5, 100.5, 169.8, (2 C), 34.1, 35.6, 36.2, 38.2, 45.6, 52.6, 56.8, 67.0, 89.2, 91.1, 168.5,
170.4 ppm. MS (ESI, MeOH + CH2Cl2): m/z (%) = 379.1 (100) [M
+ Na]+. HRMS (ESI, MeOH + CH2Cl2): calcd. for C17H24NaO8
379.1369; found 379.1354. C17H24O8 (356.14): calcd. C 57.30, H
6.79; found C 56.61, H 6.89.
169.0, 176.2, 210.4 ppm. MS (ESI, MeOH): m/z (%) = 455.1 (100)
[M + Na]+. HRMS (ESI): calcd. for C20H39ClNaO8 455.1449;
found 455.1445.
Domino Product 8a: Oxidative cleavage of 5a (50 mg, 0.19 mmol)
by using method B afforded ring-expanded domino product 8a
(44.2 mg, 61%) after flash chromatography (SiO2; heptane/EtOAc,
Domino Product 7: Oxidative cleavage of diols 5b (37 mg,
0.16 mmol) by using method B afforded 7 (37.6 mg, 86%) after
flash chromatography (SiO2; heptane/EtOAc, 4:1). White solid.
4:1). Colourless oil. IR (film): ν = 2931, 2887, 1753, 1715, 1683,
˜
M.p. 132–133 °C (heptane). IR (film): ν = 2932, 2864, 1740, 1452,
˜
1429, 1368, 1217, 1140, 1098, 1056, 1008, 946, 913, 873, 747,
666 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.74 (m, 4 H), 1.76 (dd,
J = 3.1, 14.1 Hz, 1 H), 1.85 (m, 3 H), 1.96 (dd, J = 4.4, 14.6 Hz, 1
H), 2.02 (s, 6 H), 2.08 (dd, J = 5.2, 14.6 Hz, 1 H), 2.50 (dd, J =
4.8, 9.4 Hz, 2 H), 2.92 (d, J = 3.9 Hz, 1 H), 3.74 (m, 2 H), 3.88 (m,
2 H), 4.85 (t, J = 4.7 Hz, 1 H), 6.21 (dd, J = 3.1, 6.4 Hz, 1 H), 6.35
(d, J = 3.8 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 21.0,
21.1, 23.4, 23.8, 34.6, 37.2, 38.2, 41.9, 45.6, 56.7, 64.6, 64.8, 90.1,
91.0, 101.5, 168.7, 169.2, 208.8 ppm. MS (ESI, MeOH): m/z (%) =
393.1 (100) [M + Na]+. HRMS (ESI): calcd. for C18H26NaO8
393.1525; found 393.1518. C18H26O8 (370.16): calcd. C 58.37, H
7.08; found C 54.42, H 6.41.
1368, 1229, 1175, 1056, 994, 967, 932, 905, 751 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 1.41 (td, J = 1.2, 13.0 Hz, 1 H), 1.50 (m,
3 H, 2H6), 1.62 (m, 3 H), 1.96 (dd, J = 3.9, 10.2 Hz, 2 H), 2.02
(dd, J = 5.5, 14.3 Hz, 1 H), 2.08 (dd, J = 6.3, 13.0 Hz, 1 H), 2.12
(s, 3 H), 2.25 (d, J = 14.3 Hz, 1 H), 3.62 (d, J = 2.6 Hz, 1 H), 3.78
(ddd, J = 2.7, 5.5, 12.5 Hz, 1 H), 3.90 (dt, J = 2.7, 12.5 Hz, 1 H),
5.51 (d, J = 5.5 Hz, 1 H), 6.20 (d, J = 2.6 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 20.8, 21.3 (2 C), 29.1, 31.1, 38.4, 38.6, 46.8,
58.9, 78.3, 79.0, 90.6, 97.9, 170.1 ppm. MS (ESI, MeOH): m/z (%)
= 291.1 (100) [M + Na]+. HRMS (ESI): calcd. for C14H20NaO5
291.1208; found 291.1187.
Domino Product 11: Oxidative cleavage of diols 9a (45 mg,
0.12 mmol) by using method B afforded 11 (30 mg, 79%) after flash
chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil. IR
Domino Product 8b: Oxidative cleavage of diols 5d (70 mg,
0.15 mmol) by using method B afforded 8d (71.2 mg, 81%).
Colourless oil. IR (film): ν = 3057, 3022, 2930, 2864, 1754, 1685,
˜
(film): ν = 2955, 2882, 1741, 1481, 1372, 1286, 1240, 1157, 1144,
˜
1596, 1489, 1448, 1368, 1219, 1144, 1102, 1059, 954, 923, 748, 706,
632 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.29 (m, 4 H), 1.55
(dd, J = 6.1, 14.2 Hz, 2 H), 1.66 (d, J = 4.1 Hz, 1 H), 1.71 (m, 4
H), 2.00 (s, 3 H), 2.06 (m, 2 H), 2.08 (s, 3 H), 2.58 (t, J = 4.9 Hz,
2 H), 2.89 (d, J = 3.5 Hz, 1 H), 3.25 (d, J = 6.8 Hz, 1 H), 6.21 (d,
J = 3.2, 5.9 Hz, 1 H), 6.41 (d, J = 4.1 Hz, 1 H), 7.30 (m, 9 H), 7.45
(m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.1 (2 C), 23.2,
23.8, 35.2, 36.8, 37.7, 38.1, 45.6, 57.4, 59.2, 87.2, 89.9, 90.8, 127.1
(3 C), 127.8 (6 C), 128.5 (6 C), 143.9 (3 C), 168.7, 169.0, 208.9 ppm.
MS (ESI; MeOH + CH2Cl2): m/z (%) = 593.2 (100) [M + Na]+.
HRMS (ESI, MeOH + CH2Cl2): calcd. for C35H38NaO7 593.2515;
found 593.2503. C35H38O7 (570.26): calcd. C 73.66, H 6.71; found
C 70.14, H 6.52.
1069, 1020, 973, 958, 937, 771, 729 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 1.50 (ddd, J = 4.8, 5.3, 10.1 Hz, 1 H), 1.62 (m, 2 H),
1.70 (m, 2 H), 1.81 (d, J = 13.6 Hz, 1 H), 2.02 (s, 3 H), 2.19 (td, J
= 3.8, 14.4 Hz, 1 H), 2.66 (dd, J = 4.8, 13.6 Hz, 1 H), 3.78 (s, 1
H), 3.88 (m, 4 H), 3.95 and 4.05 (ABq, J = 9.2 Hz, 2 H), 5.50 (d,
J = 4.8 Hz, 1 H), 5.88 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 18.3, 21.3, 29.9, 30.6, 42.4, 55.9, 64.4, 64.9, 74.8, 83.3, 90.4,
91.0, 98.9, 109.1, 170.0 ppm. MS (ESI, MeOH + CH2Cl2): m/z (%)
= 335.1 (100) [M + Na]+. HRMS (ESI): calcd. for C15H20NaO7
335.1107; found 335.1082. C15H20O7 (312.12): calcd. C 57.69, H
6.45; found C 56.79, H 6.61.
Domino Product 14: Oxidative cleavage of diols 12a (38 mg,
0.13 mmol) by using method B afforded 14 (24 mg, 55%) and 13a
Domino Product 8f: Oxidative cleavage of diols 5f (45 mg,
0.14 mmol) by using method B afforded 8f (43.6 mg, 71%). Colour-
(10.3 mg, 27%). Data for 14: Colourless oil. IR (film): ν = 2948,
˜
2928, 2888, 1740, 1439, 1370, 1289, 1240, 1150, 1083, 1060, 1042,
1012, 966, 950, 853, 753, 722, 667 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 1.55 (d, J = 14.7 Hz, 1 H), 1.62 (m, 1 H, H1), 1.82
(dt, J = 3.8, 13.7 Hz, 1 H), 2.00 (m, 2 H), 2.09 (s, 3 H), 2.16 (d, J
= 2.7 Hz, 2 H), 2.36 (td, J = 3.5, 14.7 Hz, 1 H), 3.80 (m, 1 H), 3.92
(m, 4 H), 3.82 and 4.10 (ABq, J = 8.6 Hz, 2 H), 5.55 (t, J = 2.7 Hz,
1 H), 5.98 (d, J = 1.1 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 21.4, 29.1, 29.5, 39.0, 49.4, 51.6, 64.1, 64.5, 75.0, 81.9, 86.2,
90.7, 98.5, 108.0, 169.9 ppm. MS (ESI, MeOH + CH2Cl2): m/z (%)
= 335.1 (100) [M + Na]+. HRMS (ESI): calcd. for C15H20NaO7
335.1107; found 335.1133. C15H20O7 (312.12): calcd. C 57.69, H
6.45; found C 56.14, H 6.33.
less oil. IR (film): ν = 2978, 2936, 1732, 1630, 1367, 1303, 1243,
˜
1214, 1177, 1122, 1141, 1003, 940, 728 cm–1. 1H NMR (300 MHz):
δ = 1.63 (m, 2 H), 1.80 (dd, J = 6.0, 14.3 Hz, 1 H), 1.88 (m, 3 H),
1.92 (m, 2 H), 2.07 (s, 2 H), 2.08 (s, 3 H), 2.22 (q, J = 6.5 Hz, 2
H), 2.59 (m, 2 H), 2.91 (d, J = 3.7 Hz, 1 H), 4.43 (m, 2 H), 6.31
(dd, J = 3.4, 5.7 Hz, 1 H), 6.43 (d, J = 4.2 Hz, 1 H), 7.45 (td, J =
1.2, 7.4 Hz, 2 H), 7.57 (m, 1 H), 8.0 (m, 2 H) ppm. 13C NMR
(125 MHz): δ = 21.1 (2 C), 23.2, 23.9, 35.2, 36.6, 36.8, 37.4, 45.5,
57.5, 60.4, 89.8, 90.6, 128.5 (2 C), 129.5 (2 C), 129.9, 133.2, 166.4,
168.7, 169.1, 208.4 ppm. MS (ESI, MeOH): m/z (%) = 455.1 (100)
[M + Na]+. HRMS (ESI): calcd. for C23H28NaO8 455.1682; found
455.1679. C23H28O8 (432.17): calcd. C 63.88, H 6.53; found C
55.67, H 5.51.
Microwave-Assisted Domino Transformations in AcOH following the
Ring-Expansion Path
Domino Product 8g: Oxidative cleavage of diols 5g (26 mg,
0.09 mmol) by using method B afforded 8g (29.7 mg, 81%).
Domino Product 4k: Oxidative cleavage of diols 1k (50 mg,
0.16 mmol) by using method B afforded 4k (41 mg, 60%) and 2k
(9 mg, 18%; the intermediate half-cascade product). Data for 4k:
Colourless oil. IR (film): ν = 2931, 2864, 2828, 1749, 1683, 1450,
˜
1370, 1219, 1190, 1126, 1056, 1008, 956, 923 cm–1. 1H NMR
Colourless oil. IR (film): ν = 2955, 2932, 1750, 1723, 1370, 1226,
(500 MHz, CDCl3): δ = 1.59 (ddd, J = 3.7, 10.7 Hz, 1 H), 1.70 (dd,
˜
1
1146, 1051, 918, 742 cm–1. H NMR (500 MHz, CDCl3): δ = 1.22 J = 6.1, 14.2 Hz, 2 H), 1.80 (d, J = 3.4 Hz, 1 H,), 1.85 (m, 4 H),
(s, 6 H), 1.65 (m, 3 H), 1.82 (dd, J = 3.5, 14.5 Hz, 2 H), 1.95 (m, 2.07 (s, 3 H), 2.08 (s, 3 H), 2.11 (m, 2 H), 2.55 (m, 2 H), 2.84 (d, J
3 H), 2.05 (s, 3 H), 2.07 (s, 3 H), 2.57 (dd, J = 4.8, 10.0 Hz, 2 H), = 3.8 Hz, 1 H), 3.43 (s, 3 H), 4.00 (ABq, 2 H), 4.26 (dt, J = 2.4,
2.88 (d, J = 3.6 Hz, 1 H), 3.92 (s, 2 H), 4.23 and 4.36 (ABq, J =
11.2 Hz, 2 H), 6.22 (t, J = 3.9 Hz, 1 H), 6.38 (d, J = 3.6 Hz, 1 H)
7.3 Hz, 2 H), 6.27 (dd, J = 3.2, 6.0 Hz, 1 H), 6.38 (d, J = 3.8 Hz,
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 21.1 (2 C), 23.2, 23.8,
2692
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2687–2694

Microwave-Assisted Competing Domino Processes in the Octaline Diol Series
35.1, 36.6 (2 C), 37.5, 45.6, 57.3, 59.4, 60.3, 69.8, 89.7, 90.6, 168.7,
169.1, 170.1, 208.4 ppm. MS (ESI, MeOH): m/z (%) = 423.1 (100)
[M + Na]+. HRMS (ESI): calcd. for C19H28NaO9 423.1631; found
423.1633. C19H28O9 (400.17): calcd. C 56.99, H 7.05; found C
60.13, H 7.66.
MeOH): m/z (%) = 339.2 (100) [M + Na]+. HRMS (ESI): calcd.
for C19H24NaO4 339.1572; found 339.1578.
Domino Product 2n: Oxidative cleavage of 1n (31 mg, 0.10 mmol)
by using method E afforded 2n (18.5 mg, 60%) after flash
chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil. IR
(film): ν = 2932, 2856, 1731, 1628, 1449, 1215, 1178, 1057,
˜
Domino Product 8i: Oxidative cleavage of diols 5i (40 mg,
0.14 mmol) by using method B afforded 8i (41.3 mg, 73%) after
flash chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil.
1
939 cm–1. H NMR (300 MHz): δ = 1.32 (m, 3 H), 1.36 (m, 3 H),
1.53 (m, 3 H), 1.70 (m, 3 H), 1.84 (m, 2 H), 1.97 (m, 2 H), 2.15 (d,
J = 14.0 Hz, 1 H), 2.27 (tt, J = 3.5, 11.0 Hz, 1 H), 4.18 (q, J =
11.2 Hz, 2 H), 4.72 (d, J = 6.2 Hz, 1 H), 5.64 (d, J = 5.5 Hz, 1 H),
6.17 (d, J = 6.2 Hz, 1 H) ppm. 13C NMR (75 MHz): δ = 20.7, 21.2,
29.3, 29.7, 31.7, 48.7, 51.7, 68.3, 73.8, 82.3, 99.4, 110.0, 127.5,
128.4, 138.4, 139.4 ppm. MS (ESI, MeOH): m/z (%) = 329.1 (100)
[M + Na]+. HRMS (ESI): calcd. for C18H26NaO3 329.1729; found
329.1720.
IR (film): ν = 2928, 2862, 1758, 1725, 1671, 1579, 1446, 1400, 1370,
˜
1262, 1210, 1194, 1172, 1045, 1017, 990, 884, 870, 834, 772,
1
745 cm–1. H NMR (500 MHz): δ = 0.78 (m, 3 H), 0.90 (m, 3 H),
1.51 (dq, J = 4.3, 7.8 Hz, 2 H), 1.69 (d, J = 6.0 Hz, 2 H), 1.73 (d,
J = 3.4 Hz, 2 H), 1.77 (m, 3 H), 2.00 (s, 3 H), 2.01 (s, 3 H), 2.50
(m, 2 H), 2.80 (d, J = 3.9 Hz, 1 H), 4.10 (m, 2 H), 6.21 (dd, J =
3.4, 6.0 Hz, 1 H), 6.33 (d, J = 3.8 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 8.5 (2 C), 12.7, 21.1 (2 C), 23.2, 23.8, 35.1,
36.6, 36.8, 37.5, 45.5, 57.4, 59.9, 89.8, 90.7, 168.7, 169.1, 174.7,
208.5 ppm. MS (ESI, MeOH): m/z (%) = 419.2 (100) [M + Na]+.
HRMS (ESI): calcd. for C20H28NaO8 419.1682; found 419.1702.
C20H28O8 (396.18): calcd. C 60.59, H 7.12; found C 60.19, H 7.03.
Domino Product 6a: Oxidative cleavage of 5a (30 mg, 0.12 mmol)
by using method E afforded 6a (14.8 mg, 50%) after flash
chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil. IR
(film): ν = 2934, 1629, 1212, 1058, 1024, 928, 792, 782, 722 cm–1.
˜
1H NMR (500 MHz, CDCl3): δ = 1.20 (m, 1 H), 1.40 (m, 3 H),
1.48, (m, 2 H), 1.63 (td, J = 3.1, 13.5 Hz, 1 H), 1.82 (dd, J = 4.6,
14.2 Hz, 1 H), 1.91 (dd, J = 5.6, 13.9 Hz, 3 H), 2.19 (d, J = 14.1 Hz,
1 H), 3.76 (m, 2 H), 3.90 (m, 2 H), 4.68 (d, J = 6.1 Hz, 1 H), 4.79
(t, J = 5.0 Hz, 1 H), 5.60 (d, J = 5.7 Hz, 1 H), 6.11 (d, J = 6.1 Hz,
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.6, 21.1, 29.3, 32.1,
34.1, 48.1, 50.0, 64.5, 64.6, 82.1, 90.5, 100.0, 109.8, 139.6 ppm.
C14H20O4 (252.13): calcd. C 66.65, H 7.99; found C 66.19, H 7.65.
Domino Product 17a: Oxidative cleavage of diols 15a (25 mg,
0.13 mmol) by using method B afforded 17a (26 mg, 67%). Colour-
less oil. IR (film): ν = 2932, 2860, 2360, 1755, 1690, 1371, 1222,
˜
1
1050, 956, 925 cm–1. H NMR (500 MHz, CDCl3): δ = 1.46–1.54
(m, 2 H), 1.71–1.83 (m, 4 H), 1.92 (dd, J = 13.9, 2.7 Hz, 1 H), 2.04
(s, 3 H), 2.08 (s, 3 H), 2.12–2.15 (m, 1 H), 2.50 (ddd, J = 3.2, 6.4,
13.8 Hz, 1 H), 2.63 (ddd, J = 3.6, 12.2, 13.5 Hz, 1 H), 3.23 (d, J =
3.8 Hz, 1 H), 5.08 (d, J = 17.7 Hz, 1 H), 5.25 (d, J = 11.1 Hz, 1
H), 5.84 (dd, J = 11.0, 17.7 Hz, 1 H), 6.23 (dd, J = 2.6, 6.7 Hz, 1
H), 6.55 (d, J = 3.8 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 21.0, 21.1, 23.9, 24.2, 38.3, 38.6, 41.7, 45.2, 53.5, 89.9, 91.4,
113.2, 145.3, 168.7, 169.2, 209.0 ppm. MS (ESI, MeOH): m/z (%)
= 333.1 (100) [M + Na]+. HRMS (ESI, MeOH + CH2Cl2): calcd.
for C16H22NaO6 333.1314; found 333.1315.
Domino Product 6j: Oxidative cleavage of 5j (45 mg, 0.14 mmol) by
using method E afforded 6j (28.2 mg, 63%) after flash chromatog-
raphy (SiO ; heptane/EtOAc, 4:1). Colourless oil. IR (film): ν =
˜
2
2932, 2857, 1729, 1630, 1451, 1246, 1212, 1172, 1058, 943, 793,
1
722 cm–1. H NMR (300 MHz): δ = 1.24 (m, 3 H), 1.38 (m, 3 H),
1.53 (m, 3 H), 1.766 (m, 3 H), 1.76 (m, 3 H), 1.90 (m, 3 H), 1.96
(m, 3 H), 2.13 (dd, J = 1.0, 13.8 Hz, 1 H), 2.26 (tt, J = 3.6, 11.2 Hz,
1 H), 4.02 (dt, J = 7.4, 11.0 Hz, 1 H), 4.14 (ddd, J = 5.8, 7.9,
11.0 Hz, 1 H), 4.74 (d, J = 6.0 Hz, 1 H), 5.66 (d, J = 5.5 Hz, 1 H),
6.17 (d, J = 6.0 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
20.7, 21.1, 25.4, 25.7, 28.7, 29.0, 29.2, 31.6, 43.2, 48.6, 51.6, 62.1,
82.2, 99.4, 109.8, 139.6, 176.1 ppm. MS (ESI, MeOH): m/z (%) =
343.2 (100) [M + Na]+. HRMS (ESI): calcd. for C19H28NaO4
343.1885; found 343.1869.
Domino Product 17b: Oxidative cleavage of diols 15b (27 mg,
0.10 mmol) by using method B afforded 17b (24 mg, 62%). Colour-
less oil. IR (film): ν = 1754, 1713, 1445, 1368, 1224, 1196, 1098,
˜
992, 923 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.31 (t, J =
7.2 Hz, 3 H), 1.49 (m, 1 H), 1.67 (m, 1 H), 1.76–1.86 (m, 2 H),
1.86–1.99 (m, 2 H), 1.99–2.14 (m, 2 H), 2.02 (s, 3 H), 2.09 (s, 3 H),
2.54 (t, J = 5.0 Hz, 2 H), 3.29 (d, J = 3.4 Hz, 1 H), 4.23 (q, J =
7.25 Hz, 2 H), 5.89 (d, J = 16.4 Hz, 1 H), 6.25 (q, J = 2.5 Hz, 1
H), 6.50 (d, J = 3.4 Hz, 1 H), 7.00 (d, J = 16.4 Hz, 1 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 14.2, 20.9, 21.0, 23.7, 24.3, 38.3,
38.6, 40.3, 45.0, 53.3, 60.8, 90.0, 90.1, 119.4, 154.4, 166.1, 168.7,
169.0, 207.7 ppm. MS (ESI, MeOH + CH2Cl2): m/z (%) = 405.1
(100) [M + Na]+. HRMS (ESI): calcd. for C19H26NaO8 405.1525;
found 405.1515.
Domino Product 10c: Oxidative cleavage of 9c (30 mg, 0.10 mmol)
by using method E afforded 10c (20.9 mg, 70%) after flash
chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil. IR
(film): ν = 2928, 2883, 1627, 1465, 1440, 1388, 1346, 1311, 1291,
˜
1255, 1241, 1197, 1148, 1106, 1088, 1037, 945, 925, 881, 817,
1
774 cm–1. H NMR (500 MHz, CDCl3): δ = 1.59 (d, J = 13.8 Hz,
1 H, H1), 1.70 (m, 3 H), 1.82 (m, 2 H), 2.01 (dd, J = 3.5, 12.4 Hz,
1 H), 2.40 (dd, J = 5.8, 13.8 Hz, 1 H), 3.36 (s, 3 H), 3.83 and 4.02
(ABq, J = 9.4 Hz, 2 H), 3.90 (m, 4 H), 4.58 (q, J = 6.1 Hz, 2 H),
4.92 (d, J = 6.1 Hz, 1 H), 5.60 (d, J = 5.7 Hz, 1 H), 6.23 (d, J =
6.1 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 18.2, 30.4,
31.3, 41.6, 55.5, 60.6, 63.6, 65.1, 70.5, 84.2, 96.7, 99.7, 109.5, 110.4,
140.6 ppm. MS (ESI, MeOH + CH2Cl2): m/z (%) = 321.1 (100)
[M + Na]+. HRMS (ESI): calcd. for C15H22NaO6 321.1314; found
321.1332. C15H22O6 (298.14): calcd. C 60.39, H 7.43; found C
60.92, H 7.44.
Microwave-Assisted Domino Transformations in Water following the
Hetero[4π+2π] Path
Domino Product 2g: Oxidative cleavage of diols 1g (35 mg,
0.11 mmol) by using method E afforded 2g (18.5 mg, 53%) after
flash chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil.
IR (film): ν = 2930, 2860, 1622, 1454, 1378, 1202, 1108, 1021, 981,
˜
1
799, 780, 730, 695 cm–1. H NMR (300 MHz): δ = 1.32 (m, 2 H),
1.40 (m, 2 H), 1.44 (m, 2 H), 1.82 (ddd, J = 5.5, 8.4, 12.8 Hz, 1
H), 1.92 (m, 1 H), 1.97 (m, 1 H), 2.15 (m, 1 H), 3.55 (m, 1 H), 3.66
(m, 1 H), 4.60 (s, 2 H), 4.76 (m, 2 H), 5.62 (d, J = 5.7 Hz, 1 H),
Domino Product 10d: Oxidative cleavage of diols 9d (30 mg,
0.09 mmol) by using method E afforded 10d (23 mg, 77%) after
6.20 (d, J = 6.3 Hz, 1 H), 7.30 (m, 5 H) ppm. 13C NMR (125 MHz): flash chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil.
δ = 20.2, 21.2, 29.3, 29.6, 48.3, 51.0, 65.8, 69.8, 82.1, 94.2, 99.2,
IR (film): ν = 2959, 2930, 2873, 1725, 1626, 1479, 1460, 1396, 1363,
˜
110.4, 127.1, 127.3 (2 C), 128.4 (2 C), 137.9, 139.8 ppm. MS (ESI,
1280, 1197, 1142, 1114, 1089, 1032, 966, 945, 928, 879, 803, 752,
Eur. J. Org. Chem. 2009, 2687–2694
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2693

S. Arseniyadis et al.
FULL PAPER
725 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.22 (s, 9 H), 1.68 (dt,
J = 4.0, 13.4 Hz, 2 H), 1.73 (d, J = 13.9 Hz, 2 H), 1.84 (m, 2 H),
2.05 (m, 1 H), 2.48 (dd, J = 5.8, 13.9 Hz, 1 H), 3.90 (m, 2 H), 4.00
(m, 2 H), 4.36 and 4.56 (ABq, J = 11.3 Hz, 2 H), 4.79 (d, J =
6.1 Hz, 1 H), 5.64 (d, J = 5.7 Hz, 1 H), 6.23 (d, J = 6.1 Hz, 1 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 18.0, 27.3 (3 C), 30.1, 31.0,
38.6, 41.8, 59.9, 63.6, 65.1, 67.2, 83.6, 99.6, 108.8, 109.7, 141.0,
177.8 ppm. MS (ESI, MeOH + CH2Cl2): m/z (%) = 361.2 (100)
[M + Na]+. HRMS (ESI): calcd. C18H26NaO6Si 361.1227; found
361.1612.
Lett. 2000, 2, 1609–1611; c) P. A. Wender, M. Fuji, C. O. Hus-
feld, J. A. Love, Org. Lett. 1999, 1, 137–139; d) P. A. Wender,
C. O. Husfeld, E. Langkopf, J. A. Love, N. Pleuss, Tetrahedron
1998, 54, 7203–7220; e) P. A. Wender, H. Rieck, M. Fuji, J.
Am. Chem. Soc. 1998, 120, 10976–10977; f) Y. Coquerel, M. H.
Filippini, D. Bensa, J. Rodriguez, Chem. Eur. J. 2008, 14, 3078–
3092 and references cited therein; B. L. Ashfeld, K. A. Miller,
A. J. Smith, K. Tran, S. F. Martin, J. Org. Chem. 2007, 72,
9018–9031.
[4] For reviews on the use of microwaves in organic synthesis, see:
a) A. de la Hoz, A. Diaz-Ortis, A. Moreno, F. Langa, Eur. J.
Org. Chem. 2000, 3659–3673; b) C. O. Kappe, A. Stadler, Mi-
crowaves in Organic and Medicinal Chemistry Wiley-VCH,
Weinheim, 2005; c) C. O. Kappe, D. Dallinger, Drug Discovery
2006, 5, 51–63.
[5] a) L. F. Tietze, U. Beifuss, Angew. Chem. 1993, 105, 137–170;
Angew. Chem. Int. Ed. Engl. 1993, 32, 131–163; b) L. F. Tietze,
Chem. Rev. 1996, 96, 115–136; c) L. F. Tietze, A. Modi, Med.
Res. Rev. 2000, 20, 304–322; d) L. F. Tietze, F. Haunert in Stim-
ulating Concepts in Chemistry (Eds.: M. Shibasaki, J. F. Stod-
dart, F. Vogtle), Wiley-VCH, Weinheim, 2000, pp. 39–64; e)
L. F. Tietze, G. Brasche, K. M. Gericke, Domino Reactions in
Organic Synthesis, Wiley-VCH, 2006 ISBN: 3-527-29060-5.
[6] For comparison, in the hydrindene diol series, these results
were unchanged by substituting toluene for the more polar sol-
vent acetic acid.
Domino Product 13a: Oxidative cleavage of 12a (50 mg, 0.17 mmol)
by using method E afforded 13a (42 mg, 65%) after flash
chromatography (SiO2; heptane/EtOAc, 4:1). Colourless oil. IR
(film): ν = 2957, 2928, 2884, 1737, 1630, 1439, 1367, 1237, 1092,
˜
1
1047, 996, 978, 944, 851, 771 cm–1. H NMR (500 MHz, CDCl3):
δ = 1.56 (m, 2 H), 1.74 (dd, J = 4.2, 14.2 Hz, 1 H), 1.92 (dd, J =
3.2, 13.7 Hz, 2 H), 2.03 (m, 2 H), 2.07 (s, 3 H), 2.22 (d, J = 14.2 Hz,
1 H), 3.92 (m, 4 H), 4.30 and 4.41 (ABq, J = 10.6 Hz, 2 H), 4.78
(d, J = 6.1 Hz, 1 H), 5.72 (d, J = 5.5 Hz, 1 H), 6.23 (d, J = 6.1 Hz,
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.9, 27.9, 29.0, 37.7,
48.6, 55.1, 63.8, 64.5, 66.1, 79.8, 99.3, 107.7, 107.8, 140.5,
171.0 ppm. MS (ESI, MeOH + CH2Cl2): m/z (%) = 319.1 (100)
[M + Na]+. HRMS (ESI): calcd. for C15H20NaO6 319.1158; found
335.1147. C15H20O6 (296.12): calcd. C 60.80, H 6.80; found C
58.87, H 6.61.
[7] Either Pb(OAc)4 or PhI(OAc)2 could be used as the domino
promoters.
[8] Water rapidly hydrolyzes Pb(OAc)4 to give PbO2 and AcOH.
For articles dealing with specific aspects of organolead chemis-
try, see: a) R. Criegee in Oxidation In Organic Chemistry (Eds.:
K. B. Wiberg), Academic Press, New York, 1965, part A, pp.
277–366; b) G. M. Rubottom in Oxidation In Organic Chemis-
try (Eds.: W. H. Trahanovsky), Academic Press, London, 1982,
vol. D, ch. 1; c) M. G. Moloney, Main Group Met. Chem. 2001,
24, 653–660.
[9] In the absence of microwave irradiation, the use of water as
solvent gives a messy reaction mixture containing 2 and 6,
along with starting diols and unidentified products.
[10] Ö. Sesenoglu, J. I. Candela Lena, E. Altinel, N. Birlirakis, S.
Arseniyadis, Tetrahedron: Asymmetry 2005, 16, 995–1015.
[11] All reactions were performed on racemic series; only one anti-
pode is represented. The stereochemistry of the diol had no
effect on the reaction, as demonstrated by control experiments
where substrates with cis diols performed identically to sub-
strates with trans diols. Ultrasonic conditions were probed for
their likely helpful advantages, but to no benefit.
[12] A. Chanu, I. Safir, R. Basak, A. Chiaroni, S. Arseniyadis, Org.
Lett. 2007, 9, 1351–1354.
[13] The stereochemistry at the secondary hydroxy groups at C2
and C3 is not important, as it is destroyed in the generation of
[4π+2π] template i (Figure 1).
[14] The low yields obtained in these reactions could be explained
by the fact that the likely domino products from the epimeric
contribution are sensitive to the workup and chromatographic
conditions used.
CCDC-708533 (for 8e) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information (see footnote on the first page of this arti-
cle): Procedures for the synthesis and characterization; 1D and 2D
1H and 13C NMR spectra for all new compounds.
Acknowledgments
Financial support from the CNRS (Centre National de la Recher-
che Scientifique) and fellowship awards from the ICSN (Institut de
Chimie des Substances Naturelles) are gratefully acknowledged.
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[15] That clearly means that oxidative cleavage under microwave
irradiation is faster than hydrolysis of the reagent.
[16] For entropic and enthalpic factors during the formation of me-
dium-sized rings, see: G. Illuminati, L. Mandolini, Acc. Chem.
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[3] For routes to gain synthetic entry into cycloheptanes as syn-
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Received: March 6, 2009
Published Online: April 16, 2009
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