A practical synthetic route to functionalized THBCs and oxygenated analogues via intramolecular Friedel-Crafts reactions

Article abstract of DOI:10.1039/b607864h

A practical catalytic approach to the synthesis of 4-substituted 1,2,3,4-tetrahydro-β-carbolines (THBCs, 1) and 1,2,3,9-tetrahydropyrano[3, 4-b]indoles (2) via InBr₃-catalyzed intramolecular Friedel-Crafts (F-C) cyclization is described. The us

Full text of DOI:10.1039/b607864h

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A practical synthetic route to functionalized THBCs and oxygenated
analogues via intramolecular Friedel–Crafts reactions†
Marco Angeli, Marco Bandini,* Andrea Garelli, Fabio Piccinelli, Simona Tommasi and Achille Umani-Ronchi*
Received 2nd June 2006, Accepted 5th July 2006
First published as an Advance Article on the web 26th July 2006
DOI: 10.1039/b607864h
A practical catalytic approach to the synthesis of 4-substituted 1,2,3,4-tetrahydro-b-carbolines
(THBCs, 1) and 1,2,3,9-tetrahydropyrano[3,4-b]indoles (2) via InBr3-catalyzed intramolecular
Friedel–Crafts (F–C) cyclization is described. The use of cross-metathesis reaction represents a direct
route to the cyclization precursors and the use of InBr3 (5 mol%) allowed polycyclic indole compounds
to be isolated in high yields under mild reaction conditions (rt, DCM, minutes). Finally, efforts toward
the development of a stereocontrolled version of the present cyclization are presented, highlighting
[salenAlCl] and bimetallic [(salenAlCl)2–InBr3] system as promising chiral Lewis acids (ee up to 60%).
The indole core is embedded in countless natural products showing
potent agrochemical and pharmacological activities.1 Among this
plethora of compounds, polycyclic chiral and achiral systems are
characterized by wide occurrence and primary roles in natural
products, and continue to inspire synthetic chemists in developing
practical, effective and environmentally benign protocols for
their preparation.2 In this regard, polyfunctionalized 1,2,3,4-
tetrahydro-b-carbolines (THBCs, 1),3 1,2,3,9-tetrahydropyrano-
[3,4-b]indoles (2)4 and more complex cyclic systems, embody L-
tryptophan as well as tryptamine motifs, proven to possess a
wide diversity of important medicinal activities such as anti-
tumoral and5 cardiovascular effects,6 and as treatments for allergic
rhinitis and asthma.7 As a result, considerable efforts have been
Fig. 1 Comparison of the P–S approach (path a) and intramolec-
ular F–C-type alkylation (path b) for the synthesis of polycyclic in-
dole-containing compounds.
devoted toward the development of new, efficient intramolecular
alkylations of indoles via activated as well as inactivated olefins.8,9
The most famous synthetic approach for the construction of the
1-type polycyclic systems is represented by the Pictet–Spengler
reported on the effectiveness of InBr3 as a Lewis acid in promoting
intramolecular F–C-type Michael conjugate addition of indole
(P–S) reaction (path a, Fig. 1).10
to enones.15 Such a protocol allowed racemic 4-functionalized
THBCs and oxygenated analogues 2 to be isolated in excellent
yields under mild conditions (low catalyst loading, aqueous
media).
In the present contribution, we will document a full account
of this investigation by updating and shortening the synthetic
protocol for the polycyclic precursors 8/12. Then, a stereocon-
trolled version of the present cyclization by using [salenAlCl] and
unprecedented bimetallic [(salenAlCl)2–InBr3] will be presented.
This biosynthetic protocol, initially documented as a valuable
route to the synthesis of tetrahydroisoquinolines, was also suc-
cessfully applied to THBCs by condensing various functionalized
tryptamines and carbonylic compounds under acidic (Brønsted
or Lewis) conditions. However, some intrinsic limitations of P–
S procedures, namely the requirement of harsh conditions and
a restricted applicability to the synthesis of biologically active 4-
substituted-THBCs (in this case time-demanding protocols for the
preparation of b-substituted tryptamine precursors are needed),
call for the development of new and milder complementary
protocols for the synthesis of polycyclic indole compounds.
Synthetic alternatives to the P–S reaction have been recently
proposed by us11 and other groups,12 (path b) involving a rational
intramolecular alkylation of indoles at the C-3 position.
Results and discussion
Multi-step synthesis optimization
As a part of our research area addressed to the catalytic Friedel–
Crafts-type (F–C)13 functionalization of indoles,14 we recently
THBC precursors. In order to develop a practical catalytic
protocol for the construction of large libraries of polycyclic
compounds, we firstly pointed our attention toward an optimal
synthetic sequence for the corresponding precursors.
Consequently, although our previously reported syntheses of
indolyl enones 5 proved to be general in scope (Scheme 1a),
they showed some limitations in applicability. In particular,
the subsequent double oxidative steps followed by the Wittig
Dipartimento di Chimica “G. Ciamician”, Universita` di Bologna, via
Selmi 2, 40126, Bologna, Italy. E-mail: marco.bandini@unibo.it, achille.
umanironchi@unibo.it; Fax: +39-051-2099456
† Electronic supplementary information (ESI) available: Typical proce-
dures for the synthesis of unknown compounds and for the asymmetric
transformations are reported. See DOI: 10.1039/b607864h
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Scheme 1 CM reaction as an alternative to the three-steps synthesis of THBC precursors. Reagents and conditions: (i) allyl amine, MgSO4, DCM;
=
(ii) NaBH4, MeOH; (iii) (Boc)2O (3 eq.), TEA, DCM; (iv) K2Os2O2(OH)4, DABCO, K3Fe(CN)6, K2CO3; (v) NaIO4, SiO2, DCM; (vi) RCOCH PPh3,
toluene; (vii) (Boc)2O (1.0 eq.), TEA, DCM; (viii) 7a, Grubbs’ II, DCM, 40 ◦C.
Table 1 Synthesis of indolyl enones 8 by cross-metathesis reactiona
reaction (4 → 5) suffered from poor reproducibility, involving
scarcely-stable indolyl aldehydes to be handled and requiring time-
consuming purification procedures.
To overcome some of these obstacles and to speed up the
entire process, we considered the olefin cross-metathesis (CM)
reaction as a markedly shorter synthetic route.16 In particular, CM
between mono-protected indole 617 and terminal a,b-unsaturated
ketones would provide directly indolyl enones type 8. In fact,
despite the low tendency of a,b-unsaturated ketones to take part
=
in metathesis coupling, the use of electron-deficient C C double
bonds in metallocarbene promoted cross-metathesis has been
already fully documented.18 Among all the catalysts tested, the use
Entry
Indole
7
Productb
Yield (%)c
of a ruthenium–carbene complex, bearing the 1,3-dimesityl-4,5-
dihydroimidazol-2-ylidene ligand (Grubbs’ II generation catalyst),
yielded 8aa in a stereochemically defined manner (E : Z > 50 : 1,
65% isolated yield), and without the need for protection of the NH
group (Scheme 1b). Here, a range of polycyclic indole precursors 8
were synthesized with a definite trans double bond configuration,
by varying both the protecting group on the amine nitrogen (R)
and the substituent directly bound to the carbonyl moiety (Rꢀ).
From the data reported in Table 1, several conclusions can be
drawn. Despite the highly coordinating character of 6, they proved
to be suitable partners for ruthenium based CM by furnishing 8
in moderate to good yields, and in the case of low conversions,
discrete amounts of unreacted starting indolyl derivatives were
recovered. Moreover, moderate yield was also obtained with
phenylvinylketone (PVK) 7b19 (8ab, 38%, entry 6).
1
2
3
4
5
6
6b
6c
6d
6e
7a
7a
7a
7a
7a
7b
8ba
8ca
8da
8ea
8fa
8ab
34 (41)
50 (10)
41 (20)
Traces
(
)-6f
Traces (30)d
38 (45)
6a
a All the reactions were carried out in degassed anhydrous CH2Cl2 (40 ◦C,
16 h) under a nitrogen atmosphere. b Isolated as the single E isomer
(determined by 1H NMR). c Isolated yields after flash chromatography. In
brackets is the amount of starting material (6) recovered after purification.
d See Scheme 2.
The substitution of the aminic nitrogen in the side chain by
electron-withdrawing moieties was necessary in order to avoid
poisoning of the ruthenium catalyst. For instance, when indole-
containing tertiary allylic aminic groups in the side chain (6e) were
employed, the desired 8ea was obtained only in traces (entry 4).
Here, even the employment of Ti(OiPr)4 as an additive20 did not
lead to any appreciable improvement.
Interestingly, the presence of phenyl groups in proximity of the
CM site (tethering chain, 6f) was detrimental for the ruthenium
mediated process. In this case in fact, the coupling mainly
furnished the saturated indolyl ketone 9 (Scheme 2). The formation
Scheme 2 Reagents and conditions: (i) 7a, Grubb’s II, CH2Cl2, 40 ◦C.
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Table 2 In(III)Br catalyzed intramolecular F–Ca
of the by-product calls for the presence in solution of ruthenium
hydrido species responsible for the initial isomerization of ( )-6f,
which could successively couple with MVK producing 6f, finally
reduced to 9.21
To date, the influence of proximal aromatic rings on the reaction
outcome is still unclear. However, we can speculate that this
particular molecular framework might account for an accelerated
decomposition in solution of the Grubbs’ catalyst leading to [Ru]-
H species or dinuclear ruthenium complexes.22
Entry
Starting
X/Y/R/Rꢀ
Product
Yield (%)b
c
1
2
3
4
5
6
7
8
9
8aa
8aa
8ab
8ba
8ca
8da
12a
12b
12c
H/N-Boc/H/Me
H/N-Boc/H/Me
H/N-Boc/H/Ph
H/N-Cbz/H/Me
H/NCO2Me/H/Me
H/NCOCF3/H/Me
H/O/Me/Me
1aa
1aa
1ab
1ba
1ca
1da
2a
—
Tetrahydropyranoindole precursors
90
95
95
95
70
98
91
98
The oxygenated THBC analogous 1,2,3,9-tetrahydropyrano-[3,4-
b]indoles 2 have been categorized as belonging to potent analgesic
families and some 1-acetic acid derivatives were successfully tested
as anti-inflammatory agents as well. Despite the well recognized
and diversified pharmacological activities, only very few routes
to their synthesis have been reported to date.4 Our previous
study permitted the synthesis of N-methylated indolyl enone (12a)
starting from the corresponding allyl ether 10a in 29% overall yield.
Also in this case, the improvement in terms of time and chemical
yields guaranteed by the use of CM was evident. In particular,
the optimal CM in comparison to the former pathway [(i), (ii),
Scheme 3]15 furnished 12a, 12b and 12c as the single E isomers in
72, 39 and 42% yield, respectively.
H/O/Me/Ph
Cl/O/Me/Me
2b
2c
a All the reactions were carried out in anhydrous CH2Cl2. b Isolated yields
after flash chromatography. c In absence of InBr3, reaction time 48 h.
processes. Additionally, the strength of the promoting agent is a
crucial issue which must be carefully addressed.
In this context, we recently reported the use of InBr3 (10 mol%)
as a powerful activator for the intramolecular Michael-type
addition of N,Nꢀ-diBoc-indolyl enones and N–Me–O-indole
enones to give 4-substituted tetrahydro-b-carbolines 1 and 4-
substituted tetrahydro-b-pyranoindoles 2, respectively.15 In this
paper, we verified the generality in scope and applicability of the
indium-catalyzed F–C protocol by extending the intramolecular
alkylation also to N-(1)H indolyl derivatives 8. As summarized
in Table 2, InBr3 proved tolerant for several protecting groups
and substitution patterns in the cyclized products by furnishing
excellent yields (70–98%) within a few minutes’ reaction time. The
effectiveness of In(III)Br as a F–C promoter was further stressed
by running a model reaction in absence of catalyst. As a matter
of fact, under these conditions the cyclization did not work to any
extent, even after 48 h (entry 1).
Stereoselective intramolecular F–C alkylation: towards the
synthesis of enantiomerically enriched polycyclic indoles
Scheme
3
Reagents and conditions: (i) K2Os2O2(OH)4, DABCO,
=
K3Fe(CN)6 (71%); (ii) NaIO4, SiO2, MeCOCH PPh3 (41%); (iii) RCO-
=
CH CH2, Grubbs’ II.
Asymmetric intramolecular alkylations of aromatic systems are
straightforward shortcuts to the synthesis of stereochemically
defined polycyclic natural and unnatural compounds bearing
benzylic stereocenters. Since the P–S pioneering paper,25 the large
volume of research efforts in this field led to the first example of
stereoselective P–S reaction to be developed in the presence of
chiral thioureas as catalysts.26 Subsequently, List and co-workers
described the use of functionalized chiral phosphoric acids as
effective Brønsted acids for stereoselective P–S condensations.27
In this context, a number of different catalytic and stereoselective
alkylations of aromatics through intramolecular Michael-type
reactions were reported.28
Again, a related stereoselective approach to the preparation of
THBCs and THGCs (tetrahydro-c-carbolines) in highly enantios-
elective manner was recently studied in our group through Pd-
catalyzed intramolecular alkylation of indole allyl carbonates.29
On the other hand, asymmetric catalytic Friedel–Crafts-type
reactions via conjugate addition of aromatic compounds to simple
InBr3 catalyzed intramolecular F–C-type alkylation.
The importance of Friedel–Crafts cyclization is noteworthy,
allowing the synthesis of prominent polyfunctionalized aromatic
as well as heteroaromatic fused compounds to be performed in
a straightforward manner. The initial procedure (stoichiometric
amounts of Lewis acids as well as harsh reaction conditions) has
been subsequently replaced by milder and more environmentally
friendly catalytic approaches. In this context, innovative Lewis
acids (LAs)23 and transition-metal C–H activators24 demonstrated
their effectiveness for the intramolecular alkylation of several
=
arenes by unfunctionalized as well as functionalized C C double
bonds, C≡C triple bonds and epoxides.9 With particular regard
to electron-rich aromatic systems, mild reaction conditions are
essential in order to prevent side-reactions such as a drop in
regiochemistry, poly-alkylations and competitive intermolecular
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Table 3 Stereoselective intramolecular F–C reactions catalyzed by 13b–
a,b-unsaturated ketones still represent a considerable synthetic
challenge. In fact, the steric similarity of the two carbonyl
substituents renders the stereodifferentiation of the two faces of
the unsaturated ketones a difficult task. In this context, we have
reported on the effectiveness of [salenAlCl]–lutidine complexes
in controlling the stereodiscriminating intermolecular Michael
addition of indoles to both aryl enones and aryl nitroalkenes.30
Then, by choosing the N–Boc protected indolylmethyl enone
8aa as the model substrate, a brief survey of commercially
available, as well as in situ-formed, chiral aluminium-based LAs
13a–f (20 mol%) were envisaged as catalysts and a collection of
results is reported in Fig. 2.
lutidenea
Entry
Indole
Product
Yield (%)b
Ee (%)c
1
2
3
4
5
8ab
8ba
8ca
8da
8fa
1ab
1ba
1ca
1da
1fa
98
69
98
47
95
27
11
11
0
29
a All the reactions were carried out in anhydrous CH2Cl2 (rt, 24 h,
20 mol% cat) under nitrogen atmosphere. b Isolated yields after flash
chromatography. c Determined by HPLC with chiral column.
nitrogen on the F–C outcome. As a matter of fact, by substituting
the Boc moiety with CBz, CO2Me and COCF3 the chiral induction
progressively dropped to a racemic product.
Interestingly, 13b–lutidine (20 mol%) failed in promoting the
intramolecular F–C alkylation of 12a. This result underlines the
importance of the N-(1) hydrogen during the whole catalytic cycle.
After 5d stirring, we decided in any case to obtain the cyclized
product and to this purpose we added InBr3 (20 mol%) to the
mixture already containing 13b (20 mol%). Astonishingly, after
16 h stirring at rt, 2a was obtained in 85% conversion and 50% ee!
It was evident that catalysis under a heterobimetallic regime was
operating.
In the last few years, catalyses under a cooperative regime have
becoming an attractive alternative to conventional LAs, due to
their superior selectivity and activity with respect to the individ-
ual components.31 Although this approach has been extensively
applied to stereocontrolled C–C bond forming reactions such as:
nitro-aldol reactions, Michael reactions, hydrophosphonylations
of aldehydes and imines, Diels–Alder reactions and epoxidations,
to our knowledge heterobimetallic catalysts have never been
employed in asymmetric F–C reactions.32
Then, 12a was allowed to cyclize in the presence of a catalytic
amount of 13a–lutidine in combination with a series of LAs.
From the data reported in Table 4, InBr3 proved to be the
most effective LA partners of 13b to control the stereochemistry
of the reaction. In particular, while scandium and ytterbium
triflates provided 2a in high yields but in a racemic form, the
enantiocontrol reached 54% ee (81% conversion) when InBr3
was used in combination with commercially available [salenAlCl]
13a.33
Such a level of stereoselectivity prompted us to investigate
further the nature of the dual catalyst {[salenAlCl]x–[InBr3]y}.
Accordingly, intramolecular F–C alkylation of 12a was carried
out with chiral Al–In systems based on different initial 13a–InBr3
ratios (Table 4, entries 5–8).
The optimal outcome in terms of chemical as well as optical
yield was obtained by adopting a 13a–In(III)Br3 2 : 1 ratio. In
this case, 2a was isolated in 80% yield and 60% enantiomeric
excess (entry 7). On the contrary, when an Al–In 4 : 1 ratio was
Fig. 2 Survey of chiral aluminium LAs as catalysts for the stereoselective
intramolecular F–C-type alkylations of 8aa.
The screening revealed generally good conversions with mod-
erate stereoselectivity. Among the catalysts tested, the Schiff–Al
complex 13a provided 1aa with the highest enantiomeric excess
(ee up to 30%). Due to the low reaction rate associated to
these processes, the lowering of the reaction temperature was not
accomplishable.
Along this line, the effect of concentration was also investigated.
To this purpose, 8aa was cyclized in the presence of 13b (20 mol%)
and lutidine (20 mol%) in a range of substrate concentrations
(8–66 mM). Despite the known influence of concentration on
intramolecular processes, in our cases the stereochemical outcome
resulted only slightly affected ranging form 19% in 66 mM
solution (98% HPLC conversion, 3d reaction time), to 27% in
8 mM reaction mixture (44% HPLC conversion, 14 d reaction
time). Then, we chose complex 13b as the model catalyst, and
a range of variously-functionalized indolyl enones 8 were tested
(Table 3). Entry 1 deals with the issue of substituent effects on
the stereocontrol of the reaction. In particular, the presence of an
aryl enone such as 8ab does not significantly affect either yield or
enantiomeric excess (98 and 27%, respectively). On the contrary,
we observed an influence of the protecting group of the tethering
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Table 4 Stereoselective intramolecular heterobimetallic F–C cyclizationa
Al–Schiff base complex through the oxygen atoms of the salen
counterpart.
Interestingly, when an excess of [salenAlCl] (Al–In 2 : 1) was
added, an inversion of the population of the species in solution
occurred, favouring the C1-adduct (80 : 20 ratio). Analogously, the
C1-species can be attributed to a dimeric {[salenAlCl]2} complex
tethered by one molecule of indium(III) salt (15).36
Entry
13a (%)
LA (%)
2
Yield (%)b
Ee (%)c
d
1
2
3
4
5
6
7
8
9
20
10
10
10
10
20
10
10
10
10
10
10
—
—
2a
—
93
95
82
—
7
7
43
54
55
60
2
25
5
(1)
Sc(OTf)3 (10)
Yb(OTf)3 (10) 2a
In(OTf)3 (10)
InBr3 (10)
InBr3 (10)
InBr3 (5)e
2a
2a
2a
2a
2a
2a
2a
2b
2c
81 (70)
77
87 (80)
93
The aforementioned ratio between the two species can be further
shifted toward the dimer 15 simply by adding an excess of 13a.
Here, the use of 13a–InBr3 in a 4 : 1 ratio gave rise to the
exclusive formation of 15 with the concomitant presence of free
[salenAlCl]. Such evidence concurred to rule out the formation
of more complex multi-metallic aggregates, probably because of
sterical reasons.
The role of the base was investigated spectroscopically as
well. To this aim, 1H NMR spectra of 13a–In(III)Br–lutidine was
recorded at rt for different Al–In ratios. Also in this case a mixture
of species were present in equilibrium in solution showing similar
pattern of NMR signals. However, because of the multitude of
signals the spectra were difficult to rationalize.
A different explanation for the enhanced reactivity of the
bimetallic complex could also arise from a study conducted
by Atwood and co-workers on heterobimetallic [salenAl]–Ga
complexes. In this case, the achiral salts did not act as distinct
LAs, but the gallium(III) halide concurred in the formation
of unexpected solvent-free pentacoordinated cationic aluminium
complexes.37 However, this working hypothesis was ruled out
by synthesizing a cationic salen–Al complex through chloride
extraction by AgSbF6 in CH2Cl2, and by testing it in the model
cyclization. Under these conditions, 2a was obtained only in traces
(reaction time 72 h) in a markedly lower enantiomeric excess
(ee = 7%).
InBr3 (2.5)e,f
InBr3 (2.5)e
InBr3 (5)g
InBr3 (5)
63
70
61
80
10
11
12
20
60
InBr3 (5)e
a All the reactions were carried out in anhydrous CH2Cl2 (rt) under nitrogen
atmosphere; 13a and lutidine were used in a 1 : 1 ratio. b HPLC conversion,
isolated yields are in brackets. c Determined by HPLC with chiral column.
d Reaction time 5 d. e A solution of InBr3 in dry Et2O (0.30 M) was used.
f TEA (10 mol%) was used as the base. g In absence of lutidine.
employed, 2a was obtained in a 63% yield and 25% ee (entry 9).
These results drove our attention towards the possibility to have
different heterobimetallic species in solution with a rapid exchange
equilibrium between them. In particular, the one constituted by
two molecules of [salenAlCl] and one molecule of InBr3 appeared
to be the most effective during the stereodifferentiating step of the
intramolecular process.
Also in the present bimetallic-catalyzed intramolecular alkyla-
tion, the use of a base in catalytic amount (lutidine) was necessary
in order to achieve the highest ee (entry 7). As a matter of fact,
when the model reaction was carried out in absence of base,
the enantioselectivity dropped to 5% (entry 10). Again, aliphatic
tertiary amines did not prove to be a suitable additive for the
present intramolecular F–C. In fact, by replacing lutidine with
TEA, 2a was yielded in quantitative yield but in almost racemic
form (ee = 2%, entry 8). This finding unambiguously proves the
active role of the additive in the in situ catalyst formation between
the aluminium and indium species.34 The optimal conditions were
finally also applied to 12b and 12c obtaining ee 20 and 60% in the
cyclized products 2b–c, respectively.
To gain some information on the nature of the {[salenAlCl]x–
[InBr3]y} species in solution, a 1H NMR analysis in CD2Cl2
with different 13a–InBr3 ratios was carried out (see the ESI). In
particular, by adding 1 eq. of In(III)Br to a solution (CD2Cl2)
of commercially available [salenAlCl], two new set of signals
characteristic for unprecedented C2-symmetry and C1-symmetry
{[salenAlCl]–InBr3} species were found. The new C2-symmetry
adduct appeared to be in a 75 : 25 ratio with the starting [salenAlCl]
and the C1-symmetrical species being the minor components of
the mixture. On the basis of previously-reported evidence from
salen–metal–LA adducts,35 we tentatively assigned the new set of
C2-symmetry signals to the monomeric bimetallic {[salenAlCl]–
InBr3} (14, eqn 1), in which the indium salt could coordinate the
Conclusions
In this study we have presented a new synthetic strategy for
the formation of polycyclic indolyl-containing compounds by
updating and optimizing our previously reported protocol. In
particular, the introduction of the CM reaction for stereocon-
=
trolled C C bond formation shortened the synthetic sequence
for the desired indolyl enones. Then, the development of a
stereoselective version of the present cyclization with chiral Lewis
acid was discussed. The use of chiral Al-based LAs furnished the
targeted THBCs in good yield and moderate enantioselectivity.
Interestingly, cyclizations of O-tethered enones 12 were performed
in the presence of a new chiral (Al–In) system, affording the
corresponding tetrahydropyranyl derivative 2 of ee up to 60%.
Spectroscopic investigations on the nature of this catalytic system
revealed the presence in solution of several heterometallic species
in equilibrium being the bimetallic {[salenAlCl]2–InBr3} probably
involved in the enantiodiscriminating step of the cyclization.
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18 A. K. Chatterjee, J. P. Morgan, M. Scholl and R. H. Grubbs, J. Am.
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Grubbs, J. Am. Chem. Soc., 2001, 123, 11312–11313; T.-L. Choi, A. K.
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1279.
19 S. Harada, N. Kumagai, T. Kinoshita, S. Matsunaga and M. Shibasaki,
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20 Q. Yang, W.-J. Xiao and Z. Yu, Org. Lett., 2005, 7, 871–874.
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Acknowledgements
This work was supported by M.I.U.R. (Rome), the PRIN Project
(Sintesi e stereocontrollo di molecole organiche per lo sviluppo
di metodologie innovative di interesse applicativo), the FIRB
Project (Progettazione, preparazione e valutazione biologica e
farmacologica di nuove molecole organiche quali potenziali
farmaci innovativi) and the University of Bologna (funds for
selected research topics).
22 S. H. Hong, M. W. Day and R. H. Grubbs, J. Am. Chem. Soc., 2004,
126, 7414–7415.
23 H. Inoue, N. Chatani and S. Murai, J. Org. Chem., 2002, 67, 1414–1417,
and references therein.
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3296 | Org. Biomol. Chem., 2006, 4, 3291–3296
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