Highly efficient molybdenum(II)-catalyzed intramolecular allylic alkylation of arenes

Article abstract of DOI:10.1002/adsc.200700607

The Friedel-Crafts-type intramolecular allylic alkylation of simple arenes is performed in the presence of a catalytic amount of [Mo(II) (CO) ₄Br₂]₂ (2.5 mol%). The moisture-tolerant protocol provided a mild and direct acc

Full text of DOI:10.1002/adsc.200700607

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DOI: 10.1002/adsc.200700607
Highly Efficient Molybdenum(II)-Catalyzed Intramolecular
Allylic Alkylation of Arenes
Marco Bandini,a,* Astrid Eichholzer,a Peter Kotrusz,a
and Achille Umani-Ronchia,*
a
Dipartimento di Chimica “G.Ciamician”, Università di Bologna, via Selmi 2, 40126 Bologna, Italy
Fax : (+39)-051-209-9456; e-mail: marco.bandini@unibo.it or achille.umanironchi@unibo.it
Received: December 21, 2007; Revised: January 23, 2008; Published online: February 27, 2008
ˇ
Dedicated to Professor Stefan Toma on the occasion of his 70th birthday.
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The Friedel–Crafts-type intramolecular
allylic alkylation of simple arenes is performed in
the presence of a catalytic amount of [Mo(II)
(CO)4Br2]2 (2.5 mol%). The moisture-tolerant pro-
tocol provided a mild and direct access to a large li-
brary of functionalized 4-vinyl-1,2,3,4-tetrahydro-
naphthalenes in high yields.
alyzing intramolecular Friedel–Crafts (FC)-type alky-
lation of arenes via allyl halide activation.[6]
In conjunction with our current research interest
toward the development of catalytic enantioselective
intramolecular allylic alkylation of arenes,[4d] we rea-
soned that the development of new approaches based
on electrophilic transition metal complexes would
provide opportunities for developing enantioselective
variants of the process.Interestingly, although asym-
metric allylic alkylation is a well established protocol
with countless combinations of allylic derivatives and
C-, N- and O-based nucleophiles,[7] the use of simple
Keywords: allylic alkylation; catalysis; cyclization;
Friedel–Crafts reaction
ˇ
´
arenes has been described only by Kocovsky and co-
workers with electron-rich benzene rings (intermolec-
The search for efficient, mild and economically ular process).[8]
friendly catalytic protocols for the intramolecular al-
Focusing on operational simplicity, we designed the
kylation (Csp2<C->Csp3 bond-forming process) of allyl carbonate 3a as the model substrate for the cata-
simple arenes is a long-sought goal for the whole lytic ring-closing process.The synthesis of 3a was
chemical community.[1] Agrochemicals, pharmaceuti- readily accomplished in a gram-scale via alkylation of
cals and “plastic electronics” are among the most im- the corresponding diethyl (3,4-dimethoxybenzyl)malo-
portant fields that would benefit from synthetic ad- nate 1a[9a] and (Z)-bromocarbonate 2[9b] (yield 80%,
vances in this transformation.Among the plethora of
electrophilic precursors employed for the alkylation
Scheme 1).
A survey of reaction conditions (i.e., metal salts,
of aromatic systems, the use of tethered C=C double solvent, temperature) was then undertaken and a rep-
bonds, bearing a leaving group in the allylic position resentative collection of results is reported in Table 1.
(allylic alkylation), is of remarkable synthetic interest,
providing highly versatile polycylic aromatic com- tive in the intramolecular allylic alkylation of indole-
pounds.[2,3] s,[4a] failed in the present cyclization, leading to large
Palladium-based catalysis, which proved to be effec-
For the present, several catalytic allylic alkylation amounts of dienyl by-product when combined with
protocols involving heteroaromatics have been de-
scribed.[4] In contrast, simple benzene derivatives
have received much less attention, because of their in-
trinsic low nucleophilicity with the consequent re-
quirement for harsh reaction conditions as well as sto-
ichiometric amounts of promoting agents.[5]
The report by Cook and Hayashi is a breakthrough
in this area describing the effectiveness of InCl3 (10–
30 mol%), in the presence of molecular sieves, in cat- Scheme 1. Synthesis of model carbonate 3a.
Adv. Synth. Catal. 2008, 350, 531 – 536
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Marco Bandini et al.
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Table 1. Optimization of the reaction conditions for the intramolecular allylic alkylation of 3a.[a]
Entry
Cat [mol%]
Time [h]
Temp.[ 8C]
Yield 4a/4aꢀ [%][b]
1
2
3
4
5
6
7
8
[Pd
[Pd
N
16
16
16
16
16
16
40
40
80
80
80
80
80
80
rt
-/-[c]
-/78[d]
-/-[c]
A
ACHTREUNG
[Mo(CO)4Br2]2 [2.5]
[Mo(CO)4Br2]2 [2.5]
[Mo(CO)4Br2]2 [1]
[Mo(CO)4Br2]2/AgOTf [2.5/10]
91/-[e]
91/-
78/-
91/-
[Mo
(acac)2Cl2]/AgOTf [5/10]
rt
26/-[f]
[a]
All the reactions were carried in reagent grade ClCH2CH2Cl (DCE) without restrictions for air, unless otherwise speci-
fied.
[b]
[c]
[d]
[e]
[f]
Isolated yields after flash chromatography.
Recovery of the starting material > 90%, reaction in THF.
With K2CO3 (2 equiv.), reaction in THF.
Under dry conditions.
70% of the starting material was recovered.
K2CO3 (entry 2).On the contrary, the absence of the
then established and a collection of results is summar-
base led to the recovery of the unaltered starting ma- ized in Table 2.
terial with a variety of Pd sources (entries 1 and 3).[10]
A wide range of functionalized and unfunctional-
These results suggest that the relatively poor nucleo- ized arenes cyclized smoothly under optimal reaction
philic character of the aromatic rings did not allow parameters ([Mo(CO)4Br2]2 2.5 mol%, ClCH2CH2Cl,
the ring-closing process on the h3-Pd intermediate 808C, 16 h) with high yields (48–97%) after flash
and, in the presence of a base (i.e., K2CO3), the b-H chromatography.For instance, the cyclization of b-
elimination of the Pd-complex became the predomi- naphthalene-carbonate 3g proceeded exclusively to
nant pathway.
the a-position (yield 96%) and meta-methoxyacyclic
Interestingly, the use of [Mo(CO)4Br2]2 (2.5 compound 3d underwent the ring-closing process with
mol%)[11] led to the desired cyclized compound 4a re- a 3:1 regioisomeric ratio.The final chemical outputs
gioselectively in 91% isolated yield (4a:4a’> 50:1, did not seem to be markedly affected by the C=C
entry 4).
configuration of 3.In fact, considerably high yields
Surprisingly, we discovered that the air-sensitive were recorded both with configurationally pure carbo-
[Mo(CO)4Br2]2 facilitated the ring-closing of 3a to a nates and with starting materials containing a mixture
comparable extent (yield 91%), even in the presence of diastereoisomers (see entry 2).
of air and with reagent-grade dichloroethane
Worthy to note is the result obtained with the chal-
(entry 5).[12] The cyclization worked smoothly also in lenging ferrocenyl carbonate 3l.It is known, in fact,
the presence of 1 mol% of catalyst (yield 78%, that catalytic alkylations of ferrocene gave often very
entry 6), and the possibility to lower the temperature poor yields with the need for time-consuming purifi-
to room temperature was demonstrated by adding 10 cations of the crude reaction product.[14] Here, by
mol% of AgOTf, implying that a more active catalyst using 5 mol% of [Mo(CO)4Br2]2, the desired cyclized
is generated in situ (yield 91%, entry 7).
compound 4l was obtained in 48% yield, as a 72:28
In contrast, disappointing results in terms of con- mixture of diastereoisomers, due to the intrinsic
version were recorded with a cationic Mo(IV) com- planar chirality[15] of 4l (entry 11).
plex (i.e., [Mo
A
A limitation of the protocol emerged from the use
described as being active in the alkylation of electron- of electron-deficient arenes (i.e., 3m) that, even under
rich arenes with allyl and cinnamyl alcohols (yield forcing reaction conditions, provided 4m in poor yield
26%, entry 8).[13]
(15%) with the major product being 5m in 45% yield
The utility of [Mo(CO)4Br2]2 for the synthesis of a and a 65:35 diastereomeric ratio (Scheme 2).
variety of substituted tetrahydronaphthalenes was
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Highly Efficient Molybdenum(II)-Catalyzed Intramolecular Allylic Alkylation of Arenes
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Table 2. Mo(II)-catalyzed cyclization of selected substrates.[a]
Entry
1
3 (Ar) (Z:E)[b]
Product 4
Yield of 4 [%][c]
3b 3,5-(MeO)2C6H3 (90:10)
72
2
3
4
5
6
7
8
9
3c 4-MeO-C6H4 (75:25)
3d 3-MeO-C6H4 (97:3)
3e 4-MeC6H4 (>98:2)
3f C6H5 (71:29)
85
81 (3:1)[d]
90
92
3g b-naphthyl (88:12)
3h 4-TBDMSO-C6H4 (>98:2)
3i 4-Ph-C6H4 (97:3)
96
71(97)[e]
84
3j 4-MeS-C6H4 (87:13)
70
10
3k 9-phenanthrenyl (98:2)
93
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Marco Bandini et al.
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Table 2. (Continued)
Entry
3 (Ar) (Z:E)[b]
Product 4
Yield of 4 [%][c]
11
3l ferrocenyl (>98:2)
48[f]
[a]
All the reactions were carried in reagent grade DCE without restrictions for air.
Determined by H1-NMR and GC/LC-MS.
After flash chromatography.
The regiochemistry was determined by GC-MS.
26% of the cyclized product was recovered with a free OH group.
5 mol% of [Mo(CO)4Br2]2 was employed.Diastereomeric ratio: 72:28.
[b]
[c]
[d]
[e]
[f]
A working reaction mechanism for the formation of
5m is depicted in Scheme 2.In the presence of deacti-
To this purpose, we synthesized in two steps the
aryl biscarbonate 3n starting from commercially avail-
vated arenes, the expected FC-type alkylation did not able 1,4-dibromoxylene (see Supporting Information
take place, but one of the ester moieties underwent for details).By increasing the loading of catalyst to 10
the intramolecular nucleophilic attack on the [Mo]-ac- mol%, complete conversion was obtained within 16 h
tivated allyl carbonate that leads to the final g-lactone under reflux (Scheme 3).Employing chromatographic
5m as a mixture of diastereoisomers.
purification it was possible to separate the 2,5-bis-cy-
To extend the usefulness of the present [Mo]-cata- clized compounds 4n (yield 55%, dr 1:1) from the cor-
lyzed ring-closing process further, we explored the responding 2,3-bis-cyclized analogues 4nꢀ obtained as
À
possibility to perform one-pot multiple C C bond the minor regioisomer (yield 3%, dr 1:1).
forming reactions that would lead to functionalized
polycyclic aromatic scaffolds.
A representative example of effective and selective
decarboxyaltion of the benzocarbocycles is described
Scheme 2. Mo-catalyzed ring-closing reaction with arenes bearing electron-withdrawing substituents.
Scheme 3. One-pot double allylic alkylation.
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Highly Efficient Molybdenum(II)-Catalyzed Intramolecular Allylic Alkylation of Arenes
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1
4a: White wax; yield: 91%; H NMR (200 MHz, CDCl3):
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J1 =11.8 Hz, J2 =13.8 Hz, 1H), 2.59 (dd, J1 =4.0 Hz, J2 =
11.8 Hz, 1H), 3.10 (d, J=16.0 Hz, 1H), 3.25 (d, J=16.0 Hz,
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6.67 (s, 1H). 13C NMR (50 MHz, CDCl3): d=14.1(2C), 34.7,
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(M+1), 747.2 (2M+Na); anal.calcd for C 20H26O6: C 66.28,
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model substrate 3a in order to rule out the potential
roles of Brønsted acidity and hydroxy [Mo] species in
the ring-closing process: i) HClEt O (10 mol%), DCE,
2
808C, 16 h=decomposition of the starting material; ii)
stirring of [Mo(CO)4Br2]2 in reagent grade DCE under
air (16 h) then catalysis=4a’ (75% yield); iii) use of hy-
drolyzed [Mo(CO)4Br2]2 in the cyclization=recovery of
unreacted 3a (91%).
ˇ
´
[13] A.V.Malkov, P.Spoor, V.Vinader, P.Koc
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Adv. Synth. Catal. 2008, 350, 531 – 536