Bismuth(III) bromide in organic synthesis. A catalytic method for the allylation of tetrahydrofuranyl and tetrahydropyranyl ethers

Article abstract of DOI:10.1016/j.tetlet.2010.08.079

A bismuth bromide-catalyzed (10.0 mol %) multicomponent reaction involving the allylation of THF- and THP-ethers, followed by in situ derivatization with acetic anhydride to generate highly functionalized esters has been developed under solvent-free conditions. To the best of our knowledge, this is the first report of a catalytic procedure for the allylation of THF- and THP-ethers to yield ring-opened products.

Full text of DOI:10.1016/j.tetlet.2010.08.079

Tetrahedron Letters 51 (2010) 5643–5645
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Bismuth(III) bromide in organic synthesis. A catalytic method for the
allylation of tetrahydrofuranyl and tetrahydropyranyl ethers
⇑
Scott W. Krabbe, Veronica V. Angeles, Ram S. Mohan
Laboratory for Environmentally Friendly Organic Synthesis, Department of Chemistry, Illinois Wesleyan University, Bloomington, IL 61701, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A bismuth bromide-catalyzed (10.0 mol %) multicomponent reaction involving the allylation of THF- and
THP-ethers, followed by in situ derivatization with acetic anhydride to generate highly functionalized
esters has been developed under solvent-free conditions. To the best of our knowledge, this is the first
report of a catalytic procedure for the allylation of THF- and THP-ethers to yield ring-opened products.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 1 August 2010
Revised 20 August 2010
Accepted 24 August 2010
Keywords:
Allylation
THP ethers
Bismuth bromide
Acetates
Tetrahydropyranyl (THP)-ethers are useful protecting groups
for alcohols and phenols but they can also be converted to other
useful functional groups.1 For example, the direct conversion of
THP-ethers to acetates has been reported.1b Despite numerous lit-
erature examples of allylations of acetals to yield homoallyl
ethers,2 very little attention has been given to the potentially use-
ful allylation of THP ethers (Scheme 1).
Despite the obvious synthetic utility of such a transformation,
to the best of our knowledge, there are only two reports of the ally-
lation of THP-ethers. Maeda et al.3 have reported the Lewis acid-in-
ronmentally unfriendly solvent. In addition, allyl sources, such as
lithium n-butyltriallylborate are not commercially available and
must be synthesized when needed. Although not examples of
THP ether allylation, a few other bismuth-catalyzed reactions that
are relevant and deserve mention include a novel stereoselective
construction of cyclic ethers using a tandem two-component
etherification developed by Evans et al.5 They utilized a BiBr3-cat-
alyzed allylation of a ketone in CH3CN followed by cyclization to
generate substituted tetrahydropyrans. They also carried out ele-
gant mechanistic studies that suggest that the active catalysts
are HBr and bismuth oxybromide, BiOBr. Daich and co-workers
duced allylation of
a-iodo mixed acetals with allylsilanes. They
found that the allylation of trans-2-(tert-butyldimethylsilyloxy)-
3-iodo-1-oxacyclopentane 1 promoted by TiCl4 (1.0 equiv) in
CH2Cl2 afforded a 58% yield of the open chain product, anti-4-
(tert-butyldimethylsilyloxy)-3-iodo-6-hepten-1-ol 2 (the ratio of
anti/syn product was >99/1) (Scheme 2). When the reaction was
carried out in the presence of TMSOTf (20.0 mol %) instead of TiCl4
(1.0 equiv), the siloxy group was replaced with the allyl group to
yield allylated-tetrahydropyran 3 in 90% yield (trans/cis ratio was
>99/1).
Hunter et al. have reported the TMSOTf (1.2 equiv)-promoted
allylation of 2-methoxytetrahydropyran, using lithium n-buty-
ltriallylborate as the allyl source.4 They reported a 40% yield of
the open chain product and 24% yield of 2-allyltetrahydro-2H-pyr-
an. As can be seen from these two examples, both these methods
require the use of highly corrosive catalysts such as TMSOTf or
TiCl4, and are carried out at low temperatures in CH2Cl2, an envi-
have reported a bismuth triflate-catalyzed intermolecular
a-ami-
doalkylation of a variety of -acetoxylactams with silanes and
a
enoxysilanes.6 Floreancig and co-workers report a very efficient
BiBr3 mediated allylation of a lactol to yield a tetrahydropyranyl
alcohol.7 This reaction was a key step in their studies directed to-
ward the construction of Leucascandrolide A, an antifungal macro-
lide. In studies devoted to the synthesis of galactofuranoside
mimics, Martin and co-workers report a highly efficient bismuth
triflate mediated allylation of a glucofuranosylamine.8 In contrast
to Bi(OTf)3, Sc(OTf)3 did not catalyze the reaction.
A lack of catalytic methods for the allylation of THP-ethers cou-
pled with our continued interest in bismuth compounds prompted
us to develop a bismuth(III) salt-based methodology for the allyla-
catalyst
allyl group source
RO
O
RO
OH
⇑
Corresponding author. Tel.: +1 309 556 3829; fax: +1 309 556 3864.
E-mail address: rmohan@iwu.edu (R.S. Mohan).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.079

5644
S. W. Krabbe et al. / Tetrahedron Letters 51 (2010) 5643–5645
TiCl4 (1.0 eq)
or
TMSOTf (0.20 eq)
t
OSiMe2 Bu
t
O
O
OSiMe2 Bu
OH
I
I
I
SiMe3
CH2Cl2, -78 °C
1
2
3
Scheme 2.
Scheme 3.
tion of THF- and THP-ethers. Bismuth compounds have attracted
considerable attention in the last decade due to their remarkably
low toxicity, low cost, and ease of handling.9 Herein, we report that
bismuth(III) bromide is a suitable catalyst for the allylation of THF-
and THP-ethers followed by in situ derivatization of the putative
alkoxide intermediate with acetic anhydride (Scheme 3) to yield
highly functionalized acetates in moderate yields (Table 1).
We recently reported a similar strategy for the allylation of
dioxolanes catalyzed by bismuth triflate as a catalyst.10 Encour-
aged by the success of this approach, we first attempted the allyla-
tion of THP-ethers using bismuth triflate as a catalyst. However,
the results were not very promising and a significant amount of
the corresponding acetate was obtained.1b Gratifyingly, bis-
muth(III) bromide, which is less expensive than bismuth(III) tri-
flate, proved more efficient for the allylations.11 These results are
summarized in Table 1.
allyltetrahydro-2H-furan or 2-allyltetrahydro-2H-pyran. Thus, in
the case of THP-ethers, the open chain product could be typically
isolated in ca. 50% yield after chromatographic purification (entries
a–g). Less satisfactory yields of the desired open chain product
were obtained when methallylsilane (entries h and i) was used
as the allyl group source, or when the allylation was attempted
on THF-ethers (entries j and k). Although, it was possible to isolate
a pure sample of 2-allyltetrahydro-2H-pyran (entries a and e), in
most cases, due to the small amount of silica used and close Rf val-
ues, the 2-allyltetrahydro-2H-pyran was isolated as a mixture with
small amounts of the corresponding acetate. In the case of THP-
ether derived from 3-phenylpropanol (entry g), the corresponding
acetate was isolated in 31% yield. All reactions were carried out un-
der solvent-free conditions and the product was isolated by direct
filtration of the reaction mixture through a silica gel column, thus
avoiding an aqueous waste stream. No reaction was observed in
the absence of BiBr3 or acetic anhydride. It was also shown that
the acetate could be easily hydrolyzed to the corresponding alcohol
As can be seen from Table 1, the allylation of all THF- and THP-
ethers gave nearly equal amounts of the open chain product and 2-
Table 1
BiBr3 catalyzed allylation of THF- and THP-ethers followed by in situ derivatization with Ac2O12
BiBr3
R2
n
O
n
Ac2O
R1OAc
O
R1O
O
R1O
O
n
R2
R2 = H, n = 0, 6
R2 = H, n = 1, 7
R2 = CH3, n = 1, 8
SiMe3
9
5a-k
4a-k
Entry
R1
R2
n
ta
Yieldb (%) 5a–k
a
b
c
d
e
f
g
h
i
CH3
H
H
H
H
H
H
H
CH3
CH3
H
1
1
1
1
1
1
1
1
1
0
0
1 h
58c
53
62
CH3(CH2)4
CH3(CH2)6
Cyclohexyl
HC„CCH2CH2
BrCH2(CH2)2
PhCH2(CH2)2
CH3(CH2)4
CH3
1 h 45 min
2 h 35 min
1 h 30 min
1 h 15 min
1 h 30 min
2 h 15 min
1 h 35 min
1 h 30 min
2 h 10 min
1 h 30 min
44
43d
45
49e
35
30f
21
j
k
CH3(CH2)6
PhCH2(CH2)2
H
25
a
Reaction progress was followed by GC or TLC.
Refers to yield of isolated, purified ester; reported yield is calculated assuming that the ester is the only product. In all cases the reaction mixture contained a significant
b
amount (20–50%, by GC) of 2-allyltetrahydro-2H-furan or 2-allyltetrahydro-2H-pyran and much smaller amounts (ca. 10%) of the corresponding acetate (9a–k). Pure samples
of the 2-allyltetrahydro-2H-furan or 2-allyltetrahydro-2H-pyran could not be isolated due to the fact that they had Rf values very similar to the corresponding acetates.
c
2-Allyltetrahydro-2H-pyran was isolated in 24% yield (96% pure by GC).
d
2-Allyltetrahydro-2H-pyran was isolated in 28% yield (99% pure by GC, 1H and 13C NMR analysis).
e
3-Phenylpropyl acetate (96% pure by GC and 1H NMR) was isolated in 31% yield.
f
2-Methallyltetrahydro-2H-pyran was isolated in 55% yield (99% pure by GC, 1H and 13C NMR analysis).

S. W. Krabbe et al. / Tetrahedron Letters 51 (2010) 5643–5645
5645
O
K2CO3 (5.0 eq)
Ph
O
O
Ph
O
OH
CH3OH
3 h 40 min
(89%)
5g
10
Scheme 4.
in an excellent yield (Scheme 4), thus providing an easy access to a
variety of highly functionalized alcohols.
spectra) associated with this article can be found, in the online ver-
sion, at doi:10.1016/j.tetlet.2010.08.079.
In summary, this methodology allows the synthesis of highly
functionalized acetates in a single step from the readily available
THF- and THP-ethers. The use of an environmentally friendly cata-
lyst, BiBr3, and the solvent free procedure add to the synthetic util-
ity of this procedure.
References and notes
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.;
Wiley: New York, 1999; The direct conversion of THP ethers to acetates
catalyzed by bismuth(III) salts has been previously reported. (i) (b)
Mohammadpoor-Baltork, I.; Khosropour, A. R. Synth. Commun. 2002, 32,
2433; (ii) Mohammadpoor-Baltork, I.; Khosropour, A. R. Monatsh. Chem. 2002,
133, 189.
Representative procedure: A homogeneous mixture of 2-(heptyl-
oxy)tetrahydro-2H-pyran12 (entry c) (0.300 g, 1.498 mmol), allyl-
trimethylsilane (0.291 g, 0.40 mL, 2.547 mmol, 1.7 equiv), and
acetic anhydride (0.260 g, 0.24 mL, 2.547 mmol, 1.7 equiv) was
stirred at rt under N2 as bismuth(III) bromide (67.2 mg,
0.150 mmol, 10 mol %) was added. The bismuth(III) bromide dis-
solved and the reaction mixture turned slightly yellow in color.
After 2 h 35 min the reaction mixture was filtered through silica
gel (25 g, EtOAc/heptane). A 240-mL prefraction was collected
(EtOAc/heptane, 1:99) followed by elution with EtOAc/heptane
(5:95). Seventy fractions (8 mL) were collected. Fractions 17–21
were combined to yield 80.3 mg of a clear liquid that was deter-
mined to be 2-allyltetrahydro-2H-pyran by 1H NMR spectroscopy.
Fractions 45–64 were combined to yield 0.263 g (62%) of a clear li-
quid that was determined to be >99% pure 5c by GC analysis, 1H
and 13C NMR spectroscopy. 1H NMR d 0.86 (t, 3H, J = 6.5 Hz),
1.22–1.36 (m, 8H), 1.40–1.66 (m, 8H), 2.02 (s, 3H), 2.14–2.32 (m,
2H), 3.20–3.29 (quintet, 1H), 3.29–3.51 (m, 2H), 4.01–4.06 (t, 2H,
J = 6.5 Hz), 5.00–5.08 (m, 2H), 5.71–5.86 (m, 1H); 13C NMR (17
peaks) d 14.1, 21.0, 21.9, 22.6, 26.2, 28.6, 29.1, 30.1, 31.8, 33.5,
38.4, 64.5, 69.2, 78.7, 116.7, 135.0, 171.2. IR vmax 2928, 1741,
1641 cmÀ1. HRMS-CI (m/z): M+ calculated for C17H33O3,
285.2430; found: 285.2431.
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Acknowledgment
We are grateful to the National Science Foundation for an RUI
(Research in Undergraduate Institutions) grant (#0650682)
awarded to R.S.M.
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Chem. 2008, 61, 419.
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Supplementary data
12. The starting materials were synthesized following
a literature procedure.
Supplementary data (detailed experimental procedures and full
characterization for all new compounds, copies of 1H and 13C NMR
Stephens, J. R.; Butler, P. L.; Clow, C. H.; Oswald, M. C.; Smith, R. C.; Mohan, R. S.
Eur. J. Org. Chem. 2003, 19, 3827.