Environmentally friendly organic synthesis using bismuth compounds. bismuth trifluoromethanesulfonate-catalyzed allylation of dioxolanes

Article abstract of DOI:10.1071/CH08109

A bismuth trifluoromethanesulfonate (triflate)-catalyzed (2.0 mol-%) multicomponent reaction involving the allylation of dioxolanes followed by in situ derivatization with anhydrides to generate highly functionalized esters has been developed under solvent-free conditions. Most reagents used to date for allylation of dioxolanes are highly corrosive and are often required in stoichiometric amounts. In contrast, the use of a relatively non-toxic and non-corrosive bismuth(iii)-based catalyst makes this methodology especially attractive for scale-up. CSIRO 2008.

Full text of DOI:10.1071/CH08109

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CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2008, 61, 419–421
Environmentally Friendly Organic Synthesis Using Bismuth
Compounds. Bismuth Trifluoromethanesulfonate-Catalyzed
Allylation of Dioxolanes
Matthew J. Spafford,A James E. Christensen,A Matthew G. Huddle,A
Joshua R. Lacey,A and Ram S. MohanA,B
ADepartment of Chemistry, Illinois Wesleyan University, Bloomington, IL 61701, USA.
BCorresponding author. Email: rmohan@iwu.edu
A bismuth trifluoromethanesulfonate (triflate)-catalyzed (2.0 mol-%) multicomponent reaction involving the allylation of
dioxolanes followed by in situ derivatization with anhydrides to generate highly functionalized esters has been developed
under solvent-free conditions. Most reagents used to date for allylation of dioxolanes are highly corrosive and are often
required in stoichiometric amounts. In contrast, the use of a relatively non-toxic and non-corrosive bismuth(iii)-based
catalyst makes this methodology especially attractive for scale-up.
Manuscript received: 17 March 2008.
Final version: 28 April 2008.
Introduction
detract from the utility of this procedure. Jiang and cowork-
ers reported the BF3·Et2O-promoted allylation reactions of
allyl(cyclopentadienyl)iron(ii) dicarbonyl complexes with diox-
olanes to give zwitterionic iron–alkene pi-complexes that on
treatment with NaI underwent demetalation to give homoallylic
alcohols.[20] One disadvantage of this method is that the source
of the allyl group, viz. the iron(ii) complex, must be synthe-
sized under strictly anhydrous conditions. Hunter and coworkers
reported the TMSOTf-catalyzed allylation of dioxolanes using
allylborates.[21] However, this method also suffers from the
fact that the required boron reagents must be prepared in the
laboratory. In addition, allylation of dioxolanes under these
conditions gave reduction products along with the expected
homoallyl alcohols. Vogel and coworkers have described the
allylation of acetals derived from sugars using allytrimethylsi-
lane and stoichiometric amounts of TMSOTf and BF3·Et2O.[22]
Suzuki and coworkers described the Sn(OTf )2-catalyzed ally-
lation of dioxolanes with allyltrimethylsilane in the presence of
benzyloxytrimethylsilane.[23] They observed that under the reac-
tionconditions, theexchangereactionbetweenthedioxolaneand
benzyloxytrimethylsilane is much faster than allylation of the
dioxolane, and hence the product is the corresponding homoal-
lyl benzyl ether, resulting from allylation of dibenzyl acetals
arising from the exchange reaction.
The allylation of acyclic acetals to generate homoallyl ethers has
been well documented in the literature. Several catalysts have
been developed for this purpose including TiCl4,[1] AlCl3,[2]
[2]
[3]
[4]
BF3·Et2O, tritylperchlorate, montmorillonite, trimethyl-
silyl bis(fluorosulfonyl)imide (TMSN(OTf)2),[5] ISiMe3,[6]
trimethylsilyl trifluoromethane sulfonate (TMSOTf),[7] dicyclo-
penta-1,3-dienylbis(trifluoromethylsulfonyloxy)titanium (TiCp2)
(CF3SO3)2,[8] tris(p-bromophenyl)aminium hexachloroanti-
monate,[9] triarylpyrilium salts,[10] TMSNTf2,[11] BiBr3,[12]
Sc(OTf)3,[13] Bi(OTf)3,[14] and CuBr.[15] In contrast, there are
fewer reports in the literature of the corresponding allylation of
dioxolanes. Bartlett and Johnson have used the TiCl4-promoted
allylation of dioxolanes using allyltrimethylsilane in the course
of synthesis of the insect pheromone γ-dodecanolactone. How-
ever, this method required the use of 1.4 equivalents of the
highly corrosive TiCl4 and 3.6 equivalents of allyltrimethyl-
silane for every mole of the dioxolane.[16] Denmark and
coworkers reported the stereoselective opening of achiral diox-
ane acetals using a range of allylmetalsilanes and TiCl4 or
TiCl2(OiPr)2.[17] However, to achieve the desired stereoselec-
tivity, an excess of the allylmetalsilane (2–8 equivalents) and
titanium reagent (1–11 equivalents) had to be used. Kuwajima
and coworkers also reported the ring-opening of a single diox-
olane, 2-hexyl-4,4-dimethyl-1,3-dioxolane, promoted by TiCl4,
AlCl3, or SnCl4.[18] They also reported that TMSOTf was inef-
fective when allyltrimethylsilane was used as the nucleophile but
theuseofallyltributyltinaffordedhomoallylalcohols. Moreover,
only yields determined by NMR spectroscopy were given and an
experimental procedure was not reported. Morelli and cowork-
ers described the TiCl4-mediated ring-opening of chiral acetals
derived from fluorinated diols using allyltributyltin.[19] The use
of 50 mol-% TiCl4 and a highly toxic organotin compound
Results and Discussion
The lack of a highly catalytic method for allylation of dioxolanes
using non-toxic reagents coupled with our continued interest in
bismuth(iii) compounds,[24–26] due largely to their remarkably
low toxicities, prompted us to investigate the bismuth(iii) trifluo-
romethanesulfonate (triflate)-catalyzed allylation of dioxolanes.
Bismuth triflate is an easy-to-handle and relatively inexpen-
sive catalyst (bismuth triflate costs US$412/0.10 mol, whereas
© CSIRO 2008
10.1071/CH08109
0004-9425/08/060419

420
M. J. Spafford et al.
Table 1. Allylation of dioxolanes using Bi(OTf)3·xH2O
scandium triflate costs US$1629/0.10 mol) that has found sev-
eral applications as a Lewis acid recently.[26e,27] Unlike many air-
and highly moisture-sensitive metal triflates, Bi(OTf )3 can be
easily handled and dispensed in air. The allylation of 2-phenyl-
1,3-dioxolane catalyzed by Bi(OTf)3 resulted in low yields of the
expected homoallyl alcohol. Instead, the isolated product was a
mixture of the starting dioxolane and benzaldehyde, along with
small amounts of the expected homoallyl alcohol. In an attempt
to capture the putative alkoxide resulting from dioxolane ring-
opening, we carried out the reaction in the presence of acetic
anhydride. Gratifyingly, under these conditions we were able to
isolate highly functionalized esters in moderate to good yields.
We have now extended this methodology to a range of
dioxolanes and anhydrides (Table 1). Although the preliminary
studies were carried out in CH3CN and the product was iso-
lated by an aqueous workup, we subsequently carried out the
reactions under solvent-free conditions. The product was iso-
lated by filtering the reaction mixture through a column of silica
gel. As can be seen from Table 1, the yield of the ester product
decreased as the anhydride became more hindered. The allyla-
tions of dioxolanes reported to date in the literature using TiCl4,
AlCl3, or SnCl4 require low temperature conditions (−78◦C)
and a high catalyst loading (50–120 mol-%). In contrast, bis-
muth triflate is effective at a catalyst loading of 2.0 mol-%
and the reactions proceed smoothly at 0◦C. According to the
principles of Green Chemistry,[28] synthetic organic chemistry
should utilize reagents and catalysts that have little or no tox-
icity. In contrast to highly toxic tin compounds and corrosive
reagents such as TiCl4, bismuth(iii) compounds are remarkably
non-toxic[23] and easy to handle. Although detailed mechanis-
tic studies were not conducted, two control experiments were
carried out to determine the possible role of triflic acid in catalyz-
ing these reactions. The allylation of 2-(2-bromophenyl)-1,3-
dioxolane using allyltrimethylsilane and acetic anhydride (entry
1a) was successfully catalyzed using CF3SO3H (2.0 mol-%
and 6.0 mol-%) at about the same rate as with Bi(OTf)3. How-
ever, the same reaction in the presence of the proton sponge
1,8-bis(dimethylamino)naphthalene[29] (7.0 mol-%) was unsuc-
cessful. No reaction was observed in the absence of any catalyst.
Although these observations suggest that triflic acid might be
the catalyst for the reaction, it is possible that the coordination
of bismuth to the amino groups[30] of the proton sponge kills the
catalytic activity of bismuth triflate. Hence the role of Bi3+ as a
Lewis acid cannot be completely ruled out.
Bi(OTf)3 (2.0mol-%)
SiMe3
OCOR2
O
O
R1
R1
O
(R2CO)2O
0°C
Reaction was carried out using 1.7 equivalents of allyltrimethylsilane and
1.7 equivalents of the anhydride
Entry
R1
R2
Time
YieldA [%]
1a
1b
1c
2
3a
3b
4a
4b
5
o-BrC6H4
o-BrC6H4
o-BrC6H4
m-BrC6H4
o-ClC6H4
o-ClC6H4
p-ClC6H4
p-ClC6H4
o-FC6H4
p-CH3C6H4
PhCH2
PhCH2
CH3(CH2)8
CH3(CH2)8
CH3
iPr
tBu
CH3
CH3
iPr
CH3
iPr
CH3
CH3
CH3
iPr
1 h
62B
47C
54C
73D
70D
53C
67C
36C
61D
43D
68B
40D
73B
44C
4 h 30 min
2 h 40 min
45 min
40 min
1 h 15 min
40 min
35 min
1 h
1 h
2 h 50 min
15 h 15 min
21 h 30 min
3 h 35 min
6
7a
7b
8a
8b
CH3
iPr
ARefers to yield of isolated and purified product unless otherwise mentioned.
Purity was estimated to be ≥98% by GC, 1H and 13C NMR spectroscopy.All
compounds were also characterized by high resolution mass spectrometry.
BReaction was carried out in CH3CN at room temperature and the product
was isolated by an aqueous workup.
CProduct was isolated by filtering the reaction mixture directly through a
silica gel column.
DProduct was isolated by an aqueous workup followed by flash chromato-
graphic purification.
Varian capillary gas chromatograph. Bismuth(iii) triflate was
purchased from Lancaster Chemical Co. and stored under vac-
uum.Allyltrimethylsilane, the various anhydrides and anhydrous
acetonitrile were purchased fromAldrich Chemical Co. and used
as received. All reported compounds are new and were charac-
1
terized by H and 13C NMR spectroscopy and HRMS. Purity
was also determined by GC.
Representative Procedure: A mixture of 2-(4-chlorophenyl)-
1,3-dioxolane (0.5523 g, 2.99 mmol), allyltrimethylsilane
(0.81 mL, 0.58 g, 5.09 mmol), and acetic anhydride (0.48 mL,
0.52 g, 5.09 mmol) was stirred at 0◦C in a flame-dried, three-
neck, round-bottom flask under N2 as bismuth(iii) triflate
(0.0393 g, 0.060 mmol, 2.0 mol-%)wasadded.Thereactionmix-
ture became warm and turned yellow. Reaction progress was
monitored by GC. After 40 min at 0◦C, the reaction mixture was
loaded onto 60 g of silica and eluted with EtOAc/heptane (10:90
v/v). Fifty-nine fractions (8 mL) were collected. Fractions 39–59
were combined to yield 0.54 g (67%) of 4a as a clear liquid that
Conclusions
In summary, a bismuth triflate-catalyzed allylation of dioxolanes
followed by in situ derivatization with a range of acid anhydrides
to give highly functionalized esters has been developed. The use
of an easy to handle catalyst, solvent-free conditions and a facile
workup make this method suitable for scale-up.
was determined to be 98% pure by GC analysis and 1H and 13
C
NMR spectroscopy. δH 2.04 (s, 3H), 2.34–2.57 (m, 2H), 3.47
(t, 2H, J 4.9 Hz), 4.15 (t, 2H, J 5.0 Hz), 4.25 (t, 1H, J 6.5 Hz),
5.01 (app. t, 2H, J 5.7 Hz), 5.70 (m, 1H), 7.27 (m, 4H). δC (12
peaks) 170.9. 140.1, 134.1, 133.3, 128.5, 128.0, 117.2, 81.6,
66.5, 63.4, 42.3, 20.8. m/z (HRMS) C14H17ClO3, 269.09471
[M + H]; C14H18ClO3 calculated 269.09445.
Experimental Procedure
NMR spectra were recorded on a JEOL Eclipse NMR spec-
trometer at 270 MHz (1H) or 67.5 MHz (13C) in CDCl3 as the
solvent. Flash chromatography was performed on Merck silica
gel (230–400 mesh). TLC was performed on aluminium-backed
silica gel plates. Spots were visualized under UV light or by
spraying the plate with phosphomolybdic acid followed by heat-
Accessory Publication
ing. Products were characterized by H NMR and 13C NMR
1
spectroscopy and high resolution mass spectrometry. Product
purity was also checked by gas chromatography (GC) on a
Detailed experimental procedures and characterization of all
compounds (1H and 13C NMR spectra and HRMS data) are

Environmentally Friendly Organic Synthesis Using Bismuth Compounds
421
available from the author, or until May 2013, the Australian
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Acknowledgements
The authors gratefully acknowledge funding from the National Science
Foundation for an RUI (Research at Undergraduate Institutions) grant (no.
0650682) awarded to R.S.M.
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