Radical reactions using decacarbonyldimanganese under biphasic conditions

Article abstract of DOI:10.1002/ejoc.200400025

Radical reactions of alkyl halides, initiated by photolysis in the presence of decacarbonyldimanganese, can be performed in biphasic media. Reactions in the presence of aqueous sodium hydroxide together with a phase-transfer catalyst result in the efficient removal of manganese halide by-products and also lead to the regeneration of decacarbonyldimanganese. A range of efficient radical couplings, cyclisations and intermolecular addition reactions were performed under these conditions. This included the development of a new tandem radical addition-ionic cyclisation sequence that was employed in a short approach to (±)-coronamic acid. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400025

FULL PAPER
Radical Reactions Using Decacarbonyldimanganese under Biphasic Conditions
Nathalie Huther,[a] P. Terry McGrail,[b] and Andrew F. Parsons*[a]
Keywords: Cyclization / Manganese / Heterocycles / Phase-transfer catalysis / Radical reactions
Radical reactions of alkyl halides, initiated by photolysis in
the presence of decacarbonyldimanganese, can be per-
formed in biphasic media. Reactions in the presence of aque-
ous sodium hydroxide together with a phase-transfer catalyst
result in the efficient removal of manganese halide by-prod-
and intermolecular addition reactions were performed under
these conditions. This included the development of a new
tandem radical addition−ionic cyclisation sequence that was
employed in a short approach to ( )-coronamic acid.
ucts and also lead to the regeneration of decacarbonyldiman- ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ganese. A range of efficient radical couplings, cyclisations
Germany, 2004)
Introduction
of Gibson and co-workers.[8] This work showed that penta-
carbonylmanganese halides, in benzene, react with aqueous
sodium hydroxide in the presence of the phase-transfer
catalyst benzyltriethylammonium chloride (BTAC) to pro-
duce a water-soluble binuclear anion 1 (Scheme 1). This
method could therefore be used to remove organic-soluble
pentacarbonylmanganese halide by-products (produced
during halogen-atom abstraction reactions) from organic
products by conversion into water-soluble salts. Further-
more, the formation of Mn2(CO)10 was observed under the
phase-transfer reactions, which could be explained by the
formation of the pentacarbonylmanganese anion,
ϪMn(CO)5, produced in the presence of the phase-transfer
catalyst, as shown in Scheme 1.[9] Hence, rather than depro-
tonation of (CO)4MnH(X)ϪMn(CO)5, nucleophilic attack
by hydroxide ion could form ϪMn(CO)5 and
(CO)4MnH(X)ϪOH. These results suggested that not only
could the manganese halide by-products be removed from
the organic layer but also that the radical initiator, namely
Mn2(CO)10, could be regenerated.
The reaction of alkyl halides with decacarbonyldiman-
ganese, Mn2(CO)10, has proved to be a particularly mild
and efficient method of forming carbon-centred radicals.[1]
Homolytic cleavage of the weak MnϪMn bond can be
achieved by heating or irradiating Mn2(CO)10 with visible
light to form the pentacarbonylmanganese radical,
·Mn(CO)5, which is able to abstract halogen atoms from
a variety of organohalides bearing weak carbonϪhalogen
bonds. Examples of radical coupling,[2] cyclisation,[3] inter-
molecular addition[4] and polymerisation reactions[5,6] have
recently been reported by our group and others. These
reactions produce pentacarbonylmanganese halides
[XMn(CO)5] as by-products, which can be removed from
the organic products either by reaction with DBU[2] or by
aerial oxidation.[5] In both cases, polar manganese products
are formed that can be removed from the organic products
by filtration and/or column chromatography. However, sep-
aration of these polar manganese compounds can be prob-
lematic when working with polar organic products. Prob-
lems also arise when using organic compounds that can re-
act with DBU, and the aerial oxidation method can be time-
consuming. In order to develop a more general method for
removing pentacarbonylmanganese halide by-products, our
attention turned to the use of phase-transfer catalysed reac-
tions.
Radical reactions in biphasic media are well-known[7]
and we became interested in the use of these conditions in
Mn2(CO)10-mediated radical reactions following the work
[a]
Department of Chemistry, University of York,
Heslington, York YO10 5DD, UK
Fax: (internat.) ϩ44-1904-432516
E-mail: afp2@york.ac.uk
[b]
Cytec Fiberite Ltd,
Scheme 1. Reaction of pentacarbonylmanganese halides in bi-
phasic media
N131 Wilton Centre, Wilton, Redcar TS10 4RF, UK
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DOI: 10.1002/ejoc.200400025
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Radical Reactions under Biphasic Conditions
FULL PAPER
biphasic conditions resulted in the efficient removal of the
pentacarbonylmanganese bromide by-product from the or-
ganic product, as indicated by the H NMR spectra of the
Results and Discussion
1
In order to investigate the use of biphasic conditions, in-
itial photolysis experiments concentrated on the dimeris-
ation of benzyl bromide using different amounts of
Mn2(CO)10, in the presence of aqueous sodium hydroxide
and the phase-transfer catalyst BTAC, as shown in
Scheme 2 and Table 1.[10] Disappointingly, when 0.5 equiva-
lents of Mn2(CO)10 were used, this resulted in the desired
dimer 2 in only 36% yield (compared to 99% yield in di-
chloromethane[2]) (Table 1, entry 1). Surprisingly, the major
by-product was benzylpentacarbonylmanganese (3), which
was only formed in the presence of the phase-transfer cata-
lyst (Table 1, entry 2). This presumably arises from a nucle-
ophilic substitution reaction of benzyl bromide with the
pentacarbonylmanganese anion, which is conventionally
prepared by reduction of Mn2(CO)10 using sodium/mer-
cury amalgam.[11]
crude products.
In order to prove that Mn2(CO)10 is regenerated from
BrMn(CO)5 under biphasic conditions, several dimerisation
experiments were conducted starting with benzyl bromide
and pentacarbonylmanganese bromide. On photolysis of
benzyl bromide in the presence of 0.5Ϫ2 equivalents of
BrMn(CO)5 for 2Ϫ7 h, bibenzyl (2) was formed in 22Ϫ60%
yield, together with benzylpentacarbonylmanganese (3) in
7Ϫ35% yield. In the absence of photolysis, only 3 was iso-
lated (in 50% yield after 4 h), which again suggests that 2
is formed from 3 during photolysis. The formation of 2 is
consistent with the conversion of BrMn(CO)5 to
Mn2(CO)10; TLC, IR and EIMS analysis of the crude prod-
ucts confirmed the presence of Mn2(CO)10. The use of
pentacarbonylmanganese iodide or pentacarbonylmanga-
nese chloride was also found to lead to the formation of 2,
although the yields were lower (typically around 23Ϫ28%)
than when using pentacarbonylmanganese bromide, under
the same conditions. To the best of our knowledge, this is
the first time that pentacarbonylmanganese halides have
been used to initiate radical reactions leading to the forma-
tion of a carbonϪcarbon bond.
Scheme 2. Radical coupling of benzyl bromide
Investigations to quantify the amount of Mn2(CO)10 pro-
duced from pentacarbonylmanganese halides (in the pres-
ence of aqueous sodium hydroxide and BTAC) were also
carried out. After photolysis for 2 h, pentacarbonylmanga-
nese bromide and iodide produced Mn2(CO)10 in 16Ϫ17%
yield, whereas a higher yield of 35% (after 2 h) or 46%
(after 1 h) was obtained when using pentacarbonylmanga-
nese chloride. This work also showed that BTAC is not re-
quired for the formation of Mn2(CO)10, since photolysis of
a solution of ClMn(CO)5 in dichloromethane, together with
aqueous sodium hydroxide, produced Mn2(CO)10 in 43%
yield after 2 h. Interestingly, when benzyl bromide was
treated with 0.5 equivalents of ClMn(CO)5 (for 4 h) in the
absence of BTAC, bibenzyl (2) was isolated in 83% yield
but benzylpentacarbonylmanganese (3) was formed in only
2% yield (cf. Table 1, entry 1). These results suggest that
Table 1. Reaction of benzyl bromide with Mn2(CO)10 in biphasic
media
Entry
Mn2(CO)10 [eq.]
Time [h]
2 [%]
3 [%]
1
0.50
0.50
0.25
0.25
0.20
0.10
0.05
2
2
2
4
6
16
96
36
80
40
80
43
0
9
0
0
0
0
2[a]
3
4
5
6
7
75
53
25 (99)[b]
[a]
[b]
No BTAC was used. Yield based on recovered starting mate-
rial.
On reducing the amount of Mn2(CO)10 to 0.25 or 0.20 whereas ClMn(CO)5 can react with the aqueous layer to
equivalents, good yields of bibenzyl (2) were obtained after form Mn2(CO)10 in the absence of BTAC, BTAC is required
4 and 6 h, respectively (Table 1, entries 3Ϫ5). Even the use to transfer the pentacarbonylmanganese anion into the or-
of 0.1 or 0.05 equivalents of Mn2(CO)10 still allowed the ganic layer, where it can form BnMn(CO)5 (3). At present,
formation of 2 in moderate yields of 53% and 25% respec- the mechanism by which ClMn(CO)5 is converted into
tively, after extended reaction times (Table 1, entries 6 and Mn2(CO)10 in the absence of BTAC is unclear.
7). Because 0.5 equivalents of Mn2(CO)10 are required for
Application of the biphasic system to a variety of alterna-
complete conversion of benzyl bromide to 2, the reason- tive coupling reactions was then investigated. Hence pho-
able-to-excellent yields obtained when using only 0.25Ϫ0.05 tolysis of 5-(bromomethyl)-1,3-benzodioxole or 5-(bromo-
equivalents of Mn2(CO)10 provide good evidence for the re- methyl)-1,2,3-trimethoxybenzene in dichloromethane with
generation of Mn2(CO)10 under the biphasic conditions. Mn2(CO)10 (0.5 equivalents) in the presence of aqueous so-
Interestingly, it should also be noted that benzylpentacar- dium hydroxide and BTAC formed the naturally occurring
bonylmanganese (3) is only isolated after short reaction dimers[13] 4 and 5 in 47% and 36% yield, respectively. Al-
times, which suggests that by increasing the reaction time, though similar reactions, carried out solely in dichloro-
3 is converted into 2. This may arise through homolysis of methane, were higher-yielding (70% and 48% for 4 and 5,
the weak MnϪC bond of 3 to give the benzyl radical,[12] respectively), addition of DBU was required in order to re-
although this could not be proved. In all cases, the use of move the BrMn(CO)5 by-product.
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N. Huther, P. T. McGrail, A. F. Parsons
FULL PAPER
The mild conditions and chemoselective nature of this
method of radical generation was further exemplified by the
formation of the pyrrolidine 9c (as a 2.5:1 mixture of dia-
stereomers) on cyclisation of the trichloroamide 8c with
BrCCl3 (3 equivalents) in the presence of BrMn(CO)5 (0.65
equivalents). It should be noted, however, that trichloroam-
ides can be reduced under these conditions in the absence
of BrCCl3. This is illustrated by the reaction of the benza-
mide 10 with BrMn(CO)5, which produced the reduced
products 11 and 12 in 46% and 26% yield, respectively, to-
gether with a 3% yield of the pyrrolidinone 13. These re-
duced products may be derived from hydrogen-atom ab-
straction reactions, or alternatively, the intermediate rad-
icals could be reduced to carbanions that are subsequently
protonated.
An interesting contrast in reactivity between Mn2(CO)10-
mediated couplings carried out in biphasic media, as op-
posed to dichloromethane, was observed on reaction with
1-bromoethylbenzene. Whereas photolysis of 1-bromoethyl-
benzene with Mn2(CO)10 (0.5 equivalents) in dichlorometh-
ane afforded only starting material, the same reaction using
0.5 equivalents of Mn2(CO)10 in biphasic media afforded
2,3-diphenylbutane (6) (as a 1:1 mixture of diastereomers)
in 70% yield. A similar reaction using one equivalent of
BrMn(CO)5 in biphasic conditions also afforded 6 in a
slightly improved yield of 79%. Also, whereas attempted
coupling
of
(1-bromo-1-methylethyl)benzene
using
Mn2(CO)10 was unsuccessful in dichloromethane, in bi-
phasic media, 2,3-dimethyl-2,3-diphenylbutane (7) was iso-
lated in 25% yield. The use of biphasic media therefore ex-
tends the scope of precursors that can be employed in
manganese carbonyl-mediated radical reactions to second-
ary and tertiary (as well as primary) benzylic halides. These
contrasting results also provide further evidence to support
the fact that the reaction mechanism in biphasic media is
different to that in dichloromethane.
In order to expand the synthetic applications of the bi-
phasic system, halogen-atom transfer cyclisations of the
1,6-dienes 8aϪc were investigated by reaction with bromo-
trichloromethane in the presence of Mn2(CO)10 or
BrMn(CO)5 (Scheme 3). Photolysis of the malonate 8a with
BrCCl3 (3 equivalents) and 0.1 equivalents of Mn2(CO)10
or 0.2 equivalents of BrMn(CO)5 both gave the cyclopen-
tane 9a in quantitative yield (in a cis:trans ratio of
10Ϫ18:1). Similarly, reaction of diallyl ether (8b) with either
Mn2(CO)10 or BrMn(CO)5, under the same conditions as
for 8a, gave the tetrahydrofuran 9b in quantitative yield (as
a 6:1 mixture of separable cis:trans diastereomers). (It
should be noted that control reactions in the absence of
Mn2(CO)10 gave unchanged starting material[3a]).
Related halogen-atom transfer cyclisations were observed
on reaction of the dienes 8aϪe with sulfonyl chlorides
(Schemes 4 and 5). Addition of benzenesulfonyl chloride (3
equivalents) to the malonate 8a (1 equivalent) in the pres-
ence of Mn2(CO)10 (0.3 equivalents), under biphasic con-
ditions, afforded the expected chlorine-atom transfer prod-
uct 14a in 78% yield (as a 2:1 mixture of cis:trans isomers).
In addition, the 3-methylcyclopentane 15a was isolated in
10% yield. The formation of 15a may be explained by ab-
straction of a hydrogen atom from dichloromethane by the
primary radical, formed by 5-exo-trig cyclisation.[3a] A simi-
lar reaction, to give the tetrahydrofurans 14b and 15b, was
observed when diallyl ether (8b) was treated with
Mn2(CO)10 under the same conditions.
Attempts to react 8a,b (1 equivalent) with methanesul-
fonyl chloride (3 equivalents) and Mn2(CO)10 under bi-
phasic conditions were disappointing, presumably due to
the instability of methanesulfonyl chloride in the presence
of water. However, these cyclisations can be carried out in
dichloromethane, and the ClMn(CO)5 by-product removed
(from the cyclic products) at the end of the reaction by ad-
ding aqueous sodium hydroxide solution and BTAC — this
has the added advantage of hydrolysing unchanged Me-
SO2Cl (which is used in threefold excess) (Scheme 5). Under
these conditions, the malonate 8a is converted into the
cyclopentanes 16a and 17a in a combined yield of 82%,
whereas diallyl ether (8b) gives rise to the methyl sulfones
16b and 17b in 59% and 35% yield, respectively. The syn-
thesis of pyrrolidines is also possible, as illustrated by the
reaction of methanesulfonyl chloride and Mn2(CO)10 with
the benzenesulfonamide 8d and benzamide 8e. As well as
the expected chlorides 16d and 16e, good yields of methyl
pyrrolidines 17d and 17e were isolated from competitive hy-
drogen-atom abstraction reactions.
Scheme 3. Radical cyclisation of 1,6-dienes using bromotrichloro-
methane
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Radical Reactions under Biphasic Conditions
FULL PAPER
Scheme 4. Radical cyclisation of 1,6-dienes using benzenesulfonyl chloride
Scheme 5. Radical cyclisation of 1,6-dienes using methanesulfonyl chloride
Following the successful removal of the manganese hal- tries 1Ϫ3). These one-pot reactions produced good-to-ex-
ide by-products from the organic products in the biphasic cellent yields of the desired cyclopropane 19, together with
radical reactions, our efforts focussed on applying these small amounts of the bromide 21, formed on reaction of
conditions to the initiation of novel sequential reactions. the enolate derived from 18 with BrCCl3 [as confirmed by
The aim was to perform a decacarbonyldimanganese-me- a control reaction in the absence of Mn2(CO)10]. However,
diated radical addition reaction to give an intermediate that the formation of 18 can be minimised by ensuring that the
could then undergo an ionic cyclisation promoted by the base is added to the reaction mixture after completion of
biphasic conditions. Of particular interest was the forma- the radical addition, which can be facilitated by increasing
tion of substituted cyclopropanes by elaboration of allyl- the number of equivalents of Mn2(CO)10. The use of CBr4
substituted 1,3-dicarbonyls such as the malonate 18 instead of BrCCl3 gave a similar result, providing the tribro-
(Scheme 6).
mocyclopropane 20 in 56% yield (Table 2, entry 4). By com-
Following manganese carbonyl-promoted radical ad- parison, the use of biphasic conditions afforded the desired
dition of BrCCl3 or CBr4 to the double bond of 18, it was cyclic products 19 and 20 in excellent yields of 80% and
envisaged that the intermediate secondary bromide or chlo- 88%, respectively (Table 2, entries 5 and 6).
ride could be deprotonated to give an enolate, which could
then undergo a 3-exo-tet anionic cyclisation leading to 19
or 20.[14] Initial reactions centred on the photolysis of 18
with various quantities of Mn2(CO)10 and BrCCl3 (3 equiv-
alents) followed, after 6 hours by addition of DBU to in-
itiate the formation of the cyclopropane ring (Table 2, en-
This methodology can be used to prepare cyclopropanes
from other 1,3-dicarbonyls. For example, photolysis of the
β-keto ester 22 with Mn2(CO)10 and BrCCl3, followed by
addition of base, gave the trichloride 23 in 60% yield as a
1:1 mixture of diastereomers.
Table 2. Reaction of diethyl allyl malonate (18) with BrCCl3 or
CBr4 and Mn2(CO)10
Entry
X
Mn2(CO)10 [eq.] Base
19 or 20 [%] 21 [%]
The resulting halogenated cyclopropanes are useful syn-
thetic intermediates. For example, the cyclopropanes 19 and
20 can be elaborated to the hydrochloride salt of (Ϯ)-cor-
onamic acid 27 (a constituent amino acid of the plant toxin
coronatine),[15] using conventional methodology, as shown
in Scheme 7. Hence, reduction of 19 and 20 using tributyltin
1
2
3
4
5
6
Cl 0.1
Cl 0.2
Cl 0.3
Br 0.1
Cl 0.3
Br 0.3
DBU
DBU
DBU
DBU
NaOH 80
NaOH 88
60
72
75
56
13
7
Ͻ5
28
0
0
Scheme 6. Formation of halogenated cyclopropanes
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N. Huther, P. T. McGrail, A. F. Parsons
FULL PAPER
Scheme 7. Synthesis of (Ϯ)-coronamic acid (27)
Mattson Genesis Series FT IR spectrometer, and samples were pre-
pared as thin films or as solutions in CHCl3 or CH2Cl2. Mass spec-
tra were recorded on a Fisons Instruments VG Analytical Autospec
Spectrometer system as low and high resolution EI and CI (NH3)
spectra. Photolysis reactions were performed with visible light (λ
Ͼ 400 nm) using an ICL 302 UV xenon lamp (300 W). Melting
points were recorded on a Gallenkamp melting point apparatus.
Thin layer chromatography (TLC) was performed using Merck
5554 aluminium-backed silica gel plates; compounds were visual-
ised by either UV lamp irradiation or staining with alkaline aque-
hydride afforded the cyclopropane 24 in 83Ϫ89% yield,
which on reaction with potassium hydroxide in ethanol re-
sulted in selective hydrolysis of the less hindered ester to
give 25.[16] Formation of the mixed anhydride by treatment
of the acid with ethyl chloroformate followed by Curtius
rearrangement and hydrolysis led to the amine hydrochlo-
ride salt 26 in a 55% yield (unoptimised). Finally, heating
26 in hydrochloric acid afforded the amino acid hydrochlo-
ride salt 27. The overall yield of this short approach to ra-
cemic 27 from diethyl allylmalonate 18 is 28% (using CBr4 ous potassium permanganate solution. Column chromatography
was carried out under gravity using Fisons Matrex Silica 60
(70Ϫ200 microns) or ICN Biomedicals GmbH flash silica 60
(32Ϫ63 microns) and the specified eluent.
in the radical addition step) or 27% (using BrCCl3).
Conclusion
General Procedure for the Homocoupling Reaction of Benzyl Bro-
mide under Biphasic Conditions: Benzyl bromide (0.25 g,
1.46 mmol) was added to
a stirred solution of Mn2(CO)10
This work has demonstrated, for the first time, that deca-
carbonyldimanganese mediated radical reactions can be
performed under biphasic conditions. The presence of
aqueous sodium hydroxide and BTAC can successfully re-
move pentacarbonylmanganese halide by-products pro-
duced from radical reactions of alkyl halides. Moreover, re-
actions under biphasic conditions using XMn(CO)5 instead
of Mn2(CO)10 have been shown to work efficiently, and the
in situ formation of Mn2(CO)10 has been established. This
may be explained by the intermediate formation of the
pentacarbonylmanganese anion, which could also explain
the formation of an organomanganese adduct on reaction
with benzyl bromide. Application of the biphasic conditions
to a range of couplings, cyclisations and intermolecular ad-
dition reactions has been successfully achieved, and
Mn2(CO)10 has been shown to react with BrCCl3, CBr4 and
sulfonyl chlorides to produce electrophilic radicals that can
add to electron-rich alkenes. This has been exploited for the
(0.14Ϫ0.40 g, 0.36Ϫ1.46 mmol) or Mn(CO)5X (X ϭ Br, Cl, I)
(0.73Ϫ2.92 mmol) in degassed dichloromethane (10 cm3). An aque-
ous solution of sodium hydroxide (5 , 10 cm3) containing benzyl-
triethylammonium chloride (0Ϫ0.04 g, 0Ϫ0.18 mmol) was then ad-
ded and the mixture was photolysed under an atmosphere of nitro-
gen for 2Ϫ27 h. The organic layer was separated, washed with
water and dried over MgSO4. The crude mixture was then adsorbed
onto silica. Column chromatography (silica, petroleum ether) gave
bibenzyl (2)[2] (11Ϫ80%) as a white solid and benzylpentacarbon-
ylmanganese (3)[12] (0Ϫ56%) as an orange solid.
Benzylpentacarbonylmanganese (3): Rf ϭ 0.22 (petroleum ether).
1
m.p. 37Ϫ39 °C. H NMR (270 MHz, CDCl3): δ ϭ 7.25Ϫ7.16 (m,
4 H, aromatics Hortho/Hmeta), 6.96 (m, 1 H, aromatic Hpara), 2.40
(s, 2 H, CH2) ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 151.8 (Cϭ
CH), 128.6 (CϭCH), 125.8 (CHϭCH), 123.4 (CHϭCH), 11.1
(CH2Mn) ppm. IR (CH2Cl2): ν˜ ϭ 2107 (m), 2043 (w), 2016 (Cϭ
O, s), 2007 (CϭO, s) cmϪ1. MS (EI): m/z (%) ϭ 287 (100) [Mϩ],
231 (40), 180 (36), 91 (86). HRMS for MnC12H7O5: calcd. 286.9752
[Mϩ]; found 286.9746.
formation of cyclopropanes using
a
new radical
5-[2-(1,3-Benzodioxol-5-yl)ethyl]-1,3-benzodioxole (4): Mn2(CO)10
(0.18 g, 0.45 mmol) was added to a stirred solution of 5-(bromo-
methyl)-1,3-benzodioxole (0.20 g, 0.90 mmol) in degassed dichloro-
methane (10 cm3) under nitrogen. An aqueous solution of NaOH
(5 , 10 cm3) containing BTAC (0.02 g, 0.11 mmol) was then added
and the mixture was irradiated under nitrogen until disappearance
of the starting material. After the reaction time, the organic layer
was separated, washed with water and dried over MgSO4. The
crude mixture was adsorbed onto silica; column chromatography
(silica, petroleum ether/ethyl acetate, 6:1) afforded 4[13b] (56 mg,
47%) as a white solid.
additionϪionic cyclisation sequence, which has been ap-
plied to a concise synthesis of (Ϯ)-coronamic acid (27).
Experimental Section
General Remarks: 1H and 13C NMR spectra were recorded on Jeol
EX 270, Jeol ECX 400, Bruker DMX 300 or Bruker AMX 500
spectrometers. Carbon spectra were recorded at 67.5 MHz and as-
signed using DEPT experiments. Coupling constants are recorded
to the nearest 0.5 Hz. Samples were prepared as solutions in CDCl3
and contained an internal tetramethylsilane standard to which
chemical shifts are referenced. IR spectra were recorded on an ATI
1,2,3-Trimethoxy-5-(3,4,5-trimethoxyphenethyl)benzene (5): Mn2-
(CO)10 (0.15 g, 0.38 mmol) was added to a stirred solution of 3,4,5-
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Radical Reactions under Biphasic Conditions
FULL PAPER
trimethoxybenzyl bromide (0.20 g, 0.77 mmol) in degassed di-
chloromethane (10 cm3) under nitrogen. An aqueous solution of
NaOH (5 , 10 cm3) containing BTAC (0.02 g, 0.09 mmol) was
added and the mixture was irradiated under nitrogen until disap-
pearance of the starting material, as indicated by TLC. After the
reaction time, the organic layer was separated, washed with water
and dried over MgSO4. The crude mixture was then adsorbed onto
silica and column chromatography (silica, petroleum ether/ethyl
acetate, 6:1) afforded 5[17] (51 mg, 36%) as a white solid.
(m, 1 H, CHBr), 3.20Ϫ3.11 (m, 1 H, CHCl), 2.99Ϫ2.84 (m, 3 H,
CHCl and 2 ϫ CHCH2) ppm. 13C NMR (67.5 MHz, [D8]Tol, 80
°C): δ ϭ 159.0 (CϭO), 99.3 (CCl3CH2), 94.8 (CCl3CϭO), 58.5,
56.3 and 53.9 (CH2CCl3 and 2 ϫ CH2N), 50.2 (CHCH2Br), 47.6
(CHCH2CCl3), 35.5 (CH2Br) ppm. IR (CHCl3): ν˜ ϭ 3031 (w), 2958
(br., w), 2888 (br., w), 1674 (CϭO, s), 1406 (m), 1230 (m) cmϪ1. MS
(CI/NH3): m/z (%) ϭ 455 (27) [79,35M ϩ NH4؉], 438 (34) [79,35M ϩ
Hϩ], 442 (100), 320 (33). HRMS (C9H11BrCl6NO): calcd. 437.8155
[
79,35M ϩ Hϩ]; found 437.8148.
Typical Procedure for the Cyclisation of Dienes 8a,b in the Presence
of Benzenesulfonyl Chloride: Mn2(CO)10 (0.11 g, 0.28 mmol) was
added to a stirred solution of benzenesulfonyl chloride (0.45 g,
2.56 mmol) and the diene 8a,b (0.86 mmol) in degassed dichloro-
methane (20 cm3) under nitrogen. An aqueous solution of NaOH
(5 , 20 cm3) containing BTAC (0.03, 0.21 mmol) was added and
the mixture photolysed for 2 h. After the reaction time, the organic
layer was separated, washed with water and dried over MgSO4. The
crude product was adsorbed onto silica; column chromatography
afforded the inseparable products 14a,b and 15a,b as oils.
2,3-Diphenylbutane (6): 1-Bromoethylbenzene (0.27 g, 1.46 mmol)
was added to a stirred solution of Mn2(CO)10 (0.28 g, 0.73 mmol)
in degassed dichloromethane (10 cm3). An aqueous solution of so-
dium hydroxide (5 , 10 cm3) containing BTAC (0.03 g, 0.18 mmol)
was added and the mixture photolysed under an atmosphere of
nitrogen for 2 h. After the reaction time, the organic layer was sepa-
rated, washed with water and dried over MgSO4. The crude mix-
ture was adsorbed onto silica; column chromatography (silica,
petroleum ether) afforded 6[18] (111 mg, 75%) as an inseparable
1
mixture of two diastereomers in a 1:1 ratio, as indicated by the H
NMR spectrum.
Diethyl 3-(Chloromethyl)-4-[(phenylsulfonyl)methyl]-1,1-cyclopen-
tanedicarboxylate (14a) and Diethyl 3-methyl-4-[(phenylsulfonyl)-
methyl]-1,1-cyclopentanedicarboxylate (15a): Pale yellow oil; Rf ϭ
0.4 (petroleum ether/ethyl acetate, 2:1). IR (CHCl3) (as an 8:1 mix-
2,3-Dimethyl-2,3-diphenylbutane (7): 1-(1-Bromo-1-methylethyl)-
benzene (0.29 g, 1.46 mmol) was added to a stirred solution of
Mn2(CO)10 (0.28 g, 0.73 mmol) in degassed dichloromethane (10
cm3). An aqueous solution of sodium hydroxide (5 , 10 cm3) con-
taining BTAC (0.03 g, 0.18 mmol) was added and the mixture pho-
tolysed under an atmosphere of nitrogen for 4 h. After the reaction
time, the organic layer was separated, washed with water and dried
over MgSO4. The crude mixture was adsorbed onto silica; column
chromatography (silica, petroleum ether) afforded 7[19] (40 mg,
25%) as a colourless oil.
1
ture of 14a and 15a, as indicated by the H NMR spectrum): ν˜ ϭ
3031 (m), 2984 (m), 1725 (CϭO, vs), 1447 (w), 1307 (s), 1266 (s),
1228 (s), 1185 (m), 1151 (s), 1087 (w), 908 (s) cmϪ1. Compound
1
14a: Yield: 78%, 2:1 ratio of diastereomers (as indicated by the H
NMR spectrum). Major (cis) isomer: 1H NMR (270 MHz, CDCl3):
δ ϭ 7.89Ϫ7.47 (m, 5 H, aromatics), 4.18Ϫ4.06 (q, J ϭ 7 Hz, 4 H,
2 ϫ CH2CH3), 3.43 (d, J ϭ 7 Hz, 1 H, CHSO2), 3.31Ϫ3.01 (m, 2
H, CHSO2 and CHCl), 2.69Ϫ1.89 (m, 7 H, CHCl, 2 ϫ CHCH2
and 2 ϫ CHCH2), 1.23Ϫ1.17 (m, 6 H, 2 ϫ CH2CH3) ppm. 13C
NMR (67.5 MHz, CDCl3): δ ϭ 172.5 (CϭO), 172.3 (CϭO), 139.9
(CϭCH), 134.5 (CϭCH), 130.0 (CHϭCH), 128.6 (CHϭCH), 62.4
(CH2CH3), 59.1 [C(CO2Et)2], 56.2 (CH2SO2), 44.9 (CHCH2Cl),
44.4 (CH2Cl), 38.9 (CHCH2SO2), 37.8 (CH2), 36.4 (CH2) ppm. The
presence of the minor (trans) isomer was indicated by: 1H NMR
(270 MHz, CDCl3): δ ϭ 3.33 (m, 1 H, CHSO2 or CHCl) ppm. MS
(CI, NH3): m/z (%) ϭ 434 (82) [35M ϩ NH4ϩ], 400 (100). HRMS
(C19H28ClNO6S): calcd. 434.1404 [35M ϩ NH4ϩ]; found 434.1398.
Compound 15a: Yield: 10%, 15:1 ratio of diastereomers (as indi-
General Procedure for Bromine-Atom Transfer Reactions Using
BrCCl3 under Biphasic Conditions: Mn2(CO)10 (0.11 g, 0.28 mmol)
or Mn(CO)5Br (0.15 g, 0.56 mmol) was added to a stirred solution
of BrCCl3 (0.51 g, 2.56 mmol) and the diene 8aϪc (0.08Ϫ0.22 g,
0.86 mmol) in dichloromethane (20 cm3) under an atmosphere of
nitrogen. An aqueous solution of sodium hydroxide (5 , 20 cm3)
containing BTAC (0.01 g, 0.07 mmol) was added and the mixture
photolysed under an atmosphere of nitrogen for 2 h. After the reac-
tion time, the organic layer was separated, washed with water and
dried over MgSO4. The crude mixture was adsorbed onto silica;
column chromatography afforded products 9a,[3a] 9b[3a] and 9c
(0.24Ϫ0.45 g, 64Ϫ99%), as colourless oils, as mixtures of dia-
stereomers in the ratio 2.5Ϫ18:1, as indicated by the 1H NMR spec-
tra.
1
cated by the H NMR spectrum). The presence of the major (cis)
isomer was indicated by: 1H NMR (270 MHz, CDCl3): δ ϭ 0.79
(d, J ϭ 7 Hz, 3 H, CH3) ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ
37.4 (CH-CH3), 15.6 (CH3). The presence of the minor (trans) iso-
1
mer was indicated by: H NMR (270 MHz, CDCl3): δ ϭ 0.91 (d,
3-(Bromomethyl)-1-(trichloroacetyl)-4-(2,2,2-trichloroethyl)-
3 H, J ϭ 7 Hz, CH3) ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ
38.0 (CHCH3), 14.5 (CH3) ppm.
pyrrolidine (9c): Major (cis) isomer: Rf ϭ 0.3 (petroleum ether/ethyl
1
acetate, 9:1). H NMR (270 MHz, [D8]Tol, 80 °C): δ ϭ 4.41 (br. s,
2 H, CH2N), 4.04 (dd, 2 H, J ϭ 6 and 12 Hz, CH2N), 3.57 (dd, 1 3-(Chloromethyl)-4-[(phenylsulfonyl)methyl]tetrahydrofuran
(14b)
and 3-Methyl-4-[(phenylsulfonyl)methyl]tetrahydrofuran (15b): Pale
yellow oil; Rf ϭ 0.4 (petroleum ether/ethyl acetate, 2:1). IR (CHCl3)
H, J ϭ 4.5 and 10 Hz, CHBr), 3.35 (1 H, apparent t, J ϭ 10 Hz,
CHBr), 3.18Ϫ3.12 (m, 1 H, CHCl), 3.02Ϫ2.88 (m, 3 H, CHCl and
2 ϫ CHCH2) ppm. 13C NMR (67.5 MHz, [D8]Tol, 80 °C): δ ϭ (as an inseparable 7:1 mixture of 14b:15b, as indicated by the 1H
159.6 (CϭO), 99.7 (CCl3CH2), 96.6 (CCl3CϭO), 54.0 and 53.8 NMR spectrum): ν˜ ϭ 3033 (w), 2927 (m), 2856 (w), 1447 (w), 1308
(CH2CCl3 and 2 ϫ CH2N), 45.2 (CHCH2Br), 40.0 (CHCH2CCl3), (s), 1228 (s), 1150 (s), 1185 (m), 1087 (m) cmϪ1. Compound 14b:
30.8 (CH2Br) ppm. IR (CHCl3): ν˜ ϭ 2964 (w), 2890 (w), 1674 (Cϭ
O, s), 1408 (m), 1245 (w), 1180 (w), 850 (m), 812 (s) cmϪ1. MS (CI/ NMR spectrum). Major (cis) isomer: 1H NMR (270 MHz, CDCl3):
NH3): m/z (%) ϭ 455 (24) [79,35M ϩ NH4؉], 438 (31) [79,35M ϩ
δ ϭ 7.94Ϫ7.57 (m, 5 H, aromatics), 4.15Ϫ4.08 (m, 1 H, OCH),
Yield: 42%, 1.7:1 ratio of diastereomers (as indicated by the 1H
Hϩ], 442 (100), 320 (31). HRMS (C9H11BrCl6NO): calcd. 437.8155 4.00Ϫ3.87 (m, 2 H, 2 ϫ OCH), 3.79Ϫ3.67 (m, 1 H, OCH),
[
79,35M ϩ Hϩ]; found 437.8153. Minor (trans) isomer: Rf ϭ 0.2 3.52Ϫ3.49 (m, 1 H, PhSO2CHAHB), 3.34Ϫ3.30 (m, 1 H, PhSO2-
1
(petroleum ether/ethyl acetate, 9:1). H NMR (270 MHz, [D8]Tol,
CHAHB), 3.22Ϫ3.03 (m, 1 H, ClCHAHB), 2.96Ϫ2.70 (m, 3 H,
80 °C): δ ϭ 4.85 (1 H, br. s, CHN), 4.49 (1 H, br. s, CHN), ClCHAHB and 2 ϫ OCH2CH) ppm. 13C NMR (67.5 MHz,
3.98Ϫ3.91 (m, 2 H, CH2N), 3.66Ϫ3.57 (m, 1 H, CHBr), 3.45Ϫ3.38 CDCl3): δ ϭ 139.6 (CϭCH), 134.7 (CϭCH), 130.1 (CHϭCH),
Eur. J. Org. Chem. 2004, 1740Ϫ1749
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1745

N. Huther, P. T. McGrail, A. F. Parsons
128.6 (CHϭCH), 71.5 (OCH2), 71.3 (OCH2), 54.9 (ClCH2), 44.5 trum. IR (CHCl3): ν˜ ϭ 3029 (s), 2956 (s), 2931 (s), 2873 (s), 1305
FULL PAPER
(CHCH2Cl), 36.7 (CHCH2SO2Ph), 30.3 (PhSO2CH2). The pres-
(vs), 1232 (vs) cmϪ1. Major (cis) isomer: 1H NMR (270 MHz,
ence of the minor (trans) isomer was indicated by: 1H NMR CDCl3): δ ϭ 4.08Ϫ3.93 (m, 3 H, OCH and 2 ϫ OCH), 3.83Ϫ3.72
(270 MHz, CDCl3): δ ϭ 3.65Ϫ3.55 (m, 1 H, PhSO2CH) ppm. 13C (m, 2 H, OCH and ClCHAHB), 3.69Ϫ3.59 (m, 1 H, SO2CHAHB),
NMR (67.5 MHz, CDCl3): δ ϭ 55.9 (ClCH2), 47.9 (CHCH2Cl)
ppm. MS (CI/NH3): m/z (%) ϭ 292 (100) [35M ϩ NH4ϩ], 258 (40),
3.54 (d, J ϭ 8 Hz, 1 H, ClCHAHB), 3.33Ϫ3.26 (m, 1 H,
SO2CHAHB), 3.14Ϫ2.73 (m, 2 H, 2 ϫ CHCH2), 2.95 (s, 3 H,
241 (6). HRMS (C12H19ClNO3S): calcd. 292.0774 [35M ϩ NH4ϩ]; CH3SO2) ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 72.2 (CH2O),
found 292.0773. Compound 15b: Yield: 6%, 4:1 ratio of dia-
71.2 (CH2O), 53.0 (CH2SO2), 44.5 (CHCH2Cl), 43.3 (CH2Cl), 42.1
(CH3), 38.3 (CHCH2SO2). The presence of the minor (trans) isomer
1
stereomers (as indicated by the H NMR spectrum). The presence
of the major (cis) isomer was indicated by: 1H NMR (270 MHz, was indicated by: 1H NMR (270 MHz, CDCl3): δ ϭ 4.14 (dd, 1 H,
CDCl3): δ ϭ 0.93 (d, J ϭ 7 Hz, 3 H, CH3) ppm. 13C NMR J ϭ 7 and 9.5 Hz, OCH), 2.93 (s, 3 H, CH3SO2) ppm. 13C NMR
(67.5 MHz, CDCl3): δ ϭ 38.6 (CHCH3), 14.8 (CH3) ppm. The
presence of the minor (trans) isomer was indicated by: 1H NMR
(67.5 MHz, CDCl3):
δ ϭ 73.6 (CH2O), 71.5 (CH2O), 58.2
(CH2SO2), 47.8 (CHCH2Cl), 46.4 (CH2Cl), 42.2 (CH3), 39.9
(270 MHz, CDCl3): δ ϭ 1.02 (d, 3 H, J ϭ 7 Hz, CH3) ppm. 13C (CHCH2SO2) ppm. MS (CI, NH3): m/z (%) ϭ 230 (100) [35M ϩ
NMR (67.5 MHz, CDCl3): δ ϭ 14.0 (CH3) ppm.
NH4ϩ]. HRMS (C7H17ClNO3S): calcd. 230.0617 [35M ϩ NH4ϩ];
found 230.0617.
Typical Procedure for the Cyclisation of the Dienes 8a,b,d,e in the
Presence of Methanesulfonyl Chloride: Mn2(CO)10 (0.11 g, 3-Methyl-4-[(methylsulfonyl)methyl]tetrahydrofuran (17b): Yield:
0.28 mmol) was added to a stirred solution of methanesulfonyl
chloride (0.29 g, 2.56 mmol) and the diene 8a,b,d,e (0.86 mmol) in
degassed dichloromethane (20 cm3) under nitrogen. The mixture
was then photolysed until disappearance of the starting material,
as indicated by thin layer chromatography. After the reaction time,
59%; pale yellow oil; Rf ϭ 0.25 (ethyl acetate-petroleum ether, 2:1);
6:1 ratio of diastereomers as indicated by the H NMR spectrum.
1
IR (CHCl3): ν˜ ϭ 3013 (s), 2966 (s), 2932 (s), 2870 (s), 1311 (vs),
1
1231 (s), 1141 (vs) cmϪ1. Major (cis) isomer: H NMR (270 MHz,
CDCl3): δ ϭ 4.07 (dd, 1 H, J ϭ 7 and 9, OCH), 3.94 (dd, J ϭ 6.5
an aqueous solution of sodium hydroxide (5 , 20 cm3) containing and 8.5 Hz, 1 H, 1 ϫ OCH), 3.68 (dd, 1 H, J ϭ 8 and 9, SO2CH-
BTAC (0.03 g, 0.21 mmol) was added and the solution stirred for
1 h. The organic layer was separated, washed with water and dried
(MgSO4). The crude mixture was adsorbed onto silica; column
chromatography afforded the desired chlorine-atom transfer prod-
ucts 16a,b,d,e (29Ϫ62%) and hydrogen-atom transfer products
17a,b,d,e (20Ϫ35%) as oils.
AHB), 3.46 (q, 1 H, J ϭ 17, 1 ϫ OCH), 3.18 (dd, 1 H, J ϭ 5 and
13.5, 1 ϫ OCH), 3.01Ϫ2.93 (m, 1 H, SO2CHAHB), 2.94 (s, 3 H,
CH3SO2), 0.98 (d, J ϭ 7 Hz, 3 H, CH3) ppm. 13C NMR
(67.5 MHz, CDCl3):
δ ϭ 75.2 (CH2O), 71.6 (CH2O), 54.0
(CH2SO2), 42.2 (SO2CH3), 36.7 (CHCH3), 36.5 (CHCH2SO2), 14.0
(CH3). The presence of the minor (trans) isomer was indicated by:
1H NMR (270 MHz, CDCl3): δ ϭ 4.14 (dd, 1 H, J ϭ 7 and 9,
OCH), 3.31 (dd, 1 H, J ϭ 5 and 13, OCH), 2.93 (s, 3 H, CH3SO2),
1.09 (d, J ϭ 7 Hz, 3 H, CH3) ppm. 13C NMR (67.5 MHz, CDCl3):
δ ϭ 57.9 (CH2SO2), 41.4 (SO2CH3), 16.7 (CH3) ppm. MS (CI,
NH3): m/z (%) ϭ 196 (100) [M ϩ NH4ϩ], 179 (13). HRMS
(C7H18NO3S): calcd. 196.1007 [M ϩ NH4ϩ]; found 196.1008.
Diethyl 3-(Chloromethyl)-4-[(methylsulfonyl)methyl]-1,1-cyclopen-
tanedicarboxylate (16a) and Diethyl 3-Methyl-4-[(methylsulfonyl)-
methyl]-1,1-cyclopentanedicarboxylate (17a): Yellow oil; Rf ϭ 0.24
(ethyl acetate-petroleum ether, 1:1). IR (CHCl3) (as an inseparable
2:1 mixture of 16a and 17a, as indicated by the 1H NMR spec-
trum): ν˜ ϭ 3058 (vs), 1767 (CϭO; s), 1368 (s), 1312 (vs), 1230 (vs)
cmϪ1. Compound 16a: Yield: 62%, 2.5:1 ratio of diastereomers (as
indicated by the 1H NMR spectrum). Major (cis) isomer: 1H NMR
cis- and trans-3-(Chloromethyl)-4-[(methylsulfonyl)methyl]-1-(phen-
ylsulfonyl)pyrrolidine (16d): Yield: 29%; colourless oil; Rf ϭ 0.5
(270 MHz, CDCl3): δ ϭ 4.23 (q, J ϭ 7 Hz, 4 H, 2 ϫ CH2CH3), (ethyl acetate); 3:1 ratio of diastereomers as indicated by the 1H
3.59 (d, J ϭ 7 Hz, 1 H, CHSO2), 3.33Ϫ2.99 (m, 2 H, CHSO2 and NMR spectrum. IR (CHCl3): ν˜ ϭ 2965 (w), 2930 (w), 2867 (w),
CHAHBCl), 3.00 (s, 3 H, CH3SO2), 2.89Ϫ1.96 (m, 7 H, CHAHBCl,
1349 (m), 1315 (vs), 1167 (s), 1095 (w) cmϪ1. Major isomer: 1H
2 ϫ CHCH2 and 2 ϫ CHCH2), 1.28 (t, J ϭ 7 Hz, 6 H, 2 ϫ NMR (270 MHz, CDCl3): δ ϭ 7.87Ϫ7.54 (m, 5 H, aromatics),
CH2CH3) ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 172.2 (CϭO), 3.67Ϫ2.40 (m, 10 H, CH2SO2, CH2Cl, CHCH2SO2, CHCH2Cl,
171.9 (CϭO), 61.8 (2
ϫ CH2CH3), 58.6 [C(CO2Et)], 55.0 NCH2, NCH2), 2.93 (s, 3 H, CH3SO2), 0.79 (d, J ϭ 7 Hz, 3 H,
(CH2SO2), 53.9 (CH2SO2), 46.3 (CH2Cl), 44.5 (CHCH3), 43.9 CHCH3) ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 136.8 (C-SO2),
(CHCH2Cl), 41.7 (CH2CH), 38.5 (CH2CH), 35.6 (CHCH2SO2), 133.7, 130.0, 128.1 (5 ϫ CHϭCH, aromatic), 52.6 (CH2N), 51.9
14.0 (2 ϫ CH2CH3). The presence of the minor (trans) isomer was
(CH2N), 50.7 (CH2SO2), 45.2 (CHCH2Cl), 43.7 (CH2Cl), 42.8
indicated by: 1H NMR (270 MHz, CDCl3): δ ϭ 3.00 (s, 3 H, (CH3SO2), 35.3 (CHCH2SO2). The presence of the minor isomer
CH3SO2) ppm. MS (CI, NH3): m/z (%) ϭ 372 (55) [35M ϩ NH4ϩ], was indicated by: 1H NMR (270 MHz, CDCl3): δ ϭ 3.61 (dd, 1 H,
355 (13) [35M ϩ Hϩ], 338 (100), 321 (27), 292 (13). HRMS
J ϭ 7 and 9, CHN) ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ
(C14H27ClNO6S): calcd. 373.1248 [35M ϩ NH4ϩ]; found 372.1247. 133.4, 139.9, 128.3 (5 ϫ CHϭCH, aromatic), 57.4 (CH2N), 53.4
Compound 17a: Yield: 20% (as indicated by the 1H NMR spec-
(CH2N), 46.1 (CHCH2Cl), 42.4 (CH3SO2), 36.4 (CHCH2SO2)
trum); 18:1 ratio of diastereomers (as indicated by the 1H NMR
ppm. MS (CI, NH3): m/z (%) ϭ 369 (41) [35M ϩ NH4ϩ], 352 (100)
spectrum). The presence of the major (cis) isomer was indicated by: [35M ϩ Hϩ], 318 (9), 130 (20). HRMS (C13H19ClNO4S2): calcd.
1H NMR (270 MHz, CDCl3): δ ϭ 0.94 (d, J ϭ 7 Hz, 3 H, CH3)
ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 41.0 (CH2CH), 37.9
(CH2CH), 36.9 (CHCH3), 36.4 (CHCH2SO2), 16.0 (CHCH3). The
presence of the minor (trans) isomer was indicated by: 1H NMR
(270 MHz, CDCl3): δ ϭ 1.10 (d, J ϭ 7 Hz, 3 H, CH3) ppm. HRMS
(C14H28NO6S): calcd. 338.1637 [M ϩ NH4ϩ]; found 338.1633.
352.0444 [35M ϩ Hϩ]; found 352.0446.
3-Methyl-4-[(methylsulfonyl)methyl]-1-(phenylsulfonyl)pyrrolidine
(17d): Yield: 27%; colourless oil; Rf ϭ 0.4 (ethyl acetate); 5:1 ratio
of diastereomers as indicated by the 1H NMR spectrum. IR
(CHCl3): ν˜ ϭ 2968 (m), 2928 (m), 2857 (w), 1348 (m), 1312 (s),
1167 (s), 1147 (m), 1095 (m), 1047 (w) cmϪ1. Major (cis) isomer:
3-(Chloromethyl)-4-[(methylsulfonyl)methyl]tetrahydrofuran (16b): 1H NMR (270 MHz, CDCl3): δ ϭ 7.82Ϫ7.51 (m, 5 H, aromatics),
Yield: 35%; pale yellow oil; Rf ϭ 0.3 (ethyl acetate-petroleum ether, 3.58Ϫ2.32 (m, 8 H, CH2SO2, CHCH2SO2, CHCH3, NCH2,
2:1); 2.5:1 ratio of diastereomers as indicated by the 1H NMR spec- NCH2), 2.87 (s, 3 H, CH3SO2), 0.79 (d, J ϭ 7 Hz, 3 H, CHCH3)
1746
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 1740Ϫ1749

Radical Reactions under Biphasic Conditions
FULL PAPER
ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 137.3 (CSO2), 133.5 General Procedure for Sequential Radical Addition؊Ionic Cycli-
(CHϭCH, aromatic), 129.8 (CHϭCH, aromatic), 128.0 (CHϭCH, sation under Biphasic Conditions: Diethyl allylmalonate (18) (0.20 g,
aromatic), 54.7 (CH2N), 53.6 (CH2N), 51.1 (CH2SO2), 42.4
0.99 mmol) and bromotrichloromethane (0.57 g, 2.97 mmol) or
(CHCH3), 39.4 (CHSO2), 36.1 (CH3SO2), 13.9 (CHCH3). The pres- carbon tetrabromide (0.99 g, 2.97 mmol) were added to a stirred
ence of the minor (trans) isomer was indicated by: 1H NMR solution of Mn2(CO)10 (0.13 g, 0.30 mmol) in degassed dichloro-
(270 MHz, CDCl3): δ ϭ 0.94 (d, J ϭ 7 Hz, 3 H, CHCH3) ppm. methane (20 cm3). The mixture was photolysed under nitrogen un-
13C NMR (67.5 MHz, CDCl3): δ ϭ 130.5 (CHϭCH, aromatic), til reaction completion, as indicated by TLC. An aqueous solution
128.1 (CHϭCH, aromatic), 57.3 (CH2N), 54.1 (CH2N), 42.0 of NaOH (5 , 10Ϫ100 cm3) containing BTAC (0.02 g, 0.11 mmol)
(CHCH3), 40.0 (CHSO2), 30.3 (CH3SO2), 14.8 (CHCH3) ppm. MS was added, and the biphasic system stirred vigorously overnight.
(CI, NH3): m/z (%) ϭ 335 (19) [M ϩ NH4ϩ], 318 (100) [M ϩ Hϩ], Column chromatography afforded the desired cyclopropanes 19
176 (13), 96 (16). HRMS (C13H20NO4S2): calcd. 318.0834 [M ϩ
and 20 (0.28Ϫ0.39 g, 80Ϫ88%) as oils.
Hϩ]; found 318.0833.
Diethyl 2-(2,2,2-Trichloroethyl)-1,1-cyclopropanedicarboxylate (19):
Yield: 75%; colourless oil; Rf ϭ 0.3 (petroleum ether/ethyl acetate,
9:1). IR (film): ν˜ ϭ 2983 (m), 2937 (w), 2908 (w), 1726 (CϭO, br.
vs), 1465 (w), 1446 (w), 1398 (m), 1369 (s), 1321 (s), 1282 (s), 1213
1-Benzoyl-3-(chloromethyl)-4-[(methylsulfonyl)methyl]pyrrolidine
(16e): Yield: 41%; colourless oil; Rf ϭ 0.2 (ethyl acetate); 1.5:1 ratio
of diastereomers as indicated by the 1H NMR spectrum. IR
(CHCl3): ν˜ ϭ 3020 (w), 2958 (w), 2929 (w), 1625 (CO; s), 1577 (m),
1148 (m), 1423 (s), 1313 (s), 1216 (m), 1143 (m) cmϪ1. Major iso-
mer: 1H NMR (300 MHz, CDCl3): δ ϭ 7.60Ϫ7.48 (m, 2 H, aro-
matics), 7.46Ϫ7.42 (m, 3 H, aromatics), 3.93Ϫ2.45 (m, 10 H, 2 ϫ
CH2N, CH2SO2, CH2Cl, CHCH2SO2, CHCH2Cl), 2.95 (s, 3 H,
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 169.9 (CϭO), 135.8
(CϭCH, aromatic), 130.2 (CHϭCH, aromatic), 128.4 (CHϭCH,
aromatic), 127.2 (CHϭCH, aromatic), 52.7 (CH2SO2), 51.9
(CH2N), 48.8 (CH2N), 43.0 (CH2Cl), 41.6 (CHCH2Cl), 41.8
(CH3SO2), 35.2 (CHCH2SO2CH3). The presence of the minor iso-
(s), 1132 (s) cmϪ1 1H NMR (400 MHz, CDCl3): δ ϭ 4.33Ϫ4.14
.
(m, 4 H, 2 ϫ CH2CH3), 3.12 (dd, 1 H, J ϭ 4 and 15 Hz,
CHAHBCCl3), 2.48 (ddd, 1 H, J ϭ 1, 9 and 15 Hz, CHAHBCCl3),
2.36Ϫ2.28 (m, 1 H, CHCH2), 1.65Ϫ1.60 (m, 2 H, CCH2CH),
1.32Ϫ1.24 (m, 6 H, 2 ϫ CH2CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 169.1 (CϭO), 167.6 (CϭO), 98.4 (CCl3), 61.7
(CH2CH3), 61.6 (CH2CH3), 52.8 (CH2CCl3), 32.5 [C(CO2Et)2],
24.2 (CHCH2), 20.7 (CCH2CH), 14.0 (CH2CH3), 13.9 (CH2CH3)
ppm. MS (CI, NH3): m/z (%) ϭ 317 (100) [35M ϩ Hϩ], 283 (20).
HRMS (C11H16Cl3O4): calcd. 317.0114 [35M
317.0113.
ϩ
Hϩ]; found
1
mer was indicated by: H NMR (300 MHz, CDCl3): δ ϭ 3.02 (s, 3
H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 52.4 (CH2N),
49.9 (CH2N), 42.4 (CH2Cl), 42.9 (CHCH2Cl), 33.8
(CHCH2SO2CH3) ppm. MS (CI, NH3): m/z (%) ϭ 316 (100) [35M
ϩ Hϩ], 282 (30), 222 (9), 105 (27). HRMS (C14H19ClNO3S): calcd.
316.0774 [35M ϩ Hϩ]; found 316.0771.
Diethyl 2-(2,2,2-Tribromoethyl)-1,1-cyclopropanedicarboxylate (20):
Yield: 76%; yellow oil; Rf ϭ 0.3 (petroleum ether/ethyl acetate, 9:1).
IR (film) ν˜ ϭ 2981 (m), 2937 (w), 2906 (w), 1726 (CϭO, br. vs),
1466 (w), 1444 (w), 1394 (m), 1369 (s), 1319 (s), 1278 (s), 1211 (s),
1130 (s) cmϪ1. 1H NMR (500 MHz, CDCl3): δ ϭ 4.26Ϫ4.16 (m, 4
H, 2 ϫ CH2CH3), 3.46 (dd, 1 H, J ϭ 4 and 15 Hz, CHAHBCBr3),
2.77 (dd, 1 H, J ϭ 9 and 15 Hz, CHAHBCBr3), 2.35Ϫ2.29 (m, 1
H, CHCH2), 1.73Ϫ1.67 (m, 2 H, CCH2CH), 1.36Ϫ1.24 (m, 6 H, 2
ϫ CH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 169.1 (Cϭ
O), 167.6 (CϭO), 61.6 (2 ϫ CH2CH3), 57.1 (CH2CBr3), 38.7
(CBr3), 32.3 [C(CO2Et)2], 26.9 (CHCH2), 21.1 (CCH2CH), 14.0
(CH2CH3), 13.9 (CH2CH3) ppm. MS (CI, NH3): m/z (%) ϭ 449
1-Benzoyl-3-methyl-4-[(methylsulfonyl)methyl]pyrrolidine
(17e).
Yield: 26%; colourless oil; Rf ϭ 0.1 (ethyl acetate); 1.3:1 ratio of
diastereomers as indicated by the 1H NMR spectrum. IR (film):
ν˜ ϭ 3056 (m), 2968 (m), 2929 (m), 2879 (m), 1720 (m), 1626 (CO,
s), 1577 (m), 1423 (s), 1305 (s), 1267 (s), 1137 (s) cmϪ1. Major
(cis) isomer: 1H NMR (270 MHz, CDCl3): δ ϭ 7.52Ϫ7.48 (m, 2
H, aromatics), 7.45Ϫ7.41 (m, 3 H, aromatics), 3.95Ϫ2.51 (m, 8 H,
2 ϫ CH2N, CH2SO2, CHCH2SO2, CHCH3), 2.92 (s, 3 H, CH3SO2),
0.95 (d, J ϭ 7 Hz, 3 H, CHCH3) ppm. 13C NMR (67.5 MHz,
CDCl3): δ ϭ 170.5 (CϭO), 136.4 (CϭCH, aromatic), 130.2, 128.5
and 127.2 (5 ϫ CHϭCH, aromatics), 56.3 (CH2SO2), 53.6 (CH2N),
51.9 (CH2N), 41.8 (CH3SO2), 35.7 and 34.6 (CHCH3 and
CHCH2SO2CH3), 13.2 (CHCH3). The presence of the minor
(31) [79,79,79M ϩ Hϩ], 451 (100) [81,79,79M ϩ Hϩ], 453 (95) [81,81,79
M
ϩ Hϩ], 455 (30) [81,81,81M ϩ Hϩ], 173 (18). HRMS (C11H16Br3O4):
calcd. 448.8599 [79,79,79M ϩ Hϩ]; found 448.8601.
Diethyl 2-Allyl-2-bromomalonate (21): Diethyl allylmalonate (18)
(0.20 g, 0.98 mmol) and bromotrichloromethane (0.58 g,
2.94 mmol) were dissolved in degassed dichloromethane (20 cm3).
DBU (0.22 g, 1.47 mmol) was added and the mixture stirred over-
night. The crude mixture was filtered through a silica plug to afford
1
(trans) isomer was indicated by: H NMR (270 MHz, CDCl3): δ ϭ
2.99 (s, 3 H, CH3SO2), 1.07 (d, J ϭ 7 Hz, 3 H, CHCH3) ppm. 13C
NMR (67.5 MHz, CDCl3): δ ϭ 53.1 (CH2N), 52.3 (CH2N), 36.1
and 34.3 (CHCH3 and CHCH2SO2CH3), 13.8 (CHCH3) ppm. MS
(CI, NH3): m/z (%) ϭ 282 (100) [M ϩ Hϩ], 188 (12), 105 (22).
HRMS (C14H20NO3S): calcd. 282.1164 [M ϩ Hϩ]; found 282.1163.
1
21 (0.17 g, 54%) as a colourless oil. H NMR (500 MHz, CDCl3):
δ ϭ 5.86Ϫ5.75 (m, 1 H, CHϭCH2), 5.20 (d, 2 H, J ϭ 13 Hz, CHϭ
CH2), 4.27 (m, 4 H, 2 ϫ CH2CH3), 3.04 (d, J ϭ 6 Hz, 2 H,
CH2CBr), 1.29 (m, 6 H, 2 ϫ CH2CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 166.3 (2 ϫ CϭO), 131.2 (CHϭCH2), 120.2 (CHϭ
CH2), 62.9 (CH2CBr), 61.8 (CBr), 42.4 (2 ϫ CH2CH3), 13.9
(CH2CH3), 13.7 (CH2CH3) ppm. MS (CI, NH3): m/z (%) ϭ 296
(77) [79M ϩ NH4ϩ], 279 (100) [79M ϩ Hϩ], 218 (21), 201 (43), 170
(21), 153 (29). HRMS (C10H16BrO4): calcd. 279.0231 [79M ϩ Hϩ];
found 279.0230.
General Procedure for Sequential Radical Addition؊Ionic Cycli-
sation Using DBU: The unsaturated 1,3-dicarbonyl compound 18
or 22 (0.50Ϫ4.94 mmol) and bromotrichloromethane (0.29Ϫ2.85 g,
1.5Ϫ14.82 mmol) or carbon tetrabromide (0.49Ϫ4.92 g,
1.5Ϫ14.82 mmol) was added to a stirred solution of Mn2(CO)10
(0.07Ϫ0.65 g, 0.15Ϫ1.48 mmol) in degassed dichloromethane
(10Ϫ100 cm3). The mixture was photolysed under nitrogen until tert-Butyl 1-Acetyl-2-(2,2,2-trichloroethyl)cyclopropanecarboxylate
reaction completion, as indicated by TLC. DBU (0.17Ϫ1.64 g,
1.10Ϫ10.8 mmol) was added dropwise and the mixture stirred over-
(23): Yield: 60%; separable mixture of two diastereomers in a 1:1
ratio, as indicated by the H NMR spectrum. Diastereoisomer 1:
1
night. Column chromatography afforded the desired cyclopropanes pale yellow oil; Rf ϭ 0.4 (petroleum ether/diethyl ether, 9:1). IR
19, 20 and 23 (0.11Ϫ0.83 g, 60Ϫ76%) as oils.
Eur. J. Org. Chem. 2004, 1740Ϫ1749
(CHCl3): ν˜ ϭ 3004 (m), 2979 (m), 2933 (m), 1724 (CϭO, br., vs),
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1747

N. Huther, P. T. McGrail, A. F. Parsons
FULL PAPER
1429 (m), 1357 (s), 1290 (s), 1249 (s), 1166 (s), 1116 (s) cmϪ1. H (0.50 g, 2.38 mmol) in ethanol (1 cm3). The solution was stirred at
NMR (400 MHz, CDCl3): δ ϭ 2.89 (dd, 1 H, J ϭ 5 and 15 Hz, room temp. for 24 h and the solvent was then evaporated under
CHAHBCCl3), 2.54 (dd, 1 H, J ϭ 5 and 15 Hz, CHAHBCCl3), 2.43 reduced pressure. The residue was dissolved in water (1 cm3) and
(s, 3 H, CH3), 2.38Ϫ2.22 (m, 1 H, CHCH2), 1.73Ϫ1.66 (m, 1 H, extracted with dichloromethane (2 ϫ 1 cm3). The aqueous layer
CCHAHBCH), 1.51 [br. s, 10 H, C(CH3)3 and CCHAHBCH] ppm. was cooled in ice and concentrated aqueous HCl (37%) was added
13C NMR (100 MHz, CDCl3): δ ϭ 202.0 (CϭO), 169.3 (CϭO), dropwise until the mixture was acidic (as indicated by litmus
98.7 (CCl3), 82.5 [C(CH3)3], 51.5 (CH2CCl3), 40.2 (COCCO), 31.0 paper). The combined organic extracts were dried over sodium sul-
(CH3CO), 27.9 [C(CH3)3], 27.5 (CHCH2CCl3), 20.9 (CCH2CH) fate and the solvents evaporated to afford 25 (0.21 g, 47%) as a
1
ppm. MS (CI, NH3): m/z (%) ϭ 332 (2) [35M ϩ NH4ϩ], 315 (10)
[35M ϩ Hϩ], 276 (100), 259 (36). Diastereoisomer 2: pale yellow
colourless oil. IR (film): ν˜ ϭ 3300Ϫ2500 (br., s), 2969 (s), 2937 (s),
2879 (s), 1714 (CϭO, br., vs), 1435 (m), 1373 (m), 1322 (m), 1209
oil; Rf ϭ 0.3 (petroleum ether/diethyl ether, 9:1). IR (CHCl3): ν˜ ϭ (m), 1145 (m), 115 (m) cmϪ1 1H NMR (400 MHz, CDCl3): δ ϭ
.
3004 (m), 2979 (m), 2933 (m), 1723 (CϭO, vs), 1458 (m), 1369 (s),
10.55 (br. s, 1 H, OH), 4.33Ϫ4.25 (m, 2 H, CH2CH3), 2.06 (1 H,
1324 (s), 1241 (m), 1209 (m), 1167 (s), 1124 (vs) cmϪ1. H NMR apparent t, J ϭ 7.5 Hz, CHCH2), 1.90 (br. s, 1 H, CCHAHBCH),
(400 MHz, CDCl3): δ ϭ 3.08 (dd, 1 H, J ϭ 5 and 15 Hz, 1.70Ϫ1.68 (m, 1 H, CCHAHBCH), 1.63Ϫ1.54 (m, 2 H, CH2CH3),
1
CHAHBCCl3), 2.69 (dd, 1 H, J ϭ 5 and 15 Hz, CHAHBCCl3), 2.42 1.32 (t, J ϭ 7.5 Hz, 3 H, OCH2CH3), 0.99 (t, J ϭ 7 Hz, 3 H, CH3)
(s, 3 H, CH3), 2.29Ϫ2.25 (m, 1 H, CHCH2), 1.51 [br. s, 11 H, ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 173.4 (CϭO), 172.4 (Cϭ
C(CH3)3, CCHAHBCH and CCHAHBCH] ppm. 13C NMR
O), 62.4 (CH2CH3), 38.4 (CHCH2), 31.2 [C(CO)2], 24.2 and 21.4
(100 MHz, CDCl3): δ ϭ 202.0 (CϭO), 168.1 (CϭO), 98.6 (CCl3), (CCH2CH and CH2CH3), 13.9 (CH2CH3), 13.1 (CH3) ppm. MS
82.9 [C(CH3)3], 52.3 (CH2CCl3), 40.7 (COCCO), 29.4 (CH3CO),
(CI, NH3): m/z (%) ϭ 187 (5) [M ϩ Hϩ], 122 (100). HRMS
28.0 [C(CH3)3], 26.1 (CHCH2CCl3), 22.1 (CCH2CH) ppm. MS (CI, (C9H15O4): calcd. 187.0970 [M ϩ Hϩ]; found 187.0972.
NH3): m/z (%) ϭ 315 (7) [35M ϩ Hϩ], 276 (100), 259 (38), 183 (28).
[(1RS,2RS)-1-(Ethoxycarbonyl)-2-ethylcyclopropyl]ammonium
Chloride (26): The carboxylic acid 25 (0.10 g, 0.52 mmol) was dis-
solved in acetone (10 cm3) at 0 °C. Triethylamine (0.09 cm3,
0.71 mmol) was added, followed by ethyl chloroformate (0.05 cm3,
0.62 mmol). The solution was stirred for 25 min before the addition
of a solution of sodium azide (0.06 g, 0.94 mmol) in water (5 cm3).
The solution was stirred for 15 min, diluted with ethyl acetate and
washed with water. The organic layer was dried over sodium sul-
fate, filtered and the solvents evaporated. The residue was then dis-
solved in toluene (100 cm3) and stirred at 90 °C for 1 h. The solvent
was then removed, the residue dissolved in a mixture of dioxane/
water/HCl (1:3:1, 20 cm3) and stirred at room temp. for 20 min.
Finally, the solvent was removed in vacuo to afford 26 (0.05 g, 53%)
as a white solid. M.p. 110Ϫ112 °C. IR (film): ν˜ ϭ 3100Ϫ2600 (br.,
s), 2969 (s), 2935 (s), 2877 (s), 1731 (CϭO, s), 1589 (m), 1529 (m),
HRMS (C12H18Cl3O3): calcd. 315.0321 [35,35M ϩ Hϩ]; found
315.0321.
Reduction of Diethyl 2-(2,2,2-Trichloroethyl)-1,1-cyclopropanedi-
carboxylate (19) Using Tributyltin Hydride: The trichloride 19
(0.86 g, 2.72 mmol), nBu3SnH (4.75 g, 16.32 mmol) and AIBN
(0.24 g, 1.36 mmol) were dissolved in degassed toluene (17 cm3).
The mixture was heated at 100 °C for 1 h, after which the mixture
was cooled to room temp. and ethyl acetate (50 cm3) added. A
saturated aqueous solution of potassium fluoride (50 cm3) was ad-
ded and the biphasic mixture was stirred overnight. After separ-
ation and filtration of the organic layer, the filtrate was washed
successively with water, brine, water and dried (MgSO4). Column
chromatography (flash silica, petroleum ether/ethyl acetate, 15:1)
afforded 24 (0.52 g, 89%) as a colourless oil. Rf ϭ 0.4 (petroleum
ether/ethyl acetate, 9:1). IR (film): ν˜ ϭ 2979 (m), 2937 (m), 2877
(w), 1726 (CϭO, s), 1465 (m), 1369 (m), 1321 (s), 1286 (s), 1207
1
1459 (m), 1379 (m), 1349 (m), 1249 (m), 1195 (s) cmϪ1. H NMR
(400 MHz, CDCl3): δ ϭ 9.01 (br. s, 2 H, NH2), 4.49 (br. s, 2 H,
CH2CH3), 1.92Ϫ1.26 (br. m, 8 H, CCH2, CH2CH, CHCH2 and
CH2CH3), 0.99 (br. s, 3 H, CH2CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 168.1 (CϭO), 62.4 (CH2CH3), 38.2 (NCCO), 30.2
(CHCH2), 19.9 and 19.7 (CCH2CH and CH2CH3), 14.1 (CH2CH3),
(s), 1132 (s) cmϪ1 1H NMR (400 MHz, CDCl3): δ ϭ 4.21Ϫ4.05
.
(m, 4 H, 2 ϫ CH2CH3), 1.83Ϫ1.72 (m, 1 H, CCHAHBCH),
1.42Ϫ1.31 (m, 1 H, CCHAHBCH), 1.30Ϫ1.15 (m, 9 H, 2 ϫ
CH2CH3, CH2CH3 and CHCH2), 0.94 (t, J ϭ 7.5 Hz, 3 H, CH3)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 170.5 (CϭO), 168.3 (Cϭ
O), 61.2 (2 ϫ CH2CH3), 34.3 [C(CO)2], 29.8 (CHCH2), 22.1 and
20.8 (CCH2CH and CH2CH3), 14.1 (CH2CH3), 14.0 (CH2CH3),
13.1 (CH3) ppm. MS (CI, NH3): m/z (%) ϭ 232 (16) [M ϩ NH4ϩ],
215 (100) [M ϩ Hϩ]. HRMS (C11H19O4): calcd. 215.1283 [M ϩ
Hϩ]; found 215.1281.
13.2 (CH3) ppm. MS (CI, NH3): m/z (%) ϭ 158 (100) [M ϩ Hϩ
Ϫ
HCl], 128 (26). HRMS (C8H16NO2): calcd. 158.1181 [M ϩ
HϩϪHCl]; found 158.1183.
[(1RS,2RS)-1-Carboxy-2-ethylcyclopropyl]ammonium
Chloride
[(؎)-Coronamic Acid Hydrochloride] (27): The propanaminium
chloride 26 (0.05 g, 0.26 mmol) was heated to reflux in 6  HCl
(5 cm3) for 7 days. After cooling to room temp., the solvent was
removed in vacuo to afford the title compound 27[15c] (0.039 g,
90%) as a white solid. M.p. 200 °C (dec.) [ref.[15c] Ͼ 190 °C (sub.)].
IR (nujol): ν˜ ϭ 2925 (br., vs), 2857 (br., s), 2759 (w), 2669 (w),
2556 (w), 1984 (w), 1720 (CϭO, s), 1591 (w), 1500 (m), 1459 (m),
1403 (m), 1252 (m). 1H NMR (400 MHz, D2O): δ ϭ 1.75Ϫ1.64 (m,
2 H, CCH2CH), 1.56Ϫ1.48 (3 H, CH2CHCH2 and CH2CH3), 0.93
(t, 3 H, J ϭ 7 Hz, CH2CH3) ppm. 13C NMR (100 MHz, D2O): δ ϭ
169.7 (CϭO), 37.9 (CCO2H), 29.8 (CH2CHCH2), 19.6 (CH2), 19.0
(CH2), 12.5 (CH3).
Reduction of Diethyl 2-(2,2,2-Trichlorethyl)-1,1-cyclopropanedicarb-
oxylate (20) Using Tributyltin Hydride: The tribromide 20 (0.36 g,
0.79 mmol) and nBu3SnH (1.38 g, 4.77 mmol) were mixed together
without solvent. The mixture was heated to 80 °C under a nitrogen
atmosphere for 3 h, then cooled to room temp. Ethyl acetate
(20 cm3), followed by a saturated aqueous solution of potassium
fluoride (20 cm3) were added, and the biphasic mixture stirred at
room temp. overnight. After separation and filtration of the or-
ganic layer, the filtrate was washed successively with water, brine,
water and dried (MgSO4). Column chromatography (flash silica,
petroleum ether/ethyl acetate, 15:1) afforded 24 (0.14 g, 83%) as a
colourless oil.
Acknowledgments
We thank Cytec Fiberite Ltd. for support and the University of
(1RS,2RS)-1-(Ethoxycarbonyl)-2-ethylcyclopropanecarboxylic Acid
(25): Potassium hydroxide (0.13 g, 2.38 mmol) in ethanol (2 cm3)
was added dropwise over 1 h to a stirred solution of the diester 24 York for funding.
1748  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2004, 1740Ϫ1749

Radical Reactions under Biphasic Conditions
FULL PAPER
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Received January 14, 2004
Eur. J. Org. Chem. 2004, 1740Ϫ1749
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1749