Initiation of radical cyclisation reactions using dimanganese decacarbonyl. A flexible approach to preparing 5-membered rings

Article abstract of DOI:10.1039/b000835o

Photolysis of dimanganese decacarbonyl [Mn₂(CO)₁₀] using visible light produces the manganese pentacarbonyl radical [Mn(CO)₅] which reacts with organohalides to form carbon-centred radicals. Efficient halogen-atom abstract

Full text of DOI:10.1039/b000835o

View Article Online / Journal Homepage / Table of Contents for this issue
Initiation of radical cyclisation reactions using dimanganese
decacarbonyl. A flexible approach to preparing 5-membered rings
Bruce C. Gilbert,a Wilhelm Kalz,a Chris I. Lindsay,b P. Terry McGrail,b Andrew F. Parsons*a
and David T. E. Whittakera
1
a Department of Chemistry, University of York, Heslington, York, UK YO10 5DD
b ICI Technology, PO Box 90, Wilton, Middlesbrough, Cleveland, UK TS90 8JE
Received (in Cambridge, UK) 31st January 2000, Accepted 28th February 2000
Published on the Web 31st March 2000
Photolysis of dimanganese decacarbonyl [Mn2(CO)10] using visible light produces the manganese pentacarbonyl
ؒ
radical [ Mn(CO)5] which reacts with organohalides to form carbon-centred radicals. Efficient halogen-atom
abstraction occurs with allylic or benzylic halides or polyhalogenated precursors bearing a weak carbon–halogen
ؒ
bond. Steric interactions are also important and primary halides generally react much faster with Mn(CO)5 than
secondary or tertiary halides. The carbon-centred radicals can undergo efficient dimerisation or, in the presence of
an acceptor double bond, cyclisation to form 5-membered rings. Cyclisation of terminal alkenes leads to primary
radicals, which can then react by iodine- or bromine-atom transfer or, on addition of propan-2-ol, hydrogen-atom
transfer. Hydroxylamines can also be formed when cyclisation reactions are carried out in the presence of TEMPO.
These high-yielding cyclisation–trapping reactions are initiated under mild reaction conditions and the manganese
halide by-products [of type XMn(CO)5] can be easily separated from products by a simple DBU work-up procedure.
Introduction
Results and discussion
Free-radical reactions, particularly cyclisations,1 have been
extensively studied over the past twenty years and the most
common method of initiation involves reaction of halide (or
related thiophenyl, thiocarbonyl or phenyl selenide) precursors
with tributyltin hydride. However, this method is far from ideal
and the toxicity and difficulty of removing tin-containing
by-products has led to the development of alternative reagents
for radical generation.2 Notable examples include tris-
(trimethylsilyl)silane,3 cobaloximes,4 manganese() acetate5
and samarium() iodide6 but the use of tributyltin hydride,
EPR spectroscopy studies
Initial experiments employed EPR spectroscopy in an attempt
to detect the formation of any carbon-centered radicals pro-
duced on photolysis (λ > 400 nm) of Mn2(CO)10 in the presence
of a variety of organohalides. In situ photolysis of Mn2(CO)10
in the presence of the organohalide and a spin trap, 2,4,6-
tribromonitrosobenzene (TBNB), allowed the detection of
organic radical spin adducts 1 formed on halogen atom abstrac-
tion (Scheme 1). These are characterised10 by nitrogen and
which provides
a flexible and mild method of radical
generation, still dominates. This has restricted the use of
radical chemistry, particularly in the pharmaceutical and
fine chemical industries, which is unfortunate because radical
reactions offer a number of advantages over ionic reactions
(e.g. no solvation, ability to assemble hindered centres, flexible
tandem and cascade sequences, and mild, neutral reaction
conditions).
As part of a programme to develop alternative and more
versatile free-radical initiators we investigated the use of
dimanganese decacarbonyl [Mn2(CO)10] in synthesis. Photolysis
of this dimer is known to lead to either decarbonylation to give
Mn2(CO)9, or homolysis of the weak manganese–manganese
bond (≈150 kJ molϪ1) to give the manganese pentacarbonyl
7
ؒ
radical [ Mn(CO)5]. This manganese-centred radical is also
known to abstract halogen atoms from a limited range of
organohalides (e.g. CBr4, CHBr3, C6H5CH2Br, CH2Br2 and
CCl4) and the rate constants for halogen-atom transfer (deter-
mined by flash photolysis techniques) have been shown to vary
from 103 (for CH2Br2) to 109 (CBr4) dm3 molϪ1 sϪ1 at 21 ЊC.8
Surprisingly, the generation of radicals using Mn2(CO)10 has
found very limited application in synthesis (chiefly in hydro-
genolysis and oligomerisation reactions)9 but the ability to
generate carbon-centred radicals, under mild reaction con-
ditions, suggests that Mn2(CO)10 could be utilised in a variety
of carbon–carbon bond forming reactions.
Scheme 1
β-hydrogen splittings given in Table 1 and a g-value of 2.0066
( 0.0001). Reaction of a variety of alkyl and aryl chlorides,
bromides or iodides in this way demonstrated that carbon-
centred radicals could only be formed from precursors bearing
a weak carbon–halogen bond (typically <310 kJ molϪ1). Thus,
carbon-centred radicals were trapped when using CCl4,
CH ᎐CH–CH Br, PhCH Br, BrCCl , CH I, ICH CONH or
᎐
2
2
2
3
3
2
2
CH3CH(I)CH3 but not for CH ᎐CH–CH Cl, EtBr or CH -
᎐
2
2
3
C(Br)CH3 (Table 1). Typical results were as follows. On
DOI: 10.1039/b000835o
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194
This journal is © The Royal Society of Chemistry 2000
1187

View Article Online
has been found to aid the removal of tin by-products12 and
Table 1 EPR hyperfine splitting constants (a/gauss 0.1) of aminoxyl
radicals generated by photolysis of halides and Mn2(CO)10 in the pres-
ence of TBNB
reaction of DBU with BrMn(CO)5 was found11 to result in
ligand exchange (rather than bromide displacement as observed
for R3SnBr) giving a complex which is retained by the silica
column (along with any excess DBU). The dimerisation
reaction could also be carried out in alternative solvents (to
dichloromethane) and 2 was isolated in 61 or 82% yield
when using ethyl acetate or methanol, respectively. However,
attempted dimerisation of benzyl bromide using Mn2(CO)10
and thermolysis (in dichloromethane or methanol) or sonolysis
(in dichloromethane), rather than photolysis, proved ineffective
and only starting material was indicated on TLC analysis.
Spin adduct 1, R
a(N)/G
a(βH)/G
CH3
CCl3
13.1
13.1
13.3
13.1
13.4
13.1
11.9 (3H)
—
10.6 (2H)
9.8 (2H)
9.7 (2H)
7.6 (1H)
a
CH2–CH᎐CH2
᎐
CH2Phb
CH2CONH2
CH(CH3)2
a Also generated from an O-allyl xanthate [CH2᎐᎐CHCH2OC(S)SMe].
b Also generated from S-benzyl xanthates [RO(S)SBn, R = ethyl or
allyl].
Atom transfer cyclisations
The novel use of Mn2(CO)10 as an initiator for atom transfer
cyclisations was then investigated using iodoethanamide 3
(Scheme 3).13 Irradiation of 3 (1 equivalent) with 0.1 equiv-
photolysis, a very strong ten-line signal attributed to spin-
7
ؒ
trapping of the Mn(CO)5 radical was initially observed and,
after irradiation, this rapidly diminished leaving a signal
corresponding to the appropriate organic spin-adduct. Thus, in
experiments for the benzyl radical, for example, the spin-adduct
signal was detected as a 1:1:1 triplet, due to splitting from
nitrogen [a(N) = 13.1 G], and with further splitting into a triplet
due to the presence of two β-hydrogens [a(βH) = 9.8 G], as
ؒ
expected for successful trapping of PhCH2 . As primary
radicals were more easily formed than secondary radicals
(e.g. PhCHBrCH3 did not react) and tertiary radicals could
only be generated from iodides such as Me3C–I, which can
also undergo direct photolysis,† steric effects are evidently
important for radical generation.
Similar selectivities were observed on photolysis of the
same organohalides with (the considerably more expensive)
Re2(CO)10. Reaction of Mn2(CO)10 with other functional groups
was also briefly explored. Although no organic radicals were
trapped from corresponding reactions of phenyl sulfides
(PhSR), photolysis of Mn2(CO)10 with xanthates [ROC(S)SR1]
led to the formation of spin-adducts (Table 1). Thus, photolysis
of Mn2(CO)10 with EtOC(S)SBn or CH ᎐CHCH OC(S)SBn
᎐
2
2
produced benzyl radicals evidently derived from cleavage of the
C–S bond. Cleavage of the C–O bond was observed from
xanthates bearing an SMe rather than SBn group; thus reaction
of Mn2(CO)10 with CH ᎐CHCH OC(S)SMe produces allyl
᎐
2
2
rather than (less stable) methyl radicals.
Preliminary dimerisation reactions
Scheme 3
Having established the prerequisites for the formation of
carbon-centred radicals, this method of initiation was then
applied to the synthesis of a variety of dimers derived from
radical (homo- and cross-) coupling reactions.11 For example,
benzyl bromide (1 equivalent) was photolysed with Mn2(CO)10
(0.5 equivalents) in dichloromethane to give 1,2-diphenylethane
2 in 99% yield (Scheme 2).11 Complete removal of the by-
alents of Mn2(CO)10 in dichloromethane for 1 h, afforded the
desired iodo-pyrrolidinone 5 in 78% yield after column chrom-
atography. This resulted from cyclisation of carbamoylmethyl
radical 4b to give a cyclic primary radical, which abstracts
an iodine atom from another molecule of starting material 3.
Unlike related reactions employing Sn2Bu6, the presence of
excess initiator [e.g. 0.5 equivalents of Mn2(CO)10] does not
significantly alter the yield of the desired product 5. Once
formed, the primary iodide does not undergo fast iodine-atom
ؒ
abstraction with the Mn(CO)5 radical. This was supported
by our finding that irradiation of a mixture of 1-iodohexane
and Mn2(CO)10 over 4 h produced no radical coupling and the
starting iodide was recovered in 77% yield. The efficient cyclis-
ation of 3 at room temperature is noteworthy as reactions of
this type are generally carried out at higher temperature14
to increase the rate of rotation of the amide bond to convert
syn-radicals 4a to anti-radicals 4b (which can then cyclise). As
the lamp did not (significantly) increase the temperature of
the reaction solution, the use of a bulky N-protecting group
(which is known14 to increase the proportion of the anti-amide
conformer) was therefore effective in promoting efficient
cyclisation.
Scheme 2
product BrMn(CO)5 (which can trail down a silica column) was
achieved by a simple work-up procedure involving reaction of
the crude reaction mixture with DBU (2 equiv.).‡ This method
† Spin adducts were observed on irradiation of alkyl iodides in the
absence of Mn2(CO)10, although the signals were weaker than those
observed for reactions using Mn2(CO)10.
‡ The use of alternative nitrogen bases (including triethylamine, pyri-
dine or imidazole) was less effective.
Related bromine-atom abstraction reactions could also be
effected on photolysis of Mn2(CO)10 and BrCCl3 in the presence
1188
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194

View Article Online
Table 2 Reaction of 3 with Mn2(CO)10 in the presence of propan-2-ol
Products (%)
Concentration Equivalents of Addition
Entry of 3/mol dmϪ3 propan-2-ol
time/ha
5
10
8
1
2
3
4
5
0.11
0.02
0.07
0.07
0.02
179
838
—
—
2
4
6
76
53
27
30
—
4
20
16
2
4
—
20
41
54
5b
2b
2b
8
a Dropwise addition of iodide 3 to a solution of Mn2(CO)10 and
propan-2-ol. b Reactions carried out using a mixed dichloromethane–
propan-2-ol solvent system.
reduction. However, when the reaction was carried out in
dichloromethane, using 5 equivalents of propan-2-ol, and
iodide 3 added dropwise to the reaction mixture over 2 h, the
desired product 8 was isolated in 20% yield (entry 3, Table 2).
Increasing the addition time, lowering the concentration and
reducing the number of equivalents of propan-2-ol produced a
further increase in the yield of 8, to a maximum of 54% (entry
5, Table 2). This compares favourably with related tributyltin
hydride-mediated cyclisations, which have been shown to
produce pyrrolidinones with similar N-protecting groups (to 8)
in 12–54% yield.19 The Mn2(CO)10–propan-2-ol reactions also
led to dimerisation of secondary radical 9 to produce pinacol
(as indicated by TLC) although no products derived from cross-
coupling of 9 with, for example, 4ab were isolated. Attempts to
increase the yield of 8 by using an alternative hydrogen-atom
donor, and reacting 3 with cyclohexa-1,4-diene (under similar
conditions to the propan-2-ol reactions) were unsuccessful. For
example, slow addition (5 h) of 3 to a solution of cyclohexa-1,4-
diene (1.1 equivalents) gave ethanamide 10 in 14% yield and
pyrrolidinone 8 in 30% yield (at 0.07 mol dmϪ3).
Interestingly, whereas efficient cyclisation of 3 to give 8
required slow addition of iodide 3 to propan-2-ol, trichloro-
amide 11 underwent cyclisation to give 13 in a comparable yield
(53% versus 54%) even when 11 was added in one portion
(Scheme 6). The slower rate of simple reduction presumably
reflects the greater stability of the intermediate dichlorocarb-
amoylmethyl radical 12 (compared to the carbamoylmethyl
radical 4ab) and/or the faster rate of cyclisation (onto the
electron-rich double bond).
Scheme 4
ؒ
of a 1,6-diene (Scheme 4). The Mn(CO)5 radical selectively
abstracts the bromine atom from BrCCl3 to give the electro-
philic CCl3 radical. This can add to an electron-rich double
ؒ
bond of diene 6a–c to give a secondary radical which is able to
undergo a 5-exo-trig cyclisation reaction. The resultant primary
radical can abstract a bromine atom from BrCCl3 to continue
the chain reaction, leading to cyclic halides 7a–c in 60–89%
yield.§ These yields are similar, or compare favourably, to those
obtained using related methods of initiation (e.g. RuII or RhIII
catalysts,15 SmI2 or AIBN–CCl417). The cis-diastereomers
16
of 7a–c were formed predominantly (as indicated by NMR
spectroscopy) and this is expected for 5-exo-trig cyclisations of
this type, which proceed via a chair-like transition state.18
Hydrogen atom transfer
Photolysis of iodide 3 with Mn2(CO)10 in the presence of a
hydrogen-atom donor was then investigated (Scheme 5, Table
2). It was envisaged that radical cyclisation of 4b could be
followed by trapping the cyclic primary radical with a hydrogen
atom from propan-2-ol, which contains a relatively weak
H–C(OH)Me2 bond (≈380 kJ molϪ1). This would produce
pyrrolidinone 8 together with secondary radical 9. Both iodine-
atom transfer to give 5 and (simple) reduction of the carb-
amoylmethyl radical 4ab to give 10 were expected to compete
with this process. Indeed, initial experiments using propan-2-ol
as the solvent and varying the concentration of 3 were disap-
pointing as only iodine-atom transfer and simple reduction
were observed (entries 1 and 2, Table 2). The higher the con-
centration of propan-2-ol, the greater the yield of simple
This method of initiation could also be applied to the
preparation of pyrrolidine rings. Hence photolysis of allylic
bromide 14 with Mn2(CO)10 and propan-2-ol produced di-
substituted pyrrolidine 15 in 43% yield as a 1:1 mixture of
diastereoisomers (Scheme 7). The formation of equal amounts
of the cis- and trans-diastereoisomers may well reflect the
stability of the allylic radical. This could lead to some revers-
ibility of the radical cyclisation, resulting in the formation of a
§ Control reactions were carried out to confirm that the cyclisations
were initiated by Mn2(CO)10. Hence, irradiation of 6a–c and BrCCl3
[in the absence of Mn2(CO)10] only gave unreacted starting material.
Scheme 5
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194
1189

View Article Online
Table 3 Mn2(CO)10 mediated cyclisations in the presence of TEMPO
Entry
Halide
X
Y
Z
TEMPO addition time/h
Products (yield, %)
1
2
3
4
5
6
7
8
3
3
I
I
I
I
Br
Cl
Cl
Cl
H
H
H
H
Br
Cl
Cl
Cl
H
H
H
H
Br
Cl
Cl
Cl
0
2
3
5
0
0
2
5
19 (61) ϩ 20a (18)
19 (55) ϩ 20a (23)
19 (11) ϩ 20a (74)
19 (7) ϩ 20a (78)
20b (72)
3
3
18
11
11
11
20c (65)
20c (74) ϩ 13 (10)
20c (61) ϩ 13 (18)
steric effects, while the exclusive formation of the E-double
bond hydroxylamines can be attributed to the greater stability
of the intermediate E-allylic radicals.23
This work was followed by irradiation of iodoethanamide 3
and Mn2(CO)10 in the presence of 1.1 equivalents of TEMPO
(Scheme 9, Table 3). Unfortunately, this resulted in predom-
Scheme 6
Scheme 7
Scheme 9
significant yield of the thermodynamically more stable trans-
isomer.20
inant trapping of the carbamoylmethyl radical (4ab), prior to
cyclisation, to give 19 in 61% yield (Table 3, entry 1). The
desired pyrrolidinone 20a was only isolated in 18% yield.
However, when TEMPO was added slowly (over 5 h) to a
mixture of iodide 3 and Mn2(CO)10, 20a was isolated in an
excellent 78% yield (Table 3, entry 4). Similar cyclisation yields
were also obtained on reaction of the tribromo- and trichloro-
amides 18 and 11 to give pyrrolidinones 20b and 20c, respec-
tively (Table 3, entries 5 and 6). It should be noted, however,
that these cyclisation reactions did not require slow addition
of TEMPO. Indeed, when TEMPO was added dropwise to 11
and Mn2(CO)10, the 4-methyl derivative 13 was also isolated
in 10–18% yield (Table 3, entries 7 and 8). This suggested a
competitive hydrogen-atom abstraction reaction involving
the solvent dichloromethane. However, this is not the only
hydrogen-atom donor because when the reaction was repeated
in deuterated dichloromethane, a mixture of the deuterated
product 21 [m/z 289 (35,35M ϩ Hϩ, 65%)] and the 4-methyl
derivative 13 [m/z 288 (35,35M ϩ Hϩ, 55%)] were formed, as
indicated by the mass spectrum (and the 1H NMR spectrum) of
the crude product.
Synthesis of hydroxylamines
The possibility of Mn2(CO)10 promoted cyclisation followed
by intermolecular trapping with tetramethylpiperidine oxide
(TEMPO) was then explored. This would allow the form-
ation of synthetically useful hydroxylamines which could, for
example, be reduced (using zinc/acetic acid)21 to alcohols or
oxidised (using MCPBA)22 to aldehydes. Model reactions using
bromides 16a–d established that this method could be used to
efficiently produce hydroxylamines 17a–d; these being derived
from coupling of the primary radical intermediates with
TEMPO (Scheme 8). The selective trapping of primary (rather
than secondary) radicals to give 17c,d is presumably due to
This work has demonstrated that photolysis of Mn2(CO)10
can efficiently initiate a number of radical reactions. A variety
of 5-membered rings, for example, can be prepared on cyclis-
ation of halide precursors followed by iodine-, bromine- or
hydrogen-atom transfer, or reaction with TEMPO. Although
the cost of Mn2(CO)10 may prohibit large scale synthesis, for
Scheme 8
1190
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194

View Article Online
small scale preparations or for halogen-atom transfer reactions
[using only a catalytic amount of Mn2(CO)10] this method has a
number of advantages over existing methods. These include
mild reaction conditions, clean and efficient cyclisation-
trapping sequences and simple removal of manganese halide
by-products (on DBU work-up).
chromatography (petrol–diethyl ether, 6:4) gave 6b (3.95 g,
76%) as a pale yellow oil; Rf 0.4 (petrol–diethyl ether, 6:4); νmax
(CHCl3) 3034 (m), 2924 (w), 1599 (m), 1343 (br, s), 1160 (s),
1093 (s), 933 (s), 731 (m) cmϪ1; δH (270 MHz, CDCl3) 7.71 (2H,
d, J = 8, aromatics), 7.29 (2H, d, J = 8, aromatics), 5.61 (2H,
ddt, J = 17.5, 10 and 6.5, 2 × CH᎐CH ), 5.18–5.11 (4H, m,
᎐
2
2 × CH᎐CH ), 3.80 (4H, d, J = 6.5, 2 × NCH ), 2.43 (3H, s,
᎐
2
2
C᎐C–CH ); δ (67.5 MHz, CDCl ) 143.0 (CH᎐C–SO ), 137.1
᎐
᎐
3
C
3
2
Experimental
(CH᎐C–CH ), 132.4 (CH᎐C–SO ), 129.5 (CH=C–CH ), 127.2
᎐
᎐
3
2
3
IR spectra were recorded on an ATI Mattison Genesis FT IR
spectrometer. 1H NMR and 13C NMR spectra were recorded on
a JEOL EX 270 or Bruker AMX 500 spectrometer. The 13C
spectra were assigned using DEPT experiments. Coupling con-
stants (J) were recorded in hertz to the nearest 0.5 Hz. EPR
spectra were recorded on a Bruker ESP_300 spectrometer. Mass
spectra were recorded on a Fisons Instruments VG Analytical
Autospec Spectrometer system. Thin layer chromatography
(TLC) was performed on Merck aluminium-backed silica gel
plates. Compounds were visualised under a UV lamp, using
alkaline potassium permanganate solution and/or iodine.
Column chromatography was performed using silica gel (Matrix
Silica 60, 70–200 micron, Fisons or ICN flash silica 60, 32–63
microns). Irradiations with visible light (>400 nm) were carried
out using an ICL 302 UV xenon lamp, 300 W. Petroleum ether
refers to the fraction with bp 40–60 ЊC. Mn2(CO)10 and dienes
6a, 6c were purchased from Sigma–Aldrich Company Ltd.
Halides 3, 11 and 18 were prepared in an analogous manner to
the corresponding N-benzyl derivatives.24
(2 × CH᎐CH ), 119.0 (2 × CH᎐CH ), 49.1 (2 × NCH ), 21.2
᎐
᎐
2
2
2
(CH᎐C–CH ); m/z (CI, NH ) 252 (M ϩ Hϩ, 100%), 224 (14), 96
᎐
3
3
(81) (Found: M ϩ Hϩ, 252.1049. C13H17NO2S requires for
M ϩ Hϩ, 252.1058).
General procedure for bromine-atom transfer reactions using
BrCCl3
Mn2(CO)10 (0.11 g, 0.28 mmol) was added to a stirred solution
of BrCCl3 (0.51 g, 2.56 mmol) and diene 6a–c (0.08–0.22 g, 0.86
mmol) in dichloromethane (20 cm3) under an atmosphere of
nitrogen. After photolysis for 2 h, DBU (0.17 g, 1.12 mmol)
was added dropwise and the solution stirred for a further 1 h.
The crude product was then adsorbed onto silica and column
chromatography afforded products 7a–c (60–89%), as colour-
less oils, as inseparable mixtures of diastereoisomers in the ratio
6–8:1 (as determined from the 1H NMR spectrum).
cis- and trans-4-Bromomethyl-3-(2,2,2-trichloroethyl)tetra-
hydrofuran 7a. Yield 87%; Rf 0.4 (petrol–diethyl ether, 8:2); νmax
(CHCl3)15 2951 (br, m), 2871 (br, m), 2248 (w), 1058 (m), 789
(m), 740 (br, s) cmϪ1; δH (270 MHz, CDCl3)15 (major cis-
isomer) 4.16 (1H, apparent t, J = 8, OCH), 4.01–3.87 (2H, m,
2 × OCH), 3.68 (1H, apparent t, J = 8, OCH), 3.53 (1H, dd,
J = 10.5 and 4, Cl3C–CHAHB), 3.34 (1H, apparent t, J = 10,
Cl3C–CHAHB), 3.04 (1H, dd, J = 14 and 3, BrCHAHB), 2.96–
2.71 (3H, m, BrCHAHB and 2 × OCH2CH); δC (67.5 MHz,
CDCl3) (major cis-isomer) 98.6 (CCl3), 71.8, 71.7 (2 × OCH2),
52.7 (BrCH2), 44.6, 40.5 (Cl3CCH2CH and BrCH2CH),
31.1 (Cl3CCH2); m/z (CI, NH3) 312 (79,35,35,35M ϩ NH4ϩ, 22%),
General procedure for EPR experiments
Mn2(CO)10 (0.02 g, 5 × 10Ϫ5 mol) or Re2(CO)10 (0.03 g, 5 × 10Ϫ5
mol) was added to a solution of the organohalide (0.04–0.12 g,
0.1 mol) and 2,4,6-tribromonitrosobenzene (3 mg, 1 × 10Ϫ5
mol) in dichloromethane (5 cm3). A sample of this solution (ca.
1 cm3) in a cylindrical quartz glass EPR tube was then irradi-
ated in situ for 1–20 minutes and the spectra recorded during
and after photolysis.
N-(4-Methoxybenzyl)-4-iodomethylpyrrolidin-2-one 5. Mn2-
(CO)10 (0.11 g, 0.28 mmol) was added in one portion to a stirred
solution of iodide 3 (1 g, 2.90 mmol) in dichloromethane (20
cm3) under a nitrogen atmosphere. After photolysis for 1 h,
DBU (0.17 g, 1.12 mmol) was added dropwise and the solution
stirred for a further 1 h. The crude product was then adsorbed
onto silica and column chromatography (diethyl ether–ethyl
acetate, 1:1) gave 5 (0.78 g, 78%) as a pale yellow oil; Rf 0.3
(diethyl ether–ethyl acetate, 1:1); νmax (CHCl3) 2933 (m), 2245
(m), 1679 (s), 1612 (m), 1512 (s), 1443 (s), 1249 (s), 1179 (m),
1035 (m) cmϪ1; δH (270 MHz, CDCl3) 7.17 (2H, d, J = 9,
aromatics), 6.86 (2H, d, J = 9, aromatics), 4.42 (1H, d, J = 14,
NCH), 4.34 (1H, d, J = 14, NCH), 3.80 (3H, s, OCH3), 3.39
(1H, dd, J = 11 and 8, NCHAHB), 3.23 (1H, dd, J = 10 and 5.5,
ICHAHB), 3.14 (1H, dd, J = 11 and 7, NCHAHB), 2.96 (1H, dd,
J = 10 and 6, ICHAHB), 2.69–2.55 (2H, m, C(O)CHAHB and
CHCH2I), 2.22 (1H, dd, J = 18 and 8, C(O)CHAHB); δC (67.5
215 (32), 200 (61), 179 (100), 106 (83), 56 (67) (Found:
ϩ
79,35,35,35M ϩ NH4
,
311.9320. C7H10BrCl3O requires for
79,35,35,35M ϩ NH4ϩ, 311.9324).
The presence of the (minor) trans-isomer was indicated by
NMR spectroscopy: δH (270 MHz, CDCl3) 4.29 (1H, dd, J = 9
and 7, BrCHAHB), 2.52–2.43 (2H, m, 2 × OCH2CH); δC (67.5
MHz, CDCl3) 98.3 (CCl3), 74.3 (2 × OCH2), 58.2 (CH2CCl3),
47.7, 42.7 (BrCH2CH and Cl3CCH2CH), 33.8 (CH2Br).
cis- and trans-1-(4-Methylphenylsulfonyl)-3-bromomethyl-4-
(2,2,2-trichloroethyl)pyrrolidine 7b. Yield 60%; Rf 0.3 (petrol–
diethyl ether, 6:4); νmax (CHCl3) 2959 (br, m), 2250 (w), 1598
(w), 1347 (br, s), 1164 (br, s), 1092 (m), 1051 (m), 816 (m), 665
(m) cmϪ1; δH (500 MHz, CDCl3) (major cis-isomer) 7.69 (2H, d,
J = 8, aromatics), 7.31 (2H, d, J = 8, aromatics), 3.62 (1H, dd,
J = 10 and 7, NCH), 3.46–3.37 (2H, m, 2 × NCH), 3.29 (1H,
dd, J = 10 and 4, BrCH), 3.18 (1H, dd, J = 10 and 8, NCH),
2.86 (1H, apparent t, J = 10, BrCH), 2.78 (1H, dd, J = 14.5 and
4, CHCCl3), 2.68–2.60 (2H, m, 2 × CH2CH), 2.50 (1H, dd,
J = 14.5 and 7, CHCCl3), 2.39 (3H, s, CCH3); δC (67.5 MHz,
CDCl3) (major cis-isomer) 143.8 (CSO2), 133.2 (CCH3), 129.8
(CH C᎐CH), 127.2 (CH᎐CSO ), 98.0 (CCl3), 52.5, 51.3
MHz, CDCl ) 158.9 (CO, CH OC᎐C), 129.3 (CH᎐CCH ),
᎐
᎐
3
3
2
128.0 (CH C᎐C), 113.9 (CH᎐COMe), 55.1 (OCH ), 52.5
᎐
᎐
2
3
(NCH2Ar), 45.7 (NCH2CH), 38.5 (NCOCH2), 33.6 (CHCH2I),
9.6 (CH2I); m/z (CI, NH3) 346 (M ϩ Hϩ, 53%), 306 (25),
236 (29), 220 (100) (Found: M ϩ Hϩ, 346.0299. C13H16INO2
requires for M ϩ Hϩ, 346.0304).
᎐
᎐
3
2
(2 × NCH2), 44.1, 39.4 (2 × CH2CH), 30.2 (BrCH2), 21.4
(CCH3); m/z (CI, NH3) 448 (79,35,35,35M ϩ Hϩ, 50%), 406 (48),
370 (26), 252 (34), 214 (36), 139 (23) (Found: 79,35,35,35M ϩ Hϩ,
447.9302. C14H17BrCl3NO2S requires for 79,35,35,35M ϩ Hϩ,
447.9307).
The presence of the (minor) trans-isomer was indicated by
NMR spectroscopy: δH (500 MHz, CDCl3) 3.78 (1H, dd, J = 18
and 10, NCH), 3.51 (1H, dd, J = 11.5 and 5, NCH), 3.14–3.04
N-(4-Methylphenylsulfonyl)-N,N-diallylamine 6b. Triethyl-
amine (2.29 g, 22.6 mmol) was added dropwise to a stirred
solution of diallylamine (2 g, 20.6 mmol) in dichloromethane
(20 cm3) at 0 ЊC. After 0.5 h, 4-methylbenzenesulfonyl chloride
(4.32 g, 22.6 mmol) in dichloromethane (20 cm3) was added
dropwise over 0.25 h, the solution was allowed to warm to rt
and stirred overnight. The crude product was washed with
water, brine, dried (MgSO4) and concentrated in vacuo. Column
(1H, m, NCH); δ (67.5 MHz, CDCl ) 127.5 (SO C᎐CH), 52.4,
᎐
2
C
3
50.2 (2 × NCH2), 43.8, 38.9 (2 × CHCH2).
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194
1191

View Article Online
cis- and trans-Diethyl 3-bromomethyl-4-(2,2,2-trichloroethyl)-
cyclopentane-1,1-dicarboxylate 7c. Yield 89%; Rf 0.25 (petrol–
diethyl ether, 9:1); νmax (CHCl3) 2984 (m), 1726 (br, s), 1445 (w),
1368 (w), 1264 (br, s), 1183 (s), 1112 (w) cmϪ1; δH (270 MHz,
CDCl3)15 (major cis-isomer) 4.21 (4H, q, J = 7, 2 × CO2CH2-
CH3), 3.51 (1H, dd, J = 10 and 6, BrCHAHB), 3.29 (1H, appar-
ent t, J = 10, BrCHAHB), 2.96 (1H, dd, J = 19 and 5, Cl3C–
CHAHB), 2.80–2.52 and 2.42–2.32 (7H, m, Cl3C–CHAHB,
2 × CCH2CH and 2 × CH2CH), 1.27 (6H, t, J = 7, 2 × CO2-
CH2CH3); δC (67.5 MHz, CDCl3) (major cis-isomer) 171.9
(2 × CO), 98.9 (CCl3), 61.7 (2 × CH3CH2O), 58.0 (CCH2CH),
54.0 (CH2CCl3), 44.5, 40.3 (CHCH2Br and CHCH2CCl3), 38.9,
38.0 (2 × CCH2CH), 33.2 (CH2Br), 13.9 (2 × OCH2CH3); m/z
(CI, NH3) 437 (79,35,35,35M ϩ Hϩ, 53%), 410 (11), 190 (15), 173
(11) (Found: 79,35,35,35M ϩ Hϩ, 436.9688. C14H20BrCl3O4
requires for 79,35,35,35M ϩ Hϩ, 436.9689).
methane (75 cm3) was added Mn2(CO)10 (0.28 g, 0.73 mmol)
and propan-2-ol (0.17 g, 2.9 mmol) under an atmosphere of
nitrogen. After photolysis for 3 h, DBU (0.89 g, 5.45 mmol) was
added and the mixture stirred overnight. The solution was then
adsorbed onto silica and column chromatography (petrol–
diethyl ether, 1:1) afforded 3,3-dichloro-N-(4-methoxybenzyl)-
4-methylpyrrolidin-2-one 13 (0.22 g, 53%) as a white solid; mp
96 ЊC (Found: C, 54.0; H, 5.2; N, 4.8. C13H15Cl2NO2 requires C,
54.3; H, 5.3; N, 4.9%); Rf 0.25 (petrol–diethyl ether, 1:1); νmax
(CHCl3) 2936 (m), 1723 (br, s), 1613 (m), 1513 (s), 1205 (br, s),
1177 (m), 823 (m), 748 (s) cmϪ1; δH (270 MHz, CDCl3) 7.17 (2H,
d, J = 9, aromatics), 6.86 (2H, d, J = 9, aromatics), 4.51 (1H, d,
J = 14.5, NCHAHB), 4.38 (1H, d, J = 14.5, NCHAHB), 3.79 (3H,
s, OCH3), 3.21 (1H, dd, J = 10 and 7, NCHAHB), 2.88 (1H, dd,
J = 10 and 7, NCHAHB), 2.78–2.70 (1H, m, NCH2CH), 1.26
(3H, d, J = 6.5, CH3CH); δC (67.5 MHz, CDCl3) 166.6 (CO),
The presence of the (minor) trans-isomer was indicated by
NMR spectroscopy: δH (270 MHz, CDCl3) 3.60 (1H, dd, J = 10
and 4, BrCHAHB), 3.40 (1H, dd, J = 10 and 6.5, BrCHAHB);
δC (67.5 MHz, CDCl3) 172.1 (2 × CO), 61.7 (2 × CH3CH2O).
159.2 (CH OC᎐C), 129.3 (CH᎐CCH ), 126.6 (CH C᎐C), 114.0
᎐ ᎐ ᎐
3 2 2
(CH᎐COMe), 87.2 (CCl ), 55.0 (OCH ), 49.0 (NCH ), 46.8
᎐
2
3
2
(NCH2), 45.0 (CHCH3), 11.5 (CHCH3); m/z (CI, NH3) 305
(
35,35M ϩ NH4ϩ, 29%), 288 (35,35M ϩ Hϩ, 34), 252 (100), 218
(23), 121 (64) (Found: 35,35M ϩ Hϩ, 288.0559. C13H15Cl2NO2
requires for 35,35M ϩ Hϩ, 288.0558).
General procedure for photolysis of iodoethanamide 3 with
Mn2(CO)10 and propan-2-ol in dichloromethane
(E)-N-Allyl-N-(4-bromobut-2-enyl)benzamide 14. Sodium
hydride (0.33 g, 13.6 mmol) was added to a stirred solution of
N-allylbenzamide25 (2 g, 12.4 mmol) in N,N-dimethylform-
amide (100 cm3). After stirring for 2 h, (E)-1,4-dibromobut-
2-ene (7.8 g, 37.2 mmol) was added in one portion and the
solution stirred overnight. The crude product was then washed
with diethyl ether, brine, dried (MgSO4) and concentrated
in vacuo. Column chromatography (petrol–diethyl ether, 3:7)
gave bromide 14 (1.04 g, 29%) as a pale yellow oil; Rf 0.3
(petrol–diethyl ether, 3:7); νmax (CHCl3) 3085 (s), 2245 (m),
1622 (br, s), 1453 (br, s), 1262 (s), 969 (m) cmϪ1; δH (270 MHz,
CDCl3) (mixture of conformers) 7.40–7.38 (5H, m, aromatics),
A solution of iodide 3 (0.5 g, 1.45 mmol) in dichloromethane
(5 cm3) was added slowly (over 2 or 5 h) to a stirred solution of
Mn2(CO)10 (0.28 g, 0.73 mmol) and propan-2-ol (2.90–11.0
mmol, 2–5 equivalents) in dichloromethane (15–75 cm3) during
continuous photolysis under an atmosphere of nitrogen. After
the addition was complete, the solution was photolysed for
a further 0.5 h, DBU (0.44 g, 2.9 mmol) was added dropwise
and after 1 h, the crude product was adsorbed onto silica.
Column chromatography afforded 5 (27–30%), 8 (20–54%) and
10 (2–16%) as colourless oils.
N-(4-Methoxybenzyl)-4-methylpyrrolidin-2-one 8. Rf 0.4
(ethyl acetate); νmax (CHCl3) 2963 (m), 2244 (w), 1668 (s), 1612
(w), 1512 (m), 1443 (s), 1248 (s), 1177 (m), 1035 (m), 753 (w)
cmϪ1; δH (270 MHz, CDCl3) 7.17 (2H, d, J = 9, aromatics), 6.86
(2H, d, J = 9, aromatics), 4.37 (2H, s, NCH2), 3.80 (3H, s,
OCH3), 3.34 (1H, dd, J = 11 and 8, NCHAHB), 2.81 (1H, dd,
J = 11 and 5.5, NCHAHB), 2.59 (1H, dd, J = 16 and 8,
C(O)CHAHB), 2.48–2.29 (1H, m, CHCH3), 2.06 (1H, dd, J = 16
and 5.5, C(O)CHAHB), 1.06 (3H, d, J = 7, CHCH3); δC (67.5
5.85–5.62 (3H, m, BrCH CH᎐CHCH and NCH CH᎐C), 5.26–
᎐
᎐
2
2
2
5.17 (2H, m, NCH CH᎐CH ), 4.13–3.84 (6H, m, BrCH and
᎐
2
2
2
2 × NCH2); δC (67.5 MHz, CDCl3) (mixture of conformers)
171.7 (NCO), 135.2 (C᎐C), 134.3, 133.8, 132.4, 129.6, 128.1,
᎐
126.8 (6 × CH᎐C), 117.8 (CH᎐CH ), 50.8, 49.1, 46.9, 45.3, 42.0
᎐
᎐
2
(2 × NCH2), 32.2, 31.6 (BrCH2CH); m/z (CI, NH3) 294
(79M ϩ Hϩ, 62%), 250 (59), 216 (100), 174 (14), 110 (13)
(Found: 79M ϩ Hϩ, 294.0492. C14H16BrNO requires for
79M ϩ Hϩ, 294.0494).
MHz, CDCl ) 158.9 (CO), 155.1 (CH OC=C), 129.5 (CH C᎐C),
᎐
2
3
3
129.4 (CH᎐CCH ), 114.0 (CH᎐COMe), 55.2 (OCH ), 54.8
᎐
᎐
2
3
N-Benzoyl-3-methyl-4-vinylpyrrolidine 15. A solution of (E)-
N-allyl-N-(4-bromobut-2-enyl)benzamide 14 (0.35 g, 1.20
mmol) in dichloromethane (5 cm3) was added over 5 h to a
stirred solution of Mn2(CO)10 (0.23 g, 0.6 mmol) and propan-
2-ol (0.14 g, 2.4 mmol) in dry dichloromethane (75 cm3),
which was irradiated under an atmosphere of nitrogen. After
the addition was complete, the mixture was photolysed for a
further 1 h, DBU (0.89 g, 5.45 mmol) was added and the
mixture stirred overnight. The crude product was adsorbed
onto silica and column chromatography (petrol–diethyl ether,
3:7) afforded 15 (0.11 g, 43%) as a colourless oil as a 1:1 mix-
ture of inseparable isomers; Rf 0.2 (petrol–diethyl ether, 3:7);
νmax (CHCl3) 3055 (br, m), 2415 (w), 2253 (s), 1617 (br, s), 1432
(m), 896 (br, s), 735 (s), 655 (s) cmϪ1; δH (270 MHz, CDCl3)
(mixture of isomers) 7.50–7.30 (5H, m, aromatics), 5.75–5.56
(NCH2Ar), 45.8 (NCOCH2), 45.1 (NCH2CH), 26.2 (CHCH3),
15.2 (CH3CH); m/z (EI) 219 (Mϩ, 82%), 188 (11), 176 (33), 146
(30), 121 (100), 78 (20) (Found: Mϩ, 219.1253. C13H17NO2
requires for Mϩ, 219.1259).
N-Allyl-N-(4-methoxybenzyl)ethanamide 10. Rf 0.75 (ethyl
acetate); νmax (CHCl3) 2934 (m), 2243 (m), 1627 (s), 1434 (s),
1248 (s), 1177 (m), 1035 (m), 821 (m), 736 (s) cmϪ1; δH (270
MHz, CDCl3) (mixture of conformers) 7.18 and 7.09
(2H, 2 × d, J = 8, aromatics), 6.89 and 6.84 (2H, 2 × d, J = 9,
aromatics), 5.82–5.66 (1H, m, CH᎐CH ), 5.23–5.06 (2H, m,
᎐
2
CH᎐CH ), 4.52 and 4.44 (2H, 2 × s, NCH ), 3.98 and 3.80 (2H,
᎐
2
2
2 × d, J = 6, NCH2), 3.79 (3H, s, OCH3), 2.14 and 2.16 (3H,
2 × s, COCH3); δC (67.5 MHz, CDCl3) (mixture of conformers)
159.4, 159.3 (CO), 133.4, 133.0 (CH᎐CCH ), 128.0 (CH᎐CH ),
᎐
᎐
2
2
(1H, m, CH᎐CH ), 5.21–5.09 (2H, m, CH᎐CH ), 3.93–3.12
᎐
᎐
2
2
117.8, 117.1 (CH᎐CH ), 114.6, 114.2 (CH᎐COMe), 55.6
᎐
᎐
2
(4H, m, 2 × NCH ), 2.37–2.30 (1H, m, CH–C᎐C), 2.04–1.89
᎐
2
(OCH3), 50.8, 50.1, 47.8 (2 × NCH2), 22.1, 22.0 (CH3CO); m/z
(CI, NH3) 220 (M ϩ Hϩ, 100%), 178 (41), 136 (37), 121 (24)
(Found: M ϩ Hϩ, 220.1340. C13H17NO2 requires for M ϩ Hϩ,
220.1340).
(1H, m, CHCH3), 1.08 and 0.89 (3H, 2 × d, J = 7, CHCH3);
δC (67.5 MHz, CDCl3) (mixture of isomers) 164.3 (CONH),
137.1, 136.5 (CH ᎐CH), 136.7 (CO–C᎐C), 129.8, 128.2, 127.1
᎐
᎐
2
(3 × CH᎐C), 117.4, 117.1 (CH᎐CH ), 56.6, 54.7 (NCH ), 53.2,
᎐
᎐
2
2
51.4 (NCH ), 51.3, 49.5 (CH–C᎐C), 39.6, 37.8 (CHCH ), 15.4,
᎐
2
3
Photolysis of trichloroamide 11 with Mn2(CO)10 and propan-2-ol
14.9 (CHCH3); m/z (CI, NH3) 216 (M ϩ Hϩ, 100%), 105 (6)
(Found: M ϩ Hϩ, 216.1382. C14H17NO requires for M ϩ Hϩ,
216.1388).
To a stirred solution of N-allyl N-(4-methoxybenzyl)-2,2,2-
trichloroethanamide 11 (0.47 g, 1.45 mmol) in dry dichloro-
1192
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194

View Article Online
General procedure for synthesis of hydroxylamines 17a–d
of Mn2(CO)10 (0.28 g, 0.73 mmol) and the organohalide 3, 11,
18 (0.47–0.60 g, 1.45 mmol) in dichloromethane (75 cm3) during
continuous photolysis under an atmosphere of nitrogen. After
the addition was complete, the solution was photolysed for a
further 1 h and DBU (0.44 g, 2.92 mmol) was added dropwise.
After 1 h, the crude product was adsorbed onto silica and
column chromatography afforded 19 (7–61%), 20a–c (18–78%)
and 13 (10–18%) as colourless oils.
Mn2(CO)10 (0.28 g, 0.73 mmol) was added to a stirred solution
of the bromide 16a–d (0.24–0.32 g, 1.45 mmol) and TEMPO
(0.25 g, 1.59 mmol) in dry dichloromethane (20 cm3) under an
atmosphere of nitrogen. The solution was then photolysed for
approximately 2 h and then DBU (0.44 g, 2.92 mmol) was
added dropwise. After 1 h, the crude product was adsorbed
onto silica and column chromatography afforded 17a–d (85–
99%) as colourless oils.
N-Allyl-N-(4-methoxybenzyl)-2-(2,2,6,6-tetramethylpiper-
idin-1-yloxy)ethanamide 19. Rf 0.4 (petrol–diethyl ether, 4:1);
νmax (CHCl3) 2940 (s), 2246 (m), 1640 (br, s), 1247 (br, s), 1178
(m), 1037 (m), 991 (w) cmϪ1; δH (270 MHz, CDCl3) (mixture of
conformers) 7.19 and 7.13 (2H, 2 × d, J = 9, aromatics), 6.87
and 6.83 (2H, 2 × d, J = 9, aromatics), 5.80–5.70 (1H, m,
tert-Butyl 2-[(2,2,6,6-tetramethylpiperidin-1-yloxy)methyl]-
acrylate 17a. Yield 85%; Rf 0.5 (petrol–diethyl ether, 10:1); νmax
(CHCl3) 2989 (s), 2947 (s), 1711 (br, s), 1493 (w), 1370 (m), 1257
(w), 1153 (s), 1059 (m) cmϪ1; δH (270 MHz, CDCl3) 6.11 (1H,
s, C᎐CH H ), 5.74 (1H, s, C᎐CH H ), 4.38 (2H, s, CH ON),
᎐
᎐
A
B
A
B
2
CH᎐CH ), 5.28–5.06 (2H, m, CH᎐CH ), 4.58–4.50 (4H, m,
᎐
᎐
2
2
2.67–1.18 (6H, m, CH2CH2CH2), 1.42 (CO2C(CH3)3), 1.10 (6H,
s, 2 × NCCH3), 1.05 (6H, s, 2 × NCCH3); δC (67.5 MHz,
NCH2 and NOCH2), 3.91 (1H, d, J = 6, NCHAHB), 3.83 (2H,
d, J = 6, NCHAHB), 3.78 (3H, s, OCH3), 1.62–1.23 (6H, m,
CH2CH2CH2), 1.18 (6H, s, 2 × CCH3), 1.10 (6H, s, 2 × CCH3);
δC (67.5 MHz, CDCl3) (mixture of conformers) 168.7, 168.5
CDCl ) 165.2 (CO ), 138.6 (C᎐CH ), 124.0 (C᎐CH ), 80.7
᎐
᎐
3
2
2
2
(CO2C), 74.7 (NOCH2), 59.8 (2 × NCCH3), 39.6 (2 × NCCH2),
32.8 (2 × NCCH3), 28.0 (CO2C(CH3)3), 20.2 (2 × NCCH3),
17.0 (CH2CH2CH2); m/z (CI, NH3) 298 (M ϩ Hϩ, 100%), 156
(34), 140 (11) (Found: M ϩ Hϩ, 298.2375. C17H31NO3 requires
for M ϩ Hϩ, 298.2382).
(NCO), 158.9, 158.8 (OC᎐CH), 133.0, 132.6 (CH᎐CCH ),
᎐
᎐
2
129.6, 129.3 (CH᎐CH ), 128.3, 128.0 (CH᎐CCH ), 117.3, 117.1
᎐
᎐
2
2
(CH᎐CH ), 114.0, 113.8 (CH᎐COMe), 77.4 (NOCH ), 59.9
᎐
᎐
2
2
(2 × NCCH3), 55.1 (OCH3), 48.0, 46.8, 46.7 (NCH2), 39.6
(2 × NCCH2), 32.8 (2 × NCCH3), 20.2 (2 × NCCH3), 16.9
(CH2CH2CH2); m/z (CI, NH3) 375 (M ϩ Hϩ, 100%), 156 (20),
140 (16), 121 (27) (Found: M ϩ Hϩ, 375.2653. C22H34N2O3
requires for M ϩ Hϩ, 375.2648).
1-Benzyloxy-2,2,6,6-tetramethylpiperidine 17b. Yield 88%; Rf
0.25 (petrol–dichloromethane, 10:1); νmax (CHCl3)26 2929 (s),
2876 (s), 1453 (m), 1363 (m), 1260 (w), 1132 (w), 1045 (m), 739
(w) cmϪ1; δH (270 MHz, CDCl3)26 7.55–7.31 (5H, m, aromatics),
4.97 (2H, s, NOCH2), 1.79–1.42 (6H, m, 3 × CH2), 1.39 (6H, s,
2 × CCH3), 1.29 (6H, s, 2 × CCH3); δC (67.5 MHz, CDCl3)
N-(4-Methoxybenzyl)-4-(2,2,6,6-tetramethylpiperidin-1-
yloxymethyl)pyrrolidin-2-one 20a. Rf 0.3 (diethyl ether); νmax
(CHCl3) 2936 (s), 2246 (w), 1672 (br, s), 1512 (m), 1445 (br, m),
1299 (w), 1248 (s), 1037 (m) cmϪ1; δH (270 MHz, CDCl3) 7.19
(2H, d, J = 9, aromatics), 6.82 (2H, d, J = 9, aromatics), 4.42
(1H, d, J = 10, NCH), 4.35 (1H, d, J = 10, NCH), 3.79 (3H, s,
OCH3), 3.68 (2H, d, J = 6.0, OCH2CH), 3.33 (1H, dd, J = 10
and 8, NCHAHB), 3.13 (1H, dd, J = 10 and 4.5, NCHAHB),
2.62–2.47 (2H, m, OCH2CH and COCHAHB), 2.31 (1H, dd,
J = 19 and 10, COCHAHB), 1.47–1.26 (6H, m, CH2CH2CH2),
1.10 (6H, s, 2 × CCH3), 1.03 (6H, s, 2 × CCH3); δC (67.5
138.3(CH C᎐C),128.2,127.4,127.3(3 × CH᎐C),78.7(NOCH ),
᎐
᎐
2
2
60.0 (2 × NCCH3), 39.7 (2 × NCCH2), 33.1 (2 × NCCH3),
20.3 (2 × NCCH3), 17.1 (CH2CH2CH2); m/z (CI, NH3) 248
(M ϩ Hϩ, 100%), 156 (28), 142 (6) (Found: M ϩ Hϩ, 248.2013.
C16H25NO requires for M ϩ Hϩ, 248.2014).
(E)-1-Cinnamyloxy-2,2,6,6-tetramethylpiperidine 17c. Yield
99%; Rf 0.1 (petrol); νmax (CHCl3) 2980 (s), 2941 (s), 1493 (w),
1452 (m), 1362 (m), 1132 (m), 1028 (m), 956 (m) cmϪ1; δH (270
MHz, CDCl3) 7.30–7.08 (5H, m, aromatics), 6.49 (1H, d,
MHz, CDCl ) 173.9 (NCO), 159.0 (OC᎐CH), 129.4 (CH᎐C),
᎐
᎐
3
J = 16, PhCH᎐CH), 6.18 (1H, dt, J = 16 and 5.5, PhCH᎐CH),
᎐
᎐
128.5 (NCH C᎐CH), 113.8 (CH᎐C), 77.7 (NOCH ), 59.8
᎐
᎐
2
2
4.35 (2H, d, J = 5.5, NOCH2), 1.43–1.17 (6H, m, 3 × CH2),
1.12 (6H, s, 2 × CCH3), 1.05 (6H, s, 2 × CCH3); δC (67.5
(2 × NCCH3), 55.2 (OCH3), 49.2, 45.8 (2 × NCH2), 39.5 (2 ×
NCCH2), 34.3 (NCOCH2), 33.0 (2 × NCCH3), 30.5 (NCH2-
CH), 19.9 (2 × NCCH3), 16.9 (CH2CH2CH2); m/z (CI, NH3)
375 (M ϩ Hϩ, 100%), 126 (22), 121 (20) (Found: M ϩ Hϩ,
375.2648. C22H34N2O3 requires for M ϩ Hϩ, 375.2648).
MHz, CDCl ) 137.4 (CH C᎐C), 130.4, 128.8, 127.8, 126.8,
᎐
2
3
125.9 (CH᎐C), 78.4 (NOCH2), 60.1 (2 × NCCH3), 40.0
᎐
(2 × NCCH2), 33.4 (2 × NCCH3), 20.6 (2 × NCCH3), 17.5
(CH2CH2CH2); m/z (CI, NH3) 274 (M ϩ Hϩ, 13%), 156 (100),
142 (22), 117 (28) (Found: M ϩ Hϩ, 274.2170. C18H27NO
requires for M ϩ Hϩ, 274.2171).
3,3-Dibromo-N-(4-methoxybenzyl)-4-(2,2,6,6-tetramethyl-
piperidin-1-yloxymethyl)pyrrolidin-2-one 20b. Oil; Rf 0.4
(petrol–diethyl ether, 1:1); νmax (CHCl3) 2971 (s), 1711 (br, s),
1612 (w), 1513 (m), 1440 (br, w), 1249 (br, s), 1177 (m), 1036
(m) cmϪ1; δH (270 MHz, CDCl3) 7.19 (2H, d, J = 8.5, arom-
atics), 6.88 (2H, d, J = 8.5, aromatics), 4.55 (1H, d, J = 15,
NCHAHB), 4.35 (1H, d, J = 15, NCHAHB), 4.19 (1H, dd, J = 9.5
and 5, NCHAHBCH), 3.88 (1H, apparent t, J = 8.5, OCH), 3.81
(3H, s, OCH3), 3.23 (1H, dd, J = 9.5 and 6.5, NCHAHBCH),
3.08–2.97 (2H, m, OCH and NCH2CH), 1.55–1.17 (6H, m,
CH2CH2CH2), 1.08 (6H, s, 2 × CCH3), 1.04 (6H, s 2 × CCH3);
Ethyl
(E)-4-(2,2,6,6-tetramethylpiperidin-1-yloxy)but-2-
enoate 17d. Yield 89%; Rf 0.4 (petrol–diethyl ether, 4:1); νmax
(CHCl3) 2942 (s), 1710 (br, s), 1659 (m), 1449 (m), 1367 (m),
1277 (s), 1182 (s), 1040 (m) cmϪ1; δH (270 MHz, CDCl3) 6.84
(1H, dt, J = 16 and 5.5, CH᎐CHCO Et), 6.03 (1H, dt, J = 16
᎐
2
and 2, CH᎐CHCO Et), 4.39 (2H, dd, J = 5.5 and 2, NOCH ),
᎐
2
2
4.13 (2H, q, J = 7, OCH2CH3), 1.56–1.30 (6H, m, 3 × CH2),
1.25 (3H, t, J = 7, CH3CH2O), 1.07 (12H, s, 4 × CCH3); δC (67.5
MHz, CDCl ) 166.5 (CO ), 143.9 (CH᎐CHCO Et), 120.2
᎐
3
2
2
δC (67.5 MHz, CDCl ) 158.6 (NCO), 139.0 (OC᎐CH), 129.4
᎐
3
(CH᎐CHCO Et), 75.6 (NOCH ), 60.2, 59.8 (2 × NCCH
᎐
2
2
3
(CH᎐C), 127.1 (NCH C᎐CH), 114.1 (CH᎐C), 75.8 (NOCH ),
᎐
᎐
᎐
2
2
and CH2CH3), 39.5 (2 × NCCH2), 32.7 (2 × NCCH3), 20.1
(2 × NCCH3), 16.9 (CH2CH2CH2), 14.2 (CH2CH3); m/z (CI,
NH3) 270 (M ϩ Hϩ, 73%), 156 (100), 140 (16), 126 (8)
(Found: M ϩ Hϩ, 270.2068. C15H27NO3 requires for M ϩ Hϩ,
270.2069).
60.0 (CBr2), 59.7 (2 × NCCH3), 55.1 (OCH3), 50.0 (NCH2-
CH), 47.2, 46.4 (2 × NCH2), 39.4 (2 × NCCH2), 32.9 (2 ×
NCCH3), 19.9 (2 × NCCH3), 16.8 (CH2CH2CH2); m/z (CI,
NH3) 531 (79.79M ϩ Hϩ, 16%), 158 (100), 142 (83), 126 (46)
(Found: 79,79M ϩ Hϩ, 531.0860. C22H32Br2N2O2 requires for
79,79M ϩ Hϩ, 531.0858).
General procedure for cyclisations in the presence of TEMPO
A solution of TEMPO (0.25 g, 1.59 mmol) in dichloromethane
(5 cm3) was added slowly, or in one portion, to a stirred solution
3,3-Dichloro-N-(4-methoxybenzyl)-4-(2,2,6,6-tetramethyl-
piperidin-1-yloxymethyl)pyrrolidin-2-one 20c. Rf 0.5 (petrol–
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194
1193

View Article Online
Dalton Trans., 1977, 551; (b) T. J. Meyer and J. V. Caspar, Chem.
Rev., 1985, 85, 187.
8 R. S. Herrick, T. R. Herrinton, H. W. Walker and T. L. Brown,
Organometallics, 1985, 4, 42.
9 Encyclopedia of Reagents for Organic Synthesis, ed. L. A. Paquette,
Wiley, Chichester, 1995, vol. 2, 1471.
10 (a) L. Grossi, S. Strazzari, B. C. Gilbert and A. C. Whitwood, J. Org.
Chem., 1998, 63, 8366; (b) P. Smith, K. R. Maples and R. L. Lau,
Can. J. Chem., 1992, 70, 116.
diethyl ether, 1:1); νmax (CHCl3) 2932 (br, s), 1725 (br, s), 1612
(w), 1513 (m), 1440 (m), 1251 (s), 1178 (m), 828 (w) cmϪ1; δH
(270 MHz, CDCl3) 7.18 (2H, d, J = 8.5, aromatics), 6.88 (2H, d,
J = 8.5, aromatics), 4.53 (1H, d, J = 14.5, NCHAHB), 4.39 (1H,
d, J = 14.5, NCHAHB), 4.19 (1H, dd, J = 9 and 5, NCHA-
HBCH), 3.88 (1H, t, J = 8, OCHAHB), 3.80 (3H, s, OCH3), 3.35
(1H, dd, J = 9 and 5, NCHAHBCH), 3.10 (1H, t, J = 8,
OCHAHB), 3.04–2.97 (1H, m, OCH2CH), 1.45–1.13 (6H, m,
CH2CH2CH2), 1.07 (6H, s, 2 × CCH3), 1.03 (6H, s, 2 × CCH3);
11 B. C. Gilbert, C. I. Lindsay, P. T. McGrail, A. F. Parsons and
D. T. E. Whittaker, Synth. Commun., 1999, 29, 2711.
12 D. P. Curran and C.-T. Chang, J. Org. Chem., 1989, 54, 3140.
δC (67.5 MHz, CDCl ) 166.3 (NCO), 159.3 (OC᎐CH), 129.4
᎐
3
(CH᎐C), 126.7 (NCH C᎐CH), 114.1 (CH᎐C), 84.0 (CCl ),
᎐
᎐
᎐
2
2
13 Part of this work has been published as
a preliminary
73.6 (NOCH2), 59.7 (2 × NCCH3), 55.1 (OCH3), 48.7
(NCH2CH), 47.0, 46.3 (2 × NCH2), 39.3 (2 × NCCH2), 32.8
(2 × NCCH3), 19.8 (2 × NCCH3), 16.8 (CH2CH2CH2); m/z (CI,
NH3) 443 (35,35M ϩ Hϩ, 100%), 409 (51), 126 (53), 121 (44)
(Found: 35,35M ϩ Hϩ, 443.1870. C22H32Cl2N2O2 requires for
35,35M ϩ Hϩ, 443.1868).
communication: B. C. Gilbert, W. Kalz, C. I. Lindsay, P. T. McGrail,
A. F. Parsons and D. T. E. Whittaker, Tetrahedron Lett., 1999, 40,
6095.
14 (a) I. De Riggi, S. Gastaldi, J.-M. Surzur, M. P. Bertrand and
A. Virgili, J. Org. Chem., 1992, 57, 6118; (b) G. Stork and R. Mah,
Heterocycles, 1989, 28, 723.
15 R. Grigg, J. Devlin, A. Ramasubbu, R. M. Scott and P. Stevenson,
J. Chem. Soc., Perkin Trans. 1, 1987, 1515.
16 S. Ma and X. Lu, J. Chem. Soc., Perkin Trans. 1, 1990, 2031.
17 I. Lachaise, K. Nohair, M. Hakiki and J. Y. Nédélec, Synth.
Commun., 1995, 22, 3529.
Acknowledgements
We thank ICI and The University of York for a University
Studentship (to D. T. E. W.) and the EU (under the
SOCRATES scheme) for funding (W. K.).
18 A. L. J. Beckwith and C. H. Schiesser, Tetrahedron, 1985, 41, 3925.
19 (a) B. Cardillo, R. Galeazzi, G. Mobbili, M. Orena and M. Rossetti,
Heterocycles, 1994, 38, 2663; (b) T. Sato, Y. Wada, M. Nishimoto,
H. Ishibashi and M. Ikeda, J. Chem. Soc., Perkin Trans. 1, 1989, 879.
20 G. Stork and M. E. Reynolds, J. Am. Chem. Soc., 1988, 110, 6911.
21 (a) A. R. Howell and G. Pattenden, J. Chem. Soc., Perkin Trans. 1,
1990, 2715; (b) J. L. Gage and B. P. Branchaud, Tetrahedron Lett.,
1997, 38, 7007; (c) D. L. Boger and J. A. McKie, J. Org. Chem., 1995,
60, 1271; (d) D. L. Boger, R. M. Garbaccio and Q. Jin, J. Org.
Chem., 1997, 62, 8875.
22 M. F. Semmelhack, C. R. Schmid and D. A. Cortés, Tetrahedron
Lett., 1986, 27, 1119.
23 R. Sustmann and D. Brandes, Chem. Ber., 1976, 109, 354.
24 (a) M. Mori, N. Kanda, I. Oda and Y. Ban, Tetrahedron, 1985, 41,
5465; (b) H. Nagashima, N. Ozaki, M. Ishii, K. Seki, M. Washiyama
and K. Itoh, J. Org. Chem., 1993, 58, 464.
References
1 (a) B. Giese, B. Kopping, T. Göbel, J. Dickhaut, G. Thoma, K. J.
Kulicke and F. Trach, Org. React., 1996, 48, 301; (b) F. Aldabbagh
and W. R. Bowman, Contemp. Org. Synth., 1997, 261; (c) W. R.
Bowman, C. F. Bridge and P. Brookes, J. Chem. Soc., Perkin
Trans. 1, 2000, 1.
2 P. A. Baguley and J. C. Walton, Angew. Chem., Int. Ed., 1998, 37,
3072.
3 M. Ballestri, C. Chatgilialoglu, K. B. Clark, D. Griller, B. Giese and
B. Kopping, J. Org. Chem., 1991, 56, 678.
4 G. Pattenden, Chem. Soc. Rev., 1988, 17, 361.
5 B. B. Snider, Chem. Rev., 1996, 96, 339.
25 T. Taniguchi and K. Ogasawara, Tetrahedron Lett., 1998, 39, 4679.
26 J. E. Anderson, D. Casarini, J. E. T. Corrie and L. Lunazzi, J. Chem.
Soc., Perkin Trans. 2, 1993, 1299.
6 G. A. Molander and C. R. Harris, Chem. Rev., 1996, 96, 307.
7 (a) A. Hudson, M. F. Lappert and B. K. Nicholson, J. Chem. Soc.,
1194
J. Chem. Soc., Perkin Trans. 1, 2000, 1187–1194