X=Y-ZH Systems as potential 1,3-dipoles. Part 54: Stereo- and facially-selective formation of bridged bicyclic N-heterocycles via a sequential one-pot electrophile induced oxime→nitrone→cycloaddition sequence. Multiplication of chirality

Article abstract of DOI:10.1016/S0040-4020(02)00564-1

Electrophile induced bridged-ring forming cyclisations creating azabicyclo-[3.3.1]- and azabicyclo-[3.2.1]-nitrones, followed by cycloaddition, occur stereo-, regio- and facially specifically in good to excellent yield. Chiral bridged-ring systems have been synthesised that involve multiplication of chiral centres from one to six and one to seven in one pot reactions.

Full text of DOI:10.1016/S0040-4020(02)00564-1

TETRAHEDRON
Pergamon
Tetrahedron 58 :2002) 5827±5836
XˆY±ZH Systems as potential 1,3-dipoles. Part 54: Stereo-
and facially-selective formation of bridged bicyclic N-heterocycles
via a sequential one-pot electrophile induced
oxime!nitrone!cycloaddition sequence.
Multiplication of chirality
H. Ali Dondas, Ronald Grigg,p Sylvie Thibault, W. Anthony Thomas and Mark Thornton-Pett
Molecular Innovation, Diversity and Automated Synthesis ꢀMIDAS) Centre, School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK
Received 14 March 2002; revised 9 May 2002; accepted 30 May 2002
AbstractÐElectrophile induced bridged-ring forming cyclisations creating azabicyclo-[3.3.1]- and azabicyclo-[3.2.1]-nitrones, followed by
cycloaddition, occur stereo-, regio- and facially speci®cally in good to excellent yield. Chiral bridged-ring systems have been synthesised
that involve multiplication of chiral centres from one to six and one to seven in one pot reactions. q 2002 Elsevier Science Ltd. All rights
reserved.
1. Introduction
2. Azabicyclo[3.3.1] systems
2.1. Cyclisation onto cyclohexenes
We have recently reported a range of 1-pot sequential and
cascade electrophile induced oxime!nitrone!cyclo-
addition reactions furnishing nitrones and their cyclo-
adducts in good yield.1±3 In a preliminary communication
we reported that phenylselenyl bromide is an excellent
reagent for effecting stereo- and regio-speci®c spiro- and
bridged-ring forming cyclisation of oximes onto proximate
alkenes.4 In a recent paper we reported a related electrophile
induced cyclisation of oxime O-allyl and O-benzyl ethers
generating the corresponding oxime ether salts. These oxyi-
minium ions can, under appropriate conditions, be trans-
formed into nitrones, imines or, by reduction,
hydroxylamines.5 Related oximinium ions have proved
versatile intermediates in solid phase synthesis.6 As part
of an ongoing research program developing new cascade
reaction we now report full details of our work on
bridged-ring forming cyclisations of oximes and oxime
ethers. Chiral bridged-ring systems have also been synthe-
sised by this strategy and these processes involve multipli-
cation of chiral centres from one to six and one to seven in
one pot reactions.
Formation of bridged ring nitrones was ®rst evaluated with
oxime :1b) prepared as a 1:1 E/Z-isomer mixture in 93%
yield from the known aldehyde 1a.7,8 Aldoxime :1b) was
treated with phenylselenyl bromide in acetonitrile at
ambient temperature for 1 h to afford the corresponding
azabicyclo[3.3.1]nonane nitrone salt :2) which, upon treat-
ment with Hunig's base afforded nitrone :3) :Scheme 1).
Keywords: facially-selective; N-heterocycles; chirality.
Corresponding author. Tel./fax: 144-113-233-6501;
e-mail: r.grigg@chemistry.leeds.ac.uk
p
Scheme 1.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020:02)00564-1

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H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
Figure 2. X-Ray crystal structure of :9).
Figure 1. X-Ray crystal structure of :5).
Nitrone :3) underwent to 1,3-dipolar cycloaddition with
N-methylmaleimide :NMM) in acetonitrile at room
temperature over 5 h. Cycloadduct :4) was obtained as a
4:1 mixture of isomers :1H NMR) in 67% overall yield
from oxime :1b) :Scheme 1). The minor isomer appears
to possess an equatorial SePh moiety :1H NMR). The stereo-
chemistry of the major isomer :4) was determined by n.O.e
and 2D-COSY studies. Cycloadduct :4) arises via an exo-
transition state which is dictated by the array of axial
protons hindering endo-transition states on both faces of
the nitrone. Sterichindrance to the exo-transition state syn
to the 3-carbon bridge is signi®cantly greater than that syn to
the 1-carbon bridge :see Fig. 4). Hence exo-cycloaddition
syn to the 1-carbon bridge is observed.
Figure 3. X-Ray crystal structure of :10).
Reductive removal of the PhSe group from the 4:1 mixture
using Bu3SnH :1 mol equiv.)/AIBN :10 mol%) gave the
expected product :5) in 78% yield as a single isomer
indicating that the observed 4:1 mixture of isomers of :4)
arises from the PhSe group and that both isomers are exo-
cycloadducts. The stereochemistry of :5) was assigned from
n.O.e. data, 2D-COSY studies and X-ray crystallography
:Fig. 1).
which comprised a 2:1 mixture of :R,R) and :R,S) isomers,
was converted to aldoxime :6b) with hydroxylamine hydro-
chlorideÐsodium acetate in 96% yield. The aldoxime :6b)
comprised a mixture of four isomers. Thus each isomer in
the 2:1 mixture of E- and Z-oximes was a 1.2:1 mixture of
:R,R) and :R,S) isomers. This oxime :6b) mixture reacted
with phenylselenyl bromide to give a mixture of :R,R) and
:R,S) nitrone salts :7) :Scheme 2). Liberation of the nitrones
:8) using potassium carbonate, and subsequent cyclo-
addition with NMM gave a 2:1 mixture of cycloadducts
:9) and :10) in 59% combined yield from 6b. The stereo-
chemistry of products :9) and :10) was determined from
n.O.e data, 2D-COSY studies and X-ray crystallography
:Figs. 2 and 3). The oxime cyclisation is regioselective
and gives exclusively the bicyclo[3.3.1]nitrone salt. No
bicyclo[3.2.2]nitrone salt, which would arise from attack
at the more substituted carbon of the alkene, was detected.
The synthesis of a further azabicyclo[3.3.1]nonane system
was investigated using oxime :6b). Aldehyde :6a), synthe-
sised9 from commercially available :1)-menth-1-en-9-ol,
Formation of cycloadduct :9) requires generation of a
dehydrogenated nitrone :Scheme 4). This can be rational-
ised by initial selective deprotonation of the R,R-salt :11)
to generate the ene-hydroxylamine :13) :Scheme 3).
Molecular models show that pseudo-axial deprotonation
of salt R,R-:11) can be easily achieved whilst the
Scheme 2.
Scheme 3.

H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
5829
Scheme 4.
pseudo-equatorial deprotonation of the R,S-salt :12) is
stereoelectronically disfavoured resulting in inhibition of
deprotonation.
Scheme 5.
bicyclo[3.3.1]nitrone cycloaddition transition states are
analogous to that for formation of :5).
Conversion of :13) into :15) could occur via hydride transfer
from the ene-hydroxylamine :13) to N-methylmaleimide
:Scheme 4). Assuming deprotonation is chemoselective
for :11) :Scheme 3) the operation of both Schemes 3 and
4 would require 1.5 mol equiv. of NMM. In Scheme 2,
1.4 mol equiv. of NMM was employed which indicates,
within experimental error, that chemoselective deproto-
nation of :11) is occurring. This concurs with the S-stereo-
chemistry at C of :10) established by X-ray crystallography
:Fig. 3).
2.2. Cyclisation onto cyclopentenes
Syntheses of optically active bridged-ring systems invol-
ving multiplication of stereocentres from one to six or one
to seven in high yielding one pot reactions have also been
achieved by analogous sequences involving cyclopentenes.
Thus the known literature rearrangement of :2)-a-pinene
epoxide10 was used to prepare R-:18a) which was converted
to its oxime :18b). The chiral oxime was a colourless liquid
which comprised a 1:1 mixture of E- and Z-isomers. The
versatility of the electrophile induced cyclisation process is
demonstrated by the cyclisation of :18b) to :19) despite the
potential for stericinhibition by the gem-dimethyl group.
Cycloaddition of :19) with NMM in the presence of Hunig's
base afforded a single cycloadduct formulated as :20),
The cycloaddition reactions of the two nitrones :15) and
:12) occurs with high facial selectivity via exo-transition
states :16) and :17) :Fig. 4) to afford the exo-cycloadducts
:9) and :10). The top face of the dipole remains more
sterically hindered even in the presence of the additional
pseudo axial methyl group on the bottom face of :17)
:Fig. 4). Consequently, exo-cycloaddition syn to the
1-carbon bridge is observed, as previously discussed
for :3), affording endo-cycloadducts :9) and :10). These
20
[a]D ˆ167 :cˆ0.8, CHCl3) in 72% overall yield from
:18b) :Scheme 5). The stereochemistry of :20) was
determined from n.O.e. data, 2D-COSY studies and X-ray
crystallography.4 This sequence results in the multiplication
of one chiral centre in :18b) to seven in :20).
3. Azabicyclo[3.2.1] systems
3.1. Cyclisation onto an exo-cyclic alkenes
Bridged-ring formation via cyclisation of a chiral oxime
onto an exo-methylene group was studied with :1R)-:2,2-
dimethyl-3-methylenecyclopentyl)-1-acetaldehyde :21a),
prepared according to the literature procedure10, which
was converted to oxime :21b) :1:1 E/Z-isomer mixture).
The oxime reacted :MeCN, rt, 1 h) with PhSeBr to give
the nitrone salt :22) which was not isolated but was treated
with Hunig's base followed by addition of NMM :MeCN,
rt). After stirring the mixture for 10 h work up gave a single
Figure 4.

5830
H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
Scheme 6.
Scheme 7.
20
exo-cycloadduct :23), [a]D ˆ264.0 :cˆ0.2, CHCl3),
:74%, from :21b)) :Scheme 6). In this sequence multipli-
cation of one chiral centre in :21b) to six chiral centres in
:23) has been achieved in a one pot process. The stereo-
chemistry of the cycloadduct was determined from n.O.e
data, 2D-COSY studies and X-ray crystallography :Fig. 5).
3.2. Cyclisation onto an endo-cyclic alkene
Figure 6.
E-Oxime :24) was synthesised from 4-acetyl-1-methyl-
cyclohexene and hydroxylamine hydrochloride in 86%
yield. Only a trace amount of Z-isomer was detected in
The conformation of the intermediate onium species derived
from oxime :24) is crucial in the cyclisation. Oxime :24)
needs to access conformation :A), as opposed to conforma-
tion :B) to enable cyclisation :Fig. 6). However the required
trajectory angle of the nitrogen lone pair necessary for cycli-
sation is reached with dif®culty and imposes angle strain in
the transition state. It is also noteworthy that this cyclisation
is highly regioselective and gives :25) exclusively.
1
the H nmr spectrum. E-Oxime :24) was then treated with
phenylselenyl bromide in acetonitrile at ambient tempera-
ture for 20 h to afford the bicyclic salt :24). Neutralisation of
the nitrone salt with potassium carbonate liberated the
nitrone :26) and cycloaddition to NMM afforded a 1.2:1
mixture of cycloadducts :27) and :28) as in 54% combined
yield together with 22% of recovered oxime :24) :Scheme
7). The stereochemistry of cycloadducts :27) and :28) was
determined on the basis of n.O.e data and 2D-COSY studies.
Both :27) and :28) arise via exo-transition states :Fig. 7)
which is dictated by the steric impediment to endo-cyclo-
addition posed by the bicyclic framework of the nitrone. The
top face of the dipole is less sterically hindered than the
bottom face. Consequently, the approach of the dipolaro-
phile from the top face of the dipole affords the major
cycloadduct :27) and approach of the dipolarophile from
the bottom face of the dipole leads to cycloadduct :28).
The cyclisation reaction in this case is slow and incomplete.
Figure 5. X-Ray crystal structure of :23).
Figure 7.

H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
5831
4. Oxime O-benzyl ether cyclisation
5. Experimental
5.1. General technical data
Oxime O-benzyl ether :29) was synthesised as a 3:1 mixture
of E- and Z-isomers from 4-acetyl-1-methyl-cyclohexene
and O-benzylhydroxylamine in 82% yield :Scheme 8).
Treatment of :29) with phenylselenyl bromide :1.0 equiv.)
at rt for 16 h resulted in incomplete conversion :TLC).
Additional phenylselenyl bromide :0.1 equiv.) was there-
fore added and the solution stirred at rt for additional 6 h.
Nuclear magnetic resonance spectra and decoupling experi-
ments were determined at 300 MHz on a QE 300 instrument
and at 400 MHz on a Bruker AM400 spectrometer as
speci®ed. Chemical shifts are given in parts per million
:d) down®eld from tetramethylsilane as internal standard.
Spectra were determined in deuteriochloroform except
where otherwise stated. The following abbreviations
are used; sˆsinglet, dˆdoublet, tˆtriplet, qˆquartet,
mˆmultiplet, brˆbroad and brsˆbroad singlet.
1
After work up the H NMR spectrum of the crude product
showed the presence of benzaldehyde, suggesting partial
fragmentation of the oximinium salt :30) to iminium ion
:31). A singlet at d 4.5 ppm was diagnosticfor the benzyl
methylene protons of salt :30).
Flash column chromatography was performed using silica
gel 60 :230±400 mesh). Kieselgel columns were packed
with silica gel GF254 :Merck 7730). Petroleum ether refers
the fraction with bp 40±608C unless otherwise speci®ed.
Melting points were determined on a Ko¯er hot stage appa-
ratus and are uncorrected. Microanalyses were obtained
using a Carlo±Erba Model 1106 instrument. Mass spectra
were recorded at 70 eV on a VG Autospec mass spectro-
meter. All calculations for selenium were based on its most
abundant isotope 80Se. Speci®c rotations were measured
at ambient temperature with an Optical Activity Ltd.,
AA-1000 polarimeter. All solvents were puri®ed according
to procedures given in Puri®cation of Laboratory
Chemicals, D. D. Perrin, W. L. F. Armarego, D. R. Perrin,
Permagon Press, 1980.
5.1.1. Cyclohex-3-enyl acetaldoxime 91b). A solution of
cyclohex-3-enyl acetaldehyde :1a)7 :0.9 g, 7.2 mmol) in
acetonitrile :40 ml) was added to a solution of hydroxyl-
amine hyrochloride :0.55 g, 1.1 equiv.) and sodium acetate
:0.71 g, 1.2 equiv.) in water :40 ml). The resulting solution
was stirred at ambient temperature for 3 h. and extracted
with chloroform :2£100 ml). The combined organic layer
was dried :MgSO4) and concentrated under reduced
pressure. The residue was subjected to column chroma-
tography on silica eluting with 3:1 v/v petroleum ether±
ether to afford the product :0.93 g, 93%) as a colourless
liquid, bp 59±628C/0.1 mm Hg which comprised a 1:1
mixture of E- and Z-isomers.
Scheme 8.
Reduction of this mixture with sodium borohydride afforded
a 1:1.6 mixture of nitrone :26) :21%) and amine :32) :34%)
from oxime ether :29). Amine :32) was converted quanti-
tatively to its hydrochloride salt :33) using HCl :gas) in
diethyl ether. Nitrone :26) was subjected to 1,3-dipolar
cycloaddition reaction with NMM to produce a 1:1
mixture of exo-cycloadducts :27) and :28) in 52% combined
yield.
:Found: C, 69.15; H, 9.3; N, 9.9, C8H13NO requires: C,
69.0; H, 9.4; N, 10.0%); dH :300 MHz, CDCl3): 9.81
and 9.03 :br, 1H, OH, isomers), 7.48 :t, 1H, E-CHvN),
6.78 :t, 1H, Z-CHvN), 5.65 :brs, 2H, CHvCH,
isomers) and 2.40±1.69 :m, 9H); m/z :%): 139 :M1, 10),
120 :17), 93 :18), 80 :100), 67 :19), 59 :72), 53 :34) and 41
:40).
5.1.2. 93aS,6S,7R,11aR,11bR)-2-Methyl-7-9phenylseleno)-
octahydro-6,10-methanopyrrolo[30,40:4,5]isoxazolo[2,3-a]-
azocine-1,393aH)-dione 94). Phenylselenyl bromide :0.2 g,
0.86 mmol) was added to a solution of oxime :1b) :0.1 g,
0.72 mmol) in dry acetonitrile :5 ml). The resulting solution
was stirred at ambient temperature for 1 h when NMM
:0.079 g, 0.72 mmol) and diisopropylethylamine :Hunig's
base) :0.11 g, 0.15 ml) were added. The resulting solution
was stirred 258C for 5 h and the solvent evaporated. The
residue was subjected to column chromatography on silica
eluting with 5:1 v/v petroleum ether±ether to afford the
In summary, the technically simple electrophile-induced
nitrone generation from oximes followed by cycloaddition
onto proximate alkenes constitutes a versatile and ef®cient
method for the stereospeci®c formation of bridged bicyclic
nitrogen heterocycles. The cyclisation step proceeds with
high regioselectivity and follows Baldwin's rules.11 The
facial selectivity is rationalised on the basis of steric
hindrance and the sequence occurs with high regio-
and stereo-selectivity and provides a major increase in
molecular complexity.

5832
H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
product :0.19 g, 67%) as a colourless solid, mp 53±548C,
that comprised 4:1 mixture of isomers.
chloride :1.0±1.1 equiv.) and sodium acetate :1.2 equiv.) in
water :7.5 ml). The resulting solution was stirred at ambient
temperature for 4±16 h. then extracted with DCM :3£
20 ml). The combined organic layers were dried :MgSO4)
and concentrated under reduced pressure. The residue was
subjected to column chromatography on silica eluting with
1:1 v/v diethyl ether±hexane.
5.3. General procedure 9B) for the PhSeBr induced
nitrone formation±cycloaddition reactions of oximes
Phenylselenyl bromide :1.0 equiv.) was added to a stirred
solution of oxime :1.0 equiv.) and stirring was continued at
ambient temperature for 2 h. Anhydrous potassium carbo-
nate :1.1 equiv.) was then added and the solution stirred at
ambient temperature for an additional 1 h. N-Methylmalei-
mide :NMM) :1.2 equiv.) was then added and the resulting
mixture was stirred at 408C or boiled under re¯ux for 16 h.
The solvent was then evaporated and the residue subjected
to ¯ash chromatography on silica.
:Found: C, 56.65; H, 5.75; N, 6.75; C19H22N2O3Se requires:
C, 56.3; H, 5.45; N, 6.90%); dH :300 MHz): 7.55 and 7.23
:m, 5H, ArH, isomers), 4.71 :d, 1H, Jˆ7.22 Hz, Ha), 4.0 :m,
1H, Hc), 3.70 :m, 1H, He), 3.51 and 3.48 :m, 1H, Hd), 3.19
:d, 1H, Jˆ7.28 Hz, Hb), 2.99 :s, 3H, NMe) and 2.36±1.41
:m, 9H); m/z :%): 406 :M1, 24), 249 :100), 207 :62), 138
:61), 111 :49), 95 :52), 67 :42) and 41 :60).
5.3.1. 2-94-Methyl-3-cyclohexen-1-yl)-propanal oxime
96b). Prepared from 2-:4-methyl-3-cyclohexen-1-yl)-propa-
nal :1.02 g, 6.7 mmol), hydroxylamine hyrochloride :0.52 g,
7.4 mmol) and sodium acetate :0.68 g, 7.4 mmol) by
general procedure :A). The oxime :1.08 g, 96%), obtained
as a colourless oil, comprised a mixture of four isomers each
of which was a 2:1 mixture of E- and Z-isomers, a 1.2:1
mixture of :R,R) and :R,S) isomers.
5.1.3.
93aS,6R,11aR,11bR)-2-Methyloctahydro-6,10-
methanopyrrolo[30,40:4,5]isoxazolo[2,3-a]azocine-1,393aH)-
dione 95). Tri-n-butyltin hydride :0.11 g, 0.37 mmol) and
2,20-azabis-:2-methyl propionitrile) :AIBN) :0.005 g, 10%
mol) were added to a stirred solution of cycloadduct :4) :4:1
isomer mixture) :0.127 g, 0.31 mmol) in toluene :15 ml) at
room temperature. The reaction mixture was stirred and
boiled under re¯ux under N2 for 4 h. After removing toluene
under reduced pressure the residue was subjected to column
chromatography on silica eluting with 1:3 v/v petroleum
ether±ether to afford the product :0.061 g, 78%) as colour-
less prisms, mp 170±1728C.
:Found: C, 71.75; H, 10.3; N, 8.1; C10H17NO requires: C,
71.85; H, 10.15; N, 8.4%); dH :250 MHz): 8.38 and 8.13 :br,
1H, OH), 7.33 :2£d, 0.5H, Jˆ7.7 Hz, E-CHvN), 6.58
:2£d, 0.5H, Jˆ8.1 Hz, Z-CHvN), 5.34 :m, 1H, CHvC),
1.64 :s, 3H, Me±CvC), 3.09±1.16 :m, 8H), 1.08 :2£d, 3H,
Jˆ6.9 Hz, Me±CH) and 1.04 :2£d, 3H, Jˆ6.9 Hz, Me±
CH); m/z :%): 167 :M1, 1), 149 :37), 134 :21), 95 :100),
79 :54) and 41 :25); nmax :®lm): 3280 :br, 1H, OH), 2900
:CH), 1650 :CvC), 1440, 1380, 1310, 1155, 1070, 960 and
800 cm21
.
5.4. Cycloadducts 99) and 910)
Prepared from oxime :6B) :0.36 g, 2.2 mmol), phenyl-
selenyl bromide :0.57 g, 2.4 mmol), anhydrous potassium
carbonate :0.36 g, 2.6 mmol) and NMM :0.36 g, 3.2
mmol) by general procedure :B) and puri®ed by ¯ash chro-
matography on silica eluting with 1:1 v/v diethyl ether±
hexane to afford the :9) :0.38 g, 41%) and :10) :0.16 g,
18%).
:Found: C, 62.45; H, 7.25; N, 11.15; C13H18N2O3 requires:
C, 62.30; H, 7.25; N, 11.19%); dH :400 MHz): 4.71 :d, 1H,
Jˆ7.3 Hz, Ha), 4.03 :m, 1H, Hc), 3.5 :m, 1H, Hd), 3.19
:d, 1H, Jˆ7.3 Hz, Hb), 3.02 :s, 3H, NMe) and 2.2±0.91
:m, 11H, aliphatic); m/z :%): 250 :M1, 38), 207 :89), 164
:100), 149 :23), 111 :21), 67 :21) and 41 :38); enhancement
:%): :Table 1).
5.4.1.
93aS,6R,7R,10R,11aS,11bS)-2,7-Dimethyl-11-
methylene-7-9phenylseleno)octanydro-6,10-methano-
pyrrolo[30,40:4,5]isoxazolo[2,3-a]azocine-1,393aH)-dione
99). Crystallised from diethylether±hexane as pale yellow
5.2. General procedure 9A) for the preparation of oximes
20
A solution of aldehyde or ketone :1.0 equiv.) in acetonitrile
:15 ml) was added to a solution of hydroxylamine hydro-
prisms, mp 119±1208C. [a]D ˆ234.0 :1.05 g/100 ml,
CHCl3).
Table 1. n.O.e data: enhancement :%)
:Found: C, 58.45; H, 5.75; N, 6.7; C21H24N2O3Se requires:
C, 58.35; H, 5.55; N, 6.5%); dH :500 MHz): 7.58±7.56 :m,
2H, ArH), 7.45±7.20 :m, 3H, ArH), 5.06 :d, 1H, Jˆ2.4 Hz,
He), 4.95 :d, 1H, Jˆ2.4 Hz, Hd), 4.63 :d, 1H, Jˆ7.2 Hz,
Ha), 4.37 :br, 1H, Hc), 3.79 :d, 1H, Jˆ7.2 Hz, Hb), 3.340
Signal irradiated
Ha
Ha
9.8
Hb
6.8
Hc
2.8
Hb
Hc2.3

H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
5833
and 17.8; m/z :%): 434 :M1, 1), 166 :100), 93 :91), 77 :31),
54 :31) and 41 :24); enhancement :%): :Table 3).
5.4.3.
91)-91R)-2,2-3-Trimethyl-3-ene-1-acetaldoxime
918b). A solution of aldehyde :18a) :2 g, 13 mmol) in aceto-
nitrile :75 ml) was added to a solution of hydroxylamine
hydrochloride :1 g, 1.1 equiv.) and sodium acetate :1.29 g,
1.2 equiv.) in water :75 ml). The resulting solution was
stirred at ambient temperature for 3 h. then extracted with
chloroform :2£200 ml). The combined organic layers were
dried :MgSO4) and concentrated under reduced pressure.
The residue was subjected to column chromatography on
silica eluting with 1:1 v/v petroleum ether±ether to afford
the product :2.1 g, 95%) as a colourless liquid, bp 66±688C/
0.1 mm Hg which comprised a 1:1 mixture of E- and
:br, 1H, Hg), 2.99 :s, 3H, NMe), 2.68 :br, 1H, Hf), 2.42±
1.58 :m, 6H) and 1.38 :s, 3H, Me); dC :125 MHz): 176.5,
175.2, 138.3, 129.1, 129.0, 128.9, 126.8, 111.9, 73.4, 64.4,
60.5, 53.6, 49.7, 36.6, 34.1, 26.6, 28.2, 24.8 and 24.1; m/z :%)
:FAB): 432 :M1, 10), 275 :100), 219 :6), 188 :5), 164 :16),
148 :11), 107 :5) and 93 :8); enhancement :%): :Table 2).
20
Z-isomers. [a]D ˆ111.2 :c 1.5 g/100 ml, CHCl3).
:Found: C, 71.6; H, 10.5; N, 8.4; C10H17NO requires: C,
71.8; H, 10.25; N, 8.4%); dH :300 MHz): 9.86 and 9.32
:br, 1H, OH, isomers), 7.46 :t, 1H, E-CHvN), 6.75 :t,
1H, Z-CHvN), 5.21 :brs, 1H, CvCH, isomers), 2.54±
1.66 :m, 5H, aliphatic-H, isomers), 1.66 and 1.60 :s, 3H,
CHvCH±Me, isomers), 1.03 and 1.00 :s, 3H, Me, isomers)
and 0.8 and 0.7 :s, 3H, Me, isomers); m/z :%): 167 :M1, 6),
150 :7), 134 :21), 108 :100), 93 :52), 67 :11) and 41 :18).
Table 2. Enhancement :%)
Signal irradiated Ha Hb HcHd
He
Hf Hg Me Ar
Ha
Hb
6.4
9.0
2.3 10.7
19.2
Hc3.1
Hd
He
0.6
16.9
21.5
7.0
8.4
Hf
Hg
Me
2.2 3.4
2.6
5.4.4. 93aS,6S,7S,9S,10aR,10bR)-2,6,11,11-Tetramethyl-
7-9phenylseleno)octahydro-1H-6,9-methanopyrrolo-
[30,40:4,5]isoxazolo[2,3-a]azepine-1,3-dione 920). Phenyl-
selenyl bromide :0.14 g, 1.2 equiv.) was added to a solution
of oxime :18b) :0.1 g, 0.6 mmol) in dry acetonitrile :5 ml).
The resulting solution was stirred at ambient temperature for
1 h when NMM :0.066 g, 1 equiv.) and diisopropylethyl-
amine :Hunig's base) :0.0773 g, 0.1 ml, 1.2 equiv.) were
added. The resulting solution was stirred 258C for 5 h and
the solvent evaporated. The residue was subjected to
column chromatography on silica, eluting with 6:1 v/v
petroleum ether±ether, to afford the product :0.19 g, 72%)
which crystallized from petroleum ether :bp 60±808C)-ether
as colourless prisms of a single stereoisomer, mp 154±
1.1
2.3
5.4.2. 93aS,6R,7R,10R,11S,11aR,11bR)-2,7,11-Trimethyl-
7-9phenylseleno)octahydro-6,10-methanopyrrolo[30,40:4,5]-
isoxazolo[2,3-a]azocine-1,393aH)-dione 910). Crystallised
from ethyl acetate±petroleum ether as pale yellow plates,
20
mp 147±1488C. [a]D ˆ222.0 :1.07 g/100 ml, CHCl3).
20
1568C; [a]D ˆ167 :c 0.8 g/100 ml, CHCl3).
:Found: C, 57.95; H, 6.15; N, 6.4; C21H26N2O3Se requires:
C, 58.15; H, 6.0, N, 6.45%); dH :500 MHz): 7.57±7.55 :m,
2H, ArH), 7.39±7.24 :m, 3H, ArH), 4.55 :d, 1H, Jˆ7.1 Hz,
Ha), 3.95 :d, 1H, Jˆ6.3 Hz, Hd), 3.51 :d, 1H, Jˆ7.1 Hz,
Hb), 3.27 :m, 1H. Hc), 2.98 :s, 3H, NMe), 2.29±1.62 :m,
8H), 1.32 :s, 3H, Me) and 1.18 :d, 3H, Jˆ7.3 Hz, Me); dC
:100 MHz): 177.3, 175.3, 138.3, 129.0, 128.9, 127.0, 74.0
62.1, 59.7, 53.3, 50.2, 35.3, 34.4, 33.4, 29.4, 28.4, 24.9, 19.2
Table 3. Enhancement :%)
:Found: C, 58.0; H, 6.05; N, 6.45; C21H26N2O3Se requires:
C, 58.2; H, 6.0; N, 6.4%). dH :300 MHz, C6D6): 7.52±6.90
:m, 5H, ArH), 4.40 :d, 1H, Jˆ8.1 Hz, Ha), 3.26 :m, 1H, Hc),
3.0 :m, 1H, Hd), 2.60 :m, 1H, Hb, 2.44s, 3H, NMe), 2.07±
1.21 :m, 5H), 1.50 :s, 3H, NC±Me), 0.82 :s, 3H, Me) and
0.74 :s, 3H, Me); m/z :%): 434 :M1, 2), 323 :40), 166 :50),
150 :38), 121 :41), 107 :100), 91 :48), 77 :58), 55 :34) and
41 :61); enhancement :%): :Table 4).
Signal irradiated
Ha
Hb
Hc14.2
Hd
Ha
5.4
Hb
6.3
HcHd
1.9
Me
Meb
3.4
5.2
a
2.8
2.2
0.9
3.7
0.5
3.3
Mea
Meb
2.3
1.3

5834
H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
Table 4. Enhancement :%)
Table 5. Enhancement :%)
Signal irradiated
Ha
Hb
Hc1.0
Hd
Ha
7.0
Hb
4.0
HcHd
Signal irradiated
Ha
Ha
9.6
Hb
5.5
Hd1
Hd2
ArH
11.0
10.0
Hb
Hd1
Hd2
11.9
2.7
5.1
17.0
10.0
27.0
5.4.5. 91R)-2,2-Dimethyl-3-methylidene cyclopentane-1-
acetaldoxime 921b). A solution of aldehyde :21a)10
:0.1 g, 0.6 mmol) in acetonitrile :10 ml) was added to
a solution of hydroxylamine hydrochloride :0.055 g,
1.1 equiv.) and sodium acetate :0.065 g, 1.2 equiv.) in
water :10 ml). The resulting solution was stirred at ambient
temperature for 3 h and extracted with chloroform
:2£50 ml). The combined organic layer was dried
:MgSO4) and concentrated under reduced pressure. The
residue was subjected to column chromatography on silica
eluting with 3:1 v/v petroleum ether±ether to afford the
product :0.098 g, 89%) as a thick colourless oil which
comprised a 1:1 mixture of E- and Z-isomers.
5.4.7. 1-94-Methyl-3-cyclohexen-1-yl)-1-ethanone oxime
924). Prepared from 4-acetyl-1-methylcyclohexene :3.0 g,
21.7 mmol), hydroxylamine hydrochloride :1.66 g, 23.8
mmol) and sodium acetate :2.15 g, 26.2 mmol) by the
general procedure :A) and puri®ed by ¯ash chromatography
on silica eluting with 1:2 v/v diethyl ether±hexane to afford
the E-oxime :2.84 g, 86%) as a colourless oil.
:Found: C, 70.8; H, 10.0; N, 9.1; C9H15NO requires: C, 70.6;
H, 9.8; N, 9.15%). d :250 MHz): 9.79 :br, 1H, OH), 5.40 :m,
1H, CHvC), 1.89 :s, 3H, Me±CvN), 1.66 :s, 3H, Me±CvC)
and 2.41±1.53 :m, 7H, cyclohexyl); m/z :%): 153 :M1, 61),
136 :48), 121 :70), 108 :48), 95 :95), 79 :73), 67 :63), 55 :31)
and 42 :100); nmax :®lm): 3240 :br, 1H, OH), 2900 :CH),
HRMS: 167.1310; C10H17NO requires: 167.1312; dH
:300 MHz): 9.05 :br, 1H, OH, isomers), 7.47 :t, 1H,
E-CHvN), 6.74 :t, 1H, Z-CHvN) 4.79 :brs, 2H,
CvCH2, isomers), 2.60 21.1 :m, 7H), and 1.08 and 0.85
:2£s, 6H, Me); m/z :%): 166 :M21, 6), 107 :100), 92 :86),
78 :53) and 41 :51).
1650 :CvC), 1440, 1370, 1150, 950, 790 and 700 cm21
.
5.5. Cycloadducts 927) and 928)
Prepared from oxime :24) :0.50 g, 3.3 mmol), phenyl-
selenyl bromide :0.79 g, 3.3 mmol), anhydrous potassium
carbonate :0.55 g, 4 mmol) and NMM :0.53 g, 4.8 mmol)
by general procedure :B) and puri®ed by ¯ash chroma-
tography on silica eluting with 1:1 v/v diethyl ether±hexane
to afford the products :27) :0.41 g, 30%) and :28) :0.33 g,
24%) :78% conversion).
5.4.6.
93aS,6R,9R,10aR,10bR)-2,11,11-Trimethyl-6-
[9phenylseleno)methyl]octahydro-1H-6,9-methanopyrrolo-
[30,40:4,5]isoxazolo[2,3-a]azepine-1,3-dione 923). Phenyl-
selenyl bromide :0.175 g, 0.63 mmol) was added to a
solution of oxime :21b) :0.1 g, 0.59 mmol) in dry aceto-
nitrile :10 ml). The resulting solution was stirred at ambient
temperature for 1 h when NMM :0.066 g, 0.59 mmol) and
diisopropylethylamine :Hunig's base) :0.093 g, 1.2 equiv.)
were added. The resulting solution was stirred 258C for 5 h
and the solvent evaporated. The residue was subjected to
column chromatography on silica eluting with 6:1 v/v petro-
leum ether±ether to afford a single cycloadduct :23)
:0.192 g, 74%) as colourless needles, mp 161±1638C.
5.5.1. 93aR,6S,7S,10S,10aR,10bS)-2,7,10a-Trimethyl-7-
9phenylseleno)octahydro-1H-6,10-methanopyrrolo-
[30,40:4,5]isoxazolo[2,3-a]azepine-1,3-dione 927). Crystal-
lised from ethyl acetate±petroleum ether as colourless
needles, mp 163±1648C.
20
[a]D ˆ264.0 :0.2 g/100 ml, CHCl3).
:Found: C, 57.4; H, 5.85; N, 6.85; C20H24N2O3Se requires:
C, 57.3; H, 5.75; N, 6.7%); dH :400 MHz): 7.60±7.57 :m,
2H, ArH), 7.39±7.26 :m, 3H, ArH), 4.85 :d, 1H, Jˆ7.6 Hz,
Ha), 3.36 :d, 1H, Jˆ7.6 Hz, Hb), 3.20 :d, 1H, Jˆ6.5 Hz,
Hc), 2.97 :s, 3H, NMe), 2.62 :d, 1H, Jˆ12.8 Hz), 2.45 :m,
1H, Hd), 1.91±1.83 :m, 2H), 1.69±1.49 :m, 3H), 1.46 :s,
3H, Me) and 1.37 :s, 3H, Me). dC :100 MHz): 174.0, 171.4,
137.9, 129.1, 128.8, 127.0, 80.8, 77.8, 74.1, 62.0, 51.9, 46.0,
33.3, 32.9, 29.1, 24.9, 23.9 and 17.1; m/z :%) :FAB): 420
:M1, 9), 263 :100), 169.:11) and 95 :8); enhancement :%):
:Table 6).
:Found: C, 58.25; H, 5.80; N, 6.40; C21H26N2O3Se requires:
C, 58.20; H, 6.05; N, 6.45%); d :400 MHz, C6H6): 7.55 and
7.01 :m, 5H, ArH), 4.57 :d, 1H, Jˆ7.8 Hz, Ha), 3.30 and
3.15 :2£d, 2H, Hd1 and Hd2), 3.19 :t, 1H, Jˆ9.1 Hz, Hc),
2.87 :t, 1H, Jˆ9.2, Hb), 2.60 :s, 3H, NMe), 1.90±1.20 :m,
7H) and 0.98 and 0.60 :2£s, 6H, Me). m/z :%) :FAB): 435
:M11, 87), 324 :6), 277 :100), 263 :10), 150 :9) and 109
:26); enhancement :%): :Table 5).

H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
5835
Table 6. Enhancement :%)
5.6. Cyclisation products 926) and 932)
Signal irradiated
Ha
Hb
Hc8.0
Hd
Me
Ha
Hb
4.5
HcHd
4.1
Ar
Phenylselenyl bromide :0.48 g, 2.0 mmol) was added to a
solution of oxime ether :29) :0.5 g, 2.0 mmol) in dry aceto-
nitrile :20 ml). The resulting solution was stirred at room
temperature for 16 h. Acetonitrile was removed under
reduced pressure and the residue was taken up in 1:1 v/v
DCM±MeOH :20 ml), NaBH4 :0.15 g, 4.0 mmol) added
and the mixture was stirred at room temperature for 2 h.
The solvent was then evaporated under reduced pressure
and the residue was subjected to column chromatography
on silica, eluting with 95:5 v/v chloroform methanol to afford
nitrone :26) :0.13 g, 21%) and amine :32) :0.2 g, 34%).
11.8
9.0
4.8
2.6
13.8
0.8
20.2
5.5.2. 93aS,6S,7S,10S,10aR,10bR)-2,7,10a-Trimethyl-7-
9phenylseleno)octahydro-1H-6,10-methanopyrrolo-
[30,40:4,5]isoxazolo[2,3-a]azepine-1,3-dione 928). Obtained
as a colourless amorphous solid, mp 45±478C. :Found: C,
57.6; H, 5.95; N, 6.5; C20H24N2O3Se requires: C, 57.3; H,
5.75; N, 6.7%); dH :400 MHz): 7.61±7.51 :m, 2H, ArH),
7.38±7.24 :m, 3H, ArH), 4.88 :d, 1H, Jˆ8.1 Hz, Ha), 3.43
:d, 1H, Jˆ8.1 Hz, Hb), 3.19 :d, 1H, Jˆ6.5 Hz, Hc), 3.00 :s,
3H, NMe), 2.81 :d, 1H, Jˆ3.3 Hz), 2.40 :d, 1H, J13.8 Hz),
2.02±1.49 :m, 3H), 1.47 :s, 3H, Me±C±N), 1.43 :s, 3H,
Me±C±Se) and 1.38±1.21 :m, 2H). dC :125 MHz): 174.8,
173.9, 138.5, 134.3, 129.6, 129.2, 79.5, 77.7, 74.4, 62.5,
52.1, 40.4, 33.8, 33.4, 29.6, 25.4, 25.2 and 24.6; m/z :%)
:FAB): 420 :M1, 4), 363 :100), 159.:6), 133 :8) and 55 :78);
enhancement :%): :Table 7).
5.6.1. Nitrone 926). Obtained as a pale yellow oil d
:300 MHz): 7.64±7.53 :m, 2H, ArH), 7.28±7.22 :m, 3H,
ArH), 3.50 :m, 1H, CH±N), 2.74±1.56 :m, 10H, cycloalkyl
and Me±CvN), and 1.52 :s, 3H, Me); m/z :%): 309 :M1, 3),
152 :91), 134 :14), 124 :44), 108 :68), 79 :100), 67 :29) and
55 :36).
5.6.2. Amine 932). Obtained as a colourless oil which
comprised a 1:1 mixture of diastereoisomers. d :300
MHz): 7.65±7.55 :m, 2H, ArH), 7.37±7.25 :m, 3H, ArH),
5.96 :br, 1H, NH), 3.75 :m, 1H, CH±N), 3.46 :m, 1H,
CH±Me), 2.56±1.52 :m, 7H, cycloalkyl) and 1.32±1.23
:m, 6H, 2£Me); m/z :%): 2.95 :M1, 1), 157 :6), 138
:100), 96 :33), 67 :15) and 55 :20). This compound was
characterised as its hydrochloride salt :33).
5.6.3. Amine hydrochloride 933). HCl gas was bubbled
through a solution of amine :32) :0.2 g, 0.67 mmol) in
diethylether :5 ml) for 5 min. The solution was concentrated
under reduced pressure and diethyl ether :10 ml) was added
to precipitate the hydrochloride salt, which after ®ltration
afforded amine hydrochloride :0.22 g, 100%) as a colourless
amorphous solid, mp 181±1828C, which comprised a 1:1
mixture of diastereoisomers.
Table 7. Enhancement :%)
Signal irradiated
Ha
Hb
Hc2.2
Me±C±N
Me±C±Se
Ha
6.2
0.6
Hb
5.4
HcMe±C±N
Me±C±Se
Ar
3.5
5.8
0.9
0.8
2.6
0.5
1.8
:Found: C, 54.35; H, 6.7; N, 4.5; C15H22NSeCl requires: C,
54.5; H, 6.65; N, 4.25%).; d :300 MHz): 7.59±7.54 :m, 2H,
ArH), 7.29±7.26 :m, 3H, ArH), 4.05 :dd, 0.5H, Jˆ2.1 and
6.5 Hz, CH±C±Se), 3.93 :dd, 0.5H, Jˆ6.9 and 10.1 Hz,
CH±C±Se), 3.64 :m, 1H, CH±Me), 2.62±1.67 :m, 7H,
cycloalkyl) and 1.55±1.42 :m, 6H, 2£Me); m/z :%): 295
:M2HCl, 1), 157 :6), 138 :100), 96 :33), 67 :15) and 55
:20).
5.5.3. 1-94-Methyl-3-cyclohexen-1-yl)-1-ethanone O-ben-
zyl oxime ether 929). A solution of 4-acetyl-1-methylcyclo-
hexene :2.0 g, 14.5 mmol), in acetonitrile was added to a
asolution of O-benzylhydroxylamine hyrochloride :2.54 g,
15.9 mmol.) and sodium acetate :1.42 g, 17.3 mmol) in
water. The mixture was stirred at room temperature for
8 h and then extracted with CHCl3:£2). Work up followed
by ¯ash chromatography on silica eluting with 1:5 v/v
diethyl ether±hexane to afford the oxime ether :2.89 g,
82%) as a colourless oil which comprised a 3:1 mixture of
E- and Z-isomers.
5.7. Single crystal X-ray analysis of 95) and 923)
Crystallographicmeasurements for these ocmpounds
were carried out on a Stoe STADI 4 diffractometer at
ambient temperature using graphite monochromated
Ê
Cu Kd X-radiation :lˆ1.54184 A). Data for both were
:Found: C, 78.7; H, 8.65; N, 5.65; C16H21NO requires: C,
79.0; H, 8.65; N, 5.75%); dH :300 MHz): 7.35±7.23 :m, 5H,
ArH), 5.40 :m, 1H, CHvC), 5.07 and 5.05 :s, 2H, CH2Ph),
2.35 :m, 1H, CH±CvN), 2.10±1.95 :m, 5H), 1.83 and 1.78
:s, 3H, E- and Z-Me±CvN), 1.64 :s, 3H, Me±CvC) and
1.57 :m, 1H, cyclaalkyl); m/z :%): 243 :M1, 27), 152 :11),
121 :12), 108 :11), 95 :27), 91 :100), 79 :17), 77 :23), 55
:10) and 42 :19).
collected in the ranges 4.0,u,658 using v/u scans. No
signi®cant variation was observed in the intensity of three
standard re¯ections. Lorentz and polarization corrections
were applied to the data sets together with a semi-empirical
absorption correction based on azimuthal c-scans. The
structures were solved by direct methods using SHELXS-
8612 and were re®ned by full-matrix least squares :based on
F2) using SHELXL-9313 which uses all data for re®nement.

5836
H. A. Dondas et al. / Tetrahedron 58 ꢀ2002) 5827±5836
5.8. Single crystal X-ray analysis of 99) and 910)
structures, which include hydrogen co-ordinates, thermal
parameters and complete bond lengths and angles,
have been deposited at the Cambridge Crystallographic
Data Centre :5: CCDC180875; 9: CCDC167659; 10:
CCDC167660; 23: CCDC180876) and are available on
request.
Crystallographicdata for these compounds were measured
on a Nonius Kappa CCD area-detector diffractometer using
a mixture of area detector v- and F-scans and graphite
Ê
monochromated Mo Ka radiation :lˆ0.71073 A). Both
structures were solved by direct methods using SHELXS-
8612 and were re®ned by full-matrix least-squares :based on
F2) using SHELXL-97.13 The weighting scheme used was
w ˆ ‰s2ꢀFo2† 1 ꢀxP†2 1 yPŠ21 where P ˆ ꢀFo2 1 2Fc2†=3: All
non-hydrogen atoms of both structures were re®ned with
anisotropicdisplaecment parameters whilst hydrogen
atoms were constrained to predicted positions using a
riding model. The residuals wR2 and R1, given below, are
Acknowledgements
One of us :H. A. D.) thanks Mersin University, Turkey for
leave of absence. We thank Leeds University and the
EPSRC for support and Dr Christian Chapuis :Firmenich)
for carrying out the pyrolysis generating 21a.
2
2 1=2
de®ned as wR2 ˆ ꢀS‰wꢀFo2Fc2† Š=S‰wFo2Š †
and R1 ˆ
SuuFouuFcuu=SuFou:
References
Crystal data for ꢀ5): C13H18N2O3, 0.48£0.35£0.20 mm3,
Mˆ250.29, monoclinic, space group P21/n.
1. :a) Dondas, H. A.; Grigg, R.; Hadjisoteriou, M.; Markandu, J.;
Thomas, W. A.; Kennewell, P. Tetrahedron 2000, 56, 10087±
10096. :b) Dondas, H. A.; Grigg, R.; Hadjisoteriou, M.;
Markandu, J.; Kennewell, P.; Thornton-Pett, M. Tetrahedron
2001, 57, 1119±1128. :c) Dondas, H. A.; Grigg, R.; Thibault,
S. Tetrahedron 2001, 57, 7035±7045. :d) Dondas, H. A.;
Cummins, J. E.; Grigg, R.; Thorton-Pett, M. Tetrahedron
2001, 57, 7951±7964.
Ê
Ê
Ê
aˆ9.3342:5) A, bˆ6.4093:4) A), cˆ20.0230:12) A, aˆ
Ê 3
908, bˆ103.076:5)8, gˆ908, Uˆ1166.83:11) A , Zˆ4,
Dxˆ1.425 g cm23, mˆ0.836 mm21, F:000)ˆ536.
Crystal data for 9: C21H24N2O3Se, 0.35£0.35£0.28 mm3,
Mˆ431.40, orthorhombic, space group P212121, aˆ
2. For a review see: Frederickson, M.; Grigg, R. Org. Prep.
Proced. 1997, 29, 33±62 see also pp 63±115.
Ê
7.5349:1),
bˆ14.0844:2),
cˆ17.9728:3) A,
Uˆ
,
1907.36:5) A , Zˆ4, Dcˆ1.51 Mg m23, mˆ1.99 mm21
Ê 3
3. :a) Grigg, R.; Hadjisoteriou, M.; Kennewell, P.; Markandu, J.;
Thornton-Pett, M. J. Chem. Soc., Chem. Commun. 1992,
1388±1389. :b) Grigg, R.; Hadjisoteriou, M.; Kennewell, P.;
Markandu, J. J. Chem. Soc., Chem. Commun. 1992, 1537±
1538. :c) Dondas, H. A.; Frederickson, M.; Grigg, R.;
Markandu, J.; Thornton-Pett, M. Tetrahedron 1997, 53,
14339±14354. :d) Markandu, J.; Dondas, H. A.; Frederickson,
M.; Grigg, R.; Thornton-Pett, M. Tetrahedron 1997, 53,
13165±13176.
F:000)ˆ896, Tˆ190 K.
Data collection: 1.0,2u,52.08; 3733 unique data were
collected [Rintˆ0.0231]; 3668 re¯ections with Fo.4.0
s:Fo).
Structure re®nement: Number of parametersˆ247, good-
ness of ®t, sˆ1.053; wR2ˆ0.0544, R1ˆ0.0199.
4. Preliminary communication: Dondas, H. A.; Grigg, R.;
Frampton, C. S. Tetrahedron Lett. 1997, 38, 5719±5722.
5. Dondas, H. A.; Grigg, R.; Markandu, J.; Perrior, T.; Suziki, T.;
Thibault, S.; Thomas, W. A.; Thornton-Pett, M. Tetrahedron
2002, 58, 161±173.
Crystal data for 10: C21H26N2O3Se, 0.4£0.35£0.1 mm3,
Mˆ433.40, monoclinic, space group P21 aˆ6.6744:7),
Ê
bˆ22.571:3), cˆ6.6555:5) A, bˆ100.943:6)8, Uˆ
984.4:8) A , Zˆ2, Dcˆ1.46 Mg m23
,
mˆ1.93 mm21
,
Ê 3
F:000)ˆ448, Tˆ190 K.
6. :a) Blaney, P.; Grigg, R.; Rankovic, Z.; Thoroughgood, M.
Tetrahedron Lett. 2000, 41, 6635±6638. :b) Blaney, P.; Grigg,
R.; Rankovic, Z.; Thoroughgood, M. Tetrahedron Lett. 2000,
41, 6639±6642.
Data collection: 1.0,2u,52.08; 3434 unique data were
collected [Rintˆ0.037]; 3296 re¯ections with Fo.4.0s:Fo).
7. Sato, F.; Sato, S.; Kodama, H.; Sato, M. J. Organomet. Chem.
1977, 142, 71±79.
Structure re®nement: Number of parametersˆ247, good-
ness of ®t, sˆ1.023; wR2ˆ0.0921, R1ˆ0.357.
8. Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651±1660.
9. Ohloff, G.; Giersch, W.; Schulte-Elte, K. H.; Kovats, E. Helv.
Chim. Acta 1969, 52, 1531.
Crystal data for ꢀ23): C21H26N2O3Se, 0.50£0.38£0.22 mm,
Mˆ433.40, monoclinic, space group P21/a
10. Chapuis, C.; Brauchli, R. Helv. Chim. Acta 1992, 75, 1527±
1546.
Ê
Ê
Ê
aˆ8.8640:3) A, bˆ12.5682:5) A), cˆ17.6878:6) A, aˆ
11. Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
12. Sheldrick, G. M. Acta Crytallogr. Sect. A 1990, 46, 467±473.
13. Sheldrichk, G. M. SHELXL 93, Program for Re®nement of
Crystal structures; University of Gottingen: Gottingen, 1993.
Ê 3
908, bˆ91.209:3)8, gˆ908, Uˆ1970.06:12) A , Zˆ4,
Dxˆ1.461 g cm23, mˆ2.774 mm21, F:000)ˆ896.
Full supplementary crystallographic data-sets for all four