Synthesis of 6-substituted purin-2-ones with potential cytokinin activity

Article abstract of DOI:10.1039/b101327k

6-Substituted purin-2-ones have been prepared by completely regioselective addition of Grignard reagents to an N-protected purin-2-one followed by rearomatisation and deprotection. The target compounds may be regarded as analogues of the potent cytokinins trans-zeatin and benzylaminopurine (BAP), and most of the BAP analogues did induce increased weight growth in radish cotyledons. N-Protected (E)-6-styrylpurin-2-one underwent head to tail [2+2] dimerisation to the 1α,2α,3β,4β-substituted cyclobutane 15, when exposed to ordinary daylight. When irradiated with UV-light, the trans-compound isomerised to the corresponding cis-isomer. The structure of compound 15 was determined by single crystal X-ray di3raction methods at 150 K.

Full text of DOI:10.1039/b101327k

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Synthesis of 6-substituted purin-2-ones with potential cytokinin
activity
Geir Andresen,a Aud Berglen Eriksen,b Bjørn Dalhus,a Lise-Lotte Gundersena and Frode Risea
1
a Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315, Oslo, Norway
b Department of Biology, University of Oslo, P.O. Box 1066, Blindern, N-0316, Oslo, Norway
Received (in Cambridge, UK) 9th February 2001, Accepted 31st May 2001
First published as an Advance Article on the web 26th June 2001
6-Substituted purin-2-ones have been prepared by completely regioselective addition of Grignard reagents to an
N-protected purin-2-one followed by rearomatisation and deprotection. The target compounds may be regarded
as analogues of the potent cytokinins trans-zeatin and benzylaminopurine (BAP), and most of the BAP analogues
did induce increased weight growth in radish cotyledons. N-Protected (E)-6-styrylpurin-2-one underwent head
to tail [2+2] dimerisation to the 1α,2α,3β,4β-substituted cyclobutane 15, when exposed to ordinary daylight.
When irradiated with UV-light, the trans-compound isomerised to the corresponding cis-isomer. The structure
of compound 15 was determined by single crystal X-ray diffraction methods at 150 K.
Introduction
Cytokinins are plant hormones with a wide range of biological
effects.1 They promote cell division and cell growth and they
are involved in the retardation of senescence. All known natur-
ally occurring cytokinins are 6-alkylaminopurines. In most
instances, these compounds are unsubstituted in the purine
2- and 8-positions, but 6-alkylaminopurin-2-ones have recently
been isolated from both higher plants and micro-organisms,2
and identified as plant growth stimulators. This kind of bio-
logical activity is also found among synthetic 6-alkylamino-
Fig. 1 Structures of the cytokinines 6-benzylaminopurine (BAP) and
trans-zeatin and general structure of the target analogues.
purin-2-ones.3 The NH group in the purine 6-position in
natural cytokinins is not essential for all hormonal activities.
Several purine derivatives bearing alkynyl, alkenyl or alkyl sub-
stituents in the 6-position do exhibit stimulating effects on plant
growth.4 We have previously demonstrated that C–C bond
formation in the 6-position of N,N-dialkylated purin-2-ones5
as well as N,N,N-trialkylated 2-oxopurinium salts,6 easily can
be achieved by regioselective addition of Grignard reagents, and
we report herein that this strategy can be utilised in syntheses of
6-substituted purin-2-ones with potential cytokinin activity.
Both 6-benzylaminopurine (BAP) and trans-zeatin are highly
active naturally occurring cytokinins,1 and in this study we
chose BAP analogues and zeatin analogues with the general
structure outlined in Fig. 1 as our target molecules.
Results and discussion
The Grignard reagents required for the introduction of the
C-6 substituents in the BAP analogues were generated from 1-
chloro-2-phenylethane, (E)-styryl bromide and phenylacetylene
respectively, and the syntheses of the reagents required for
the trans-zeatin analogue side chains are outlined in Scheme 1.
It is claimed that both halides 2 are available from cyclopropyl-
oxiranes,7 but the experimental details reported for the syn-
thesis of the oxirane as well as for the ring-openings are sparse.
Instead the halides 1 were prepared from cyclopropyl methyl
ketone by addition of methylmagnesium halide and subsequent
Julia rearrangement on the resulting carbinol as previously
described.8 The hydroxy function in compounds 2 was intro-
duced by allylic oxidation of the alkenes 1 with selenium
dioxide and tert-butyl hydroperoxide, essentially as reported for
2b before,9 and, finally, the allylic alcohols were O-silylated with
Scheme 1 Reagents and conditions: i, SeO2, t-BuO2H, CH2Cl2; ii,
TDS-Cl, base, DMF; iii, for 3a, NaI, acetone, ∆; iv, TDS-Cl, DMAP,
Et3N, CH2Cl2 for 5a; v, TBS-Cl, imidazole, DMF for 5b; vi, t-BuLi,
oxirane, THF, Ϫ78 ЊC; vii, Ts-Cl, pyridine; viii, NaI, acetone; ix, see
refs. 11 and 4.
1662
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b101327k

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Table 1 Synthesis of compounds 13 and 14
R in 13
Yield (%)
RЈ in 13 and 14
13a
14b
d
–CH2CH2Si(CH3)2
–Si(CH3)2But
–Si(CH3)2But
–Si(CH3)2But
–Si(CH3)2But
–Si(CH3)2But
–Si(CH3)2But
–Si(CH3)2But
–Si(CH3)2But
–Si(CH3)2But
–CH2CH2Ph
–CH2CH2Ph
47, 13ac
66, 13b
67, 13c
71, 13de
76, 13e
61, 13f
78, 13g
63, 13h
49, 13i
82, 13j
—
81, 14a
(E)-CH᎐CHPh
90, 14b
᎐
f
(Z)-CH᎐CHPh
—
᎐
᎐
–C᎐C–Ph
69, 14dg
80, 14e
79, 14f
—
68, 14g
76, 14h
᎐
(E)-CH2CH2CH᎐C(CH3)CH2OHh
᎐
–CH2CH2CH᎐C(CH3)2
᎐
–CH᎐CH2
᎐
(E,E)-CH᎐CH–CH᎐C(CH3)CH2OHij
᎐
᎐
j
᎐
(E)-C᎐C–CH᎐C(CH3)CH2OH
᎐
᎐
a Yield of isolated compounds prepared by addition of Grignard reagent to the oxopurines 11 followed by DDQ oxidation unless otherwise noted.
b Yield of isolated compounds. c The oxidation was achieved with MnO2 in CH2Cl2. d Complex mixture. e Formed by isomerisation of compound 13c.
f A ca. 2 : 1 mixture of E and Z-isomers was formed. g The cleavage was performed with Me4NF in EtOH followed by AcOH. h In compound 13, the
hydroxy group is protected as a TDS ether. i Formed by Heck coupling on compound 13h. j In compound 13, the hydroxy group is protected as a TBS
ether.
thexyldimethylsilyl† chloride (TDS-Cl) to give the desired
halides 3. In the synthesis of the iodide 3a, some of the corre-
sponding chloride was formed during silylation and the crude
product was therefore treated with sodium iodide.
Compound 3a was also synthesised by an alternative route.
Geometrically pure vinyl iodide 4 is readily available in large
quantities by literature methods,10 and we chose this compound
as starting material for the preparation of alkyne 9, and alkyl
halide 3a. Compound 4 was O-silylated with thexyldimethylsilyl
chloride (TDS-Cl), treated with tert-butyllithium (t-BuLi) and
the lithiated alkene thus formed was trapped with oxirane to
give the alcohol 6 together with the terminal alkene 7 from
the unreacted alkenyllithium. Compound 6 could readily be
converted to iodide 3a via the toluene-p-sulfonate 8. For the
synthesis of the reagents required for the enyne side chain in
᎐
the target compound (X = –C᎐C–; Fig. 1), vinyl iodide 4 was
᎐
converted to the alkyne 9 as described before.4,11
Previously we have introduced substituents at the 6-position
of N,N-dibenzylpurin-2-ones5 by addition of Grignard
reagents, but for the synthesis of the cytokinin analogues
shown in Fig. 1, easily removable N-substituents were required.
We chose silicon-based protecting groups, and when purin-
2-one 106 was reacted with 2-(trimethylsilyl)ethoxymethyl
chloride (SEM-Cl)12,13 or (tert-butyldimethylsilyloxy)methyl
chloride,14,15 1,9-dialkylated purines 11 were formed together
with various amounts of trialkylated water adducts 12 as well
as minor amounts of other unidentified dialkylated isomers
(Scheme 2). These results are consistent with our earlier results
from N-benzylation of purin-2-one 10.5,6,16 As before, the
position of the N-substituents was confirmed by long-range
HETCOR NMR techniques.5,6
The 6-substituents were introduced by completely regio-
selective addition of the desired Grignard reagent followed
by rearomatisation of the crude adducts with 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) (Scheme 2, Table 1). Again
long-range HETCOR NMR techniques were employed in
the structure elucidation of the products 13. For the synthesis
of the diene 13i we chose to introduce the side chain in two
steps: first, addition of the ethenyl Grignard reagent followed
by DDQ oxidation to give compound 13h; and secondly,
subjection of compound 13h to Heck coupling with the iodide
5b. When unprotected iodo alcohol 4 was used in the Heck
reaction, some aldehyde was also formed in addition to the
desired allylic alcohol.
Scheme 2 Reagents and conditions: i, ROCH2Cl, EtN(i-Pr)2, CH2Cl2;
ii, RЈMgX, THF, Ϫ78 ЊC; iii, DDQ, PhH; iv, Me4NF, MeCN;
v, Me4NF, EtOH; vi, AcOH; vii, compound 5b, Pd(OAc)2, EtN(i-Pr)2,
DMF, 55 ЊC.
pounds 13 were reacted with tetramethylammonium fluoride,
the target compounds 14 were formed cleanly.
When exposed to ordinary daylight, the (E)-6-styrylpurine
13c underwent head to tail [2+2] dimerisation to the sub-
stituted cyclobutane 15 (Scheme 3). The regiochemistry was
confirmed by X-ray crystallography (Fig. 2, Table 2), which
also revealed that the relative stereochemistry of the cyclo-
butane was 1α,2α,3β,4β. Extensive decomposition took place
when tetramethylammonium fluoride-mediated deprotection of
compound 15 was attempted.
When irradiated with UV-light, the (Z)-styryl isomer 13d
was formed in more than 80% yield from both the (E)-isomer
13c and the cyclobutane 15 (Scheme 3, Table 3). Irradiating
the (Z)-compound 13d under the same conditions resulted in
only minor isomerisation to the (E)-isomer 13c. Tetramethyl-
ammonium fluoride-mediated removal of the N-protecting
groups in the (Z)-compound 13d gave a ca. 2 : 1 mixture of (E)-
isomer 14b and (Z)-isomer 14c. UV-Irradiation of the mixture
only resulted in additional (Z) to (E) isomerisation, and
pure (E)-compound 14b was completely inert under these
conditions. It appears that the unprotected 6-styryl-2-oxo-
purines 14b and 14c and the N-protected analogues 13c and
Attempts to remove the SEM-protecting groups from
compound 13a with tetrabutylammonium fluoride (TBAF) or
tetramethylammonium fluoride resulted in a complex mixture,
but when the (tert-butyldimethylsilyloxy)methyl-protected com-
† The IUPAC name for thexyl is 1,1,2-trimethylpropyl.
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672
1663

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Scheme 3 Reagents and conditions: i, daylight; ii, hν, EtOH; iii, Me4NF, MeCN.
Table 2 Crystal data and intensity collection and refinement data for
15
Formula
C54H84N8O6Si4
1053.65
Formula weight/g molϪ1
Crystal size/mm
Color, shape
0.8 × 0.5 × 0.3
Pale yellow, block
Orthorhombic
Pca21 (No. 29)
a = 11.7867(3)
b = 15.9615(4)
c = 33.1308(9)
6233.0(3)
4
Crystal system
Space group
Cell dimensions/Å
Volume/Å3
Z
ρcalc/g cmϪ3
1.123
F(000)
Diffractometer
Radiation
Monochromator
T /K
2272
Siemens SMART21
Mo-Kα (λ = 0.71073 Å)
Graphite crystal
150
Scan mode
ω-scans
5
45
5.0
2.56–60.00
Ϫ16 ≤ h ≤ 12
Ϫ22 ≤ k ≤ 22
Ϫ46 ≤ l ≤ 44
Multi-scan21
71281
No. of sets of exposures
Exposure time per frame/s
Crystal to detector distance/cm
2θ range/Њ
Fig. 2 Molecular structure of 15 with partial atomic numbering.
Displacement ellipsoids are drawn at the 50% probability level.
H-atoms are left out for clarity.
Index ranges
Absorption correction
13d exhibit exactly opposite behaviour under photochemical
conditions. Furthermore, the photochemical properties of (E)-
6-styryl-2-oxopurine 14b also differ from those reported for
(E)-6-styrylpurine. The latter compound is isomerised to the
(Z)-isomer under photochemical conditions.17
No. of reflections measured
No. of reflections used in refinement
No. of reflections with I > 2σ(I), n
Refinement
17916
14539
On F2
No. of refined parameters, p
709
0.0581
0.1477
1.038
R = Σ|∆F|/|Fo|a [I > 2σ(I)]
1
–
2
2
Rw = {Σ[w(∆F) /w(Fo) ]} b [I > 2σ(I)]
The evaluation of the cytokinin activity of the 6-substituted
2-oxopurines 14 was based on their ability to stimulate radish
cotyledon growth and the results are given in Table 4. The seeds
were treated with 10 µM solutions of the purines and the
growth effects were measured as the increase in cotyledon
weight after 72 h compared to a control sample. For com-
parison, the potent cytokinin BAP was also included and
the difference in weight between the cotyledons grown in the
presence of BAP and the control sample was defined as 100%
weight increase. The results for compounds 14 are given as a
percentage of the increase obtained with BAP.
2
1
–
2
2
S = {Σ[w(∆F) /(n Ϫ p)]} [I > 2σ(I)]
Residual electron density/e ÅϪ3
+1.137, Ϫ0.444
a ∆F = |F0| Ϫ |Fc|.
b w = (σ2(FO2) + (0.083P)2 + 3.500P)Ϫ1
,
where
P=(FO2 + 2FC)/3.
induce increased growth at 10 µM concentration (Table 4,
entries 2–4). The effects were ca. 30–60% of that obtained using
BAP. The ineffectiveness of the alkyne 14d as a cytokinin (Table
4, entry 5) was not totally unexpected. In connection with our
study on antimycobacterial purines,18 we have previously found
high cytotoxicity for 6-alkynylpurin-2-ones.19 In addition to
stimulation of growth, naturally occurring cytokinins also
In contrast to the zeatin analogues we have studied before,4
the purin-2-ones 14e–h (Table 4, entries 6–9) were essentially
inactive. In many instances some weight retardation was
actually seen. The BAP analogues 14a–c, on the other hand, did
1664
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672

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Table 3 Photochemical isomerisation of 6-styrylpurines
Product distribution (%) from 1H NMR
Starting material
Conditions
(E)-Isomer 13c or 14b
Cyclobutane
(Z)-Isomer 13d or 14c
a
13c
13c
15
13d
14b
hν, EtOH, 20 h
hν, EtOH, 72 hb
hν, EtOH, 24 h
hν, EtOH, 72 hb
hν, EtOH, 72 h
50 (13c)
15 (13c)
6 (13c)
18 (13c)
100 (14b)
—
—
50 (13d)
85 (13d)
90 (13d)
82 (13d)
a
4 (16)
a
—
—
a
a
—
a Not detectable in the 1H NMR spectrum. b No further significant changes after 140–190 h.
Table 4 Cytokinin activity of benzylaminopurine (BAP) and 6-substituted 2-oxopurines
Entry
Compound
Substituent in the 2-oxopurine 6-positiona
% Weight increase relative to BAP (10 µM conc.)a
1
2
3
4
BAP
14a
14b
–NHCH2Phb
–CH2CH2Ph
100
27
30
(E)-CH᎐CHPh
᎐
14b–14c (ca. 2 : 1)
(Z)-CH᎐CHPh in 14c
56
᎐
᎐
5
6
7
8
9
14d
14e
14f
14g
14h
–C᎐C–Ph
4
᎐
c
(E)-CH2CH2CH᎐C(CH3)CH2OH
–CH2CH2CH᎐C(CH3)2
(E,E)-CH᎐CH–CH᎐C(CH3)CH2OH
(E)-C᎐C–CH᎐C(CH3)CH2OH
—
2
2
᎐
᎐
᎐
᎐
d
᎐
—
᎐
᎐
a Comparison of weight gain between radish cotyledon grown in 0 µM and 1, 10 or 100 µM purine solution, the results are given as % of the weight
increase obtained with BAP. b The structure of BAP is shown in Fig. 1. c No change compared to control. d Weight retardation relative to control
(0 µM) was observed.
delay senescence most probably by acting as antioxidants.1
Studies of the antioxidant/radical scavenging properties of the
cytokinin analogues 14 are in progress in our laboratories and
preliminary results indicate that substantially increased
antioxidant activity is found among compounds 14 compared
with the plant hormones BAP and trans-zeatin.
and (E)-1-bromo-2-phenylethene20 were prepared according
to literature procedures. All other reagents were commercially
available and used as received. Single crystals of 15 were
obtained by slow crystallisation from EtOAc–hexane.
Crystal structure determination of compound 15‡
Crystal data. C54H84N8O6Si4, M = 1053.65, orthorhombic,
a = 11.7867(3), b = 15.9615(4), c = 33.1308(9) Å, U = 6233.0(3)
Å3, T = 150 K, space group Pca21 (No. 29), Z = 4, µ(Mo-Kα) =
Experimental
The 1H NMR spectra were recorded at 500 MHz with a
Bruker Avance DRX 500 instrument, at 300 MHz with a Bruker
Avance DPX 300 instrument or at 200 MHz with a Bruker
Avance DPX 200 instrument. The 1H decoupled 13C NMR
spectra were recorded at 125, 75 or 50 MHz using the above-
mentioned spectrometers. J values are given in Hz. Mass
spectra under electron impact conditions (EI) were recorded at
70 eV ionising voltage with a VG Prospec instrument, and are
presented as m/z (% rel. int.). CH4 was employed as the ionis-
ation gas for chemical ionisation (CI). Electrospray MS spectra
were recorded with a Bruker Apex 47e FT-ICR mass spec-
trometer. Elemental analyses were performed by Ilse Beetz
Mikroanalytisches Laboratorium, Kronach, Germany. Melting
points are uncorrected. Silica gel for flash chromatography was
purchased from Merck, Darmstadt, Germany (Merck No.
9385). Analytical thin layer chromatography was performed
with E. Merck silica gel 60F254 0.25 mm plates (Merck
No. 1.05554). THF and Et2O were distilled from sodium–
benzophenone. PhH was dried over sodium wire. CH2Cl2 was
predried with CaCl2, distilled from CaH2 and stored over 4 Å
molecular sieves. Acetone was dried with boric anhydride prior
to distillation. MeCN, DMF, triethylamine, N-ethyldiiso-
propylamine and pyridine were distilled from CaH2 and stored
over 4 Å molecular sieves. Tetramethylammonium fluoride
tetrahydrate was dried by azeotropic distillation with absolute
EtOH and the residue was dissolved in dry MeCN. 5-Iodo-
2-methylpent-2-ene 1a,8 5-bromo-2-methylpent-2-ene 1b,8
(E)-3-iodo-2-methylprop-2-en-1-ol 4,10 (E)-1-(tert-butyldi-
methylsilyloxy)-2-methylpent-2-en-4-yne 9,4,11 1,9-dihydro-2H-
purin-2-one 10,6 (tert-butyldimethylsilyloxy)methyl chloride,14
0.145 mmϪ1
, 71281 reflections measured, 17916 unique
(Rint = 0.0432) which were used in the refinement. Final
R(F2) = 0.0581 and wR(F2) = 0.1477.
Data collection and structure solution. Single-crystal X-ray
data was collected with a Siemens SMART CCD diffract-
ometer.21 Sadabs22 was used to correct for absorption. The
Bravais lattice is primitive orthorhombic with systematic
absences corresponding to either Pca21 (non-centrosymmetric)
or Pcam (centrosymmetric). Statistics for the normalised struc-
ture factors (|E2 Ϫ 1| = 0.804 compared to the theoretical values
0.968 and 0.736 for centrosymmetric and non-centrosymmetric
space groups, respectively) indicate that the structure is
non-centrosymmetric. The structure was readily solved by
direct methods in the space group Pca21
Refinement. Refinement performed with SHELXTL.23
Positional parameters for all heavy atoms were refined.
Hydrogen atoms were kept in idealised positions, refining a
single C–H distance for all H atoms connected to the same C
atom. Heavy atoms were refined anisotropically, whereas Uiso
for the hydrogen atoms were fixed at 1.2Ueq (–CH– and –CH2–)
and 1.5Ueq (–CH3) of the parent C atom. Experimental data,
crystal data and refinement results are summarised in Table 2.
Atomic scattering factors are taken from ref. 24.
‡ CCDC reference number 163628. See http://www.rsc.org/suppdata/
p1/b1/b101327k/ for crystallographic files in .cif or other electronic
format.
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672
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(E)-5-Iodo-2-methylpent-2-en-1-ol 2a7
(CI) 368 (M+, 1%), 283 (54), 241 (23), 209 (21), 157 (100), 155
(22), 83 (53), 81 (46), 75 (32) and 73 (19).
To a mixture of selenium dioxide (262 mg, 2.36 mmol) in dry
CH2Cl2 (5 cm3) at ambient temperature was added tert-butyl
hydroperoxide (5.5 M solution in decane, 1.7 cm3, 9.35 mmol).
The mixture was stirred for 30 minutes under N2 before 5-iodo-
2-methylpent-2-ene 1a (990 mg, 4.7 mmol) in dry CH2Cl2
(5 cm3) was added. After an additional 2.5 h, benzene (5 cm3)
was added and the mixture evaporated in vacuo. The residue
was dissolved in diethyl ether (20 cm3) and washed with 10%
aqueous potassium hydroxide (6 × 5 cm3) followed by brine
(5 cm3) prior to drying (MgSO4) and evaporation in vacuo. The
product was purified by flash chromatography eluting with
EtOAc–hexane (1 : 6) followed by EtOAc–hexane (1 : 4) to give
the iodo alcohol 2a (480 mg, 45%) as a colourless oil; Rf 0.16
(1 : 3, EtOAc–hexane); δH(200 MHz; CDCl3; Me4Si) 1.61 (3 H,
s, Me), 2.10 (1 H, s, OH), 2.59 (2 H, q, J 7.2, CH2), 3.10 (2 H, t,
J 7.2, ICH2), 3.95 (2 H, s, OCH2) and 5.34 (1 H, br t, J 7.2, CH);
δC(50 MHz; CDCl3; Me4Si) 5.4 (ICH2), 13.8 (Me), 31.7 (CH2),
Method B. Sodium iodide (833 mg, 5.56 mmol) was added
to a stirred solution of crude (E)-5-thexyldimethylsilyloxy-4-
methylpent-3-en-1-yl toluene-p-sulfonate 8 in dry acetone (40
cm3). The solution was heated at reflux for 44 h under N2 before
the solvent was evaporated in vacuo. The residue was
partitioned between water and diethyl ether (1 : 1, 40 cm3). The
separated aqueous phase was extracted with diethyl ether
(2 × 20 cm3) and the combined organic solutions were washed
with brine (20 cm3) prior to drying (MgSO4) and evaporation
in vacuo. The residue was purified by flash chromatography
eluting with EtOAc–hexane (1 : 50) to give the iodide 3a (401
mg, 78% from 6) as a colourless oil.
(E)-5-Bromo-1-thexyldimethylsilyloxy-2-methylpent-2-ene 3b
N-Ethyldiisopropylamine (0.5 cm3, 2.92 mmol) was added to a
solution of (E)-5-bromo-2-methylpent-2-en-1-ol 2b (435 mg,
2.43 mmol) in dry CH2Cl2 (10 cm3) and dry DMF (10 cm3)
under N2 at 0 ЊC. Thexyldimethylsilyl chloride (480 mg, 2.67
mmol) was added dropwise and the resulting mixture was left in
the refrigerator for 72 h and diluted with water (10 cm3) and
saturated NH4Cl solution (10 cm3). The aqueous phase was
extracted with diethyl ether (2 × 25 cm3). The combined organic
solutions were washed with 1 M HCl (2 × 20 cm3), water (20
cm3), and brine (20 cm3) prior to drying (MgSO4) and evap-
oration in vacuo. The residue was purified by flash chrom-
atography eluting with EtOAc–hexane (1 : 100) to give the
bromide 3b (680 mg, 87%) as a colourless oil (Found: C, 52.7; H,
9.3. C14H29BrOSi requires C, 52.3; H, 9.1%); δH(300 MHz;
CDCl3; Me4Si) 0.08 (6 H, s, SiMe2), 0.84 (6 H, s, Me in thexyl),
0.87 (6 H, d, J 6.9, Me in thexyl), 1.59 (3 H, s, Me), 1.64 (1 H,
m, CH in thexyl), 2.59 (2 H, m, CH2), 3.34 (2 H, t, J 7.3,
68.1 (OCH ), 123.7 (᎐CH) and 137.4 (᎐C); m/z (EI) 225.9848
᎐
᎐
2
(M+. C6H11IO requires 225.9855), 99 (23%), 81 (32), 49 (30), 43
(100) and 41 (61).
(E)-5-Bromo-2-methylpent-2-en-1-ol 2b
The compound was prepared from 5-bromo-2-methylpent-2-
ene 1b (4.89 g, 30 mmol), selenium dioxide (1.65 g, 15 mmol)
and tert-butyl hydroperoxide (5.5 M solution in decane, 12 cm3,
60 mmol) in dry CH2Cl2 (25 cm3) as described for 1a above. The
product was purified by flash chromatography eluting with
EtOAc–hexane 1 : 9, 1 : 6 and finally 1 : 3 to give the bromo
alcohol 2b (2.88 g, 54%) as a colourless oil; Rf 0.15 (1 : 3,
EtOAc–hexane); δH(200 MHz; CDCl3; Me4Si) 1.63 (3 H, s, Me),
1.92 (1 H, s, OH), 2.58 (2 H, q, J 7.2, CH2), 3.33 (2 H, t, J 7.2,
BrCH2), 3.97 (2 H, s, OCH2) and 5.38 (1 H, br t, J 7.2, CH);
δC(50 MHz; CDCl3; Me4Si) 13.8 (Me), 31.1 (CH2), 32.4
CH Br), 3.98 (2 H, s, CH O) and 5.39 (1 H, m, ᎐CH); δ (75
᎐
2
2
C
(BrCH ), 68.1 (OCH ), 121.7 (᎐CH) and 137.9 (᎐C); m/z
᎐
᎐
2
2
MHz; CDCl3; Me4Si) Ϫ3.4 (SiMe2), 13.6 (Me), 18.5 (Me in
thexyl), 20.3 (Me in thexyl), 25.2 (C in thexyl), 31.2 (CH2Br),
(EI) 179.9971/177.9993 (M+. C6H11BrO requires 179.9973/
177.9993), 85 (25%), 81 (20), 71 (100), 57 (11), 55 (11), 43 (43)
and 41 (31). Spectroscopic data are in good agreement with
those reported before.9
32.5 (CH ), 34.1 (CH in thexyl), 67.8 (CH O), 120.3 (᎐CH) and
᎐
2
2
137.7 (᎐C); m/z (CI) 321/319 (M + 1, 1/1%), 251 (22), 237 (60),
᎐
235 (59), 157 (67), 85 (21), 81 (100), 75 (65), 73 (40) and 67 (23).
(E)-1-Thexyldimethylsilyloxy-5-iodo-2-methylpent-2-ene 3a
(E)-1-Thexyldimethylsilyloxy-3-iodo-2-methylprop-2-ene 5a
Method A. Imidazole (569 mg, 8.36 mmol) was added to a
solution of (E)-5-iodo-2-methylpent-2-en-1-ol 2a (630 mg, 2.79
mmol) in dry DMF (10 cm3) under N2 at 0 ЊC. Thexyldimethyl-
silyl chloride (600 mg, 3.36 mmol) was added dropwise and the
resulting mixture was left in the refrigerator for 62 h and poured
into brine and diethyl ether (1 : 1, 40 cm3). The aqueous phase
was extracted with diethyl ether (4 × 20 cm3), and the combined
organic solutions were washed with brine (2 × 30 cm3) prior to
drying (MgSO4) and evaporation in vacuo. The crude product
was dissolved in dry acetone (25 cm3), sodium iodide (1.67 g,
11.1 mmol) was added and the solution was heated at reflux for
70 h under N2 before the solvent was evaporated in vacuo. The
residue was partitioned between water and diethyl ether (1 : 1,
40 cm3) and the layers were separated. The aqueous phase was
extracted with diethyl ether (2 × 20 cm3) and the combined
organic solutions were washed with brine (20 cm3) prior to dry-
ing (MgSO4) and evaporation in vacuo. The residue was purified
by flash chromatography eluting with EtOAc–hexane (1 : 50) to
give the iodide 3a (700 mg, 68%) as a colourless oil (Found:
C, 45.3; H, 8.2. C14H29IOSi requires C, 45.6; H, 7.9%); δH(300
MHz; CDCl3; Me4Si) 0.09 (6 H, s, SiMe2), 0.85 (6 H, s, Me in
thexyl), 0.87 (6 H, d, J 6.9, Me in thexyl), 1.57 (3 H, s, Me), 1.62
(1 H, m, CH in thexyl), 2.61 (2 H, m, CH2), 3.11 (2 H, t, J 7.4,
To a solution of (E)-3-iodo-2-methylprop-2-en-1-ol 4 (3.0 g,
15.2 mmol) in dry CH2Cl2 (20 cm3) under N2 at 0 ЊC were added
triethylamine (4.7 cm3, 30.4 mmol), DMAP (41 mg, 0.33 mmol)
and thexyldimethylsilyl chloride (3.5 cm3, 16.0 mmol). After
stirring for 2 h at 0 ЊC and 16 h at ambient temperature under
N2 the solvent was removed in vacuo and the residue dissolved
in diethyl ether (35 cm3). The solution was washed with satur-
ated aqueous ammonium chloride (80 cm3) and 5% aqueous
sodium hydrogen carbonate (35 cm3) prior to drying (MgSO4)
and evaporation in vacuo. The product was purified by
Kugelrohr distillation (0.4 mm Hg, 100 ЊC) to give the vinyl
iodide 5a (4.95 g, 86%) as a colourless oil (Found: C, 42.4; H,
7.6. C12H25IOSi requires C, 42.35; H, 7.4%); δH(200 MHz;
CDCl3; Me4Si) 0.08 (6 H, s, SiMe2), 0.83 (6 H, s, Me in thexyl),
0.86 (6 H, d, J 7.1, Me in thexyl), 1.5–1.7 (1 H, m, CH in
thexyl), 1.75 (3 H, s, Me), 4.06 (2 H, s, CH2) and 6.17 (1 H, br s,
᎐CH); δ (50 MHz; CDCl ; Me Si) Ϫ3.5 (SiMe ), 18.5 (Me in
᎐
C
3
4
2
thexyl), 20.2 (Me in thexyl), 21.1 (Me), 25.1 (C in thexyl), 34.1
(CH in thexyl), 66.9 (CH ), 75.8 (᎐CH) and 146.7 (᎐C); m/z (CI)
᎐
᎐
2
340 (M+, 4%), 256 (13), 255 (100), 215 (7), 185 (54), 129 (6), 128
(7), 127 (10) and 113 (7).
(E)-1-tert-Butyldimethylsilyloxy-3-iodo-2-methylprop-2-ene 5b
CH I), 3.96 (2 H, s, CH O) and 5.36 (1 H, m, ᎐CH); δ (50 MHz;
᎐
2
2
C
CDCl3; Me4Si) Ϫ3.3 (SiMe2), 5.5 (CH2I), 13.7 (Me), 18.5 (Me in
thexyl), 20.4 (Me in thexyl), 25.3 (C in thexyl), 31.9 (CH2), 34.2
To a solution of (E)-3-iodo-2-methylprop-2-en-1-ol 4 (1.12 g,
5.7 mmol) in dry DMF (5 cm3) under N2 were added imidazole
(0.77 g, 11.4 mmol) and tert-butyldimethylsilyl chloride (0.9 g,
(CH in thexyl), 67.8 (CH O), 122.3 (᎐CH) and 137.2 (᎐C); m/z
᎐
᎐
2
1666
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672

View Article Online
5.97 mmol). After stirring for 19 h at ambient temperature
under N2, the solution was diluted with water (5 cm3) and Et2O
(25 cm3). The phases were separated and the organic phase
washed with aqueous 1 M HCl (5 cm3), saturated aqueous
sodium hydrogen carbonate (5 cm3) and brine (5 cm3) prior
to drying (MgSO4) and evaporation in vacuo. This gave the
protected alcohol 5b (1.58 g, 89%) as a colourless oil which was
used without further purification. Spectroscopic data were in
good agreement with those reported before.25
21.6 (ArMe), 25.2 (C in thexyl), 27.4 (CH2), 34.1 (CH in thexyl),
67.8 (CH OSi), 69.7 (CH OAr), 117.1 (᎐CH), 127.9 (CH in Ar),
᎐
2
2
129.8 (CH in Ar), 133.3 (C in Ar), 138.5 (᎐C) and 144.6 (C in
᎐
Ar); m/z (CI) 413 (M+1, 1%), 229 (69), 157 (43), 93 (21), 83 (20),
81 (100), 75 (35), 69 (22) and 55 (18).
1,9-Dihydro-1,9-bis{[2-(trimethylsilyl)ethoxy]methyl}-2H-purin-
2-one 11a and 6-hydroxy-1,3,6,7-tetrahydro-1,3,7-tris{[2-(tri-
methylsilyl)ethoxy]methyl}-2H-purin-2-one 12a
[2-(Trimethylsilyl)ethoxy]methyl chloride (1.020 g, 6.12 mmol)
in dry CH2Cl2 (10 cm3) was added slowly to a mixture of 1,9-
dihydro-2H-purin-2-one 10 (178 mg, 1.31 mmol) and N-
ethyldiisopropylamine (0.57 cm3, 3.25 mmol) in dry CH2Cl2
(10 cm3) under N2 at 0 ЊC. After stirring for 1 h at 0 ЊC and
an additional 17 h at ambient temperature, the mixture was
evaporated in vacuo, and the products were separated by flash
chromatography eluting with EtOAc–hexane (1 : 1) followed
by EtOAc–hexane (2 : 1), EtOAc, EtOAc–EtOH (25 : 1) and
EtOAc–EtOH (10 : 1).
The more polar fraction yielded the dialkyl purine 11a (164
mg, 32%) as a yellow oil. Recrystallisation from EtOAc–hexane
gave colourless crystals, mp 103–105 ЊC (Found: C, 51.8; H, 8.1.
C17H32N4O3Si2 requires C, 51.5; H, 8.1%); δH(500 MHz; CDCl3;
Me4Si) Ϫ0.06 (9 H, s, SiMe3), Ϫ0.03 (9 H, s, SiMe3), 0.89 (2 H,
t, J 8.2, SiCH2), 0.96 (2 H, t, J 8.5, SiCH2), 3.60 (2 H, t, J 8.2,
OCH2), 3.67 (2 H, t, J 8.5, OCH2), 5.39 [2 H, s, N(9)CH2], 5.43
[2 H, s, N(1)CH2], 7.92 (1 H, s, H-8) and 8.30 (1 H, s, H-6);
δC(50 MHz; CDCl3; Me4Si) Ϫ1.5 (2 × SiMe3), 17.8 (SiCH2),
18.1 (SiCH2), 67.5 (OCH2), 68.2 (OCH2), 71.5 [N(9)CH2], 79.3
[N(1)CH2], 123.9 (C-5), 137.7 (C-6), 147.3 (C-8), 155.6 (C-2)
and 159.9 (C-4); m/z (CI) 396 (M+, 3%), 295 (11), 281 (14), 280
(55), 265 (19), 222 (32), 193 (12) and 73 (100).
(E)-5-Thexyldimethylsilyloxy-4-methylpent-3-en-1-ol 6 and
1-thexyldimethylsilyloxy-2-methylprop-2-ene 7
To a stirred solution of (E)-1-thexyldimethylsilyloxy-3-iodo-2-
methylprop-2-ene 5a (1.02 g, 3.0 mmol) in dry THF (10 cm3)
under N2 at Ϫ78 ЊC was added tert-butyllithium (1.5 M in
pentane, 4 cm3, 6 mmol) dropwise during 25 min before oxirane
(1 g, 23 mmol) in dry THF (2 cm3) was added. The resulting
mixture was stirred for 1 h at Ϫ78 ЊC and 1.5 h at ambient
temperature under N2, cooled to 0 ЊC and diluted with satur-
ated aqueous ammonium chloride (15 cm3). The phases were
separated and the aqueous phase extracted with CH2Cl2 (3 ×
15 cm3). The combined organic phases were dried (MgSO4)
and evaporated in vacuo. The products were isolated by flash
chromatography eluting with EtOAc–hexane (1 : 12) followed
by EtOAc–hexane (1 : 6).
The more polar fraction yielded the alcohol 6 (457 mg, 59%)
as a colourless oil (Found: C, 65.1; H, 11.65. C14H30O2Si
requires C, 65.05; H, 11.7%); δH(300 MHz; CDCl3; Me4Si) 0.07
(6 H, s, SiMe2), 0.84 (6 H, s, Me in thexyl), 0.86 (6 H, d, J 6.8,
Me in thexyl), 1.49 (1 H, m, OH), 1.61 (4 H, m, CH in thexyl
and Me), 2.30 (2 H, m, CH2), 3.62 (2 H, m, CH2), 3.98 (2 H, s,
CH OSi) and 5.38 (1 H, m, ᎐CH); δ (50 MHz; CDCl ; Me Si)
᎐
2
C
3
4
Ϫ3.4 (SiMe2), 13.6 (Me), 18.5 (Me in thexyl), 20.3 (Me in
thexyl), 25.2 (C in thexyl), 31.1 (CH2), 34.1 (CH in thexyl), 62.3
The less polar fraction yielded the adduct 12a (177 mg, 25%)
as a yellow oil (Found: C, 50.7; H, 8.5. C23H48N4O5Si3 requires
C, 50.7; H, 8.9%); δH(500 MHz; CDCl3; Me4Si) Ϫ0.02 (9 H, s,
SiMe3), 0.007 (9 H, s, SiMe3), 0.009 (9 H, s, SiMe3), 0.8–1.0
(6 H, m, 3 × SiCH2), 2.75 (1 H, br s, OH), 3.5–3.7 (6 H, m,
3 × OCH2), 5.06 [1 H, d, J 10.4, HA in N(1)CH2], 5.15 [1 H, d,
J 10.7, HA in N(7)CH2], 5.27 [1 H, d, J 10.7, HB in N(7)CH2],
5.34 [2 H, s, N(3)CH2], 5.40 [1 H, d, J 10.4, HB in N(1)CH2],
6.26 (1 H, d, J 5.9, H-6) and 7.36 (1 H, s, H-8); δC(125 MHz;
CDCl3; Me4Si) Ϫ1.6 (3 × SiMe3), 17.5 (SiCH2), 17.8 (SiCH2),
17.9 (SiCH2), 65.8 (OCH2), 66.1 (OCH2), 66.3 (OCH2), 71.0
[N(3)CH2], 73.9 (C-6), 74.8 [N(1)CH2 and N(7)CH2], 106.3
(C-5), 135.6 (C-8), 138.8 (C-4) and 152.0 (C-2); m/z (CI) 544
(M+, 1%), 528 (19), 527 (39), 441 (29), 280 (12), 268 (17), 75 (30)
and 73 (100).
(CH ), 68.1 (CH ), 119.6 (᎐CH) and 137.9 (᎐C); m/z (CI) 259
᎐
᎐
2
2
(M+1, 1%), 258 (1), 173 (78), 159 (20), 157 (20), 155 (21), 143
(27), 105 (31), 81 (69) and 75 (100).
The less polar fraction yielded the alkene 7 (213 mg, 33%) as
a colourless oil (Found: C, 67.6; H, 12.0. C12H26OSi requires
C, 67.2; H, 12.2%); δH(300 MHz; CDCl3; Me4Si) 0.09 (6 H, s,
SiMe2), 0.86 (6 H, s, Me in thexyl), 0.88 (6 H, d, J 6.9, Me in
thexyl), 1.64 (1 H, m, J 6.9, CH in thexyl), 1.68 (3 H, s, Me),
4.00 (2 H, s, CH ), 4.78 (1 H, m, ᎐CH) and 4.96 (1 H, m, ᎐CH);
᎐
᎐
2
δC(50 MHz; CDCl3; Me4Si) Ϫ3.5 (SiMe2), 18.5 (Me in thexyl),
19.0 (Me), 20.3 (Me in thexyl), 25.2 (C in thexyl), 34.2 (CH in
thexyl), 66.6 (CH ), 109.1 (᎐CH ) and 144.7 (᎐C); m/z (CI) 215
᎐
᎐
2
2
(M+1, 3%), 131 (14), 130 (13), 129 (100), 115 (13), 85 (6), 84
(14), 76 (3), 75 (40) and 73 (13).
1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-2H-
purin-2-one 11b and 6-hydroxy-1,3,6,7-tetrahydro-1,3,7-tris-
[(tert-butyldimethylsilyloxy)methyl]-2H-purin-2-one 12b
(E)-5-Thexyldimethylsilyloxy-4-methylpent-3-en-1-yl toluene-p-
sulfonate 8
A solution of tosyl chloride (531 mg, 2.78 mmol) in dry pyr-
idine (8 cm3) was stirred under N2 at 0 ЊC for 30 min and added
to (E)-5-thexyldimethylsilyloxy-4-methylpent-3-en-1-ol 6 (360
mg, 1.39 mmol). The resulting solution was stirred under N2 at
0 ЊC for 3 h and left in the refrigerator for 40 h. The solution
was then poured into ice–water (40 cm3) and extracted with
diethyl ether (80 cm3). The organic phase was washed with
aqueous 1 M HCl (40 cm3), saturated aqueous sodium hydro-
gen carbonate (40 cm3) and brine (40 cm3) prior to drying
(MgSO4) and evaporation in vacuo. This gave the toluene-p-
sulfonate 8 as a colourless oil which was used without further
purification; δH(300 MHz; CDCl3; Me4Si) 0.05 (6 H, s, SiMe2),
0.82 (6 H, s, Me in thexyl), 0.86 (6 H, d, J 6.9, Me in thexyl),
1.52 (3 H, s, Me), 1.60 (1 H, m, CH in thexyl), 2.33 (2 H, m,
CH2), 2.43 (3 H, s, ArMe), 3.91 (2 H, s, CH2OSi), 3.99 (2 H, t,
(tert-Butyldimethylsilyloxy)methyl chloride (1.106 g, 6.12
mmol) in dry CH2Cl2 (10 cm3) was added slowly to a mixture
of 1,9-dihydro-2H-purin-2-one 10 (278 mg, 2.04 mmol) and
N-ethyldiisopropylamine (1.04 cm3, 6.12 mmol) in dry CH2Cl2
(10 cm3) under N2 at 0 ЊC. After stirring for 1 h at 0 ЊC and
an additional 21 h at ambient temperature, the mixture was
evaporated in vacuo, and the products were separated by flash
chromatography eluting with EtOAc–hexane (2 : 3) followed by
EtOAc–hexane (1 : 1) and EtOAc–hexane–EtOH–NH3(conc.)
(40 : 20 : 1 : 1).
The more polar fraction yielded the dialkyl purine 11b (325
mg, 38%) as colourless crystals mp 164–166 ЊC (from EtOAc–
hexane) (Found: C, 54.15; H, 8.5. C19H36N4O3Si2 requires C,
53.7; H, 8.5%); δH(500 MHz; CDCl3; Me4Si) 0.10 (6 H, s,
SiMe2), 0.16 (6 H, s, SiMe2), 0.86 (9 H, s, t-Bu), 0.93 (9 H, s,
t-Bu), 5.51 [2 H, s, N(1)CH2], 5.59 [2 H, s, N(9)CH2], 7.97 (1 H,
s, H-8) and 8.45 (1 H, s, H-6); δC(75 MHz; CDCl3; Me4Si) Ϫ5.3
(2 × SiMe2), 17.9 (C in t-Bu), 18.1 (C in t-Bu), 25.5 (Me in
J 7.1, CH OAr), 5.25 (1 H, m, ᎐CH), 7.32 (2 H, d, J 8.0, Ar) and
᎐
2
7.76 (2 H, d, J 8.0, Ar); δC(50 MHz; CDCl3; Me4Si) Ϫ3.4
(SiMe2), 13.5 (Me), 18.5 (Me in thexyl), 20.3 (Me in thexyl),
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672
1667

View Article Online
t-Bu), 25.6 (Me in t-Bu), 66.8 [N(9)CH2], 73.9 [N(1)CH2], 123.7
(C-5), 136.4 (C-6), 146.3 (C-8), 154.7 (C-2) and 158.3 (C-4); m/z
(EI) 424 (M+, 0.3%), 368 (23), 367 (78), 338 (27), 337 (100), 307
(22), 75 (19) and 73 (91).
chloride (2 × 10 cm3) and saturated aqueous sodium hydrogen
carbonate (2 × 10 cm3), dried (MgSO4) and evaporated in
vacuo. The crude product was dissolved in dry benzene (30
cm3), DDQ (150 mg, 0.68 mmol) was added and the resulting
mixture was stirred at ambient temperature for 4 h under N2
before the mixture was filtered and the solvent evaporated
in vacuo. The product was isolated by flash chromatography
eluting with EtOAc–hexane (1 : 1) to give the phenylethylpurine
13b (239 mg, 66%) as yellow crystals. Recrystallisation from
EtOAc–hexane gave colourless crystals, mp 112–113 ЊC
(Found: C, 61.65; H, 8.4. C27H44N4O3Si2 requires C, 61.3; H,
8.4%); δH(300 MHz; CDCl3; Me4Si) 0.09 (6 H, s, SiMe2), 0.13
(6 H, s, SiMe2), 0.84 (9 H, s, t-Bu), 0.85 (9 H, s, t-Bu), 3.15 (2 H,
m, PhCH2), 3.47 [2 H, m, C(6)CH2], 5.52 [2 H, s, N(9)CH2], 5.64
[2 H, s, N(1)CH2], 7.1–7.3 (5 H, m, Ph) and 7.83 (1 H, s, H-8);
δC(75 MHz; CDCl3; Me4Si) Ϫ5.3 (SiMe), Ϫ5.2 (SiMe), 17.9
(C in t-Bu), 18.0 (C in t-Bu), 25.5 (Me in t-Bu), 25.7 (Me in
t-Bu), 30.6 [C(6)CH2], 35.1 (PhCH2), 66.6 [N(9)CH2], 69.5
[N(1)CH2], 123.1 (C-5), 126.7 (CH in Ph), 128.3 (CH in Ph),
128.7 (CH in Ph), 139.7 (C in Ph), 144.7 (C-8), 154.8 (C-6),
155.8 (C-2) and 157.2 (C-4); m/z (EI) 528 (M+, 1%), 472 (18),
471 (50), 443 (13), 442 (36), 441 (100) and 73 (34).
The less polar fraction yielded the adduct 12b which was
purified further by flash chromatography eluting with EtOAc–
hexane–Et3N (30 : 20 : 1) to give the adduct 12b (145 mg, 12%)
as a colourless oil (Found: C, 53.5; H, 9.0. C26H54N4O5Si3
requires C, 53.2; H, 9.3%); δH(500 MHz; CDCl3; Me4Si) Ϫ0.04
(3 H, s, SiMe), Ϫ0.01 (3 H, s, SiMe), 0.00 (3 H, s, SiMe), 0.002
(3 H, s, SiMe), 0.04 (3 H, s, SiMe), 0.05 (3 H, s, SiMe), 0.76
(9 H, s, Me in t-Bu), 0.79 (18 H, s, 2 × Me in t-Bu), 3.65 (1 H, d,
J 8.5, OH), 5.15 [1 H, d, J 9.2, HA in N(1)CH2], 5.30 [1 H, d,
J 9.6, HA in N(7)CH2], 5.30 [1 H, d, J 9.2, HB in N(1)CH2], 5.31
[1 H, d, J 9.3, HA in N(3)CH2], 5.35 [1 H, d, J 9.3, HB in
N(3)CH2], 5.45 [1 H, d, J 9.6, HB in N(7)CH2], 6.18 (1 H, d,
J 8.5, H-6) and 7.18 (1 H, s, H-8); δC(75 MHz; CDCl3; Me4Si)
Ϫ5.3 (SiMe), Ϫ5.2 (2 × SiMe), Ϫ5.1 (SiMe), Ϫ5.0 (2 × SiMe),
18.3 (C in t-Bu), 18.4 (C in t-Bu), 18.5 (C in t-Bu), 25.7 (Me in
t-Bu), 25.9 (Me in t-Bu), 26.0 (Me in t-Bu), 66.4 [N(3)CH2],
70.2 [N(1)CH2 and N(7)CH2], 74.0 (C-6), 106.9 (C-5), 135.4 (C-
8), 139.0 (C-4) and 151.4 (C-2); m/z (EI) 530 (18%), 529 (53),
367 (21), 337 (16), 115 (21), 89 (56), 75 (48), 73 (100), 57 (43)
and 56 (15).
(E)-1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
[2-(phenyl)ethenyl]-2H-purin-2-one 13c
1,9-Dihydro-1,9-bis{[2-(trimethylsilyl)ethoxy]methyl}-6-
[2-(phenyl)ethyl]-2H-purin-2-one 13a
To a solution of (E)-1-bromo-2-phenylethene (490 mg, 2.13
mmol) in dry Et2O (4 cm3) under N2 at Ϫ78 ЊC was added
t-BuLi (1.4 M in pentane, 3.1 cm3, 4.26 mmol). After stirring
for 1 h at Ϫ78 ЊC and 1.5 h at Ϫ35 ЊC, MgBr2 [generated from
1,2-dibromoethane (480 mg, 2.56 mmol) and Mg (62 mg,
2.56 mmol)] in dry Et2O (2 cm3) was added. The resulting mix-
ture was kept for 30 min at Ϫ35 ЊC and 30 min at ambient
temperature before it was dropwise added to 1,9-dihydro-
1,9-bis[(tert-butyldimethylsilyloxy)methyl]-2H-purin-2-one 11b
(600 mg, 1.41 mmol) in dry THF (10 cm3) under N2 at Ϫ78 ЊC.
The mixture was allowed to slowly reach ambient temperature.
After 20 h the mixture was worked up and oxidised with DDQ
(320 mg, 1.41 mmol) as described for compound 13b above. The
product was isolated by flash chromatography eluting with
EtOAc–hexane (1 : 1) to give the phenylethenylpurine 13c (500
mg, 67%) as a yellow oil; Rf 0.18 (2 : 3, EtOAc–hexane); δH(300
MHz; CDCl3; Me4Si) 0.09 (6 H, s, SiMe2), 0.14 (6 H, s, SiMe2),
0.84 (9 H, s, t-Bu), 0.87 (9 H, s, t-Bu), 5.55 [2 H, s, N(9)CH2],
5.86 [2 H, s, N(1)CH2], 7.35–7.4 (3 H, m, Ph), 7.44 [1 H, d,
J 16.2, C(6)CH], 7.60 (2 H, m, Ph), 7.93 (1 H, s, H-8) and 8.50
(1 H, J 16.2, CH); δC(75 MHz; CDCl3; Me4Si) Ϫ4.9 (SiMe),
Ϫ4.8 (SiMe), 18.3 (2 × C in t-Bu), 25.9 (Me in t-Bu), 26.0 (Me
in t-Bu), 67.2 [N(9)CH2], 70.7 [N(1)CH2], 116.5 [C(6)CH], 122.1
(C-5), 128.3 (CH in Ph), 129.2 (CH in Ph), 130.8 (CH in Ph),
To a solution of 1,9-dihydro-1,9-bis{[2-(trimethylsilyl)ethoxy]-
methyl}-2H-purin-2-one 11a (200 mg, 0.47 mmol) in dry THF
(5 cm3) under N2 at Ϫ78 ЊC was added dropwise a 1 M solution
of Grignard reagent (0.94 cm3, 0.94 mmol, generated from
1-chloro-2-phenylethane and magnesium in dry THF under
N2). The mixture was stirred for 19 h while slowly being allowed
to reach ambient temperature. The solution was diluted with
saturated aqueous ammonium chloride (5 cm3), the phases were
separated and the aqueous phase extracted with EtOAc (3 ×
6 cm3). The combined organic phases were dried (MgSO4)
and evaporated in vacuo. The crude product was dissolved in
CH2Cl2 (15 cm3) and MnO2 (2.2 g) was added. The resulting
mixture was stirred at ambient temperature for 3 h under N2
and filtered through a plug of silica gel before the solvent was
evaporated in vacuo. The product was isolated by flash chrom-
atography eluting with EtOAc–hexane (2 : 1) followed by
EtOAc–hexane (3 : 1) and EtOAc to give the phenylethylpurine
13a (90 mg, 47%) as a yellow oil; Rf 0.18 (1 : 3, EtOAc–hexane);
δH(500 MHz; CDCl3; Me4Si) Ϫ0.04 (18 H, s, 2 × SiMe3), 0.85–
0.90 (4 H, m, 2 × SiCH2), 3.12 (2 H, t, J 7.8, PhCH2), 3.46 [2 H,
t, J 7.8, C(6)CH2], 3.61 (2 H, t, J 8.2, OCH2), 3.72 (2 H, t, J 8.2,
OCH2), 5.37 [2 H, s, N(9)CH2], 5.56 [2 H, s, N(1)CH2], 7.2–7.3
(5 H, m, Ph) and 7.84 (1 H, s, H-8); δC(125 MHz; CDCl3; Me4Si)
Ϫ1.4 (2 × SiMe3), 17.8 (SiCH2), 18.3 (SiCH2), 30.9 [C(6)CH2],
35.2 (PhCH2), 67.4 (OCH2), 67.5 (OCH2), 71.5 [N(9)CH2], 74.5
[N(1)CH2], 123.1 (C-5), 126.8 (CH in Ph), 128.3 (CH in Ph),
128.7 (CH in Ph), 139.6 (C in Ph), 145.3 (C-8), 155.5 (C-6),
156.6 (C-2) and 158.0 (C-4); m/z (CI) 501 (M + 1, 1%), 442 (29),
385 (17), 384 (48), 311 (24), 91 (17), 75 (38) and 73 (100);
m/z (electrospray) 501.2712 (M + 1. C25H41N4O3Si2 requires
501.2712).
136.0 (C in Ph), 145.8 (C-8), 147.6 (᎐CH), 148.7 (C-6), 156.1
᎐
(C-2) and 157.9 (C-4); m/z (EI) 469 (M+ Ϫ t-Bu, 41%), 439 (58),
182 (94), 145 (84), 85 (64), 75 (52), 71 (85), 57 (100), 55 (42) and
43 (87); m/z (electrospray) 527.2890 (M + 1. C27H44N4O3Si2
requires 527.2868).
(Z)-1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
[2-(phenyl)ethenyl]-2H-purin-2-one 13d
A solution of (E)-1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-6-[2-(phenyl)ethenyl]-2H-purin-2-one 13c (80 mg)
in ethanol (10 cm3) was irradiated with a Hg-lamp for 8 days.
Flash chromatography on silica gel eluting with hexane–EtOAc
(1 : 1) followed by hexane–EtOAc (1 : 4) gave the phenylethen-
ylpurine 13d as a yellow oil (57 mg, 71%) (Found: C, 61.6; H,
6.7. C27H42N4O3Si2 requires C, 61.6; H, 6.9%); δH(300 MHz;
CDCl3; Me4Si) 0.02 (6 H, s, SiMe2), 0.10 (6 H, s, SiMe2), 0.79
(9 H, s, t-Bu), 0.81 (9 H, s, t-Bu), 5.44 [2 H, s, N(9)CH2], 5.74
[2 H, s, N(1)CH2], 6.59 [1 H, d, J 12.4, C(6)CH], 7.1–7.2 (3 H,
m, Ph), 7.14 (1 H, J 12.4, CH) and 7.63 (1 H, s, H-8); δC(75
MHz; CDCl3; Me4Si) Ϫ5.3 (SiMe2), 17.8 (C in t-Bu), 18.0 (C in
1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
[2-(phenyl)ethyl]-2H-purin-2-one 13b
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-2H-purin-2-one 11b (288 mg, 0.68 mmol) in dry
THF (10 cm3) under N2 at Ϫ78 ЊC was added dropwise a 1 M
solution of Grignard reagent (1.0 cm3, 1.0 mmol, generated
from 1-chloro-2-phenylethane and magnesium in dry THF
under N2). The mixture was stirred for 2 h at Ϫ78 ЊC and 1 h
at ambient temperature and diluted with CH2Cl2 (10 cm3).
The solution was washed with saturated aqueous ammonium
1668
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672

View Article Online
t-Bu), 25.4 (Me in t-Bu), 25.6 (Me in t-Bu), 66.5 [N(9)CH2],
70.6 [N(1)CH2], 115.7 [C(6)CH], 121.8 (C-5), 128.4 (CH in Ph),
oxy)methyl]-2H-purin-2-one 11b (200 mg, 0.47 mmol) in dry
THF (5 cm3) under N2 at Ϫ78 ЊC was added dropwise a 0.53 M
solution of Grignard reagent (2 cm3, 0.8 mmol, generated
from 5-bromo-2-methylpent-2-ene 1b and magnesium in dry
THF under N2). The mixture was stirred for 18 h while slowly
being allowed to reach ambient temperature and worked up and
oxidised with DDQ as described for compound 13b above. The
product was isolated by flash chromatography eluting with
EtOAc–hexane (1 : 1) to give the alkene 13g (186 mg, 78%) as a
yellow oil (Found: C, 59.2; H, 9.0. C25H46N4O3Si2 requires C,
59.2; H, 9.15%); δH(500 MHz; CDCl3; Me4Si) 0.06 (6 H, s,
SiMe2), 0.11 (6 H, s, SiMe2), 0.83 (18 H, s, 2 × t-Bu), 1.52 (3 H,
s, Me), 1.62 (3 H, s, Me), 2.49 (2 H, m, CH2), 3.19 (2 H, t, J 7.6,
128.7 (CH in Ph), 135.0 (C in Ph), 139.7 (᎐CH), 145.5 (C-8),
᎐
149.7 (C-6), 155.7 (C-2) and 157.9 (C-4); m/z (EI) 526 (M+, 1%),
471 (20), 470 (28), 469 (69), 441 (27), 440 (40), 439 (100), 73 (50)
and 57 (16).
1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
[2-(phenyl)ethynyl]-2H-purin-2-one 13e
To a solution of EtMgBr (1 M in THF, 1 cm3, 1 mmol) in dry
THF (1 cm3) was added phenylethyne (122 mg, 1.2 mmol) in
dry THF (1 cm3) under N2 at Ϫ78 ЊC. The resulting white
suspension was allowed to reach ambient temperature and
heated to reflux for 2 h before it was cooled to ambient tem-
perature, and added dropwise to a solution of 1,9-dihydro-
1,9-bis[(tert-butyldimethylsilyloxy)methyl]-2H-purin-2-one 11b
(200 mg, 0.47 mmol) in dry THF (4 cm3) under N2 at Ϫ78 ЊC.
The solution was allowed to slowly reach ambient temperature.
After 13 h the reaction mixture was worked up and oxidised
with DDQ as described for compound 13b above. The product
was isolated by flash chromatography eluting with EtOAc–
hexane (1 : 1) to give the phenylethynylpurine 13e (187 mg, 76%)
as pale yellow crystals, mp 158–160 ЊC (from EtOAc–hexane)
(Found: C, 61.4; H, 7.7. C27H40N4O3Si2 requires C, 61.8; H,
7.7%); δH(300 MHz; CDCl3; Me4Si) 0.06 (6 H, s, SiMe2), 0.10
(6 H, s, SiMe2), 0.83 (18 H, s, 2 × t-Bu), 5.52 [2 H, s, N(9)CH2],
5.87 [2 H, s, N(1)CH2], 7.3–7.6 (5 H, m, Ph) and 7.94 (1 H, s,
H-8); δC(75 MHz; CDCl3; Me4Si) Ϫ5.3 (2 × SiMe), 17.9 (C in
t-Bu), 18.0 (C in t-Bu), 25.5 (Me in t-Bu), 25.6 (Me in t-Bu),
CH ), 5.15 (1 H, m, ᎐CH), 5.50 [2 H, s, N(9)CH ], 5.74 [2 H, s,
᎐
2
2
N(1)CH2] and 7.83 (1 H, s, H-8); δC(75 MHz; CDCl3; Me4Si)
Ϫ5.4 (2 × SiMe2), 17.5 (Me), 17.8 (C in t-Bu), 17.9 (C in t-Bu),
25.4 (Me in t-Bu), 25.5 (Me in t-Bu), 27.6 (CH2), 28.4
[C(6)CH ], 66.6 [N(9)CH ], 69.4 [N(1)CH ], 121.4 (᎐CH), 123.1
᎐
2
2
2
(C-5), 134.2 (᎐C), 144.6 (C-8), 155.5 (C-2), 155.9 (C-6) and
᎐
156.9 (C-4); m/z (CI) 503 (M + 1, 28%), 449 (24), 115 (25), 89
(21), 75 (65), 73 (34), 69 (33), 58 (20), 57 (100), 56 (32) and 55
(51).
1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
ethenyl-2H-purin-2-one 13h
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-2H-purin-2-one 11b (212 mg, 0.5 mmol) in dry
THF (5 cm3) under N2 at Ϫ78 ЊC was added dropwise a solu-
tion of ethenylmagnesium bromide (1 M in THF, 0.75 cm3, 0.75
mmol). The resulting solution was allowed to slowly reach
ambient temperature. After 17 h the reaction mixture was
worked up and oxidised with DDQ (113 mg, 0.5 mmol) as
described for compound 13b above. The product was isolated
by flash chromatography eluting with EtOAc–hexane (1 : 1)
followed by EtOAc–hexane (3 : 2) to give the ethenylpurine 13h
(142 mg, 63%) as a yellow oil; Rf 0.13 (1 : 1, EtOAc–hexane);
δH(300 MHz; CDCl3; Me4Si) 0.08 (6 H, s, SiMe2), 0.11 (6 H, s,
SiMe2), 0.83 (9 H, s, 2 × t-Bu), 0.84 (9 H, s, 2 × t-Bu), 5.52 [2 H,
᎐
᎐
66.7 [N(9)CH ], 71.8 [N(1)CH ], 78.0 (Pur-C᎐), 107.0 (᎐C-Ph),
᎐
᎐
2
2
120.2 (C in Ph), 126.1 (C-5), 128.6 (CH in Ph), 130.8 (CH in
Ph), 132.5 (CH in Ph), 133.2 (C-6), 146.7 (C-8), 155.1 (C-2) and
158.2 (C-4); m/z (EI) 524 (M+, 1%), 469 (15), 468 (25), 467 (59),
440 (11), 439 (31), 437 (100), 190 (14), 159 (11) and 73 (42).
(E)-1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
(4-methyl-5-thexyldimethylsilyloxypent-3-en-1-yl)-2H-purin-2-
one 13f
s, N(9)CH ], 5.75 [2 H, s, N(1)CH ], 6.1–6.2 (1 H, m, ᎐CH ),
᎐
2
2
2
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-2H-purin-2-one 11b (287 mg, 0.68 mmol) in dry
THF (9 cm3) under N2 at Ϫ78 ЊC was added dropwise a 0.3 M
solution of Grignard reagent [4.0 cm3, 1.2 mmol, generated
from (E)-5-bromo-1-thexyldimethylsilyloxy-2-methylpent-2-
ene 3b and magnesium in dry Et2O under N2]. The mixture was
stirred for 24 h while being allowed to reach ambient temper-
ature and worked up and oxidised with DDQ as described
for compound 13b above. The product was isolated by flash
chromatography on silica gel eluting with EtOAc–hexane (1 : 1)
to give the silylated allyl alcohol 13f (275 mg, 61%) as a yellow
oil (Found: C, 59.3; H, 9.7. C33H64N4O4Si3 requires C, 59.6; H,
9.7%); δH(300 MHz; CDCl3; Me4Si) 0.01 (6 H, s, SiMe2), 0.02
(6 H, s, SiMe2), 0.06 (6 H, s, SiMe2), 0.76–0.80 (30 H, m, 2 ×
t-Bu and 4 × Me in thexyl), 1.47 (3 H, s, Me), 1.53 (1 H, m, CH
in thexyl), 2.49 (2 H, m, CH2), 3.17 [2 H, t, J 7.6, C(6)CH2], 3.87
6.9–7.1 (2 H, m, CH᎐ and ᎐CH ) and 7.89 (1 H, s, H-8); δ (75
MHz; CDCl3; Me4Si) Ϫ5.3 (2 × SiMe2), 17.9 (2 × C in t-Bu),
25.5 (Me in t-Bu), 25.6 (Me in t-Bu), 66.7 [N(9)CH2], 70.1
᎐
᎐
2
C
[N(1)CH ], 121.9 (C-5), 125.4 (᎐CH ), 132.8 (CH=), 145.9
᎐
2
2
(C-8), 148.1 (C-6), 155.4 (C-2) and 158.1 (C-4); m/z (EI) 450
(M+, 0.3%), 394 (18), 393 (52), 365 (17), 364 (29), 363 (100), 89
(11), 73 (47) and 28 (49). HRMS: found 450.2458, calc. for
C21H38N4O3Si2 450.2482.
(E,E)-1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-
6-(5-tert-butyldimethylsilyloxy-4-methylpenta-1,3-dien-1-yl)-
2H-purin-2-one 13i
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-6-ethenyl-2H-purin-2-one 13h (148 mg, 0.33
mmol) in dry DMF (1 cm3) under N2 were added N-ethyl-
diisopropylamine (0.17 cm3, 0.99 mmol), palladium() acetate
(7 mg, 0.033 mmol) and (E)-1-tert-butyldimethylsilyloxy-3-
iodo-2-methylprop-2-ene 5b (123 mg, 0.39 mmol) in dry DMF
(1 cm3). The resulting mixture was heated at 40 ЊC for 17 h
before saturated aqueous ammonium chloride (15 cm3) was
added and the mixture was extracted with EtOAc (3 × 25 cm3),
dried (Na2SO4) and evaporated in vacuo. The product was
isolated by flash chromatography eluting with EtOAc–hexane
(1 : 3), followed by EtOAc–hexane (1 : 2) and finally 2 : 3 to give
the diene 13i (102 mg, 49%) as a yellow oil; Rf 0.30 (1 : 1,
EtOAc–hexane); δH(200 MHz; CDCl3; Me4Si) 0.07 (6 H, s,
SiMe2), 0.08 (6 H, s, SiMe2), 0.11 (6 H, s, SiMe2), 0.84 (18 H, s,
t-Bu), 0.91 (9 H, s, t-Bu), 1.90 (3 H, s, Me), 4.17 (2 H, m,
CH2OSi), 5.53 [2 H, s, N(9)CH2], 5.80 [2 H, s, N(1)CH2], 6.44
(2 H, s, OCH ), 5.41 (1 H, m, ᎐CH), 5.45 [2 H, s, N(9)CH ], 5.69
᎐
2
2
[2 H, s, N(1)CH2] and 7.78 (1 H, s, H-8); δC(75 MHz; CDCl3;
Me4Si) Ϫ5.4 (SiMe), Ϫ3.6 (SiMe), 13.3 (Me), 17.8 (C in t-Bu),
18.3 (C in t-Bu), 20.2 (Me in thexyl), 25.0 (C in thexyl), 25.4
(Me in t-Bu), 25.5 (Me in t-Bu), 27.1 (CH2), 28.2 [C(6)CH2],
34.0 (CH in thexyl), 66.5 [N(9)CH2], 67.5 (OCH2), 69.4
[N(1)CH ], 120.7 (᎐CH), 123.0 (C-5), 137.0 (᎐C), 144.5 (C-8),
᎐
᎐
2
155.3 (C-2), 155.8 (C-6) and 157.0 (C-4); m/z (EI) 664 (M+, 1%),
609 (22), 608 (49), 607 (100), 580 (15), 579 (33), 578 (20), 577
(41), 549 (19) and 73 (46).
1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
(4-methylpent-3-en-1-yl)-2H-purin-2-one 13g
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
(1 H, d, J 11.7, CH᎐), 6.82 (1 H, d, J 15.2, CH᎐), 7.85 (1 H, s,
᎐ ᎐
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672
1669

View Article Online
H-8) and 8.58 (1 H, dd, J 11.7, J 15.2, ᎐CH); δ (50 MHz;
The product was isolated by flash chromatography on silica
᎐
1
2
C
CDCl3; Me4Si) Ϫ5.4 (SiMe), Ϫ5.2 (SiMe), 14.8 (Me), 17.9 (C in
t-Bu), 18.3 (C in t-Bu), 25.5 (Me in t-Bu), 25.6 (Me in t-Bu),
25.8 (Me in t-Bu), 66.7 [N(9)CH2], 67.1 (OCH2), 70.0
gel eluting with CHCl3–MeOH–NH3 (50 : 10 : 1) followed
by CHCl3–MeOH–NH3 (20 : 6 : 1), CHCl3–MeOH–NH3
(10 : 4 : 1) and CHCl3–MeOH–NH3 (5 : 3 : 1) to give the ethe-
nylpurine 14b (55 mg, 90%) as yellow crystals, mp >300 ЊC
(darkened above 150 ЊC.); Rf 0.19 (10 : 4 : 1, CHCl3–MeOH–
NH3); δH(200 MHz; DMSO-d6; Me4Si) 7.29 (1 H, d, J 16.4,
[N(1)CH ], 118.5 (CH᎐), 121.3 (C-5), 123.3 (CH᎐), 144.0
᎐
᎐
2
(᎐CH), 144.6 (C-8), 148.6 (᎐C), 148.9 (C-6), 155.5 (C-2) and
᎐
᎐
157.2 (C-4); m/z (EI) 635 (M+, 0.4%), 578 (31), 577 (62), 548
(37), 547 (70) and 89 (36); m/z (electrospray) 635.3809 (M + 1.
C31H58N4O4Si3 requires 635.3839).
CH᎐), 7.4–7.5 (3 H, m, CH in Ph), 7.6–7.7 (2 H, m, CH in Ph),
᎐
8.20 (1 H, s, H-8), 8.37 (1 H, d, J 16.4, ᎐CH) and 9.4 (2 H, br s,
᎐
2 × NH); δC(125 MHz; DMSO-d6; Me4Si) 118.6 [C(6)CH],
120.8 (C-5), 127.1 (CH in Ph), 128.6 (CH in Ph), 129.4 (CH in
(E)-1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
(5-tert-butyldimethylsilyloxy-4-methylpent-3-en-1-yn-1-yl)-2H-
purin-2-one 13j
Ph), 135.2 (C in Ph), 140.8 (᎐CH), 144.9 (C-8), 146.3 (C-6),
᎐
156.7 (C-2) and 159.1 (C-4); m/z (electrospray) 239.0936
(M + 1. C13H10N4O requires 239.0927).
To a solution of EtMgBr (1 M in THF, 1 cm3, 1 mmol) in dry
THF (1 cm3) was added (E)-1-(tert-butyldimethylsilyloxy)-2-
methylpent-2-en-4-yne 9 (252 mg, 1.2 mmol) in dry THF
(1 cm3) under N2 at Ϫ78 ЊC. The resulting white suspension was
allowed to reach ambient temperature, heated to reflux for 2 h
and cooled to ambient temperature before the Grignard reagent
was added dropwise to a solution of 1,9-dihydro-1,9-bis[(tert-
butyldimethylsilyloxy)methyl]-2H-purin-2-one 11b (200 mg,
0.47 mmol) in dry THF (4 cm3) under N2 at Ϫ78 ЊC. The solu-
tion was allowed to slowly reach ambient temperature and after
13 h it was worked up and oxidised with DDQ as described
for compound 13b above. The product was isolated by flash
chromatography eluting with EtOAc–hexane (3 : 2) followed by
EtOAc–hexane (1 : 1) to give the enyne 13j (245 mg, 82%) as
pale yellow crystals, mp 114–117 ЊC (Found: C, 59.2; H, 8.8.
C31H56N4O4Si3 requires C, 58.8; H, 8.9%); δH(300 MHz; CDCl3;
Me4Si) Ϫ0.01 (6 H, s, SiMe2), 0.01 (6 H, s, SiMe2), 0.05 (6 H,
s, SiMe2), 0.76 (9 H, s, t-Bu), 0.77 (9 H, s, t-Bu), 0.83 (9 H, s,
t-Bu), 1.94 (3 H, s, Me), 4.12 (2 H, s, CH2OSi), 5.46 [2 H, s,
(Z)-1,9-Dihydro-6-[2-(phenyl)ethenyl]-2H-purin-2-one 14c
To a solution of (Z)-1,9-dihydro-1,9-di[(tert-butyldimethylsilyl-
oxy)methyl]-6-[2-(phenyl)ethenyl]-2H-purin-2-one 13d (57 mg,
0.11 mmol) in dry acetonitrile (3 cm3) under N2 was added
a 1 M solution of tetramethylammonium fluoride in dry
acetonitrile (0.43 cm3). The solution was stirred for 19 h at
ambient temperature before the solution was evaporated
in vacuo. The crude product was purified by flash chrom-
atography on silica gel eluting with CHCl3–MeOH–NH3
(50 : 10 : 1) followed by CHCl3–MeOH–NH3 (20 : 6 : 1) to give
a 2 : 1 mixture of the styrylpurines 14b and 14c (20 mg, 78%
total yield) as yellow crystals. The 1H NMR resonances belong-
ing to the Z-isomer 14c are given; δH(300 MHz; DMSO-d6;
Me Si) 6.60 (1 H, br d, CH᎐), 7.05 (1 H, d, J 12.1, ᎐CH),
᎐
᎐
4
7.2–7.3 (m, 5 H, CH in Ph) and 7.99 (1 H, s, H-8).
1,9-Dihydro-6-[2-(phenyl)ethynyl]-2H-purin-2-one 14d
N(9)CH ], 5.76 [2 H, s, N(1)CH ], 5.97 (1 H, s, ᎐CH) and 7.84
᎐
2
2
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-6-[2-(phenyl)ethynyl]-2H-purin-2-one 13e (81 mg,
0.154 mmol) in dry ethanol (5 cm3) under N2 was added a 1 M
solution of tetramethylammonium fluoride in dry ethanol (0.62
cm3). The solution was stirred for 23 h at ambient temperature
before AcOH (conc.) was added. After an additional 5 h the
solution was evaporated in vacuo. The product was isolated by
flash chromatography on silica gel eluting with CHCl3–MeOH–
NH3 (20 : 6 : 1) followed by CHCl3–MeOH–NH3 (10 : 4 : 1) to
give the alkyne 14d (25 mg, 69%) as yellow crystals, mp >300 ЊC
(darkened above ca. 200 ЊC); Rf 0.14 (10 : 4 : 1, CHCl3–MeOH–
NH3) (Found: C, 65.55; H, 3.5. C13H8N4O requires C, 66.1; H,
3.4%); δH(300 MHz; DMSO-d6; Me4Si) 7.4–7.7 (5 H, m, CH in
Ph), 8.31 (1 H, s, H-8) and 12.5 (2 H, br s, 2 × NH); δC(75 MHz;
(1 H, s, H-8); δC(50 MHz; CDCl3; Me4Si) Ϫ5.7 (SiMe), Ϫ5.43
(SiMe), Ϫ5.41 (SiMe), 16.9 (Me), 17.7 (C in t-Bu), 17.9 (C in
t-Bu), 18.1 (C in t-Bu), 25.4 (Me in t-Bu), 25.5 (Me in t-Bu),
25.6 (Me in t-Bu), 66.1 (CH2OSi), 66.5 [N(9)CH2], 71.6
᎐
᎐
[N(1)CH ], 81.7 (C᎐), 101.6 (᎐CH), 106.2 (C᎐), 125.7 (C-5),
᎐
᎐
᎐
2
133.8 (C-6), 146.1 (C-8), 155.1 (C-2), 157.9 (C-4) and 159.0
(᎐C); m/z (EI) 632 (M+, 0.4%), 577 (25), 576 (48), 575 (100), 547
᎐
(11), 546 (19), 545 (39), 228 (19), 75 (16) and 73 (46).
1,9-Dihydro-6-[2-(phenyl)ethyl]-2H-purin-2-one 14a
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-6-[2-(phenyl)ethyl]-2H-purin-2-one 13b (59 mg,
0.11 mmol) in dry acetonitrile (4 cm3) was added a 1 M solution
of tetramethylammonium fluoride in dry acetonitrile (0.45
cm3). The solution was stirred under N2 for 24 h at ambient
temperature before the solution was evaporated in vacuo. The
product was isolated by flash chromatography on silica gel
eluting with CHCl3–MeOH–NH3 (20 : 6 : 1) to give the
phenylethylpurine 14a (81%, 22 mg) as yellow crystals, mp
>300 ЊC (decomp.) (Found: C, 64.5; H, 5.1. C13H12N4O requires
C, 65.0; H, 5.0%); δH(500 MHz; DMSO-d6; Me4Si) 3.09 (4 H, m,
2 × CH2), 7.1–7.3 (5 H, m, Ph), 8.06 (1 H, s, H-8) and 12.1 (2 H,
br s, 2 × NH); δC(125 MHz; DMSO-d6; Me4Si) 30.6 (CH2), 32.8
(CH2), 122.1 (C-5), 125.8 (CH in Ph), 127.9 (CH in Ph), 128.0
(CH in Ph), 140.1 (C in Ph), 144.3 (C-8), 152.8 (C-6), 156.5
(C-2) and 159.1 (C-4); m/z (EI) 240 (M+, 100%), 239 (57), 163
(34), 150 (11), 91 (47) and 65 (9).
᎐
᎐
DMSO-d ; 60 ЊC; Me Si) 82.2 (C᎐), 97.5 (C᎐), 120.2 (C in Ph),
᎐
᎐
6
4
125.8 (C-5), 128.7 (CH in Ph), 130.1 (CH in Ph), 131.8 (CH in
Ph), 135.0 (C-6), 145.4 (C-8), 158.2 (C-2) and 158.7 (C-4); m/z
(electrospray) 237.0775 (M + 1. C13H8N4O requires 237.0776).
(E)-1,9-Dihydro-6-(5-hydroxy-4-methylpent-3-en-1-yl)-2H-
purin-2-one 14e
To a solution of (E)-1,9-dihydro-1,9-bis[(tert-butyldimethylsil-
yloxy)methyl]-6-(4-methyl-5-thexyldimethylsilyloxypent-3-en-
1-yl)-2H-purin-2-one 13f (100 mg, 0.15 mmol) was added
tetramethylammonium fluoride (1.2 mmol) in dry acetonitrile
(4 cm3). The solution was stirred under N2 for 40 h at ambient
temperature before the solution was evaporated in vacuo. The
product was isolated by flash chromatography on silica gel
eluting with CHCl3–MeOH–NH3 (10 : 4 : 1) to give the allylic
alcohol 14e (28, mg, 80%) as yellow crystals, mp >200 ЊC
(decomp.); Rf 0.18 (10 : 4 : 1, CHCl3–MeOH–NH3); δH(300
MHz; DMSO-d6; Me4Si) 1.49 (3 H, s, Me), 2.47 (2 H, q, J 7.3,
CH2), 2.84 [2 H, t, J 7.3, C(6)CH2], 3.72 [2 H, s, CH2OH], 4.68
(E)-1,9-Dihydro-6-[2-(phenyl)ethenyl]-2H-purin-2-one 14b
To a solution of (E)-1,9-dihydro-1,9-bis[(tert-butyldimethyl-
silyloxy)methyl]-6-[2-(phenyl)ethenyl]-2H-purin-2-one 13c (126
mg, 0.26 mmol) in dry acetonitrile (4 cm3) was added a 1 M
solution of tetramethylammonium fluoride in dry acetonitrile
(1.0 cm3). The solution was stirred under N2 for 15 h at ambient
temperature before the solution was evaporated in vacuo.
(1 H, br s, OH), 5.32 (1 H, m, ᎐CH), 8.05 (1 H, s, H-8); δ (75
᎐
C
MHz; DMSO-d6; Me4Si) 13.5 (Me), 25.8 (CH2), 29.0
[C(6)CH ], 66.1 (CH OH), 121.1 (᎐CH), 121.9 (C-5), 137.2
᎐
2
2
1670
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672

View Article Online
(᎐C), 144.6 (C-8), 153.1 (C-6), 156.6 (C-2) and 159.7 (C-4); m/z
(1ꢀ,2ꢀ,3ꢁ,4ꢁ)-1,3-Bis{1,9-dihydro-1,9-bis[(tert-butyldimethyl-
silyloxy)methyl]-2-oxo-2H-purin-6-yl}-2,4-diphenylcyclobutane
15
᎐
(EI) 234 (M+, 1%), 121 (76), 107 (29), 95 (26), 93 (66), 80 (32),
79 (79), 67 (64) and 66 (63). m/z (electrospray) 235.1190 (M + 1.
C11H15N4O2 requires 235.1190).
(E)-1,9-Dihydro-1,9-bis[(tert-butyldimethylsilyloxy)methyl]-6-
[2-(phenyl)ethenyl]-2H-purin-2-one 13c (95 mg, 0.18 mmol)
was stored in a round-bottomed flask without protection from
daylight for 14 days. Flash chromatography on silica gel, eluting
with hexane–EtOAc (3 : 2) followed by hexane–EtOAc (1 : 1),
gave the cyclobutane 15 as a yellow oil (46 mg, 48%). Recrystal-
lisation from EtOAc–hexane gave colourless crystals, mp 241–
244 ЊC (Found: C, 61.8; H, 7.9. C54H84N8O6Si4 requires C,
61.55; H, 8.0%); δH(200 MHz; CDCl3; Me4Si) Ϫ0.05 (6 H, s,
SiMe2), Ϫ0.01 (6 H, s, SiMe2), 0.07 (6 H, s, SiMe2), 0.23 (6 H, s,
SiMe2), 0.79 (18 H, s, Me in t-Bu), 0.86 (18 H, s, Me in t-Bu),
5.29 [1 H, d, J 9.5, HA in N(1)CH2], 5.39 [1 H, d, J 9.7, HA in
N(9)CH2], 5.52 [1 H, d, J 9.7, HB in N(9)CH2], 5.56 [1 H, dd,
J1 17.0, J2 7.7, C(6)CH in cyclobutane], 6.12 [1 H, dd, J1 17.0,
J2 7.7, PhCH in cyclobutane], 5.52 [1 H, d, J 9.7, HB in N(1)CH2],
7.0–7.1 (6 H, m, CH in Ph), 7.2–7.3 (4 H, m, CH in Ph), 7.87
(H-8) and 12.5 (1 H, br s, NH); δC(75 MHz; CDCl3; Me4Si)
Ϫ5.6 (SiMe), Ϫ5.3 (SiMe), Ϫ5.1 (SiMe), Ϫ4.9 (SiMe), 17.9
(C in t-Bu), 25.6 (Me in t-Bu), 44.2 [C(6)CH in cyclobutane],
44.7 (PhCH in cyclobutane), 66.6 [N(9)CH2], 69.8 [N(1)CH2],
124.3 (C-5), 127.6 (CH in Ph), 128.5 (CH in Ph), 138.0 (C
in Ph), 144.7 (C-8), 152.5 (C-6), 155.6 (C-2) and 157.8 (C-4);
m/z (electrospray) 1053.5688 (M + 1. C54H84N8O6Si4 requires
1053.5664).
1,9-Dihydro-6-(4-methylpent-3-en-1-yl)-2H-purin-2-one 14f
To a solution of 1,9-dihydro-1,9-bis[(tert-butyldimethylsilyl-
oxy)methyl]-6-(4-methylpent-3-en-1-yl)-2H-purin-2-one
13g
(80 mg, 0.16 mmol) in dry acetonitrile (4 cm3) was added a 1 M
solution of tetramethylammonium fluoride in dry acetonitrile
(0.63 cm3). The solution was stirred under N2 for 24 h at ambi-
ent temperature before the solution was evaporated in vacuo.
The product was isolated by flash chromatography on silica gel
eluting with CHCl3–MeOH–NH3 (50 : 10 : 1) to give the alkene
14f (27 mg, 79%) as yellow crystals, mp >250 ЊC (decomp.); Rf
0.17 (50 : 10 : 1, CHCl3–MeOH–NH3) (Found: C, 60.3; H, 6.3.
C11H14N4O requires C, 60.5; H, 6.5%); δH(500 MHz; DMSO-d6;
Me4Si) 1.50 (3 H, s, Me), 1.60 (3 H, s, Me), 2.43 (2 H, m, CH2),
2.81 [2 H, t, J 7.5, C(6)CH ], 5.10 (1 H, m, ᎐CH), 8.03 (1 H, s,
᎐
2
H-8) and 12.1 (2 H, br s, 2 × NH); δC(75 MHz; DMSO-d6;
Me4Si) 17.5 (Me), 25.4 (Me), 26.3 (CH2), 29.1 [C(6)CH2], 121.9
(C-5), 122.3 (᎐CH), 132.6 (᎐C), 144.5 (C-8), 153.1 (C-6), 156.6
᎐
᎐
(C-2) and 159.6 (C-4); m/z (EI) 218 (M+, 34%), 203 (31), 175
(14), 163 (8), 151 (9), 150 (100), 135 (6), 122 (10) and 69 (11).
(E,E)-1,9-Dihydro-6-(5-hydroxy-4-methylpenta-1,3-dien-1-yl)-
2H-purin-2-one 14g
To a solution of (E,E)-1,9-dihydro-1,9-bis[(tert-butyldimethyl-
silyloxy)methyl]-6-(5-tert-butyldimethylsilyloxy-4-methylpenta-
1,3-dien-1-yl)-2H-purin-2-one 13i in dry acetonitrile (3 cm3)
was added a 1 M solution of tetramethylammonium fluoride in
dry acetonitrile (0.96 cm3). The solution was stirred under N2
for 22 h at ambient temperature before the solution was evap-
orated in vacuo. The product was isolated by flash chrom-
atography on silica gel eluting with CHCl3–MeOH–NH3
(50 : 10 : 1) followed by CHCl3–MeOH–NH3 (20 : 6 : 1) and
CHCl3–MeOH–NH3 (10 : 4 : 1) to give the diene 14g (25 mg,
68%) as yellow crystals, mp >300 ЊC (darkened above ca.
140 ЊC); Rf 0.28 (10 : 4 : 1, CHCl3–MeOH–NH3); δH(300 MHz;
DMSO-d6; Me4Si) 1.86 (3 H, s, Me), 4.00 (2 H, s, CH2OH), 5.09
Procedure for determination of cytokinin activity
The cytokinin activities of the compounds were determined
using the bioassay described by Letham,26 and in ref. 4.
Acknowledgements
The purchase of the 200, 300 and 500 MHz Bruker Spectrospin
Avance instruments as well as the Siemens SMART diffract-
ometer used in this study was made possible through financial
support from The Research Council of Norway (NFR).
References
(1 H, br s, OH), 6.35 (1 H, d, J 11.2, CH᎐), 6.58 (1 H, d, J 15.5,
᎐
CH᎐), 8.11 (1 H, s, H-8), 8.35 (1 H, dd, J 15.5, J 11.2, ᎐CH) and
᎐
᎐
1 See for instance: S. Matsubara, Crit. Rev. Plant Sci., 1990, 9, 17;
F. B. Salisbury and C. W. Ross, Plant Physiology, 4th edn.,
Wadsworth, Belmont, 1992, Ch. 18; G. Shaw, in Cytokinins:
Chemistry, Activity and Function, eds. D. W. S. Mok and M. C. Mok,
CRD Press, Boca Raton, 1994, Ch. 2.
2 A. H. A. Farooqi, Y. N. Shukla, A. Shukla and D. S. Bhakuni,
Phytochemistry, 1990, 29, 2061; J. S. Dahiya and J. P. Tewari,
Phytochemistry, 1991, 30, 2825; T. Fujii, M. Ohba, T. Haneishi,
S. Matsubara, A. H. A. Farooqi and Y. N. Shukla, Heterocycles,
1992, 34, 21; T. Fujii, M. Ohba, H. Kawamura, T. Haneishi and
S. Matsubara, Chem. Pharm. Bull., 1993, 41, 1362; A. H. A.
Farooqi, Y. N. Shukla, S. Sharma and R. P. Bansal, Plant Growth
Regul., 1994, 14, 109.
3 S. M. Hecht, N. J. Leonard, R. Y. Schmitz and F. Skoog,
Phytochemistry, 1974, 13, 329; C.-m. Chen, O. C. Smith and J. D.
McChesney, Biochemistry, 1975, 14, 3088.
4 A. Bråthe, L.-L. Gundersen, F. Rise, A. B. Eriksen, A. V. Vollsnes
and L. Wang, Tetrahedron, 1999, 55, 211 and references therein.
5 G. Andresen, L.-L. Gundersen and F. Rise, Tetrahedron, 1996, 52,
12979.
10.0 (2 H, br s, 2 × NH); δC(75 MHz; DMSO-d6; Me4Si) 14.6
(Me), 65.4 (CH OH), 118.5 (HC᎐), 120.4 (C-5), 122.0 (᎐CH),
᎐
᎐
2
125.6 (᎐C), 139.0 (᎐CH), 145.3 (C-8), 149.8 (HC᎐), 156.5
᎐
᎐
᎐
(C-2) and 160.0 (C-4); m/z (electrospray) 233.1049 (M + 1.
C11H12N4O2 requires 233.1033).
(E)-1,9-Dihydro-6-(5-hydroxy-4-methylpent-3-en-1-yn-1-yl)-
2H-purin-2-one 14h
To a solution of (E)-1,9-dihydro-1,9-bis[(tert-butyldimethyl-
silyloxy)methyl]-6-(5-tert-butyldimethylsilyloxy-4-methylpent-
3-en-1-yn-1-yl)-2H-purin-2-one 13j (126 mg, 0.20 mmol) in dry
acetonitrile (4 cm3) was added a 1 M solution of tetramethyl-
ammonium fluoride in dry acetonitrile (1.2 cm3). The solution
was stirred under N2 for 24 h at ambient temperature before the
solution was evaporated in vacuo. The product was subjected to
flash chromatography twice on silica gel eluting with CHCl3–
MeOH–NH3 (6 : 3 : 1) the first time and CHCl3–MeOH–NH3
(10 : 4 : 1) the second time to give the enyne 14h (35 mg, 76%) as
yellow crystals, mp >300 ЊC (darkened above 150 ЊC.); Rf 0.16
(10 : 4 : 1, CHCl3–MeOH–NH3); δH(300 MHz; DMSO-d6;
Me4Si) 1.97 (3 H, s, Me), 4.03 (2 H, d, J 5.4, CH2), 5.24 (1 H, t,
6 G. Andresen, L.-L. Gundersen, M. Lundmark, F. Rise and
S. Sundell, Tetrahedron, 1995, 51, 3655.
7 H. Nakamura, H. Yamamoto and H. Nozaki, Tetrahedron Lett.,
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8 W. Biernacki and A. Gdula, Synthesis, 1979, 37.
9 L. A. Paquette, G. Y. Lassalle and C. J. Lovely, J. Org. Chem., 1993,
58, 4254; P. A. Zoretic, Y. Zhang and A. A. Ribeiro, Tetrahedron
Lett., 1996, 37, 1751.
10 R. Baker and J. L. Castro, J. Chem. Soc., Perkin Trans. 1, 1990,
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11 A. R. de Lera, B. Iglesias, J. Rodrígues, R. Alvares, S. Lópes,
X. Villanueva and E. Padrós, J. Am. Chem. Soc., 1995, 117, 8220.
J 5.4, OH), 5.89 (1 H, s, ᎐CH), 8.20 (1 H, s, H-8) and 12.3 (2 H,
᎐
br s, 2 × NH); δC(75 MHz; DMSO-d6; Me4Si) 16.9 (Me), 64.6
᎐
᎐
(CH ), 84.6 (C᎐), 98.5 (C᎐), 100.6 (᎐CH), 125.9 (C-5), 134.1
᎐
᎐
᎐
2
(C-6), 145.8 (C-8), 158.1 (C-2), 159.0 (C-4) and 160.1 (᎐C); m/z
᎐
(electrospray) 231.0877 (M + 1. C11H10N4O2 requires 231.0882).
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672
1671

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Nolsøe, Bioorg. Med. Chem. Lett., 2000, 10, 1207.
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20 N. A. Petasis and I. A. Zavialov, Tetrahedron Lett., 1996, 37,
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22 G. M. Sheldrick, Sadabs, program for absorption correction,
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12 B. H. Lipshutz and J. J. Pegram, Tetrahedron Lett., 1980, 21, 3343.
13 For applications of the SEM-moiety as an N-protecting group, see
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49, 203; M. P. Edwards, A. M. Doherty, S. V. Ley and H. M. Organ,
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McCarty, J. Org. Chem., 1986, 51, 1891; B. H. Lipshutz, W. Vaccaro
and B. Huff, Tetrahedron Lett., 1986, 27, 4095.
14 For synthesis and applications of this reagent for N-protection of
pyrimidinones, see: T. Benneche, L.-L. Gundersen and K. Undheim,
Acta Chem. Scand. Ser. B, 1988, 42, 384.
15 For application of this protecting group in purine chemistry, see:
G. Magnin, J. Dauvergne, A. Burger and J.-F. Biellmann,
Tetrahedron Lett., 1996, 37, 7833; P. Lang, G. Magnin, G. Mathis,
A. Burger and J.-F. Biellmann, J. Org. Chem., 2000, 65, 7825.
16 A. Gogoll, L.-L. Gundersen, F. Rise and M. Valli, Heterocycles,
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25 G. R. Scarlato, J. A. DeMattei, L. S. Chong, A. K. Ogawa, M. R.
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1672
J. Chem. Soc., Perkin Trans. 1, 2001, 1662–1672