Highly diastereoselective allylation reactions of dilithiated 4-(phenylsulfonyl)-cyclopent-2-enol

Article abstract of DOI:10.1016/j.tetlet.2009.10.074

A two-step synthesis of 4-(phenylsulfonyl)cyclopent-2-enol using epoxide ring-opening and ring-closing alkene metathesis is described. Treatment of the dianion of 4-(phenylsulfonyl)cyclopent-2-enol with allylic bromides gave the corresponding alkylated products with excellent to complete diastereoselectivity.

Full text of DOI:10.1016/j.tetlet.2009.10.074

Tetrahedron Letters 51 (2010) 99–101
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly diastereoselective allylation reactions of dilithiated
4-(phenylsulfonyl)-cyclopent-2-enol
*
Donald Craig , Pengfei Lu, Andrew J. P. White
Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A two-step synthesis of 4-(phenylsulfonyl)cyclopent-2-enol using epoxide ring-opening and ring-closing
alkene metathesis is described. Treatment of the dianion of 4-(phenylsulfonyl)cyclopent-2-enol with
allylic bromides gave the corresponding alkylated products with excellent to complete
diastereoselectivity.
Received 28 September 2009
Revised 15 October 2009
Accepted 19 October 2009
Available online 22 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Coordination
Cyclopentene
Diastereoselective alkylation
Diene
Ring-closing metathesis
Cyclopentenes continue to be the subject of significant research
interest,1–3 which stems from their importance both in synthesis
method development and as intermediates in natural product syn-
thesis.4–7 Amongst the many methods developed for the assembly
of cyclopentenes, ring-closing metathesis (RCM) is one of the most
attractive options.8–12 In connection with studies of ring-rear-
rangement metathesis (RRM) reactions of cyclopentenes for the
synthesis of substituted cyclohexenes, we became interested in
the lithiation and stereoselective allylation of 4-(phenylsulfo-
nyl)cyclopent-2-enol 1. Our intention was to convert the allylated
congeners of 1 into their cyclohexene isomers using RRM (Scheme
1). This Letter describes highly the diastereoselective allylation
reactions of 1, and provides further examples of chirality transfer
in the ring-opening reactions of strained heterocycles by sulfone-
stabilised carbanionic nucleophiles.
Initial attempts to make 1 involved the reaction of lithiated ally-
lsulfonylbenzene 2 with butadiene monoxide 3; the anticipated
diene product would be subjected to ring-closing alkene metathe-
sis to provide the cyclopentene. However, under the conditions
shown, a 1.7:1 mixture (determined by 1H NMR analysis) of vinylic
sulfones 4 and 5 was formed (Scheme 2).13 Although the double-
bond stereochemistry was not rigorously proved, the assignment
of E-geometry followed from our previous studies of vinylic sulf-
ones possessing methyl groups in the b-position;14 similar results
were reported by Cheng et al.15 This unwanted double bond migra-
tion was suppressed effectively by the introduction of a conjugat-
ing group at the c-position of the sulfone nucleophile: treatment of
3 with lithiated cinnamylsulfonylbenzene 6 gave a 3.5:1 mixture of
allylic sulfones 7a,b and 8 in 80% combined yield.16 This indicates
significantly enhanced regioselectivity in the reaction with 3 of the
more sterically demanding nucleophile Li-6 compared with Li-2.
Compound 7 was formed as a 3:1 mixture of diastereoisomers.
Assignment of the structure 7a to the major isomer followed from
the conversion, using Grubbs’ second-generation catalyst, of the
3:1 mixture of 7 into a 3:1 mixture of 1, the major component of
which was identical to syn-4-(phenylsulfonyl)cyclopent-2-enol
formed in 42% yield by the Pd(0)-catalysed reaction of sodium phe-
nylsulfinate with cyclopentadiene monoxide.17,18 The predominant
formation of 7a may be rationalised in terms of the minimisation
of steric interactions between the phenylsulfonyl and vinyl groups
in the nucleophile and electrophile, respectively. In contrast, regio-
isomer 8 was formed with complete diastereoselectivity (Scheme
2). We have assigned the structure shown since it would arise
via the less sterically congested transition state in a manner similar
to 7a; additionally, the stereochemistry shown corresponds to that
observed in our studies of reactions of lithio-6 with a vinylaziri-
dine, where the adduct structure was unequivocally assigned by
X-ray crystallographic analysis.19 As regioisomers 7 and 8 were dif-
ficult to separate on large scales, a procedure was developed
whereby the crude reaction mixture of 7a,b and 8 was subjected
directly to the subsequent RCM step: 1 was obtained as a 3:1 sy-
n:anti mixture (determined by 1H NMR spectroscopic analysis) in
54% overall yield starting from 45 g of 6.
Next,
a-alkylation reactions of the cyclopentenols 1 were inves-
* Corresponding author.
tigated. Exposure of the 3:1 mixture of syn and anti 1 to a twofold
E-mail address: d.craig@imperial.ac.uk (D. Craig).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.074

100
D. Craig et al. / Tetrahedron Letters 51 (2010) 99–101
PhSO2
PhSO2
OH
OH
OH
PhSO2
OH
PhSO2
1
Scheme 1.
PhSO2
PhSO2
OH
PhSO2
PhSO2
PhSO2
OH
n
BuLi (1.0 equiv), THF
O
+
then
3
4 (29%)
5 (17%)
2
−20 →rt, 2.5 h
ºC
PhSO2
OH
OH
n
BuLi (1.0 equiv), THF
+
then 3
−20 →rt, 1.75 h
ºC
Ph
Ph
Ph
8 (18%; >99:1 d.r.)
6
7a,b (62%; 3:1 syn:anti)
O
PhSO2
OH
Grubbs' 2nd-generation catalyst (0.005
equiv.), CH2Cl2, reflux, 30 min
H
H
H
H
PhSO2
OH
54% from 6
PhSO2
Ph
7a
Ph
1 (3:1 syn:anti
)
Scheme 2.
excess of nBuLi was followed by the addition of one equivalent of
electrophile. Allylation reactions of the dianion of 1 were found
to be highly or completely stereoselective in the four cases studied.
Doubly deprotonated 1 reacted smoothly with 3-bromo-1-propene
to give a 10:1 mixture of cyclopentenols 9a. Similar reactions using
(E)-1-bromo-2-butene and (E)-(3-bromoprop-1-enyl)benzene
were observed, giving 9b and 9c, respectively; in these cases com-
plete stereoselectivity was observed. Combination of dilithiated 1
with (E)-1-bromo-3-methyl-2-butene gave a single, crystalline
substitution product 9d. X-ray crystallographic analysis showed
that allylation had occurred anti to the hydroxy group, and this ste-
reochemistry was inferred also for the major/exclusive products
from the other three reactions (Scheme 3). In no case were any
by-products detected corresponding to the conjugate elimination
from the dianion of 1.
The selectivity observed in these processes is striking. This may
be a consequence of simple steric hindrance, where the electro-
phile approaches a planar20 allylic sulfone
a-carbon atom in an anti
sense with respect to the solvated, and therefore bulky lithiated
oxygen atom. Alternatively, the geometry of the carbanionic centre
may deviate significantly from planar geometry, with the alkoxyli-
thium moiety internally coordinated via a PhSO2 oxygen–lithium
interaction.21–25 The molecular structure of 9d provided some sup-
port for the latter hypothesis, showing an intramolecular hydro-
gen-bond between the pro-S sulfone oxygen atom [with respect
to the (1R,4S) enantiomer shown] and the alcohol –OH (Fig. 1).26
This suggests that an analogous S@OÁ Á ÁLi–O interaction would be
feasible if the dianion of 1 were significantly pyramidalised.20
In summary, we have developed a facile two-step sequence for
the synthesis of 4-(phenylsulfonyl)cyclopent-2-enol
1 using
R1
R2
nBuLi (2.0 equiv), THF
then R1R2C=CHCH2Br
PhSO2
OH
PhSO2
OH
1 (3:1 syn:anti )
R1 = R2 = H
61%
−20 ºC→rt, 1.5−2.5 h
9a:
9b:
9c:
9d:
R1 = H; R2 = Me 67%
R1 = H; R2 = Ph
49%
40%
R1 = R2 = Me
Scheme 3.

D. Craig et al. / Tetrahedron Letters 51 (2010) 99–101
101
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13. 1H NMR data for vinylic sulfones: Compound 4: dH (270 MHz, CDCl3) 7.86–7.79
(2H, m, ortho PhSO2), 7.65–7.45 (3H, m, para and meta PhSO2), 7.12 (1H, q, J
7.0 Hz, CH@CSO2Ph), 5.86–5.72 (1H, m, CH2@CHCHOH), 5.21 (1H, d, J 18.0 Hz,
cis CHH@CH), 5.07 (1H, d, J 11.0 Hz, trans CHH@CH), 4.12–4.30 (1H, m, CHOH),
2.44–2.38 (2H, m, CH2CHOH), 1.89 (3H, d, J 7.0 Hz, Me), 1.20 (1H, br s, OH); 5:
dH (500 MHz, CDCl3) 7.90–7.87 (2H, m, ortho PhSO2), 7.64 (1H, m, para PhSO2),
7.56–7.53 (2H, m, meta PhSO2), 7.16 (1H, q, J 7.0 Hz, CH@CSO2Ph), 5.71–5.64
(1H, m, CH2@CH), 4.96 (1H, dd, J 10.0, 1.5 Hz, trans CHH@CH), 4.79 (1H, dd, J
17.0, 1.5 Hz, cis CHH@CH), 3.79 (2H, d, J 7.5 Hz, CH2OH), 3.53 (1H, dt, J 14.5,
7.5 Hz, CHCH2OH), 1.95 (3H, d, J 7.0 Hz, CH3), 1.28–1.18 (1H, m, OH).
14. Craig, D.; Ikin, N. J.; Mathews, N.; Smith, A. M. Tetrahedron 1999, 55, 13471.
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16. 1H NMR data for 7a: dH (270 MHz, CDCl3) 7.83 (2H, d, J 8.0 Hz, ortho PhSO2), 7.60
(1H, t, J 8.0 Hz, para PhSO2), 7.54 (2H, t, J 8.0 Hz, meta PhSO2), 7.26–7.24 (5H, m,
PhCH), 6.30 (1H, d, J 16.0 Hz, PhCH@CH), 5.99–5.82 (2H, m, PhCH@CH and
CH2@CH), 5.23 (1H, dd, J 16.0, 5.5 Hz, cis CHH@CH), 5.13 (1H, dd, J 10.5, 5.5 Hz,
trans CHH@CH), 4.13–4.03 (2H, m, CHSO2Ph and CHOH), 2.33 (1H, ddd, J 20.5,
11.0, 3.0 Hz, CHHCHOH), 1.96 (1H, ddd, J 20.5, 11.0, 3.0 Hz, CHHCHOH), 1.55-
1.52 (1H, d, J 3.5 Hz, OH).
17. (a) Crandall, J. K.; Banks, D. B.; Colyer, R. A.; Watkins, R. J.; Arrington, J. P. J. Org.
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18. 1H NMR data for syn-1: dH (270 MHz, CDCl3) 7.90 (2H, d, J 7.0 Hz, ortho PhSO2),
7.67 (1H, t, J 7.0 Hz, para PhSO2), 7.57 (2H, t, J 7.0 Hz, meta PhSO2), 6.36–6.35
(1H, m, CH@CHCHOH), 5.74–5.73 (1H, m, CH@CHCHOH), 4.72–4.70 (1H, m,
CHSO2Ph), 4.16–4.01 (1H, m, CHOH), 2.26–2.21 (2H, m, CH2).
19. Carballares, S.; Craig, D.; Hyland, C. J. T.; Lu, P.; Mathie, T.; White, A. J. P. Chem.
Commun. 2009, 451.
Figure 1. The molecular structure of ( )-9d. The O–HÁ Á ÁO hydrogen bond (a) has
OÁ Á ÁO and HÁ Á ÁO separations of 2.9949(18) and 2.16 Å, respectively, with an
O–HÁ Á ÁO angle of 154°.
epoxide ring-opening and ring-closing alkene metathesis as the
key steps. The dilithio dianion of 1 undergoes highly diastereose-
lective allylation reactions, the selectivity of which may be ex-
plained in terms of a planar, solvated or pyramidalised, internally
coordinated sulfone
a-carbanion. In addition, the stereoselective
formation of 7 and 8 in the reaction of Li-6 with 3 demonstrates
that as with the analogous aziridines, chirality transfer may be
achieved in the ring-opening reactions of epoxides by sulfone-sta-
bilised carbanions.
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7059.
Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.10.074.
References and notes
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a = 17.906(4), b = 6.3895(18), c = 12.901(4) Å, b = 99.06(2)°, V = 1457.6(7) Å3,
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Z = 4, Dcalcd = 1.332 g cmÀ3 ) = 2.012 mmÀ1, T = 173 K, colourless block-
, l(Cu-Ka
like needles, Oxford Diffraction Xcalibur PX Ultra diffractometer; 2803
independent measured reflections (Rint = 0.0314), F2 refinement, R1(obs) =
0.0313, wR2(all) = 0.0931, 2362 independent observed absorption-corrected
reflections [|Fo| > 4r(|Fo|), 2hmax = 142°], 188 parameters. CCDC 749015.