Conjugate addition of allylic and prop-2-ynylic alcohols to 3-halogeno-1-phenylsulfonylprop-1-enes; synthesis and radical induced cyclization of 2-alkenyloxy-3-halogenopropylphenyl sulfones

Article abstract of DOI:10.1039/a705180h

Allylic and prop-2-ynylic alcohols add in a conjugate fashion to 3-halogeno-1-phenylsulfonylprop-1-enes in the presence of KF-basic alumina and the resulting halogenoallyl sulfones can be efficiently cyclized using tributyltin hydride under various conditions.

Full text of DOI:10.1039/a705180h

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Conjugate addition of allylic and prop-2-ynylic alcohols to
3-halogeno-1-phenylsulfonylprop-1-enes; synthesis and radical induced
cyclization of 2-alkenyloxy-3-halogenopropylphenyl sulfones
Riccardo Giovannini and Marino Petrini*
Dipartimento di Scienze Chimiche, Universita` di Camerino, via S. Agostino, 1 I-62032 Camerino, Italy
Allylic and prop-2-ynylic alcohols add in a conjugate fashion
to 3-halogeno-1-phenylsulfonylprop-1-enes in the presence
of KF–basic alumina and the resulting halogenoallyl sul-
fones can be efficiently cyclized using tributyltin hydride
under various conditions.
tuted allylic alcohols (Table 1, entries 8–11) which react poorly
with the bromide derivative 1a. No solvent is required for this
procedure, and the presence of solvents as THF, CH2Cl2 and
Et2O gives rise to complex product mixtures and prolonged
reaction times. Steric crowding around the reaction centre also
has a deleterious effect on reactivity. Every attempt to obtain
addition products from vinyl sulfone 1c results in a fast,
base-assisted dehydrobromination that produces (E)-1-phenyl-
sulfonylbuta-1,3-diene 4 in 40% yield.
The ability of vinyl sulfones to act as two carbon acceptors in
Michael additions is the basis of their widespread use in
synthesis.1 In this context, 3-halogeno-1-alkenyl sulfones 1
A completely different result is observed when short chain
alcohol such as methanol, ethanol or phenol are used. In this
instance an ordinary direct nucleophilic displacement of the
halogen atom occurs, followed by a partial regioisomerisation
of the double bond with consequent formation of products 5 and
6 [eqn. (2)].6
R1 R2
PhSO2
X
1a X = Br, R1 = R2 = H
b X = Cl, R1 = R2 = H
c X = Br, R1 = H, R2 = Me
d X = Br, R1 = R2 = Me
PhSO2
Br
PhSO2
OR
5
+
1a
+
ROH
KF–Al2O3
(2)
possess two electrophilic adjacent carbon atoms in their
structure and therefore conjugate additions would compete with
direct SN2 displacements of the halogen atom. Allylic and aryl
Grignard reagents are able to attack the double bond of 1a and
ultimately lead to substituted cyclopropanes via a subsequent
nucleophilic displacement of the bromide anion.2 On the
contrary, sodium enolates afford direct substitution products
when reacted with 1a.3
The behaviour of these systems towards different nucleo-
philes has been studied in great detail by Bordwell and co-
workers.4 They showed that weakly basic nucleophiles react
with primary halogeno derivatives 1a,b giving exclusively
direct substitution products arising from an SN2 process.
Michael adducts are obtained only when tertiary halogeno
derivative 1d, which is almost unreactive towards SN2 substitu-
tions, reacts with sodium methoxide in MeOH.4b
OR
2 h, room temp.
PhSO2
R = Me, Et, Ph
6
The allylic ethers 3 prepared by this procedure were
recognized immediately as ideal candidates for the synthesis of
a tetrahydrofuran moiety via a radical cyclization route [eqn.
(3)].7 Ring closure of compound 3 under standard conditions
R
R
X
Bu3SnH
(3)
method A or B
O
O
PhSO2
PhSO2
3
7
We report here that allylic, prop-2-ynylic and benzylic
alcohols efficiently add to the double bond of vinyl sulfones
1a,b in the presence of KF–basic alumina [eqn. (1)].5 The
(Bu3SnH, AIBN catalytic, benzene at reflux)§ gives the
corresponding 2,4-disubstituted tetrahydrofuran derivatives 7
Table 1 Products and yields of the reaction between vinyl sulfones 1 and
alcohols 2 in the presence of KF–basic alumina without solvent at room
temperature
PhSO2
R
X
1a,b
O
X
R
KF–Al2O3
PhSO2
(1)
+
2 h, room temp.
OH
Vinyl
Entry
sulfone
Alcohol 2
Product
Yield (%)
2
3
1
2
3
4
5
6
7
8
9
1a
1b
1a
1b
1a
1b
1a
1b
1b
1b
1b
CH2NCHCH2OH
CH2NCHCH2OH
CH·CCH2OH
3a
3b
3c
3d
3e
3f
3g
3h
3i
80
75
78
73
55
71
77
70
80
83
65
reaction is carried out under heterogeneous conditions by
simply mixing the vinyl sulfone 1 with the appropriate alcohol
and adding the solid base at room temperature.† The corre-
sponding adducts are usually obtained in satisfactory yields
upon extraction with CH2Cl2 and purification by column
chromatography (Table 1).‡ The yields of these adducts
obtained starting from bromide 1a are generally comparable
with those attained using chloride 1b, especially when simple
allylic and prop-2-ynylic alcohols are used (Table 1, entries
1–4). Chloride 1b displays enhanced reactivity towards substi-
CH·CCH2OH
BnOCH2C·CCH2OH
BnOCH2C·CCH2OH
BnOH
PhCHNCHCH2OH
EtCHNCHCH2OH
2-(furyl)CH2OH
Me2CNCHCH2OH
10
11
3j
3k
Chem. Commun., 1997
1829

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Table 2 Products and yields of the radical cyclization of unsaturated
sulfones 3 in the presence of Bu3SnH
O
O
SO2Ph
SO2Ph
8
8a
trans:cis
Tetrahydrofuran
7
ratio
(method)a
Yield
(%)
Scheme 1
Entry
1
Sulfone
The authors thank the University of Camerino for financial
assistance.
Me
3a
68:32 (A)
86:14 (B)b
92
88
PhSO2
O
Footnotes and References
* E-mail: petrini@camserv.unicam.it
† Typical experimental procedure for Michael addition: Vinyl sulfone 1 (5
mmol) was mixed with the appropriate alcohol 2 (15 mmol) and cooled to
0 °C. KF–basic alumina (1 g) was added, the mixture was shaken vigorously
for 5 min and then left to stand for 2 h at room temperature. After this time,
the mixture was washed with CH2Cl2 (5 3 10 ml) and, after evaporation of
the solvent at reduced pressure, the crude product was purified by column
chromatography.
2
3
3c
3e
(A)
88
PhSO2
O
OBn
55:45 (A)c
60:40 (B)b,c
50
83
PhSO2
PhSO2
‡ Selected data for 3b: oil, nmax/cm21 3060, 1600, 1290, 1130; dH (300
MHz, CDCl3) 3.47 (2 H, dd, J 1.5, 6.3), 3.66 (2 H, dd, J 1.4, 4.5), 3.94–4.05
(2 H, m), 4.12–4.20 (1 H, m), 5.11–5.20 (2 H, m), 5.62–5.78 (1 H, m),
7.52–7.67 (3 H, m), 7.91–7.95 (2 H, m); m/z 181, 141, 77, 75. For 3c: oil,
nmax/cm21 3260, 2100, 1290, 1140; dH 2.46 (1 H, t, J 2.4), 3.49 (2 H, d, J
5.1), 3.60 (2 H, d, J 4.8), 4.17 (2 H, d, J 2.4), 4.32–4.37 (1 H, m), 7.53–7.68
(3 H, m), 7.91–7.96 (2 H, m); m/z 317 (M+), 223, 141, 125, 77, 51, 39. For
7a: mp 39 °C; nmax/cm21 3050, 1580, 1290, 1130; dH 1.00 (3 H, d, J 6.8),
1.73–1.90 (2 H, m), 2.28–2.31 (1 H, m), 3.21–3.45 (3 H, m), 3.94–3.92 (1
H, m), 4.35–4.41 (1 H, m), 7.51–7.65 (3 H, m), 7.89–7.92 (m, 2 H); dC
17.75, 18.04, 33.38, 33.64, 40.07, 41.38, 61.88, 62.17, 72.98, 73.93. 75.14,
75.48, 128.55, 129.66, 134.17, 140.41; m/z 240 (M+), 98, 85, 77.
§ Typical experimental procedure for ring closure of compounds 3: Method
A: Bu3SnH (1.5 mmol) and AIBN (0.15 mmol) were added to a benzene
solution (0.06 m) of compound 3 (1 mmol). The mixture was refluxed for 1
h and then the solvent was evaporated at reduced pressure. The oily residue
was taken up in Et2O (40 ml) and washed with aqueous 10% KF. Usual
work up gave the crude product, which is purified by column chromatog-
raphy.
O
Bn
4
5
6
3h
3i
85:15 (A)
90:10 (B)b,d
75
78
O
Pr
73:27 (A)
80:20 (B)b
83
90
PhSO2
PhSO2
O
Pri
3k
66:34 (A)
77:23 (B)b
85
88
O
a Method A: Bu3SnH, AIBN, benzene at reflux. Method B: Bu3SnH, Et3B,
O2, 278 °C. b Cyclization is conducted on the iodide obtained by refluxing
the corresponding halide with sodium iodide in acetone. c This ratio refers
to the E/Z stereoisomers. d Reaction conducted at room temperature.
Method B: Bu3SnH (1.5 mmol) and BEt3 (0.3 mmol) were added to a
CH2Cl2 solution (0.05 m) of compound 3. The mixture was cooled to
278 °C and then O2 (8 ml) was slowly (45 min) bubbled through the
mixture via a syringe. After 1 h the mixture was warmed, the solvent was
evaporated and the residue was worked up as described in method A.
as a diastereoisomeric mixture, usually in good yields (Table 2,
method A).‡ These diastereoisomers are inseparable by stan-
dard chromatographic techniques, but a survey of available
literature data on similar compounds allowed us to assign the
trans configuration to the major component of the mixture.8 It
is known that radical cyclizations of monohalogeno derivatives
of type 7 proceed following a chair-like transition state in which
the phenylsulfonylmethyl group and the alkene prefer an
equatorial orientation 8 (Scheme 1) that produces the trans
isomer.9 The diastereoselectivity obtainable in refluxing ben-
zene is, however, rather poor as witnessed for the cyclization of
compound 3a (Table 2, entry 1, method A, trans:cis 68:32).
Better results are achieved using BEt3 initiator (Bu3SnH, BEt3,
O2, CH2Cl2, method B),§ which permits rapid cyclization even
at very low temperatures (278 °C).10 In this way the
diastereoisomeric ratio can be substantially improved for ring
closure of 3a (Table 2, entry 1, method B, trans:cis 86:14),
although in other entries (Table 2, entries 4–6) this gain in
diastereoselectivity is rather small, as the isomeric ratio is
already quite satisfactory even with method A. The cyclization
of alkyne derivative 3e proceeds with a low degree of
stereoselectivity (Table 2, entry 3). This is not surprising since
the stereochemistry of compound 7e is governed by the topicity
of the hydrogen abstraction, in which the intermediate alkenyl
radical is involved.11
1 N. S. Simpkins, Sulphones in Organic Synthesis, Pergamon, Oxford,
1993; N. S. Simpkins, Tetrahedron, 1990, 46, 6951; P. L. Fuchs and
T. F. Braish, Chem. Rev., 1986, 86, 903.
2 J. J. Eisch and J. E. Galle, J. Org. Chem., 1979, 44, 3277.
3 Y. Masuyama, K. Yamada, H. Tanaka and Y. Kusuru, Synth. Commun.,
1987, 17, 1525.
4 (a) F. G. Bordwell and T. G. Mecca, J. Am. Chem. Soc., 1972, 94, 5829;
(b) F. G. Bordwell and G. A. Pagani, J. Am. Chem. Soc., 1975, 97,
118.
5 KF–basic alumina was prepared according to: D. E. Bergbreiter and
J. J. Lalonde, J. Org. Chem., 1987, 52, 1601; Review: G. W. Kabalka
and R. M. Pagni, Tetrahedron, 1997, 53, 7999.
6 B. M. Trost and M. R. Ghadiri, Bull. Soc. Chim. Fr., 1993, 130, 433.
7 D. P. Curran, N. A. Porter and B. Giese, Stereochemistry of Radical
Reactions: Concepts, Guidelines and Synthetic Applications, VCH,
Weinheim, 1996; D. P. Curran, in Comprehensive Organic Synthesis,
ed. B. M. Trost, I. Fleming and M. F. Semmelhack, Pergamon, Oxford,
1991, p. 799; B. Giese, Radicals in Organic Synthesis: Formation of
Carbon–Carbon Bonds, Pergamon, Oxford, 1986.
8 E. Montaudon, X. Lubeight and B. Maillard, J. Chem. Soc., Perkin
Trans 1, 1991, 1531.
9 A. L. J. Beckwith, C. J. Easton, T. Lawrence and A. K. Serelis, Aust.
J. Chem., 1983, 36, 545; D. C. Spellmeyer and K. N. Houk, J. Org.
Chem., 1987, 52, 959; Y. Watanabe and T. Endo, Tetrahedron Lett.,
1988, 29, 321; V. H. Rawal, S. P. Singh, C. Dufour and C. Michoud,
J. Org. Chem., 1993, 58, 7718.
10 K. Miura, Y. Ichinose, K. Nozaki, K. Fugami, K. Oshima and
K. Utimoto, Bull. Chem. Soc. Jpn., 1989, 42, 143.
11 T. Ooi, Y. Hokke and K. Maruoka, Angew. Chem., Int. Ed. Engl., 1997,
36, 1181; B. Giese, J. A. Gonzalez-Gomez, S. Lachhein and J. O. Metz-
ger, Angew. Chem., Int. Ed. Engl., 1987, 26, 479.
In conclusion, a chemoselective conjugate addition of
unsaturated alcohols to 3-halogenovinyl sulfones has been
accomplished using KF–basic alumina as the basic medium.
The resulting adducts can be stereoselectively cyclized by a
radical process, affording functionalized 2,4-disubstituted tetra-
hydrofurans that are suitable for further transformations.
Received in Cambridge, UK, 21st July 1997; 7/05180H
1830
Chem. Commun., 1997