Stereoselective radical aryl migrations from sulfur to carbon

Article abstract of DOI:10.1039/a806718j

Stereoselective radical 1,5 aryl migrations from sulfur (in arenesulfonates) to carbon with diastereoselectivities of up to 14:1 are presented.

Full text of DOI:10.1039/a806718j

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Stereoselective radical aryl migrations from sulfur to carbon
Armido Studer*† and Martin Bossart
Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule, ETH-Zentrum, Universitätstrasse 16, CH-8092
Zürich, Switzerland
Stereoselective radical 1,5 aryl migrations from sulfur (in
arenesulfonates) to carbon with diastereoselectivities of up
to 14:1 are presented.
the thienyl transfer (9, 74%, 9:1, entry 4). As a side product, the
corresponding reduced (dehalogenated) sulfonate was always
observed in these aryl migration reactions.
In order to study the 1,2-stereoinduction, sulfonate 11 was
prepared as a 1:1 mixture of diastereoisomers. Aryl migration
under analoguous conditions provided alcohol 12 in 49% yield
(l:u = 7:1, Scheme 2). The relative configuration of the major
isomer was assigned after oxidation (Swern) to the correspond-
ing known12 aldehyde.
C(sp2)–C(sp3) bonds occur in many natural products and new
methods for their stereoselective formation are important. In the
literature, there are only a very few methods for stereoselective
C(sp3)–aryl bond formation. The Heck1 and Michael2 reactions
have to be mentioned at this point. Numerous examples of
radical aryl transfers (C?C,3 N?C,4 O?C5 and S?C6) have
been published, however, we were surprised to find only three
reports of stereoselective radical aryl migrations.7 Herein we
describe highly diastereoselective 1,5 aryl migrations from
sulfur to carbon.
O
O
S
Ph
O
OH
i
I
Motherwell, in his pioneering studies, has shown that
intramolecular ipso substitution in arenesulfonates by aryl
radicals is an efficient method for biaryl synthesis.6 Based on
our work on the stereoselective phenyl migration from Si to C8
we decided to test arenesulfonates as possible ‘arene sources’ in
the intramolecular stereoselective radical ipso substitution
reaction. To this end, arenesulfonates 1–5 were prepared in
moderate to good yields (50–90%) from (like)-4-iodopentan-
2-ol and the corresponding commercially available sulfonyl
chlorides in pyridine.9 The racemic‡ iodo alcohol was easily
prepared from (meso)-pentan-2,4-diol according to established
procedures.10 We were pleased to find that ipso substitution
occurs smoothly (Scheme 1, Table 1). Slow addition of tin
hydride to 1 in refluxing benzene under optimized conditions§
afforded the known11 alcohol 6 in 76% yield with high
selectivity (u:l = 13:1, entry 1). Both electron poor and electron
rich arenes can be stereoselectively transferred. Thus, the
p-fluorophenyl derivative 7 was obtained in 59% yield with a
slightly lower selectivity (10:1, entry 2).¶ In the case of the
electron rich anisyl and dansyl derivatives a lower yield was
observed (8, 50%, 9:1; 10, 52%, 11:1, entries 3 and 5). Even
heteroarenes can be used in the ipso substitution as shown for
11
12 (49%, l : u = 7 : 1)
Scheme 2 Reagents and conditions: i, Bu3SnH, AIBN, syringe pump,
benzene (0.05
M
)
From the stereochemical outcome of the reactions discussed
above, we suggest the following model to explain the observed
selectivities: radical 13 undergoes intramolecular ipso attack at
the aryl group of the sulfonate to form cyclohexadienyl radical
14. Products derived from 1,7 addition were not observed. We
assume that the low energy transition state for the formation of
14 resembles a chair with the substituents in equatorial
positions. Fragmentation (re-aromatization) then affords radical
15 which after SO2 extrusion and reduction leads to the
corresponding alcohol. It is not clear how fast the SO2 extrusion
process is by which the corresponding alkoxyl radical is formed.
However, in the crude product mixture of the aryl migration
reactions, we never observed sulfur-containing products de-
rived from 15; therefore, we assume that the SO2 extrusion is
faster than trapping of the intermediate radical 15 with
Bu3SnH.∑ According to this model, the observed 1,3- (? unlike
products) and 1,2-selectivity (? like product) can be readily
understood.
O
O
S
OH
Aryl
O
i
O
O
O
O
•
S
O
R3
Aryl
S
I
•
Ph
O
O
O
•
S
R1
R3
R1
R3
1–5
6–10
R1
R2
13
O
R2
R2
15
Scheme 1 Reagents and conditions: i, Bu3SnH, AIBN, syringe pump,
benzene (0.03
M)
14
Table 1 Stereoselective aryl transfer from sulfur to carbon
As a first application of this method we studied a one pot
reaction sequence where a radical addition reaction is followed
by a stereoselective phenyl migration. Sulfonate 16 was
prepared from the corresponding homoallylic alcohol and
benzenesulfonyl chloride as described above (43%).9 Radical
acceptor 16 and ethyl iodoacetate (1.5 equiv.) were reacted
under atom transfer conditions13 in benzene [Bu3SnSnBu3
Yield
Product (%)
Ratio
Entry
Sulfonate Aryl
(u:l)a
1
2
3
4
5
1
2
3
4
5
Ph
4-FC6H4
4-MeOC6H4
thienyl
5-Me2N-naphthyl
6
7
8
9
10
76
59
50
74
52
13:1
10:1
9:1
9:1
11:1b
(10%), hn, 300 W sun lamp, 0.1
after dilution (? 0.05 ) was directly transformed upon slow
addition of Bu3SnH (1.8 equiv. over 7 h) and AIBN (0.25
M
] to afford iodide 17, which
M
a Determined by GC analysis. b Determined by 1H NMR spectroscopy.
Chem. Commun., 1998
2127

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(MeLi treatment is not neccessary but advantageous since the tin halide
formed is transformed to the corresponding methylated compound which is
easily removed.)
¶ The relative configurations of the alcohols 7–10, and 18 were assigned by
analogy to 6 based on the characteristic chemical shift of the hydrogen atom
(of the major isomer) at the newly formed stereogenic center.
∑ We believe that the products are formed under kinetic control; however,
Motherwell has shown that SO2 extrusion is rather slow in his systems and
that in the biaryl synthesis the entire process is probably reversible [ref.
6(c)]. Experiments to elucidate the mechanism are planned.
O
O
O
O
S
S
Ph
Ph
O
I
O
i
CO2Et
16
17
ii
OH
Ph
CO2Et
1 M. Shibasaki, in Advances in Metal-Organic Chemistry, ed. L. S.
Liebeskind, JAI, Greenwich, 1996, vol. 5, p. 119.
2 R. E. Gawley and J. Aubé, in Principles of Asymmetric Synthesis, ed.
J. E. Baldwin FRS and P. D. Magnus FRS, Pergamon, 1996, p. 145; N.
Krause, Angew. Chem., Int. Ed., 1998, 37, 283.
18 (24%, u : l = 14 : 1)
Scheme 3 Reagents and conditions: i, Bu3SnSnBu3 (10%), hn, ICH2CO2Et,
benzene (0.1 ); ii, Bu3SnH, AIBN, syringe pump, benzene (0.05 M)
M
3 L. Giraud, E. Lacôte and P. Renaud, Helv. Chim. Acta, 1997, 80, 2148
and references cited therein.
4 E. Lee, H. S. Whang and C. K. Chung, Tetrahedron Lett., 1995, 36,
913.
5 E. Lee, C. Lee, J. S. Tae, H. S. Wang and K. S. Li, Tetrahedron Lett.,
1993, 34, 2343; D. Crich and J.-T. Hwang, J. Org. Chem., 1998, 63,
2765.
equiv.) to 18 (Scheme 3). Hydroxy ester 18 was isolated in 24%
yield (unoptimized) as a 14:1 (u:l) mixture of diastereoisomers.
The intermediate iodide 17 was formed with no selectivity, as
shown in a separate experiment by H NMR analysis of a
sample taken after the iodine transfer reaction.
In summary, we have shown that the intramolecular ipso
substitution is an efficient method for the stereoselective
C(sp2)–C(sp3) bond formation. Since many sulfonyl chlorides
are commercially available, a variety of aryl groups can be
stereoselectively transferred to form products which are
difficult to prepare by any other method.
We are grateful to Professor Dr D. Seebach for generous
financial support and to Professor Dr D. P. Curran for helpful
discussions.
1
6 (a) S. Caddick, K. Aboutayab, K. Jenkins and R. I. West, J. Chem. Soc.,
Perkin Trans. 1, 1996, 675; F. Aldabbagh and W. R. Bowmann,
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Pennell, J. Chem. Soc., Chem. Commun., 1991, 877; M. L. E. N. da
Mata, W. B. Motherwell and F. Ujjainwalla, Tetrahedron Lett., 1997,
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Tetrahedron Lett., 1997, 38, 141; E. Bonfand, W. B. Motherwell,
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Notes and References
8 A. Studer, M. Bossart and H. Steen, submitted for publication.
9 R. S. Tipson, J. Org. Chem., 1944, 9, 235.
10 P. Place, M.-L. Roumestant and J. Goré, Bull. Soc. Chim. Fr., 1976,
169.
11 J. M. Brown and R. G. Naik, J. Chem. Soc., Chem. Commun., 1982,
348.
12 I. Fleming and J. J. Lewis, J. Chem. Soc., Perkin Trans. 1, 1992,
3257.
† E-mail: studer@org.chem.ethz.ch
‡ All the compounds described herein were prepared as racemic mixtures.
In the schemes only one enantiomer is shown.
§ General procedure: Bu3SnH (1.5 equiv.) and AIBN (0.3 equiv.) in
benzene (0.8–1.2
M) were added over 7 h (syringe pump) to a refluxing
solution of the iodide in benzene (0.03
M). After complete addition the
reaction mixture was stirred under reflux for additional 30 min. The mixture
was then allowed to cool to room temperature and MeLi (5 equiv.) was
slowly added. After stirring for 30 min the reaction mixture was hydrolyzed
with saturated aq. NH4Cl. Extraction with Et2O and washing of the organic
phase with brine afforded, after drying (MgSO4) and purification by flash
column chromatography (SiO2, pentane–Et2O), the corresponding alcohol.
13 D. P. Curran, M-H. Chen and D. Kim, J. Am. Chem. Soc., 1989, 111,
6265.
Received in Cambridge, UK, 27th August 1998; 8/06718I
2128
Chem. Commun., 1998