Diastereoselective allylation of aldehydes with an enantiopure 2-sulfinylallyl halide under environmentally friendly barbier-type conditions

Article abstract of DOI:10.1021/ol991412j

(Formula presented) A simple, efficient, and diastereoselective zinc-promoted allylation of aldehydes with enantiopure (S_S)-3-chloro-2-(p-tolylsulfinyl)-1-propene [(S_S)-1] under aqueous Barbier conditions is described. The observed d

Full text of DOI:10.1021/ol991412j

ORGANIC
LETTERS
2000
Vol. 2, No. 4
547-549
Diastereoselective Allylation of
Aldehydes with an Enantiopure
2-Sulfinylallyl Halide under
Environmentally Friendly Barbier-Type
Conditions
,†
Francesc Ma´rquez,†,‡ Amadeu Llebaria,‡ and Antonio Delgado*
Facultat de Farma`cia, Unitat de Qu´ımica Farmace`utica, UniVersitat de Barcelona,
AVgda. Joan XXIII, s/n, 08028 Barcelona, Spain, and Departament de Qu´ımica
Orga`nica Biolo`gica, Institut d'InVestigacions Qu´ımiques i Ambientals de Barcelona
(IIQAB-C.S.I.C), Jordi Girona 18-26, 08034 Barcelona, Spain
adcqob@cid.csic.es
Received December 31, 1999
ABSTRACT
A simple, efficient, and diastereoselective zinc-promoted allylation of aldehydes with enantiopure (SS)-3-chloro-2-(p-tolylsulfinyl)-1-propene
[(SS)-1] under aqueous Barbier conditions is described. The observed diastereoselectivity can be explained via an acyclic antiperiplanar transition
state model.
The allylation of carbonyl derivatives to afford homoallylic
alcohols is a useful synthetic transformation that has attracted
considerable attention over the past few years.1 Recently,
much effort has been devoted to the development of new
methods for enantioselective carbonyl allylation by means
of either enantiopure allylmetal derivatives2 or asymmetric
Lewis acid catalysis.3 However, reports on enantioselective
carbonyl allylations in aqueous medium are limited,4 despite
the increasing demand for clean and environmentally safe
chemical technologies and the availability of well-prece-
dented methodology enabling the combination of water with
different organometallic systems.5
Our interest in the development of new building blocks
based on the use of sulfoxides as chiral auxiliaries6 prompted
us to focus on enantiopure (S)-3-chloro-2-(p-tolylsulfinyl)-
† Universitat de Barcelona.
‡ Institut d'Investigacions Qu´ımiques i Ambientals de Barcelona.
(1) For reviews, see: (a) Roush, W. R. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991;
Vol. 2; pp 1-53. (b) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207-
2293.
1997, 62, 2322-2323. Allyl titanates: (h) Riediker, M.; Duthaler, R. Angew.
Chem., Int. Ed. Engl. 1989, 494-495. (i) Hafner, A.; Duthaler, R.; Marti,
R.; Rihs, G.; Rothestreit, P.; Schwarzenbach, F. J. Am. Chem. Soc. 1992,
114, 2321-2336.
(2) Allylboronates: (a) Roush, W. R.; Hoong, L. K.; Palmer, M. A.;
Park, J. C. J. Org. Chem. 1990, 55, 4109-4117. (b) Roush, W. R.; Ando,
K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L. J. Am. Chem. Soc.
1990, 112, 6339-6348. (c) Roush, W. R.; Hoong, L. K.; Palmer, M. A.;
Straub, J. A.; Palkowitz, A. D. J. Org. Chem. 1990, 55, 4117-4126.
Allylstannanes: (d) Boldrini, G. P.; Tagliavini, E.; Trombini, C.; Umaniron-
chi, A. J. Chem. Soc., Chem. Commun. 1986, 685-686. (e) Costa, A. L.;
Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. J. Am. Chem.
Soc. 1993, 115, 7001-7002. Allylzinc: (f) Cozzi, P. G.; Orioli, P.;
Tagliavini, E.; Umanironchi, A. Tetrahedron Lett. 1997, 38, 145-148.
Allylchromium: (g) Sugimoto, K.; Aoyagi, S.; Kibayashi, C. J. Org. Chem.
(3) (a) Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993,
115, 8467-8468. (b) Bedeschi, P.; Casolari, S.; Costa, A. L.; Tagliavini,
E.; Umanironchi, A. Tetrahedron Lett. 1995, 36, 7897-7900. (c) Cozzi, P.
G.; Tagliavini, E.; Umanironchi, A. Gazz. Chim. Ital. 1997, 127, 247-
254. (d) Marshall, J. A.; Palovich, M. R. J. Org. Chem. 1998, 63, 4381-
4384.
(4) Loh, T. P.; Zhou, J. R. Tetrahedron Lett. 1999, 40, 9115-9118.
(5) (a) Lubineau, A.; Auge´, J.; Queneau, Y. Synthesis 1994, 741-760.
(b) Lubineau, A. Chem. Ind. 1996, 4, 123-126. (c) Li, C. J. Tetrahedron
1996, 52, 5643-5668. (d) Li, C.-J.; Chan, T.-H. Organic Reactions in
Aqueous Media; John Wiley & Sons: New York, 1997.
10.1021/ol991412j CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/03/2000

1-propene ((SS)-1)7 and to study its application to the
diastereoselective synthesis of 2-sulfinyl-2-propenylmetha-
nols 3 using environmentally friendly protocols. The versatil-
ity of this strategy relies on both the diversity of commer-
cially available starting aldehydes and the synthetic potential
of the vinylsulfinyl moiety.8
Preliminary studies were carried out with benzaldehyde
and racemic 3-halo-2-(phenylsulfinyl)-1-propenes (()-4a9 or
(()-4b10 and under In- or Zn-promoted Barbier-type ally-
lations in different solvent systems (Table 1).11
out to be more efficient in terms of diastereoselectivity,
overall yields, and reaction rates.13 Allylation with (()-4a
and Zn in 6/1 saturated aqueous NH4Cl/THF afforded
homoallylic alcohol 5a in high yield and moderate diastereo-
selectivity (entry 4). The use of iodide (()-4b increased the
diastereoselectivity, at the expense of the reaction yield (entry
5). This moderate yield can be attributed, in part, to the
unstability of the starting iodide under the reaction conditions.
Interestingly, both yield and diastereoselectivity could be
optimized using (()-4a in the presence of an excess of iodide
(entry 6). It is conceivable that iodide (()-4b, or a related
species, can be formed in situ under the above conditions.
Enantiomerically pure 2-sulfinylallyl chloride (SS)-1 behaved
similarly to (()-4a, giving 3a (3:1 diastereomeric mixture)
in high yield (entry 7). It is noteworthy that the diastereo-
selectivity of this process could be further increased up to
6:1 by carrying out the reaction at 0 °C in the presence of
excess iodide (entry 9). These conditions were further applied
to a range of aldehydes 2a-g as shown in Table 2.14
Table 1. Allylation of Benzaldehyde with
2-Arylsulfinyl-3-halo-1-propenes
Table 2. Allylation of Aldehydes with (SS)-1
entry
halide
metal
systema
condb
drc
yieldd,e
1
2
3
4
5
6
7
8
9
(()-4a
(()-4a
(()-4a
(()-4a
(()-4b
(()-4a
(Ss)-1
(Ss)-1
(Ss)-1
In
In
In
Zn
Zn
Zn
Zn
Zn
Zn
A
B
C
D
D
E
D
D
E
72; rt
24; rt
15; rt
4; rt
3:1
4:1
5:1
4:1
6:1
5:1
3:1
4:1
6:1
59d
74d
60e
89d
40d
82d
85e
83d
80d
1; rt
18; rt
16; rt
24; 0
24; 0
entry
R
drb
6:1
5:1
3:1
5:1
5:1
4:1
2:1
yieldc
1
2
3
4
5
6
7
a
b
c
d
e
f
Ph
80d
60
67
60
70
60
75
cyclohexyl
n-Bu
a Solvent system: A, THF; B, THF-H2O (1:1); C, H2O; D, saturaed
aqueous NH4Cl/THF (6:1); E, NaI (3 equiv.), 1.6 N aqueous NH4I/THF
(6:1). b Conditions: reaction time (h); temperature (°C). c Diastereomeric
ratio calculated by 1H NMR. d Isolated. e Calculated by 1H NMR in the
presence of dimethyl terephthalate as an external standard.
t-Bu
p-(OCH)3Ph
2-furyl
BnOCH2-
g
a Zn (2 equiv)/NaI (3 equiv)/1.6 N aqueous NH4I/THF (6:1); 0 °C. For
a detailed experimental procedure, see ref 14. b Calculated by 1H NMR.
c Calculated by 1H NMR in the presence of dimethyl terephthalate as an
external standard. d Isolated yield.
Indium-promoted allylations with (()-4a took place in a
variety of H2O-THF mixtures in moderate yields and
diastereoselectivities (entries 1-3).12,13 The use of Zn turned
The configuration of the new stereogenic center in the
major diastereomer of homoallylic alcohols 3a,b was as-
signed as R from ozonolysis15 to the corresponding enan-
tiopure â-hydroxyacid and comparison with reported litera-
(6) (a) Villar, J. M.; Delgado, A.; Llebaria, A.; Moreto, J. M. Tetrahe-
dron: Asymmetry 1995, 6, 665-668. (b) Villar, J. M.; Delgado, A.; Llebaria,
A.; Moreto´, J. M.; Molins, E.; Miravitlles, C. Tetrahedron 1996, 52, 10525-
10546. (c) Henrich, M. L.; Delgado, A.; Molins, E.; Roig, A.; Llebaria, A.
Tetrahedron Lett. 1999, 40, 4259-4262. For a review on applications of
sulfoxides to asymmetric synthesis, see: Carren˜o, M. C. Chem. ReV. 1995,
95, 1717-1760.
(7) Prepared as follows: A solution of (SS)-2-(p-tolylsulfinyl)-1-propen-
1-ol20 (1.1 g, 5.6 mmol) in anhydrous DMF (8 mL) under argon is treated
at 0 °C with Et3N (63 mg, 6.2 mmol) and methanesulfonyl chloride (705
mg, 6.2 mmol). The reaction mixture is allowed to warm to room
temperature and monitored by TLC (CH2Cl2/MeOH 97:3) untilthe starting
alcohol is not detected. The mixture is next diluted with additional anhydrous
DMF (10 mL), and LiCl (952 mg, 22.4 mmol) is added portionwise. Stirring
at room temperature is continued until TLC monitoring indicates total
consumption of the intermediate mesylate. The reaction mixture is then
evaporated to dryness, and the oily residue is taken up in ether and washed
with brine. Drying of the organic phase (anhydrous Na2SO4) and evaporation
afforded a crude that was flash-chromatographed (hexanes-EtOAc 85:15)
to afford allylic chloride (SS)-1 in 65% yield: [R]25D +128 (c, 0.68 MeOH);
1H NMR (CDCl3) 2.38 (3H), 3.79 (1H, J ) 14.5; J′ ) 1.2; J′′ ) 0.9), 4.10
(1H, J ) 14.5; J′ ) 1.6; J′′ ) 1.0), 5.99 (1H), 6.22 (1H), 7.29 (2H), 7.49
(2H); 13C NMR (CDCl3) 150.7, 142.4, 138.3, 130.2, 125.1, 120.5, 39.0,
21.4.
(8) For synthetic applications of closely related (()-3-halo-2-sulfonyl-
1-propenes, see: (a) Knochel, P.; Normant, J. F. Tetrahedron Lett. 1985,
26, 425-428. (b) Auvray, P.; Knochel, P.; Normant, J. F. Tetrahedron Lett.
1985, 26, 4455-4458. (c) Knochel, P.; Normant, J. F. J. Organomet. Chem.
1986, 309, 1-23. (d) Auvray, P.; Knochel, P.; Normant, J. F. Tetrahedron
Lett. 1986, 5095-5098. (e) Auvray, P.; Knochel, P.; Normant, J. F.
Tetrahedron 1988, 44, 6095-6106. (f) Auvray, P.; Knochel, P.; Normant,
J. F. Tetrahedron 1988, 44, 4509-4519.
(9) Anzeveno, P. B.; Matthews, D. P.; Barney, C. L.; Barbuch, R. J. J.
Org. Chem. 1984, 49, 3134-3138.
(10) Prepared from (()-4a by reaction with excess NaI in refluxing
acetone.
(11) For carbonyl allylations of related 2-sulfonyl-substituted allylic
halides under nonaqueous conditions, see: (a) Auvray, P.; Knochel, P.;
Normant, J. F. Tetrahedron Lett. 1985, 26, 2329-2332. (b) Auvray, P.;
Knochel, P.; Normant, J. F. Tetrahedron Lett. 1986, 5091-5094. (c) Auvray,
P.; Knochel, P.; Normant, J. F. Tetrahedron 1988, 44, 4495-4508.
(12) Iodide (()-4b afforded similar results.
548
Org. Lett., Vol. 2, No. 4, 2000

ture data.16 Thus, â-hydroxy acids of opposite optical rotation
to that described in the literature for the corresponding S
enantiomers were obtained (Scheme 1).17
transition state for the metal-mediated coupling of allylic
halides with aldehydes in aqueous media were operative.5c,d
For this reason, the observed diastereoselectivity can be better
explained by an open antiperiplanar transition state model,18
in which the above interactions are avoided (Scheme 2).19
Scheme 1
Scheme 2
From a mechanistic standpoint, a highly energetic 1,3-
diaxial interaction between R and the sulfoxide moiety would
be required if the currently accepted six-membered cyclic
In conclusion, we have developed a simple, efficient, and
environmentally friendly protocol for the diastereoselective
allylation of aldehydes with enantiopure 2-sulfinylallyl
chloride (SS)-1. Further studies addressing the use of the
synthetic potential of the resulting 2-sulfinyl-2-propenyl-
methanols 3 are currently underway and will be reported in
due course.
(13) Experiments with Yb(OTf)3, a water-compatible Lewis acid, did
not significantly improve either the yields or the diastereoselectivities in In
and Zn-promoted allylations, although reaction rates were generally higher;
for the use of lanthanides as Lewis acids in the allylation of aldehydes in
aqueous medium, see: (a) Diana, S. C. H.; Sim, K. Y.; Loh, T. P. Synlett
1996, 263. (b) Kobayashi, S.; Wakabayashi, T.; Oyamada, H. Chem. Lett.
1997, 831-832. (c) Loh, T. P.; Cao, G. Q.; Pei, J. Tetrahedron Lett. 1998,
39, 1453-1456.
(14) Allylations with sulfinyl halide (SS)-1: A solution of (SS)-1 (1 mmol)
in THF (1.0 mL) is treated with NaI (450 mg, 3 mmol) and stirred at room
temperature. After 5 min, 9 mL of 1.6 N aqueous NH4I is added dropwise,
followed by a solution of the aldehyde 2a-g (1 mmol) in THF (0.5 mL).
The mixture is cooled to 0 °C (ice bath), and Zn dust (130 mg, 2 mmol) is
added portionwise. The reaction mixture is stirred at 0 °C until consumption
of the starting halide (TLC monitoring) and diluted with EtOAc. The organic
extracts are separated, dried (MgSO4), and concentrated to give 3a-g as a
mixture of diastereomers, which can be separated by careful flash
chromatography on hexanes-EtOAc (8:2 or 7:3).
Acknowledgment. Financial support from Direccio´n
General de Ensen˜anza Superior, Ministerio de Educacio´n y
Cultura (PB97-1171), and Comissionat per a Universitats i
Recerca, Generalitat de Catalunya (Projects 1997SGR00140
and SGR00187), is gratefully acknowledged. F.M. is also
grateful to Ministerio de Educacio´n y Cultura for a predoc-
toral fellowship.
OL991412J
(15) For ozonolysis of vinyl sulfoxides, see: Griesbaum, K.; Kim, W.
S. Erdoel Ergdgas Kohle 1995, 111, 485-486 (Chem. Abstr. 1996, 124,
55322).
(16) Since olefinic protons in sulfinyl homoallylic alcohols 3a-g showed
an almost superimposable 1H NMR pattern, an identical diastereochemical
induction was assumed in all cases.
(18) Yamamoto, Y. Acc. Chem. Res. 1987, 20, 243-249.
(19) The observed stereochemical outcome is also in agreement with an
intermolecular chelated acyclic model postulated for the allylation of
aldehydes with a sulfinylallylstannane under Lewis acid catalysis in
nonaqueous medium (Mortlock, S. V.; Thomas, E. J. Tetrahedron 1998,
54, 4663-4672).
(17) Wang, Z.; Zhao, C.; Pierce, M. E.; Fortunak, J. M. Tetrahedron:
Asymmetry 1999, 10, 225-228.
(20) Hayes, P.; Maignan, C. Synthesis 1999, 783-786.
Org. Lett., Vol. 2, No. 4, 2000
549