A new cine-substitution of alkenyl sulfones with aryltitanium reagents catalyzed by rhodium: Mechanistic studies and catalytic asymmetric synthesis of allylarenes

Article abstract of DOI:10.1021/ja0295568

The reaction of alkenyl sulfones with aryltitanium triisopropoxide (ArTi(OPr-i )₃) in the presence of 3 mol % of [Rh(OH)((S)-binap)]₂ in THF at 40 °C gave high yield of cine-substitution products. The catalytic cycle was established by deuterium-labeling studies, and it was applied to catalytic asymmetric synthesis of allylarenes which proceeds with over 99% enantioselectivity. Copyright

Full text of DOI:10.1021/ja0295568

Published on Web 02/13/2003
A New cine-Substitution of Alkenyl Sulfones with Aryltitanium Reagents
Catalyzed by Rhodium: Mechanistic Studies and Catalytic Asymmetric
Synthesis of Allylarenes
Kazuhiro Yoshida and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received December 2, 2002 ; E-mail: thayashi@kuchem.kyoto-u.ac.jp
Scheme 1
The cine-substitution reaction has attracted considerable attention
as a result of its rather unusual substitution pattern and its synthetic
utility.1 It takes place mostly in aromatic systems, and only a few
types have been reported on the cine-substitution in nonaromatic
systems, the representatives being those observed as competing side
reactions in palladium-catalyzed cross-couplings of alkenylstannanes
and -silanes.2 On the other hand, we have reported the rhodium-
catalyzed asymmetric addition of organoboron3,4 and -titanium5
reagents to various types of electron-deficient olefins which
proceeds through carbo-rhodation of the olefins as a key step, giving
the corresponding 1,4-addition products with high enantioselectivity.
On using alkenyl sulfones6 as substrates for the rhodium-catalyzed
addition of organometallic reagents, we found a new type of cine-
substitution where the sulfonyl group is eliminated after the carbo-
rhodation step.7 Here we wish to report the catalytic cine-
substitution reaction, its catalytic cycle established by deuterium-
labeling studies and its application to catalytic asymmetric synthesis
Scheme 2
of allylarenes with over 99% enantioselectivity.
In the first set of experiments, a pair of regioisomeric alkenyl
sulfones, (E)-1-phenylsulfonyl-1-octene (1a) and 2-phenylsulfonyl-
1-octene (1b), were allowed to react with phenyltitanium triiso-
propoxide (PhTi(OPr-i)3)8 (2m) in the presence of 3 mol % of
[Rh(OH)((S)-binap)]23j in THF at 40 °C for 12 h (Scheme 1). The
reaction of 1a gave 87% yield of 2-phenyl-1-octene (3am), and
that of 1b gave 93% yield of (E)-1-phenyl-1-octene (3bm) with
perfect regioselectivity in both reactions. Thus, cine-substitution
where the phenylsulfonyl group is substituted with the phenyl group
on the next carbon took place in both regioisomeric alkenyl sulfones
Scheme 3
1a and 1b. The cine-substitution was also observed in the reaction
of (E)-1-phenylsulfonyl-2-phenylethene (1c) with PhTi(OPr-i)3 (2m)
and those containing an electron-donating or -withdrawing group
on the phenyl 2n,o, which gave the corresponding substitution
products 3cm, 3cn, and 3co, respectively, in a quantitative yield.
With organoboron reagents such as phenyl-9BBN or triphenylcy-
clotriboroxane ((PhBO)3) in place of the aryltitanium reagents,
neither this type of cine-substitution nor the 1,4-addition took place.
Deuterium-labeling experiments shown in Scheme 2 gave us an
insight into the mechanism of the present cine-substitution. The
rhodium-catalyzed reaction of (E)-2-deuterio-1-phenylsulfonyl-1-
octene (1a-2-d1) (99% D) with PhTi(OPr-i)3 (2m) gave (E)-1-
deuterio-2-phenyl-1-octene ((E)-3am-d1) where the deuterium
content at the E position is 97%. Consistent with this deuterium
shift, the reaction of (E)-1-deuterio-1-phenylsulfonyl-1-octene (1a-
1-d1) (99% D) gave (Z)-1-deuterio-2-phenyl-1-octene ((Z)-3am-
d1) with the deuterium content of 97% at the Z position. Scheme 3
illustrates the formation of the cine-substitution product using for
an example the reaction starting from 1a-2-d1. Addition of a phenyl-
rhodium species5 to the alkenyl sulfone in a syn fashion generating
alkyl-rhodium intermediate A followed by â-deuterium elimination
with syn stereochemistry and readdition of the deuterium-rhodium
to the double bond with syn stereochemistry and with opposite
regiochemistry forms new alkyl-rhodium intermediate B. The last
step, elimination of the sulfonyl group and the rhodium from B,
should proceed in an anti fashion to give the cine-substitution
product (E)-3am-d1 where the deuterium is at E position to the
phenyl.9 It is likely that the last step consists of nucleophilic attack
of the phenyltitanium on the rhodium and E2 elimination of the
phenylsulfonyl as a leaving group.
9
2872
J. AM. CHEM. SOC. 2003, 125, 2872-2873
10.1021/ja0295568 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Scheme 4
deuterium-labeling studies. In some cases, the catalytic asymmetric
carbon-carbon bond formation was realized with high enantiose-
lectivity (>99% ee).
Acknowledgment. This work was supported in part by a Grant-
in-Aid for Scientific Research from the Ministry of Education,
Science, Sports, and Culture, Japan. K.Y. thanks the Japan Society
for the Promotion of Science for the award of a fellowship for
graduate students.
Supporting Information Available: Experimental procedures,
spectroscopic and analytical data for the products (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
References
(1) For a review: Suwinski. J.; Swierczek K. Tetrahedron 2001, 57, 1639.
(2) (a) Kikukawa, K.; Umekawa, H.; Matsuda, T. J. Organomet. Chem. 1986,
311, C44. (b) Ennis, D. S.; Gilchrist, T. L. Tetrahedron Lett. 1989, 30,
3735. (c) Stork, G.; Isaacs, R. C. A. J. Am. Chem. Soc. 1990, 112, 7339.
(d) Crisp, G. T.; Glink, P. T. Tetrahedron 1994, 50, 3213. (e) Busacca,
C. A.; Swestock, J.; Johnson, R. E.; Bailey, T. R.; Musza, L.; Rodger, C.
A. J. Org. Chem. 1994, 59, 7553. (f) Farina, V.; Hossain, M. A.
Tetrahedron Lett. 1996, 37, 6997. (g) Chen, S.-H. Tetrahedron Lett. 1997,
38, 4741. (h) Quayle, P.; Wang, J.; Xu, J.; Urch, C. J. Tetrahedron Lett.
1998, 39, 489. (i) Flohr, A. Tetrahedron Lett. 1998, 39, 5177. (j) Anderson,
J. C.; Anguille, S.; Bailey, R. Chem. Commun. 2002, 2018.
(3) (a) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N. J.
Am. Chem. Soc. 1998, 120, 5579. (b) Takaya, Y.; Ogasawara, M.; Hayashi,
T. Tetrahedron Lett. 1998, 39, 8479. (c) Takaya, Y.; Senda, T.; Kurushima,
H.; Ogasawara, M.; Hayashi, T. Tetrahedron: Asymmetry 1999, 10, 4047.
(d) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron Lett. 1999, 40,
6957. (e) Hayashi, T.; Senda, T.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 1999, 121, 11591. (f) Takaya, Y.; Ogasawara, M.; Hayashi, T.
Chirality 2000, 12, 469. (g) Hayashi, T.; Senda, T.; Ogasawara, M. J.
Am. Chem. Soc. 2000, 122, 10716. (h) Hayashi, T. Synlett 2001, 879. (i)
Senda, T.; Ogasawara, M.; Hayashi, T. J. Org. Chem. 2001, 66, 6852. (j)
Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 2002, 124, 5052.
(4) (a) Sakuma, S.; Sakai, M.; Itooka, R.; Miyaura, N. J. Org. Chem. 2000,
65, 5951. (b) Kuriyama, M.; Tomioka, K. Tetrahedron Lett. 2001, 42,
921. (c) Sakuma, S.; Miyaura, N. J. Org. Chem. 2001, 66, 8944. (d) Reetz,
M. T.; Moulin, D.; Gosberg, A. Org. Lett. 2001, 3, 4083. (e) Lautens,
M.; Dockendorff, C.; Fagnou, K.; Malicki, A. Org. Lett. 2002, 4, 1311.
(f) Kuriyama, M.; Nagai, K.; Yamada, K.; Miwa, Y.; Taga, T.; Tomioka,
K. J. Am. Chem. Soc. 2002, 124, 8932.
In the reaction of cyclic alkenyl sulfone, the asymmetric carbon
center created at the carbo-rhodation step is retained in the
substitution product (Scheme 4). Thus, the reaction of 1-phenyl-
sulfonylcyclohexene (4) with PhTi(OPr-i)3 (2m) in the presence
of [Rh(OH)((S)-binap)]2 gave 94% yield of (R)-3-phenylcyclohex-
ene (5m) whose enantiomeric excess turned out to be over 99% ee
by GC analysis with a chiral stationary phase column.10 The very
high enantioselectivity (99.9% ee) was also observed in the reaction
with 4-MeOC6H4Ti(OPr-i)3 (2n) giving the corresponding 3-aryl-
cyclohexene (5n).11,12 The coordination of 4 to the (S)-binap/Rh
with its 1si face at the insertion into the aryl-rhodium intermediate3a,c,e
leads to the R configuration of the substitution products 5. Because
the alkyl-rhodium intermediate C formed by the insertion does not
have the syn â-hydrogen on the aryl-substituted carbon, the
â-hydrogen elimination takes place for the syn â-hydrogen on the
other neighboring carbon. Subsequent syn hydro-rhodation and the
anti elimination from D produces the allylic arenes 5.
The selective formation of allylic arene was also observed in
the reaction of (E)-2-phenylsulfonyl-2-nonene (6) which is a sulfone
of internal alkene. Although the yield was not high enough, the
enantioselectivity forming allylarene 7 in the reaction with 2n was
surprisingly high (99.2% ee).13 For this alkenyl sulfone 6, the
hydrogen on the methyl carbon is abstracted at the â-hydrogen
elimination on the alkyl-rhodium intermediate much more readily
than that on the sterically congested carbon substituted with phenyl
and hexyl groups, resulting in the selective formation of 7.
In conclusion, we found a new type of cine-substitution reaction
of alkenyl sulfones with aryltitanium reagents, which is catalyzed
by a rhodium complex, and we established its catalytic cycle by
(5) Hayashi, T.; Tokunaga, N.; Yoshida, K.; Han, J. W. J. Am. Chem. Soc.
2002, 124, 12102.
(6) For a review: Simpkins, N. S. Tetrahedron 1990, 46, 6951.
(7) Noncatalytic cine-substitution of alkenyl sulfones with potassium or lithium
cyanides has been reported: (a) Taber, D. F.; Saleh S. A. J. Org. Chem.
1981, 46, 4817. (b) Bailey, P. L.; Jackson, R. F. W. Tetrahedron Lett.
1991, 32, 3119.
(8) For reviews on organotitanium reagents: (a) Duthaler, R. O.; Hafner, A.
In Transition Metals for Organic Synthesis; Beller, M., Bolm, C., Eds.;
Wiley-VCH: Weinheim, 1998; Vol. 1, p 447. (b) Reetz, M. T. Organ-
otitanium Reagents in Organic Synthesis; Springer: Verlag: 1986. (c)
Sato, F.; Urabe, H.; Okamoto, S. Chem. ReV. 2000, 100, 2835. (d) Ferreri,
C.; Palumbo, G.; Caputo, R. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Schreiber, S. L., Eds.; Pergamon Press: Oxford, 1991;
Vol. 1, p 139.
(9) A similar reaction mechanism has been reported in the palladium-catalyzed
cross-coupling reaction (See ref 2a).
(10) GC analysis with chiral stationary phase column, CP-CHIRASIL-DEX-
CB. For the asymmetric synthesis of 5 by nickel-catalyzed allylic
alkylation: Chung, K.-G.; Miyake, Y.; Uemura, S. J. Chem. Soc., Perkin
Trans. 1 2000, 2725 and references therein.
(11) The enantiomeric purity was determined by HPLC analysis with chiral
stationary phase column, Chiralcel OB-H (hexane).
(12) The reaction of 1-phenylsulfonylcyclpentene under the same conditions
gave a lower yield (ca. 5%) of 3-phenylcyclopentene.
(13) The enantiomeric purity was determined by HPLC analysis with chiral
stationary phase column, Chiralcel OJ (hexane).
JA0295568
9
J. AM. CHEM. SOC. VOL. 125, NO. 10, 2003 2873