Rhenium-catalyzed regio- and stereoselective addition of two carbon units to terminal alkynes via carbon-carbon bond cleavage of β-keto sulfones

Article abstract of DOI:10.1021/ol2008507

Treatment of β-keto sulfones with terminal alkynes gave unsaturated δ-keto sulfones in good to excellent yields under rhenium catalysis. In this reaction, the insertion of the alkynes into the nonstrained carbon-carbon single bond between the α- and β-pos

Full text of DOI:10.1021/ol2008507

ORGANIC
LETTERS
2011
Vol. 13, No. 11
2959–2961
Rhenium-Catalyzed Regio- and
Stereoselective Addition of Two Carbon
Units to Terminal Alkynes via CarbonÀ
Carbon Bond Cleavage of
β-Keto Sulfones
Yoichiro Kuninobu,* Hironori Matsuzaki, Mitsumi Nishi, and Kazuhiko Takai*
Division of Chemistry and Biochemistry, Graduate School of Natural Science and
Technology, Okayama University, Tsushima, Kita-ku, Okayama 700-8530, Japan
kuninobu@cc.okayama-u.ac.jp; ktakai@cc.okayama-u.ac.jp
Received April 1, 2011
ABSTRACT
Treatment of β-keto sulfones with terminal alkynes gave unsaturated δ-keto sulfones in good to excellent yields under rhenium catalysis. In this
reaction, the insertion of the alkynes into the nonstrained carbonÀcarbon single bond between the R- and β-positions of the β-keto sulfones
proceeded smoothly, and (Z)-isomers were produced with high regio- and stereoselectivities.
It is important to develop efficient and powerful meth-
ods to construct new carbonÀcarbon bonds. As one ideal
strategy, the addition of two carbon units to carbonÀ
carbon triple or double bonds is an efficient and powerful
method. To realize such reactions, the insertion of unsat-
urated bonds into a carbonÀcarbon single bond of organic
molecules is a realistic method. There have been several
examples of such transformations: unsaturated molecules
have been inserted into carbonÀcarbon bonds of three- or
four-membered cyclic compounds,1 norbornenes were in-
corporated into the CÀC single bonds of cyclobutenones
and cyclobutenediones,2 both alkynes3 and norbornenes4
have been inserted into CÀCN bonds, and metal-free
insertion of cyclohexyne into the CÀC single bond of cyclic
ketones.5 We have recently reported rhenium- and man-
ganese-catalyzed transformations via the insertion of al-
kynes into a nonstrained carbonÀcarbon single bond of
cyclic and acyclic β-keto esters.6 However, when using
acyclic β-keto esters, the products were obtained as mix-
tures of regio- and stereoisomers.6c,e
Initially, theoretical calculations on four olefinic regio-
and stereoisomers, the products of the reaction between
2-(methylsulfonyl)-1-phenylethanone (β-keto sulfone) and
phenylacetylene (terminal alkyne), were carried out. It was
found that one isomer [δ-keto sulfone: (Z)-4-(methyl-
sulfonyl)-1,3-diphenyl-2-buten-1-one] was more stable
(1) (a) Noyori, R.; Odagi, T.; Takaya, H. J. Am. Chem. Soc. 1970, 92,
5780. (b) Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem. Soc.
2005, 127, 6932. (c) Murakami, M.; Ashida, S. Chem. Commun. 2006,
4599.
(2) (a) Hamner, E. R.; Kemmitt, R. D. W.; Smith, M. A. R. J. Chem.
Soc., Chem. Commun. 1974, 841. (b) Liebeskind, L. S.; Baysdon, S. L.;
South, M. S.; Blount, J. F. J. Organomet. Chem. 1980, 202, C73. (c)
Liebeskind, L. S.; Bayson, S. L.; South, M. S.; Iyer, S.; Leeds, J. P.
Tetrahedron 1985, 41, 5839. (d) Huffman, M. A.; Liebeskind, L. S. J. Am.
Chem. Soc. 1991, 113, 2771. (e) Huffman, M. A.; Liebeskind, L. S.;
Pennington, W. T. Organometallics 1992, 11, 255. (f) Kondo, T.;
Nakamura, A.; Okada, T.; Suzuki, N.; Wada, K.; Mitsudo, T. J. Am.
Chem. Soc. 2000, 122, 6319. (g) Kondo, T.; Taguchi, Y.; Kaneko, Y.;
Niimi, M.; Mitsudo, T. Angew. Chem., Int. Ed. 2004, 43, 5369.
(3) (a) Nozaki, K.; Sato, N.; Takaya, H. Bull. Chem. Soc. Jpn. 1996,
69, 1629. (b) Nakao, Y.; Oda, S.; Hiyama, T. J. Am. Chem. Soc. 2004,
126, 13904.
(4) Nishihara, Y.; Inoue, Y.; Itazaki, M.; Takagi, K. Org. Lett. 2005,
7, 2639.
(5) Gampe, C. M.; Boulos, S.; Carreira, E. M. Angew. Chem., Int. Ed.
2010, 49, 4092.
(6) (a) Kuninobu, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc. 2006,
128, 11368. (b) Kuninobu, Y.; Takata, H.; Kawata, A.; Takai, K. Org.
Lett. 2008, 10, 3133. (c) Kuninobu, Y.; Kawata, A.; Nishi, M.; Takata,
H.; Takai, K. Chem. Commun. 2008, 6360. (d) Kuninobu, Y.; Morita, A.;
Nishi, M.; Kawata, A.; Takai, K. Org. Lett. 2009, 11, 2535. (e)
Kuninobu, Y.; Kawata, A.; Nishi, M.; Yudha, S. S.; Chen, J.; Takai,
K. Chem.;Asian J. 2009, 4, 1424.
r
10.1021/ol2008507
2011 American Chemical Society
Published on Web 05/09/2011

[4.2À11.2 kcal/mol, B3LYP 6-31G(d)] than the others.
Therefore, we considered that single products might be
obtained by the reactions between β-keto sulfones and
alkynes. We report herein the regio- and stereoselective
insertion of alkynes into a carbonÀcarbon single bond of
β-keto sulfones.
Treatment of β-keto sulfone 1a with p-tolylacetylene
(2a) in the presence of a catalytic amount of a rhenium
complex, Re2(CO)10, gave unsaturated δ-keto sulfone3ain
75% yield (eq1).7À9 Interestingly, product3awasobtained
regio- and stereoselectively, and no other products were
formed. This selectivity is in sharp contrast to our previous
report, in which unsaturated δ-keto esters were formed asa
mixture of olefinic regio- and stereoisomers by the reac-
tions between β-keto esters and alkynes.6c,e
1g, and 1h, provided the corresponding unsaturated δ-keto
sulfones 3fÀ3h in 24À68% yields (entries 5À7). The
corresponding unsaturated δ-keto sulfone 3i wasproduced
in 52% yield using the β-keto sulfone with a methyl group
at the R2 position, 1i (entry 8).10 However, when using a
β-keto sulfone with a substituent at the active methylene
moiety (1-phenyl-2-tosylpropan-1-one), the correspond-
ing unsaturated δ-keto sulfone was not formed.
Table 2. Reactions between β-Keto Sulfones 1a and Several
Alkynes 2a
Next, the reactions of several β-keto sulfones 1 with
p-tolylacetylene (2a) were investigated (Table 1). β-Keto
sulfones with electron-donating groups on the aromatic
ring (R1), 1b and 1c, gave unsaturated δ-keto sulfones 3b
and 3c in 56% and 61% yields, respectively (entries 1 and
2). The yield of an unsaturated δ-keto sulfone decreased
when the β-keto sulfone possessed an electron-withdraw-
ing group on the aromatic ring (R1), 1d (entry 3). The
corresponding δ-keto sulfone 3e was generated using a
β-keto sulfone with a bromine atom, 1e, without loss of the
bromine atom (entry 4). β-Keto sulfones with primary,
secondary, or tertiary alkyl groups at the R1 position, 1f,
a 2a (total: 2.4 equiv). At the beginning of the reaction, 2a (1.2 equiv);
additional 2a (1.2 equiv) after 12 h. b Re2(CO)10 (5.0 mol %). The
product was obtained as a mixture of three compounds. The major
product was 3q. The structures of two minor products were not
determined. c 1H NMR yield.
Then, we investigated the scope and limitations of
several alkynes (Table 2). By using an alkyne with an
electron-donating group, 2b, the insertion reactions
proceeded well, and unsaturated δ-keto sulfone 3j was
obtained in 86% yield (entry 1). The structure of 3j was
determined by single crystal X-ray analysis (Figure 1; see
also the Supporting Information).11 This result shows that
the aryl group of the alkyne was introduced at the C2
position, and 3j has the regio- and stereochemistry as
shown in Figure 1. The bond length between C1 and C2
Table 1. Reactions between Several β-Keto Sulfones 1 and
p-Tolylacetylene (2a)a
(7) Investigation of several catalysts: ReBr(CO)5, 4%; [HRe(CO)4]n,
47%. The desired product 3a was not formed using the following
complexes: [ReBr(CO)3(thf)]2, ReOCl3(PPh3)3, Mn2(CO)10, MnBr(CO)5,
Mn(OAc)2, Cr(CO)6, W(CO)6, Fe2(CO)9, Fe3(CO)12, Ru3(CO)12, Co2-
(CO)8, and In(OTf)3.
entry
R1
R2
yield/%
1
2
3
4
5
6
7
8
4-(MeO)C6H4
4-MeC6H4
4-(CF3)C6H4
4-BrC6H4
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
1b
lc
3b
3c
3d
3e
3f
56
61
44
52
24
68
31
52
(8) Toluene, 64%; THF, 7%; CH2ClCH2Cl, 31%; DMF, 0%; etha-
nol, 0%; neat, 4%.
1d
le
(9) In this reaction, while p-tolylacetylene (2a) was consumed, β-keto
sulfone 1a was recovered in 16% yield. However, the yield of the product
3a was not improved by treatment with additional alkyne 2a.
(10) In Table 1, entries 1À8, β-keto sulfones 1 were recovered. The
total yields of the products 3 and the recovery of β-keto sulfones 1 were
between 84 and 98%. Therefore, the yields of 3 based on the conversion
were relatively high.
(11) The olefin configurations of other products were assigned by the
comparison of the chemical shifts of the olefinic protons of the products
with those of 3f.
1f
Cy
1g
1h
1i
3g
3h
3i
tBu
Ph
a 2a (total: 2.4 equiv). At the beginning of the reaction, 2a (1.2 equiv);
additional 2a (1.2 equiv) after 12 h.
2960
Org. Lett., Vol. 13, No. 11, 2011

rhenium catalyst; (2-a) reductive elimination of the
rhenium catalyst from the formed rhenium cyclopen-
tene intermediate to give a cyclobutene intermediate; (3)
carbonÀcarbon single bond cleavage of the cyclobutene
intermediate to generate an acyclic intermediate; and
(4) protonation to give the product. Another possible
pathway for the formation of the cyclobutene intermediate
is (1-b) nucleophilic addition of the β-keto sulfone to a
terminal alkyne and (2-b) intramolecular nucleophilic
cyclization. We assume that the stereochemistry of the
products is determined kinetically, and no isomerization of
the products occurred to other regio- and stereoisomers
under the reaction conditions.
Figure 1. X-ray crystal structure of δ-keto sulfone 3j. Thermal
ellipsoids set at 50% probability. Hydrogen atoms are omitted
for clarity.
Scheme 1. Proposed Mechanism for the Insertion of Alkynes 2
into a CarbonÀCarbon Single Bond of β-Keto Sulfones 1
˚
is 1.351(3) A, which is suitable for a carbonÀcarbon
double bond. The corresponding unsaturated δ-keto sul-
fone 3k was produced in 56% yield by employing pheny-
lacetylene (2c) as a substrate (entry 2). The yields of
unsaturated δ-keto sulfones 3l and 3m decreased when
alkynes with electron-withdrawing groups, 2d and 2e, were
treated with β-keto sulfone 1a (entries 3 and 4). Aryl
alkynes bearing a methyl group at the meta- or ortho-
position, 2f or 2g, afforded unsaturated δ-keto sulfones 3n
and 3o in 73% and 60% yields, respectively (entries 5 and
6). The corresponding δ-keto sulfone 3p was provided in
56% yield using enyne 2h (entry 7). An aliphatic acetylene,
such as 1-dodecyne (2j), generated the corresponding
δ-keto sulfone, but in low yield (entry 8).12 Diphenylace-
tylene and 1-phenyl-1-propyne (internal alkynes) did not
promote the insertion.
In order to examine the tolerance of functional groups,
reactions between β-keto sulfone 1a and p-tolylacetylene
(2a) were carried out in the presence of the follow-
ing compounds. Recovery of the compounds after the
completion of the reactions (3a: 68À74% yields) are
as follows: 4-methylstyrene (94%), 1-phenyl-1-propyne
(96%), 5-nonanone (>99%), and methyl benzoate
(>99%). In contrast, the reaction proceeded with
19% and 14% yields, respectively, when benzo- and
nonanenitrile were added to the mixture.
In summary, we have succeeded in the regio- and
stereoselective insertion of terminal alkynes into a non-
strained carbonÀcarbon single bond of β-keto sulfones.
Previously, insertion of unsaturated molecules into CÀC
single bonds was difficult to achieve regio- and stereoselec-
tively. We hope that this reaction will serve as a useful tool
for synthetic organic chemists.
Acknowledgment. This work was partially supported
by the Ministry of Education, Culture, Sports, Science,
and Technology of Japan. We also thank Dr. Koichi
Mitsudo and Prof. Seiji Suga, Division of Chemistry and
Biochemistry, Graduate School of Natural Science and
Technology, Okayama University, for their support in the
DFT calculations.
The proposed mechanism for the insertion of an alkyne
into a carbonÀcarbon single bond of a β-keto sulfone is as
follows (Scheme 1): (1-a) oxidative cycloaddition of the
enol form of the β-keto sulfone, an alkyne, and the
Supporting Information Available. General experimen-
tal procedure and characterization data for unsaturated
δ-keto sulfones. This material is available free of charge
via the Internet at http://pubs.acs.org.
(12) In Table 2, entries 1À9, β-keto sulfones 1 were recovered. The
total yields of the products 3 and the recovery of β-keto sulfones 1 were
in the range 88À99%. Therefore, the yields of 3 based on the conversion
were relatively high.
Org. Lett., Vol. 13, No. 11, 2011
2961