Palladium-catalyzed preparation of silyl enolates from α,β- unsaturated ketones or cyclopropyl ketones with hydrosilanes

Article abstract of DOI:10.1021/jo901513v

(Chemical Equation Presented). α,β-Unsaturated ketones and cyclopropyl ketones undergo palladium-catalyzed hydrosilylation with hydrosilanes to yield (Z)-silyl enolates.

Full text of DOI:10.1021/jo901513v

pubs.acs.org/joc
SCHEME 1. Palladium-Catalyzed Reaction of Chalcone with
Hydrosilane
Palladium-Catalyzed Preparation of Silyl Enolates
from r,β-Unsaturated Ketones or Cyclopropyl
Ketones with Hydrosilanes
Yuto Sumida, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of
Engineering, Kyoto University, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
1,4-hydrosilylation of R,β-unsaturated ketones with
hydrosilanes yielding silyl enolates with high Z selectivity.
Treatment of chalcone (1a) with tBuMe2SiH in the presence
of a palladium/tricyclohexylphosphine catalyst in toluene
at 60 °C afforded (Z)-silyl enolate 2a in 94% yield
(Scheme 1).6
yori@orgrxn.mbox.media.kyoto-u.ac.jp; oshima@orgrxn.
mbox.media.kyoto-u.ac.jp
Received July 15, 2009
A variety of R,β-unsaturated ketones were subjected to the
reaction, and the results are summarized in Table 1. The
electronic nature of the aryl group at the β-position had little
effect on the yields of 2 (entries 1 and 2). The substituents
R and R0 are not limited to aryl groups (entries 3-5), and
aliphatic ketone 1f could undergo efficient 1,4-hydrosilyla-
tion. Heteroaromatic rings were compatible with the reac-
tion conditions (entries 6 and 7).
We then examined the scope of hydrosilanes. Upon treat-
ment of chalcone with PhMe2SiH, an excellent yield of the
corresponding product 2i was obtained (entry 8). While the
reaction with Et3SiH gave 2j2a smoothly (entry 9), no reac-
tion took place with iPr3SiH (entry 10).
In contrast to the reactions of acyclic ketones, the reaction
of 2-cyclohexenone with tBuMe2SiH gave silyl enolate 2l in
very low yield, even when the reaction temperature was
raised to 80 °C (Scheme 2). Moreover, we obtained trace
amounts of the desired products when β,β-disubstituted or
R-substituted enones were employed.
On the basis of the fact that the reactivities of acyclic
ketones and cyclohexenone are different, a plausible me-
chanism is proposed in Scheme 3. Formation of oxapallada-
cycle intermediate A would occur by oxidative cyclization of
the R,β-unsaturated ketone with palladium(0).7 Competitive
oxidative addition of the hydrosilane to palladium(0)6
should be relatively slow, otherwise cyclohexenone would
react as smoothly as acyclic enones by the conventional 1,4-
hydrosilylation process. Transmetalation between A and the
hydrosilane would then take place to give alkylpalladium
intermediate B, which bears a silyl enolate moiety. Reductive
elimination produces the silyl enolate with regeneration of
the initial palladium(0) complex.
We could not eliminate the pathway that involves oxida-
tive addition of the hydrosilane to palladium(0), 1,4-hydro-
palladation, reductive elimination because in the case of
cyclic 1i (Scheme 2), which would be able to form an
oxapalladacycle, a low yield of 2l was obtained. Conse-
quently, both mechanisms could be in competition in the
case of acyclic R,β-unsaturated ketones.
R,β-Unsaturated ketones and cyclopropyl ketones under-
go palladium-catalyzed hydrosilylation with hydrosilanes
to yield (Z)-silyl enolates.
Silyl enolates are extremely useful and valuable reagents
for carbon-carbon bond formation in organic synthesis.1
Nowadays, transition-metal-catalyzed 1,4-hydrosilylation
of R,β-unsaturated carbonyl compounds is one of the most
powerful methods to synthesize silyl enolates. Although
some examples of 1,4-hydrosilylation of R,β-unsaturated
carbonyl compounds catalyzed by Rh,2 Pt,3 Cu,4 and B-
5
(C6F5)3 are known, the stereoselectivities are not satisfac-
tory in the cases of acyclic enones2,3 and 1,2-hydrosilylation
competes in some cases.2,3 Hence, the highly selective synthe-
sis of (Z)-silyl enolates remains a challenge.
Herein, we report that a combination of palladium
acetate and tricyclohexylphosphine (PCy3) is effective for
(1) (a) Mukaiyama, T. Angew. Chem., Int. Ed. 1977, 16, 817–826.
(b) Kobayashi, S.; Manabe, K.; Ishitani, H.; Matsuo, J. Science of Synthesis;
Fleming, I., Ed.; Thieme: Stuttgart, Germany, 1999; Vol. 4, Chapter 4.16. (c) Miura,
K.; Hosomi, A. Main Group Metals in Organis Synthesis; Yamamoto, H., Oshima,
K., Eds.; Wiley-VCH: Weinheim, Germany, 2004; Vol. 2, Chapter 10.2.
(2) (a) Ojima, I.; Kogure, T. Organometallics 1982, 1, 1390–1399.
(b) Zheng, G. Z.; Chan, T. H. Organometallics 1995, 14, 70–79. (c) Mori,
A.; Kato, T. Synlett 2002, 1167–1169. (d) Anada, M.; Tanaka, M.; Suzuki,
K.; Nambu, H.; Hashimoto, S. Chem. Pharm. Bull. 2006, 54, 1622–1623.
(e) Anada, M.; Tanaka, M.; Washio, T.; Yamawaki, M.; Abe, T.; Hashimo-
to, S. Org. Lett. 2007, 9, 4559–4562.
(3) (a) Bnrlow, A. P.; Boag, N. M.; Stone, F. G. A. J. Organomet. Chem.
1980, 191, 39–47. (b) Johnson, C. R.; Raheja, R. K. J. Org. Chem. 1994, 59,
2287–2288.
(4) Lipshutz, B. H.; Chrisman, W.; Noson, K.; Papa, P.; Sclafani, J. A.;
Vivian, R. W.; Keith, J. M. Tetrahedron 2002, 56, 2779–2788.
(5) Blackwell, J. M.; Morrison, D. J.; Piers, W. E. Tetrahedron 2002, 58,
8247–8254.
(6) For palladium-catalyzed conjugate reduction of R,β-unsaturated
carbonyl compounds with hydrosilanes, see: Keinan, E.; Greenspoon, N.
J. Am. Chem. Soc. 1986, 108, 7314–7325.
(7) Canovese, L.; Santo, C.; Visentin, F. Organometallics 2008, 27, 3577–
3581.
7986 J. Org. Chem. 2009, 74, 7986–7989
Published on Web 09/18/2009
DOI: 10.1021/jo901513v
r
2009 American Chemical Society

Sumida et al.
JOCNote
TABLE 1. Scope of R,β-Unsaturated Ketones
SCHEME 2. Reaction of Cyclic R,β-Unsaturated Ketones
SCHEME 3. Plausible Mechanism for Acyclic R,β-Unsaturated
Ketones
SCHEME 4. Ring-Opening Reaction of Cyclopropyl Ketones
palladium-catalyzed hydrosilylative ring-opening reaction
(Scheme 4, eq 2).
Indeed, treatment of cyclopropyl phenyl ketone (3a) with
tBuMe2SiH in the presence of palladium/tricyclohexylpho-
sphine and a small amount of MeOH as an additive in
toluene at 60 °C afforded the corresponding silyl enolate
2d in 93% yield with high Z selectivity (Table 2, entry 1). This
result encouraged us to examine the scope of various cyclo-
propyl ketones in the reaction, which is summarized in
Table 2.
aIsolated yields. bZ/E=96:4. cZ/E=94:6. dZ/E=99:1.
The implication of the formation of the oxapalladacycle
intermediate led us to investigate the reaction of cyclopropyl
ketones as well. Very recently, we reported a nickel-catalyzed
borylative ring-opening reaction of aryl cyclopropyl ketones
with bis(pinacolato)diboron yielding synthetically useful
4-oxoalkylboronates (Scheme 4, eq 1).8 This reaction in-
cludes the formation of an oxanickelacycle as a key inter-
mediate by oxidative cyclization of cyclopropyl ketone
with nickel.9 In the course of this study, we found that
palladium was also effective for the oxidative cyclization
of cyclopropyl ketones, and we decided to investigate a
The reactions of 3b and 3c with Et3SiH gave 2m and 2n in
81% and 72% yields, respectively (Table 2, entries 2 and 3).
The use of 3d having an ester group afforded silyl enolate 2o
in 87% yield (entry 4). Treatment of 3a with Et3SiH instead
t
of BuMe2SiH yielded 2p2a,e with a slightly inferior result
(entry 5). To our delight, alkyl cyclopropyl ketones partici-
pated in the hydrosilylation, even though they were unreac-
tive in the nickel-catalyzed borylation (entries 6-9).8 In the
(8) Sumida, Y.; Yorimitsu, H.; Oshima, K. J. Org. Chem. 2009, 74, 3196–
3198.
(9) Oxidative cyclization of cyclopropyl ketones with nickel complex:
(a) Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am. Chem. Soc. 2006, 128, 5350–
5351. (b) Liu, L.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 5348–5349.
(10) (a) Stork, G.; Hudrlik, P. F. J. Am. Chem. Soc. 1968, 90, 4462–4464.
(b) House, H. O.; Czuba, L. J.; Gall, M.; Olmstead, H. D. J. Org. Chem. 1969,
34, 2324–2336. For kinetic control, see: Henderson, K. W.; Kerr, W. J.;
Moir, J. H. Tetrahedron 2002, 58, 4573–4587. For thermodynamic control,
see: Yamamoto, Y.; Matui, C. Organometallics 1997, 16, 2204–2206.
J. Org. Chem. Vol. 74, No. 20, 2009 7987

Sumida et al.
SCHEME 6. Reaction of Cyclopropyl Ketone with Et3SiD
JOCNote
TABLE 2. Scope of Cyclopropyl Ketones
SCHEME 7. Plausible Mechanism for Cyclopropyl Ketones
entry
R
Si
2
yield (%)a
1
2
3
4
5
6
7
8
9
Ph (3a)
tBuMe2Si
Et3Si
Et3Si
Et3Si
Et3Si
2d
2m
2n
2o
2p
2q
2r
93b
4-MeC6H4 (3b)
4-MeOC6H4 (3c)
4-EtOC(O)C6H4 (3d)
Ph (3a)
Me (3e)
Me (3e)
81b
72b
87
81b
Et3Si
tBuMe2Si
Et3Si
(45)c,d
79d
PhCH2 (3f)
PhCH2 (3f)
2s
2t
(52)c,d
85d
tBuMe2Si
aIsolated yields. bZ/E = 99:1. cNMR yields. dAt 80 °C.
SCHEME 5. Reaction of Disubstituted Cyclopropane
it may activate hydrosilane species as a Lewis base and
promote transmetalation.13
reactions of alkyl cyclopropyl ketones 3e and 3f, tBuMe2SiH
was more reactive than Et3SiH. Benzyl cyclopropyl ketone
(3f) was transformed to the corresponding enolate 2t, which
is difficult to synthesize by using known methods.10 In all
cases, we could prepare silyl enolates with high Z selectivity.
When cyclopropyl ketone 3g having an additional sub-
stituent on the cyclopropane ring was used, the hydrosilyla-
tive ring-opening reaction of 3g predominantly gave 2u
through selective cleavage of the most substituted C-C bond
(Scheme 5).
To study the reaction mechanism in detail, the reaction of
cyclopropyl phenyl ketone with deuterated silane, Et3SiD,11
was examined. Contrary to our expectations (Scheme 4, eq 2),
deuterium was introduced into the β-position (Scheme 6).
Accordingly, we propose the reaction mechanism
as follows (Scheme 7). Oxidative cyclization of the cyclopro-
pyl ketone to palladium(0) gives six-membered oxapal-
ladacycle intermediate A0. The subsequent β-hydride elim-
ination generates palladium hydride species B0. Intra-
molecular hydropalladation would occur rapidly to afford
five-membered oxapalladacycle intermediate C0 analogous
in the case of R,β-unsaturated ketones. Although the release
of 1d and palladium(0) might be possible, they could be
converted smoothly to the five-membered oxapalladacycle
intermediate C0 reversibly.12 The remaining steps are similar
to those of the proposed mechanism outlined in Scheme 3.
Although the role of MeOH is not clear at this stage, the
reaction required MeOH to achieve a high yield. We suspect
In 1999, Slough et al. reported a rhodium-catalyzed
hydrosilylation of cyclopropyl phenyl ketones with Et3-
SiH.14 Since they observed silyl ether 5 (Scheme 7), in
addition to E/Z mixtures of silyl enolates, they proposed a
different mechanism in which occurred oxidative addition of
Et3SiH to rhodium complex followed by 1,2-hydrosilylation
of a cyclopropyl ketone. Although no generation of silyl
ether 5 was observed in our case, the mechanism they
proposed could not be excluded as a possibility.
In summary, we have developed a new hydrosilylation
reaction under palladium catalysis by using R,β-unsaturated
ketones or cyclopropyl ketones as substrates, which allows
the highly Z selective synthesis of silyl enolates.
Experimental Section
Typical Procedure for Synthesis of Silyl Enolate. Pd(OAc)2 (5.6
mg, 0.025 mmol) and PCy3 (14 mg, 0.05 mmol) were placed in a 20-
mL reaction flask under argon. After toluene (1.5 mL) was added at
0 °C, the resulting solution was stirred for 10 min. Chalcone (1a)
(104 mg, 0.50 mmol) and tBuMe2SiH (0.16 mL, 1.0 mmol) were then
added. The mixture was allowed to warm to 60 °C and stirred for
10 h. The reaction mixture was filtered by alumina (Wako, activated),
and the filtrate was concentrated in vacuo to afford an oil. The crude
oil was purified on silica gel (Kanto Chemical, silica gel 60N, hexane)
by using a dry ice/acetone-jacketed chromatographic column to
yield 2a (152 mg, 0.47 mmol) in 94% yield. (Z)-1-tert-Butyldimethyl-
siloxy-1,3-diphenyl-1-propene (2a): IR (neat) 2930, 2857, 1647, 1493,
1390, 1254, 1006, 939, 668 cm-1; 1H NMR (CDCl3) δ 0.01 (s, 6H),
1.03 (s, 9H), 3.60 (d, J=7.5 Hz, 2H), 5.32 (t, J=7.5 Hz 1H), 7.20
(t, J=6.5 Hz, 1H), 7.24-7.32 (m, 7H), 7.49 (d, J=7.5 Hz, 2H);
(11) Et3SiD were obtained according to the literature procedure: Caseri,
W.; Pregosin, P. S. J. Organomet. Chem. 1988, 356, 259–269.
(12) In the absence of triethylsilane, Pd-catalyzed isomerization of cyclo-
propyl ketone to R,β-unsaturated ketone indeed took place although the
resulting R,β-unsaturated ketone immediately underwent dimerization in
situ as reported previously (ref 9).
(13) (a) Corriu, R. J. P.; Perz, R.; Reye, C. Tetrahedron 1983, 39, 999–
1009. (b) Sakada, H.; Watanabe, S.; Kabuto, C.; Kabuto, K. J. Am. Chem.
Soc. 2003, 125, 2842–2843. (c) Leigh, W. J.; Owens, T. R.; Bendikov, M.;
Zade, S. S.; Apeloig, Y. J. Am. Chem. Soc. 2006, 128, 10772–10783.
(14) Sun, C.; Tu, A.; Slough, G. A. J. Organomet. Chem. 1999, 582, 235–
245.
7988 J. Org. Chem. Vol. 74, No. 20, 2009

Sumida et al.
JOCNote
13C NMR (CDCl3) δ -3.9, 18.3, 25.9, 32.3, 110.3, 125.8, 126.0,
127.6, 127.9, 128.3, 128.4, 139.5, 141.6, 150.0; HRMS (EI)
found 324.1911 [Mþ], calcd for C21H28OSi 324.1909
Programs from JSPS. Y.S. acknowledges JSPS for financial
support.
Supporting Information Available: Characterization data
for products. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. This work was supported by Grants-in-
Aid for Scientific Research and Global COE Research
J. Org. Chem. Vol. 74, No. 20, 2009 7989