Homolytic carbostannylation of alkenes and alkynes with tributylstannyl enolates

Article abstract of DOI:10.1021/ol016797w

matrix presented In the presence of AIBN, tributylstannyl enolates derived from aromatic ketones reacted with electron-deficient alkenes and a variety of alkynes to give the corresponding carbostannylated adducts. The reactions with methyl acrylate gave α-tributylstannylmethyl-γ-ketoesters, unlike the known Michael-type reaction of stannyl enolates forming δ-ketoesters. The carbostannylation of alkynes proceeded in an anti addition mode to afford β,γ-unsaturated ketones. The reactivity of stannyl enolates as radical transfer agents could be utilized for radical cyclization of 1,6-enynes.

Full text of DOI:10.1021/ol016797w

ORGANIC
LETTERS
2001
Vol. 3, No. 25
4055-4057
Homolytic Carbostannylation of Alkenes
and Alkynes with Tributylstannyl
Enolates
Katsukiyo Miura, Hiroshi Saito, Naoki Fujisawa, Di Wang, Hisashi Nishikori, and
Akira Hosomi*
Department of Chemistry, Graduate School of Pure and Applied Sciences,
UniVersity of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
hosomi@chem.tsukuba.ac.jp
Received September 21, 2001
ABSTRACT
In the presence of AIBN, tributylstannyl enolates derived from aromatic ketones reacted with electron-deficient alkenes and a variety of alkynes
to give the corresponding carbostannylated adducts. The reactions with methyl acrylate gave r-tributylstannylmethyl-γ-ketoesters, unlike the
known Michael-type reaction of stannyl enolates forming δ-ketoesters. The carbostannylation of alkynes proceeded in an anti addition mode
to afford â,γ-unsaturated ketones. The reactivity of stannyl enolates as radical transfer agents could be utilized for radical cyclization of
1,6-enynes.
Carbometalation of alkenes and alkynes with metal enolates
has been intensively studied in recent years because it
provides a straightforward and stereoselective method for
carbon chain elongation and functionalization of carbonyl
compounds.1-3 However, the intermolecular version has
remained comparatively unexplored. The known approaches
to this challenging subject include the use of metalated
unsaturated bonds or zinc enolates of hydrazones and
esters.2,3 The carbometalation of common (unmetalated)
alkenes and alkynes with ketone enolates has not yet been
established.
allyltributylstannanes work as radical transfer agents to
perform allylation of carbon radical intermediates ac-
companied by generation of a tributylstannyl radical (Scheme
1, X ) CH2).5 Although stannyl enolates, oxygen analogues
Scheme 1
Previously, we have reported homolytic allylstannylation
of alkenes and alkynes via a radical chain process,4 in which
(1) Intramolecular reactions: (a) Karoyan, P.; Chassaing, G. Tetrahedron
Lett. 1997, 38, 85. (b) Lorthiois, E.; Marek, I.; Normant, J.-F. Tetrahedron
Lett. 1997, 38, 89. (c) Nakamura, E.; Sakata, G.; Kubota, K. Tetrahedron
Lett. 1998, 39, 2157. (d) Kitagawa, O.; Suzuki, T.; Fujiwara, H.; Taguchi,
T. Tetrahedron Lett. 1999, 40, 2549 and references therein.
(2) (a) Yamaguchi, M.; Tsukagoshi, T.; Arisawa, M. J. Am. Chem. Soc.
1999, 121, 4074. (b) Yamaguchi, M.; Hayashi, A.; Hirama, M. J. Am. Chem.
Soc. 1993, 115, 3362 and references therein.
of allylstannanes, also have been proposed to undergo the
SH2′ reaction with carbon radicals,6 no reliable evidence
supporting the evolution of stannyl radicals has been reported
yet, and the synthetic utility of stannyl enolates as radical
(3) (a) Nakamura, E.; Kubota, K.; Sakata, G. J. Am. Chem. Soc. 1997,
119, 5457. (b) Kubota, K.; Nakamura, E. Angew. Chem., Int. Ed. Engl.
1997, 36, 2491.
(4) Miura, K.; Saito, H.; Itoh, D.; Matsuda, T.; Fujisawa, N.; Wang, D.;
Hosomi, A. J. Org. Chem. 2001, 66, 3348.
10.1021/ol016797w CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/20/2001

transfer agents is rather limited.7 Therefore, our interest was
focused on homolytic carbostannylation utilizing the reactiv-
ity of stannyl enolates. We describe herein the AIBN-initiated
carbostannylation of alkenes and alkynes with ketone stannyl
enolates (Scheme 1, X ) O) and its application to the
cyclization of 1,6-enynes.
Trialkylstannyl enolates are in metalotropic equilibrium
between O- and C-stannylated forms (enol and keto forms).8
The keto form would not be available for the homolytic
substitution.6 Our study commenced with cyclohexanone
tributylstannyl enolate,9 which exists only as the enol form.8
Contrary to our expectation, the AIBN-initiated reaction of
methyl acrylate (2a), a good stannyl radical acceptor, with
the enolate resulted in no desired adduct. As the result of
experiments with several stannyl enolates, aromatic ketone
enolates were found to be generally reactive toward carbo-
metalation of electron-deficient alkenes.
Introduction of a fluorine atom at the para position of 1a
(1b, keto:enol ) 74:26) did not affect the reactivity toward
carbostannylation (entry 1 in Table 1). Interestingly, p-
Table 1. Carbostannylation of Alkenes 2 with Stannyl Enolates
1a
Acetophenone tributylstannyl enolate (1a) forms a 74:26
tautomeric mixture of keto and enol forms in C6D6 at room
temperature.10 In the presence of AIBN (0.2 equiv), treatment
of 2a with 1a (4 equiv) in benzene at 80 °C gave the
carbostannylated product 3aa in 40% yield (Scheme 2). The
Scheme 2
reactivity of acrylonitrile (2b) to 1a was similar to that of
2a. Without AIBN, the carbometalation was completely
suppressed. Baba et al. have reported that the bromide anion
promoted reaction of 2a with 1a affords the Michael adduct
4.11 This observation is consistent with the well-established
reactivity of stannyl enolates as carbon nucleophiles.12 In
contrast, the present reaction did not form 4 at all. Thus, the
radical-initiated system dramatically changed the reaction
course of 1a.
a All reactions were performed with 1 (2.00 mmol), 2 (0.50 mmol), and
AIBN (0.10 mmol) in benzene (2.5 mL) at 80 °C. b Sn ) SnBu3. The ratios
of keto to enol in C6D6 at room temperature are as follows: 1b, 74:26; 1c,
99:<1; 1d-f, <1:99. The value “<1” means that the minor tautomer was
not detected by 270 MHz 1H NMR. c The relative configuration was not
determined. d 2c: cyclohexyl acrylate (R1 ) CO2-c-Hex).
methoxy derivative 1c takes only the keto form. As predicted
from the structure, 1c was insensitive to 2a (entry 2). Stannyl
enolate 1d derived from propiophenone consists of only the
enol form feasible for the SH2′ reaction; however, the use
of 1d was not effective in improving the efficiency of
carbostannylation (entry 3). On the other hand, indanone and
tetralone stannyl enolates, 1e and 1f, showed higher reactivity
to electron-deficient alkenes, although they also are substi-
tuted at the reaction site (entries 4-8). Unfortunately, the
carbostannylation of styrene and 1-octene did not proceed
even with 1f.
As shown in Table 2, the carbostannylation of alkynes
with stannyl enolates 1a and 1f proceeded in an anti addition
mode to afford â,γ-unsaturated ketones.13 A similar trend
in stereoselectivity was observed in our previous study on
the radical-based allylstannylation.4 The stereochemical
(5) (a) Curran, D. P. ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, p 715. (b) Pereyre,
M.; Quintard, J.-P.; Rahm, A. Tin in Organic Synthesis; Butterworth:
London, 1987.
(6) (a) Russell, G. A.; Herold, L. L. J. Org. Chem. 1985, 50, 1037. (b)
Watanabe, Y.; Yoneda, T.; Ueno, Y.; Toru, T. Tetrahedron Lett. 1990, 31,
6669.
(7) Quite recently, we have reported homolytic alkylation using stannyl
enolates: Miura, K.; Fujisawa, N.; Saito, H.; Wang, D.; Hosomi, A. Org.
Lett. 2001, 3, 2591.
(8) Kobayashi, K.; Kawanisi, M.; Hitomi, T.; Kozima, S. Chem. Lett.
1984, 497.
(9) For preparation of stannyl enolates, see: Pereyre, M.; Bellegarde,
B.; Mendelsohn, J.; Valade, J. J. Organomet. Chem. 1968, 11, 97.
(10) Yasuda, M.; Katoh, Y.; Shibata, I.; Baba, A.; Matsuda, H.; Sonoda,
N. J. Org. Chem. 1994, 59, 4386.
(11) Yasuda, M.; Ohigashi, N.; Shibata, I.; Baba, A. J. Org. Chem. 1999,
64, 2180.
(12) Davies, A. G. Organotin Chemistry; VCH: Weinheim, 1997.
4056
Org. Lett., Vol. 3, No. 25, 2001

Scheme 3
Table 2. Carbostannylation of Alkynes 5 with Stannyl
Enolates 1a
alkyne
time, product,
entry enolate
R2
R3
(h)
yield (%)
mixture of the cyclized product 8a and unidentified impuri-
ties. After protonolysis of the mixture with HCl-CH3CN,
methylenecyclopentane 9a was isolated in 49% yield. Allyl
propargyl ether 7b and amine 7c were smoothly converted
to the stannylated heterocycles 8b and 8c in reasonable
isolated yields. Unlike the above results, 1f was not effective
in the cyclization of 7.
In conclusion, we have developed a novel type of
carbometalation reaction via a radical chain process. To the
best of our knowledge, the present reaction is the first
example of intermolecular carbometalation of unmetalated
C-C multiple bonds with ketone metal enolates. The
formation of carbostannylated products 3, 6, and 8 provides
reliable evidence that trialkylstannyl enolates actually un-
dergo the SH2′ reaction to generate a trialkylstannyl radical.
In addition, we have disclosed the synthetic utility of stannyl
enolates as radical transfer agents.
1
2
3
4
5
6
7
8
1a
1f
1f
1f
1f
1f
1f
1f
5a
5a
5b
5c
5d
5e
5f
H
H
H
H
H
H
H
CO2Et
CO2Et
Ph
5
4
4
5
5
5
4
4
6a , 26
6ba ,b 66
6bb, 70
6bc, 69
6bd , 50
6be, 15
6bf, 16
6bg, 41
C6H4-p-Me
cyclohexen-1-yl
10H21
C
SPh
5g CO2Me CO2Me
a See footnote a in Table 1. Except for entry 2, only anti adducts were
obtained. b Z:E ) 82:18. See ref 13.
outcome is probably a result of the approach of the stannyl
enolates to vinyl radical intermediates from the opposite side
of the stannyl group to avoid its steric hindrance (Scheme
1).14 Stannyl enolate 1f exhibited higher reactivity than 1a
as in the reaction with alkenes (entries 1 and 2). Not only
electron-deficient alkynes but also other conjugated alkynes
were available for the carbostannylation with 1f in moderate
to good yields (entries 3-5). In addition, electron-rich
alkynes such as 1-dodecyne and ethynyl phenyl sulfide could
be carbostannylated, although the yields were rather low
(entries 6 and 7).
Acknowledgment. This work was partly supported by
Grants-in-Aid for Scientific Research from the Japan Society
for the Promotion of Science (JSPS) and CREST, Science
and Technology Corporation (JST).
The reactivity of stannyl enolates as radical transfer agents
is applicable to radical cyclization of 1,6-enynes (Scheme
3).15 The AIBN-initiated reaction of 7a with 1a gave a
Supporting Information Available: Experimental details
and spectroscopy data of stannyl enolates and the products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(13) The formation of (E)-6ba (syn adduct) in entry 2 of Table 2 is
attributable to the tributylstannyl radical-mediated isomerization of (Z)-
6ba (anti adduct). (a) Taniguchi, M.; Nozaki, K.; Miura, K.; Oshima, K.;
Utimoto, K. Bull. Chem. Soc. Jpn. 1992, 65, 349. (b) Leusink, A. J.;
Budding, H. A.; Drenth, W. J. Organomet. Chem. 1968, 11, 541.
(14) Giese, B.; Gonza´lez-Go´mez, J. A.; Lachhein, S.; Metzger, J. O.
Angew. Chem., Int. Ed. Engl. 1987, 26, 479.
OL016797W
(15) We have reported radical cyclization of 1,6-enynes using allylstan-
nanes: Miura, K.; Saito, H.; Fujisawa, N.; Hosomi, A. J. Org. Chem. 2000,
65, 8119.
Org. Lett., Vol. 3, No. 25, 2001
4057