Rhenium(I)-catalyzed intramolecular geminal carbofunctionalization of alkynes: Tandem cyclization of ω-acetylenic dienol silyl ethers

Article abstract of DOI:10.1002/anie.200461559

(Chemical Equation Presented) Bicycle production: The low-valent rhenium complex [ReCl(CO)₅] catalyzes a tandem intramolecular cyclization reaction of ω-acetylenic dienol silyl ethers. The alkyne undergoes a geminal carbofunctionalization in the presence of 0.5-3.0 mol % [ReCl(CO) ₅] under photoirradiation to give bicyclic enol silyl ethers in high yields (see scheme, TIPS = triisopropylsilyl).

Full text of DOI:10.1002/anie.200461559

Communications
Homogeneous Catalysis
Rhenium(i)-Catalyzed Intramolecular Geminal
Carbofunctionalization of Alkynes: Tandem
Cyclization of w-Acetylenic Dienol Silyl Ethers**
Hiroyuki Kusama, Hokuto Yamabe, Yuji Onizawa,
Takahiko Hoshino, and Nobuharu Iwasawa*
1,2-Vicinal functionalization of alkynes can readily be carried
out by carbometalation using various kinds of organometallic
reagents, such as Cu, Al, Zr, etc., followed by reaction of the
resulting alkenyl metallic species with electrophiles
(Scheme 1).[1] However, geminal functionalization, and in
particular geminal carbofunctionalization of alkynes, has
remained unexplored despite its high potential as a synthetic
method.[2,3]
Scheme 1. Vicinal- or geminal-functionalization of alkynes.
We have already reported that [W(CO)5(L)] can effec-
tively activate terminal alkynes towards the intramolecular
nucleophilic attack of enol silyl ethers to give various kinds of
carbocycles catalytically.[4] The aim of these studies was to
realize geminal carbofunctionalization of alkynes by using
this strategy. Thus, by appropriate choice of the metallic
reagent, the alkenyl metallic species produced by addition of
carbo-nucleophiles to the electrophilically activated alkynes
would react with carbo-electrophiles not at the a-position but
at the b-position to the metal center to give carbene complex
intermediates, in a similar way to the anions of Fischer-type
carbene complexes[5] (Scheme 1). Further reaction of the
[*] Dr. H. Kusama, H. Yamabe, Y. Onizawa, T. Hoshino,
Prof. Dr. N. Iwasawa
Department of Chemistry
Tokyo Institute of Technology
2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551 (Japan)
Fax: (+81)3-5734-2931
E-mail: niwasawa@chem.titech.ac.jp
[**] This research was partly supported by the Novartis Science
Foundation and a Grant-in-Aid for Scientific Research from the
Ministry of Education, Culture, Sports, Science, and Technology of
Japan. H.Y. was granted a Research Fellowship of the Japan Society
for the Promotion of Science for Young Scientists. We also thank
Central Glass Co., for their generous gift of trifluoromethanesul-
fonic acid.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
468
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DOI: 10.1002/anie.200461559
Angew. Chem. Int. Ed. 2005, 44, 468 –470

Angewandte
Chemie
carbene moiety to release the reactive metallic species would
constitute a catalytic method for the geminal carbofunction-
alization of alkynes.
On the basis of the above considerations we designed the
system shown in Scheme 2. Thus, treatment of acetylenic
examined the possibility of using other transition-metal
[2b,c,e,f]
[2d,e]
complexes. PtCl2
(67% yield) and AuBr3
(79%
yield) also showed moderate catalytic activity towards this
transformation, and furthermore [ReCl(CO)5] was found to
have an extremely high activity. The reaction proceeded even
with 0.5 mol% of [ReCl(CO)5] to give the cyclized products
2a and 3a in 92% yield in a ratio of 86:14 by carrying out the
reaction in toluene under photoirradiation.[9,10] Formation of
the tricyclic compound 3a explicitly implicates the presence
of the intermediate carbene complex C, in which the carbene
À
moiety inserts into the neighboring benzylic C H bond.
Once we established that [ReCl(CO)5] catalyzed the
geminal carbofunctionalization reaction very efficiently, the
reaction of several substrates was examined (Table 2). The
Table 2: Rhenium-catalyzed reaction of dienol silyl ethers (1b–j).
Scheme 2. Tandem cyclization of dienol silyl ethers.
Entry R1
R2
R3
[ReCl(CO)5] [mol%] Yield [%] 2-a:2-b
dienol silyl ethers 1 with an appropriate metallic reagent
should give zwitterionic intermediates B by 5-endo nucleo-
philic cyclization of the enol silyl ether to the electrophilically
activated h2-alkyne complexes A. The alkenyl metallic moiety
produced should then undergo an intramolecular attack at the
b-position of the metal center to the a,b-unsaturated sily-
loxonium moiety to generate bicyclic unstable carbene
complexes C. Finally, the destabilized carbene complex
moiety would undergo a typical carbene reaction, such as
1,2-hydrogen migration, to give the products with regener-
ation of the reactive metallic species.[6]
1
2
3
4
5
6
7
8
9
H
H
H
H
Me Me 1b
Et Me 1c
iPr Me 1d
Ph Me 1e
0.5
0.5
1.0
1.0
3.0
1.0
1.0
1.0
3.0
92
92
86
73
68
76
51
81
74
67:33
70:30
70:30
50:50
22:78
32:68
–
Me Me Me 1 f
Me Ph Me 1g
H
Me
H
H
H
Ph
Me 1h
Me 1i
H
–
1j
85:15
We first examined the reaction of w-acetylenic dienol silyl
ether 1a with 10 mol% of [W(CO)6] under photoirradiation
in toluene in the presence of molecular sieves (4 ꢀ) (Table 1).
Although the tungsten-catalyzed cyclization reaction of enol
silyl ethers with an internal alkyne moiety has not been
examined before,[7] the reaction proceeded as expected and
the desired bicyclic enol silyl ether 2a was obtained in high
yield as a mixture of diastereomers accompanied by a small
amount of tricyclic compound 3a.[8] Since geminal carbofunc-
tionalization was found to proceed as expected, we further
trisubstituted dienes (1b–e)[11] with a methyl, primary, or
secondary alkyl group as well as a phenyl group at the b-
position (R2) were cyclized to afford the corresponding
bicyclic enol silyl ethers in high yield (Table 2, entries 1–4).
Even the reaction of the tetrasubstituted dienes (1 f, 1g)[11]
proceeded to afford the corresponding substituted bicyclic
enol silyl ethers in high yield. The [ReCl(CO)5]-catalyzed
reaction gave superior results in most cases relative to that
catalyzed by [W(CO)5(L)].[12] In particular, the rhenium-
catalyzed reaction of dienyl silyl ethers 1h and 1i with no
substituent at the b-position (R2 =
H) afforded the desired bicyclic
Table 1: Reaction of dienol silyl ether 1a.
enol silyl ethers in moderate to
high yields. However, the corre-
sponding tungsten-catalyzed reac-
tion proceeded in very low yield
(17%) even with a stoichiometric
amount of [W(CO)5(L)] for 1i. In
addition, a substrate possessing a
terminal alkyne moiety 1j[11] could
Conditions
t [h]
Yield (2a+3a) [%]
2a(a:b):3a
also be employed for this reaction
[W(CO)6] (10 mol%), hn
[PtCl2] (10 mol%), 708C
[AuBr3] (10 mol%), RT
[ReCl(CO)5] (10 mol%), hn
[ReCl(CO)5] (0.5 mol%), hn
4
88
67
79
98
92
86(9:1):14
(Table 2, entry 9). The use of low-
valent rhenium complexes in cata-
lytic synthetic reactions, in partic-
48
24
3
59(1.3:1):41
65(7.7:1):35
91(12.5:1):9
86(4.2:1):14
16
À
ular for C C bond forming reac-
Z=CO2Me, TIPS=triisopropylsilyl, MS=molecular sieves.
tions, is quite limited.[13] The
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469

Communications
2003, 68, 8505; f) K. Miki, T. Yokoi, F. Nishino, Y. Kato, Y.
Washitake, K. Ohe, S. Uemura, J. Org. Chem. 2004, 69, 1557.
[4] a) K. Maeyama, N. Iwasawa, J. Am. Chem. Soc. 1998, 120, 1928;
b) N. Iwasawa, K. Maeyama, H. Kusama, Org. Lett. 2001, 3,
3871; c) H. Kusama, H. Yamabe, N. Iwasawa, Org. Lett. 2002, 4,
2569; d) N. Iwasawa, T. Miura, K. Kiyota, H. Kusama, K. Lee,
P. H. Lee, Org. Lett. 2002, 4, 4463.
[5] For examples of the reaction of Group VI alkenyl metallic
species with carbo-electrophiles, see; a) W. D. Wulff, S. R.
Gilbertson, J. Am. Chem. Soc. 1985, 107, 503; b) Y.-C. Xu,
W. D. Wulff, J. Org. Chem. 1987, 52, 3263; c) R. Aumann, H.
Heinen, Chem. Ber. 1987, 120, 537; d) B. A. Anderson, W. D.
Wulff, A. Rahm, J. Am. Chem. Soc. 1993, 115, 4602.
[6] Non-heteroatom-substituted alkyl carbene complexes, especially
those having an a-hydrogen atom, are highly reactive to give 1,2-
hydrogen migration products, see: a) C. P. Casey, L. D. Albin,
T. J. Burkhardt, J. Am. Chem. Soc. 1977, 99, 2533; b) J.
Barluenga, A. Ballesteros, R. de la R. Bernardo, J. Santamarꢆa,
E. Rubio, M. Tomꢄs, J. Am. Chem. Soc. 2003, 125, 1834.
[7] The [W(CO)5(L)]-catalyzed cyclizations are assumed to proceed
through both a h2-alkyne complex and a vinylidene complex as
determined by deuterium experiments on the cyclization of an
w-acetylenic enol silyl ether.[4a]
extremely high activity of a rhenium(I)–carbonyl complex for
the electrophilic activation of alkynes towards attack of
carbo-nucleophiles observed here should be noted as a new
potential use of rhenium complexes in organic synthesis.[14]
In summary, we have developed a geminal carbofunction-
alization reaction of alkynes catalyzed by [ReCl(CO)4(L)].
À
Utilization of this intermediate carbene moiety for further C
C bond formations will enable the construction of up to four
À
C C bonds onto an alkyne in a single operation.
Experimental Section
Cyclization of 1a: Compound 1a (292 mg, 0.60 mmol) was added to a
mixture of [ReCl(CO)5] (1.1 mg, 0.0030 mmol, 0.5 mol%) and
activated 4-ꢀ molecular sieves in degassed toluene (1.0 mL). The
mixture was photoirradiated (250 W super high-pressure Hg lamp)
for 16 h, and then the reaction mixture was directly passed through
silica gel deactivated with 5 wt% of water (10% ethyl acetate in
hexane) to give the crude product, which was purified by preparative
thin-layer chromatography (10% ethyl acetate in hexane) to give
269 mg (0.55 mmol, 92%) of 2a and 3a (2a-a:2a-b:3a = 69:17:14).
[8] The tricyclic enol silyl ether 3 was not obtained when the
substrates without a gem-diester (1b–i) were employed.
[9] The reaction of 1a with 0.5 mol% of [W(CO)6] under photo-
irradiation in toluene proceeded to only a small extent after 16 h
to give < 5% of cyclized product 2a.
[10] It has already been reported that coordinatively unsaturated
species [ReX(CO)4(L)] was generated by thermal liberation of
carbon monoxide from [ReX(CO)5] and acted as a Lewis acid
for a Friedel–Crafts type acylation.[13a] The reactions of 1b with
1.0 mol% [ReCl(CO)5] in refluxing toluene without photoirra-
diation also gave bicyclic product 2b in 47% yield. On the basis
of these results, we currently believe that [ReCl(CO)4(L)] is the
active species in this reaction.
Received: August 6, 2004
Keywords: alkynes · cyclization · homogeneous catalysis ·
.
rhenium · silyl ethers
[1] For reviews on carbometalation, see: a) I. Marek, J. F. Normant
in Metal-catalyzed Cross-coupling Reactions (Eds.: F. Diederich,
P. J. Stang), Wiley-VCH, Weinheim, 1997, p. 271; b) W.
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Engl. 1989, 28, 38; c) E. Negishi, Chem. Eur. J. 1999, 5, 411.
[2] To the best of our knowledge, the geminal carbofunctionaliza-
tion reactions previously reported have been confined to
cyclopropanations to generate cyclopropyl carbene complexes,
see: a) N. Chatani, K. Kataoka, S. Murai, J. Am. Chem. Soc.
1998, 120, 9104; b) A. Fꢁrstner, F. Stelzer, H. Szillat, J. Am.
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Echavarren, J. Am. Chem. Soc. 2001, 123, 10511; d) C. Nieto-
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A. M. Echavarren, Angew. Chem. 2004, 116, 2456; Angew.
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Harrak, C. Blaszykowski, M. Bernard, K. Cariou, E. Mainetti, V.
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Chem. Soc. 2004, 126, 9524; h) M. R. Luzung, J. P. Markham,
F. D. Toste, J. Am. Chem. Soc. 2004, 126, 10858.
[11] The geometry of the major isomer is shown in the scheme; see
the Supporting Information for details of the isomeric ratio of
the starting materials.
[12] The reactions of 1a–g and 1j gave bicyclic silyl enol ethers in
high yield (67–81% yield) with 5–20 mol% [W(CO)6] under
photoirradiation in toluene. The [W(CO)5(L)]-catalyzed reac-
tions of 1e and 1g gave slightly better results than the
corresponding rhenium-catalyzed reactions, but they required
a larger amount of tungsten complex (for 1e, 5 mol% of
[W(CO)6] gave 2e in 81% yield; for 1g, 10 mol% of [W(CO)6]
gave 2g in 79% yield).
À
[13] For examples of [ReX(CO)5] (X = Cl, Br)-catalyzed C C bond
forming reactions, see: a) H. Kusama, K. Narasaka, Bull. Chem.
Soc. Jpn. 1995, 68, 2379; b) Y. Nishiyama, F. Kakushou, N.
Sonoda, Bull. Chem. Soc. Jpn. 2000, 73, 2779; See also, Ref. [2a].
À
For examples of [ReCl(N2)(PMe2Ph)4]-catalyzed C C bond-
forming reactions, see: c) Y. Koga, H. Kusama, K. Narasaka,
[3] For examples of geminal functionalization of alkynes involving
heteroatom–carbon bond formation, see: a) N. Iwasawa, M.
Shido, H. Kusama, J. Am. Chem. Soc. 2001, 123, 5814; b) H.
Kusama, J. Takaya, N. Iwasawa, J. Am. Chem. Soc. 2002, 124,
11592; c) J. Takaya, H. Kusama, N. Iwasawa, Chem. Lett. 2004,
33, 16; d) F. Nishino, K. Miki, Y. Kato, K. Ohe, S. Uemura, Org.
Lett. 2003, 5, 2615; e) K. Miki, K. Ohe, S. Uemura, J. Org. Chem.
Bull. Chem. Soc. Jpn. 1998, 71, 475. For examples of
À
[ReOCl3(dppm)]-catalyzed C C bond-forming reactions
(dppm = bis(diphenylphosphanyl)methane),
see:
d) M. R.
Luzung, F. D. Toste, J. Am. Chem. Soc. 2003, 125, 15760.
[14] For examples of [ReBr(CO)5]-catalyzed additions of carboxylic
acids to terminal alkynes, see; R. Hua, X. Tian, J. Org. Chem.
2004, 69, 5782.
470
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Angew. Chem. Int. Ed. 2005, 44, 468 –470