Tandem [W(CO)5]-catalyzed cycloisomerization-cyclopropanation reactions directed toward the synthesis of eight-membered carbocycles

Full text of DOI:10.1002/anie.200461414

Communications
Medium-Ring Compounds
Tandem [W(CO)5]-Catalyzed
Cycloisomerization–Cyclopropanation Reactions
Directed toward the Synthesis ofEight-
Membered Carbocycles**
JosØ Barluenga,* Alejandro DiØguez, FØlix Rodríguez,
and Francisco J. Faæanµs
Dedicated to Professor JosØ Elguero
on the occasion of his 70th birthday
The development of new metal-catalyzed reactions for the
formation of carbon–carbon bonds is a major research area in
organic chemistry.[1] Of particular significance are those
tandem processes which allow the formation of several new
bonds in a single step from readily available starting materials,
thus increasing efficiency and minimizing the amount of waste
generated.[2] The potential of Group 6 Fischer carbene com-
plexes to undergo unusual reactions has been widely demon-
strated since their discovery almost 40 years ago.[3] However,
one of the most important drawbacks of these complexes is
that a stoichiometric amount has to be used. Only very few
examples of catalytic processes in which a Group 6 Fischer
carbene complex is implied have been reported.[4,5] Moreover,
for several years we have pursued a program related to the
development of new methodologies for the synthesis of
medium-sized rings promoted by Fischer carbene com-
plexes.[6] Thus,recently we reported a new one-pot process
for the synthesis of eight-membered carbocycles by the use of
ketone enolates and alkenyl carbene complexes.[7] To avoid
the use of stoichiometric amounts of metallic species and to
extend the scope of this method,we initiated an investigation
directed toward the design of a catalytic version of this
process. These studies culminated with the discovery of a
tandem [W(CO)5]-catalyzed cycloisomerization–cyclopropa-
nation reaction,which has been used as the key step for the
synthesis of eight-membered carbocycles.
In our previous studies in this field we demonstrated that
eight-membered rings 1 were readily available from tricyclic
compounds 2 generated from cyclic Fischer carbene com-
plexes 3 (Scheme 1).[7] We envisaged that these complexes 3
could be obtained through a cycloisomerization reaction of 4-
alkyn-1-ol derivatives 4 promoted by pentacarbonyltungsten
[*] Prof. Dr. J. Barluenga, A. DiØguez, Dr. F. Rodríguez, Dr. F. J. Faæanµs
Instituto Universitario de Química Organometµlica “Enrique
Moles”
Unidad Asociada al C.S.I.C.
Universidad de Oviedo
Juliµn Clavería, 8, 33006 Oviedo (Spain)
Fax: (+34)98-5103-450
E-mail: barluenga@uniovi.es
[**] We gratefully acknowledge financial support from the DGICYT
(BQU-2001-3853), FICYT (grant to A.D.), and MCYT (“Ramón y
Cajal” contract to F.R.).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
126
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DOI: 10.1002/anie.200461414
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Angewandte
Chemie
Table 1: Tricyclic compounds 2 from the catalytic cycloisomerization
reaction of alkynol derivatives 4.
4
R1
R2
2
Method A[a]
Yield [%][c]
Method B[b]
Yield [%][c]
4a[d]
4b[d]
4c[d]
4d[d]
4e[d]
4 f[d]
4g[d]
4h[d]
4i[f]
H
Me
Bu
allyl
c-C3H5
Ph
4-MeOC6H4
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2 f
90
69
85
74
60
82
84
80
88
91
–
70
87
80[e]
61
83
84
82
86
–
2g
2h
2i
Scheme 1. Proposed catalytic cycle for the synthesis of tricyclic com-
pounds 2, and further transformation into eight-membered carbocycles
1.
=
(E)-PhCH CH
À
À
(CH2)4
4j[g]
H
OBn
2j[h]
[a] The alkynol 4 was stirred as a solution in THF with preformed
[(thf)W(CO)5] (25 mol%) at room temperature for 24 h. [b] A solution of
the alkynol 4 in THF was irradiated with [W(CO)6] (10 mol%) and Et3N
(2 mol%) for 12 h. [c] Yield of the isolated product based on the starting
alkynol 4. [d] Racemic mixture. [e] In this case the amount of [W(CO)6]
can be decreased to 5 mol% without any observed decrease in the yield
of the reaction. [f] The racemic 1S*,2S* diastereoisomer was used.
[g] The 4S,5S enantiomer was used. [h] The 1R,3S,5S,6S enantiomer was
obtained; [a]2D0 =À26.7 (c=0.45, CH2Cl2).
complexes.[8] The subsequent cyclopropanation reaction of
complexes 3 should generate the tricyclic compounds 2,with
regeneration of the pentacarbonyltungsten species. Thus,a
catalytic process as shown in Scheme 1 could be feasible.
Our initial attempts to promote the tandem sequence
described above employed the method developed by McDo-
nald et al. for the synthesis of cyclic enol ethers from 4-alkyn-
1-ol derivatives.[4c] The established conditions for this cyclo-
isomerization are treatment with triethylamine or 1,4-diaza-
bicyclo[2.2.2]octane (dabco,200 mol%) in the presence of
[W(CO)6] (5–25 mol%) under constant irradiation,with THF
as the solvent.
secondary and tertiary alcohol derivatives 4. The reaction is
completely diastereoselective,and a single diastereoisomer of
the product was observed in all cases.[9] It should be noted that
the alternative diastereoisomer would be significantly more
strained. The enantiopure tricyclic compound 2j was isolated
when the reaction was performed with the alkynol derivative
4j.
Unfortunately,when we employed this method with the
starting alkynol derivative 4a,the reaction did not lead to the
expected tricyclic compound 2a; instead the cyclic enol ether
5 was obtained exclusively (Scheme 2). This result indicates
A minor drawback of this method for the catalytic
synthesis of tricyclic compounds 2 is the fact that the catalyst
has to be generated in a separate vessel by irradiation of a
solution of [W(CO)6] in THF and then added to the solution
of the corresponding alkynol derivative. However,the con-
ditions described by McDonald et al.[4c] for the in situ
generation of [W(CO)5] species were shown not to be
applicable to our substrates as a result of the amine-promoted
formation of enol ethers analogous to 5 (see Scheme 1). We
reasoned that we could find appropriate catalytic conditions if
we were able to lower the amount of amine used to such an
extent that the amine could only act to stabilize the [W(CO)5]
species. With this idea in mind,we carried out a set of
experiments with different [W(CO)6]/triethylamine ratios
under a variety of reaction conditions. We were delighted to
find that constant irradiation at 350 nm of a solution of the
corresponding alkynol 4 in THF in the presence of 10 mol%
of [W(CO)6] and only 2 mol% of triethylamine gave similar
results to those obtained when preformed [(thf)W(CO)5] was
used (Scheme 3 and Table 1,method B). As before,the
Scheme 2. Different reaction conditions for the cycloisomerization
reaction of the alkynol derivative 4a.
that the carbene complex 3a (R1 = R2 = H) formed does not
undergo cyclopropanation of the double bond of the allylic
moiety,but instead reacts with the triethylamine present in
the reaction medium to give the enol ether 5. It was clear at
this point that an alternative method to generate the catalytic
[W(CO)5] species in the absence of an amine was required.
We next turned our attention to the use of preformed
[(thf)W(CO)5]. To our delight,when we treated the alkynol
derivative 4a with [(thf)W(CO)5] (25 mol%) in THF at room
temperature for 24 h,the tricyclic compound 2a was obtained
in 90% yield (Scheme 2; for clarity,a 3D representation of
compound 2a has been included).[9]
To check the scope of the reaction,a number of allyl-
substituted 4-alkynol derivatives 4 were tested. As summar-
ized in Table 1 (method A),the reaction gave the expected
tricyclic compounds 2 in very high yield starting from both
Scheme 3. Cycloisomerization reactions of alkynols 4 with catalytic
amounts of [W(CO)6] and Et3N to give compounds 2.
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127

Communications
reaction led to a single diastereoisomer of the products in all
cases studied.[9]
[1] a) Transition Metal Reagents and Catalysts: Innovations in
Organic Synthesis (Ed.: J. Tsuji),Wiley,Chichester, 2000;
To illustrate the synthetic utility of the tungsten-catalyzed
process described,we further transformed the tricyclic com-
pounds 2 into eight-membered carbocycles 1 following the
protocol developed previously by our research group.[7] Thus,
the treatment of compounds 2 with hydrochloric acid in
acetone at room temperature yielded the corresponding
eight-membered carbocycles 1 (Table 2).[9] Under the same
b) Catalytic Asymmetric Synthesis (Ed.: I. Ojima),Wiley-VCH,
Weinheim, 2000.
[2] L. F. Tietze,F. Hautner in Stimulating Concepts in Chemistry
(Eds.: F. Vögtle,J. F. Stoddart,M. Shibasaki),Wiley-VCH,
Weinheim, 2000,p. 38; c) K. C. Nicolaou,E. W. Yue,T. Oshima
in The New Chemistry (Ed.: N. Hall),Cambridge University
Press,Cambridge, 2001,p. 168; d) L. F. Tietze, Chem. Rev. 1996,
96,115; e) L. F. Tietze,U. Beifuss, Angew. Chem. 1993, 105,103;
Angew. Chem. Int. Ed. Engl. 1993, 32,131.
Table 2: Eight-membered carbocycles 1 or 6 from tricyclic compounds 2.
[3] a) J. Barluenga,J. Santamaría,M. Tomµs, Chem. Rev. 2004, 104,
2259; b) A. de Meijere,H. Schirmer,M. Duetsch, Angew. Chem.
2000, 112,4124; Angew. Chem. Int. Ed. 2000, 39,3964; c) W. D.
Wulff in Comprehensive Organometallic Chemistry II, Vol. 12
(Eds.: E. W. Abel,F. G. A. Stone,G. Wilkinson),Pergamon,
Oxford, 1995,p. 470; d) W. D. Wulff in Comprehensive Organic
Synthesis, Vol. 5 (Eds.: B. M. Trost,I. Fleming),Pergamon,
Oxford, 1991,p. 1065.
[4] a) P. Wipf,T. H. Graham, J. Org. Chem. 2003, 68,8798; b) F. E.
McDonald,K. S. Reddy, Angew. Chem. 2001, 113,3765; Angew.
Chem. Int. Ed. 2001, 40,3653; c) F. E. McDonald,K. S. Reddy,Y.
Díaz, J. Am. Chem. Soc. 2000, 122,4304.
[5] For some examples in which Group 6 nonstabilized Fischer
carbene complexes are proposed as intermediates in the catalytic
cycle,see: a) K. Miki,T. Yokoi,F. Nishino,Y. Kato,Y.
Washitake,K. Ohe,S. Uemura, J. Org. Chem. 2003, 68,1557;
b) T. Miura,K. Kiyota,H. Kusama,K. Lee,H. Kim,S. Kim,P. H.
Lee,N. Iwasawa, Org. Lett. 2003, 5,1725; c) N. Iwasawa,T.
Miura,K. Kiyota,H. Kusama,K. Lee,P. H. Lee, Org. Lett. 2002,
4,4463; d) H. Kusama,H. Yamabe,N. Iwasawa, Org. Lett. 2002,
4,2569; e) H. Kusama,J. Takaya,N. Iwasawa, J. Am. Chem. Soc.
2
R1
R2
Product
Yield [%][a]
2a
2b
2c
2d
2e
2 f
2g
2h
2i
H
Me
Bu
allyl
H
H
H
H
H
H
H
H
1a
1b
1c
1d
1e
1 f
6a
6b
1g
1h[b]
98
97
97
95
98
98
95
97
96
97
c-C3H5
Ph
4-MeOC6H4
(E)-PhCH CH
(CH2)4
H
=
2j
OBn
[a] Yield of the isolated product based on the starting cyclic ether 2.
[b] The 1R,4S,5S enantiomer was obtained; [a]2D0 =À13.0 (c=1.15,
CH2Cl2).
2002, 124,11592; f) K. Miki,F. Nishino,K. Ohe,S. Uemura,
Am. Chem. Soc. 2002, 124,5260; g) K. Ohe,T. Yokoi,K. Miki,F.
J.
Nishino,S. Uemura, J. Am. Chem. Soc. 2002, 124,526; h) T.
Miura,N. Iwasawa, J. Am. Chem. Soc. 2002, 124,518; i) N.
Iwasawa,K. Maeyama,H. Kusama, Org. Lett. 2001, 3,3871; j) N.
Iwasawa,M. Shido,H. Kusama, J. Am. Chem. Soc. 2001, 123,
5814; k) K. Maeyama,N. Iwasawa, J. Org. Chem. 1999, 64,1344;
l) K. Maeyama,N. Iwasawa, J. Am. Chem. Soc. 1998, 120,1928;
m) J. Pfeiffer,K. H. Dötz, Angew. Chem. 1997, 109,2948;
Angew. Chem. Int. Ed. Engl. 1997, 36,2828.
reaction conditions,dehydrated compounds 6 were obtained
when the R1 group of the starting compound 2 was an
electron-rich aryl group (i.e. 2g) or an alkenyl group (i.e. 2h).
Interestingly,compounds with structures analogous to that of
1h (R1 = H,R 2 = OBn,1 R,4S,5S enantiomer) have shown
remarkable activity as herbicides. The methodology described
herein provides straightforward access to such compounds.[10]
In summary,we have developed an effective and general
method for the synthesis of eight-membered carbocycles
based on a new tandem tungsten-catalyzed cycloisomeriza-
tion–cyclopropanation reaction. This process is one of very
few examples of a catalytic reaction in which a heteroatom-
stabilized Fischer carbene complex is implied. The method
described herein opens the door to the development of new
catalytic methods which avoid the use of large quantities of
metallic species,thus overcoming one of the main limitations
of Fischer carbene complexes. Moreover,as the procedure
has been shown to be applicable to the synthesis of
functionalized and biologically active compounds from very
simple starting materials,it is expected to find wide applica-
tion in organic synthesis.
[6] For some leading references from our research group on the
synthesis of seven- and eight-membered rings,see: a) J. Bar-
luenga,P. Barrio,L. A. López,M. Tomµs,S. García-Granda,C.
Alvarez-Rffla, Angew. Chem. 2003, 115,3116; Angew. Chem. Int.
Ed. 2003, 42,3008; b) J. Barluenga,F. Aznar,M. A. Palomero,
Angew. Chem. 2000, 112,4514; Angew. Chem. Int. Ed. 2000, 39,
4346; c) J. Barluenga,J. Alonso,F. Rodríguez,F. J. Faæanµs,
Angew. Chem. 2000, 112,2555; Angew. Chem. Int. Ed. 2000, 39,
2460; d) J. Barluenga,M. Tomµs,E. Rubio,J. A. López-Pelegrin,
S. García-Granda,M. PØrez-Priede, J. Am. Chem. Soc. 1999, 121,
3065; e) J. Barluenga,M. Tomµs,A. Ballesteros,J. Santamaría,F.
López-Ortiz,R. Carbajo,S. García-Granda,P. Pertierra, Chem.
Eur. J. 1996, 2,180; f) J. Barluenga,F. Aznar,A. Martín,J. T.
Vµzquez, J. Am. Chem. Soc. 1995, 117,9419.
[7] J. Barluenga,A. DiØguez,F. Rodríguez,J. Flórez,F. J. Faæanµs, J.
Am. Chem. Soc. 2002, 124,9056.
[8] For some recent reviews,see: B. Weyershausen,K. H. Dötz, Eur.
J. Inorg. Chem. 1999,1057; b) F. E. McDonald, Chem. Eur. J.
1999, 5,3103.
[9] The relative configuration of the chiral centers was ascertained
unequivocally by NMR spectroscopic experiments (including
HMQC,HMBC,COSY,and NOESY).
Received: July 23,2004
[10] M. F. Schlecht (du Pont de Nemours,E. I.,and Co.,USA),PCT
Int. Appl. 1992,WO 9203440; [ Chem. Abstr. 1992, 116,255482].
Keywords: alkynols · medium-ring compounds ·
synthetic methods · tandem reactions · tungsten
.
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