Asymmetric benzopentaannulation from tungsten ((-)- menthyloxy)(aryl)carbene complexes, alkynyllithiums, and methyl triflate [3]

Full text of DOI:10.1021/ja982036l

J. Am. Chem. Soc. 1998, 120, 12129-12130
12129
Scheme 1a
Asymmetric Benzopentaannulation from Tungsten
((-)-Menthyloxy)(aryl)carbene Complexes,
Alkynyllithiums, and Methyl Triflate
Jose´ Barluenga,*,† Andre´s A. Trabanco,† Josefa Flo´rez,†
Santiago Garc´ıa-Granda,‡ and Mar´ıa-Amparo LLorca‡
Instituto UniVersitario de Qu´ımica Organometa´lica
“Enrique Moles”, Unidad Asociada al CSIC, and
Departamento de Qu´ımica F´ısica y Anal´ıtica,
UniVersidad de OViedo, Julia´n ClaVer´ıa 8
33071 OViedo, Spain
ReceiVed June 11, 1998
We recently reported the regio- and stereoselective conjugate
nucleophilic addition of sec-butyl-, tert-butyl-, or phenyllithium
to the aromatic nucleus of (menthyloxy)(aryl)carbene complexes
of chromium. Further reaction with methyl triflate of the initially
formed 1,4- or 1,6-adducts resulted in the development of a new
asymmetric dearomatization reaction.1 To evaluate the scope of
this reaction depending on the nature of the organolithium
compound, we decided to study the behavior of alkynyllithiums,
which indeed underwent a completely different type of reaction,
1,2-addition followed by 1,3-propargylic shift, leading to the
synthesis of enantiomerically enriched trans-2,3-disubstituted-1-
indanones through a novel metal-assisted diastereoselective ben-
zopentaannulation.2 The addition of alkynyllithiums to the carbene
carbon of complexes bearing a small alkoxy group (methoxyphe-
nyl- or alkylcarbene complexes of tungsten) has been previously
described.3 The reactions of the propargyl metallic species thus
generated with electrophiles have been proposed to occur with
1,2-migration of the metal group to generate a vinylmetal species
which was detected by NMR studies of the protonation reaction
with methanol, but whose exact structure is still unknown.4
The reactions of tungsten ((-)-menthyloxy)(aryl)carbene com-
plexes 1a,b with phenylethynyllithium (2a) were carried out in
THF between -40 °C and room temperature (rt). Subsequent
addition of methyl triflate in Et2O having previously removed
THF under reduced pressure resulted in the formation with
moderate chemical yields of a nearly equimolecular mixture of a
five-membered ring benzannulated product 3 and a propargylic
ether 4, each one as a mixture of diastereoisomers (Scheme 1).
Whereas the propargylic ethers 4a,b were isolated as an 1:1
diastereoisomeric mixture, the indenyl ethers 3a,b (only the major
isomer is shown) were formed with acceptable diastereoselection
(5.2:1 for 3a and slightly lower 3.5:1 for 3b).5 The structural
isomers 3 and 4 were separated by column chromatography on
silica gel which in addition allowed, in each case, purification of
the major C5 annulated isomer 3a or 3b as well as the slower
moving isomer of acetylenic products 4a,b. Acid hydrolysis of
enol ethers 3a as a single diastereoisomer and 3b as a 5.3:1
mixture of diastereoisomers furnished selectively the correspond-
ing trans-2,3-disubstituted-benzocyclopentanones 5a,b as enan-
a (i) THF, -40 °C to rt; (ii) MeOTf, Et2O, 0 °C.
Scheme 2
Scheme 3a
a (ii) PhCHO, BF3‚OEt2, -78 °C to rt; (iii) 1 N HCl.
tiomerically enriched compounds (90-68% ee, determined by
HPLC analysis on a chiral support in comparison with the
corresponding racemic mixtures). The trans relative configuration
of ketones 5 was ascertained from NOE studies, and the
assignment of the absolute configuration to compounds 3 and 5
was made on the grounds of an X-ray analysis as shown below.
To gain mechanistic insight, we focused on either the isolation
or characterization of reaction intermediates. Thus, as shown in
Scheme 2, the reaction of carbene complex 1a with 2a followed
by cation exchange with an aqueous solution of tetraethylammo-
nium bromide6 gave 6a as a stable yellow solid, which was further
purified by recrystallization from CH2Cl2 at -20 °C. An X-ray
structural analysis of 6a showed it to be a novel anionic metal
allenyl complex,7 indicating that the intermediate formed at rt in
the first reaction step has an allenic structure. On the other hand,
the final product isolated when the reaction of rac-1a with 2a
was treated with benzaldehyde was different depending on the
temperature of the first reaction step (Scheme 3). While furan
7, which presumably is the evolution product during acidic work
up of homoallenic alcohol 8, was isolated when PhCHO was
added to a reaction mixture kept at -40 °C, homopropargylic
alcohol 9 was formed by adding PhCHO to a reaction mixture
which had previously reached rt. In addition, the reaction of
† Instituto Universitario de Qu´ımica Organometa´lica “Enrique Moles”.
‡ Departamento de Qu´ımica F´ısica y Anal´ıtica. X-ray analyses.
(1) Barluenga, J.; Trabanco, A. A.; Flo´rez, J.; Garc´ıa-Granda, S.; Mart´ın,
E. J. Am. Chem. Soc. 1996, 118, 13099.
(2) For a recent review on transition-metal-assisted cycloaddition reactions,
see: Fru¨hauf, H.-W. Chem. ReV. 1997, 97, 523.
(3) (a) Iwasawa, N.; Maeyama, K.; Saitou, M. J. Am. Chem. Soc. 1997,
119, 1486. (b) Iwasawa, N.; Maeyama, K. J. Org. Chem. 1997, 62, 1918.
(4) (a) Iwasawa, N.; Ochiai, T.; Maeyama, K. Organometallics 1997, 16,
5137. (b) Iwasawa, N.; Ochiai, T.; Maeyama, K. J. Org. Chem. 1998, 63,
3164.
(5) The diastereoselectivity of the benzopentaannulation reaction was
significantly higher (8:1) when the (-)-8-phenylmenthyloxy derivative
analogous to 1a was used, but unfortunately, the major product of this reaction
was an 1,2-dialkoxy-1,3-enyne. These results will be reported separately.
(6) Casey, C. P.; Polichnowski, S. W.; Tuinstra, H. E.; Albin, L. D.;
Calabrese, J. C. Inorg. Chem. 1978, 17, 3045.
(7) To our knowledge, the only group 6 metal allenyl species which have
been reported, are the following. Betaine compounds: (a) Berke, H.; Ha¨rter,
P.; Huttner, G.; Zsolnai, L. Z. Naturforsch. B 1981, 36, 929. (b) Fischer, H.;
Reindl, D.; Troll, C.; Leroux, F. J. Organomet. Chem. 1995, 490, 221. Neutral
compounds: (c) Keng, R.-S.; Lin, Y.-C. Organometallics 1990, 9, 289. (d)
Chen, M.-C.; Keng, R.-S.; Lin, Y.-C.; Wang, Y.; Cheng, M.-C.; Lee, G.-H.
J. Chem. Soc., Chem. Commun. 1990, 1138.
10.1021/ja982036l CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/06/1998

12130 J. Am. Chem. Soc., Vol. 120, No. 46, 1998
Communications to the Editor
Scheme 4
Scheme 6
Scheme 5
carbon atom (C2), furnishing initially the nonheteroatom-stabilized
2-phenylvinylcarbene complex F, an undetected intermediate
which is analogous to that accepted in the Do¨tz benzannulation
reaction and which would undergo subsequent direct cyclization,
according to one of the previously proposed mechanisms,14 to
yield indene-derived product 3a.15 The formation of intermediate
F is supported by the isolation of heteroatom-stabilized 2-phe-
nylvinylcarbene complex 10 (Scheme 4), although on heating, it
did not yield the corresponding indene product despite the
apparently structural similarity with a previously reported com-
plex.16 This different behavior could be a consequence of a more
favorable thermal decomposition of 10 to enol ether 11 with
elimination of the metal fragment and a menthyl group, the latter
presumably as an alkene. If the methylation of B at C2 is not a
diastereoselective reaction, as seems to indicate the result of
Scheme 4, and given that only the E configuration shown for F
in Scheme 5 has the appropriate geometry for cyclization, it could
be possible that the presumably formed Z isomer of F would be
undergoing decomposition to unidentified products which could
account for the moderate yields of reactions in Scheme 1.
Given that racemic methyl indenyl ethers analogous to com-
pounds 3 have been formed either upon photolysis or in thermal
reactions of tungsten (methoxy)(aryl)carbene complexes with
internal alkynes,15 we decided to test this thermal cycloaddition
with chiral carbene complex 1a.17 Refluxing a toluene solution
of complex 1a and 1-phenylpropyne for 1.5 h led to the
corresponding benzopentaannulated product as the tungsten
tricarbonyl complex 12 with excellent chemical yield but low
diastereoselectivity (only the major isomer is shown), presumably
due to the much higher reaction temperature (110 Vs 0 °C).
Removal of the metal fragment by exposing an acetonitrile
solution of 12 to air and light occurred with concurrent hydrolysis
of the enol ether, affording the same ketone previously obtained
5a as a 2:1 mixture of enantiomers. Yellow crystals of 12 were
obtained by hexane/CH2Cl2 recrystallization of a 13:1 diastere-
oisomeric mixture, and a single-crystal X-ray structure determi-
nation allowed assignment of the absolute configuration depicted
for compounds 3, 5, and 12 (Schemes 1 and 6).
carbene complex 1a with the in situ generated enantiomerically
pure lithium 2-alkoxyacetylide 2b8 afforded exclusively (alkoxy)-
(2-phenylvinyl)carbene complex 10 as an 1.4:1 mixture of
diastereoisomers (Scheme 4). Further thermolysis of this complex
resulted in the diastereoselective formation of the open-chain
2-alkoxyvinyl ketone 11. A reaction pathway accounting for all
of these results is outlined in Scheme 5 with compounds 1a and
2a. Lithium acetylide 2a reacts with (menthyloxy)(aryl)carbene
complex 1a to give selectively the 1,2-adduct A. This anionic
propargyltungsten species is stable at low temperature (-40 °C),
but on warming to rt, it undergoes a 1,3-propargylic rearrange-
ment9 to afford anionic allenyltungsten intermediate B. Direct
evidence of this thermal 1,3-migration of the (CO)5W moiety was
obtained by monitoring the conversion of a THF-d8 solution of
A to B by NMR spectroscopy. Between -40 and -10 °C the
1H and 13C NMR spectra showed exclusively the resonances
attributed to A. Upon warming to 0 °C, new NMR signals grow
in, and at 0 °C, only the resonances corresponding to B show
up.10 The driving force for this rapid isomerization may arise from
the presumably greater stability of the alkenylmetal beside the
alkylmetal and the relief of crowding at the quaternary propargyl
terminus.11 These organometallic derivatives A and B combine
regioselectively with carbonyl electrophiles with concomitant
rearrangement of the hydrocarbon fragment (SE2′ addition):12 the
acetylenic derivative A to an allenic structure C (attack at C3),13
and the allenyl intermediate B to an acetylenic product D (attack
at C1). However, in the reaction of allenyl complex B with
MeOTf, in addition to propargyl ether 4a (D, E ) Me, attack at
C1), the attack of the electrophile takes place at the central allenic
In summary, we report a three-component benzopentaannula-
tion of ((-)-menthyloxy)(aryl)carbene complexes via a novel
anionic allenyltungsten intermediate. Ongoing efforts focus on
increasing chemical yield and/or diastereoselectivity.
(8) Kann, N.; Bernardes, V.; Greene, A. E. Org. Synth. 1996, 74, 13.
(9) An 1,3-propargylic migration of the (CO)5M (M ) Cr, W) moiety has
been invoked to explain a final reaction product but has not been directly
observed: (a) Aumann, R.; Fro¨hlich, R.; Zippel, F. Organometallics 1997,
16, 2571. For 1,3-allylic migration of the (CO)5M unit, see: (b) Sleiman, H.
F.; McElwee-White, L. J. Am. Chem. Soc. 1988, 110, 8700. (c) Hegedus, L.
S.; Lundmark, B. R. J. Am. Chem. Soc. 1989, 111, 9194. (d) Fischer, H.;
Schlageter, A.; Bidell, W.; Fru¨h, A. Organometallics 1991, 10, 389.
(10) A similar variable-temperature NMR study carried out with [(meth-
oxy)(phenyl)methylene]pentacarbonyltungsten and 2a revealed that in this case
the 1,3-shift of the (CO)5W moiety was a slower process which required
slightly higher temperature (10 °C) to be complete. In addition, treatment of
the allenylmetal species thus generated with MeOTf in Et2O afforded
exclusively the corresponding propargyl ether (attack at C1, 71%).
(11) Allenyl isomers are typically more stable than propargyl isomers: (a)
Pu, J.; Peng, T.-S.; Arif, A. M.; Gladysz, J. A. Organometallics 1992, 11,
3232. (b) Ogoshi, S.; Fukunishi, Y.; Tsutsumi, K.; Kurosawa, H. J. Chem.
Soc., Chem. Commun. 1995, 2485. (c) Cunico, R. F. J. Org. Chem. 1997, 62,
8955. (d) O’Connor, J. M.; Chen, M.-C.; Fong, B. S.; Wenzel, A.; Gantzel,
P. J. Am. Chem. Soc. 1998, 120, 1100. See also refs 7c,d.
Acknowledgment. This research was supported by the DGICYT
(Grants PB92-1005 and PB96-0556).
Supporting Information Available: Experimental procedures, ana-
lytical and spectral data for compounds 3-7 and 9-12, and X-ray
crystallographic data of 6a and 12 (32 pages, print/PDF). See any current
masthead page for ordering information and Web access instructions.
JA982036L
(14) Chan, K. S.; Peterson, G. A.; Brandvold, T. A.; Faron, K. L.; Challener,
C. A.; Hyldahl, C.; Wulff, W. D. J. Organomet. Chem. 1987, 334, 9.
(15) For a review, see: (a) Schore, N. E. Chem. ReV. 1988, 88, 1081. (b)
Foley, H. C.; Strubinger, L. M.; Targos, T. S.; Geoffroy, G. L. J. Am. Chem.
Soc. 1983, 105, 3064. (c) Yamashita, A.; Toy, A.; Watt, W.; Muchmore, C.
R. Tetrahedron Lett. 1988, 29, 3403. (d) Do¨tz, K. H.; Larbig, H. Bull. Soc.
Chim. Fr. 1992, 129, 579. (e) Barluenga, J.; Aznar, F.; Barluenga, S. J. Chem.
Soc., Chem. Commun. 1995, 1973.
(16) (a) Do¨tz, K. H.; Pruskil, I. Chem. Ber. 1978, 111, 2059. See also: (b)
Do¨tz. K. H.; Neugebauer, D. Angew. Chem., Int. Ed. Engl. 1978, 17, 851. (c)
Aumann, R.; Jasper, B.; Fro¨hlich, R. Organometallics 1995, 14, 231.
(17) Do¨tz benzannulation reaction of the corresponding chromium carbene
complex with a terminal alkyne has been described: Do¨tz, K. H.; Stinner,
C.; Nieger, M. J. Chem. Soc., Chem. Commun. 1995, 2535.
(12) (a) Yamamoto, H. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: New York, 1991; Vol. 2, p 81. (b) Chen, C.-C.;
Fan, J.-S.; Lee, G.-H.; Peng, S.-M.; Wang, S.-L.; Liu, R.-S. J. Am. Chem.
Soc. 1995, 117, 2933.
(13) Presumably, the reaction of the propargyl complex A with the aldehyde
could occur through an initial 1,2-migration of the (CO)5W fragment: see ref
4 and references therein.