[3+2] and [4+1] cycloaddition reactions of fischer alkoxy(alkenyl)carbene complexes with electronically neutral 1,3-dienes

Article abstract of DOI:10.1002/anie.200390087

Regio- and stereochemically controlled formation of cyclopentenes has been achieved through the reaction of transition-metal-alkoxy(alkenyl)carbene complexes and neutral 1,3-dienes (see scheme; BHT=2,6-di-tert-butyl-4-methylphenol). Reaction conditions di

Full text of DOI:10.1002/anie.200390087

Angewandte
Chemie
Controlled Cycloadditions
reaction of the carbene ligand as a three-carbon-atom
synthon, which seems to be more general than that in which
it acts as a one-carbon-atom synthon, took place with total
regio- and diastereoselectivity, and high asymmetric induction
can be observed when alkenylcarbene complexes derived
from (À)-8-phenylmenthol are used.[14]
[3þ2] and [4þ1] Cycloaddition Reactions of
Fischer Alkoxy(alkenyl)carbene Complexes with
Electronically Neutral 1,3-Dienes**
In the initial experiment, the standard protocol previously
established for the intermolecular cyclopropanation of simple
alkenes with alkenylcarbene complexes[15] was utilized to
evaluate the reaction of methoxycarbene complex 1a with
isoprene (2a). Accordingly, this reaction was conducted in
THF with five equivalents of diene 2a in the presence of a
catalytic quantity (10 mol% with respect to the diene) of 2,6-
di-tert-butyl-4-methylphenol (BHT).[16] After heating for 9 h
at 808C, a nearly equimolar mixture of tetrasubstituted
cyclopentene enol ether 3a and trisubstituted cyclopentene
4a was obtained (Scheme 1). These structural isomers were
easily separated by column chromatography. Compound 3a
was formed as a single diastereoisomer. We observed that
performing the reaction in toluene led exclusively to the
[3þ2] cycloadduct 3a in high yield, whereas heating the
reaction in THF at 1208C in a sealed flask gave only the [4þ1]
cycloadduct 4a, although only in moderate yield. The
reactions of other alkenylcarbene complexes with different
1,3-dienes were carried out under both of the above-
mentioned reaction conditions to produce the corresponding
[3þ2] or [4þ1] cycloadducts; the results are summarized in
both Table 1 and Scheme 2.
The reaction of 3-aryl/heteroaryl- or 3-alkyl-substituted
alkenylcarbene chromium complexes 1a d with 1,3-dienes
2a c in toluene proceeded smoothly to afford the cyclo-
pentenes 3a f diastereoselectively and with high efficiency
(Table 1, entries 1 6). The reaction with the structurally
analogous molybdenum carbene complex 1e, which was
conducted at 458C, was less efficient (entry 7), while treat-
ment with the corresponding tungsten complex 1 f gave
compound 3a with comparable yield, but required a much
longer reaction time (entry 8).[17] Acid hydrolysis of enol
ethers 3a d and f (where R2 is not H) furnished cyclo-
Josÿ Barluenga,* Salomÿ LÛpez, and Josefa FlÛrez
Dedicated to Professor Julio D. MartÌn
on the occasion of his 60th birthday
Reactions of the heteroatom-stabilized carbene complexes of
group 6 metals with conjugated carbodienes allow for the
construction of cyclic products with different ring sizes[1] that
depend upon both the nature of the reaction partners and the
reaction conditions.[2] Electron-deficient 1,3-dienes are
known to react when heated with alkoxy(aryl/alkyl)carbene
complexes to afford [2Dþ1C][3] cycloadducts with high selec-
tivity.[4] While analogous reactions with aminocarbene com-
plexes provide a [4Dþ1C] cycloadduct with pentacarbonyl-
[(N,N-dimethylamino)methylene]chromium[5] or [4Dþ3C] cy-
cloadducts with molybdenum amino(alkenyl)carbene com-
plexes.[6] Electron-rich 1,3-dienes also react with alkoxy(alke-
nyl)carbene complexes, which undergo a [4Dþ3C] cycloaddi-
tion reaction in the case of the chromium derivatives,[7] and a
[4Dþ2C] cycloaddition process when tungsten carbene com-
plexes are involved.[8,9] Nevertheless, the corresponding
[4Dþ1C] adduct was isolated when a Cr complex was mixed
at room temperature with 2-methyl-1,3-dimorpholino-1,3-
butadiene.[7c] In addition, the reaction of alkenylcarbene
derivatives with a 1-acceptor-3-donor-substituted 1,3-diene
furnished cyclopentenes, which are the [3Cþ2D] adducts of the
corresponding carbene ligand to the electron-rich terminal
double bond of the silyloxydiene.[7d,10] Simple 1,3-dienes have
been shown to undergo either a thermally selective mono-
cyclopropanation reaction ([2Dþ1C] cycloaddition) with alk-
oxy(alkyl/aryl)carbene complexes of Mo and Cr,[11] or a room-
temperature Diels Alder reaction ([4Dþ2C] annulation) with
alkoxy(alkenyl)carbene complexes of Cr and W.[8a,c,12] On the
other hand, the photolytic reaction of chromium alkoxy(alk-
yl/aryl)carbene complexes with simple cyclic 1,3-dienes
produced bicyclic cyclobutanones ([2Dþ1Cþ1CO] annulation
products) with a high degree of selectivity.[13]
Me
OMe
2a
OMe
+
(CO)5Cr
Ph
10% BHT
MeO
Ph
sealed flask
1a
3a
4a
Ph
Herein, we report the first examples of [3Cþ2D] or [4Dþ1C]
cycloaddition reactions between alkoxy(alkenyl)carbene
complexes and electronically neutral 1,3-dienes. The transfer
THF
PhCH3 80 °C 9 h
THF 120 °C 1 h
80 °C 9 h
42%
94%
–
36%
–
47%
Scheme 1. Illustration of [3þ2] and [4þ1] cycloaddition reactions.
[*] Prof. Dr. J. Barluenga, S. LÛpez, Dr. J. FlÛrez
Instituto Universitario de QuÌmica Organometµlica ™Enrique Mo-
les∫
R2
THF, 120 °C
10% BHT
R2
OMe
Unidad Asociada al CSIC, Universidad de Oviedo
Juliµn ClaverÌa 8, 33071 Oviedo (Spain)
Fax: (þ34)98-510-3450
OMe
+
R1
(CO)5Cr
sealed flask
R1
1a
1b
2c
2a
2 h
1 h
4b 31%
4c 30%
E-mail: barluenga@sauron.quimica.uniovi.es
[**] This research was supported by the DGICYT (PB97-1271). We thank
Dr. Eduardo Rubio for assistance with the 2D NMR spectra.
4b R1 = Ph, R2 = (CH2)2CH=CMe2
4c R1 = 2-furyl, R2 = Me
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Scheme 2. [4þ1] Cycloaddition reactions.
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Table 1: [3þ2] Cycloaddition reactions of alkenylcarbene complexes with simple 1,3-dienes and their
subsequent hydrolysis reactions.
provided a 2:1 mix-
ture of cyclopenta-
none 5 f and cyclo-
hexene derivative
7, respectively (Ta-
ble 2, entry 1), whereas the analo-
gous reaction with the trisubstituted
1,3-diene 2 f afforded only the cor-
responding [3þ2] adduct 5h (Ta-
ble 2, entry 4). Formation of the
minor compound 7, which is the
formal [4Dþ2C] cycloadduct/oxida-
tion product, was completely sup-
pressed by using the menthyloxy-
carbene complex 1g, which on
treatment with either of the disub-
stituted 1,3-dienes 2d or 2e afford-
ed cyclopentanones 5 f and g (Ta-
ble 2, entries 2 and 3).[18]
Entry
1
2
t [h][d]
3
Yield [%][e]
5 or 6
Yield [%][f]
1
2
3
4
5
6
7
8
1a
2a
2a
2a
2a
2b
2c
2a
2a
9
3a
3b
3c
3d
3e
3 f
3a
3a
94
91
94
75[g]
95
86
50[i]
80[i]
5a
5b
5c
5d
6a
5e
70
85
90
90
86
78
1b
1c
1d
1a
1a
1e
1 f
10.5
24
5.5
5
11
24[h]
72
In contrast, the thermal reaction
(1208C in THF) of alkenylcarbene
chromium complexes 1a and b with
1,3-dienes 2a and c led to cyclo-
pentene [4þ1] adducts 4b and c
with low efficiency. A considerable
quantity of unidentified products
were obtained in these experiments
(Scheme 2).[19,20] The connectivity
of the atoms in 3 and 4 and the
stereochemistry of 3, 5, 6, and 7
were ascertained by NMR experi-
ments (including HMQC, HMBC,
COSY, and NOESY).
Finally, the possibility to pre-
pare enantiomerically enriched cy-
clopentanones 5 and 6 was exam-
ined using 8-phenylmenthyloxy
(alkenyl)carbene chromium com-
plexes 1h and i.[14] These chiral
complexes reacted with dienes 2a
and b to give the [3þ2] adducts 3g i
with variable diastereomeric ex-
cesses (Table 3). The most success-
ful result was achieved in the reac-
[a] PhCH3, 5 equiv of 2, 10% BHT (with respect to the diene), 808C (bath temperature), sealed flask.
[b] 2n HCl, THF, room temperature, 10 15 min. [c] Fc¼ferrocenyl. [d] Reaction time required for
complete disappearance of starting carbene complex 1. [e] Yield obtained from the cycloaddition
reaction. [f] Yield obtained after hydrolysis. [g] Crude yield of impure product, which was submitted to
hydrolysis without characterization. [h] Reaction temperature¼458C. [i] Crude yield.
Table 2: [3þ2] Cycloadditions of tungsten carbene complexes 1 f and g with 1,3-dienes 2d f.
Entry
1
R3
2
R4
R5
R6
t [d][c]
5
Yield [%]
1
2
3
4
1 f
1g
1g
1 f
Me
2d
2d
2e
2 f
Me
Me
H
H
H
Me
Me
H
H
H
Me
2.5
8
2
5 f
5 f
5g
5h
50[d]
60
80
menthyl[e]
menthyl[e]
Me
H
4
65
[a] PhCH3, 5 equiv of 2, 10% BHT (with respect to the 1,3-diene), 808C (bath temperature), sealed flask.
[b] The crude product was treated with 2n HCl, THF, room temperature, 10 15 min (for R3 ¼Me) or 1 h
(for R3 ¼menthyl). [c] Reaction time required for complete disappearance of starting carbene complex 1
at 808C. [d] In this experiment compound 7 was also isolated in 25% yield. [e] (À)-Menthol was used to
prepare the starting carbene complex 1g.
pentanones 5a e (entries 1 4, 6), while the same hydrolysis
reaction of enol ether 3e (R2 ¼ H) occurred with concomitant
tion of 1h and 2b, in which 3h was obtained as a
diastereomerically pure material. Acid hydrolysis of 3h led
to the isolation of the enantiomerically pure 2-ethylidene-4-
phenylcyclopentanone (þ)-6a. The geometry of (þ)-5 and
(þ)-6 was assumed from X-ray analysis of a single crystal of
the major enantiomer (þ)-6b, which exhibits an absolute
configuration R for the newly created stereogenic center, and
¼
isomerization of the terminal C C bond to form 2-ethyl-
idenecyclopentanone 6a (entry 5). Both compounds 5 and 6
were isolated as unique diastereoisomers.
In addition, we have found that the more-substituted 1,3-
dienes 2d and e led to a complicated mixture of products
when they were treated with chromium carbene complex 1a
(5 equiv of 2, 10% BHT, PhCH3, 808C, 8 21 h). In contrast,
tungsten carbene complexes 1 f and g reacted with 1,3-dienes
2d f to give the corresponding [3þ2] cycloadducts, which
after subsequent acid hydrolysis were all isolated as the 2-
vinylcyclopentanones 5 as a single diastereoisomer (Table 2).
The reaction of methoxycarbene complex 1 f with a disub-
stituted 1,3-diene, such as 2,3-dimethyl-1,3-butadiene (2d),
[21]
¼
confirmed the E configuration of the exocyclic C C bond.
Formation of products 3 and 4 can be rationalized,
according to previous models,[5,7d,10,17d] by means of a metal-
la-Diels Alder reaction, which presumably occurs after an
initial thermally induced dissociation of a CO ligand, followed
by reductive elimination of the metal moiety (Scheme 3). The
final [3þ2] adduct 3 or [4þ1] adduct 4 would involve the
initial formal addition of the alkenylcarbene complex as a
232
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Angewandte
Chemie
Table 3: Asymmetric [3þ2] cycloaddition reactions.[a]
[7] a) W. D. Wulff, D. C. Yang, C. K.
Murray, J. Am. Chem. Soc. 1988,
110, 2653; b) J. Barluenga, F. Az-
nar, A. MartÌn, J. T. Vµzquez, J.
Am. Chem. Soc. 1995, 117, 9419;
c) J. Barluenga, F. Aznar, M.
Fernµndez, Chem. Eur. J. 1997, 3,
1629; d) M. Hoffmann, M. Buchert,
H.-U. Reissig, Chem. Eur. J. 1999,
5, 876.
1
R1
2
R2
3
Yield [%][d]
de [%][e]
5 or 6
Yield [%]
ee [%][f]
1h
1h
1i
Ph
Ph
Fc
2a
2b
2b
Me
H
H
3g
3h
3i
94
90
95
74
>99
80
(þ)-5a
(þ)-6a
(þ)-6b
73
90
85
70
>99
79
[8] a) W. D. Wulff, W. E. Bauta, R. W.
Kaesler, P. J. Lankford, R. A. Mil-
ler, C. K. Murray, D. C. Yang, J.
Am. Chem. Soc. 1990, 112, 3642;
b) J. Barluenga, F. Aznar, A. Mar-
tÌn, S. Barluenga, Tetrahedron 1997,
53, 9323. For reactions with ami-
[a] R*¼8-Phenylmenthyl; (À)-8-Phenylmenthol was used to prepare carbene complexes 1h and i.
[b] PhCH3, 10 mol% BHT, 808C (bath temperature), sealed flask, 4 24 h. [c] 2n HCl, THF, room
temperature, 1 h. [d] Crude yield. [e] Determined by integration of 1H NMR spectra of the crude product.
[f] Determined by HPLC analysis on a chiral support.
R2
R2
no(alkenyl)carbene complexes, see: c) T. S. Powers, W. Jiang, J.
Su, W. D. Wulff, J. Am. Chem. Soc. 1997, 119, 6438.
[9] For reactions of acetoxy(alkenyl)carbene complexes, see: K.
Takeda, Y. Okamoto, A. Nakajima, E. Yoshii, T. Koizumi,
Synlett 1997, 1181.
[10] M. Hoffmann, M. Buchert, H.-U. Reissig, Angew. Chem. 1997,
109, 281; Angew. Chem. Int. Ed. Engl. 1997, 36, 283.
[11] D. F. Harvey, K. P. Lund, J. Am. Chem. Soc. 1991, 113, 8916.
[12] a) W. D. Wulff, D. C. Yang, J. Am. Chem. Soc. 1983, 105, 6726;
b) K. H. Dˆtz, W. Kuhn, G. M¸ller, B. Huber, H. G. Alt, Angew.
Chem. 1986, 98, 826; Angew. Chem. Int. Ed. Engl. 1986, 25, 812.
[13] a) B. C. Sˆderberg, L. S. Hegedus, M. A. Sierra, J. Am. Chem.
Soc. 1990, 112, 4364; b) S. Kˆbbing, J. Mattay, G. Raabe, Chem.
Ber. 1993, 126, 1849.
Cr(CO)5
(CO)4Cr
R*O
3
4
R1
H
O
R1
CO
A
R1
MeO
OMe
R2
Cr(CO)4
(CO)5Cr
R1
R2
CO
Scheme 3. Proposed models for the [3þ2] and [4þ1] cycloaddition re-
actions.
[14] J. Barluenga, J. M. Montserrat, J. FlÛrez, S. GarcÌa-Granda, E.
MartÌn, Chem. Eur. J. 1995, 1, 236.
[15] J. Barluenga, S. LÛpez, A. A. Trabanco, A. Fernµndez-Acebes, J.
FlÛrez, J. Am. Chem. Soc. 2000, 122, 8145.
[16] With 1,3-dienes, the presence of this additive is required to
inhibit polymerization.
¼
1-chroma-1,3-diene and as a Cr C dienophile, respectively.
The sense of diastereochemical induction, which is in agree-
ment with previous results,[14,17d] involves approach of the
dienophile to the less-hindered face (front side in model A) of
the metalladiene.
In conclusion, a general, selective synthesis of enantio-
merically enriched alkenyl-substituted cyclopentanones is
reported. The process is based on the new annulation of a
three-carbon-atom unit of an alkoxy(alkenyl)carbene com-
plex to a two-carbon-atom unit of a simple 1,3-diene. Studies
of the scope of these cycloaddition reactions are currently in
progress.
[17] For other [3þ2] cycloadditions involving a three-carbon-atom
synthon alkenylcarbene ligand, and other substrates, see for
example: electron-deficient olefins: a) M. Hoffmann, H.-U.
Reissig, Synlett 1995, 625; Enamines: b) J. Barluenga, M. Tomµs,
A. Ballesteros, J. SantamarÌa, C. Brillet, S. GarcÌa-Granda, A.
PiÊera-Nicolµs, J. T. Vµzquez, J. Am. Chem. Soc. 1999, 121, 4516;
Methyl ketone enolates: c) J. Barluenga, J. Alonso, F. RodrÌguez,
F. J. FaÊanµs, Angew. Chem. 2000, 112, 2556; Angew. Chem. Int.
Ed. 2000, 39, 2460; Imines: d) H. Kagoshima, T. Okamura, T.
Akiyama, J. Am. Chem. Soc. 2001, 123, 7182; Alkynes: e) W. D.
Wulff, B. M. Bax, T. A. Brandvold, K. S. Chan, A. M. Gilbert,
R. P. Hsung, J. Mitchell, J. Clardy, Organometallics 1994, 13, 102.
[18] No asymmetric induction was observed in the cycloaddition
reactions with the chiral menthyloxycarbene complex 1g.
[19] The analogous treatment (10% BHT, THF, 1208C, 0.5 h) of
complex 1a with 2b exclusively provided the [3þ2] adduct 3d
(75%).
[20] For other [4þ1] cycloadditions involving a one-carbon-atom
synthon alkenylcarbene ligand, see: J. Barluenga, A. Ballesteros,
J. SantamarÌa, M. Tomµs, J. Organomet. Chem. 2002, 643 644,
363, and references therein.
[21] For full details of the X-ray study, see: J. F. Van der Maelen UrÌa,
S. GarcÌa-Granda, S. LÛpez, Acta Crystallogr. Sect. E 2002, 58,
m613.
Received: October 2, 2002 [Z50281]
[1] H.-W. Fr¸hauf, Chem. Rev. 1997, 97, 523.
[2] For recent reviews, see: a) K. H. Dˆtz, P. Tomuschat, Chem. Soc.
Rev. 1999, 28, 187; b) J. W. Herndon, Tetrahedron 2000, 56, 1257;
c) A. de Meijere, H. Schirmer, M. Duetsch, Angew. Chem. 2000,
112, 4124; Angew. Chem. Int. Ed. 2000, 39, 3964.
[3] The topological identification of the reaction type is used in a
formal sense to describe the number of carbon atoms provided
by each fragment to the final cycloadduct, regardless of the
mechanism and the number of steps involved. The subscripts D
and C refer to the corresponding reagent: D ¼ 1,3-diene, C ¼
carbene ligand (complex).
[4] a) M. Buchert, H.-U. Reissig, Chem. Ber. 1992, 125, 2723; b) M.
Buchert, M. Hoffmann, H.-U. Reissig, Chem. Ber. 1995, 128, 605.
[5] M. A. Sierra, B. Sˆderberg, P. A. Lander, L. S. Hegedus,
Organometallics 1993, 12, 3769.
[6] J. Barluenga, F. Aznar, A. MartÌn, Organometallics 1995, 14,
1429.
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