RhI-catalyzed [6+2] cycloaddition of alkyne-allenylcyclobutanes: A new entry for the synthesis of bicyclo[6.m.0] skeletons

Article abstract of DOI:10.1002/chem.201101441

Bicyclo under construction! The [RhCl(dppp)₂]-catalyzed intramolecular [6+2] cycloisomerization of alkyne-allenylcyclobutanes efficiently produced bicyclo[6.4.0]dodecatriene and bicyclo[6.3.0]undecatriene skeletons (see scheme). Straightforward cleavage of the unfunctionalized simple cyclobutane and construction of the bicyclo[6.m.0] frameworks could be achieved under mild conditions.

Full text of DOI:10.1002/chem.201101441

DOI: 10.1002/chem.201101441
RhI-Catalyzed [6+2] Cycloaddition of Alkyne–Allenylcyclobutanes: A New
Entry for the Synthesis of BicycloACTHNUTRGNEUNG[6.m.0] Skeletons
Fuyuhiko Inagaki, Katsuya Sugikubo, Yuki Oura, and Chisato Mukai*[a]
The strained cyclobutanone has been shown to serve as a
unique four-carbon unit in the transition-metal-catalyzed
ring-closing reaction leading to the formation of a variety of
ring systems.[1] The rhodium(I)-catalyzed intramolecular
[6+2] cycloaddition between 2-vinylyclobutanone and olefin
moieties[2] efficiently provided the corresponding bicyclo-
lated that the replacement of the highly strained allenylcy-
clopropane by the strained allenylcyclobutane might still
give rise to the facile formation of the one-carbon homolo-
gated bicyclic eight-membered rings 3 (n=2, Scheme 1). We
now report the rhodium(I)-catalyzed [6+2] cycloaddition of
alkyne–allenylcyclobutanes resulting in the efficient prepa-
A
ration of the bicycloACHTGNUTERNNU[G 6.4.0] and bicycloACTHUNGTREN[NUNG 6.3.0] frameworks, in
compounds could not be obtained when either the cyclobu-
tanone was replaced by a simple unfunctionalized cyclobu-
tane or the p counterpart was changed from the alkene to
alkyne functionality. The nickel(0) catalyst was highly effec-
which the functionalized cyclobutanes, such as a cyclobuta-
none, a hydroxycyclobutane[6,8] or a cyclobutylidene[9] unit,
were not mandatory, but the simplest cyclobutane could
serve as a suitable four-carbon unit.
tive for the synthesis of the bicyclo
A
Our initial evaluation was carried out as follows: a solu-
via the intermolecular [4+2+2] cycloaddition of cyclobuta-
nones with the 1,6-diynes. The coordination of the carbonyl
functionality of the cyclobutanone with the nickel catalyst is
regarded as one of the significant processes in the proposed
mechanism. These two transformations might indicate that
some suitable functional groups, such as a carbonyl group
seems to be essential for the ring cleavage of the strained
four-carbon unit[4–6] during the transition-metal-catalyzed cy-
cloaddition.
tion of the N-tosyl derivative 1a[10] was heated at 808C in
1,2-dichloroethane (DCE, 0.025m) in the presence of
[11]
[RhCl(CO)2]2
(10 mol%) for 0.2 h to afford the desired
bicycloACTHNUGNRTE[NUG 6.4.0]dodecatriene 3a in 40% yield and the monocy-
clic compound 4a in 52% yield (Table 1, entry 1). Com-
pound 3a became the major product (80%) along with the
formation of 4a (16%) when 1a was exposed to
[RhCl(CO)dppp]2 in toluene[11] (Table 1, entry 2). Conver-
sion of 1a into 3a could also be realized even at room tem-
perature, although the reaction rate was significantly de-
creased (Table 1, entry 3). Other rhodium carbonyl catalysts
gave unsatisfactory results (Table 1, entries 4–7). [RhCl-
On the other hand, we recently reported that the rhodi-
ACHTUNGTRENNUNGum(I)-catalyzed cycloisomerization of alkyne–allenylcyclo-
propanes 1 (n=1) effected the [5+2] ring-forming reaction[7]
under rather milder conditions to afford the bicyclic seven-
membered compounds 2 (n=1, Scheme 1). Based on the
easy cleavage of the unfunctionalized cyclopropane ring that
was activated by the adjacent allenyl moiety, we next postu-
AHCTUNGTRENNUNG
(dppp)2][12] afforded the best result (84%, Table 1, entry 10)
among the examined monomeric rhodium catalysts without
the carbon monoxide ligand (Table 1, entries 8–12). A de-
crease in loading amount of [RhCl
5 mol% led to the lower yield of 3a (68%) and 4a (13%).
However, 5 mol% [RhCl(dppp)2] in dioxane at 808C for
ACHTUNGTERN(NGNU dppp)2] from 10 to
AHCTUNGTRENNUNG
0.2 h provided a similar result (3a (82%) and 4a (15%)) to
that of entry 10 (Table 1). Finally, the highest yield (87%) of
compound 3a was unexpectedly attained when the reaction
was performed in 0.1m dioxane solution in the presence of
5 mol% [RhClACTHUNRGTNEUNG(dppp)2] for 0.2 h (see Table 2, entry 1).
Scheme 1. RhI-catalyzed cycloisomerization of alkyne–allenylcyclopro-
panes and alkyne–allenylcyclobutanes.
The formation of 3a and 4a was tentatively interpreted
by the mechanism shown in Scheme 2. The first coordina-
tion of 1a with RhI would occur between three components;
an allenic distal double bond, an alkyne, and the carbon–
carbon single bond of the strained cyclobutane ring to form
the intermediate A, which should immediately collapse to
[a] Dr. F. Inagaki, K. Sugikubo, Y. Oura, Prof. Dr. C. Mukai
Division of Pharmaceutical Sciences
Graduate School of Natural Science and Technology
Kanazawa University, Kakuma-machi
Kanazawa 920-1192 (Japan)
Fax : (+81)76-234-4410
E-mail: cmukai@kenroku.kanazawa-u.ac.jp
the rhodabicycloACTHNUTRGNEUNG
[4.3.0]nonadiene skeleton B.[2,13] The cyclo-
butane ring of the intermediate B is opened by a b-carbon
elimination,[1,3] which releases the ring strain to generate the
nine-membered intermediate C; the reductive elimination of
which would result in the formation of 3a. On the other
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101441.
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COMMUNICATION
Table 1. Cycloaddition reaction of alkyne–allenylcyclobutane 1a in the
presence of various Rh catalysts.[a]
Entry
Catalyst
[RhCl(CO)2]2
[RhCl(CO)dppp]2
[RhCl(CO)dppp]2
[RhCl(CO)dppm]2
[RhCl(CO)dppe][e]
[RhCl(CO)dppb]2
[RhCl(cod)]2
[RhCl(dppm)2]
[RhCl(dppe)2]
[RhCl(dppp)2]
[RhCl(dppb)2]
[RhCl(PPh3)3]
t [h]
Product and Yield [%][b]
1[c]
2
G
0.2
0.2
33
0.2
0.2
1
7
12
0.5
0.2
0.5
0.2
3a: 40
3a: 80
3a: 16
3a: 24
3a: 64
3a: 48
3a: 17
3a: 25
4a: 48
3a: 84
3a: 40
3a: 25
4a: 52
4a: 16
ACHTUNGTRENNUNG
3[d]
4
ACHTUNGTRENNUNG
R
4a: 66
4a: 23
4a: 52
4a: 81
4a: 55
5: 50
4a: 16
4a: 43
4a: 73
5
6
7
8
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
N
U
N
E
9
N
N
10[f,g]
11
12[h]
G
U
N
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
[a] A solution of 1a in toluene (0.025m solution) was heated at 808C in
the presence of Rh catalyst (10 mol%). [b] Yield of isolated product.
[c] Reaction was performed in 1,2-dichloroethane (DCE). [d] Reaction
was carried at room temperature. [e] 20mol% of Rh catalyst was used.
[f] [RhCl
[g] When the reaction was carried out in dioxane in the presence of
[RhCl(dppp)2] (5 mol%), 3a (82%) was obtained together with 4a
(15%). [h] When the reaction was carried out in the presence of AgOTf,
3a (30%) and 4a (66%) were obtained. No significant difference be-
tween chemical yield of 3a with and without AgOTf could be observed.
ACHTUNGTRENNUNG(dppp)2] (5 mol%) in toluene gave 3a (68%) and 4a (13%).
Scheme 2. Plausible mechanism for the formation of 3 and 4.
ACHTUNGTRENNUNG
rather longer (Table 2, entry 3). The benzyloxymethyl and
ethoxycarbonyl derivatives 1d and 1e exclusively gave 3d
and 3e in 85 and 67% yields, respectively (Table 2, entries 4
and 5). This ring-closing reaction was found to be applicable
to the internal alkyne species and 3 f was obtained in 91%
yield (Table 2, entry 6). The oxygen congeners 1g and 1h re-
vealed behaviors similar to those of 1a and 1b (Table 2, en-
tries 7 and 8). It was shown that the carbon homologues 1i
and 1k, without a substituent at the allenic position a, tend
to produce significant amounts of the b-hydride elimination
products 4i and 4k (37 and 21% yields, respectively,
Table 2, entries 9 and 11) compared with those the nitrogen
and oxygen species 1a and 1g.[17] The introduction of a
methyl group at the allenic position a (1j and, 1l, and 1m)
again led to the efficient production of the eight-membered
products 3j, 3l, and 3m in high yields as expected (Table 2,
entries 10, 12, and 13). It is noteworthy that the simple
carbon analogue 1n, which does not possess the geminal di-
Ts=p-toluenesulfonyl;
dppm=1,1-bis(diphenylphosphino)methane;
dppp=1,3-bis(diphenylphosphino)propane;
dppe=1,2-bis(diphenyl-
phosphino)ethane; dppb=1,2-bis(diphenylphosphino)butane; cod=1,5-
cyclooctadiene.
hand, the b-hydride elimination, instead of the b-carbon
elimination of the common intermediate B, must produce
the intermediate D, which should give 4a through the reduc-
tive elimination step. Another plausible mechanism might
involve the rhodacycloheptene intermediate E, which should
be derived from the intermediate A through ring-opening of
2
III
ꢀ
the cyclobutane. The insertion reaction of the sp C Rh
bond of E into the triple bond leading to the intermediate
C.[14–16] The previously reported RhI-catalyzed [5+2] cyclo-
addition of alkyne–allenylcyclopropane[7] produced cyclo-
pentenylidene derivatives F (n=1) as a byproduct which
would strongly rationalize this pathway (A!E!C). How-
ever, in the case of 1a, the corresponding cyclohexenylidene
derivative F (n=2) could not be detected. Thus, the reaction
path via the intermediate B would be more understandable
than the one via intermediate E.
AHCTUNGTRENNUNG
substituted effect[18] on the carbon tether, such as 1j, l, or m,
produced the corresponding bicycloACTHNUTRGNEUNG[6.4.0]dodecatriene 3n
in an acceptable yield[19] (Table 2, entry 14).
The one-carbon shortened substrate 6 was also efficiently
transformed into the bicycloACHTNUTRGNE[UNG 6.3.0]undecatriene derivative
7[20] in a high yield (>99%) under the standard conditions
(Table 2, entry 15). Thus, it became clear that alkyne–alle-
nylcyclobutanes possessing a substituent at the allenic posi-
If the starting material 1a possesses a substituent at the
allenic position a (Scheme 2), an unfavorable b-hydride
elimination of the intermediate B might be completely re-
tarded. As a matter of fact, the methyl derivative 1b was ex-
tion consistently produced the bicyclo
ACHTUNGERTN[NUNG 6.4.0]dodecatrienes
and bicyclo[6.3.0]undecatriene in high yields. Finally, the
AHCTUNGTRENNUNG
posed to the optimized conditions ([RhCl
(dppp)2]
phenylsulfonyl group on the allenyl moiety was shown not
to be mandatory for this efficient ring-closing reaction.
Indeed, compound 8 gave the bicyclic derivative 9 in a high
yield (>99%) under dioxane heated at reflux for 0.5 h
(Table 2, entry 16).
(5 mol%), and dioxane (0.1m) solution at 808C) to produce
the desired eight-membered product 3b in 98% yield
(Table 2, entry 2). The butyl derivative 3c (76%) was also
obtained as the sole product, although the reaction time was
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C. Mukai et al.
Table 2. RhI-catalyzed [6+2] cycloaddition reaction of alkyne–allenylcyclobutanes.[a]
successfully applied to the con-
Product (yield [%])[b]
t [h]
struction
of
the
bicyclo-
Entry
Substrate
AHCTUNGTRENGN[UN 6.3.0]undecatriene ring system.
Acknowledgements
1
2
3
4
1a: R=R’=H
3a: R=R’=H (87)
4a (13)
0.2
0.2
7
5
4
1b: R=Me, R’=H
1c: R=nBu, R’=H
1d: R=CH2OBn, R’=H
1e: R=CO2Et, R’=H
1 f: R=Me, R’=nBu
3b: R=Me, R’=H (98)
3c: R=nBu, R’=H (76)
3d: R=CH2OBn, R’=H (85)
3e: R=CO2Et, R’=H (67)
3 f: R=Me, R’=nBu (91)
This work was supported in part by a
Grant-in Aid for Scientific Research
from the Ministry of Education, Cul-
ture, Sports, Science and Technology,
Japan, for which we are thankful.
5
6[c]
3
Keywords: allenes
compounds cycloaddition
cyclobutanes · rhodium
·
bicyclic
·
·
7
8
1g: R=H
1h: R=Me
3g: R=H (82)
3h: R=Me (86)
4g (10)
0.2
2
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1
0.5
11
12
1k: R=H
1l: R=Me
3k: R=H (46)
3l: R=Me (>99)
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1m
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8
9 (>99)
0.5
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cycloaddition of 1-siloxy-1-allenylcyclobutane and CO. Judging from
the proposed reaction mechanism, cyclobutane seemed to cleave
without assistance of siloxy group. It is, however, still uncertain if
the siloxy group is mandatory (or not) for the cleavage of cyclobu-
tane ring. See: P. A. Wender, N. M. Deschamps, R. Sun, Angew.
Chem. 2006, 118, 4061–4064; Angew. Chem. Int. Ed. 2006, 45, 3957–
3960.
lyzed intramolecular [6+2] cycloisomerization reaction be-
tween alkyne and allenylcyclobutane functionalities under
mild conditions leading to the efficient formation of the cor-
responding bicycloACHTUNGTRENNUNG[6.4.0]dodecatriene frameworks, in which
the unfunctionalized simple cyclobutane ring served as a
four-carbon component. Furthermore, this method was also
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RhI-Catalyzed [6+2] Cycloaddition
COMMUNICATION
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two
sets
of
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and
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bicyclic seven-membered compounds 2 (n=1), see Ref. [7].
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sponding bicyclo
ratio of 3 to 1.
[20] The demethylated derivative of 6 afforded a mixture of the corre-
ACHTUNGTREN[NGNU 6.4.0] derivative and cyclohexene derivative in the
sponding bicyclo
ratio of 1 to 1.
ACHTUNGTREN[NGNU 6.3.0] derivative and cyclopentene derivative in the
Received: May 11, 2011
Published online: July 15, 2011
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