Palladium-catalysed asymmetric [4 + 2] cycloaddition of vinylallene with 1,3-diene

Article abstract of DOI:10.1039/b007781j

A catalytic asymmetric [4 + 2] cycloaddition reaction of a vinylallene with buta-1,3-diene was developed in which a palladium complex modified by a ferrocene-derived chiral monophosphine ligand acted as a template transferring chirality to the product.

Full text of DOI:10.1039/b007781j

Palladium-catalysed asymmetric [4 + 2] cycloaddition of vinylallene with
,3-diene
1
Masahiro Murakami,* Ryo Minamida, Kenichiro Itami, Masaya Sawamura† and Yoshihiko Ito*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Yoshida, Kyoto 606-8501, Japan
Received (in Cambridge, UK) 6th September 2000, Accepted 5th October 2000
First published as an Advance Article on the web 7th November 2000
A catalytic asymmetric [4 + 2] cycloaddition reaction of a
vinylallene with buta-1,3-diene was developed in which a
palladium complex modified by a ferrocene-derived chiral
monophosphine ligand acted as a template transferring
chirality to the product.
Cycloaddition reactions are among the most powerful methods
for the rapid construction of carbocycles and heterocycles
1
alike. The [4 + 2] cycloaddition is most widely used to build
six-membered ring carbon skeletons. However, strenuous
reaction conditions are required for the combination of
(1)
1,3-dienes and dienophiles lacking electron-withdrawing or
-
donating substituents, which limits the range of the synthetic
dium complex modified by a ferrocene-derived chiral mono-
phosphine ligand as a template.
Initially, a variety of chiral phosphines were screened in the
standard test cycloaddition reaction using vinylallene 2a and
buta-1,3-diene (excess). The catalyst complex was prepared by
2
utility. The use of transition metal complexes as the promoter
provides considerably wider substrate scope. The transition
metal acts as the template bringing the unsaturated substrates
together in an array to promote the cycloaddition reaction. We
have developed the palladium-catalysed directed intermolecular
2 3 3
treatment of [Pd (dba) ·CHCl ] with a chiral phosphine ligand
[
4 + 2] cycloaddition between a vinylallene and an ordinary
in situ. Highly reputed bidentate chiral diphosphine ligands like
DuPHOS (1,2-bis[2,5-dimethylphospholanyl]benzene) and
CHIRAPHOS (2,3-bis(diphenylphosphino)butane gave only
low enantioselectivities. No reaction occurred with BINAP.
Since our proposed mechanism involves a square planar
palladium(II) intermediate 1 in which three of the four
coordination sites are occupied by the cycloaddition partners,
we supposed that monodentate ligands would be more effective
transmitters of chirality. Whereas MOP (2-diphenylphosphino-
1,1A-binaphthalene) afforded only 15% ee, a better result was
,3-diene.3 The initially formed palladacyclopentene inter-
–5
1
mediate couples with a 1,3-diene before undergoing a ring-
flipping isomerization, resulting in a highly stereospecific
reaction [eqn. (1)]. We anticipated that a palladium complex
modified by a chiral ligand would possibly differentiate the
enantiofaces of vinylallene in its s-cis form and that this
differentiation would be directly transferred to the product. This
paper describes the catalytic asymmetric [4 + 2] cycloaddition
6
of a vinylallene with buta-1,3-diene which employs a palla-
Table 1 Asymmetric induction in palladium-catalysed directed [4 + 2] cycloaddition of 2a with buta-1,3-diene
DOI: 10.1039/b007781j
Chem. Commun., 2000, 2293–2294
This journal is © The Royal Society of Chemistry 2000
2293

Table 2 Palladium-catalysed asymmetric [4 + 2] cycloaddition of
vinylallenes (2) with 1,3-dienes
A number of highly successful asymmetric [4 + 2] cycloaddi-
tions have been reported in which the carbonyl group of an
electron-deficient dienophile coordinates to a chiral Lewis acid
a
1
to induce an excellent enantioselection. On the other hand, it is
difficult to gain stereocontrol over a substrate lacking coordinat-
ing heteroatom functionalities. The asymmetric [4 + 2]
cycloaddition documented herein presents a promising new
example which may be applied to such unactivated substrates.
The full potential of this new process remains to be eluci-
dated.
Notes and references
†
Present address: Department of Chemistry, The University of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
The chiral ferrocenyl phosphines 3 were prepared as follows [eqn. (3)]:
‡
(3)
ortho-lithiation of (R)-N,N-dimethyl-1-ferrocenylethylamine (5) with bu-
tyllithium followed by treatment with chlorosilane afforded (S)-1-silyl-
2
-[(R)-1-(dimethylamino)ethyl]ferrocene 6. A diarylphosphinyl group was
then introduced by successive treatment of 6 with excess acetic anhydride,
and then with diarylphosphine in acetic acid to furnish (S)-1-silyl-2-[(R)-
1
-(diarylphosphino)ethyl]ferrocene 3.
§
The experimental procedure for the formation of 4a is as follows: to a
mixture of [Pd
7
1
2
(dba)
.9 mmol) in CH Cl
,3-diene (4.4 M in CH
3
·CHCl
(3 mL) under N
Cl , 0.3 mL, 1.32 mmol) and the vinylallene 2a
3
] (3.4 mg, 3.3 mmol) and the ligand 3k (7.4 mg,
2
2
2
at rt were successively added buta-
2
2
(
32.0 mg, 0.132 mmol). The reaction was complete within 10 min. The
obtained with PPFA (2-(1-dimethylaminoethyl)-1-diphenyl-
phosphinoferrocene 27% ee). Among ferrocene-derived li-
gands, the monodentate phosphine ligand 3a gave a moderate
selectivity (Table 1, entry 1). This result directed our detailed
investigation to ligands of analogous structures. The ligands
mixture was evaporated under vacuum, and the residue was subjected to
preparative TLC (silica gel, ether–hexane = 1:10) to afford 4a (33.2 mg,
85%) as a colorless oil. [a]2
0
D
3
+ 12.3 (c 1.0, CHCl ). The enantioselectivity
was determined to be 83% ee by chiral HPLC analysis [SUMICHIRAL OA-
21
2
2
¶
500-I (4.0 3 250 mm), 1.0 mL min , hexane–ClCH
000:20:1, (4S,6R) t = 17 min, (4R,6S) t = 19 min].
Platinum was also tested as a metal using Pt(cod) and provided 77% ee.
2 2
CH Cl–EtOH =
1
2
3
b–k listed in Table 1 were prepared‡ and applied to the test
2
reaction. Ligand 3b lacking a silyl group at the ortho position
gave a low selectivity (entry 2). The triphenylsilyl-substituted
ligand 3c gave slightly better selectivity than the trimethylsilyl-
substituted ligand 3a (entry 3). Diphenylphosphine-substituted
ligands were significantly more effective than dicyclohex-
ylphosphine derivatives (entry 4). The effect of the electronic
nature of the diarylphosphinyl group was examined in detail
However, platinum suffered from low conversion.
∑
1
Cyclohexa-1,3-diene failed to undergo the cycloaddition, suggesting that
,3-diene reacts in its s-cis form as shown in eqn. (1).
1 For reviews, see: (a) W. Carruthers, Cycloaddition Reactions in Organic
Synthesis, Pergamon, Oxford, 1990; (b) Advances in Cycloaddition, ed.
D. P. Curran, Vol. 1–3, JAI Press, Connecticut, 1994.
2
3
4
For a review of transition metal-mediated cycloaddition reactions, see:
M. Lautens, W. Klute and W. Tam, Chem. Rev., 1996, 96, 49.
M. Murakami, K. Itami and Y. Ito, J. Am. Chem. Soc., 1997, 119,
(entries 5–11). Ligands having an electron-withdrawing group
gave comparable or better selectivities than 3c. In particular, the
phosphine possessing two 3,5-bis(trifluoromethyl)phenyl
groups (3k) afforded the highest enantioselectivity of 83% ee.§¶
Although solvents other than DCM were also screened, little
effect was observed in terms of the enantioselectivity. The
absolute stereochemistry of the major enantiomer was deter-
mined to be (4R,6S) by an X-ray crystallographic study of the
amide derived from 4a and (S)-1-phenylethylamine [eqn. (2)].
7
163.
For thermal Diels-Alder reactions of vinylallenes, see: J. Spino, C.
Thibault and S. Gingras, J. Org. Chem., 1998, 63, 5283; U. Koop, G.
Handke and N. Krause, Liebigs Ann., 1996, 1487 and refs. therein.
5 For other examples of transition metal-catalysed cycloaddition reactions
of vinylallenes, see: (a) H. Siegel, H. Hopf, A. Germer and P. Binger,
Chem. Ber., 1978, 111, 3112; (b) T. Mandai, S. Suzuki, A. Ikawa, T.
Murakami, M. Kawada and J. Tsuji, Tetrahedron Lett., 1991, 32, 7687;
(
(
c) M. S. Sigman and B. E. Eaton, J. Am. Chem. Soc., 1996, 118, 11 783;
d) T. Mandai, J. Tsuji and Y. Tsujiguchi, J. Am. Chem. Soc., 1993, 115,
5
865; (e) C. Darcel, C. Bruneau and P. H. Dixneuf, Synlett, 1996, 218; (f)
M. Murakami, K. Itami and Y. Ito, Angew. Chem., Int. Ed. Engl., 1995,
3
1
4, 2691; (g) M. Murakami, K. Itami and Y. Ito, J. Am. Chem. Soc., 1997,
19, 2950; (h) M. Murakami, M. Ubukata, K. Itami and Y. Ito, Angew.
(2)
Chem., Int. Ed., 1998, 37, 2248; (i) M. Murakami, K. Itami and Y. Ito,
Organometallics, 1999, 18, 1326; (j) M. Murakami, K. Itami and Y. Ito,
J. Am. Chem. Soc., 1999, 121, 4340; (k) M. Murakami, K. Itami and Y.
Ito, Angew. Chem., Int. Ed., 1998, 37, 3418; (l) M. Murakami, K. Itami
and Y. Ito, Synlett, 1999, 951.
Thus, 3k proved to be the ligand of choice, and was applied
to the reactions of other vinylallenes with buta-1,3-dienes.∑ The
[
4 + 2] cycloadducts were produced with moderate to good
6
For allene-participating [4 + 2] cycloaddition reactions which involve
chirality transfer, see: (a) I. Ikeda, K. Honda, E. Osawa, M. Shiro, M. Aso
and K. Kanematsu, J. Org. Chem., 1996, 61, 2031; (b) P. A. Wender,
T. E. Jenkins and S. Suzuki, J. Am. Chem. Soc., 1995, 117, 1843; (c) X.
Wang, J. Donovalova, A. Hollis, D. Johnson, A. Rodriguez, G. D.
Kennedy, G. Krishnan and H. Banks, J. Heterocycl. Chem., 1994, 31,
871.
enantioselectivities in good yields (Table 2). Note that a useful
level of asymmetric induction was obtained in the case of 2c
lacking any coordinating heteroatom functionalities (entry 2).
For the unsymmetrical 1,3-diene (2-methylbuta-1,3-diene),
incorporation of the more substituted C–C double bond was
favoured to afford 4e as the predominant product (entry 4).
2294
Chem. Commun., 2000, 2293–2294