Palladium-catalyzed asymmetric alkylation of 2,3-alkadienyl phosphates. Synthesis of optically active 2-(2,3-alkadienyl)malonates

Article abstract of DOI:10.1246/cl.2002.140

Asymmetric alkylation of 2,3-alkadienyl phosphates with soft carbon nucleophiles proceeds efficiently in the presence of palladium complex catalyst bearing MeOBIPHEP or BINAP ligand to give optically active functionalized allenes up to 90% ee.

Full text of DOI:10.1246/cl.2002.140

140
Chemistry Letters 2002
Palladium-Catalyzed Asymmetric Alkylation of 2,3-Alkadienyl Phosphates.
Synthesis of Optically Active 2-(2,3-Alkadienyl)malonates
Yasushi Imada,ꢀ Katsuya Ueno, Koji Kutsuwa, and Shun-Ichi Murahashiꢀ
Department of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531
Department of Chemistry, Faculty of Engineering Okayama University of Science, 1-1 Ridaicho, Okayama 700-0005
(Received November 5, 2001; CL-011109)
Table 1. Asymmetric alkylation of diethyl 2,3-alkadienyl phosphates 1
with malonates 2a
Entry Phosphate Malonate Time/h Product Yield/%b Ee/%c
Asymmetric alkylation of 2,3-alkadienyl phosphates with soft
carbon nucleophiles proceeds efficiently in the presence of
palladium complex catalyst bearing MeOBIPHEP or BINAP ligand
to give optically active functionalized allenes up to 90% ee.
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1a
1a
1f
2a
2a
2a
2a
2a
2b
2c
2d
8
6
6
12
8
2
3a
3b
3c
3d
3e
3f
76
72
89
69
8060
85
74
9070
73
77
81
90
Optically active allenes bearing axial chirality are important
synthetic intermediates for various naturally occurring biologically
active compounds.1 Therefore, much attention has been paid to the
asymmetric synthesis of this class of compounds. Optically active
allenes have been prepared by either optical resolution of racemic
allenes1 or chirality transfer reactions of optically active pre-
cursors.2;3 Preparation of optically active allenes using chiral
catalyst is an attractive method; however, the reported methods give
moderate enantioselectivity (20–60% ee)4 except kinetic resolution
byasymmetric oxidative degradation of allenes.5 Recently, Hayashi
et al. reported that palladium-catalyzed reaction of 2-bromo-1,3-
butadienes gives optically active allenes with enantioselectivity up
to 89% ee.6 We wish to report that palladium-catalyzed asymmetric
reaction of racemic 2,3-alkadienyl phosphates 1 with soft carbon
nucleophiles 2 gives optically active functionalized allenes 3
(Scheme 1).7 This is based on the non-asymmetric reaction reported
by Gore et al.8
76
69
3
8
3g
3h
aAll reactions were carried out in THF (0.1 M) at room temperature. The
ratio of 1/2/BSA/Pd2(dba)3ꢁCHCl3/(R)-MeOBIPHEP was 100/110/120/
1/4. bIsolated yield based on 1. cDetermined by HPLC analysis with
chiral stationary phase column.
The palladium-catalyzed reactions of phosphates 1a–e with
diethyl 2-acetamidomalonate (2a) give the corresponding functio-
nalized allenes 3a–e with 60–90% ee in good yields (entries 1–5).
The catalytic reactions of the phosphate 1a with diethyl 2-
phenylmalonate (2b) and diethyl 2-methylmalonate (2c) gave 3f
and 3g, respectively, with similar enantio-selectivities (entries 6 and
7), indicating that the acetamido group is not essential for getting
high level of enantioselectivity. Noteworthy is that the reaction of
the phosphate 1f with dimethyl malonate (2d) afforded monosub-
stituted malonate 3h as a sole product. Disubstituted malonate could
not be detected among the products (entry 8).
Alkylations of 2,3-alkadienyl phosphates 1 with soft carbon
nucleophiles 2 were examined in the presence of N; O-bis(tri-
methylsilyl)acetamide (BSA) and the palladium catalyst prepared
9
10
ꢁ
Typically, asymmetric reaction of diethyl 5,5-dimethyl-2,3-
hexadienyl phosphate (1d) with acetamidomalonate 2a was carried
out in THF at room temperature for 12 h in the presence of BSA and
from Pd2(dba)3 CHCl3 and MeOBIPHEP or BINAP in THF at
room temperature (Scheme 1). The representative results of the
reactions are summarized in Table 1.
ꢁ
the palladium catalyst prepared in situ from Pd2(dba)3 CHCl3 (0.01
equiv) and (R)-MeOBIPHEP (0.04 equiv). Ethyl 2-acetamido-2-
ethoxycarbonyl-7,7-dimethyl-4,5-octadienoate [(ꢂ)-3d] was ob-
tained with 90% ee in 69% isolated yield. The absolute configura-
tion of (ꢂ)-3d was determined to be (R) on the basis of the Lowe’s
rule.11
A survey of chiral bidentate phosphine ligands revealed that the
C2 ligands bearing binaphthyl and biphenyl backbone, such as
MeOBIPHEP and BINAP are effective.
The palladium-catalyzed reaction of 2,3-alkadienyl phosphates
1 with soft carbon nucleophiles8 can be rationalized by assuming the
mechanism shown in Scheme 2. The first step is facile formation of
1–3-ꢀ3-1,3-alkadienylpalladium 4 from allyl esters bearing highly
reactive leaving group OP(O)(OEt)2.12 Soft carbon nucleophiles
attack at the less hindered ꢁ-position of the palladium complex 4. It
is in contrast to the ꢂ-attack of hard carbon nucleophiles,8;13 such as
organozinc and Grignard reagents, and carbon monoxide14 via ꢀ1-
1,3-alkadien-3-yl-palladium 5 to give conjugated dienes.
An equilibrium is present between two diastereomeric ꢀ3-
alkadienylpalladium complexes (Sp)-4 and (Rp)-4 through ꢀ1-
alkadienylpalladium complex 5. Preferential nucleophilic attack of
malonate anion to (Sp)-4 at the less hindered allylic terminus from
the opposite side to the palladium would give the optically active
Scheme 1.
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
141
References and Notes
1
For reviews, see: H. F. Schuster and G. M. Coppola, ‘‘Allenes in Organic
Synthesis,’’ Weily-Interscience, New York (1984); S. R. Landor, ‘‘The
Chemistry of Allenes,’’ Academic Press, New York (1982); R. Rossi and P.
Diversi, Synthesis, 1973, 25.
2
From optically active propargyl compounds: a) Alkylations with organo-
cuprates: A. Alexakis, Pure & Appl. Chem., 64, 387 (1992), and references
cited therein. b) Sigmatropic rearrangements: M. A. Henderson and C. H.
Heathcock, J. Org. Chem., 53, 4736 (1988); J. A. Marshall and X. Wang, J.
Org. Chem., 56, 4913 (1991); A. G. Myers and B. Zheng, J. Am. Chem. Soc.,
118, 4492 (1996). c) Chiral allenylmetal mediated reactions: S. Dreller, M.
Dyrbusch, and D. Hoppe, Synlett, 1991, 397; J. A. Marshall and C. M. Grant,
J. Org. Chem., 64, 696 (1999). d) Pd-catalyzed reactions: J. Tsuji and T.
Mandai, Angew. Chem., Int. Ed. Engl., 34, 2589 (1995); M. Suginome, A.
Matsumoto, and Y. Ito, J. Org. Chem., 61, 4884 (1996); J. A. Marshall, M. A.
Wolf, and E. M. Wallace, J. Org. Chem., 62, 367 (1997); P. H. Dixneuf, T.
Guyot, M. D. Ness, and S. M. Roberts, Chem. Commun., 1997, 2083.
From optically active reagents: a) Chiral diselenides in asymmetric
selenoxide elimination: Y. Nishibayashi, J. D. Singh, S. Fukuzawa, and S.
Uemura, J. Org. Chem., 60, 4114 (1995). b) Chiral ester groups in
diastereofacial dehydrohalogenation: I. Ikeda, K. Honda, E. Osawa, M.
Shiro, M. Aso, and K. Kanematsu, J. Org. Chem., 61, 2031 (1996). c) Chiral
organoeuropium reagents in deracemization: Y. Naruse, H. Watanabe, Y.
Ishiyama, and T. Yoshida, J. Org. Chem., 62, 3862 (1997). d) Chiral
phosphonoacetates in asymmetric Horner-Wasdsworth-Emmons reaction:
K. Tanaka, K. Otsubo, and K. Fuji, Ttetrahedron Lett., 37, 3735 (1996). e)
Chiral alcohols in dynamic kinetic protonation: K. Mikami and A. Yoshida,
Angew. Chem., Int. Ed. Engl., 36, 858 (1997).
Scheme 2.
3
functionalized allene (R)-3.
Fast equilibrium between two diastereomeric ꢀ3-alkadienyl-
palladium complexes (Sp)-4 and (Rp)-4 was confirmed by the
following control experiment. When enantiomerically pure (S)-1a15
was allowed to react with malonate 2a in the presence of BSA and
ꢁ
the palladium catalyst, prepared from Pd2(dba)3 CHCl3 and 1,4-
bisdiphenylphosphinobutane, in THF at room temperature for 2 h,
the racemic allene 3a was obtained in 76% yield.
4
a) Pd-catalyzed arylation of allenylzinc compounds: W. de Graaf, J.
Boersma, G. van Koten, and C. J. Elsevier, J. Organomel. Chem., 378, 115
(1989). b) Pd-catalyzed hydroboration of enynes: Y. Matsumoto, M. Naito,
Y. Uozumi, and T. Hayashi, J. Chem. Soc., Chem. Commun., 1993, 1468. c)
Rh-catalyzed hydrosilylation of diynes: A. Tillack, D. Michalik, C. Koy, and
M. Michalik, Tetrahedron Lett., 40, 6567 (1999).
Y. Noguchi, H. Takiyama, and T. Katsuki, Synlett, 1998, 543.
M. Ogasawara, H. Ikeda, T. Nagano, and T. Hayashi, J. Am. Chem. Soc., 123,
2089 (2001).
The participation of ꢀ1-alkadienylpalladium complex 5 was
confirmed from the reaction of phosphate 1b with Pd(PPh3)4. The
1H and 31P NMR spectra of the product derived from the reaction of
the phosphate 1b with an equivalent of Pd(PPh3)4 in C6D6 in an
NMR tube showed a facile, exclusive formation of ꢀ1-pentadi-
enylpalladium 5a.16 The chloro complex 5b was obtained by ligand
exchange reaction upon treatment with zinc chloride as shown in
Scheme 3. The structure of 5b was confirmed by single-crystal X-
ray analysis.17
5
6
7
8
9
Reported in part: Y. Imada, K. Ueno, and S.-I. Murahashi, 74th CSJ National
Meeting, Kyoto, March 1998, Abstr., No. 3D709.
D. Djahanbini, B. Cazes, and J. Gore, Tetrahedron Lett., 25, 203 (1984); D.
Djahanbini, B. Cazes, and J. Gore, Tetrahedron, 43, 3441 (1987).
(6,60-Dimethoxybiphenyl-2,20-diyl)bis(diphenylphosphine): R. Schmid, J.
Foricher, M. Cereghetti, and P. Sch nholzer, Helv. Chim. Acta, 74, 370
(1991).
102,2 0-Bis(diphenylphosphino)-1,10-binaphthyl: A. Miyashita, A. Yasuda, H.
Takaya, K. Toriumi, T. Ito, T. Souchi, and R. Noyori, J. Am. Chem. Soc., 102,
7932 (1980).
11 G. Lowe, J. Chem. Soc., Chem. Commun., 1965, 411; J. H. Brewster, Topics
in Stereochemistry, 2, 1 (1967).
12 Y. Tanigawa, K. Nishimura, A. Kawasaki, and S.-I. Murahashi, Tetrahedron
Lett., 23, 5549 (1982).
13 Kleijin, H. Westmijze, J. Meijer, and P. Vermeer, Recl. Trav. Chim. Pays-
Bas, 100, 378 (1983).
14 J. Nokami, A. Maihara, and J. Tsuji, Tetrahedron Lett., 31, 5629 (1990); M.
E. Piotti and H. Alper, J. Org. Chem., 59, 1956 (1994); Y. Imada, G.
Vasapollo, and H. Alper, J. Org. Chem., 61, 7982 (1996).
15 Enantiomerically pure (S)-1a {[ꢁ]D 48.1 ꢃ (c 1.1, CHCl3)g was obtained by
the optical resolution of racemic 1a by HPLC with a chiral stationary phase
(Chiralcel OD).
Scheme 3.
16 5a: 1H NMR (500 MHz, C6D6, selected data) ꢃ 0.60 (t, J ¼ 7 Hz, 6 H), 1.57
(d, J ¼ 7 Hz, 3 H, He), 3.25 (dq, J ¼ 7, 7 Hz, 4 H), 4.51 (br, 1 H, Hd), 4.60(d,
J ¼ 10 Hz, Hb), 5,27 (dd, J ¼ 10, 17 Hz, Hc), 6,13 (d, J ¼ 17 Hz, Ha). 5b: 1H
NMR (500 MHz, C6D6, selected data) ꢃ1.72 (d, J ¼ 7 Hz, 3 H, He), 4.71 (dd,
J ¼ 2, 11 Hz, Hb), 4.97 (br, 1 H, Hd), 5,68 (ddd, J ¼ 2, 10, 16 Hz, Hc), 6,07
(dd, J ¼ 2, 16 Hz, Ha), 31P{1Hg NMR (202 MHz, C6D6) ꢃ 25.73. For related
(ꢀ1-1,3-butadien-2-yl)palladium complexes generated from Pd(PPh3)4 and
2,3-butadienyl chlorides, see: S. A. Benyunes, L. Brandt, A. Fries, M. Green,
M. F. Mahon, and T. M. T. Papworth, J. Chem. Soc., Dalton Trans., 1993,
3785.
In summary, we succeeded in asymmetric synthesis of
functionalized allenes 3 with high enantioselectivity by the
palladium-catalyzed asymmetric alkylation of racemic 2,3-alka-
dienyl phosphates 1 using palladium–MeOBIPHEP catalyst.
Further mechanistic study and application are in progress.
This work was supported by Research for the Future program,
the Japan Society for the Promotion of Science, and a Grant-in-Aid
for Scientific Research, the Ministry of Education, Science, Sports
and Culture of Japan.
17 Crystal data for 5bꢁ3C6H6: C59H55ClP2Pd, fw ¼ 967:82, Rigaku RAXIS-
RAPID, monoclinic, Cc (No. 9), a ¼ 20:1149(10) A, b ¼ 17:3353(11) A,
c ¼ 13:9252(8) A, ꢄ ¼ 94:843(2) ꢃ, V ¼ 4838:4(5) A3 Z ¼ 4, T ¼
101(2) K, Dcalcd ¼ 1:329 Mg mꢂ3, ꢅ ¼ 0:71069 A, Fð000Þ ¼ 2008, R1
0:0314; wR2 ¼ 0:0676 for all 5532 reflections, GOF ¼ 1:040.
¼
This paper is dedicated to Prof. Teruaki Mukaiyama on the
occasion of his 75th birthday.