Effects of monodentate oxazoline ligands in Ni/Al-catalyzed regioselective cyclotrimerization of enones and alkynes

Article abstract of DOI:10.1039/b001151g

A nickel and aluminium system including monodentate oxazoline ligands catalyzed the regioselective cyclotrimerization of enones and alkynes.

Full text of DOI:10.1039/b001151g

Effects of monodentate oxazoline ligands in Ni/Al-catalyzed regioselective
cyclotrimerization of enones and alkynes†
Shin-ichi Ikeda,* Hirokazu Kondo and Naoyoshi Mori
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
E-mail: ikeshin@phar.nagoya-cu.ac.jp
Received (in Cambridge, UK) 10th February 2000, Accepted 3rd April 2000
Published on the Web 20th April 2000
A nickel and aluminium system including monodentate
oxazoline ligands catalyzed the regioselective cyclotrimer-
ization of enones and alkynes.
adducts (regioisomeric mixture) obtained were treated with
DBU in air to convert them to the corresponding aromatic
compounds 3 and/or 4, owing to the ease of regiochemical
analysis by 1H NMR spectroscopy. The reaction in the presence
of PPh3 or P(C6H4Me-o)3 gave 4aa as the sole product (runs 1
and 2), while the addition of other organophosphorus ligands or
AsPh3 failed (runs 3–6). In sharp contrast, the reaction using
pyridine or 5 led to the selective synthesis of 3aa (runs 7 and 8).
Monodentate oxazoline ligands 6 strongly affected the re-
gioselective cycloaddition (runs 9–14).5,6 Most strikingly, when
the reaction was carried out in the presence of 6d–f, 3aa was
obtained in 95–96% selectivity (runs 12–14). Thus, ligands 6 in
place of triarylphosphines caused switching of the regioselectiv-
ity in the cyclotrimerization. When a bidentate bis-oxazoline 7
(10 mol%) was used in the reaction,7 the yield of 3aa was low,
even after 24 h (run 15).
The results of the catalytic cyclotrimerization of a variety of
enones 1 and alkynes 2 are summarized in Table 2. In our initial
efforts to achieve the regioselective cyclotrimerization of 1 and
2 using a Ni(acac)2/PPh3/Me3Al/PhOH catalytic system, 2b
was reacted with 1a to selectively give 4ab (entry 1).4 However,
when the reaction was carried out in the presence of a Ni/Al
catalytic system using 6e, 3ab was obtained predominantly
(entry 2). A similar tendency was found in the reactions of 2a
with 1b (entry 5 vs. 6). The product ratio of 8 and 9 derived from
the reaction of 1c with 2a also depended on the nature of the
employed ligands (L) (Scheme 2).8 On the other hand, the
reactions of alkyl-substituted alkynes such as 2c and 2d with 1
using 6e gave a higher regioselection of 3 than those using PPh3
(entries 3 vs. 4 and 7 vs. 8).
Since the pioneering work by Reppe,1 the cyclotrimerization of
unsaturated hydrocarbons using various transition-metal cata-
lysts has represented a new method for preparing six-membered
cyclic compounds.2 In particular, intramolecular reactions have
been used as an efficient synthetic approach.3 In contrast, two-
or three-component intermolecular cyclotrimerization has not
yet been shown to be useful, since it is more difficult to control
the chemo-, regio-, and stereo-selectivity. We recently reported
a new cyclotrimerization of enones 1 and alkynes 2 by the
synergistic effects of nickel and aluminium catalysts (L = PPh3
in Scheme 1).4 In this reaction, however, regioselection was
dependent on the nature of 2 used (vide infra). We report here,
a more efficient catalytic system for regioselective cyclotrimer-
ization of 1 and 2.
We investigated the effects of some ligands (L) on re-
gioselection in the cyclotrimerization of 2-cyclopenten-1-one
1a with (trimethylsilyl)acetylene 2a by the Ni(acac)2/L/Me3Al/
PhOH catalytic system (Table 1).‡ The cyclotrimerization
In summary, we have clarified the effects of monodentate
oxazolines 6, which have scarcely been used as ligands in
catalytic reactions, in the Ni/Al-catalyzed cyclotrimerization of
Table 1 Cyclotrimerization of 1a and 2a in the presence of the Ni(acac)2/L
/Me3Al/PhOH catalytic systema
Yieldb (%)
Ratioc
Run
L
Time/h
(3aa + 4aa) (3aa+4aa)
1d
2
3
4
5
6
7
8
9
10
11
12
13
14
15
PPh3
P(C6H4Me-o)3
2
2
33
49
Trace
Trace
No reaction
Trace
6
12
61
60
61
59
69
59
23
0+100
0+100
PBu3
P(OPh)3
dppee
AsPh3
Pyridine
5
6a
6b
6c
6d
24
24
24
24
24
24
2
2
2
2
2
—
—
—
—
72+28
80+20
86+14
72:+8
85+15
95+5
96+4
96+3
97+3
6e
6f
7
Scheme 1 Reagents and conditions: i, Ni(acac)2 (10 mol%), L (20 mol%),
Me3Al (80 mol%), PnOH (200 mol%), THF, room temp.; ii, DBU, air,
overnight.
2
24
a Reaction conditions as in Scheme 1. b Yield after purification by silica gel
chromatography. c Determined by 1H NMR. d See ref. 4. e 1,2-Bis(diphe-
nylphosphino)ethane.
† Electronic supplementary information (ESI) available: experimental and
characterization data. See http://www.rsc.org/suppdata/cc/b0/b001151g/
DOI: 10.1039/b001151g
Chem. Commun., 2000, 815–816
This journal is © The Royal Society of Chemistry 2000
815

Table 2 Cyclotrimerization of 1 and 2 in the presence of the Ni(acac)2/L
/Me3Al/PhOH catalytic system (L = PPh3 vs. 6e)a
Notes and references
‡ Typical experimental procedure (entry 2 in Table 2): to a solution of
Ni(acac)2 (27 mg, 0.1 mmol) and 6e (0.1 mmol) in THF (4 mL) was added
Me3Al in 1.0 M hexane solution (0.8 mL) at 0 °C under N2. After stirring
for 5 min, PhOH (190 mg, 2.0 mmol) was added, and the mixture was stirred
for 5 min. To the resulting dark red solution were added 1a (1.0 mmol) and
2b (2.0 mmol) at 0 °C. After the addition was completed, the whole mixture
was stirred at room temperature for 2 h. DBU (350 mg, 2.3 mmol) was
added to this reaction mixture in air, and this was again stirred at room
temperature overnight. Aqueous HCl (0.2 M, 30 mL) was added, and
stirring was continued for 10 min. The aqueous layer was extracted with
diethyl ether. The combined organic layer was washed with NaHCO3 and
then with brine, dried over MgSO4 for 30 min, filtered, and concentrated in
vacuo. The residue was purified by column chromatography on silica gel
(hexane–AcOEt, 14:1) to yield 3ab (67%) as the sole product as a colorless
oil; dH(400 MHz, CDCl3, Me4Si) 1.36 (s, 9 H, CH3), 1.47 (s, 9 H, CH3), 2.66
(t, J 6.1 Hz, 2 H, CH2), 3.07 (t, J 6.1 Hz, 2 H, CH2), 7.29 (s, 1 H, NCH), 7.40
(s, 1 H, NCH); dC(100 MHz, CDCl3, Me4Si) 25.85, 29.75, 31.12, 35.37,
35.95, 37.54 (CH3, CH2 and C), 121.20, 122.26, 132.30, 151.41, 157.81,
158.80 (Ar), 206.07 (CO); IR(neat) 1705 (nCO) cm21; GC–MS (EI, 70 eV)
m/z (rel int, %) 244 (M+, 55), 229 (100). Anal. Calc. for C17H24O: C, 83.55;
H, 9.90. Found: C, 83.51; H, 9.99%.
Yieldb
(%)
(3 + 4) (3+4)
Product(s)
Ratioc
Entry
1
2
L
major, (minor)
1d,e
2e
3d
4
1a
1a
1b
1b
2b
2c
2a
2d
PPh3
6e
PPh3
6e
PPh3
6e
PPh3
6e
4ab (3ab)
3ab
3ac (4ac)
3ac
4ba (3ba)
3ba
3bd (4bd)
3bd
45
67
81
87
29
78
83
81
11+89
100+0
92+8
100+0
17+83
100+0
92+8
5f
6
7d,g
8g
100+0
a Reaction conditions as in Scheme 1. Unless stated otherwise, the
cycloadditions were performed with stirring for
2
h. b Yield after
purification by silica gel chromatography. c Determined by 1H NMR. d See
ref. 4. e The aromatization was carried out with 0.2 M NaOH in MeOH.
f Reaction time: 24 h. g Reagents: 1+2:Ni(acac)2:L+Me3Al+PhOH
1+2+0.05+0.1+0.4+4+1.
=
1 W. Reppe and W. J. Schweckendiek, Justus Liebigs Ann. Chem., 1948,
560, 104.
2 N. E. Schore, in Comprehensive Organic Synthesis, ed. B. M. Trost and
I. Fleming, Pergamon, Oxford, 1991, vol. 5, ch. 9.4, p. 1129; D. B.
Grotjahn, in Comprehensive Organometallic Chemistry II, ed. L. S.
Hegedus, Pergamon, Oxford, 1995, vol. 12, ch. 7.4; N. E. Schore, Chem.
Rev., 1988, 88, 1081.
3 K. P. C. Vollhardt, Angew. Chem., Int. Ed. Engl., 1984, 23, 539; M.
Lautens, W. Klute and W. Tam, Chem. Rev., 1996, 96, 49.
4 S. Ikeda, N. Mori and Y. Sato, J. Am. Chem. Soc., 1997, 119, 4779; N.
Mori, S. Ikeda and Y. Sato, J. Am. Chem. Soc., 1999, 121, 2722.
5 D. J. Ager, I. Prakash and D. R. Schaad, Chem. Rev., 1996, 96, 835; K.
Kamata, I. Agata and A. I. Meyers, J. Org. Chem., 1998, 63, 3113.
6 For the efficiency of mono-oxazoline ligands in a catalytic asymmetric
multiple-component domino coupling, see: S. Ikeda, D.-M. Cui and Y.
Sato, J. Am. Chem. Soc., 1999, 121, 4712.
Scheme 2 Reagents and conditions: i, 1c (1 equiv.), 2a (2 equiv.) Ni(acac)2
(10 mol%), L (20 mol%), Me3Al (80 mol%), PnOH (200 mol%), THF,
room temp., 24 h.
enones 1 and alkynes 2. The reaction using 6 resulted in the
selective formation of 3, independent on the alkynes used.
This work was supported by a Grants-in-Aid for Scientific
Research (No. 11672112) from Japan Society for the Promotion
of Science.
7 A. Pfaltz, Acc. Chem. Res., 1993, 26, 339.
8 Attempted conversion of a mixture of 8 and 9 to the corresponding
aromatic compounds by treatment with base (DBU or NaOH/MeOH)
failed.
816
Chem. Commun., 2000, 815–816