New 1,10-phenanthroline ligands for asymmetric catalysis: Enantioselective palladium catalyzed allylic substitution

Article abstract of DOI:10.1016/S0957-4166(98)00279-1

A number of new chiral C₁-symmetric 1.10-phenathrolines have been prepared and assessed in the enantioselective palladium catalyzed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethylmalonate. Enantioselectivitics up to 84% we

Full text of DOI:10.1016/S0957-4166(98)00279-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2575–2578
New 1,10-phenanthroline ligands for asymmetric catalysis:
enantioselective palladium catalyzed allylic substitution
Giorgio Chelucci ∗ and Antonio Saba
Dipartimento di Chimica, Universitità di Sassari, via Vienna 2, 1-07100 Sassari, Italy
Received 24 June 1998; accepted 10 July 1998
Abstract
A number of new chiral C1-symmetric 1,10-phenathrolines have been prepared and assessed in the enantio-
selective palladium catalyzed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethylmalonate.
Enantioselectivities up to 84% were obtained. © 1998 Elsevier Science Ltd. All rights reserved.
Recently, continuing our interest in the synthesis and application of chiral pyridine derivatives as
ligands for metal complexes in enantioselective catalysis1 we have evaluated the potential utility of a
number of chiral ligands with sp2-nitrogen donors as chiral controllers for enantioselective palladium
catalyzed allylic substitutions.2 This preliminary investigation indicated that in a series of alkyl C1-
symmetric phenanthroline–bipyridine–terpyridine, in which the same substituent was present on the
heterocycle, the phenanthroline gave not only the more reactive catalytic species but also the higher
enantioselection. Moreover, phenanthrolines gave catalysts whose reactivity and enantioselectivity was
dependent on the distance of the chiral substituent from the heterocyclic nitrogen. Thus, between the 2-
and 3-(2,2-dimethylnorpynan-2-yl)-1,10-phenanthroline (1a and 1b, respectively) the best enantioselect-
ivity (50% ee) was obtained with the ligand 1a.
These promising results prompted us to prepare and assess in this catalytic process C1-symmetric
phenanthrolines in which the substituents on the stereocentre bound to the heterocyclic ring are arranged
in a rigid backbone in such a way as to provide a more rigid array of the ligand around the metal
∗
Corresponding author.
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00279-1

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centre. In this communication we report the synthesis and application of a number of new chiral 1,10-
phenanthrolines 5,63 in the enantioselective palladium catalyzed allylic substitution of 1,3-diphenylprop-
2-enyl acetate with dimethylmalonate.
The dihydrophenathroline 4 was prepared by conjugate addition of the lithium enolate of tetrahydro-
quinolone 2 [generated by treatment with lithium diisopropylamine (LDA) at −78°C for 2 h] with (−)-
pinocarvone 34 (−78°C to room temperature) followed by azaanellation of the unisolated 1,5-dicarbonyl
intermediate with the ammonium acetate/acetic acid system5 (63% overall yield; Scheme 1). Then, the
phenanthroline 5 was obtained by heating under reflux a decaline solution of 4 in the presence of 10%
palladium on carbon (90% yield). Finally, the red solution of lithiated phenanthroline 5 (obtained by
treatment with LDA at −40°C for 2 h) was quenched with the proper alkyl iodide to give ligands 6a–d
in 35–67% yield).6 The use of alkyl iodide was necessary on account of the unexpectedly low reactivity
of the lithium salt of 5. Thus, the reaction with benzyl bromide, isopropyl iodide or acetone failed even
if hexamethylphosphoric triamime (HMPA) or tetramethylethylenediamine were used as co-solvents.
Scheme 1.
To test the ability of new ligands to provide asymmetric induction in the palladium catalyzed allylic
substitutions we examined the alkylation of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate
which serves as a model substrate to compare the outcome of different ligands.7 Allylic substitutions
were carried out at room temperature employing [Pd(η3-C3H5)Cl]2 as a procatalyst in a methylene
chloride solution of dimethyl malonate, N,O-bis(trimethylsilyl)acetamide (BSA) and potassium acetate.8
The results of the catalytic reaction are reported in Table 1.
1,10-Phenanthrolines 5–6 were able to provide effective palladium catalysts. Total conversion of the
starting material was achieved with these ligands in less than 45 min to give high yields of dimethyl 1,3-
diphenylprop-2-enylmalonate 8. The introduction of alkyl groups at the 11-position of phenanthroline
5 was crucial for the stereoselectivity of the process. Thus, phenanthroline 5 gave a much lower
enantiomeric excess than the 11-substituted phenanthroline 6. The best stereoselectivity (84% ee) was
obtained with the n-butyl substituted ligand 6b, whereas a drop of enantioselectivity was observed with
a branched substituent (entry 3 versus 4 and 5).
In all cases, the absolute configuration of the substitution product 8 was controlled by the absolute
configuration at the stereogenic centre at the 11-position of the heterocyclic ring, resulting in the preferred
formation of (R)-8. Moreover, since the 11-unsubstituted phenanthroline 5 gave the same sense of

G. Chelucci, A. Saba / Tetrahedron: Asymmetry 9 (1998) 2575–2578
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Table 1
Allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethyl malonatea
enantioselection than the 11-substituted one, it is reasonable to assume that in phenanthroline 6 the
stereocentre at the 11-position and those at the 8,10-positions are not in a mismatching relation.
Finally, since the enantiomeric excess of ligands 5 and 6 is 91%, a higher asymmetric induction
can be foreseen, excluding asymmetric amplification processes, if the same ligands could be used in
enantiomerically pure form. Thus, for the enantiomerically pure ligand 6b an enantiomeric excess of
92% should be expected.
In conclusion, in this paper we have reported the first synthesis of phenanthroline ligands9 in which
the substituent on the stereocentre bonded to the heterocyclic ring is arranged in a rigid backbone, and
good preliminary results have been obtained with these ligands in enantioselective allylation reactions.10
References
1. Chelucci, G.; Berta, D.; Fabbri, D.; Pinna, G. A.; Saba, A.; Ulgheri, F. Tetrahedron: Asymmetry, 1998, 9, 1933. Chelucci,
G.; Pinna, G. A.; Saba, A. Tetrahedron: Asymmetry, 1998, 9, 531. Chelucci, G.; Medici, S.; Saba, A. Tetrahedron:
Asymmetry, 1997, 8, 3183. Chelucci, G.; Pinna, G. A.; Saba, A. Tetrahedron: Asymmetry, 1997, 8, 2571. Chelucci, G.;
Marchetti, M.; Sechi, B. J. Mol. Catal., 1997, 122, 111. Chelucci, G.; Berta, D.; Saba, A. Tetrahedron, 1997, 53, 3843.
Chelucci, G.; Pinna, G. A.; Saba, A. Tetrahedron: Asymmetry, 1997, 8, 2571. Chelucci, G. Tetrahedron: Asymmetry, 1997,
8, 2667 and references therein.
2. Chelucci, G.; Caria, V.; Saba, A. J. Mol. Catal. A, 1998, 130, 51.
3. The name tentatively attributed to 5 is 8,10-methano-9,9-dimethyl-8,9,10,11-tetrahydrobenzo[b] [1,10]phenanthroline.
4. (−)-Pinocarvone was prepared from (1R)-(+)-α-pinene (91% ee by GLC, Aldrich): Mihelich, E. D.; Eickhoff, D. J. J. Org.
Chem., 1983, 48, 4135.
5. Kröhnke, F. Angew. Chem., Int. Ed. Engl., 1963, 2, 225, 380.
6. All compounds showed satisfactory spectroscopic and analytical data. Compound 5 was isolated in 90% yield: mp
25
1
229–230°C; [α]D +102.6 (c 1.4, CHCl3); H-NMR (CDCl3): δ 9.22 (dd, 1H, J=4.2, 1.5), 8.25 (dd, 1H, J=8.1, 1.8),
7.74 (s, 3H), 7.60 (dd, 1H, J=8.1, 4.5), 3.61 (d, 2H, J=3.9), 3.06 (t, 1H, J=5.7), 2.84 (m, 1H), 2.52 (m, 1H), 1.51 (s,
3H), 1.42 (d, 1H, J=9.6), 0.74 (s, 3H). Compound 6a was isolated in 67% yield after flash chromatography (petroleum
25
ether/ethyl acetate): mp 77–78°C; [α]D +2.3 (c 0.7 CHCl3); 1H-NMR (CDCl3): δ 9.19 (dd, 1H, J=4.2, 1.5), 8.20 (dd,

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G. Chelucci, A. Saba / Tetrahedron: Asymmetry 9 (1998) 2575–2578
1H, J=8.1, 1.8), 7.71 (s, 2H), 7.68 (s, 1H), 7.56 (dd, 1H, J=8.1, 4.2), 3.66 (m, 1H), 3.02 (t, 1H, J=5.4), 2.68 (m, 1H),
2.27 (m, 1H), 1.64 (d, 3H, J=6.9), 1.48 (s, 3H), 1.45 (d, 1H, J=10.2), 0.68 (s, 3H). Compound 6b: was isolated in 43%
25
yield after chromatographic purification on Al2O3 (petroleum ether:ethyl acetate=1:1): mp 65–66°C; [α]D −33.9 (c 1.3,
CHCl3); 1H-NMR (CDCl3): δ 9.18 (dd, 1H, J=4.2, 1.5), 8.17 (dd, 1H, J=8.1, 1.8), 7.67 (s, 2H), 7.65 (s, 1H), 7.53 (dd, 1H,
J=8.1, 4.5), 3.60 (m, 1H), 2.99 (t, 1H, J=5.7), 2.19 (m, 1H), 2.52–2.40 (m, 2H), 1.80 (m, 1H), 1.66 (m, 1H), 1.48 (s, 3H),
1.44 (d, 1H, J=9.6), 1.09 (d, 3H, J=6.6), 1.00 (d, 3H, J=6.6), 0.65 (s, 3H). Compound 6c: was isolated in 35% yield after
25
chromatographic purification on Al2O3 (petroleum ether:ethyl acetate=1:1): mp 72–73°C; [α]D −49.1 (c 0.9 CHCl3);
1H-NMR (CDCl3): δ 9.19 (dd, 1H, J=4.2, 1.5), 8.20 (dd, 1H, J=8.1, 1.8), 7.71 (s, 2H), 7.68 (s, 1H), 7.56 (dd, 1H, J=8.1,
4.2), 3.66 (m, 1H), 3.02 (t, 1H, J=5.4), 2.62 (m, 1H), 2.27 (m, 1H), 1.64 (d, 3H, J=6.9), 1.48 (s, 3H), 1.45 (d, 1H, J=10.2),
0.68 (s, 3H). Compound 6d: was isolated in 55% yield after chromatographic purification on Al2O3 (petroleum ether:ethyl
25
1
acetate=1:1): mp 70–71°C; [α]D +56.1 (c 1.1 CHCl3); H-NMR (CDCl3): δ 9.20 (dd, 1H, J=4.5, 1.8), 8.18 (dd, 1H,
J=8.1, 1.8), 7.70 (s, 1H), 7.69 (s, 2H), 7.54 (dd, 1H, J=8.1, 4.2), 7.40–7.18 (m, 5H), 4.22 (dd, 1H, J=13.5, 4.23), 3.86 (m,
1H), 3.00 (t, 1H, J=5.7), 2.83 (dd, 1H, J=13.5, 11.7), 2.60 (m, 1H), 2.14 (m, 1H), 1.54 (d, 1H, J=9.9), 1.36 (s, 3H), 0.64 (s,
3H).
7. Trost, B. M.; Van Vranken, D. L. Chem. Rev., 1996, 96, 395. Reiser, O. Angew. Chem., 1993, 105, 576; Angew. Chem., Int.
Ed. Engl., 1993, 32, 547. Hayashi, T. In Catalytic Asymmetric Synthesis, Ojima, I., Ed.; VCH: Weinheim, 1993. Frost, C.
G.; Howarth, J.; Williams, J. M. J. Tetrahedron: Asymmetry, 1992, 3, 1089.
8. Trost, B. M.; Murphy, D. J. Organometallics, 1985, 34, 2015.
9. For a leading reference, see: Chelucci, G. Gazz. Chim. Ital., 1992, 122, 89. For more recent applications in asymmetric
catalysis, see: Chelucci, G.; Cabras, M. A.; Saba, A. J. Mol. Catal. A., 1995, 95, L7–L10 and Ref. 2.
10. After the submission of this paper, two important references have come to our attention: Riesgo, E. C.; Credi, A.; De Cola,
L.; Thummel, R. P. Inorg. Chem., 1998, 37, 2145. Poña-Cabrera, E.; Norby, P. O.; Sjógren, M.; Vitagliano, A.; De Felice,
V.; Oslob, I.; Ishii, S.; O’Neill, D.; Åkermark, B.; Helquist, P. J. Am. Chem. Soc., 1996, 118, 4299.