Unusual chemoselective addition of diisopropylzinc to 2,2′-bipyridine-5,5′-dicarbonyl compounds in the 2-position and autoxidative reconversion with carbon-carbon bond cleavage

Article abstract of DOI:10.1039/b009474i

The chemoselective addition of diisopropylzinc to 2,2′-bipyridine-5,5′-dicarbonyl compounds in the 2-position and autoxidative reconversion with carbon-carbon bond cleavage was presented. It was shown that i-Pr₂Zn do not add to the aldehyde moiety but to the 2-position of the bipyridine to afford possessing a quaternary carbon atom in a yield of 69%. It was found that the i-Pr₂Zn does not add to the aldehyde but to the 2-position of the bipyridine ring by destroying the aromaticity of the pyridine ring.

Full text of DOI:10.1039/b009474i

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Unusual chemoselective addition of diisopropylzinc to
,2Ј-bipyridine-5,5Ј-dicarbonyl compounds in the 2-position
2
and autoxidative reconversion with carbon–carbon bond
cleavage
1
Shigehisa Tanji, Takanori Shibata, Itaru Sato and Kenso Soai*
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo,
Kagurazaka, Shinjuku-ku, Tokyo, 162-8601 Japan. E-mail: ksoai@ch.kagu.sut.ac.jp
Received 27th November 2000, Accepted 20th December 2000
First published as an Advance Article on the web 11th January 2001
Unusual chemoselective addition of diisopropylzinc to the
-position of 2,2Ј-bipyridine-5,5Ј-dicarbonyl compounds
affords the adducts with a quaternary carbon, and
autoxidation of the adducts reconverts them into the initial
compounds with carbon–carbon bond cleavage.
magnesium bromide did not add to bipyridine but exclusively
added to the aldehyde to give the corresponding alkanol 3a and
diol 4a in a total 52% yield (run 2). In the case of the addition
using isopropyllithium, 2a was not formed. The reduction of
aldehyde as a side reaction, was a major reaction, and alkanol
2
3
a and diol 4a were obtained in low yields (run 3). Addition of
Synthetic utilities of organozinc reagents have dramatically
increased during this decade. The relatively mild nucleo-
diethylzinc and di(n-butyl)zinc occurred at the 2-position of 1a
to give the corresponding adducts but in low yields along with
the alkylated aldehyde products (runs 4 and 5). Thus, only
1
philicity of dialkylzincs compared with alkyllithiums and
Grignard reagents makes dialkylzincs more chemoselective
reagents. For example, chiral amino alcohol catalysts enhance
the nucleophilicity of dialkylzincs to add to aldehydes in an
i-Pr Zn gave 2a in a high yield by the chemoselective addition to
the 2-position of 1a.
2
Generality of the addition of i-Pr Zn to the 2-positions of
2
2
enantioselective manner. On the other hand, addition of
2,2Ј-bipyridine-5,5Ј-dicarbonyl derivatives 1a–d is shown in
9,10
organometallic reagents to simple 2,2Ј-bipyridine normally
Table 2. 2,2Ј-Bipyridine derivatives possessing two carbonyl
substituents such as methoxycarbonyl, acetyl and dimethyl-
carbamoyl at the 5,5Ј-positions underwent the addition of
3,4
occurs at the 6-position. To the best of our knowledge, the
addition of organometallic reagents to the 2-position of
2
2
,2Ј-bipyridine is very rare due to the steric hindrance of the
-position. Meanwhile, the formation of the pyridine ring is
i-Pr Zn to the 2-position to afford the adducts 2b–d in high
2
5
yields of 88%, 93% and 82%, respectively (runs 2–4). Diiso-
propylzinc added to the 2-position of even 2,2Ј-bipyridine-5-
carbonyl derivatives, possessing only one carbonyl substituent,
to afford the corresponding adducts 2e–h in moderate yields
(runs 5–8). On the other hand, in the cases of 2,2Ј-bipyridines
(1i and 1j) without any carbonyl substituent at the 5,5Ј-
positions, no alkylation occurred even at room temperature
(runs 9 and 10). These results show that electron-withdrawing
carbonyl substituent(s) at the 5- (and 5Ј-) position(s) activates
hardly known by autoxidative carbon–carbon bond cleavage
without using transition metals.
We here report an unprecedented chemoselective addition
of diisopropylzinc to the 2-position of 2,2Ј-bipyridine-5,5Ј-
dicarbonyl compounds and the reconversion into the initial
compounds with autoxidative carbon–carbon bond cleavage.
In the course of our study on asymmetric autocatalysis of
6
3
-pyridylalkanol in the addition of diisopropylzinc (i-Pr Zn)
2
to the aldehyde moiety of 5-carbamoylpyridine-3-
bipyridine to undergo the addition of i-Pr Zn to the 2-position
2
7
carbaldehyde, we examined the reaction of i-Pr Zn with
of 2,2Ј-bipyridine derivatives. This also explains the faster
reactions with 1a–c possessing two carbonyl functionalities
2
8
2
(
,2Ј-bipyridine-5,5Ј-dicarbaldehyde 1a. Unexpectedly, i-Pr Zn
1.1 mol equiv.) did not add to the aldehyde moiety but to
2
(1.1 mol equiv. of i-Pr Zn, 1 h) compared with 1e–g with one
2
the 2-position of the bipyridine to afford 2a possessing a
carbonyl functionality (3.0 mol equiv. of i-Pr Zn, 10–20 h).
2
9
quaternary carbon atom in a yield of 69%. It should be
When 6-phenylpyridine-3-carbaldehyde, without the 2,2Ј-
emphasized that this chemoselectivity is quite unusual: the
bipyridine skeleton, reacted with i-Pr Zn in the presence of
2
i-Pr Zn does not add to the aldehyde but to the 2-position of
N,N-dibutylaminoethanol as a Lewis base, i-Pr Zn added only
2
2
the bipyridine ring by destroying the aromaticity of the pyridine
ring (Scheme 1).
We examined other organometallic reagents in the addition
reaction to 1a at 0 ЊC. As shown in Table 1, isopropyl-
to the aldehyde moiety to afford pyridylalkanol in 60% yield.
Thus, the structure of 2,2Ј-bipyridine is necessary for i-Pr Zn
2
to add regioselectively to the 2-position. We think that the
chelation by nitrogen atoms of bipyridine to the zinc atom
Scheme 1
DOI: 10.1039/b009474i
J. Chem. Soc., Perkin Trans. 1, 2001, 217–218
This journal is © The Royal Society of Chemistry 2001
217

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Table 1 Nucleophilic addition of organometallic reagents to 2,2Ј-bipyridine-5,5Ј-dicarbaldehyde
Run
1
R M (equiv.)
Solvent
Toluene
THF–Et O
Toluene–pentane
Toluene
Yield of 2 (%)
2a 69
Yield of 3 (%)
Yield of 4 (%)
n
i-Pr Zn (1.1)
3a
0
4a
0
2
a
2
3
i-PrMgBr (5.0)
i-PrLi (3.0)
2a
2a
0
0
19
17
3a 17
4a 35
2
a,b
3a
3
18
26
4a
9
24
15
4
5
Et Zn (5.0)
2
n-Bu Zn (5.0)
Toluene
2
a
b
Reactions were carried out at rt. Reduction of aldehyde to primary alcohol is a major reaction.
Table 2 Addition of diisopropylzinc to the 2-position of 2,2Ј-
unique adducts with quaternary carbons. Autoxidation of
the adducts liberates the initial 2,2Ј-bipyridine-5,5Ј-dicarbonyl
compounds and isopropyl hydroperoxide.
bipyridine derivatives
2
,2Ј-Bipyridine
i-Pr Zn
Yield of
2
Run
derivative 1
(equiv.)
Time/h
adduct 2 (%)
Notes and references
a
1
2
3
4
5
6
7
8
1a
1.1
1.1
1.1
5.0
3.0
3.0
3.0
5.0
3.0
3.0
1
1
1
48
10
20
12
48
24
24
2a 69
2b 88
2c 93
2d 82
2e 43
2f 71
2g 71
2h 64
0
a
1 Organozinc Reagents, ed. P. Knochel and P. Jones, Oxford
University Press, New York, 1999.
2 K. Soai and S. Niwa, Chem. Rev., 1992, 92, 833.
3 T. Kauffmann, J. König and A. Woltermann, Chem. Ber., 1976, 109,
3864.
1b
a
1c
a
1d
a
1e
a
1f
a
4 Reviews on dihydropyridine: (a) D. M. Stout and A. I. Meyers,
Chem. Rev., 1982, 82, 223; (b) U. Eisner and J. Kuthan, Chem. Rev.,
1972, 72, 1.
1g
b
1h
b
9
0
2,2Ј-Bipyridine 1i
5,5Ј-Dimethyl-2,2Ј-
bipyridine 1j
b
5 For the addition of Grignard reagent to the 2-position of
1
0
2
,2Ј-biquinolyl, S. Wakabayashi, Y. Kubo, T. Takeda, J. Uenishi and
S. Oae, Bull. Chem. Soc. Jpn., 1989, 62, 2338.
a
b
Reactions were carried out at 0 ЊC. Reactions were carried out at rt.
6
For the formation of a pyridine ring by carbon–carbon bond
cleavage of 1,4-dihydropyridine using manganese dioxide, J. J.
Vanden Eynde, F. Delfosse, A. Mayence and Y. van Haverbeke,
Tetrahedron, 1995, 51, 6511.
11
of i-Pr Zn has two effects: (1) it enhances the nucleophilicity
of i-Pr Zn, (2) it places i-Pr Zn near to the reaction site, i.e., the
-position of the 2,2Ј-bipyridine.
The adduct 2a can be isolated and is stable under an argon
atmosphere. We also found that, on exposure to the air at rt
in dichloromethane, adduct 2a converts into the initial 2,2Ј-
bipyridine-5,5Ј-dicarbaldehyde 1a in an almost quantitative
yield (99%) (Scheme 1). In the NMR sample tube, we
observed the formation of equimolar amounts of the initial 1a
and isopropyl hydroperoxide (confirmed by H and C NMR
and GLC analysis). The dealkylative autoxidation is probably
due to the release of the steric congestion around the quater-
nary carbon atom (the 2-position) of 2a and to the stabilization
by aromatization. The addition of a radical initiator (AIBN)
or UV irradiation in air accelerated the autoxidation. Con-
versely, autoxidation was suppressed by the addition of a
radical scavenger such as 2,6-di-tert-butylphenol. Under the
same conditions (air, CH Cl , rt, 1–7 d) adducts 2b–h were
2
2
2
7 (a) T. Shibata, H. Morioka, S. Tanji, T. Hayase, Y. Kodaka and
K. Soai, Tetrahedron Lett., 1996, 37, 8783; (b) K. Soai, S. Niwa
and H. Hori, J. Chem. Soc., Chem. Commun., 1990, 982; (c) K. Soai,
T. Shibata and I. Sato, Acc. Chem. Res., 2000, 33, 382.
2
8
(a) J. de Mendoza, E. Mesa, J.-C. Rodriguez-Ubis, P. Vázquez,
F. Vögtle, P.-M. Windscheif, K. Rissanen, J.-M. Lehn, D.
Lilienbaum and R. Ziessel, Angew. Chem., Int. Ed. Engl., 1991, 30,
1
331; (b) F. Ebmeyer and F. Vögtle, Chem. Ber., 1989, 122, 1725.
1 13
9
Satisfactory results were obtained from H and C NMR, IR, high
resolution mass spectra (HRMS) and/or elemental analyses for all
new compounds.
1
13
10 A typical experimental procedure is as follows (Table 1, run 1): a
toluene solution of diisopropylzinc (1 M, 0.22 mL) was added
dropwise to a stirred solution of dialdehyde 1a (42.4 mg, 0.2 mmol)
in toluene (7.0 mL) at 0 ЊC. After 1 h, the reaction was quenched by
the addition of sat. aq. NaHCO (10 mL) at 0 ЊC. The mixture was
3
extracted with ethyl acetate. The extract was dried over anhydrous
sodium sulfate and evaporated under reduced pressure. Purifi-
cation of the residue by TLC on silica gel gave pure adduct 2a as a
colorless oil (35.4 mg) in 69% yield.
1 (a) C. Bolm, M. Ewald and M. Felder, Chem. Ber., 1992, 125, 1205;
(b) C. Bolm, M. Ewald, M. Felder and G. Schlingloff, Chem. Ber.,
1992, 125, 1169.
2
2
easily converted into the corresponding initial 2,2Ј-bipyridines
b–h in high to quantitative (91% - quant.) yields.
As described, chemoselective addition of i-Pr Zn to the 2-
1
1
2
position of 2,2Ј-bipyridine-5,5Ј-dicarbonyl compounds affords
2
18
J. Chem. Soc., Perkin Trans. 1, 2001, 217–218