Zn-promoted regio- and sequence-selective one-pot joining reactions of three components: vinylpyridines, alkyl iodides, and carbonyl compounds (or nitriles)

Article abstract of DOI:10.1016/j.tet.2009.06.073

Addition of alkyl iodides (3) into the solution containing 2-(or 4-)vinylpyridine (1 or 2) and carbonyl compounds (6) in the presence of Zn-powder (99.9%) in acetonitrile under refluxing brought about regio- and sequence-selective joining reaction of thre

Full text of DOI:10.1016/j.tet.2009.06.073

Tetrahedron 65 (2009) 7706–7711
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Tetrahedron
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Zn-promoted regio- and sequence-selective one-pot joining reactions
of three components: vinylpyridines, alkyl iodides, and carbonyl
compounds (or nitriles)
*
Kenji Mineyama, Hirofumi Maekawa, Akihiro Kohsaka, Yoshimasa Yamamoto, Ikuzo Nishiguchi
Department of Chemistry, Nagaoka University of Technology, 1603-1, Kamitomioka-cho, Nagaoka, Niigata 940-2188, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 May 2009
Received in revised form 18 June 2009
Accepted 19 June 2009
Available online 24 June 2009
Addition of alkyl iodides (3) into the solution containing 2-(or 4-)vinylpyridine (1 or 2) and carbonyl
compounds (6) in the presence of Zn-powder (99.9%) in acetonitrile under refluxing brought about regio-
and sequence-selective joining reaction of three components to give the corresponding (2-hydroxy-
ethyl)pyridines (7 or 8) in good to moderate yields. On the other hand, 2-(2- or 4-pyridyl)ethyl alkyl
ketones (10 or 11) were obtained from the similar joining reaction of three components by addition of
alkyl iodides (3) into the solution of 2-(or 4-)vinylpyridine (1 or 2), and nitriles (9) in toluene containing
Zn-powder (99.9%) under the similar reaction conditions.
Keywords:
Three components-coupling
Vinylpyridine
Ó 2009 Elsevier Ltd. All rights reserved.
Alkyl iodide
Carbonyl compound
Nitrile
1. Introduction
(or nitriles or acid anhydrides).12 It was instructive that the re-
actions proceeded regio- and sequence-selectively through the first
Pyridine derivatives1 have been of much importance and use-
fulness as bioactive natural products, pharmaceutical drugs, agro-
chemicals and various types of organic functional compounds such
as electronic information materials, semi-conductors and battery
materials, although only some reactions have been reported on
carbon–carbon bond formation for pyridine derivatives, such as
simple nucleophilic attack of stable carbanions to 2-vinylpyridine,2
alkylation to the
ond C-acylation by acid anhydrides (or electrophilic attack by car-
bonyl compounds to the -carbanions).
In this study, we wish to report Zn-promoted one-pot highly
selective joining reactions of three components, 2-(or 4-)vinyl-
pyridines (1 or 2), alkyl iodides (3), and carbonyl compounds (6) (or
nitriles (9)) in regio- and sequence-selective manners to give the
corresponding (2-hydroxyethyl)pyridines (7 or 8) or 2-(2- or 4-
pyridyl) ethyl alkyl ketones (10 or 11) in good to moderate yields, as
is shown in Scheme 1.
b-carbons by alkyl iodide, and the following sec-
a
and similar attack of a-carbanions generated from 2-(or 4-)vinyl
pyridine to styrene derivatives.3,4
On the other hand, conjugate addition of organozinc or orga-
nocopper reagents to a,b
-unsaturated carbonyl compounds,5 fol-
lowed by the subsequent trapping of the anionic intermediates has
been reported successfully to proceed using alkyl halides,6 acid
chlorides,7 aldehydes,8 and phenylselenyl halides.9 However, the
preparation and the handling of these organometallic reagents are
troublesome and not necessarily simple, and these one-pot re-
actions, in principle, require two steps at low temperatures such as
ꢀ78 ꢁC.
2
R
Zn(99.9%)
1
R1I
CH CH2
O
CH
CH2R
R2
R3
+
+
CH3CN
R3
N
N
HO
Y= 72-33%
1: 2-Vinyl
2: 4-Vinyl
3
6
7: 2-Vinyl
8: 4-Vinyl
Zn(99.9%)
CH2R1
1
R I
R4-CN
CH
CH CH2
We have already reported Zn-promoted one-pot joining re-
+
+
Toluene
N
N
action of three components among alkyl iodides,
a,b-unsaturated
O
esters (or
a,b
-unsaturated nitriles), and carbonyl compounds10,11
R4
10: 2-Vinyl
11: 4-Vinyl
Y=95-15%
1:2-Vinyl
2:4-Vinyl
3
9
* Corresponding author. Tel.: þ81 258 47 9005; fax: þ81 258 47 9300.
E-mail address: nishiiku@vos.nagaokaut.ac.jp (I. Nishiguchi).
Scheme 1. Zn-promoted regio- and sequenceselective joining reaction of three
components.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.073

K. Mineyama et al. / Tetrahedron 65 (2009) 7706–7711
7707
Table 2
2. Results and discussion
Zn-promoted joining reaction of three components 2- (or 4-)vinylpyridine,
isopropyl iodide and carbonyl compounds
As typical procedure for formation of (2-hydroxy) ethyl-
pyridines (7 or 8), alkyl iodide (3) was added dropwise into a so-
lution of 2-(or 4-)vinylpyridines (1 or 2) and carbonyl compounds
(6) in acetonitrile under gentle refluxing to give the corresponding
joining products of those three components in good to moderate
yields. Interestingly, replacement of acetone (6a) by acetonitrile
(9a) as the reagent and that of acetonitrile by toluene as the solvent
in this reaction, brought about formation of 5-methyl-3-(2-
pyridyl)hexan-2-one (10a;a) in a 82% yield as the almost single
product, suggesting that acetone is more reactive than acetonitrile
as an electrophile in the present Zn-promoted one-pot highly se-
lective joining reaction of three components.
R3
R2
N
C
R2
R3
OH
Zn
(CH3)2CH-I
CH(CH3)2
CH=CH2
CH-CH2
C=O
N
CH3CN
7 (a;a-g): 2-alkyl
8 (a;a-g): 4-alkyl
1 : 2-Vinyl
2 : 4-Vinyl
6a-g
3a
R2
R3
Yield (%)
7(a; a–g): 2-alkyl
8(a; a–g): 4-alkyl
CH3
CH3CH2
CH3
CH3CH2
(CH3)2CH
60 (7a; a)
63 (7a; b)
72 (7a; c)
33 (7a; d)
67 (7a; e)
57 (7a; f)
66 (7a; g)
48 (8a; a)
51 (8a; b)
Trace
46 (8a; d)
65 (8a; e)
55 (8a; f)
65 (8a; g)
(CH3)2CH
–(CH2)5–
(CH3)2CH
C2H5(CH3)CH
(C2H5)2CH
It may be quite noteworthy that complete regioselectivity was
clearly observed that the alkyl groups of halides (3) form carbon–
carbon bonds at b-position of the vinyl groups of 2-(or 4-)vinyl-
pyridines (1 or 2), while the carbon atoms of the carbonyl groups of
H
H
H
Reaction conditions: substrate 1 or 2 (10 mmol), isopropyl iodide 3 (40 mmol),
carbonyl compound 4 (500 mmol), Zn (99.9% pure, 40 mmol), acetonitrile (100 ml),
reflux for 0.5–1.0 h, N2 atmosphere.
6 or the cyano groups of nitriles (9) were attached with
the vinyl groups of 1 or 2.
a-carbon of
As shown in Table 1, effect of halides (3a–f) on the yield of the
products (4a–f and 5a–f) in the joining reaction using water may
indicate that secondary alkyl iodides were superior to primary or
aryl iodides and activated bromides.
Table 3
Zn-promoted joining reaction of three components: 2-(or 4-) vinylpyridines (1 or 2),
isopropyl iodide (3a,b, g–i) and nitriles (9a–d)
CH-CH2R1
Zn
Table 1
R1-X
R4-CN
CH=CH2
Zn-promoted alkylation of 2- (or 4-) vinyl pyridines (1 or 2) and alkyl halides (3) in
the presence of water
N
Toluene
reflux
10 (a,b,g-i;a-d): 2-(ketoalkyl)
C
R4
N
O
1: 2-Vinyl
2: 4-Vinyl
CH2 CH2 R1
Zn
9a-d
3a,b,g-i
R1
X
CH CH2
+
11 (a,b,g-i;a-d): 4-(ketoalkyl)
N
N
CH3CN - H2O
4a-f : 2-alkyl
5a-f : 4-alkyl
1 : 2-Vinyl
2 : 4-Vinyl
3a-f
R1 of 3
R4 of 9
Yield (%)
10: 2-(ketoalkyl)
11: 4-(ketoalkyl)
Alkyl halides (3)
Isolated yield (%)
(CH3)2CH (3a)
(CH3)2CH (3a)
(CH3)2CH (3a)
(CH3)2CH (3a)
CH3CH2 (3b)
Cyclo-C6H11 (3g)
(CH3)3C (3h)
CH3CH2CH2 (3i)
CH3 (9a)
CH2CH3 (9b)
CH3CH2CH2 (9c)
C6H5 (9d)
CH3 (9a)
CH3 (9a)
CH3 (9a)
CH3 (9a)
82 (10a; a)
95 (10a; b)
88 (10a; c)
77 (10a; d)
28 (10b; a)
84 (10g; a)
90 (10h; a)
24 (10i; a)
52 (11a; a)
50 (11a; b)
44 (11a; c)
64 (11a; d)
0
48 (11g; a)
70 (11h; a)
15 (11i; a)
4a–f: 2-alkyl
5a–f: 4-alkyl
(CH3)2CH–I (3a)
CH3CH2–I (3b)
CH3(CH2)3–I (3c)
CH3CH2CH(CH3)–I (3d)
C6H5CH2–Br (3e)
H5C2OOCCH2–Br (3f)
64 (4a)
25 (4b)
40 (4c)
47 (4d)
23 (4e)
42 (4f)
60 (5a)
5 (5b)
25 (5c)
31 (5d)
13 (5e)
18 (5f)
Reaction conditions: substrate 1 or 2 (10 mmol), alkyl halide (40 mmol), water
(500 mmol), acetonitrile (50 ml), Zn (99.9% pure, 40 mmol), reflux for 0.5–1.0 h, N2
atmosphere.
Reaction conditions: substrate 1 or 2 (10 mmol), alkyl iodide 3 (40 mmol), alkyl
nitrile (500 mmol), Zn (99.9% pure, 40 mmol), toluene (100 ml), reflux for
0.5–1.0 h, N2 atmosphere.
9
Furthermore, addition of isopropyl iodide (3a) into acetonitrile
solution of 2-(or 4-)vinylpyridine (1 or 2) and a variety of carbonyl
compounds (6a–g) under gentle reflux led to selective formation of
the corresponding one-pot joining products of regioselective three
components (7a; a–g or 8a; a–g),13 as shown in Table 2.
All of the products were characterized by comparison of their
gas or liquid chromatographic behaviors with those of the au-
thentic samples,7 or their spectroscopic (1H NMR, 13C NMR, MASS,
and IR) and elemental analyses for new compounds.
It may be surprising that 2-(2- or 4-pyridyl)ethyl alkyl ketones
(10a,b,g–i; a–d or 11a,g–i; a–d) were formed as the predominant
products from the similar one-pot joining reaction of three com-
ponents by addition of alkyl iodides (3a,b,g–i) into the solution of
2-(or 4-)-vinylpyridine (1 or 2), and nitriles (9a–d) in toluene
containing Zn-powder (99.9%)14 under the similar reaction condi-
tions, as shown in Table 3.
corresponding joining products of three components (7a; a–g) and
(10a,b,g–i; a–d) in better yields than that of the products (8a; a–g)
and (11a,g–i; a–d) formed from 4-vinylpyridine (2).
The present regioselective joining reaction of three components
includes dual carbon–carbon bond formations in a one-pot opera-
tion, and their sequence is found to be distinctly selective by the
following experimental fact. While the first addition of alkyl iodides
(3) into the solution of acetonitrile containing Zn, 2- (or 4-)vinyl-
pyridine (1 or 2), and carbonyl compounds (6) gave the corre-
sponding joining products (7 or 8), any reaction did not take place
without addition of alkyl iodides (3) under the similar conditions to
result in quantitative recovery of 1 or 2. This result clearly indicates
that the addition of 3 initiates alkylation at the b-position of 1 or 2
at the first step, followed by electrophilic attack of 6 at the
sition of 1 or 2 at the second step, as shown in Scheme 2.
a-po-
It was found that use of benzene or THF as the solvent of the
reaction gave the same products even in lower yields whereas that
of n-hexane, cyclohexane, DMF and NMP did not give the desired
products at all.
It may be a common tendency that use of 2-vinylpyridine (1) as
a starting compound in both of the coupling reactions of carbonyl
compounds (6a–g) and nitriles (9a–d) resulted in formation of the
Some of control experiments provided us important in-
formation for proposal of reaction mechanism of the present
one-pot regio- and sequence-selective joining reaction of three
components. For example, use of EtZnI or Et2Zn reagent instead of
combination of Zn (99.9%) and EtI led to no formation of the cor-
responding three-components joining products. Similarly, electro-
reduction of a mixture of 2- (or 4-) vinylpyridine (1 or 2), isopropyl

7708
K. Mineyama et al. / Tetrahedron 65 (2009) 7706–7711
Zn
and zinc powder (99.9% purity, 40 mmol)14 in 100 ml of freshly
The substrates were
CH=CH2
1, 2
(CH ) C=O
3 2
+
distilled acetonitrile, was added several drops of an alkyl iodide 3
(40 mmol) under a nitrogen atmosphere. After a short period, an
exothermic reaction took place. After the vigorous reflux subsided,
the remaining alkyl iodide 3 added dropwise over 10 min to the
stirred mixture, making refluxing violently by each addition of 3.
After the addition was completed, the reaction mixture was
refluxed for 30 min with stirring. After the reaction, the mixture
was poured into 200 ml of a saturated water of NaHCO3. Then the
mixture was filtered and extracted with three 100 ml portions of
ethyl acetate. The combined ethereal solution was washed with
saturated water of NaCl, and dried over anhydrous MgSO4. After
filtration of the drying agent and evaporation of the solvent under
reduced pressure, preparative column chromatography of the
crude product gave the corresponding joining product of three
components (7a; a–g or 8a; a–g) in a good to moderate yield, as
shown in Table 2, in which isopropyl iodide was only used as an
alkyl iodide.
quantitatively recovered.
CH3CN
N
6a
R2-CO-R3
R1
6
CH
CH2
R3
R2
1
R
R1I / Zn
CH=CH2
N
C
CH-CH2
HO
R4CN
7,
8
R1
N
N
1,2
9
CH
CH2
R4
N
C
First Step
Alkylation at the β-position
Second Step
O
10, 11
Reaction with Electrophliles at the α-position
Scheme 2. Selectivity of reaction sequence in the Znpromoted one-pot regio- and
sequenceselective joining reaction of three-components.
iodide (3a) and acetone (6a) in an acetonitrile solution containing
Et4NOTs as a supporting electrolyte gave the corresponding dimer
(1,4-di (2- or 4-)pyridinylbutane) as the almost sole product in
60–65% yields and no corresponding joining products of the three
components.
From these experimental results and the reported fundamental
reactivity as an alkyl radical generated from the combination of Zn
metal and alkyl iodide, the following reaction scheme may be
proposed as the most plausible reaction mechanism, as shown in
Scheme 3.
Table 1 shows the results on formation of a-alkylation products
(4a–f or 5a–f), which were obtained when water was used in re-
place of an aliphatic ketone (or aldehyde) (6a–g). Replacement
of an aliphatic ketone (or aldehyde) (6a–g) by an aliphatic or an
aromatic nitriles (9a–d) as the reagent and that of acetonitrile by
toluene as the solvent in this procedure, led to formation of new
joining reaction of three components, that is vinylpyridine (1 or 2),
an alkyl iodide (3a,b,g–i) and a nitriles (9a–d) in good to moderate
yields, as shown in Table 3.
+e(Zn)
-I-
R1
R1
CH=CH2
N
1 or 2
R1I
CH-CH2
3.2. Analytical data for new compounds among the products
Radical
3
N
Zn
Addition
R1
ZnI
12
3.2.1. 2,5-Dimethyl-3-(2-pyridyl)hexa-2-ol [7a; a]
1H NMR (400 MHz, CDCl3)
J¼6.6 Hz, 3H), 0.96 (s, 3H), 1.06–1.08 (m, 1H), 1.29 (s, 3H), 1.56–1.62
(m, 1H), 1.93–2.00 (m, 1H), 2.66 (dd, J¼3.2, 11.5 Hz, 1H), 5.20 (s, 1H),
7.11–7.17 (m, 2H), 7.59–7.63 (m, 1H) and 8.53–8.54 (m, 1H) ppm. 13C
d
0.80 (d, J¼6.6 Hz, 3H), 0.88 (d,
R4CN
9
R1
CH-CH2
R1
CH
CH2
H3O+
+e (Zn)
N
R4
10 or 11
CH-CH2-R1
C
O
N
R2-CO-R3
6
NMR (100 MHz, CDCl3)
d 21.32, 24.13, 25.62, 27.63, 30.39, 39.03,
53.35, 72.35, 121.39, 124.70, 136.27, 148.90, and 164.08 ppm. IR
(neat): 3393, 2869, 1594, 1470, and 1146 cmꢀ1. EIMS: m/z 207 (Mþ).
Anal. Calcd for C13H21NO: C, 75.32; H, 10.21; N, 6.76. Found: C,
75.49; H, 10.07; N, 6.48.
N
C R3
R2
HO
7 or 8
Scheme 3. Proposed reaction mechanism.
3.2.2. 2,5-Dimethyl-3-(4-pyridyl)hexa-2-ol [8a; a]
Interaction of alkyl iodides (3) with Zn metal with 99.9% purity
may generate radical pairs between zinc and alkyl radicals (or alkyl
radical generated by one electron reduction by Zn metal, followed
by elimination of I- anion), which may make radical attack to the
1H NMR (400 MHz, CDCl3)
d
0.80 (d, J¼6.6 Hz, 3H), 0.84 (d,
J¼6.6 Hz, 3H), 1.14 (s, 3H), 1.17–1.18 (m, 1H), 1.21 (s, 3H), 1.50–1.57
(m, 1H), 1.80–1.87 (m, 1H), 2.65 (dd, J¼3.2, 12.1 Hz, 1H), 7.18 (d,
J¼6.1 Hz, 2H) and 8.51 (d, J¼5.9 Hz, 2H) ppm. 13C NMR (100 MHz,
b-positions of 2- (or 4-)vinylpyridine (1 or 2) to give the
a
-radical
CDCl3) d 20.86, 24.18, 25.57, 28.19, 28.27, 38.09, 54.25, 72.37, 125.04,
intermediates (12). Successive fast one-electron reduction from Zn
metal may promptly form the corresponding carbanion species,
which may react with electrophiles such as carbonyl compounds
(6) and nitriles (9) to give the corresponding (2-hydroxy-
ethyl)pyridines (7 or 8) and 2-(2- or 4-pyridyl)ethyl alkyl ketones
(10 or 11), respectively, in moderate to good yields.
Because of high selectivity in regiochemistry and reaction-se-
quence, unique reaction pattern of joining condensation of three-
components, simple one-pot procedure and satisfactory yield, the
present three-components joining may be quite important, in-
teresting and useful method in synthetic organic chemistry.
149.40 and 152.46 ppm. IR (neat): 3331, 2951, 1601, 1420, and
1131 cmꢀ1. EIMS: m/z 208 (Mþ). Anal. Calcd for C13H21NO: C, 75.32;
H, 10.21; N, 6.76. Found: C, 75.54; H, 10.17; N, 6.33.
3.2.3. 3-Ethyl-6-methyl-4-(2-pyridyl)hepta-3-ol [7a; b]
1H NMR (400 MHz, CDCl3)
d
0.74 (d, J¼7.3 Hz, 3H), 0.77–0.85 (m,
6H), 0.88 (d, J¼7.3 Hz, 3H), 1.03–1.16 (m, 2H), 1.47–1.54 (m, 1H),
1.57–1.74 (m, 3H), 1.92–1.99 (m, 1H), 2.66 (dd, J¼3.2, 11.7 Hz, 1H),
5.34 (s, 1H), 7.11–7.16 (m, 2H), 7.58–7.62 (m, 1H) and 8.52–8.53 (m,
1H) ppm. 13C NMR (100 MHz, CDCl3)
d 7.86, 7.90, 21.29, 24.24, 25.41,
26.86, 30.33, 38.37, 48.96, 76.45, 121.28, 124.97, 136.20, 148.92 and
164.14 ppm. IR (neat): 3380, 2961,1594,1470, and 1438 cmꢀ1. EIMS:
m/z 236 (Mþ). Anal. Calcd for C15H25NO: C, 76.55; H, 10.71; N, 5.95.
Found: C, 76.59; H, 10.63; N, 5.82.
3. Experimental section
3.1. General procedure for Zn-promoted one-pot joining
reaction of three components
3.2.4. 3-Ethyl-6-methyl-4-(4-pyridyl)hepta-3-ol [8a; b]
1H NMR (400 MHz, CDCl3)
d 0.79–0.90 (m, 12H), 1.08–1.13 (m,
Into a refluxing solution of 2-(or 4-) vinylpyridine (1 or 2) 1.05 g
(10 mmol), an aliphatic ketone (or aldehyde) (6a–g) (40 mmol),
1H), 1.15–1.23 (m, 1H), 1.24–1.34 (m, 1H), 1.39–1.46 (m, 1H), 1.59–
1.65 (m, 2H), 1.82–1.89 (m, 1H), 2.70–2.74 (m, 1H), 7.21 (d,

K. Mineyama et al. / Tetrahedron 65 (2009) 7706–7711
7709
J¼5.9 Hz, 2H) and 8.47 (d, J¼5.9 Hz, 2H) ppm. 13C NMR (100 MHz,
8.52–8.53 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d
11.01, 14.64,
CDCl3)
d
7.47, 7.95, 20.76, 24.24, 25.31, 28.05, 39.32, 37.66, 49.34,
21.41, 24.13, 25.34, 25.61, 36.70, 37.76, 46.03, 78.00, 121.45, 123.56,
136.46, 149.02 and 164.50 ppm. IR (neat): 3235, 2955, 1596, 1438,
and 992 cmꢀ1. EIMS: m/z 236 (Mþ). Anal. Calcd for C15H25NO: C,
76.55; H, 10.71; N, 5.95. Found: C, 76.73; H, 10.70; N, 5.61.
76.02, 125.37, 149.21 and 151.37 ppm. IR (neat): 3291, 2958, 1602,
1463, and 1418 cmꢀ1 EIMS: m/z 236 (Mþ). Anal. Calcd for
.
C15H25NO: C, 76.55; H, 10.71; N, 5.95. Found: C, 76.67; H, 10.54; N,
5.89.
3.2.11. 3,7-Dimethyl-5-(4-pyridyl)octa-4-ol [8a; f]
3.2.5. 2,6-Dimethyl-3-isopropyl-4-(2-pyridyl)hepta-3-ol [7a; c]
1H NMR (400 MHz, CDCl3)
d
0.83 (d, J¼4.4 Hz, 3H), 0.84 (d,
1H NMR (400 MHz, CDCl3)
d
0.51 (d, J¼7.3 Hz, 3H), 0.77–0.95 (m,
J¼4.4 Hz, 3H), 0.89–0.94 (m, 6H), 1.19–1.66 (m, 6H), 2.79–2.84 (m,
1H), 3.58–3.61 (dd, J¼4.1, 7.6 Hz, 1H), 7.18–7.23 (m, 2H) and 8.48–
10H), 1.07 (d, J¼7.3 Hz, 3H), 1.09 (d, J¼6.8 Hz, 3H), 1.51–1.58 (m, 1H),
1.61–1.68 (m, 2H), 1.97–2.04 (m, 1H), 2.23–2.30 (m, 1H), 3.23 (dd,
J¼3.2, 12.0 Hz, 1H), 5.92 (s, 1H), 7.13–7.18 (m, 2H), 7.57–7.62 (m, 1H)
8.51 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3)
d 11.65, 12.43, 21.13,
23.87, 25.13, 26.74, 36.76, 40.82, 46.82, 77.55, 124.40, 149.69 and
152.22 ppm. IR (neat): 3204, 2959,1603,1463 and 1419 cmꢀ1. EIMS:
m/z 236 (Mþ). Anal. Calcd for C15H25NO: C, 76.55; H, 10.71; N, 5.95.
Found: C, 76.91; H, 10.69; N, 5.60.
and 8.50–8.51 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d 18.58,
18.65, 19.00, 19.20, 21.09, 24.42, 25.21, 33.92, 35.23, 39.21, 46.11,
79.04, 121.24, 125.16, 136.12, 148.56 and 164.65 ppm. IR (neat):
3304, 2957, 1595, 1467, and 1439 cmꢀ1. EIMS: m/z 264 (Mþ). Anal.
Calcd for C17H29NO: C, 77.51; H, 11.10; N, 5.32. Found: C, 77.78; H,
10.99; N, 4.93.
3.2.12. 3-Ethyl-7-methyl-5-(2-pyridyl)octa-4-ol [7a; g]
1H NMR (400 MHz, CDCl3)
d
0.81 (d, J¼6.6 Hz, 3H), 0.83–0.88 (m,
6H), 0.91 (d, J¼6.6 Hz, 3H), 1.13–1.16 (m, 1H), 1.31–1.50 (m, 5H),
1.68–1.72 (m, 1H), 1.90–1.97 (m, 1H), 2.96 (ddd, J¼2.7, 2.9, 11.7 Hz,
1H), 3.69–3.70 (m, 1H), 4.88 (s, 1H), 7.10–7.17 (m, 2H), 7.59–7.63 (m,
3.2.6. 1-(3-Methyl-1-(2-pyridyl)butyl)cyclohexanol [7a; d]
1H NMR (400 MHz, CDCl3)
d
0.73 (d, J¼6.6 Hz, 3H), 0.81 (d,
J¼6.6 Hz, 3H), 0.96–1.91 (m, 13H), 2.96 (dd, J¼3.2, 11.5 Hz, 1H), 5.15
1H) and 8.52–8.53 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d 10.17,
(s, 1H), 7.01–7.09 (m, 2H), 7.50–7.54 (m, 1H) and 8.46–8.47 (m,
10.42, 20.38, 20.72, 21.41, 24.17, 25.33, 37.18, 41.93, 45.57, 75.44,
121.48, 123.56, 136.49, 148.97 and 164.81 ppm. IR (neat): 3244,
2955, 1595, 1438, and 1001 cmꢀ1. EIMS: m/z 250 (Mþ). Anal. Calcd
for C16H27NO: C, 77.06; H, 10.91; N, 5.62. Found: C, 77.09; H, 10.86;
N, 5.54.
1H) ppm. 13C NMR (100 MHz, CDCl3)
d 21.36, 21.37, 22.18, 22.30,
24.17, 25.51, 25.92, 35.56, 38.13, 38.41, 73.03, 121.27, 124.89, 136.19,
148.97 and 164.03 ppm. IR (neat): 3384, 2933, 1593, 1471 and
1437 cmꢀ1. EIMS: m/z 248 (Mþ). Anal. Calcd for C16H25NO: C, 77.68;
H, 10.19; N, 5.66. Found: C, 77.62; H, 10.14; N, 5.61.
3.2.13. 3-Ethyl-7-methyl-5-(4-pyridyl)octa-4-ol [8a; g]
3.2.7. 1-(3-Methyl-1-(4-pyridyl)butyl)cyclohexanol [8a; d]
1H NMR (400 MHz, CDCl3)
d 0.83–0.85 (m, 6H), 0.88–0.92 (m,
1H NMR (400 MHz, CDCl3)
d
0.79 (d, J¼6.6 Hz, 3H), 0.83 (d,
6H), 1.22–1.70 (m, 8H), 2.84–2.90 (m, 1H), 3.67–3.70 (m, 1H), 7.21
J¼6.6 Hz, 3H), 1.12–1.86 (m, 13H), 2.60–2.64 (m, 1H), 7.18 (d,
(d, J¼5.9 Hz, 2H) and 8.48 (d, J¼5.9 Hz, 2H) ppm. 13C NMR
J¼6.1 Hz, 2H) and 8.49 (d, J¼6.1 Hz, 2H) ppm. 13C NMR (100 MHz,
(100 MHz, CDCl3)
d 11.11, 11.39, 20.00, 21.29, 22.10, 23.75, 25.20,
CDCl3)
d
20.85, 21.78, 21.79, 21.88, 24.20, 25.43, 25.58, 35.72, 36.15,
41.36, 42.96, 46.37, 75.84, 124.60, 149.37 and 152.39 ppm. IR (neat):
3206, 2959, 1603, 1464 and 1316 cmꢀ1. EIMS: m/z 250 (Mþ). Anal.
Calcd for C16H27NO: C, 77.06; H, 10.91; N, 5.62. Found: C, 77.22; H,
10.89; N, 5.44.
37.29, 72.72, 125.23, 149.28 and 152.49 ppm. IR (neat): 3319, 2929,
1597, 1417, and 978 cmꢀ1. EIMS: m/z 248 (Mþ). Anal. Calcd for
C16H25NO: C, 77.68; H, 10.19; N, 5.66. Found: C, 77.19; H, 10.01; N,
5.72.
3.2.14. 5-Methyl-3-(2-pyridyl)hexa-2-one [10a; a]
3.2.8. 2,6-Dimethyl-4-(2-pyridyl)hepta-3-ol [7a; e]
1H NMR (400 MHz, CDCl3)
J¼6.6 Hz, 3H), 1.37–1.44 (m, 1H), 1.75–1.82 (m, 1H), 1.92–1.99 (m,
1H), 2.12 (s, 3H), 4.01 (dd, J¼7.3, 7.8 Hz, 1H), 7.17–7.23 (m, 2H), 7.63–
7.67 (m, 1H) and 8.57–8.58 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d
0.88 (d, J¼6.8 Hz, 3H), 0.91 (d,
1H NMR (400 MHz, CDCl3)
d
0.81 (d, J¼6.3 Hz, 3H), 0.91 (d,
J¼6.3 Hz, 3H), 0.91–1.05 (m, 6H), 1.13–1.15 (m, 1H), 1.41–1.48 (m,
1H), 1.76–1.84 (m, 1H), 1.89–1.96 (m, 1H), 2.94–2.98 (m, 1H), 3.41–
3.43 (m, 1H), 5.23 (s, 1H), 7.10–7.17 (m, 2H), 7.59–7.63 (m, 1H) and
d
22.20, 22.87, 25.78, 29.11, 39.91, 60.08, 122.04, 122.79, 136.76,
8.51–8.52 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d
18.99, 19.48,
149.63, 159.02 and 207.90 ppm. IR (neat): 2956, 1714, 1589, 1470,
and 1434 cmꢀ1. EIMS: m/z 191 (Mþ). Anal. Calcd for C12H17NO: C,
75.35; H, 8.96; N, 7.32. Found: C, 75.48; H, 8.74; N, 7.00.
21.37, 24.16, 25.22, 30.63, 36.82, 45.47, 79.96, 121.52, 123.62, 136.53,
148.91 and 164.74 ppm. IR (neat): 3233, 2952, 1595, 1484, and
997 cmꢀ1. EIMS: m/z 222 (Mþ). Anal. Calcd for C14H23NO: C, 75.97;
H, 10.47; N, 6.33. Found: C, 76.16; H, 10.39; N, 5.98.
3.2.15. 5-Methyl-3-(4-pyridyl)hexa-2-one [11a; a]
1H NMR (400 MHz, CDCl3)
d
0.88 (d, J¼6.3 Hz, 3H), 0.89 (d,
3.2.9. 2,6-Dimethyl-4-(4-pyridyl)hepta-3-ol [8a; e]
J¼6.6 Hz, 3H), 1.32–1.42 (m, 1H), 1.78 (ddd, J¼6.3, 8.3, 13.9 Hz, 1H),
1.86–1.93 (m, 1H), 2.12 (s, 3H), 3.73 (dd, J¼7.6, 7.6 Hz, 1H), 7.17 (d,
J¼6.1 Hz, 2H) and 8.56 (d, J¼6.1 Hz, 2H) ppm. 13C NMR (100 MHz,
1H NMR (400 MHz, CDCl3)
J¼6.6 Hz, 3H), 0.92 (d, J¼6.8 Hz, 3H), 0.97 (d, J¼6.8 Hz, 3H), 1.16–
1.29 (m, 1H), 1.41–1.75 (m, 2H), 2.76–2.85 (m, 1H), 3.39–3.45 (m,
1H), 7.12–7.22 (m, 2H) and 8.49–8.50 (m, 2H) ppm. 13C NMR
d
0.83 (d, J¼6.6 Hz, 3H), 0.88 (d,
CDCl3)
d 21.98, 22.87, 25.59, 29.26, 40.47, 56.92, 123.47, 147.85,
150.27 and 206.84 ppm. IR (neat): 2957, 1714, 1595, 1414, and
1355 cmꢀ1. EIMS: m/z 192 (Mþ). Anal. Calcd for C12H17NO: C, 75.35;
H, 8.96; N, 7.32. Found: C, 75.71; H, 8.92; N, 7.00.
(100 MHz, CDCl3)
d 16.00, 16.67, 20.04, 24.17, 25.16, 30.63, 39.07,
46.22, 79.63, 123.87, 149.78 and 152.73 ppm. IR (neat): 3222, 2957,
1604, 1465, and 1054 cmꢀ1. EIMS: m/z 222 (Mþ). Anal. Calcd for
C14H23NO: C, 75.97; H, 10.47; N, 6.33. Found: C, 76.00; H, 10.31; N,
6.31.
3.2.16. 6-Methyl-4-(2-pyridyl)hepta-3-one [10a; b]
1H NMR (400 MHz, CDCl3)
d
0.89 (d, J¼7.8 Hz, 3H), 0.90 (d,
J¼7.0 Hz, 3H), 0.98 (t, J¼7.3 Hz, 3H), 1.36–1.43 (m, 1H), 1.72–1.79 (m,
1H), 1.93–2.00 (m, 1H), 2.47 (q, J¼7.3 Hz, 2H), 4.05 (dd, J¼7.3, 7.8 Hz,
1H), 7.15–7.25 (m, 2H), 7.62–7.66 (m, 1H) and 8.55–8.56 (m,
3.2.10. 3,7-Dimethyl-5-(2-pyridyl)octa-4-ol [7a; f]
1H NMR (400 MHz, CDCl3)
6H), 0.98 (d, J¼6.6 Hz, 3H), 1.13–1.20 (m, 2H), 1.47–1.53 (m, 3H),
1.87–1.94 (m, 1H), 2.98 (dt, J¼3.4, 11.5 Hz, 1H), 3.59 (dd, J¼3.4,
7.1 Hz, 1H), 4.59 (s, 1H), 7.10–7.16 (m, 2H), 7.58–7.63 (m, 1H) and
d
0.80 (d, J¼6.6 Hz, 3H), 0.87–0.91 (m,
1H) ppm. 13C NMR (100 MHz, CDCl3)
d 7.75, 22.30, 22.85, 25.86,
35.33, 40.31, 59.17, 121.98, 122.61, 136.72, 149.51, 159.29 and
210.57 ppm. IR (neat): 2956, 1716, 1587, 1470, and 1434 cmꢀ1. EIMS:

7710
K. Mineyama et al. / Tetrahedron 65 (2009) 7706–7711
m/z 205 (Mþ). Anal. Calcd for C13H19NO: C, 76.06; H, 9.33; N, 6.82.
Found: C, 76.23; H, 9.13; N, 6.70.
3.2.23. 4-Cyclohexyl-3-(2-pyridyl)buta-2-one [10g; a]
1H NMR (400 MHz, CDCl3)
0.92–1.66 (m, 10H), 1.72–1.79 (m,
d
2H), 1.95–2.09 (m, 1H), 2.11 (s, 3H), 4.03 (dd, J¼7.3, 7.6 Hz, 1H), 7.16–
3.2.17. 6-Methyl-4-(4-pyridyl)hepta-3-one [11a; b]
7.22 (m, 2H), 7.63–7.67 (m, 1H) and 8.56–8.57 (m, 1H) ppm. 13C
1H NMR (400 MHz, CDCl3)
d
0.88 (d, J¼6.6 Hz, 6H), 0.99 (t,
NMR (100 MHz, CDCl3) d 26.09, 26.14, 26.44, 29.10, 32.97, 33.52,
J¼7.3 Hz, 3H), 1.32–1.39 (m, 1H), 1.60–1.67 (m, 1H), 1.86–1.93 (m,
1H), 2.43 (q, J¼7.3 Hz, 2H), 3.75 (dd, J¼7.3, 7.6 Hz, 1H), 7.17 (d,
J¼5.9 Hz, 2H) and 8.54 (d, J¼5.9 Hz, 2H) ppm. 13C NMR (100 MHz,
35.24, 38.50, 59.35, 122.02, 122.76, 136.75, 149.62, 159.01 and
208.03 ppm. IR (neat): 2920,1714,1588, 1471, and 1434 cmꢀ1. EIMS:
m/z 232 (Mþ). Anal. Calcd for C15H21NO: C, 77.88; H, 9.15; N, 6.05.
Found: C, 77.88; H, 9.05; N, 5.89.
CDCl3) d 7.74, 22.06, 22.84, 25.67, 35.56, 40.98, 55.93, 123.47, 148.16,
150.17 and 209.62 ppm. IR (neat): 2957, 1716, 1596, 1467, and
1415 cmꢀ1. EIMS: m/z 205 (Mþ). Anal. Calcd for C13H19NO: C, 76.06;
H, 9.33; N, 6.82. Found: C, 76.24; H, 9.35; N, 6.91.
3.2.24. 4-Cyclohexyl-3-(4-pyridyl)buta-2-one [11g; a]
1H NMR (400 MHz, CDCl3)
d 0.84–1.73 (m, 12H), 1.89–1.96 (m,
1H), 2.09 (s, 3H), 3.77 (dd, J¼7.6, 7.6 Hz, 1H), 7.16 (d, J¼5.9 Hz, 2H)
3.2.18. 7-Methyl-5-(2-pyridyl)octa-4-one [10a; c]
and 8.56 (d, J¼5.9 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3)
d 25.98,
1H NMR (400 MHz, CDCl3)
d
0.80 (t, J¼7.3 Hz, 3H), 0.88 (d,
26.04, 26.29, 29.28, 32.79, 33.52, 35.04, 39.08, 56.51, 123.35, 123.57,
147.99, 150.21, 150.25 and 206.88 ppm. IR (neat): 2924, 1715, 1595,
J¼6.6 Hz, 3H), 0.90 (d, J¼6.6 Hz, 3H), 1.36–1.42 (m, 1H), 1.49–1.56
(m, 2H), 1.74–1.79 (m, 1H), 1.92–1.99 (m, 1H), 2.41 (t, J¼7.3 Hz, 2H),
4.03 (dd, J¼7.6, 7.6 Hz, 1H), 7.15–7.24 (m, 2H), 7.62–7.66 (m, 1H) and
1448, and 1415 cmꢀ1 EIMS: m/z 232 (Mþ). Anal. Calcd for
.
C15H21NO: C, 77.88; H, 9.15; N, 6.05. Found: C, 77.92; H, 9.08; N,
5.85.
8.55–8.56 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d 13.55, 17.04,
22.30, 22.84, 25.85, 40.19, 44.00, 59.43, 121.96, 122.64, 136.67,
149.50, 159.18 and 209.92 ppm. IR (neat): 2958, 1715, 1588, 1469,
and 1434 cmꢀ1. EIMS: m/z 220 (Mþ). Anal. Calcd for C14H21NO: C,
76.67; H, 9.65; N, 6.39. Found: C, 76.70; H, 9.46; N, 6.35.
3.2.25. 5,5-Dimethyl-3-(2-pyridyl)hexa-2-one [10h; a]
1H NMR (400 MHz, CDCl3)
d 0.85 (s, 9H), 1.74 (m, 1H), 2.15 (s,
3H), 2.25–2.30 (m, 1H), 4.04–4.07 (m, 1H), 7.15–7.29 (m, 2H), 7.61–
7.66 (m, 1H) and 8.54–8.56 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
3.2.19. 7-Methyl-5-(4-pyridyl)octa-4-one [11a; c]
d 29.15, 29.50, 29.57, 29.63, 30.89, 44.11, 59.40, 121.82, 122.72,
1H NMR (400 MHz, CDCl3)
d
0.80 (t, J¼7.3 Hz, 3H), 0.88 (d,
136.77, 149.34, 160.05 and 207.71 ppm. IR (neat): 2954, 1718, 1589,
1471, and 1365 cmꢀ1. EIMS: m/z 206 (Mþ). Anal. Calcd for C13H19NO:
C, 76.06; H, 9.33; N, 6.82. Found: C, 76.14; H, 9.07; N, 6.82.
J¼6.6 Hz, 6H), 1.32–1.39 (m, 1H), 1.48–1.56 (m, 2H), 1.59–1.66 (m,
1H), 1.85–1.93 (m, 1H), 2.39–2.42 (m, 2H), 3.74 (dd, J¼7.3, 7.6 Hz,
1H), 7.17 (d, J¼5.9 Hz, 2H) and 8.55 (d, J¼5.9 Hz, 2H) ppm. 13C NMR
(100 MHz, CDCl3)
d
13.50, 16.98, 22.07, 22.84, 25.65, 40.88, 44.24,
3.2.26. 5,5-Dimethyl-3-(4-pyridyl)hexa-2-one [11h; a]
56.17, 123.50, 148.04, 150.18 and 209.00 ppm. IR (neat): 2959, 1715,
1595, 1467, and 1414 cmꢀ1. EIMS: m/z 220 (Mþ). Anal. Calcd for
C14H21NO: C, 76.67; H, 9.65; N, 6.39. Found: C, 76.43; H, 9.61; N,
6.36.
1H NMR (400 MHz, CDCl3)
d
0.86 (s, 9H), 1.49 (dd, J¼4.9, 14.1 Hz,
1H), 2.13 (s, 3H), 2.33 (dd, J¼7.3, 14.1 Hz, 1H), 3.75 (dd, J¼4.9, 7.3 Hz,
1H), 7.17 (d, J¼4.4 Hz, 2H) and 8.54 (d, J¼4.4 Hz, 2H) ppm. 13C NMR
(100 MHz, CDCl3)
d 29.19, 29.49, 30.91, 45.07, 55.47, 123.33, 149.33,
150.10 and 206.44 ppm. IR (neat): 2956, 1720, 1595, 1475, and
1415 cmꢀ1. EIMS: m/z 206 (Mþ). Anal. Calcd for C13H19NO: C, 76.06;
H, 9.33; N, 6.82. Found: C, 76.13; H, 9.30; N, 6.72.
3.2.20. 4-Methyl-1-phenyl-2-(2-pyridyl)penta-1-one [10a; d]
1H NMR (400 MHz, CDCl3)
d
0.90 (d, J¼6.6 Hz, 3H), 0.96 (d,
J¼6.6 Hz, 3H), 1.48–1.54 (m, 1H), 1.79–1.86 (m, 1H), 2.11–2.18 (m,
1H), 5.00 (dd, J¼7.3, 7.3 Hz, 1H), 7.10–7.62 (m, 6H), 8.07–8.09 (m,
3.2.27. 3-(2-Pyridyl)hepta-2-one [10i; a]
2H) and 8.53–8.54 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d
22.47,
1H NMR (400 MHz, CDCl3)
4H), 1.80–1.89 (m, 1H), 2.04–2.17 (m, 1H), 2.11 (s, 3H), 3.87 (dd,
d
0.86 (t, J¼7.3 Hz, 3H), 1.10–1.35 (m,
22.71, 42.14, 53.80, 54.96, 121.68, 122.18, 128.39, 128.60, 128.81,
128.97, 132.87, 136.73, 138.86, 149.40, 159.83 and 199.41 ppm. IR
(neat): 2956, 1716, 1587, 1470, and 1434 cmꢀ1. EIMS: m/z 254 (Mþ).
Anal. Calcd for C17H19NO: C, 80.60; H, 7.56; N, 5.53. Found: C, 80.81;
H, 7.65; N, 5.34.
J¼7.6, 7.6 Hz, 1H), 7.17–7.23 (m, 2H), 7.63–7.68 (m, 1H) and 8.57–
8.58 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d 13.86, 22.59, 29.17,
29.61, 30.76, 62.10, 122.06, 122.74, 136.77, 149.64, 158.94 and
207.93 ppm. IR (neat): 2956,1715,1589, 1470, and 1434 cmꢀ1. EIMS:
m/z 191 (Mþ). Anal. Calcd for C12H17NO: C, 75.35; H, 8.96; N, 7.32.
Found: C, 75.23; H, 8.68; N, 7.24.
3.2.21. 4-Methyl-1-phenyl-2-(4-pyridyl)penta-1-one [11a; d]
1H NMR (400 MHz, CDCl3)
d
0.90 (d, J¼6.8 Hz, 3H), 0.95 (d,
J¼6.6 Hz, 3H), 1.44–1.54 (m, 1H), 1.69–1.76 (m, 1H), 2.06–2.13 (m,
3.2.28. 3-(4-Pyridyl)hepta-2-one [11i; a]
1H), 4.68 (dd, J¼7.3, 7.3 Hz, 1H), 7.25–7.56 (m, 6H), 7.94–7.96 (m,
1H NMR (400 MHz, CDCl3)
2H), 1.24–1.34 (m, 2H), 1.65–1.74 (m, 1H), 2.00–2.07 (m, 1H), 2.09 (s,
d
0.86 (t, J¼7.3 Hz, 3H), 1.11–1.22 (m,
2H) and 8.51–8.53 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d
22.27,
22.75, 25.97, 42.77, 51.05, 123.35, 123.63, 128.39, 128.56, 128.66,
128.82, 133.33, 136.46, 148.64, 150.13, 150.22 and 198.81 ppm. IR
(neat): 2954, 1677, 1592, 1466, and 1416 cmꢀ1. EIMS: m/z 206 (Mþ).
Anal. Calcd for C17H19NO: C, 80.60; H, 7.56; N, 5.53. Found: C, 80.92;
H, 7.73; N, 5.01.
3H), 3.61 (dd, J¼7.3, 7.6 Hz, 1H), 7.16 (dd, J¼1.7, 4.4 Hz, 2H) and 8.56
(dd, J¼1.7, 4.4 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3)
d 13.79,
22.48, 29.38, 29.50, 31.37, 59.25, 123.37, 123.52, 147.83, 150.25 and
206.91 ppm. IR (neat): 2957, 1715, 1596, 1414, and 1357 cmꢀ1. EIMS:
m/z 192 (Mþ). Anal. Calcd for C12H17NO: C, 75.35; H, 8.96; N, 7.32.
Found: C, 75.68; H, 8.95; N, 7.13.
3.2.22. 3-(2-Pyridyl)hexa-2-one [10b; a]
1H NMR (400 MHz, CDCl3)
2H), 1.79–1.88 (m, 1H), 2.02–2.14 (m, 1H), 2.12 (s, 3H), 3.90 (dd,
d
0.91 (t, J¼7.3 Hz, 3H), 1.18–1.30 (m,
Acknowledgements
J¼7.3, 7.6 Hz, 1H), 7.17–7.23 (m, 2H), 7.63–7.68 (m, 1H) and 8.57–
8.58 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)
d
13.92, 20.61, 29.18,
The authors wish to express sincere gratitude for partial support
of this research through a Grant-in Aid for Scientific Research
(No. 19020018) on Priority Areas ‘Advanced Molecular Trans-
formation of Carbon Resources’ from the Ministry of Education,
Sports, Culture, Science and Technology, Japan.
33.11, 62.39, 122.06, 122.75, 136.76, 149.70, 158.90 and 207.90 ppm.
IR (neat): 2959, 1715, 1589, 1470, and 1434 cmꢀ1. EIMS: m/z 177
(Mþ). Anal. Calcd for C11H15NO: C, 74.54; H, 8.53; N, 7.90. Found: C,
74.37; H, 8.11; N, 7.74.

K. Mineyama et al. / Tetrahedron 65 (2009) 7706–7711
7711
7. Tanaka, T.; Kurozumi, S.; Toru, T.; Kobayashi, M.; Miura, S.; Ishimoto, S. Tetra-
hedron 1977, 33, 1105.
References and notes
8. Crump, R. A. N. C.; Fleming, L.; Urch, C. J. J. Chem. Soc., Perkin Trans. 1 1994,
701.
9. Reich, H. J.; Renga, J. M.; Reich, I. L. J. Org. Chem. 1974, 39, 2133.
10. Shono, T.; Nishiguchi, I.; Sasaki, M. J. Am. Chem. Soc. 1978, 100, 4314.
11. Similar reaction was also reported by K. Takai’s group; Takai, K.; Ueda, T.; Ikeda,
N.; Moriwaki, T. J. Org. Chem. 1996, 61, 7990.
12. Yamamoto, Y.; Nakano, S.; Maekawa, H.; Nishiguchi, I. Org. Lett. 2004, 6,
799.
13. For expression of the products 7(a;a–g), 8(a;a,b,d–g), 10(a,b.g–i;a–d), and 11(a,
g–i; a–d) in Tables 2 and 3, the first alphabets correspond to those of alkyl
halides 3a,b,g–i, while the second ones are derived from those of carbonyl
compounds 6a–g and nitriles 9a–d, respectively.
1. Smith, D. M. In Comprehensive Carbon Chemistry; Sammers, P. G., Ed.; Pergamon:
Oxford, 1979; Vol. 4, pp 4–84.
2. (a) Boekelheide, V.; Rothchild, S. J. Am. Chem. Soc. 1949, 71, 879; (b) Boe-
kelheide, V.; Agnello, E. J. J. Am. Chem. Soc. 1950, 72, 5005; (c) Boekelheide, V.;
O’Grady, L. P.; Lamborg, M. J. Am. Chem. Soc. 1953, 75, 3243.
3. Pines, H.; Sartoris, N. E. J. Org. Chem. 1969, 34, 2113.
4. Mukherjee, A.; Duggan, A. M.; Agosta, W. C. J. Org. Chem. 1994, 59, 178.
5. (a) Posner, G. H. Org. React. 1972, 19, 1; (b) Rossiter, B. E.; Swingle, N. M. Chem.
Rev. 1992, 92, 771; (c) Knochel, P. J. Am. Chem. Soc. 1990, 112, 7431.
6. (a) Coates, R. M.; Sandefur, L. O. J. Org. Chem. 1974, 39, 275; (b) Grieco, P. A.;
Finkelhor, R. J. Org. Chem. 1973, 38, 2100; (c) Boeckman, R. K., Jr. J. Org. Chem.
1973, 38, 4450; (d) Takahashi, T.; Nakazawa, M.; Kanoh, M.; Yamamoto, K.
Tetrahedron Lett. 1990, 31, 7349; (e) Petrier, C.; Barbosa, J. C. S; Dupuy, C.; Luche,
J.-L. J. Org. Chem. 1985, 50, 5761.
14. Zn powder with 99.9% purity was purchased from KOJUNDO CHEMICAL LAB-
ORATRY Co., Ltd.