1,2-asymmetric induction in the conjugate addition of organocopper reagents to γ-aryl α,β-unsaturated carbonyl derivatives

Article abstract of DOI:10.1016/S0040-4020(00)00137-X

The diastereoselectivity in the conjugate addition of organocopper reagents to γ-aryl α,β-unsaturated carbonyl derivatives 8-14 was investigated. The syn-diastereoselectivity was obtained irrespective of the reagents type in the addition of 8, while the anti-diastereoselectivity was obtained in the addition of 10-14 with RCu and RCu(CN)Li (R=Me and Bu) and the syn-selectivity was produced in the addition of 10-14 with R₂CuLi and R₂Cu(CN)Li₂. The reagent controlled and substrate dependent diastereoselectivity are explained by two different reaction pathways: either π-complex formation or ordinary nucleophilic addition. Reduction potentials of the Michael acceptors and electron donating ability of organocopper reagents control the reaction pathway. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00137-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2821±2831
1,2-Asymmetric Induction in the Conjugate Addition of
Organocopper Reagents to g-Aryl a,b-Unsaturated
Carbonyl Derivatives
Yukiyasu Chounan,a Yasuo Ono,b Shinji Nishii,c Haruo Kitahara,a Shoei Itob and
Yoshinori Yamamotoc,
*
aDepartment of Natural Science, Faculty of Education, Hirosaki University, Hirosaki 036-8560, Japan
bDepartment of Materials Science and Technology, Faculty of Science and Technology, Hirosaki University, Hirosaki 036-8561, Japan
cDepartment of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Received 23 September 1999; revised 20 December 1999; accepted 23 December 1999
AbstractÐThe diastereoselectivity in the conjugate addition of organocopper reagents to g-aryl a,b-unsaturated carbonyl derivatives 8±14
was investigated. The syn-diastereoselectivity was obtained irrespective of the reagents type in the addition of 8, while the anti-diastereo-
selectivity was obtained in the addition of 10±14 with RCu and RCu(CN)Li (RˆMe and Bu) and the syn-selectivity was produced in the
addition of 10±14 with R2CuLi and R2Cu(CN)Li2. The reagent controlled and substrate dependent diastereoselectivity are explained by two
different reaction pathways: either p-complex formation or ordinary nucleophilic addition. Reduction potentials of the Michael acceptors and
electron donating ability of organocopper reagents control the reaction pathway. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
dif®cult to perform straightforward interpretation on the dia-
stereoselectivity relationship between the reagent type and
the substrate structure.
The diastereoselectivity of nucleophilic addition to
a-alkoxy aldehydes having a-chiral center can be inter-
preted and predicted either by a Felkin±Anh transition
state model 11 or by a chelation model 22 (Fig. 1). On the
other hand, the diastereoselectivity of nucleophilic con-
jugate addition to g-alkoxy a,b-unsaturated carbonyl
derivatives having g-chiral center was puzzling.3 Previously
we carried out a systematic study on this problem and
reported that the diastereoselectivity of organocopper con-
jugate addition to such enoates depended on the substrate
structure and the reagent type.4 The alkylcopper addition to
a trans-mono-enoate proceeds through the inside alkoxy
model 3 to give the anti-adduct predominantly, while the
addition to a cis-mono-enoate proceeds through the outside
alkoxy model 4 to afford the syn-adduct preferentially.
When stronger Michael acceptors and/or copper reagents
having lower oxidation potentials are used, the p-complex
model 5 is involved which gives the syn-adduct predomi-
nantly. The 1,2-asymmetric induction of g-alkoxy-enoates
could be elucidated by the above three different models.
However, a chelation controlled addition of organocopper
reagents may intervene, depending upon OR' group, in
certain cases of those g-alkoxy enoates, which makes it
On the other hand, the 1,2-asymmetric induction of a-aryl
substituted chiral aldehydes is straightforward, and can be
explained by the Felkin±Anh model 6: it is not necessary to
consider other models such as a chelation model. It occurred
to us that the 1,2-asymmetric induction of g-aryl substituted
a,b-enoates having g-chiral center must also be straight-
forward in comparison with that of g-alkoxy analogs and
therefore more deep insight into the p-complex mechanism
must be gained. We now detail the results for the diastereo-
selectivities on conjugate addition to g-aryl substituted
a,b-unsaturated carbonyl derivatives 7 and report that
p-complex formation is in fact a key for dictating the
direction of 1,2-asymmetric induction.
Results and Discussion
Diesters and related systems
Diesters 11±14 and other Michael acceptors 8±10 were
prepared by the standard procedure.5 All the Michael
acceptors have a substituent (Me, CN, or CO2Et) cis to the
a-phenyl-ethyl group and therefore it is reasonable to
assume that similar level of the allylic strain to the chiral
center is operative. Although all the substrates are racemic,
the structures 8±14 are drawn in (S) form for convenience.
Keywords: Michael reactions; copper and compounds; diastereoselectivity;
substituent effects.
* Corresponding author. Tel.: 181-22-217-6581; fax: 81-22-217-6784;
e-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00137-X

2822
Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
Figure 1.
Reduction potentials of 8±14 were measured by cyclic
voltammetry and Ered values are shown in Fig. 2. Those of
12±14 were too low, i.e. below 22.0 V, to be measured
exactly by this method. The reactions of 3 equiv. organo-
copper reagents with the Michael acceptors were carried out
in diethyl ether at 2788C and then the mixtures were
allowed to warm to ca. 2208C. The reactions were quenched
with aqueous ammonium chloride solution, and the isomer
distribution was investigated by GLC and/or 1H NMR
analysis. The stereochemistries of the conjugate adducts
were determined unambiguously by the spectroscopic
method (1H NMR) and/or by correlation with their authentic
compounds (see Experimental section). The results are
summarized in Table 1.
substrates, gave the syn-adduct 16 predominantly regardless
of the reagent type (entries 1±5). The yields of the conjugate
adducts 15 and 16 were low; the starting material was recov-
ered in most cases and, for example, 8 was recovered in 54%
yield in entry 1. The reagent controlled diastereoselectivity
was observed in the conjugate addition to 9 (Eredˆ
21.43 V). The addition with MeCu(CN)Li and
BuCu(CN)Li gave the anti-adduct 17 predominantly,
whereas the reaction with MeCu, Me2Cu(CN)Li2, Me2CuLi,
BuCu, Bu2Cu(CN)Li2, and Bu2CuLi afforded the syn-adduct
18 preferentially (entries 6±13). The diastereoselectivity of
10 (Eredˆ21.68 V) is very interesting in comparison with
that of 9; here also the reagent controlled diastereo-
selectivity was observed, but MeCu and BuCu gave the
anti-isomer 19 predominantly whereas Me2CuLi and
Bu2CuLi afforded the syn-isomer 20 preferentially (entries
14±17). The electronic effect of the para-substituent of
The conjugate addition to the nitro-ole®n 8, which has the
highest reduction potential (Eredˆ21.33 V) among the
Figure 2.

Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
2823
Table 1. Conjugate addition of RCuLn to Michael acceptors 8±14 in diethyl ether (all reactions were carried out in diethyl ether at 2788C with Michael
acceptor (0.3 mmol) and organocopper (0.9 mmol))
Entry
Michael acceptor
Reagent
Conjugate adduct (%)a
Isomer ratiob anti:syn
15:16
33:67
24:76
21:79
13:87
19:81
17:18
1
2
3
4
5
8
MeCu
27
47
35
45
28
MeCu´TMSCl
Me2CuLi
BuCu
Bu2CuLi
6
7
8
9
10
11
12
13
9
MeCu(CN)Li
MeCu
Me2Cu(CN)Li2
Me2CuLi
BuCu(CN)Li
BuCu
Bu2Cu(CN)Li2
Bu2CuLi
81
72
79
73
81
89
77
79
69:31
23:77
21:79
13:87
62:38
23:77
14:86
9:91
19:20
14
15
16
17
10
11
12
MeCu
92
91
79
68
62:38
38:62
75:25
25:75
21:22
Me2CuLi
BuCu
Bu2CuLi
18
19
20
21
MeCu(CN)Li
MeCu
Me2Cu(CN)Li2
Me2CuLi
58
58
62
64
26:74
21:79
26:74
35:65
23:24
22
23
24
25
26
27
28
29
30
MeCu(CN)Li
MeCu
Me2Cu(CN)Li2
Me2CuLi
BuCu(CN)Li
BuCu
Bu2Cu(CN)Li2
Bu2CuLi
Bu2CuLi´BF3
88
93
94
87
92
83
88
90
95
83:17
75:25
23:77
32:68
73:27
69:31
26:74
33:67
7:93
25:26
31
32
33
34
13
14
MeCu(CN)Li
MeCu
Me2Cu(CN)Li2
Me2CuLi
70
87
81
81
90:10
81:19
17:83
24:76
27:28
35
36
37
38
MeCu(CN)Li
MeCu
Me2Cu(CN)Li2
Me2CuLi
67
64
59
63
63:37
77:23
27:73
29:71
a Isolated yield.
b By 1H NMR and/or GLC analysis.
phenyl ring was investigated with four different diesters
11±14. The para-CF3, as an electron withdrawing group,
substituted diester 11 (Eredˆ21.45 V) produced the syn-
adduct 22 predominantly irrespective of the reagent type
(entries 18±21). Diester 12 (Eredˆ,22.0 V), non-substi-
tuted at the para-position, exhibited the reagent controlled
diastereoselectivity; MeCu and BuCu afforded the anti-
isomer 23 preferentially, while Me2CuLi and Bu2CuLi
gave the syn-isomer 24 predominantly (entries 22±29). In
the case of the Michael acceptor 13 (Eredˆ,22.0 V) having
the para-Me, as an electron donating group, substituted
phenyl group, the reactions with MeCu(CN)Li and MeCu
gave the anti-isomer 25 preferentially, whereas those with
Me2CuLi and Me2Cu(CN)Li2 afforded the syn-isomer 26
predominantly (entries 31±34). The para-MeO, as an
electron donating group, substituted phenyl derivative 14
(Eredˆ,22.0 V) exhibited a reagent-controlled diastereo-
selectivity similar to 12 and 13; the addition of
MeCu(CN)Li and MeCu produced the anti-adduct 27 as a
major isomer whereas that of Me2Cu(CN)Li2 and Me2CuLi
gave the syn-adduct 28 predominantly (Fig. 3) (entries
35±38).
A clear-cut trend on the diastereoselectivity was observed
and it depended upon both the reagent type and the substrate
structure. The relationships between reagents type, substrate
structures and diastereoselectivities are summarized in
Table 2 (for MeCuLn) and in Table 3 (for BuCuLn). The
Michael acceptor 8 having the highest reduction potential
gave the syn-diastereoselectivity regardless of the reagent

2824
Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
Figure 3.
Table 2. Diastereoselectivities of MeCuLn addition
Reagent
Substrate (Ered
10 (21.68)
)
8 (21.33)
9 (21.43)
11 (21.45)
12 (,22.0)
13 (,22.0)
14 (,22.0)
MeCu(CN)Li
MeCu
Me2Cu(CN)Li2
Me2CuLi
anti
syn
syn
syn
syn
syn
syn
syn
anti
anti
syn
syn
anti
anti
syn
syn
anti
anti
syn
syn
syn
syn
syn
anti
syn
type. With decrease of reduction potential of substrates, the
anti-selectivity appears in the table. Previously, we
proposed the order of the oxidation potential of alkylcopper
reagents by using a certain chemical scale.6 The electron
transfer ability of methylcopper reagents is in the following
order: Me2CuLi@Me2Cu(CN)Li2.MeCu.MeCu(CN)Li;
and that of butylcopper reagents is in the following order:
Bu2CuLi.Bu2Cu(CN)Li2<BuCu(CN)Li.BuCu. Table 2
clearly shows that methylcopper reagents with higher
electron transfer ability are prone to produce syn-selectivity.
Thus, Me2CuLi and Me2Cu(CN)Li2 produce syn-diastereo-
selectivity irrespective of the substrate structures. MeCu
reagent gives anti-selectivity in the case of the Michael
acceptors with lower reduction potentials, while it affords
syn-selectivity in the case of those with higher reduction
potentials. The diastereoselectivities of 11 seem to be not
straightforward and, if we count that this is an exceptional
case, the addition of MeCu(CN)Li to most Michael
acceptors produces anti-selectivity. The addition of
MeCu(CN)Li to 8 was so sluggish, and essentially no
reaction took place even after prolonged reaction times. A
similar trend was observed in the case of BuCu reagents
although fewer examples were studied (Table 3). Bu2CuLi
produces syn-selectivity regardless of the substrate struc-
ture, and BuCu affords syn-selectivity in the case of the
Michael acceptors (8 and 9) with higher reduction potentials
while it gives anti-selectivity in the case of 10 and 12 with
lower potentials. The diastereoselectivity of the cyano-
cuprates, Bu2Cu(CN)Li2 and BuCu(CN)Li, is not straight-
forward. In the case of 9, its diastereoselectivity trend is the
same as that of methylcopper reagents, but the order of
electron transfer ability of butyl cyanocoppers is a bit
different from that of methyl cyanocoppers; according to
the chemical scale,6b the order of electron transfer ability
of BuCu(CN)Li is higher than that of BuCu.
The syn-diastereoselectivity of 8±14 can be explained by
the p-complex model 29 (Fig. 4). `Hydrogen' should be
inside in order to alleviate both an allylic strain and steric
repulsion of the R group approaching the b-carbon. The
formation of the p-complex would become much easier
when the `matched' combination between Michael
acceptors having higher reduction potentials and organo-
copper reagents having higher electron donating ability
was used. Even with enoates having lower reduction poten-
tials, such as 12±14, the organocuprate reagents having
higher electron donating ability would be able to form
such p-complex, leading to the syn-diastereoselectivity.
On the other hand, even with the alkylcopper and alkyl-
cyanocopper reagents having lower electron donating
ability, the Michael acceptor 8 having the highest reduction
potential would also be able to form p-complex, leading
to syn-diastereoselectivity. However, in the case of
`mismatched' combination, p-complex formation would
Table 3. Diastereoselectivities of BuCuLn addition
Reagent
Substrate (Ered)
8 (21.33) 9 (21.43) 10 (21.68)
12 (,22.0)
BuCu(CN)Li
BuCu
Bu2Cu(CN)Li2
Bu2CuLi
anti
anti
anti
syn
syn
syn
syn
syn
syn
syn
anti
syn

Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
2825
Figure 4.
Table 4. Reaction of mono-esters (in the case of mono-esters, the use of Me- and Bu-organocopper reagents in the absence of BF3´OEt2 resulted in very low
yields of the conjugate adducts)
Entry
Mono-ester
Reagent
Conjugate adduct (%)a
Isomer ratiob anti:syn
33:34
85:15
87:13
88:12
80:20
70:30
21:79
33:67
30:70
1
2
3
4
5
6
7
8
31
MeCu´BF3
Me3CuLi2´BF3
BuCu´BF3
Bu2Cu(CN)Li2´BF3
Bu2CuLi´BF3
Me3CuLi2´BF3
Bu2Cu(CN)Li2´BF3
Bu2CuLi´BF3
10
46
82
29
90
67
26
89
32
a Isolated yield.
b By 1H NMR and/or GLC analysis.
be not possible but an ordinary nucleophilic attack 30 from
the outside would intervene in the conjugate addition,
giving the anti-diastereoselectivity. `Hydrogen' should be
outside in order to diminish the steric repulsion of the
incoming R group and `Me' may be inside since its steric
demand is rather small (A-value of Meˆ1.70 and that of
Phˆ3.0).7 The pairs between Michael acceptors 10±14
having relatively lower reduction potentials and RCu (and/
or RCu(CN)Li) having relatively lower electron donating
ability area `mismatched' combination.
obtained irrespective of the reagent type. On the other hand,
in the case of 12±14, the anti-selectivity was produced with
MeCu and the syn-selectivity was obtained with Me2CuLi.
It is now clear that only the electronic effect of the phenyl
ring dictates the diastereoselectivity, and this can be
explained either by p-complex formation or by an ordinary
nucleophilic mechanism.
Mono-esters
a,b-Unsaturated mono-esters 31 and 32 were prepared by
the standard procedures (Fig. 5).8 The reduction potentials
of those mono-esters must be lower than those of diester 12,
and therefore it is reasonable to assume that p-complex
formation becomes more dif®cult for these mono-esters in
comparison with the corresponding diester. Since the
reaction of the mono-esters was more sluggish even with
reactive cuprate reagents than that of the di-esters, the Lewis
acid mediated addition was used.4,9±11 The presence of
BF3´OEt2 as a Lewis acid in these reactions did not exert
signi®cant in¯uence upon the diastereoselectivity of the
conjugate adducts (entry 30, Table 1). The results are
summarized in Table 4. The trans ester 31 produced the
anti-adduct 33 predominantly irrespective of the reagent
type (entries 1±5), while cis ester 32 afforded the
The comparison of the diastereoselectivity difference
among 11±14 is especially noteworthy. Only structural
difference of these substrates is their para-substitutents of
the aromatic ring and therefore it is clear that there is no
difference among the substrates on the steric effect such as
allylic strain. The reduction potential of 11 is the highest
among them. Although the exact data on the reduction
potentials of 12±14 could not be obtained due to their
lower values, the 13C-chemical shifts at the b-carbons
suggested the order of the electron density of the ole®nic
bond; 150.48 ppm for 11, 151.74 ppm for 12, 153.06 ppm
for 13, and 158.61 ppm for 14. Accordingly, it is not
unreasonable to assume that the order of electron accepting
ability is 11.12.13.14. With 11, the syn-selectivity was
Figure 5.

2826
Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
Figure 6.
syn-isomer 34 preferentially (Fig. 5) regardless of the
reagents (entries 6±8).
reagents and the cis enoate 32, and with the stereoselectivity
switch from anti to syn upon changing the enoate from the
trans 31 to the cis enoate 32.
It is now clear that the double bond geometry plays an
important role in controlling the diastereoselectivity of the
conjugate addition to mono ole®ns (Fig. 6). The reactions of
the monoesters (31 and 32) with alkyl copper reagents must
proceed via the ordinary nucleophilic attack. The addition of
the copper reagents proceeds through a BuÈrgi±Dunitz
trajectory1c,g from the outside position of a transition state
geometry 35 in which phenyl group is anti and methyl group
is inside, giving the anti isomer predominantly. If the double
bond geometry changes from trans to cis, the inside methyl
conformation would be destabilized due to the steric
repulsion between the ester and phenyl group (as shown
in 36), and thus the transition state geometry 37 would
become more favorable in order to minimize the allylic
strain. The syn isomer is produced from 37, and this
mechanism is in good agreement with the diastereo-
selectivity observed in the reaction between alkyl cooper
Conjugate addition of methallylcopper reagents
The conjugate additions of methallylcopper reagents to
11±14 were investigated. The results are summarized in
Table 5. The reactions with methallylcopper reagents
afforded the syn isomer preferentially regardless of the
reagent type and the para-substituents of the substrates,
except for one case (entry 6). The reason for this exception
is not clear at present. The reaction of 11±14 with
methallylcopper reagents would proceed through
p-complex formation 29 irrespective of the reagent type
since the methallylcopper reagents may possess higher
electron donating ability than the corresponding methyl-
copper reagents.4b A hydrogen is on the inside position
because nucleophile attacks from inside. It is further
con®rmed by the result of methallylcopper reagents that
Table 5. Conjugate addition of methallylcopper reagents to Michael acceptors 11±14 in diethyl ether (all reactions were carried out in diethyl ether at 2408C
with Michael acceptor (0.3 mmol) and organocopper (0.9 mmol))
Entry
Michael acceptor
Reagent
Conjugate adduct (%)a
Isomer ratiob anti:syn
21:22
43:57
24:76
12:88
43:57
23:24
48:52
67:33
30:70
44:56
25:26
32:68
31:69
29:71
23:77
27:28
34:66
14:86
34:66
42:58
1
2
3
4
11
(Methallyl)Cu(CN)Li
(Methallyl)Cu
(Methallyl)2Cu(CN)Li2
(Methallyl)2CuLi
77
75
77
87
5
6
7
8
12
13
14
(Methallyl)Cu(CN)Li
(Methallyl)Cu
(Methallyl)2Cu(CN)Li2
(Methallyl)2CuLi
72
75
87
78
9
(Methallyl)Cu(CN)Li
(Methallyl)Cu
(Methallyl)2Cu(CN)Li2
(Methallyl)2CuLi
80
75
69
63
10
11
12
13
14
15
16
(Methallyl)Cu(CN)Li
(Methallyl)Cu
(Methallyl)2Cu(CN)Li2
(Methallyl)2CuLi
65
75
77
87
a Isolated yield.
b By 1H NMR and/or GLC analysis.

Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
2827
a `matched pair' produces syn-diastereoselectivity via
p-complex formation.
3H), 3.63 (dq, Jˆ7 and 11 Hz, 1H), 7.00±7.30 (m, 6H); IR
1390, 1330, 1020, 980, 910, 850, 760, 720, 700 cm21
HRMS m/z Calcd for C11H13NO2:191.0946. Found:
191.0944.
(neat) 3040, 2980, 2950, 1670, 1610, 1520, 1500, 1450,
;
Conclusion
Ethyl 2-cyano-4-phenyl-2-pentenoate (10). The nitrile 10
was prepared by the reaction of 2-phenylpropionaldehyde
with ethyl cyanoacetate according to the literature5 in 87%
The 1,2-asymmetric induction in the conjugate addition of
organocopper reagents to g-aryl a,b-unsaturated carbonyl
derivatives is rather straightforward in comparison with that
of the addition to g-alkoxy-analogs. Two different types of
transition state geometries are involved: an ordinary nucleo-
philic addition and p-complex formation. If the combina-
tion between organocopper reagents and Michael acceptors
is `matched pair', p-complex formation takes place, giving
the syn-diastereoselectivity. In the case of `mismatched
pair', the anti-diastereoselectivity is produced through the
ordinary nucleophilic addition. `Matched pair' implies the
reaction between organocopper reagents having higher elec-
tron donating ability and Michael acceptors having higher
reduction potentials. `Mismatched pair' implies the reaction
between organocoppers having lower electron donating
ability and Michael acceptors having lower reduction poten-
tials.
1
yield. H NMR (CDCl3) d 1.35 (t, Jˆ7.5 Hz, 3H), 1.55 (d,
Jˆ7 Hz, 3H), 4.10 (dq, Jˆ7 and 11 Hz, 1H), 4.25 (q,
Jˆ7.5 Hz, 2H), 7.21 (m, 5H), 7.45 (d, Jˆ11 Hz, 1H); IR
(neat) 3040, 2980, 2940, 2240, 1730, 1620, 1600, 1490,
1450, 1370, 1300, 1280, 1250, 1100, 1080, 1020,
700 cm21; HRMS m/z Calcd for C14H15NO2:229.1103.
Found: 229.1103.
Ethyl 4-methyl-2-(ethoxycarbonyl)-4-p-tri¯uoromethyl-
phenyl-2-butenoate (11). (a,a,a-Tri¯uoro-p-tolyl)acetic
acid was converted to the methyl ester with diazomethane
according to the literature procedure (97% yield).12 To a
THF (140 mL) solution of diisopropylamine (3.14 mL,
22.1 mmol) cooled at 08C under Ar was added slowly a
n-hexane solution of n-BuLi (20.1 mmol), and the mixture
was stirred at 08C for 15 min and then cooled to 2788C. A
THF (10 mL) solution of the methyl ester obtained above
(4.38 g, 20.1 mmol) was slowly added, and the mixture was
stirred for 30 min at 2788C. To this solution was slowly
added a HMPA (4.5 mL) solution of methyl iodide (1.4 mL,
22.1 mmol), and the mixture was stirred for 30 min at
2788C. Addition of saturated NH4Cl aqueous solution at
08C, extraction three times with diethyl ether, washing the
organic layer with brine, drying with anhydrous MgSO4,
concentration under vacuum, and puri®cation two times
by ¯ash column chromatography (n-hexane:CH2Cl2:
AcOEtˆ100:10:5 and 100:20:10) gave methyl 2-(a,a,a-
tri¯uoro-p-tolyl)propionate (3.50 g) in 74% yield. To
lithium aluminum hydride (0.85 g, 22.4 mmol) in diethyl
ether (25 mL) at 08C was added a diethyl ether solution
(5 mL) of the ester obtained. The mixture was stirred for
2 h at room temperature and then cooled to 08C. The reac-
tion was quenched with 1N HCl. Extraction with CH2Cl2,
washing with brine, drying with anhydrous Na2SO4, concen-
tration, and puri®cation with ¯ash column chromatography
(n-hexane:AcOEtˆ5:1) gave 2-(a,a,a-tri¯uoro-p-tolyl)pro-
pan-1-ol in 74% yield. To a CH2Cl2 solution (25 mL) of
PDC (7.65 g, 20 mmol) was added a CH2Cl2 solution
(5 mL) of the alcohol, and the mixture was stirred for
16 h. Filtration with Celite followed by puri®cation with a
short column (n-pentane:diethyl etherˆ20:1) gave 2-(a,a,a-
tri¯uoro-p-tolyl)propanal. To diethyl malonate in benzene
(8 mL) at 508C was added a benzene solution (2.5 mL) of
the aldehyde obtained (0.3 g, 2.12 mmol). Piperidine
(0.01 mL, 0.08 mmol), acetic acid (0.01 mL, 0.4 mmol)
and benzene (20 mL) were added. The mixture was heated
at 1058C for 4 h with Dean-Stark distillation head to remove
water produced in the reaction, and then stirred for 12 h at
808C. Addition of ether (10 mL), 1% HCl (5 mL) and 1%
NaHCO3 aqueous solution (5 mL) at 08C, washing two
times with water, extraction three times with ether, drying
with anhydrous Na2SO4, concentration under vacuum, and
puri®cation two times by ¯ash column chromatography
(n-hexane: CH2Cl2:AcOEtˆ50:1:2 and 20:1:2) gave 11 in
Experimental
General methods
Melting points were determined on either a Yamoto MP-21
capillary melting point apparatus or a MRK No. 8026.
Analytical thin-layer chromatography (TLC) was
performed on E. Merck precoated silica gel 60F254 plates.
Solvents for extraction and chromatography were reagent
grade. THF and diethyl ether were distilled from benzo-
phenone ketyl under argon immediately prior to use. Butyl-
lithium and methyllithium were obtained from the Kanto
Chemical Co., Inc. and Aldrich Chemical Company, respec-
tively, as standardized solutions. In vacuo removal of
solvent refers to the use of a rotary operating aspirator and
then rotary pump pressure. Column chromatography was
carried out with E. Merck silica gel 60 (70±230 mesh
ASTM). Flush chromatography was carried out with
E. Merck silica gel 60 (230±400 mesh ASTM). HPLC
was performed on a HITACHI L-6000 model using a
GASUKURO KOGYO HPLC Packed Column Intertisil
SIL (5 mm 4.6£250 nm2). GC analysis was carried out on
a Shimadzu 14A model equipped with a fused silica-
capillary column (Shimadzu CPB1-M25-025). Infrared
spectra were recorded on a HITACHI model 260-10.
Peaks are recorded (in cm-1). NMR spectra were recorded
on a JEOL GSX-270 and GSX-400 spectrometers. Low-
resolution mass spectra were obtained on a HITACHI
M-2500S spectrometer using electron impact (EI) obtained
at 13.5 eV. High-resolution mass spectra were obtained on
JEOL JMS-HX 110. Combustion analyses were performed
by the Analytical Center of the Graduate School of Science
at Tohoku University.
(E)-2-Nitro-4-phenyl-2-pentene (8). The nitroole®ne 8
was prepared by the reaction of 2-phenylpropionaldehyde
with nitroethane according to the literature5 in 64% yield.
1H NMR (CDCl3) d 1.46 (d, Jˆ7 Hz, 3H), 2.17 (d, Jˆ1 Hz,

2828
Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
1
38% yield from 2-(a,a,a-tri¯uoro-p-tolyl)propan-1-ol: H
NMR (CDCl3) d 1.28 (t, Jˆ7.0 Hz, 3H), 1.36 (t,
Jˆ7.0 Hz, 3H), 1.48 (d, Jˆ7.3 Hz, 3H), 3.94±4.05 (m,
1H), 4.23 (q, Jˆ7.0 Hz, 2H), 4.32 (q, Jˆ7.0 Hz, 2H), 6.95
(d, Jˆ10.8 Hz, 1H), 7.38 (d, Jˆ7.8 Hz, 2H), 7.58 (d,
Jˆ7.8 Hz, 2H); 13C NMR (CDCl3) d 14.11, 14.19, 26.73,
39.42, 61.57, 125.76, 127.66, 127.93, 128.72, 150.48,
163.94, 165.33; IR (neat) 3026, 2928, 2854, 1733, 1646,
1449, 1437, 1367, 1255, 1233, 1194, 1156, 1066, 1055,
999, 949, 932, 838, 758, 729, 669 cm21; HRMS m/z
Calcd for C17H19O4F3:344.1235. Found: 344.1229. The
general procedure mentioned above for the preparation of
tri¯uoro ester was applied for the synthesis of 13 (from ethyl
p-tolylacetate) and 14 (from ethyl p-methoxyphenyl-
acetate).
was stirred for 1 or 2 h at 2788C. The usual workup gave the
products, whose diastereomer ratios were determined by a
GLC and by 1H NMR. Methylcopper reagents were
prepared as follows. MeCu: A diethyl ether solution of
MeLi´LiBr (0.86 M£1.05 mL, 0.9 mmol) was slowly
added to a precooled diethyl ether (3 mL) suspension of
CuI (171.4 mg, 0.9 mmol) at 08C, stirring was continued
for 5 min at this temperature, and then the mixture was
cooled to 2788C. Me2CuLi: a procedure similar to above,
except for the use of 2 equiv. MeLi´LiBr, was used.
MeCu(CN)Li: a diethyl ether solution of MeLi´LiBr
(0.86 M£1.05 mL, 0.9 mmol) was added slowly to a
precooled diethyl ether (3 mL) suspension of CuCN
(80.6 mg, 0.9 mmol) at 2788C. The mixture was allowed
to warm to 08C, and a homogeneous solution was obtained.
After a few minutes, the solution was cooled to 788C.
Me2Cu(CN)Li2: a procedure similar to above, except for
the use of 2 equiv. of MeLi´LiBr.
Ethyl 2-ethoxycarbonyl-4-phenyl-2-butenoate (12). The
diester 12 was prepared by the reaction of 2-phenylpropion-
aldehyde with diethyl malonate under the Lehnert's
condition5 in 70% yield: 1H NMR (CDCl3) d 1.27 (t,
Jˆ7.0 Hz, 3H), 1.31 (t, Jˆ7.0 Hz, 3H), 1.44 (d, Jˆ7.0 Hz,
3H), 3.87 (dq, Jˆ7 and 11 Hz, 1H), 4.16 (q, Jˆ7 Hz, 2H),
4.24 (q, Jˆ7 and 11 Hz, 2H), 6.85 (d, Jˆ11 Hz, 1H), 7.22
(m, 5H); IR (neat) 2980, 1730, 1640, 1600, 1500, 1450,
1370, 1250, 1220, 1140, 1100, 1070, 1020, 860, 760,
700 cm21; HRMS m/z Calcd for C16H20O4:276.1362.
Found: 276.1363.
Reaction of butylcopper reagents
A procedure similar to that above, except for the use of
BuLi-hexane solution instead of MeLi´LiBr and for the
use of 2508C instead of 08C.
Reaction of methallylcopper reagents
To a diethyl ether solution of 3 equiv. of the copper
reagents, cooled at 2408C, was added a diethyl ether
(2 mL) solution of substrate (0.3 mmol), and the mixture
was stirred for 1 h at 2408C. The usual workup followed
by a short silica-gel column chromatography (n-hexane as
an eluent) to remove tributyltin residues gave the products,
which were analyzed by a capillary GLC. Methallyllithium
was prepared from methallyltributyltin and n-BuLi accor-
ding to the literature procedure.13 Methallylcopper reagents
were prepared in the following way. (Methallyl)Cu:
Methallyllithium (0.9 mmol) was slowly added to a diethyl
ether (3 mL) suspension of CuI (171.4 mg, 0.9 mmol) at
2408C, and the mixture was stirred for 10 min. (Methal-
lyl)2CuLi: 2 equiv. of methallyllithium were used at
2408C. (Methallyl)Cu(CN)Li: Methallyllithium (0.9
mmol) was slowly added to a diethyl ether (3 mL) solution
of CuCN (80.6 mg, 0.9 mmol), cooled at 2408C, and the
mixture was stirred for 10 min at this temperature.
(Methallyl)2Cu(CN)Li2: a procedure similar to above,
except for the use of 2 equiv. of methallyllithium.
Methyl 4-methyl-2-(methoxycarbonyl)-4-p-tolyl-2-buteno-
ate (13). Puri®cation of the crude product two times by ¯ash
column chromatography (n-hexane:AcOEtˆ50:1 and 20:1)
gave 13 in 10% yield from 2-(p-tolyl)propan-1-ol: 1H NMR
(CDCl3) d 1.43 (d, Jˆ7.0 Hz, 3H), 2.32 (s, 3H), 3.75 (s,
3H), 3.85 (s, 3H), 3.81±3.89 (m, 1H), 7.01 (d, Jˆ10.8 Hz,
1H), 7.13 (s, 4H); 13C NMR (CDCl3) d 20.27, 20.99, 39.27,
52.29, 52.34, 125.90, 126.99, 129.48, 136.63, 193.36,
153.06, 164.49, 165.86; IR (neat) 3025, 2954, 2927, 2875,
2849, 1735, 1644, 1514, 1437, 1364, 1309, 1275, 1248,
1223, 1195, 1143, 1077, 1047, 1017, 988, 942, 843, 812,
768, 668, 540 cm21
; HRMS m/z Calcd for
C15H18O4:262.1205. Found: 262.1206.
Ethyl 4-methyl-2-(ethoxycarbonyl)-4-p-methoxylphenyl-
2-butenoate (14). Puri®cation of the crude product two
times by ¯ash column chromatography (CH2Cl2:diethyl
etherˆ200:1 and 100:1) gave 14 in 35% yield from
2-(p-methoxyphenyl)propan-1-ol: 1H NMR (CDCl3) d
1.27 (t, Jˆ7.3 Hz, 3H), 1.34 (t, Jˆ7.3 Hz, 3H), 1.42 (d,
Jˆ7.0 Hz, 3H), 3.78 (s, 1H), 3.81±3.88 (m, 1H), 4.21 (q,
Jˆ7.0 Hz, 2H), 4.33 (q, Jˆ7.0 Hz, 1H), 6.86 (d, Jˆ8.9 Hz,
2H), 6.93 (d, Jˆ10.5 Hz, 1H), 7.18 (d, Jˆ8.9 Hz, 2H); 13C
NMR (CDCl3) d 14.11, 14.20, 38.71, 55.29, 61.31, 114.20,
126.53, 128.12, 134.52, 152.03, 158.61, 164.10, 165.55; IR
(neat) 2983, 2938, 2909, 2838, 1733, 1608, 1514, 1465,
1445, 1369, 1307, 1251, 1181, 1118, 1096, 1072, 1033,
858, 831, 808, 756, 669 cm21; HRMS m/z Calcd for
C17H22O5:306.1468. Found: 306.1470.
1
3-Methyl-4-phenyl-2-pentanone (15a and 16a). 15a: H
NMR (CDCl3) d 1.25 (d, Jˆ6.6 Hz, 3H), 1.31 (d, Jˆ7.0 Hz,
3H), 2.19 (s, 3H), 2.79 (m, 1H), 3.00 (m, 1H), 7.15±7.33 (m,
5H); 16a: 1H NMR (CDCl3) d 1.11 (d, Jˆ6.6 Hz, 3H), 1.24
(d, Jˆ7.0 Hz, 3H), 1.88 (s, 3H), 2.79 (m, 1H), 3.00 (m, 1H),
7.15±7.33 (m, 5H); IR (neat) 2990, 2950, 1710, 1550, 1500,
1460, 1360, 1170, 1080, 770, 710 cm21; HRMS m/z Calcd
for C12H16O: 176.1201. Found: 176.1197.
1
3-Butyl-4-phenyl-2-pentanone (15b and 16b). 15b: H
Reaction of methylcopper reagents
NMR (CDCl3) d 0.77±0.96 (m, 3H), 1.05±1.57 (m, 9H),
2.14 (s, 3H), 2.30±2.95 (m, 2H), 7.09 (m, 5H); 16b: H
1
To a diethyl ether solution of 3 equiv. of the copper
reagents, cooled at 2788C, was slowly added a diethyl
ether (2 mL) solution of substrate (0.3 mmol); the mixture
NMR (CDCl3) d 0.77±0.96 (m, 3H), 1.05±1.57 (m, 9H),
1.25 (d, Jˆ7.0 Hz, 3H), 1.74 (s, 3H), 2.30±2.95 (m, 2H),
7.09 (m, 5H); IR (neat) 2980, 2940, 1710, 1550, 1500, 1460,

Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
2829
1360, 1160, 770, 700 cm21; HRMS m/z Calcd for C15H22O:
218.1671. Found: 218.1672.
Ethyl 3-butyl-2-ethoxycarbonyl-4-phenylpentanoate (23b
and 24b). 23b: H NMR (CDCl3) d 0.75±0.87 (m, 3H),
1
1.16±1.35 (m, 15H), 2.23 (m, 1H), 2.86 (m, 1H), 3.35 (d,
Jˆ6.0 Hz, 1H), 4.06 (q, Jˆ7.0 Hz, 4H), 7.08 (m, 5H); 24b:
1H NMR (CDCl3) d 0.75±0.87 (m, 3H), 1.16±1.35 (m,
15H), 2.23 (m, 1H), 2.86 (m, 1H), 3.08 (d, Jˆ6.0 Hz, 1H),
4.03 (q, Jˆ7.0 Hz, 4H), 7.08 (m, 5H); IR (CCl4) 2970, 2890,
1750, 1730, 1600, 1500, 1470, 1460, 1380, 1300, 1250,
1160, 1040, 860, 770, 700 cm21; HRMS m/z Calcd for
C20H30O4: 334.2144. Found: 334.2147.
Ethyl 2-cyano-3-methyl-4-phenylpentanoate (19a and
20a). H NMR (CDCl3); The following signals were of
1
four diastereomeric mixtures. d 0.86 (d, Jˆ6.6 Hz)10.90
(d, Jˆ6.6 Hz) (3H), 1.19±1.36 (m, 3H), 2.42 (m, 1H), 2.72±
3.02 (m, 1H), 3.21 (d, Jˆ3.3 Hz) 13.37 (d, Jˆ6.2 Hz)
13.84 (d, Jˆ4.0 Hz) (1H), 4.21 (d, Jˆ7.0 Hz) 14.29 (d,
Jˆ7.0 Hz) (2H), 7.28 (m, 5H); IR (neat) 2990, 2950,
2270, 1740, 1610, 1500, 1460, 1380, 1310, 1260, 1200,
1100, 1030, 860, 780, 710 cm21; HRMS m/z Calcd for
C15H19NO2: 245.1416. Found: 245.1416.
Ethyl 2-ethoxycarbonyl-3-methallyl-4-phenylpentanoate
(23c and 24c). 23c: H NMR (CDCl3) d 1.18±1.32 (m,
1
11H), 1.64 (s, 3H), 2.01 (d, Jˆ17.6 Hz, 1H), 2.81±3.05
(m, 2H), 2.15±2.38 (m, 1H), 2.61±2.79 (m, 1H), 2.94±
3.09 (m, 1H), 3.52 (d, Jˆ5.1 Hz, 1H), 3.99±4.20 (m, 4H),
4.71 (d, Jˆ7.6 Hz, 2H), 5.48 (dt, Jˆ10.8 and 16.2 Hz, 1H),
7.18±7.29 (m, 5H); 24c: 1H NMR (CDCl3) d 1.18±1.32 (m,
11H), 1.56 (s, 3H), 2.01 (d, Jˆ17.6 Hz, 1H), 2.81±3.05 (m,
2H), 2.15±2.38 (m, 1H), 2.61±2.79 (m, 1H), 2.94±3.09 (m,
1H), 3.33 (d, Jˆ6.5 Hz, 1H), 3.99±4.20 (m, 4H), 4.71 (d,
Jˆ7.6 Hz, 2H), 5.48 (dt, Jˆ10.8 and 16.2 Hz, 1H), 7.18±
7.29 (m, 5H); IR (CCl4) 3076, 3029, 2982, 2938, 1749,
1732, 1495, 1452, 1373, 1252, 1222, 1174, 1156, 1038,
849, 701 cm21; HRMS m/z Calcd for C20H28O4: 322.1987.
Found: 322.1982.
Ethyl 3-butyl-2-cyano-4-phenylpentanoate (19b and
20b). H NMR (CDCl3); the following signals were of
1
four diastereomeric mixtures. d 0.77±0.91 (m, 3H), 1.15±
1.66 (m, 12H), 2.41 (m, 1H), 2.75±2.99 (m, 1H), 3.24 (d,
Jˆ3.3 Hz) 13.56 (d, Jˆ3.3 Hz) 13.64 (d, Jˆ2.9 Hz)
13.70 (d, Jˆ2.9 Hz) (1H), 4.20±4.28 (m, 2H), 7.24 (m,
5H); IR (neat) 2970, 2880, 2260, 1740, 1610, 1500, 1470,
1460, 1380, 1250, 1030, 770, 410 cm21; HRMS m/z Calcd
for C18H25NO2: 287.1885. Found: 287.1890.
Ethyl 2-ethoxycarbonyl-3-methyl-4-p-tri¯uoromethyl-
phenylpentanoate (21a and 22a). 21a: H NMR (CDCl3)
1
d 0.83 (d, Jˆ7.0 Hz, 3H), 1.22±1.33 (m, 9H), 2.48±2.54
(m, 1H), 2.83±2.96 (m, 1H), 3.23 (d, Jˆ6.8 Hz, 1H), 4.13±
4.24 (m, 4H), 7.34 (d, Jˆ7.8 Hz, 2H), 7.66 (d, Jˆ7.8 Hz,
Methyl 2-methoxycarbonyl-3-methyl-4-p-tolylpentanoate
(25a and 26a). 25a: 1H NMR (CDCl3) d 0.81 (d, Jˆ7.0 Hz,
3H), 1.28 (d, Jˆ7.3 Hz, 3H), 2.31 (s, 3H), 2.41±2.50 (m,
1H), 2.73±2.80 (m, 1H), 3.45 (d, Jˆ7.6 Hz, 1H), 3.69 (d,
Jˆ1.4 Hz, 6H), 7.00±7.10 (m, 4H); 26a: 1H NMR (CDCl3)
d 1.00 (d, Jˆ6.8 Hz, 3H), 1.21 (d, Jˆ7.0 Hz, 3H), 2.31 (s,
3H), 2.41±2.50 (m, 1H), 2.73±2.80 (m, 1H), 3.30 (d,
Jˆ6.5 Hz, 1H), 3.69 (d, Jˆ1.4 Hz, 6H), 7.00±7.10 (m,
4H); IR (CCl4) 2973, 2953, 2927, 1756, 1738, 1515, 1456,
1436, 1363, 1311, 1264, 1232, 1195, 1160, 1033, 1021,
545 cm21; HRMS m/z Calcd for C16H22O4: 278.1518.
Found: 278.1521.
1
2H); 22a: H NMR (CDCl3) d 1.00 (d, Jˆ7.0 Hz, 3H),
1.22±1.33 (m, 9H), 2.48±2.54 (m, 1H), 2.83±2.96 (m,
1H), 3.21 (d, Jˆ6.8 Hz, 1H), 4.13±4.24 (m, 4H), 7.34 (d,
Jˆ7.8 Hz, 2H), 7.66 (d, Jˆ7.8 Hz, 2H); IR (CCl4) 2981,
2938, 2879, 1752, 1734, 1619, 1369, 1326, 1131, 1072,
1036, 1017 cm21; HRMS m/z Calcd for C18H23O4F3:
360.1548. Found: 360.1541.
Ethyl 2-ethoxycarbonyl-3-methallyl-4-p-tri¯uoromethyl-
phenylpentanoate (21b and 22b): 21b. H NMR (CDCl3)
1
d 1.16±1.65 (m, 12H), 1.95±2.35 (m, 2H), 2.62±2.80 (m,
1H), 3.00±3.20 (m, 1H), 3.51 (d, Jˆ4.7 Hz, 1H), 3.96±4.24
(m, 4H), 4.69±4.77 (m, 2H), 7.32 (d, Jˆ7.8 Hz, 2H), 7.55
(d, Jˆ8.1 Hz, 2H); 22b: 1H NMR (CDCl3) d 1.16±1.65 (m,
12H), 1.95±2.35 (m, 2H), 2.62±2.80 (m, 1H), 3.00±3.20
(m, 1H), 3.33 (d, Jˆ6.5 Hz, 1H), 3.96±4.24 (m, 4H),
4.69±4.77 (m, 2H), 7.39 (d, Jˆ8.1 Hz, 2H), 7.55 (d,
Jˆ8.1 Hz, 2H); IR (CCl4) 2981, 2962, 2931, 1749, 1733,
1619, 1465, 1446, 1376, 1327, 1168, 1131, 1071,
1017 cm21; HRMS m/z Calcd for C21H27O4F3: 400.1861
Found: 400.1859.
Methyl 2-methoxycarbonyl-3-methallyl-4-p-tolylpenta-
noate (25b and 26b). 25b: H NMR (CDCl3) d 1.22 (d,
1
Jˆ6.8 Hz, 3H), 1.65 (s, 3H), 2.08±2.28 (m, 2H), 2.31 (s,
3H), 2.59±2.72 (m, 1H), 2.89±3.02 (m, 1H), 3.52 (d,
Jˆ6.5 Hz, 1H), 3.62 (s, 3H), 3.71 (s, 3H), 4.71 (t,
1
Jˆ8.6 Hz, 2H), 7.11 (d, Jˆ8.6 Hz, 2H); 26b: H NMR
(CDCl3) d 1.22 (d, Jˆ7.3 Hz, 3H), 1.65 (s, 3H), 2.08±
2.28 (m, 2H), 2.31 (s, 3H), 2.59±2.72 (m, 1H), 2.89±3.02
(m, 1H), 3.37 (d, Jˆ6.2 Hz, 1H), 3.57 (s, 3H), 3.68 (s, 3H),
4.71 (t, Jˆ8.6 Hz, 2H), 7.11 (d, Jˆ8.6 Hz, 2H); IR (CCl4)
2969, 2952, 2924, 1754, 1739, 1647, 1514, 1458, 1435,
Ethyl 2-ethoxycarbonyl-3-methyl-4-phenylpentanoate
(23a and 24a). 23a: 1H NMR (CDCl3) d 0.83 (d,
Jˆ7.0 Hz, 3H), 1.29 (t, Jˆ7.0 Hz, 6H), 1.31 (d, Jˆ7.0 Hz,
3H), 2.36 (m, 1H), 2.81 (m, 1H), 3.30 (d, Jˆ6.0 Hz, 1H),
4.12 (q, Jˆ7.0 Hz, 4H), 7.12 (m, 5H); 24a: 1H NMR
(CDCl3) d 1.01 (d, Jˆ7.0 Hz, 3H), 1.23 (d, Jˆ7.0 Hz,
3H), 1.25 (t, Jˆ7.0 Hz, 6H), 2.36 (m, 1H), 2.81 (m, 1H),
3.07 (d, Jˆ6.0 Hz, 1H), 4.08 (q, Jˆ7.0 Hz, 4H), 7.12 (m,
5H); IR (CCl4) 2980, 1750, 1730, 1600, 1500, 1460, 1370,
1159, 894 cm21
; HRMS m/z Calcd for C19H26O4:
318.1831. Found: 318.1835.
Ethyl 2-ethoxycarbonyl-3-methyl-4-p-methoxyphenyl-
pentanoate (27a and 28a). 27a: H NMR (CDCl3) d 0.81
1
(d, Jˆ6.8 Hz, 3H), 0.83±1.90 (m, 11H), 2.63±2.73 (m, 1H),
3.07 (dt, Jˆ5.4 and 10.8 Hz, 1H), 3.60 (d, Jˆ10.3 Hz, 1H),
3.70 (s, 3H), 3.73 (s, 3H), 4.97±5.12 (m, 2H), 5.93 (dt,
1
Jˆ10.8 and 16.2 Hz, 1H); 28a: H NMR (CDCl3) d 0.81
1310, 1260, 1230, 1170, 1150, 1030, 860, 770, 700 cm21
;
HRMS m/z Calcd for C17H24O4: 292.1675. Found:
292.1676.
(d, Jˆ6.8 Hz, 3H), 0.83±1.90 (m, 11H), 2.63±2.73 (m, 1H),
3.07 (dt, Jˆ5.4 and 10.8 Hz, 1H), 3.70 (d, Jˆ3.0 Hz, 1H),
3.70 (s, 3H), 3.73 (s, 3H), 4.97±5.12 (m, 2H), 5.68 (dt,

2830
Y. Chounan et al. / Tetrahedron 56 (2000) 2821±2831
Jˆ8.1 and 16.2 Hz, 1H); IR (CCl4) 2952, 2927, 2854, 1761,
1741, 1457, 1449, 1435, 1261, 1196, 1146, 924 cm21
HRMS m/z Calcd for C18H26O5: 322.1780. Found:
HRMS m/z Calcd for C17H26O2: 262.1939. Found:
262.1936.
;
322.1783.
References
Ethyl 2-ethoxycarbonyl-3-methallyl-4-p-methoxyphenyl-
pentanoate (27b and 28b). 27b: 1H NMR (CDCl3) d
1.18±1.31 (m, 9H), 1.52 (s, 3H), 2.01±2.28 (m, 2H), 3.49
(d, Jˆ5.1 Hz, 1H), 3.79 (s, 3H), 4.02±4.19 (m, 4H), 4.59±
4.64 (m, 2H), 6.83 (d, Jˆ8.9 Hz, 2H), 7.11 (d, Jˆ8.6 Hz,
2H); 28b: 1H NMR (CDCl3) d 1.18±1.31 (m, 9H), 1.52 (s,
3H), 2.01±2.28 (m, 2H), 3.33 (d, Jˆ6.8 Hz, 1H), 3.79 (s,
3H), 4.02±4.19 (m, 4H), 4.59±4.64 (m, 2H), 6.83 (d,
Jˆ8.9 Hz, 2H), 7.16 (d, Jˆ8.4 Hz, 2H); IR (CCl4) 2982,
2937, 2909, 2836, 1748, 1733, 1612, 1513, 1464, 1443,
1373, 1303, 1249, 1177, 1155, 1041, 894 cm21; HRMS m/
z Calcd for C21H30O5: 362.2093. Found: 362.2094.
Â
1. (a) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968,
Â
2199. (b) Cherest, M.; Felkin, H. Tetrahedron Lett. 1968, 2205. (c)
BuÈrgi, H. B.; Dunitz, J. D.; Lehn, J.-M.; Wipff, G. Tetrahedron
1974, 30, 1563. (d) Anh, N. T.; Eisenstein, O. Nouv. J. Chem. 1977,
Â
1, 61. (e) Anh, N. T. Top. Curr. Chem. 1980, 88, 145. (f) Cherest,
M.; Prudent, N. Tetrahedron 1980, 36, 1599. (g) BuÈrgi, H. B.;
Dunitz, J. D. Acc. Chem. Res. 1983, 16, 153. (h) Wu, Y.-D.;
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Transformations; Bartmann, W., Sharpless, K. B., Eds.; VCH:
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N. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon Press: Oxford, 1991; Vol. 8, pp 1000.
trans Ester 31 and cis ester 32 were prepared by the reaction
of commercially available 2-phenylpropanal with
(MeO)2POCH2CO2Et according to the general procedure.8
The 77:23 mixture of trans and cis ester was easily sepa-
rated by column chromatography on silica gel (hexane:
diethyl etherˆ20:1). trans Ester 31 was obtained in 76%
yield, and cis ester 32 was gained 22% yield.
2. (a) Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81,
2748. (b) Cram, D. J.; Wilson, D. R. J. Am. Chem. Soc. 1963, 85,
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3. See, for example: (a) Isobe, M.; Kitamura, M.; Goto, T.
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Tetrahedron Lett. 1980, 21, 4727; Alcarez, C.; Carretero, J. C.;
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Salomon, R. G.; Miller, D. B.; Raychaudhuri, S. R.; Avasthi, K.;
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(E)-Ethyl 4-phenyl-2-pentenoate (31). 1H NMR (CDCl3) d
1.24 (t, Jˆ7 Hz, 3H), 1.40 (d, Jˆ7 Hz, 3H), 3.57 (dq, Jˆ7
and 7 Hz, 1H), 4.11 (q, Jˆ7 Hz, 2H), 5.72 (dd, Jˆ2 and
16 Hz, 1H), 7.05 (dd, Jˆ7 and 16 Hz, 1H), 7.18 (m, 5H);
IR (neat) 2980, 1720, 1650, 1600, 1495, 1450, 1370, 1270,
1170, 1030, 980, 860, 760, 700 cm21; HRMS m/z Calcd for
C13H16O2: 204.1150. Found: 204.1150.
(Z)-Ethyl 4-phenyl-2-pentenoate (32). 1H NMR (CDCl3) d
1.28 (t, Jˆ7 Hz, 3H), 1.39 (d, Jˆ7 Hz, 3H), 4.14 (q,
Jˆ7 Hz, 2H), 4.94 (dq, Jˆ7 and 11 Hz, 1H), 5.65 (d,
Jˆ11 Hz, 1H), 6.16 (dd, Jˆ11 and 11 Hz, 1H), 7.25 (m,
5H); IR (neat) 2980, 2940, 1720, 1640, 1450, 1410, 1390,
1200, 1110, 1080, 1030, 830, 740, 700 cm21; HRMS m/z
Calcd for C13H16O2: 204.1150. Found: 204.1151.
Ethyl 3-methyl-4-phenylpentanoate (33 and 34, RˆMe).
1
33: H NMR (CDCl3) d 0.81 (d, Jˆ6.6 Hz, 3H), 1.25 (t,
Jˆ7.3 Hz, 3H), 1.27 (d, Jˆ7.0 Hz, 3H), 2.05 (dd, Jˆ9.0 and
14.3 Hz, 1H), 2.21 (m, 1H), 2.44 (dd, Jˆ4.8 and 14.3 Hz,
1H), 2.65 (m, 1H), 4.12 (q, Jˆ7.3 Hz, 1H), 7.15±7.31 (m,
Ã
Ryan, G. Tetrahedron Lett. 1987, 28, 2525; Larcheveque, M.;
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J. Org. Chem. 1991, 56, 2050.
1
5H); 34: H NMR (CDCl3) d 0.97 (d, Jˆ6.6 Hz, 3H), 1.24
(t, Jˆ7.3 Hz, 3H), 1.25 (d, Jˆ7.0 Hz, 3H), 2.05 (dd, Jˆ9.0
and 14.3 Hz, 1H), 2.21 (m, 1H), 2.44 (dd, Jˆ4.8 and
14.3 Hz, 1H), 2.65 (m, 1H), 4.12 (q, Jˆ7.3 Hz, 1H),
7.15±7.31 (m, 5H); IR (neat) 2980, 1730, 1600, 1500,
1450, 1380, 1260, 1170, 1030, 770, 700 cm21; HRMS m/z
Calcd for C14H20O2: 220.1463. Found: 220.1466.
4. (a) Yamamoto, Y.; Nishii, S.; Ibuka, T. J. Chem. Soc., Chem.
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1992, 114, 7652.
Ethyl 3-butyl-4-phenylpentanoate (33 and 34, RˆBu).
1
33: H NMR (CDCl3) d 0.82±0.91 (m, 3H), 1.12±1.40
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(m, 12H), 2.11±2.30 (m, 3H), 2.84 (dq, Jˆ7.0 and 7.0 Hz,
1
1H), 4.08 (q, Jˆ7.1 Hz, 2H), 7.17±7.29 (m, 5H); 34: H
NMR (CDCl3) d 0.82±0.91 (m, 3H), 1.12±1.40 (m, 12H),
2.11±2.30 (m, 3H), 2.77 (dq, Jˆ7.0 and 7.0 Hz, 1H), 4.08
(q, Jˆ7.1 Hz, 2H), 7.17±7.29 (m, 5H); IR (neat) 2980,
2950, 1730, 1460, 1380, 1170, 1040, 770, 700 cm21
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