The 1,4-addition of organometallic reagents to enoates derived from pinanediol

Article abstract of DOI:10.1016/S0957-4166(02)00688-2

The complex-induced, proximity effect-promoted 1,4-addition of RCu·BF₃ and R₂CuLi to enoates derived from (-)-pinanediol leads to adducts with the opposite sense of chirality (up to 98% d.e.).

Full text of DOI:10.1016/S0957-4166(02)00688-2

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2513–2517
The 1,4-addition of organometallic reagents to enoates derived
from pinanediol
Sergio Pinheiro,a,* Se´rgio F. Pedraza,a Moˆnica A. Peralta,a Rafael C. Teixeira,a
Florence M. C. de Farias,a V´ıtor F. Ferreiraa and Paulo R. R. Costab
aInstituto de Qu´ımica, Universidade Federal Fluminense, CEG, Centro, 24210-150, Nitero´i, RJ, Brazil
bLQB, Nu´cleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, CCS, 21941-590, Rio de Janeiro, RJ,
Brazil
Received 19 June 2002; accepted 2 October 2002
Abstract—The complex-induced, proximity effect-promoted 1,4-addition of RCu·BF3 and R2CuLi to enoates derived from
(−)-pinanediol leads to adducts with the opposite sense of chirality (up to 98% d.e.). © 2002 Published by Elsevier Science Ltd.
The stereoselective 1,4-addition of organometallic
Reaction of crotonyl chloride and cinnamoyl chloride
reagents to a,b-unsaturated carbonyl compounds has
with (−)-pinanediol (cat. DMAP, CH2Cl2, Et3N, rt, 24
been widely employed for asymmetric carbonꢀcarbon
bond formation. Although the enantioselective
approaches based on asymmetric catalysis have enjoyed
a surge in popularity,1 the use of chiral auxiliaries
attached to the enoate moiety remains an attractive
method for the diastereoselective 1,4-addition of the
Gilman cuprate R2CuLi, as well as RCu·BF3 and
RMgBr/CuI reagents to chiral enoates.2,3
h)7,8 led to the chiral enoates 1a and 1b in yields of 50
and 65%, respectively (Table 1).9,10 The 1,4-addition
reactions to 1a and 1b were carried out following
typical procedures.4h,11 While the treatment of 1a with
n-BuCu·BF3 (10 equiv.) led to the adduct 2a in high
stereoselectivity (entry 1), the use of n-Bu2CuLi (5
equiv.) gave the opposite isomer 3a in the same selectiv-
ity (entry 2).12,13 The additions of both n-BuCu·BF3
and n-Bu2CuLi to the less reactive enoate 1b produced
a mixture of 2b and 3b with a deleterious effect on the
Some commercially unavailable cyclic diols have been
used as chiral auxiliaries in 1,4-addition of organo-
metallic reagents to enoates (up to 88% d.e.).4 In these
cases the diastereoselectivities can be explained by the
‘complex-induced proximity effect’ (CIPE).5
Some time ago we described chiral auxiliaries derived
from (−)-pinanediol in asymmetric a-alkylation and
aldol reactions.6 Herein, we report the use of this
structurally rigid and readily available diol as a chiral
auxiliary for the CIPE-promoted 1,4-addition of
RCu·BF3 and R2CuLi to the enoates 1 (Scheme 1). The
CIPE arises from chelation between the oxygen at the 2
position of 1 and the metal (M) followed by complexa-
tion of copper with the double bond leading to a
p-complex. The p-facial stereoselection in the conjugate
addition produces the 1,4-adducts 2.
Scheme 1. CIPE-promoted 1,4-addition of R1CuM to the
enoate 1.
* Corresponding author. Fax: 005521-27193349; e-mail: spin@
rmn.uff.br
0957-4166/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0957-4166(02)00688-2

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S. Pinheiro et al. / Tetrahedron: Asymmetry 13 (2002) 2513–2517
Table 1. Stereoselectivities in the conjugate additions to the enoates 1a,b
Entry
1
R
1,4-Additiona
Adducts
Yield (%)b
2:3c
1
2
3
4
5
6
7
a
a
b
b
a
a
b
CH3
CH3
Ph
n-BuCu·BF3, Et2O, −30°C, 3 h
n-Bu2CuLi, Et2O, −30°C, 1 h
n-BuCu·BF3, Et2O, −30°C, 3 h
n-Bu2CuLi, Et2O, −30°C, 1 h
Ph2CuLi, Et2O, −30°C, 1 h
a
a
b
b
c
65
90
50
85
85
75
65
99:1
1:99
73:27
Ph
25:75
CH3
CH3
Ph
30:70d
CH3NO2, DBU, CH3CN, rt, 24 h
CH3NO2, DBU, CH3CN, rt, 72 h
d
e
ND (35% d.e.)e
ND (32% d.e.)e,f
a Reactions were performed using 2 mmol of enoates 1a,b.
b Yields for the purified mixture of adducts 2a–e and 3a–e.
c By the signals for the CꢁO in the 13C NMR spectra unless noted.
d By the signals of the CH3 groups in the 1H NMR spectra at 300 MHz.
e The major isomer, 2 or 3, was not determined.
f % d.e. by the signal of the CH2 adjacent to the CꢁO in the 13C NMR.
stereoselectivity (entries 3 and 4).14 Moderate selectivity
was obtained in the 1,4-addition of Ph2CuLi to 1a and
the mixture of adducts 2c and 3c was not separated
(entry 5).15 According to a previous report in the litera-
ture for addition of Me2CuLi to an enoate derived from
diol,4c the reaction of 1b with both BuCu·BF3 and
Me2CuLi was not successful. The addition of the anion
derived from nitromethane16 to 1a led to mixture of the
adducts 2d and 3d in low stereoselectivity (entry 6)17
and this tendency was also observed for the mixture of
the adducts 2e and 3e (entry 7).18 In both cases the
absolute configurations of the major isomers were not
determined. The low stereoselectivities obtained from
entries 6 and 7 can be attributed to the absence of the
CIPE-promoted 1,4-addition since the anion produced
from CH3NO2 and DBU cannot be coordinated by the
oxygen in position 2 of 1a,b.
diastereomeric ratio, so the selectivity of this reaction
was obtained from the relative intensities of the signals
of the CꢁO groups in quantitative 13C NMR spectrum
of the isomeric mixture using the ‘gated decoupled’
procedure.
The absolute configurations of the newly created cen-
ters in the isomers 2a,b and 3a–c were determined by
hydrolysis (aq. KOH, EtOH, reflux, 3 h) of each iso-
meric mixture to the known (S)-(−)-3-methylheptanoic
acid (75% yield), (S)-(+)-3-phenylbutyric acid (93%
yield) and (R)-(−)-3-phenyl-heptanoic acid (95% yield),
respectively.4c,22
A possible stereochemical pathway to produce the
adducts 2a,b and 3a–c is proposed in Scheme 3. As
n-Bu2CuLi and n-BuCu·BF3 were prepared in Et2O
from n-BuLi and CuI, they can exist as a mixed cyclic
cluster, n-Bu2CuLi·LiI and a six-centered cluster, n-
BuCu·2LiI, respectively.23 The CIPE is proposed to
arise from the coordination of the lithium of these
clusters by the oxygen in the position 2 of the enoates
1a and 1b. In the additions of n-BuCu·BF3 both
enoates 1a and 1b react in their s-trans conformations
leading to the p-complex 6, where the carbonyl group
adopts a syn-periplanar relationship to H3.23,24 Simi-
larly to the 1,4-addition of mixed cuprates having a
dummy ligand,23a,25 we can assume an additional coor-
dination of copper with the oxygen at C-2 and the
CIPE-promoted 1,4-addition would occur mainly from
the Cb-re face of 6 leading to transition state 7. In the
reactions with n-Bu2CuLi and Ph2CuLi the enoates 1a
and 1b react in their s-trans conformations leading to
the p-complex 8.23 In this intermediate the OꢀLi bond
The addition n-Bu2CuLi to the enoate 4, which was
prepared from (+)-isopinocampheol (crotonic acid,
DCC, cat. DMAP, CCl4, rt, 96 h, 35%) gave the adduct
5 with low selectivity (Scheme 2).19–21 This reaction also
showed an opposite sense of chirality in comparison to
the additions of n-Bu2CuLi and Ph2CuLi to 1a,b, show-
ing the importance of the hydroxyl group in 1a,b for
the CIPE-promoted reaction.
The signals in the 1H NMR spectra of the mixture of 2b
and 3b are too close together for determining the
,
length (1.92–2.00 A) allows the formation of a seven-
membered ring (where lithium is coordinated by the
carbonyl oxygen), which adopts an anticlinal relation-
ship to H3. This would allow Cb-si attack leading to the
transition state 9.
Scheme 2. Low stereoselectivity in 1,4-addition to the enoate 4.

S. Pinheiro et al. / Tetrahedron: Asymmetry 13 (2002) 2513–2517
2515
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K. Tetrahedron Lett. 1990, 31, 4751–4754.
5. For examples, see: (a) Mikami, K.; Shimizu, M.; Zhang,
H.-C.; Maryanoff, B. E. Tetrahedron 2001, 57, 2917–2951
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D.; Du, H.; Beak, P. J. Org. Chem. 1998, 63, 2–3 and
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Lett. 1996, 37, 2915–2918.
6. (a) Pinheiro, S.; Gonc¸alves, C. B. S. S.; Lima, M. B.;
Farias, F. M. C. Tetrahedron: Asymmetry 2000, 11, 3495–
3502; (b) Costa, P. R. R.; Ferreira, V. F.; Arau´jo Filho,
H. C.; Pinheiro, S. J. Braz. Chem. Soc. 1996, 7, 67–73.
7. (−)-Pinanediol (97% e.e.) is available from Aldrich Chem.
Co.
Scheme 3. Possible pathways for 1,4-addition to the enoates
1a,b.
In summary, this first report on the use of (−)-pinane-
diol as a chiral auxiliary for 1,4-addition reactions
shows that cuprate reagents such as R2CuLi and
RCu·BF3 lead to an opposite sense of stereochemistry
in the CIPE-promoted reaction, thus allowing the for-
mation of adducts with different configurations simply
by changing the nucleophile.
8. Ireland, R. E.; Norbeck, D. M. J. Am. Chem. Soc. 1985,
107, 3279–3285.
9. Enoate 1a: Pale yellow oil. [h]2D5 +4.9 (c 1, CHCl3). IR
(neat, cm−1): 3600–3300, 3010, 2988, 2914, 1714, 1653,
1441, 1375, 1185, 1014. 1H NMR (300 MHz, CDCl3,
ppm): 7.04 (dq, 15.6 Hz, 6.9 Hz, CH), 5.94 (dq, 15.4 Hz,
1.5 Hz, CH), 5.20 (dd, 9.6 Hz, 5.4 Hz, H-3), 2.60–2.46
(m, H-4b and OH), 2.29–2.17 (m, H-7b), 2.01 (t, 5.7 Hz,
H-5), 1.98–1.94 (m, H-1), 1.89 (dd, 6.8 Hz, 1.5 Hz, CH3),
1.67 (ddd, 14.1 Hz, 5.4 Hz, 2.4 Hz, H-4a), 1.54 (d, 10.5
Acknowledgements
The authors thank FAPERJ for financial support and
are indebted to Dr. Maria Cec´ılia B. V. de Souza
(UFF) for NMR spectra, to Dr. Marcos Eberlin
(Unicamp) for Mass spectra and to Dr. Jose´ O. Previ-
atto (UFRJ) for optical rotation measurements. We are
grateful to CNPq and CAPES for research fellowship.
Hz, H-7a), 1.31 (s, CH3), 1.29 (s, CH3), 1.01 (s, CH3). 13
C
NMR (CDCl3, ppm): 165.5 (C-1%), 145.3 (C-3%), 122.3
(C-2%), 73.8 (C-2), 71.3 (C-3), 54.0 (C-1), 40.2 (C-5), 38.5
(C-6), 34.7 (C-4), 29.7 (CH3), 27.5 (CH3), 28.1 (C-7), 24.2
(CH3), 17.9 (CH3). MS (70 eV, m/z): 221 (10), 152 (25),
126 (61), 109 (42), 99 (91), 83 (28), 71 (73), 69 (100).
Calcd for C14H22O3: 70.56% C, 9.30% H. Found: 70.88%
C, 9.14% H.
References
1. Recent reviews: (a) Williams, D. R.; Kissel, W. S.; Li, J.
J.; Mollins, R. J. Tetrahedron Lett. 2002, 43, 3723–3727
and references cited therein; (b) Woodward, S. Tetra-
hedron 2002, 58, 1017–1050; (c) Krause, N.; Hoffmann-
Roder, A. Synthesis 2001, 171–196; (d) Sibi, M. P.;
Manyem, S. Tetrahedron 2000, 56, 8033–8061; (e)
Feringa, B. L. Acc. Chem. Res. 2000, 33, 346–353.
2. Review: Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992,
92, 771–806.
10. Enoate 1b: White solid, mp 47–48°C. [h]2D5 +5.1 (c 0.33,
CH2Cl2). IR (KBr, cm−1): 3600–3400, 3013, 2978, 2918,
1723, 1706, 1639, 1337, 1311, 1182, 1167, 1143, 711, 684.
1H NMR (300 MHz, CDCl3, ppm): 7.75 (d, 16.2 Hz,
CH); 7.59–7.52 (m, 2Harom.), 7.44–7.37 (m, 3Harom.), 6.53
(d, 15.9 Hz, CH), 5.30 (dd, 9.6 Hz, 5.4 Hz, H-3), 2.63–
2.52 (m, H-4b), 2.34–2.24 (m, H-7b), 2.02 (t, 5.5 Hz,
H-5), 2.20–1.95 (m, H-1), 1.78 (ddd, 13.8 Hz, 5.6 Hz, 2.4
3. For recent examples, see: (a) Pollock, P.; Dambacher, J.;
Anness, R.; Bergdahl, M. Tetrahedron Lett. 2002, 43,

2516
S. Pinheiro et al. / Tetrahedron: Asymmetry 13 (2002) 2513–2517
Hz, H-4a), 1.56 (d, 10.5 Hz, H-7a), 1.38 (s, CH3), 1.32 (s,
of 2b), 34.3 (C-4 of 3b), 28.2 (C-7 of 2b), 28.0 (C-7 of 3b),
29.3 and 22.4 (CH2), 29.4, 27.7 and 24.0 (CH3), 13.8
(CH3). MS (70 eV, m/z): 358 (M+,18), 341 (100), 340 (33),
283 (29), 189 (56), 147 (98), 126 (37), 99 (30), 91 (73).
HREIMS calcd for C24H34O3 (M+): 358.4720. Found:
358.4518.
CH3), 1.05 (s, CH3). 13C NMR (CDCl3, ppm): 166.1(C-
1%), 145.2 (C-3%), 134.1(Carom.), 130.3, 128.8 and 128.0
(Carom.), 117.6 (C-2%); 73.9 (C-2), 71.7 (C-3), 54.0 (C-1),
40.3 (C-5), 38.6 (C-6), 34.5 (C-4), 29.8 (CH3), 28.1 (CH3),
27.7 (C-7), 24.1 (CH3). MS (70 eV, m/z): 300 (M+, 8), 169
(17), 152 (21), 131 (100), 126 (30), 103 (49), 99 (66), 71
(57). HREIMS calcd for C19H24O3 (M+): 300.3520.
Found: 300. 3642.
15. Mixture of adducts 2c and 3c: 40% d.e.: Pale yellow oil.
[h]2D5 +9.8 (c 0.44, CH2Cl2). IR (neat, cm−1): 3612–3290,
3027, 2963, 2923, 2871, 1733, 1452, 1374, 1267, 1164,
1018, 764, 701. 1H NMR (300 MHz, CDCl3, ppm):
7.35–7.18 (m, Harom.), 5.04 (dd, 9.7 Hz, 4.5 Hz, H-3 of
2c), 5.03 (dd, 9.6 Hz, 5.7 Hz, H-3 of 3c), 3.34–3.24 (m,
H-3%), 2.70 (dd, 16.7 Hz, 8.7 Hz, H-2% of 3c), 2.69 (dd,
13.5 Hz, 7.2 Hz, H-2% of 2c), 2.44–2.31 (m, H-4b), 2.22–
2.14 (m, H-7b), 1.95–1.84 (m, H-1 and H-5), 1.51 (ddd,
13.9 Hz, 5.8 Hz, 2.4 Hz, H-4a), 1.41 (d, 10.3 Hz, H-7a of
3c), 1.40 (d, 10.5 Hz, H-7a of 2c), 1.34 (d, 7.2 Hz, CH3 of
3c), 1.32 (d, 6.9 Hz, CH3 of 2c), 1.25 (s, CH3), 1.16 (s,
CH3 of 2c), 1.05 (s, CH3 of 3c), 0.94 (s, CH3). 13C NMR
(CDCl3, ppm): 170.8 (C-1% of 3c), 170.5 (C-1% of 2c), 144.6
(Carom. of 2c), 144.4 (Carom. of 3c), 127.9 (Carom. of 3c),
127.8 (Carom. of 2c), 126.0 (Carom. of 3c), 125.9 (Carom. of
2c), 125.8 (Carom. of 3c), 125.7 (Carom. of 2c), 72.8 (C-2 of
2c), 72.6 (C-2 of 3c), 70.9 (C-3 of 2c), 70.8 (C-3 of 3c),
53.2 (C-1 or C-5 of 2c), 53.1 (C-1 or C-5 of 3c), 42.4 (C-2%
of 3c), 42.0 (C-2% of 3c), 39.5 (C-1 or C-5 of 3c), 39.4 (C-1
or C-5 of 2c), 37.8 (C-6), 36.5 (C-3% of 3c), 35.8 (C-3% of
2c), 33.9 (C-4 of 3c), 33.8 (C-4 of 2c), 28.8 (CH3 of 2c),
28.7 (CH3 of 3c), 27.5 (C-7 of 3c), 27.4 (C-7 of 2c),
27.1(CH3 of 3c), 27.0 (CH3 of 2c), 23.3 (CH3), 21.6
(CH3). Calcd for C20H28O3: 75.92% C, 8.92% H. Found:
75.74% C, 9.44% H.
11. Helmchen, G.; Wegner, G. Tetrahedron Lett. 1985, 26,
6051–6054.
12. Adduct 2a: 98% d.e.: Pale yellow oil. [h]2D5 −1.6 (c 0.64,
CH2Cl2). IR (neat, cm−1): 3620–3360, 2929, 2847, 1748,
1
1458, 1372. H NMR (300 MHz, CDCl3, ppm): 5.16 (dd,
9.6 Hz, 5.7 Hz, H-3); 2.55–2.45 (m, H-4b), 2.39 (dd, 14.6
Hz, 6.3 Hz, H-2%), 2.26–2.20 (m, H-7b), 2.20 (dd, 14.7 Hz,
8.1 Hz, H-2%), 2.01 (t, 5.4 Hz, H-5), 1.97–1.94 (m, H-1),
1.63 (ddd, 13.9 Hz, 5.7 Hz, 2.1 Hz, H-4a), 1.50 (d, 10.5
Hz, H-7a), 1.30 (s, CH3), 1.29 (s, CH3), 1.27–1.23 (m,
H-3%-H-6%), 1.01 (s, CH3), 0.97 (d, 6.6 Hz, CH3), 0.90 (t,
6.3 Hz, CH3). 13C NMR (CDCl3, ppm): 172.2 (C-1%), 73.5
(C-2), 71.3 (C-3), 53.9 (C-1), 41.8 (C-2%), 40.2 (C-5), 38.4
(C-6), 36.2, 28.9 and 22.6 (C-4%-C-6%), 34.6 (C-4), 30.3
(C-3%), 29.6 and 27.7 (CH3), 28.0 (C-7), 24.0 (CH3), 19.5
(CH3), 13.9 (CH3). MS (70 eV, m/z): 169 (15), 152 (30),
135 (32), 127 (67), 126 (57), 109 (41), 108 (33), 99 (100),
93 (50), 85 (37), 71 (57), 69 (38), 57 (85), 55 (41). Calcd
for C18H32O3: 72.94% C, 10.88% H. Found: 73.18% C,
10.54% H.
13. Adduct 3a: 98% d.e.: Pale yellow oil. [h]2D5 +0.9 (c 1.72,
CH2Cl2). IR (neat, cm−1): 3620–3360, 2923, 2851, 1739,
1
1455, 1370. H NMR (300 MHz, CDCl3, ppm): 5.16 (dd,
9.6 Hz, 5.4 Hz, H-3), 2.56–2.45 (m, H,4b), 2.39 (dd, 14.4
Hz, 6.0 Hz, H-2%), 2.29–2.21 (m, H,7b), 2.19 (dd, 14.5 Hz,
8.0 Hz, H-2%), 2.01 (t, 5.7 Hz, H-5), 1.98–1.91 (m, H-1),
1.63 (ddd, 14.1 Hz, 5.6 Hz, 2.3 Hz, H-4a), 1.49 (d, 10.8
Hz, H-7a), 1.31 (s, CH3), 1.29 (s, CH3), 1.32–1.22 (m,
H-3%-H-6%), 1.01 (s, CH3), 0.96 (d, 6.2 Hz, CH3), 0.92 (t,
6.0 Hz, CH3). MS (70 eV, m/z) 296 (M+, 3), 169 (21), 135
(27), 127 (56), 126 (45), 109 (32), 99 (100), 93 (57), 85
(29), 71 (48), 69 (53), 57 (80). HREIMS calcd for
C18H32O3 (M+): 296.3975. Found: 296.4117.
16. Pinto, A. C.; Freita, C. B. L.; Dias, A. G.; Pereira, V. L.
P.; Tinant, B.; Declercq, J.-P.; Costa, P. R. R. Tetra-
hedron: Asymmetry 2002, 13, 1025–1031.
17. Mixture of adducts 2d and 3d: 35% d.e.: Yellow oil. [h]D25
−4.44 (c 11, CH2Cl2). IR (neat, cm−1): 3650–3300, 2922,
1
2871, 1731, 1551, 1454, 1379, 1181, 1011, 901. H NMR
(300 MHz, CDCl3, ppm): 5.17 (dd, 9.6 Hz, 5.4 Hz, H-3),
4.53 (dd, 16.2 Hz, 6.3 Hz, H-4% of the minor isomer), 4.51
(dd, 16.3 Hz, 7.8 Hz, H-4% of the major isomer), 4.41 (dd,
16.2 Hz, 7.8 Hz, H-4% of the major isomer), 4.39 (dd, 16.1
Hz, 6.6 Hz, H-4% of the minor isomer), 2.88–2.77 (m,
H-3%), 2.58–2.41 (m, H-2% and H-4b), 2.30–2.22 (m, H-7b),
2.02–1.95 (m, H-1 and H-5), 1.69 (ddd, 9.1 Hz, 5.0 Hz,
2.3 Hz, H-4a), 1.44 (d, 10.5 Hz, H-7a of the minor
isomer), 1.43 (d, 10.5 Hz, H-7a of the major isomer), 1.34
(s, CH3), 1.29 (s, CH3), 1.14 (d, 6.6 Hz, CH3), 0.99 (s,
CH3). 13C NMR (CDCl3, ppm): 169.9 (C-1% of the minor
isomer), 169.8 (C-1% of the major isomer), 79.5 (C-4% of
the minor isomer), 79.4 (C-4% of the major isomer), 73.3
(C-2), 71.7 (C-3 of the major isomer), 71.6 (C-3 of the
minor isomer), 53.7 (C-1 or C-5 of the major isomer),
53.6 (C-1 or C-5 of the minor isomer), 39.7 (C-1 or C-5
of the minor isomer), 39.6 (C-1 or C-5 of the major
isomer), 38.1 (C-6), 34.0 (C-4), 37.5 (C-2% of the major
isomer), 37.4 (C-2% of the minor isomer), 29.0 (CH3), 28.9
(C-3% of the major isomer), 28.8 (C-3% of the minor
isomer), 27.3 (C-7 of the major isomer), 27.2 (C-7 of the
minor isomer), 27.0 (CH3), 23.4 (CH3), 16.7 (CH3). MS
(70 eV, m/z): 299 (M+, 9), 144 (14), 126 (27), 113 (28), 99
(100), 71 (40), 69 (29). HREIMS calcd for C15H25NO2
(M+): 299.1733. Found: 299.1827.
14. Mixture of adducts 2b and 3b: Pale yellow oil. [h]2D5 +18.6
(c 5.44, CH2Cl2) for 2b:3b=73:27 and [h]2D5 −4.5 (c 1.97,
CH2Cl2) for 2b:3b=25:75. IR (neat, cm−1): 3615–3330,
3021, 2944, 2915, 2862, 1732, 1635, 1448, 1371, 1262,
1161, 773, 698. 1H NMR (300 MHz, CDCl3, ppm):
7.35–7.18 (m, Harom.), 5.00 (dd, 9.4 Hz, 5.6 Hz, H-3 of
3b), 4.99 (dd, 9.5 Hz, 5.9 Hz, H-3 of 2b), 3.13–3.05 (m,
H-3%), 2.76–2.62 (m, H-2%), 2.41–2.31 (m, H-4b), 2.21–2.12
(m, H,7b), 1.94–1.85 (m, H-1 and H-5), 1.72–1.60 (m,
CH2), 1.47 (ddd, 14.2 Hz, 6.1 Hz, 2.5 Hz, H-4a), 1.41 (d,
10.5 Hz, H-7a), 1.36–1.10 (m, 2×CH2), 1.24 (s, CH3), 1.13
(s, CH3 of 3b), 0.96 (s, CH3 of 2b), 0.94 (s, CH3), 0.83 (t,
6.6 Hz, CH3). 13C NMR (CDCl3, ppm): 171.6 (C-1% of
2b), 171.3 (C-1% of 3b), 143.8 (Carom. of 3b), 143.6 (Carom.
of 2b), 128.4 (Carom. of 2b), 128.3 (Carom. of 3b), 127.3
(Carom. of 2b), 127.2 (Carom. of 3b), 126.6 (Carom. of 2b),
126.4 (Carom. of 3b), 73.4 (C-2 of 3b), 73.2 (C-2 of 2b),
71.5 (C-3 of 3b), 71.3 (C-3 of 3b), 53.9 (C-1 of 3b), 53.7
(C-1 of 2b), 42.8 (C-3% of 2b), 42.1 (C-3% of 3b), 42.0 (C-2%
of 2b), 41.4 (C-2% of 3b), 40.2 (C-5 of 2b), 40.1 (C-5 of 3b),
38.4 (C-6), 36.4 (CH2 of 3b), 36.3 (CH2 of 2b), 34.4 (C-4

S. Pinheiro et al. / Tetrahedron: Asymmetry 13 (2002) 2513–2517
2517
18. Mixture of adducts 2e and 3e: 32% d.e.: Yellow oil. [h]D25
−2.63 (c 8, CH2Cl2). IR (neat, cm−1): 3620–3340, 3033,
2988, 2921, 2871, 1734, 1554, 1454, 1379, 1270, 1163,
1083, 766, 701. 1H NMR (300 MHz, CDCl3, ppm):
7.39–7.25 (m, Harom.), 5.07 (dd, 9.8 Hz, 5.1 Hz, H-3 of the
minor isomer), 5.06 (dd, 9.8 Hz, 5.4 Hz, H-3 of the major
isomer), 4.80–4.61 (m, H-4%), 4.08–3.96 (m, H-3%), 2.87
(dd, 8.8 Hz, 7.8 Hz, H-2%), 2.43–2.30 (m, H-4b), 2.50–2.16
(m, H-7b), 1.96–1.87 (m, H-1 and H-5), 1.83 (OH), 1.51
(ddd, 8.8 Hz, 5.2 Hz, 2.4 Hz, H-4a), 1.38 (d, 10.2 Hz,
H-7a of the major isomer), 1.35 (d, 10.5 Hz, H-7a of the
minor isomer), 1.26 (s, CH3), 1.20 (s, CH3 of the minor
isomer), 1.12 (s, CH3 of the major isomer), 0.94 (s, CH3).
13C NMR (CDCl3, ppm): 169.8 (C-1%), 138.0 (Carom. of
the minor isomer), 137.9 (Carom. of the major isomer),
129.0 (CHarom.), 128.2 (Carom. of the major isomer), 128.1
(Carom. of the minor isomer), 127.3 (Carom. of the major
isomer), 127.2 (Carom. of the minor isomer), 79.6 (C-4% of
the minor isomer), 79.4 (C-4% of the major isomer), 73.6
(C-2 of the minor isomer), 73.5 (C-2 of the major isomer),
72.3 (C-3 of the minor isomer), 72.2 (C-3 of the major
isomer), 54.0 (C-1 or C-5 of the minor isomer), 53.9 (C-1
or C-5 of the major isomer), 40.5 (C-3%), 40.2 (C-1 or C-5
of the minor isomer), 40.1 (C-1 or C-5 of the major
isomer), 38.5 (C-6), 38.0 (C-2% of the major isomer), 37.6
(C-2% of the minor isomer), 34.3 (C-4 of the major iso-
mer), 34.2 (C-4 of the minor isomer), 29.4 (CH3), 27.9
(C-7 of the major isomer), 27.8 (C-7 of the minor isomer),
27.6 (CH3 of the major isomer), 27.5 (CH3 of the minor
isomer), 24.0 (CH3). MS (70 eV, m/z): 361 (M+, 4), 282
(11), 135 (40), 130 (39), 126 (30), 99 (100), 71 (31).
HREIMS calcd for C20H27NO5 (M+): 361.1889. Found:
361.2072.
Hz, 4.2 Hz, H-3), 2.65–2.55 (m, H-4b), 2.42–2.33 (m,
H-7b), 2.20–2.10 (m, H-2), 1.97–1.80 (m, H-1 and H-5),
1.88 (dd, 6.9 Hz, 1.8 Hz, CH3), 1.69 (ddd, 14.3 Hz, 4.0
Hz, 3.0 Hz, H-4a), 1.23 (s, CH3), 1.11 (d, 7.5 Hz, CH3),
1.08 (d, 9.6 Hz, H-7a), 0.98 (s, CH3). 13C NMR (CDCl3,
ppm): 166.5 (C-1%), 144.0 (C-3%), 123.3 (C-2%), 78.7 (C-3),
47.4 and 41.2 (C-1 and C-5), 43.7 (C-2), 38.2 (C-6), 35.9
(C-4), 33.4 (C-7), 27.4 (CH3), 23.7 (CH3), 20.4 (CH3),
17.9 (CH3). MS (70 eV, m/z): 222 (M+, 1), 167 (18), 149
(55), 137 (89), 93 (67), 81 (100), 71 (56), 69 (67), 57 (85),
56 (74). HREIMS calcd for C14H22O2 (M+): 222.1619.
Found: 222.1807.
20. Adduct 5: <10% d.e.: Pale yellow oil. [h]2D5 +50 (c 0.02,
CH2Cl2). IR (neat, cm−1): 2972, 2930, 2872, 1732, 1466,
1
1378, 1153, 729, 666. H NMR (300 MHz, CDCl3, ppm):
5.09–5.02 (m, H-3), 2.64–2.54 (m, H-4b), 2.41–2.32 (m,
H-7b), 2.31–2.20 (m, H-2%), 2.18–2.06 (m, H-2), 1.70–1.50
(m, H-1, H-4a and H-5), 1.48–1.40 (m, H-3%), 1.35–1.20
(m, H-4%-H-6%), 1.23 (s, CH3), 1.05 (d, 9.9 Hz, H-7a), 0.97
(s, CH3), 0.94 (d, 6.6 Hz, CH3 of 3S-isomer), 0.93 (d, 6.5
Hz, CH3 of 3R-isomer), 0.91 (t, 6.9 Hz, CH3 of 3S-iso-
mer), 0.89 (t, 6.6 Hz, CH3 of 3R-isomer). MS (70 eV,
m/z): 280 (M+, 2), 185 (41), 137 (100), 136 (81), 127 (64),
121 (37). HREIMS calcd for C18H32O2 (M+): 280.2402.
Found: 280.2560.
21. The stereoselectivity was determined from the relative
intensities of the signals due to the methyl groups at 0.91
1
and 0.89 ppm in the crude H NMR spectra.
22. Oppolzer, W.; Lo¨her, H. J. Helv. Chim. Acta 1981, 64,
2808–2811.
23. For reviews on organocuprates, see: (a) Nakamura, E.;
Mori, S. Angew. Chem., Int. Ed. 2000, 39, 3750–3771; (b)
Woodward, S. Chem. Soc. Rev. 2000, 29, 393–401.
24. Pinheiro, S.; Pedraza, S. F.; Peralta, M. A.; Carvalho, E.
M.; Farias, F. M. C.; Ferreira, V. F. J. Carbohydr. Chem.
1998, 17, 901–913 and references cited therein.
25. Nakamura, E.; Yamanaka, M. J. Am. Chem. Soc. 1999,
121, 8941–8942.
19. Enoate 4: Pale yellow oil. [h]2D5 +34.7 (c 0.62, CH2Cl2). IR
(neat, cm−1): 2911, 1718, 1659, 1447, 1375, 1307, 1265,
1183, 1155, 1101, 1008, 969, 838, 666. 1H NMR (300
MHz, CDCl3, ppm): 6.96 (dq, 15.5 Hz, 6.8 Hz, H-3%),
5.86 (dq, 15.5 Hz, 1.5 Hz, H-2%), 5.10 (ddd, 9.5 Hz, 5.0