A pinene-based chiral auxiliary for α-alkylation and aldol reactions: An unexpected effect of the base on the stereoselectivity

Article abstract of DOI:10.1016/S0957-4166(00)00301-3

While the use of LDA as the base in the kinetic deprotonation step of the pinene-based ester 3 led to moderate diastereoselectivities in α-alkylation and aldol reactions, the use of LICA and LTMP resulted in a reduction in the anti/syn ratios and π-facial selectivities. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00301-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 3495–3502
A pinene-based chiral auxiliary for a-alkylation and aldol
reactions: an unexpected effect of the base on the
stereoselectivity
Sergio Pinheiro,* Clara B. S. S. Gonc¸alves, Marcelo B. de Lima and
Florence M. C. de Farias
Instituto de Qu´ımica, GQO, Universidade Federal Fluminense, CEG, Centro, 24210-150 Nitero´i, RJ, Brazil
Received 2 June 2000; accepted 21 July 2000
Abstract
While the use of LDA as the base in the kinetic deprotonation step of the pinene-based ester 3 led to
moderate diastereoselectivities in a-alkylation and aldol reactions, the use of LICA and LTMP resulted
in a reduction in the anti/syn ratios and p-facial selectivities. © 2000 Elsevier Science Ltd. All rights
reserved.
1. Introduction
Stereoselective aldol addition reactions have been the subject of extensive investigations over
the last few decades because of their wide applicability to the syntheses of complex molecules.
Although the enantioselective approaches have been shown to be attractive,1 the use of chiral
auxiliaries attached to the enolate moiety remains the most common and predictable method for
effecting asymmetric aldol reactions. However, while the preparation of syn-aldols can be
readily achieved,2 approaches for the direct elaboration of anti-aldols from carboxylic esters
have met with limited success3 and efforts are currently in progress to explore the synthetic
methods for this counterpart employing covalently bound chiral auxiliaries derived from
available chiral pool compounds.
In kinetic aldol reactions from carboxylic esters attached to chiral auxiliaries, the similar bases
LDA and LICA have enjoyed widespread acceptance and are equally used in the stereoselective
generation of both E-lithium enolates4 and anti-aldol adducts.3a–k Improvements in the anti/syn
ratios in aldol reactions are achieved by employing either silyl ketene acetals instead of lithium
enolates3e–k or the more sterically hindered amide LTMP in the deprotonation step.4
* Corresponding author. E-mail: spin@rmn.uff.br
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00301-3

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S. Pinheiro et al. / Tetrahedron: Asymmetry 11 (2000) 3495–3502
The application of chiral auxiliaries and reagents derived from a-pinene in asymmetric
synthesis is well known.5 However, this natural and readily available starting material has been
scarcely employed to build chiral auxiliaries for aldol reactions.6 Previously, we described
(−)-pinanediol as a chiral auxiliary in asymmetric a-alkylations of ester enolates in satisfactory
selectivity but in low yields.7 Herein we report its benzyl derivative at position 3 as a chiral
auxiliary in kinetic a-alkylations and aldol reactions, as well as the deleterious effect on the
stereoselectivities of these reactions by the use of LICA and LTMP as bases instead of LDA in
the kinetic deprotonation step.
2. Results and discussion
8
The hydroxylation of (−)-a-pinene 1 in the presence of catalytic OsO4 was followed by
reaction with benzyl chloride to afford the chiral auxiliary 2 in a multigram scale procedure
(Scheme 1). The subsequent esterification using propionyl chloride in the presence of AgCN9
provided the propionate 3.
Scheme 1. (a) See Ref. 8; (b) NaH, DMSO then benzyl chloride, rt, 90 min, 92%; (c) EtCOCl, AgCN, benzene, reflux,
90 min, 78%; (d) see Table 1; (e) LiAlH4, THF, rt, 2 h; (f) see Table 2
Kinetic aldol reactions of ester 3 with benzaldehyde were carried out following typical
procedures already described in the literature (Table 1). The aldolization of 3 using LDA in
THF at −78°C10 produced compound 4 as the main isomer in a characteristic anti/syn ratio and
satisfactory p-facial diastereoselectivity (entry 1). As expected,11 the enolization performed in the
presence of HMPA was less selective (entry 2). Surprisingly the use of LICA3d and LTMP4 as
bases instead of LDA (entries 3 and 4) led to somewhat smaller anti/syn and 4/5 ratios.
Interestingly the reaction conducted by means of the corresponding silyl ketene acetal (entry
5)3e–k did not lead to an increased anti/syn ratio in comparison with the enolization in LDA.
Attempts at increasing the p-facial diastereoselectivities in the presence of LiBr (entry 6)12 or
Et3N (entry 7)13 as additives were not successful and this latter protocol showed a deleterious
effect on the anti/syn ratio.

S. Pinheiro et al. / Tetrahedron: Asymmetry 11 (2000) 3495–3502
3497
Table 1
Stereoselectivities in aldol reactions of propionate 3 with benzaldehyde
a
Entry
Aldol
%
Anti/synb
4/5b
1
2
3
4
5
6
7
LDA, THF, −78°C then PhCHO
LDA, THF, –23% HMPA, −78°C then PhCHO
LICA, THF, −78°C then PhCHO
80
74
80
78
70
90
81
80/20
60/40
74/26
70/30
80/20
80/20
64/36
87/13
69/31
75/25
80/20
70/30
29/71
77/23
LTMP, THF, −78°C then PhCHO
LDA, THF, −78°C then TBDMSCl, HMPA and PhCHO, TiCl4
LDA, THF, −78°C then LiBr and PhCHO
LDA, THF, −78°C then Et3N and PhCHO
a For the mixture of anti- and syn-aldols.
1
b Ratios by H NMR (300 MHz) from the signals of H8%.
Both the anti/syn and 4/5 ratios were determined from the signals due to the H8% hydrogens
1
in the H NMR spectra at 300 MHz of this crude mixture. A syn-aldol minor isomer, whose
stereochemistry was not determined, was separated from the mixture of anti-aldols 4 and 5 by
flash chromatography on silica gel, allowing the signals of each isomer to be assigned in the
NMR spectra. The absolute configurations of the newly created asymmetric centers in the main
isomer 4 were determined by reduction of the mixture obtained from entry 1 with LiAlH4 to the
known14 diol 6, which was also produced in an anti/syn=80/20 ratio.15 The chiral auxiliary 2
was quantitatively recovered unchanged during the purification of 6 by flash chromatography on
silica gel (50% EtOAc in hexane as eluant).
Due to the drop in the stereoselectivity using LICA, we decided to investigate the reactions of
3 with allyl and benzyl bromides (Table 2). The a-alkylations of 3 using LDA in THF at −78°C9
leading to compounds (2%S)-7a,b (entries 1 and 2) occurred with lower p-facial selectivities than
in the aldolization of 3 with this base (see entry 1 in Table 1). Similar to the aldol reaction, the
use of LICA as base16 in the deprotonation step led to a significant drop in the d.e. (entries 3
and 4) and the stereoselectivity of the reaction conducted in the presence of HMPA was almost
Table 2
Stereoselectivities in a-alkylation reactions of propionate 3 in THF at −78°C
a
Entry
Base
RꢀBr
7
%
% d.e.b
1
2
3
4
5
6
7
LDA
LDA
H2CꢁCHCH2Br
PhCH2Br
H2CꢁCHCH2Br
PhCH2Br
H2CꢁCHCH2Br
H2CꢁCHCH2Br
H2CꢁCHCH2Br
a
b
a
b
a
a
a
52
57
50
55
60
41
53
21
08
–
LICA
LICA
LDAc
LDAd
LDAe
54
NRf
NRf
–
a For the mixture of (2%S)-7 and (2%R)-7.
b Determined by quantitative 13C NMR from the signals of the carbonyl.
c THF–23% HMPA was used as the solvent.
d In the presence of LiBr as the additive.12
e Et3N was used as the additive.13
f
No reaction occurred even with an excess of the additives.

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nonexistent (entry 5). Interestingly, in the presence of LiBr12 and Et3N13 (entries 6 and 7) no
reaction occurred and ester 3 was unchanged and recovered completely.
1
Since all the signals in the crude H NMR spectra of the mixtures of (2%S)-7a,b and their
opposite isomers (2%R)-7a,b are too close together, the diastereoselectivities were determined
from the relative intensities of the signals of the carbonyl groups in quantitative 13C NMR
spectra of the mixture of these isomers using the ‘gated decoupled’ procedure. The reductions9
of the major isomers (2%S)-7a,b obtained from entries 1 and 4 gave the unchanged chiral
auxiliary 1 quantitatively along with the known (S)-alcohols (S)-8a,b.17,18
Although the enolate geometries in the kinetic deprotonation of propionate 3 with LDA,
LICA and LTMP were not determined, the formation of the main isomers 4 and (2%S)-7 from
enolization of 3 using LDA in THF can be explained by the widely accepted3a–d initial formation
of the E-enolate intermediate, with the aldolization step occurring by a Zimmerman–Traxler
transition state.
The unexpected striking drop in the anti/syn ratios and the p-facial stereoselectivities in the
a-alkylation and aldol reactions from ester 3 when using LICA and LTMP instead of LDA is,
to the best of our knowledge, without precedent. However, the results obtained in this first
report on the use of alcohol 2 as a chiral auxiliary in these reactions show that the chiral moiety
of pinenes is promising and can be further exploited in the chemistry of enolates.
3. Experimental
3.1. General
The (−)-a-pinene (81% e.e.) was purchased from Aldrich Chemical Co. Melting points were
determined with a Thomas–Hoover apparatus and are uncorrected. Optical rotations were
recorded with a Perkin–Elmer 24B polarimeter. Flash chromatography was performed on silica
gel 230–400 mesh (Merck). Infrared spectra were recorded with a Perkin–Elmer 1420 spec-
trophotometer. High-resolution electron-impact mass spectra (HREIMS) and low-resolution
electron-impact mass spectra (LREIMS) were measured on a V.G. Auto Spec. Q spectrometer.
NMR spectra were recorded with a Varian VXR (300 MHz) for solutions in CDCl3. Elemental
analyses were determined with a Carlo Erba 1104 apparatus.
3.2. (1R,2R,3S,5R)-3-O-Benzylpinanediol 2
DMSO (31.2 mL) was added dropwise to 50% sodium hydride in mineral oil (3.384 g) washed
previously with hexane (3×20 mL) and the mixture was stirred under a nitrogen atmosphere for
30 min. A solution of (−)-pinanediol (8.0 g, 47 mmol)8 in DMSO (20 mL) was added dropwise
and the mixture was stirred at room temperature for 10 h. Benzyl chloride (8.88 g, 69.42 mmol)
was added to this solution over a period of 30 min and the resulting mixture was stirred for an
additional hour, diluted with cold water (20 mL) and partitioned with hexane (3×40 mL). The
combined organic layers were washed with brine (3×40 mL) and dried over Na2SO4. Solvent
removal in vacuo was followed by flash chromatography on silica gel using 5% EtOAc in hexane
as eluant to give 2 as a colorless oil (11.24 g, 92% yield). [h]2D5 +33.4 (c 5.26; CH2Cl2). IR (neat,
cm−1): 3610–3320; 3074; 2982; 2860; 1705; 1691; 1521; 1484; 1462; 1365; 1289; 1048; 1032; 754;
1
712. H NMR (CDCl3, 300 MHz, ppm): 7.38–7.29 (m, H13–H15); 4.70 (d, 11.7 Hz, H11); 4.61

S. Pinheiro et al. / Tetrahedron: Asymmetry 11 (2000) 3495–3502
3499
(d, 11.7 Hz, H11); 3.75 (dd, 9.0 Hz, 5.1 Hz, H3); 2.45–2.34 (m, H4); 2.27–2.14 (m, H7); 1.97 (t,
5.7 Hz, H1); 1.95–1.89 (m, H5); 1.78 (ddd, 13.6 Hz, 5.0 Hz, 2.4 Hz, H4); 1.45 (d, 10.5 Hz, H7);
1.27 (s, CH3); 1.26 (s, CH3); 0.89 (s, CH3). 13C NMR (CDCl3, 75 MHz, ppm): 137.8 (s, C12);
128.3, 127.7 and 127.6 (d, C13–C15); 76.1 (d, C3); 73.2 (s, C2); 72.0 (t, C11); 53.7 (d, C1); 40.2
(d, C5); 38.2 (s, C6); 35.1 (t, C4); 30.6 (q, CH3); 28.1 (t, C7); 27.7 (q, CH3); 24.2 (q, CH3).
LREIMS (70 eV, m/z): 151 (34); 126 (57); 111 (39); 99 (46); 91 (100); 83 (34); 71 (82). Calcd for
C17H24O2: 78.42% C, 9.3% H. Found: 78.38% C, 9.28% H.
3.3. (1R,2R,3S,5R)-3-O-Benzylpinanediol propionate 3
A solution of the alcohol 2 (2.24 g, 8.62 mmol) in dry benzene (14 mL) was added dropwise
to freshly prepared9 AgCN (2.68 g, 20 mmol) under a nitrogen atmosphere. Propionyl chloride
(1.48 mL, 16.92 mmol) was added dropwise and the resulting solution was refluxed for 90 min
and allowed to reach room temperature. The mixture was filtered through silica gel and 10%
aqueous NaHCO3 (80 mL) was added to the filtrate. This solution was partitioned with ethyl
acetate (3×100 mL) and dried over anhydrous Na2SO4. Solvent removal in vacuo was followed
by flash chromatography on silica gel using 5% EtOAc in hexane as eluant to give 3 as a pale
yellow oil (2.12 g, 78% yield). [h]D25 +8.0 (c 3.26; CH2Cl2). IR (neat, cm−1): 3058; 3023; 2947;
1
2871; 1746; 1451; 1355; 1193; 1138; 1076; 736; 697. H NMR (CDCl3, 300 MHz, ppm):
7.29–7.19 (m, H13–H15); 4.66 (d, 11.7 Hz, H11); 4.60 (d, 11.7 Hz, H11); 3.87 (dd, 8.7 Hz, 6.2
Hz, H3); 2.74 (t, 6.0 Hz, H1); 2.31–2.22 (m, H4); 2.21 (q, 7.5 Hz, H2%); 2.18–2.12 (m, H7);
1.98–1.93 (m, H5); 1.77 (ddd, 13.7 Hz, 4.9 Hz, 2.4 Hz, H4); 1.61 (s, CH3); 1.38 (d, 10.2 Hz, H7);
1.20 (s, CH3); 0.98 (t, 7.5 Hz, H3%); 0.82 (s, CH3). 13C NMR (CDCl3, 75 MHz, ppm): 173.6 (s,
CꢁO); 138.7 (s, C12); 128.2, 127.6 and 127.4 (d, C13–C15); 85.2 (s, C2); 77.3 (d, C3); 72.2 (t,
C11); 52.1 (d, C1); 40.0 (d, C5); 38.4 (s, C6); 35.0 (t, C4); 28.8 (t, C2%); 28.1 (t, C7); 27.6 (q,
CH3); 26.4 (q, CH3); 23.8 (q, CH3); 9.1 (q, C3%). LREIMS (70 eV, m/z): 105 (100); 91 (84); 77
(24); 57 (65). Calcd for C20H28O3: 75.92% C, 8.92% H. Found: 75.88% C, 8.94% H.
3.4. Chiral hydroxyesters 4 and 5: aldol in LDA, THF
A solution of the ester 3 (0.5 g, 1.582 mmol) in dry THF (3 mL) was added dropwise to a cold
(−78°C) 1 M solution of LDA in THF (1.9 mL) under a nitrogen atmosphere and the resulting
yellowish solution was stirred for 45 min. A solution of benzaldehyde (0.18 mL, 1.741 mmol) in
THF (1 mL) was added dropwise and the mixture was stirred at −78°C for 5 min. The reaction
was quenched by the addition of sat. NH4Cl (5 mL) and the mixture was allowed to reach room
temperature. The mixture was diluted in ethyl acetate (10 mL) and washed with 10% aqueous
NaHCO3 (10 mL). The phases were separated and the aqueous layer was extracted with ethyl
acetate (3×20 mL). The combined organic layers were washed with brine (3×20 mL) and dried
over anhydrous Na2SO4. Solvent removal in vacuo was followed by flash chromatography on
silica gel using 5% EtOAc in hexane as eluant to give a mixture of 4 and 5 along with a syn-aldol
(anti/syn=80/20; 74% d.e.) as a white solid (0.530 g, 80% yield). Mp 82–86°C. [h]2D5 +13.3 (c
1.15; CH2Cl2).
Anti-aldols 4 and 5. IR (KBr, cm−1): 3558; 3042; 2996; 2910; 1741; 1454; 1278; 1143; 766; 712.
1H NMR (CDCl3, 300 MHz, ppm): 7.42–7.21 (m, H5%–H7% and H13–H15); 4.74 (d, 11.8 Hz,
H11); 4.64 (d, 9.3 Hz, H3%); 4.60 (s, OH); 4.56 (d, 11.8 Hz, H11); 3.84 (dd, 9.0 Hz, 6.6 Hz, H3
of 5); 3.83 (dd, 9.0 Hz, 6.6 Hz, H3 of 4); 2.85–2.77 (m, H2%); 2.74 (t, 6.0 Hz, H1 of 4); 2.69 (t,

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S. Pinheiro et al. / Tetrahedron: Asymmetry 11 (2000) 3495–3502
6.0 Hz, H1 of 5); 2.43–2.33 (m, H4); 2.24–2.15 (m, H7); 2.02–1.99 (m, H5); 1.86 (ddd, 13.7 Hz,
5.7 Hz, 2.4 Hz, H4); 1.40 (s, CH3); 1.38 (d, 11.1 Hz, H7); 1.26 (s, CH3 of 4); 1.24 (s, CH3 of 5);
1.16 (d, 7.5 Hz, H8% of 4); 1.02 (d, 7.2 Hz, H8% of 5); 0.88 (s, CH3 of 5); 0.86 (s, CH3 of 4). 13C
NMR (CDCl3, 75 MHz, ppm): 173.8 (s, CꢁO of 5); 173.0 (s, CꢁO of 4); 142.3 and 137.5 (s, C4%
and C12); 128.4, 128.3, 128.0, 127.9, 127.2 and 126.2 (d, C5%–C7% and C13–C15 of 4); 128.2,
128.1, 128.0, 127.8, 127.3 and 126.3 (d, C5%–C7% and C13–C15 of 5); 86.4 (s, C2 of 5); 86.0 (s,
C2 of 4); 76.2 (d, C3 of 5); 75.8 (d, C3 of 4); 75.6 (d, C3% of 5); 75.1 (d, C3% of 4); 71.9 (t, C11
of 5); 71.5 (t, C11 of 4); 51.7 (d, C1); 48.2 (d, C2% of 4); 47.4 (d, C2% of 5); 40.1 (d, C5); 38.3 (s,
C6); 34.5 (d, C4); 28.1 (q, CH3); 27.9 (t, C7 of 4); 27.5 (t, C7 of 5); 24.8 (q, CH3); 23.8 (q, CH3);
15.2 (q, C8% of 4); 14.6 (q, C8% of 5). LREIMS (70 eV, m/z): 107 (31); 91 (100); 83 (54); 69 (70);
57 (89). Calcd for C27H34O4: 76.75% C, 8.11% H. Found: 76.86% C, 7.88% H.
1
Syn-aldol. H NMR (CDCl3, 300 MHz, ppm): 7.40–7.23 (m, H5%–H7% and H13–H15); 5.13 (s,
OH); 4.74 (d, 12.3 Hz, H11); 4.58 (d, 12.3 Hz, H11); 4.45 (d, 2.4 Hz, H3%); 3.85 (dd, 8.9 Hz, 6.6
Hz, H3); 2.80 (t, 6.0 Hz, H1); 2.63 (dq, 7.2 Hz, 2.4 Hz, H2%); 2.44–2.34 (m, H4); 2.23–2.12 (m,
H7); 2.04–1.96 (m, H5); 1.87 (ddd, 13.5 Hz, 6.3 Hz, 2.1 Hz, H4); 1.59 (s, CH3); 1.37 (d, 10.5 Hz,
H7); 1.27 (s, CH3); 1.05 (d, 7.2 Hz, H8%); 0.89 (s, CH3). 13C NMR (CDCl3, 75 MHz, ppm): 173.3
(s, CꢁO); 141.3 and 137.7 (s, C4% and C12); 128.4, 128.3, 128.1, 127.8, 126.3 and 126.0 (d,
C5%–C7% and C13–C15); 86.1 (s, C2); 76.0 (d, C3); 75.1 (d, C3%); 71.6 (t, C11); 51.8 (d, C1); 47.5
(d, C2%); 39.9 (d, C5); 38.2 (s, C6); 34.7 (d, C4); 28.0 (q, CH3); 27.8 (t, C7); 25.6 (q, CH3); 25.2
(q, CH3); 10.5 (q, C8%).
3.5. Chiral esters 7a,b: alkylation in LDA, THF
A solution of the ester 3 (0.4 g, 1.264 mmol) in dry THF (2.4 mL) was added dropwise to a
cold (−78°C) 1 M solution of LDA in dry THF (0.7 mL) under a nitrogen atmosphere and the
resulting yellowish solution was stirred for 45 min. A 1 M solution of the appropriate alkyl
bromide (3.0 equiv.) in dry THF was added dropwise and the mixture was stirred for 6 h.
Saturated aqueous NH4Cl (4 mL) was added and the mixture was allowed to reach room
temperature. The mixture was diluted in ethyl acetate (10 mL) and washed with 10% aqueous
NaHCO3 (10 mL). The phases were separated and the aqueous layer was extracted with ethyl
acetate (3×20 mL). The combined organic layers were washed with brine (3×20 mL) and dried
over anhydrous Na2SO4. Solvent removal in vacuo was followed by flash chromatography on
silica gel using 5% EtOAc in hexane as eluant to give 7a,b as colorless oils in the yields shown
in Table 2.
Ester 7a (60% d.e.). [h]2D5 +10.5 (c 3.15; CH2Cl2). IR (neat, cm−1): 3058; 3020; 2962; 2921; 2863;
1
1741; 1638; 1492; 1448; 1371; 1355; 1183; 1142; 1115; 910; 732; 693. H NMR (CDCl3, 300
MHz, ppm): 7.41–7.25 (m, H13–H15); 5.82–5.67 (m, H4%); 5.07–4.95 (m, H5%); 4.68 (d, 11.7 Hz,
H11 of (2%R)-7a); 4.67 (d, 11.7 Hz, H11 of (2%S)-7a); 4.60 (d, 11.7 Hz, H11 of (2%S)-7a and
(2%R)-7a); 3.88 (dd, 8.9 Hz, 5.7 Hz, H3); 2.79 (t, 5.7 Hz, H1 of (2%R)-7a); 2.76 (t, 5.7 Hz, H1 of
(2%S)-7a); 2.54–2.35 (m, H2% and H3%); 2.20–2.06 (m, H4 and H7); 1.99–1.93 (m, H5); 1.86 (ddd,
13.7 Hz, 5.7 Hz, 2.4 Hz, H4); 1.69 (s, CH3); 1.43 (d, 10.2 Hz, H7 of (2%S)-7a); 1.42 (d, 10.2 Hz,
H7 of (2%R)-7a); 1.27 (s, CH3); 1.10 (d, 6.9 Hz, H6% of (2%S)-7a); 1.09 (d, 6.9 Hz, H6% of (2%R)-7a);
0.93 (s, CH3 of (2%S)-7a); 0.88 (s, CH3 of (2%R)-7a). 13C NMR (CDCl3, 50 MHz, ppm): 175.1 (s,
CꢁO of (2%R)-7a); 175.0 (s, CꢁO of (2%S)-7a); 138.7 (s, C12 of (2%R)-7a); 135.9 (s, C12 of
(2%S)-7a); 128.1, 127.5 and 127.4 (d, C13–C15 of (2%S)-7a); 128.0, 127.3 and 127.2 (d, C13–C15
of (2%R)-7a); 116.4 (t, C5% of (2%R)-7a); 116.3 (t, C5% of (2%S)-7a); 85.3 (s, C2 of (2%R)-7a); 85.2

S. Pinheiro et al. / Tetrahedron: Asymmetry 11 (2000) 3495–3502
3501
(s, C2 of (2%S)-7a); 77.5 (d, C3); 72.2 (t, C11 of (2%S)-7a); 67.8 (t, C11 of (2%R)-7a); 51.9 (d, C1
of (2%S)-7a); 49.1 (d, C1 of (2%R)-7a); 40.2 (d, C2% of (2%S)-7a); 40.0 (d, C2% of (2%R)-7a); 39.9 (d,
C5); 38.4 (s, C6); 37.8 (t, C3% of (2%R)-7a); 37.5 (t, C3% of (2%S)-7a); 35.2 (t, C4); 28.0 (q, CH3);
27.6 (t, C7); 26.4 (q, CH3); 25.5 (q, CH3 of (2%R)-7a); 23.8 (q, CH3); 16.6 (q, C6% of (2%S)-7a);
16.4 (q, C6% of (2%R)-7a). LREIMS (70 eV, m/z): 356 (M+, 3); 160 (22); 151 (26); 108 (27); 105
(25); 91 (100); 69 (71). HREIMS calcd for C23H32O3 (M+): 356.456. Found: 356.4594.
Ester 7b (41% d.e.). [h]2D5 +7.3 (c 3.36; CH2Cl2). IR (neat, cm−1): 3080; 3057; 3021; 2962; 2918;
1
2863; 1743; 1493; 1449; 1372; 1357; 1271; 1149; 1116; 731; 696. H NMR (CDCl3, 300 MHz,
ppm): 7.41–7.10 (m, H5%–H7% and H13–H15); 4.65 (d, 11.7 Hz, H11 of (2%S)-7b); 4.59 (d, 11.7
Hz, H11 of (2%S)-7b); 4.51 (d, 11.7 Hz, H11 of (2%R)-7b); 4.43 (d, 11.7 Hz, H11 of (2%R)-7b); 3.87
(dd, 9.0 Hz, 6.0 Hz, H3 of (2%S)-7b); 3.82 (dd, 9.0 Hz, 6.0 Hz, H3 of (2%R)-7b); 3.05 (dd, 13.2
Hz, 7.2 Hz, H3% of (2%S)-7b); 2.99 (dd, 13.2 Hz, 7.2 Hz, H3% of (2%R)-7b); 2.79 (t, 5.7 Hz, H1 of
(2%R)-7b); 2.75–2.63 (m, H2%); 2.70 (t, 5.7 Hz, H1 of (2%S)-7b); 2.56 (dd, 13.2 Hz, 7.2 Hz, H3% of
(2%S)-7b); 2.55 (dd, 13.2 Hz, 7.2 Hz, H3% of (2%R)-7b); 2.46–2.33 (m, H4); 2.18–2.08 (m, H7 of
(2%R)-7b); 2.08–2.01 (m, H7 of (2%S)-7b); 1.96–1.89 (m, H5); 1.88–1.79 (m, H4); 1.66 (s, CH3 of
(2%S)-7b); 1.58 (s, CH3 of (2%R)-7b); 1.37 (d, 10.2 Hz, H7 of (2%R)-7b); 1.30 (d, 10.2 Hz, H7 of
(2%S)-7b); 1.29 (s, CH3 of (2%R)-7b); 1.25 (s, CH3 of (2%S)-7b); 1.09 (d, 6.6 Hz, H8% of (2%R)-7b);
1.08 (d, 6.6 Hz, H8% of (2%S)-7b); 0.91 (s, CH3 of (2%S)-7b); 0.90 (s, CH3 of (2%R)-7b). 13C NMR
(CDCl3, 75 MHz, ppm): 175.1 (s, CꢁO of (2%R)-7b); 174.9 (s, CꢁO of (2%S)-7b); 139.7 and 138.7
(s, C4% and C12); 128.9, 128.2, 127.9, 127.4, 127.3 and 125.9 (d, C5%–C7% and C13–C15 of
(2%S)-7b); 129.0, 128.1, 128.0, 127.4, 127.2 and 126.0 (d, C5%–C7% and C13–C15 of (2%R)-7b); 85.3
(s, C2 of (2%S)-7b); 85.2 (s, C2 of (2%R)-7b); 77.5 (d, C3 of (2%S)-7b); 77.1 (d, C3 of (2%R)-7b); 72.2
(t, C11 of (2%S)-7b); 72.1(t, C11 of (2%R)-7b); 51.9 (d, C1 of (2%S)-7b); 51.8 (d, C1 of (2%R)-7b);
42.5 (d, C2% of (2%R)-7b); 42.3 (d, C2% of (2%S)-7b); 39.9 (d, C5); 39.8 (t, C3% of (2%R)-7b); 39.3 (t,
C3% of (2%S)-7b); 38.3 (s, C6); 35.3 (t, C4 of (2%R)-7b); 35.2 (t, C4 of (2%S)-7b); 28.0 (q, CH3 of
(2%S)-7b); 27.9 (q, CH3 of (2%R)-7b); 27.4 (t, C7 of (2%S)-7b); 27.3 (t, C7 of (2%R)-7b); 26.5 (q,
CH3 of (2%R)-7b); 26.3 (q, CH3 of (2%S)-7b); 23.8 (q, CH3); 16.9 (d, C8% of (2%R)-7b); 16.8 (d, C8%
of (2%S)-7b). LREIMS (70 eV, m/z); 406 (M+, 2); 243 (22); 199 (24); 160 (32); 151 (41); 109 (36);
97 (70); 91 (67); 69 (100). HREIMS calcd for C27H34O3 (M+): 406.512. Found: 406.5480.
Acknowledgements
The authors would like to thank the PADCT-CNPq (National Council of Research of Brazil)
for financial support and are indebted to Dr. Maria Cec´ılia B. V. de Souza (UFF) for the 300
MHz NMR spectra, to Dr. Gilberto A. Romeiro (UFF) for the mass spectra and to Dr. Jose´
O. Previatto (UFRJ) for the optical rotation measurements.
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18. All spectral data are in agreement with the literature. For (S)-7a (60% e.e.): [h]2D5 −1.2 (c 1.5; C6H6). Lit.17a for
(S)-7a (99% e.e.): [h]2D5 −2.1 (c 1.5; C6H6). For (S)-7b (21% e.e.): [h]2D5 −2.4 (c 1.3; C6H6). Lit.17b for (R)-7b (98%
e.e.): [h]2D5 +11 (c 1.15; C6H6).
.