Regio- and diastereoselective boron-mediated aldol reactions of chiral α,β,γ,δ-unsaturated N-acyloxazolidinones

Article abstract of DOI:10.1016/S0957-4166(98)00459-5

Chiral N-acyloxazolidinones derived from conjugated dienoic acids undergo boron-mediated aldol condensation in good yield and with high regio- and diastereoselectivity to provide a convenient method for introducing a 1,3-diene subunit. The condensation of

Full text of DOI:10.1016/S0957-4166(98)00459-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 4313–4324
Regio- and diastereoselective boron-mediated aldol reactions of
chiral α,β,γ,δ-unsaturated N-acyloxazolidinones
James M. Takacs,∗ Mohamad R. Jaber, Benjamin J. Swanson and Steven J. Mehrman
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA
Received 17 September 1998; accepted 27 October 1998
Abstract
Chiral N-acyloxazolidinones derived from conjugated dienoic acids undergo boron-mediated aldol condensation
in good yield and with high regio- and diastereoselectivity to provide a convenient method for introducing a 1,3-
diene subunit. The condensation of a homologous triene derivative is also described. © 1998 Elsevier Science Ltd.
All rights reserved.
In the course of other studies, we require ready access to substrates bearing one or more 1,3-diene
subunits within their structures.1 While there are a number of reliable methods for the construction of
conjugated dienes,2 the development of new methods, particularly one applicable to enantioselective
synthesis, still presents a timely challenge.3,4
Evans and co-workers reported the regio- and diastereoselective boron-mediated aldol condensation of
crotonic acid derived N-acyloxazolidinones.5 Condensation occurs at the alpha position of the presumed
extended enolate to afford β,γ-unsaturated products with high diastereoselection. For example, N-
acyloxazolidinone 1a is reported to condense with isobutyraldehyde to afford 2a in 90% yield and
greater than 98% isomeric purity. One limitation to the method is that higher homologues of 1, that is
α,β-unsaturated substrates leading to vicinal disubstituted alkene-containing products, afford a mixture
of double bond isomers. For example, N-acyloxazolidinone 1b affords an E:Z mixture of products 2b
(95% yield).6,7 In spite of this potentially problematic lack of stereochemical control, we prepared the
N-acyloxazolidinone (E,E)-1c derived from sorbic acid and examined its reaction with isobutyraldehyde.
Under the conditions reported by Evans for the reaction of 1a, treatment of 1c with dibutylboron
triflate8 (−78°C, 15 min) and triethylamine (1h at −78°C, 15 min at 0°C) followed by the addition
of isobutyraldehyde (1 h at −78°C, 1 h at 0°C) and oxidative work-up (H2O2) affords the β,γ,δ,ε-
unsaturated condensation product 3 in good yield (82%) and high regio- and diastereoselectivity. As
is the case for the other examples described in this paper, the product is of greater than 95% isomeric
purity as judged by analysis of the 1H and 13C NMR spectra. The E double bond stereochemistry in 3 was
∗
Corresponding author. E-mail: jtakacs@unl.edu
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00459-5

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assigned based on the relevant vicinal coupling constant (14.9 Hz). The remaining stereochemistry shown
in structure 3 was assigned by hydrogenation and comparison of the product to an authentic sample of 5
prepared via the boron-mediated condensation of 4 with isobutyraldehyde (Scheme 1).
Scheme 1. The regio- and diastereoselective aldol condensation of the sorbic acid derived chiral N-acyloxazolidinone 1c
N-Acyloxazolidinone 1c undergoes efficient boron-mediated aldol condensation with several other
simple aldehydes to afford diene-containing products with good efficiency. The results are summarized
in Scheme 2. For example, condensation with isovaleraldehyde affords compound 6 (83% yield).
Condensation with the γ,δ-unsaturated aldehyde 7 proceeds in 79% yield to afford compound 8. We
see no evidence for competing cycloaddition under the reaction conditions employed, but this example
illustrates how the method might be used to efficiently assemble substrates for subsequent intramolecular
Diels–Alder cycloaddition or other cyclization reactions.9 The condensation of 1c with a prototypical
α,β-unsaturated aldehyde proves more difficult. Retro-aldol proceeds readily in the case of (E)-2-
hexenal and somewhat different reaction conditions need to be employed. The presumed boron enolate
is generated from 1c as described earlier, but after addition of 2-hexenal, the reaction is held at low
temperature (1 h at −78°C, 3 h at −50°C) then quenched cold. In addition, the labile aldol adduct is
immediately reduced by treatment of the crude product with LiBH4. Under these conditions diol 10 is
isolated in good overall yield (79%) and as a single diastereomer as judged by NMR. The embedded
1,5-diene moiety within diol 10 suggests that this methodology should be useful for preparing substrates
suitable for examining novel oxy-Cope rearrangements, a strategy that has been developed for enoate
derived substrates.10
The scope and limitations with respect to the oxazolidinone component have also been briefly
surveyed. The results are summarized in Table 1. The norephedrine derived oxazolidinone 11a affords
the condensation product corresponding to 3 but possessing the opposite absolute configuration at
the newly formed tetrahedral stereocenters. An additional substituent at the 5-position of the starting
oxazolidinone is tolerated, whether that substituent is an acyclic group (entry b, 83%) or part of a
cyclic ring system (entry c, 55%). Entry d reveals a limitation to the method, similar to that reported
for compound 1b and related substrates.6,7 The propyl substituent in substrate (E,E)-11d affords a near
1:1 mixture of double bond isomers in product 12d (84%). From the NMR spectrum, we determined
that the products are isomeric only at the δ,ꢀ-double bond as indicated in structure 12d. It should
be noted however, that in contrast to the lack of diastereoselectivity exhibited by the (E)-2-hexenoate
derivative 1b, Schneider found that (E)- and (Z)-3-pentenoate derivatives (i.e. β,γ-unsaturated rather
than α,β-unsaturated oxazolidinone starting materials) retain their double bond stereochemistry upon

J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
4315
Scheme 2. Condensations involving several representative aldehyde partners
boron-mediated aldol condensation.10 Thus, in analogy to the Schneider work, it may prove possible
to prepare products such as 12d with control of the double bond geometry by starting with a partially
deconjugated dienoate derivative. Finally, the isopropyl substituted derivative 11e shows that it is feasible
to prepare products possessing a trisubstituted alkene as part of the newly formed 1,3-diene moiety.
We wondered whether this aldol strategy could be further extended to the preparation of longer
conjugated polyene systems. As a simple test case, we prepared triene 13 and found that it too undergoes a
facile regio- and stereoselective aldol condensation with isobutyraldehyde to afford the triene-containing
product 14 in 79% yield and high isomeric purity.
1. Conclusions
We have extended the methodology introduced by Evans and co-workers for the regio- and dia-
stereoselective boron-mediated aldol condensation of crotonic acid derived N-acyloxazolidinones to
chiral N-acyloxazolidinones derived from dienoic acids. These substrates undergo boron-mediated aldol
condensation in good yield, and with the exception of 12d, the product obtained is of 95% or greater
diastereomeric purity as judged by NMR. The method provides a convenient way to introduce a 1,3-diene
subunit, and we have shown that the strategy can be extended to the preparation of longer conjugated
polyene systems.

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Table 1
Some of the scope with respect to the N-acyloxazolidinone partner
2. Experimental
2.1. General
All solvents were distilled immediately before use under nitrogen. THF was distilled from
Na/benzophenone, and dichloromethane (DCM) was distilled from CaH2. Flash column chromatography
used 60–200 mesh silica gel. NMR spectra were recorded on General Electric Omega 500 and 300.
1H NMR spectral data in CDCl3, unless otherwise mentioned, are reported in ppm from an internal
standard tetramethylsilane or residual chloroform (δ 7.25 ppm). 13C spectra are decoupled and reported
in ppm from an internal standard deuterochloroform. FT-IR spectra were recorded using the attenuate
total reflectance (ATR, ZnSe crystal) technique and reported in cm−1. High resolution mass spectral
determinations were performed by the Nebraska Center for Mass Spectrometry, UNL, Lincoln,
Nebraska, USA.

J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
4317
2.2. General procedure for the preparation of N-acyloxazolidinones
To a stirred, cooled (−78°C) solution of the dienoic acid (1 equiv.) and Et3N (1.25 equiv.) in THF
(ca. 0.2 M in acid) was added pivaloyl chloride (1.05 equiv.). The resulting slurry was stirred for 15
min at −78°C, and 45 min at 0°C, and then recooled to −78°C. In a separate flask, a stirred, cooled
(−78°C) solution of (4S)-isopropyl-2-oxazolidinone or (4R,5S)-4-methyl-5-phenyl-2-oxazolidinone (1.1
equiv. relative to dienoic acid) in THF (ca. 0.2 M in oxazolidinone) was treated with n-BuLi (2.50 M
solution in hexane, 1.1 equiv. relative to dienoic acid). The resulting metalated oxazolidinone was added,
via cannula, to the dienoate slurry. The resulting viscous slurry was stirred for 20 min at −78°C, and then
warmed to room temperature and stirred for 15 h. The reaction mixture was quenched by the addition
of H2O and the organic solvents removed via rotovap. The residue was taken up in DCM and washed
successively with portions of 0.5 N HCl, saturated aqueous NaHCO3, and brine. The organic layer was
dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica gel afforded the diene
oxazolidinone.
2.2.1. Preparation of 1c
(4S)-Isopropyl-2-oxazolidinone (1.26 g, 9.81 mmol) was condensed with (2E,4E)-2,4-hexadienoic
acid (sorbic acid, 1.00 g, 8.92 mmol) via the general procedure described earlier, using pivaloyl chloride
(2.60 ml, 21.1 mmol), Et3N (1.57 ml, 11.2 mmol), and n-BuLi (3.92 ml, 2.50 M solution in hexane, 9.81
mmol) to afford the N-acyloxazolidinone 1c (1.50 g, 75%) as a viscous oil after flash chromatography
1
(4:1 hexane:EtOAc): TLC analysis (7:3 hexane:EtOAc) Rf=0.36; [α]D +87.8 (c 1.4, CHCl3); H NMR
(500 MHz, CDCl3) δ 7.31 (1H, dd, J=10.9, 4.0 Hz), 7.13 (1H, d, J=14.9 Hz), 6.21 (1H, dd, J=11.3,
4.0 Hz), 6.15–6.07 (1H, m), 4.45–4.38 (1H, m), 4.20 (1H, t, J=8.9 Hz), 4.11 (1H, dd, J=2.8, 6.0 Hz),
2.40–2.30 (1H, m), 1.77 (3H, d, J=6.4 Hz), 0.83 (3H, d, J=6.8 Hz), 0.78 (3H, d, J=6.8 Hz); 13C NMR
(125 MHz, CDCl3) δ 165.1 (s), 153.8 (s), 146.2 (d), 140.4 (d), 130.1 (d), 117.9 (d), 63.1 (t), 58.3 (d),
28.3 (d), 18.4 (q), 17.6 (q), 14.3 (q); FTIR (ATR) 1767 (s, C_O), 1677 (s, C_O), 1635 (s, C_C), 1600
(s, C_C); HRMS analysis (EI, C12H17NO3=223.1208) found 223.1209 m/z.
2.2.2. Preparation of 11a
(4R,5S)-4-Methyl-5-phenyl-2-oxazolidinone (3.93 g, 22.5 mmol) was condensed with (2E,4E)-2,4-
hexadienoic acid (2.44 g, 21.8 mmol) via the general procedure described earlier using pivaloyl chloride
(2.60 ml, 21.1 mmol), Et3N (3.60 ml, 25.8 mmol), and n-BuLi (10.00 ml, 2.35 M solution in hexane, 23.5
mmol) to afford the N-acyloxazolidinone (3.97 g, 69%) as a viscous oil after flash chromatography (19:1
hexane:EtOAc): TLC analysis (19:1 hexane:EtOAc) Rf=0.18; [α]D +36.0 (c 0.66, CHCl3); 1H NMR (500
MHz, CDCl3) δ 7.43–7.20 (7H, m), 6.33–6.18 (2H, m), 5.66 (1H, d, J=7.2 Hz), 4.83–4.78 (1H, m), 1.85
(3H, d, J=6.4 Hz), 0.9 (3H, d, J=6.9 Hz); 13C NMR (125 MHz, CDCl3) δ 165.1 (s), 152.9 (s), 146.6 (d),
140.9 (d), 133.6 (s), 130.3 (d), 128.5 (two aromatic resonances overlapping, d), 125.6 (d), 117.9 (d), 78.8
(d), 54.8 (d), 18.7 (q), 14.5 (q); FTIR (ATR) 1750 (s, C_O), 1677 (s, C_O), 1635 (s, C_C), 1601 (s,
C_C); HRMS analysis (EI, C16H17NO3=271.1208) found 271.1218 m/z.
2.2.3. Preparation of 11b
(4R,5S)-4-Methyl-5-phenyl-2-oxazolidinone (1.97 g, 11.3 mmol) was condensed with (2E)-5-methyl-
2,4-hexadienoic acid11 (1.29 g, 10.3 mmol) via the general procedure described earlier using pivaloyl
chloride (1.35 ml, 11.0 mmol), Et3N (1.80 ml, 12.9 mmol), and n-BuLi (4.51 ml, 2.5 M in hexane,
11.3 mmol) to afford the N-acyloxazolidinone (2.07 g, 72%) as a white solid after flash chromatography
(19:1 hexane:EtOAc): TLC analysis (7:3 hexane:EtOAc) Rf=0.43; m.p.=99–101°C; [α]D +23.6 (c 1.65,

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J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
1
CHCl3); H NMR (500 MHz, CDCl3) δ 7.76 (1H, dd, J=11.7, 3.2 Hz), 7.40–7.19 (6H, m), 6.11 (1H,
dd, J=0.7, 11.0 Hz), 5.65 (1H, d, J=7.3 Hz), 4.83–4.78 (1H, m), 1.87 (6H, d, J=9.7 Hz), 0.90 (3H, d,
J=6.7 Hz); 13C NMR (125 MHz, CDCl3) δ 165.4 (s), 152.9 (s), 148.2 (s), 142.5 (d), 133.4 (s), 128.5 (two
aromatic resonances overlapping, d), 125.5 (d), 124.3 (d), 117.4 (d), 78.7 (d), 54.8 (d), 26.6 (q), 18.9 (q),
14.5 (q); FTIR (ATR) 1769 (s, C_O), 1670 (s, C_O), 1626 (s, C_C), 1590 (s, C_C); HRMS analysis
(FAB, C17H19NO3+H=286.1443) found 286.1444 m/z.
2.2.4. Preparation of 11c
(4R,5S)-4-Methyl-5-phenyl-2-oxazolidinone (300 mg, 1.65 mmol) was condensed with (2E)-5-
cyclohexyl-2,4-pentadienoic acid12 (250 mg, 1.50 mmol) via the general procedure described earlier
using pivaloyl chloride (0.20 ml, 1.62 mmol), Et3N (0.26 ml, 1.87 mmol), and n-BuLi (0.66 ml, 2.50
M solution in hexane, 1.65 mmol) to afford the N-acyloxazolidinone (360 mg, 76%) as a yellow
solid after flash chromatography (19:1 hexane:EtOAc): TLC analysis (19:1 hexane:EtOAc) Rf=0.13;
m.p.=118–120°C; [α]D +16.1 (c 0.74, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.83 (1H, dd, J=11.7, 2.9
Hz), 7.42–7.2 (6H, m), 6.07 (1H, d, J=11.9 Hz), 5.65 (1H, d, J=7.5 Hz), 4.84–4.80 (1H, m), 2.44–2.38
(2H, m), 2.25–2.18 (2H, m), 1.63–1.58 (6H, m), 0.90 (3H, d, J=6.5 Hz); 13C NMR (125 MHz, CDCl3)
δ 165.6 (s), 156.3 (s), 152.9 (s), 142.0 (d), 133.4 (s), 128.5 (d), 125.5 (d), 125.5 (d), 121.7 (d), 117.6
(d), 78.7 (d), 54.8 (d), 37.7 (t), 29.8 (t), 28.4 (t), 27.9 (t), 26.3 (t), 14.5 (q); FTIR (ATR) 1740 (s, C_O),
1698 (s, C_O), 1618 (s, C_C), 1591 (s, C_C); HRMS analysis (FAB, C20H23NO3+H=326.1756) found
326.1745 m/z.
2.2.5. Preparation of 11d
(4R,5S)-4-Methyl-5-phenyl-2-oxazolidinone (2.41 g, 13.6 mmol), was condensed with (2E,4E)-2,4-
octadienoic acid13 (1.59 g, 11.3 mmol) via the general procedure described earlier using pivaloyl chloride
(1.54 ml, 12.5 mmol), Et3N (1.90 ml, 13.6 mmol), and n-BuLi (5.79 ml, 2.35 M solution in hexane, 13.6
mmol) to afford the N-acyloxazolidinone (3.00 g, 88%) as a viscous oil after flash chromatography (85:15
hexane:EtOAc): TLC analysis (3:1 hexane:EtOAc) Rf=0.50; [α]D +37.1 (c 1.64, CHCl3); 1H NMR (500
MHz, CDCl3) δ 7.50–7.20 (7H, m), 6.28 (1H, dd, J=10.9, 4.0 Hz), 6.20–6.15 (1H, m), 5.64 (1H, d, J=7.7
Hz), 4.85–4.70 (1H, m), 2.14 (2H, q, J=7.2 Hz), 1.43 (2H, m), 0.90–0.80 (6H, m); 13C NMR (125 MHz,
CDCl3) δ 165.0 (s), 152.8 (s), 146.5 (d), 145.9 (d), 133.4 (s), 129.0 (d), 128.4 (d), 125.5 (d), 125.4 (d),
118.2 (d), 78.7 (d), 54.7 (d), 34.9 (t), 21.6 (t), 14.4 (q), 13.4 (q); FTIR (ATR) 1772 (s, C_O), 1677 (s,
C_O), 1631 (s, C_C), 1602 (s, C_C); HRMS analysis (EI, C18H21NO3=299.1521) found 299.1511 m/z.
2.2.6. Preparation of 11e
2.2.6.1. (2E,4E)-6-Methyl-2,4-heptadienoic acid. Ethyl-(2E,4E)-6-methyl-2,4-heptadienoate14 (1.25
g, 7.4 mmol) was treated with KOH (0.97 mg, 17 mmol) in methanol:water (30:5 ml). The mixture
was stirred for 15 h at room temperature. The methanol was removed via rotovap. Standard acid–base
extractive workup afforded the title acid as a yellow solid (1.03 g, quantitative): TLC analysis (70:30
hexane:EtOAc) Rf=0.24; m.p.=34–36°C; 1H NMR (500 MHz, CDCl3) δ 7.37–7.31 (1H, m), 6.15–6.14
(2H, m), 5.79 (1H, d, J=15.3 Hz), 2.45–2.38 (1H, m), 1.03 (6H, d, J=6.8 Hz); 13C NMR (125 MHz,
CDCl3) δ 173.0 (s), 152.5 (d), 147.7 (d), 125.3 (d), 118.5 (d), 31.5 (d), 21.6 (q); FTIR (ATR) 3500 (br s,
OH), 1682 (s, C_O), 1675 (s, C_C); HRMS analysis (C8H12O2+H=141.0915) found 141.0914 m/z.
2.2.6.2. Compound 11e. (4R,5S)-4-Methyl-5-phenyl-2-oxazolidinone (777 mg, 4.46 mmol) was con-
densed with (2E,4E)-6-methyl-2,4-heptadienoic acid (450 mg, 3.21 mmol) via the general procedure

J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
4319
described earlier using pivaloyl chloride (0.55 ml, 4.5 mmol), Et3N (0.71 ml, 5.1 mmol), and n-BuLi
(1.80 ml, 2.5 M in hexane, 4.5 mmol) to afford the N-acyloxazolidinone (932.7 mg, 97%) as a viscous
oil after flash chromatography (85:15 hexane:EtOAc): TLC analysis (4:1 hexane:EtOAc) Rf=0.53; [α]D
+31.6 (c 0.55, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.42–7.18 (7H, m), 6.25–6.11 (2H, m), 5.6 (1H,
d, J=9.3 Hz), 4.81–4.76 (1H, m), 2.42–2.39 (1H, m), 1.00 (6H, d, J=6.6 Hz), 0.87 (3H, d, J=6.5); 13C
NMR (125 MHz, CDCl3) δ 164.9 (s), 152.8 (s), 152.6 (d), 146.8 (d), 133.3 (s), 128.4 (two aromatic
resonances overlapping, d), 125.9 (d), 125.5 (d), 118.3 (d), 78.7 (d), 54.7 (d), 31.3 (d), 21.5 (q), 14.4
(q); FTIR (ATR) 1769 (s, C_O), 1676 (s, C_O), 1631 (s, C_C), 1601 (s, C_C); HRMS analysis (FAB,
C18H21NO3+H=300.1560) found 300.1601 m/z.
2.2.7. Preparation of 13
2.2.7.1. Ethyl-(2E,4E)-7-cyclohexyl-2,4,6-heptatrienoate. A suspension of (2E)-5-cyclohexyl-2,4-
pentadienal15 (1.87 g, 12.5 mmol), triethyl phosphonocrotonate (3.08 g, 13.7 mmol), lithium hydroxide
monohydrate (576.0 mg) and 4A molecular sieves (beads, 19.0 g) in THF (75 ml) was heated at reflux
for 3 h.16 The reaction mixture was filtered through a short plug of silica gel (ether), concentrated via
rotovap and the residue subjected to flash chromatography (19:1 hexane:EtOAc) to afford the title ester
1
(1.82 g, 66%) as a white solid: TLC analysis (9:1 hexane:EtOAc) Rf=0.55; m.p. 55–57°C; H NMR
(500 MHz, CDCl3) δ 7.21 (1H, dd, J=11.3, 4.0 Hz), 6.69 (1H, dd, J=11.7, 2.8 Hz), 6.07 (1H, dd,
J=11.3, 3.2 Hz), 5.74 (1H, d, J=11.3 Hz), 5.67 (1H, d, J=15.3 Hz), 4.04 (2H, q, J=6.8 Hz), 2.20–2.15
(2H, m), 2.10–2.00 (2H, m), 1.50–1.40 (6H, m), 1.14 (3H, t, J=7.2 Hz); 13C NMR (125 MHz, CDCl3)
δ 166.5 (s), 149.2 (s), 144.7 (d), 136.1 (d), 127.4 (d), 121.8 (d), 118.9 (d), 59.5 (t), 37.2 (t), 29.2 (t),
28.2 (t), 27.4 (t), 26.2 (t), 13.9 (q); FTIR (ATR) 1725 (s, C_O), 1610 (s, C_C); HRMS analysis (EI,
C14H20NO2=220.1463) found 220.1461 m/z.
2.2.7.2. (2E,4E)-7-Cyclohexyl-2,4,6-heptatrienoic acid. Ethyl-(2E,4E)-7-cyclohexyl-2,4,6-heptatri-
enoate (1.57 g, 7.13 mmol) was treated with KOH (939.7 mg, 16.8 mmol) in methanol:water (30:5
ml). The mixture was stirred for 15 h at room temperature. Standard acid–base extractive work-up
afforded the desired acid as a white solid (1.01 g, 74%): TLC analysis (9:1 hexane:EtOAc) Rf=0.10;
1
m.p. 109–111°C; H NMR (500 MHz, CDCl3) δ 11.50 (1H, br s), 7.43 (1H, dd, J=11.7, 3.6 Hz),
6.88 (1H, dd, J=11.3, 3.2 Hz), 6.24 (1H, dd, J=11.7, 2.8 Hz), 5.90 (1H, d, J=11.7 Hz), 5.81 (1H, d,
J=15.3 Hz), 2.40–2.30 (2H, m), 2.20–2.10 (2H, m), 1.60–1.50 (6H, m); 13C NMR (125 MHz, CDCl3)
δ 172.9 (s), 151.0 (s), 147.6 (d), 137.9 (d), 127.4 (d), 122.0 (d), 118.2 (d), 37.6 (t), 29.6 (t), 28.5 (t),
27.8 (t), 26.5 (t); FTIR (ATR) 3500 (br s, OH), 1682 (s, C_O), 1605 (s, C_C); HRMS analysis (FAB,
C12H16NO2=192.1150) found 192.1151 m/z.
2.2.7.3. Compound 13. (4S)-Isopropyl-2-oxazolidinone (687.3 mg, 5.32 mmol), was condensed with
(2E,4E)-7-cyclohexyl-2,4,6-heptatrienoic acid (930.0 mg, 4.84 mmol) via the general procedure descri-
bed earlier using pivaloyl chloride (0.64 ml, 5.2 mmol), Et3N (0.85 ml, 6.1 mmol), and n-BuLi (2.26 ml,
2.35 M solution in hexane, 5.3 mmol) to afford the N-acyloxazolidinone (752.2 mg, 52%) as a yellow
solid after flash chromatography (4:1 hexane:EtOAc): TLC analysis (3:1 hexane:EtOAc) Rf=0.48; m.p.
140–142°C; [α]D +90.0 (c 0.85, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.45 (1H, dd, J=11.3, 3.6 Hz),
7.20 (1H, d, J=14.9 Hz), 6.84 (1H, dd, J=11.7, 2.8 Hz), 6.27 (1H, dd, J=11.7, 2.8 Hz), 5.85 (1H, d,
J=11.3 Hz), 4.45–4.38 (1H, m), 4.20 (1H, t, J=8.9 Hz), 4.11 (1H, dd, J=2.8, 6.0 Hz), 2.40–2.30 (3H, m),
2.20–2.10 (2H, m), 1.60–1.50 (6H, m) 0.85 (3H, d, J=6.8 Hz), 0.79 (3H, d, J=6.8 Hz); 13C NMR (125
MHz, CDCl3) δ 165.0 (s), 153.8 (s), 150.6 (s), 146.7 (d), 137.8 (d), 128.1 (d), 122.0 (d), 117.9 (d), 63.1

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(t), 58.3 (d), 37.4 (t), 29.5 (t), 28.3 (d), 28.2 (t), 27.6 (t), 26.3 (t), 17.7 (q), 14.5 (q); FTIR (ATR) 1771
(s, C_O), 1677 (s, C_O), 1596 (s, C_C), 1486 (s, C_C); HRMS analysis (EI, C18H25NO3=303.1834)
found 303.1837 m/z.
2.3. General procedure for the asymmetric boron-mediated aldol condensation of the dienoate
derivatives
To a stirred, cooled (−78°C) solution of N-acyloxazolidinone (1 equiv.) in DCM (ca. 0.2 M) was added
Bu2BOTf (1.2 equiv.) dropwise.8 After 5 min, Et3N (1.4 equiv.) was added dropwise. After stirring for
an additional 1 h (−78°C), the reaction was warmed to 0°C (15 min), and then re-cooled (−78°C). The
appropriate aldehyde (1.47 equiv.) was added dropwise, and the resulting mixture was stirred for 1 h
(−78°C), and then warmed to 0°C. After ca. 1 h at 0°C (follow by TLC), the reaction was partitioned
between 1 M aqueous NaHSO4 and DCM. The organic layer was separated, cooled to 0°C then treated
with pH 7 phosphate buffer (ca. 5 ml on a 3 mmol scale reaction) and 30% H2O2 (ca. 2 ml on this scale).
After stirring rapidly for 1 h, the mixture was partitioned between saturated NaHCO3 and DCM. The
organic layer was dried (Na2SO4) and concentrated. Flash chromatography on silica afforded the desired
β-hydroxyoxazolidinone derivative.
2.3.1. Preparation of 3
(4S)-4-Isopropyl-3((2E,4E)-1-oxo-2,4-hexadienyl)-2-oxazolidinone (450.0 mg, 2.01 mmol) was con-
densed with isobutyraldehyde (0.27 ml, 3.0 mmol) via the general procedure described earlier using
Bu2BOTf (0.61 ml, 2.4 mmol) and Et3N (0.39 ml, 2.8 mmol) to afford the β-hydroxyoxazolidinone
(483.8 mg, 82%) as an oil after flash chromatography (4:1 hexane:EtOAc): HPLC analysis (E. Merck
LiChrosorb Si 60, 80:20 hexane:EtOAc, 1.0 ml/min) 6.2 (95%), 8.1 (5%); TLC analysis (3:1 hex-
ane:EtOAc) Rf=0.38; [α]D +47.5 (c 0.59, CHCl3); 1H NMR (500 MHz, CDCl3) δ 6.41 (1H, dd, J=10.9,
4.4 Hz), 6.33 (1H, dd, J=10.1, 6.4 Hz), 5.83 (1H, dd, J=9.3, 6.1 Hz), 5.20 (1H, d, J=16.9 Hz), 5.08 (1H,
d, J=10.9 Hz), 4.84 (1H, dd, J=3.2, 6.4 Hz), 4.50–4.45 (1H, m), 4.30–4.20 (2H, m), 3.63–3.60 (1H, m),
3.23 (1H, d, J=1.2 Hz), 2.40–2.30 (1H, m), 1.75–1.68 (1H, m), 1.00–0.80 (12H, m); 13C NMR (125
MHz, CDCl3) δ 174.6 (s), 153.2 (s), 136.5 (d), 136.2 (d), 126.5 (d), 117.7 (t), 76.5 (d), 63.0 (t), 58.1 (d),
48.2 (d), 30.9 (d), 28.0 (d), 18.8 (q), 18.3 (q), 17.6 (q), 14.3 (q); FTIR (ATR) 3500 (br s, OH), 1776 (s,
C_O), 1687 (s, C_O); HRMS analysis (CI, C15H25NO4+H=296.1862) found 296.1854 m/z.
2.3.1.1. Hydrogenation of 3. A sample of 3 (75.0 mg, 0.25 mmol) in EtOH (3 ml) was treated with 5%
Rh/alumina (ca. 2 mg) under an atmosphere of H2 (room temperature, 24 h). The resulting mixture was
then filtered through a short plug of silica gel and the solvent was removed under vacuum to give the
reduced product (72.1 mg, 95%) which was identical to compound 5 prepared as set out below.
2.3.2. Preparation of 5
(4S)-4-Isopropyl-3-(1-oxohexanoyl)-2-oxazolidinone17 (500.0 mg, 2.20 mmol) was condensed with
isobutyraldehyde (0.22 ml, 2.4 mmol) via the general procedure described earlier using Bu2BOTf (0.61
ml, 2.4 mmol) and diisopropylethylamine (0.43 ml, 2.5 mmol) to afford the β-hydroxyoxazolidinone
(602.1 mg, 91%) as an oil after flash chromatography (4:1 hexane:EtOAc): TLC analysis (3:1 hex-
1
ane:EtOAc) Rf=0.35; [α]D +47.2 (c 0.89, CHCl3); H NMR (500 MHz, CDCl3) δ 4.42–4.38 (1H, m),
4.20–4.10 (3H, m), 3.63–3.60 (1H, m), 3.36 (1H, dd, J=4.0, 2.8 Hz), 2.30–2.20 (1H, m), 1.80–1.70 (1H,
m), 1.60–1.50 (2H, m), 1.30–1.10 (4H, m), 1.00–0.80 (15H, m); 13C NMR (125 MHz, CDCl3) δ 176.6
(s), 153.4 (s), 76.6 (d), 62.7 (t), 58.4 (d), 44.5 (d), 31.0 (d), 29.2 (t), 28.1 (d), 26.0 (t), 22.6 (t), 18.9

J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
4321
(q), 18.2 (q), 17.6 (q), 14.2 (q), 13.6 (q); FTIR (ATR) 3500 (br s, OH), 1774 (s, C_O), 1686 (s, C_O);
HRMS analysis (FAB, C16H29NO4+H=300.2175) found 300.2178 m/z.
2.3.3. Preparation of 6
(4S)-4-Isopropyl-3((2E,4E)-1-oxo-2,4-hexadienyl)-2-oxazolidinone (375.7 mg, 1.68 mmol) was con-
densed with isovaleraldehyde (0.26 ml, 2.5 mmol) via the general procedure described earlier using
Bu2BOTf (0.51 ml, 2.0 mmol) and Et3N (0.33 ml, 2.4 mmol) to afford the β-hydroxyoxazolidinone
(430.2 mg, 83%) as an oil after flash chromatography (4:1 hexane:EtOAc): TLC analysis (3:1 hex-
1
ane:EtOAc) Rf=0.38; [α]D +55.8 (c 0.86, CHCl3); H NMR (500 MHz, CDCl3) δ 6.40–6.20 (2H, m),
5.78 (1H, dd, J=9.3, 5.2 Hz), 5.15 (1H, d, J=16.9 Hz), 5.03 (1H, d, J=10.0 Hz), 4.50 (1H, dd, J=3.2, 3.2
Hz), 4.45–4.40 (1H, m), 4.24 (1H, t, J=8.9 Hz), 4.15 (1H, dd, J=3.2, 6.0 Hz), 4.05–4.00 (1H, m), 3.20
(1H, br s), 2.40–2.30 (1H, m), 1.75–1.68 (1H, m), 1.42–1.38 (1H, m), 1.10–1.00 (1H, m), 0.90–0.85 (12H,
m); 13C NMR (125 MHz, CDCl3) δ 174.4 (s), 153.3 (s), 136.7 (d), 136.2 (d), 126.4 (d), 117.7 (t), 69.5 (d),
63.0 (t), 58.0 (d), 51.0 (d), 43.0 (t), 27.9 (d), 24.1 (d), 23.3 (q), 21.6 (q), 17.6 (q), 14.3 (q); FTIR (ATR)
3500 (br s, OH), 1774 (s, C_O), 1687 (s, C_O); HRMS analysis (FAB, C17H27NO4+Li=316.2100)
found 316.2103 m/z.
2.3.4. Preparation of 8
(4S)-4-Isopropyl-3((2E,4E)-1-oxo-2,4-hexadienyl)-2-oxazolidinone (170 mg, 0.75 mmol) was con-
densed with (E)-ethyl 6-oxo-hex-2-eneoate18 (180 mg, 1.1 mmol) via the general procedure descri-
bed earlier using Bu2BOTf (0.21 ml, 0.83 mmol) and Et3N (0.15 ml, 1.1 mmol) to afford the β-
hydroxyoxazolidinone (220 mg, 79%) as an oil after flash chromatography (85:15 hexane:EtOAc): TLC
analysis (50:50 hexane:EtOAc) Rf=0.52; HPLC analysis (E. Merck LiChrosorb Si 60 column, 70:30
1
hexane:EtOAc) 9.3 (100%); [α]D −3.9 (c 0.90, MeOH); H NMR (500 MHz, C6D6) δ 7.00–6.90 (1H,
dd, J=15.7 Hz), 6.45 (1H, dd, J=10.5 Hz), 6.30 (ddd, 1H, J=16.9, 10.1, 10.1 Hz), 5.95–5.85 (1H, m),
5.87 (1H, d, J=15.3 Hz), 5.01 (1H, d, J=16.9 Hz), 4.87 (1H, d, J=10.1 Hz), 4.70 (1H, dd, J=9.7, 3.6 Hz),
4.10–3.90 (4H, m), 3.40 (2H, d, J=5.6 Hz), 2.30–2.05 (2H, m), 2.00–1.90 (1H, m), 1.70–1.55 (2H, m),
1.00–0.90 (3H, m), 0.42 (3H, d, J=6.9 Hz), 0.34 (3H, d, J=6.9 Hz); 13C NMR (125 MHz) δ 174.4 (s),
166.6 (s), 153.7 (s), 150.0 (d), 137.1 (d), 137.0 (d), 127.5 (d), 122.2 (d), 118.0 (t), 71.2 (d), 62.8 (t), 60.2
(t), 58.1 (d), 51.5 (d), 32.9 (t), 28.7 (t), 28.2 (d), 17.4 (q), 14.1 (q), 14.0 (q); FTIR (ATR) 3500 (br s, OH),
1776 (s, C_O), 1696 (s, C_O), 1651 (s, C_O); HRMS analysis (FAB, C20H29NO6+H=380.2073) found
380.2073 m/z.
2.3.5. Preparation of 10
To a stirred, cooled (−78°C) solution of (4S)-4-isopropyl-3((2E,4E)-1-oxo-2,4-hexadienyl)-2-
oxazolidinone (220 mg, 1.0 mmol) in DCM (5 ml) was added Bu2BOTf (0.30 ml, 1.2 mmol) dropwise.
After the Bu2BOTf dissolved, Et3N (0.21 ml, 1.4 mmol) was added dropwise. Upon additional stirring
for 1 h at −78°C, the mixture was warmed to 0°C for 15 min, then re-cooled to −78°C. Freshly distilled
(E)-2-hexenal (0.17 ml, 1.5 mmol) was added, and the resulting mixture stirred at −78°C (1 h) and
−50°C (3 h). The reaction mixture was partitioned between 1 M NaHSO4 and DCM. The organic layer
was separated, dried, and concentrated to afford the crude β-hydroxyoxazolidinone as a yellow oil. A
cooled (0°C) solution of the crude product in THF was treated with LiBH4 (10.0 ml, 0.2 M in THF,
2 mmol), which was added dropwise over 5 min. The resulting mixture was stirred at 0°C (1 h), and
then quenched by the addition of pH 7 buffer (2 ml) and H2O2 (2 ml). After stirring for an additional 1
h at 0°C, the reaction mixture was diluted with Et2O and washed sequentially with saturated aqueous
NaHCO3 (10 ml) and brine (10 ml). The resulting organic layer was dried (Na2SO4) and concentrated.

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J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
Chromatography on silica (70:30 hexane:EtOAc) afforded diol 10 (153 mg, 79%) as a clear viscous oil:
TLC analysis (50:50 hexane:EtOAc) Rf=0.23; [α]D +1.2 (c 0.82, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 6.29 (1H, ddd, J=14.9, 10.3, 10.3 Hz), 6.11 (1H, dd, J=15.3, 10.5 Hz), 5.65–5.55 (2H, m), 5.11 (1H,
d, J=16.9 Hz), 5.00 (1H, d, J=10.1 Hz), 4.20 (1H, dd, J=4.8, 6.1 Hz), 3.72 (1H, dd, J=7.3, 6.9 Hz), 3.60
(1H, dd, J=5.6, 5.6 Hz), 3.30–2.90 (2H, m), 2.45–2.35 (1H, m), 2.00–1.95 (2H, m), 1.40–1.30 (2H, m),
0.85 (3H, t, J=7.3 Hz); 13C NMR (125 MHz) δ 136.7 (d), 134.4 (d), 133.1 (d), 130.6 (d), 130.1 (d),
116.3 (t), 73.9 (d), 63.7 (t), 50.2 (d), 34.2 (t), 22.2 (t), 13.5 (q); FTIR (ATR) 3500 (br s, OH), 1781 (s,
C_O), 1651 (m, C_C); HRMS analysis (FAB, C12H20O2+Li=203.1623) found 203.1619 m/z.
2.3.6. Preparation of 12a
(4R,5S)-4-Methyl-5-phenyl-3-((2E,4E)-1-oxo-2,4-hexadienyl)-2-oxazolidinone (11a, 537 mg, 2.00
mmol) was condensed with isobutyraldehyde (0.25 ml, 2.8 mmol) via the general procedure described
earlier using Bu2BOTf (2.20 ml, 1.0 M in DCM, 2.20 mmol) and Et3N (0.35 ml, 2.51 mmol) to
afford the β-hydroxyoxazolidinone (515 mg, 75%) as a viscous oil after flash chromatography (85:15
hexane:EtOAc): HPLC analysis (E. Merck LiChrosorb Si 60, 80:20 hexane:EtOAc, 1.0 ml/min) 5.5 (5%),
1
6.9 (95%); [α]D +96.3 (c 0.41, CHCl3); H NMR (500 MHz, CDCl3) δ 7.45–7.22 (5H, m), 6.44–6.30
(2H, m), 5.87–5.82 (1H, m), 5.68 (1H, d, J=7.3 Hz), 5.25–5.21 (1H, m), 5.12–5.09 (1H, m), 4.85–4.78
(2H, m), 3.65–3.63 (1H, m), 3.14 (1H, br s), 1.78–1.63 (1H, m), 1.01 (3H, d, J=6.9 Hz), 0.95 (3H, d,
J=6.9 Hz), 0.86 (3H, d, J=6.5 Hz); 13C NMR (125 MHz, CDCl3) δ 174.5 (s), 153.0 (s), 136.6 (d), 136.4
(d), 133.0 (s), 128.8 (d), 128.7 (d), 126.1 (d), 125.6 (d), 117.9 (t), 78.8 (d), 76.9 (d), 54.8 (d), 48.6 (d),
31.1 (d), 18.9 (q), 18.5 (q), 14.2 (q); FTIR (ATR) 3500 (br s, OH), 1775 (s, C_O), 1692 (s, C_O); HRMS
(FAB, C20H25NO4+Na=366.1681) found 366.1670 m/z.
2.3.7. Preparation of 12b
(4R,5S)-4-Methyl-5-phenyl-3-((2E)-5-methyl-1-oxo-2,4-hexdienyl)-2-oxazolidinone (11b, 1.00 g,
3.50 mmol) was condensed with isobutyraldehyde (0.47 ml, 5.4 mmol) via the general procedure
described earlier using Bu2BOTf (0.97 ml, 3.8 mmol) and Et3N (0.69 ml, 4.9 mmol) to afford the β-
hydroxyoxazolidinone (1.04 g, 83%) as a viscous oil after flash chromatography (70:30 hexane:EtOAc):
1
TLC analysis (70:30, hexane:EtOAc) Rf=0.32; [α]D +138.3 (c 0.84, CHCl3); H NMR (500 MHz,
CDCl3) δ 7.41–7.2 (5H, m), 6.44 (1H, d, J=15.7 Hz), 5.77 (1H, dd, J=9.3, 6.9 Hz), 5.65 (1H, d, J=7.3
Hz), 5.0 (2H, s), 4.78–4.75 (2H, m), 3.63 (1H, dd, J=3.2, 4.4 Hz), 3.18 (1H, s), 1.80 (3H, s), 1.70–1.61
(1H, m), 0.98 (3H, d, J=6.4 Hz), 0.92 (3H, d, J=6.9 Hz), 0.82 (3H, d, J=6.9 Hz); 13C NMR (125
MHz, CDCl3) δ 174.3 (s), 152.3 (s), 141.3 (s), 138.2 (d), 133.0 (s), 128.6 (d), 128.5 (d), 125.5 (s),
122.2 (d), 117.0 (t), 78.7 (d), 76.8 (d), 54.6 (d), 48.8 (d), 31.0 (d), 18.3 (q), 18.8 (q), 18.3 (q), 14.0 (q);
FTIR (ATR) 3500 (br s, OH), 1778 (s, C_O), 1695 (s, C_O), 1608 (s, C_C); HRMS analysis (FAB,
C21H27NO4+Li=364.2100) found 364.2107 m/z.
2.3.8. Preparation of 12c
(4R,5S)-4-Methyl-5-phenyl-3-((2E)-5-cyclohexyl-1-oxo-2,4-pentadienyl)-2-oxazolidinone
(11c,
980.0 mg, 3.00 mmol) was condensed with isobutyraldehyde (0.40 ml, 4.4 mmol) via the general
procedure described earlier using Bu2BOTf (0.82 ml, 3.3 mmol) and Et3N (0.59 ml, 4.2 mmol) to
afford the β-hydroxyoxazolidinone (660.0 mg, 55%) as a viscous oil after flash chromatography (70:30
hexane:EtOAc): HPLC analysis (E. Merck LiChrosorb Si 60, 80:20 hexane:EtOAc, 1.00 ml/min) 3.6
(4%), 5.6 (96%); TLC analysis (70:30, hexane:EtOAc) Rf=0.25; [α]D +135.5 (c 0.54, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.41–7.22 (5H, m), 6.32 (1H, d, J=15.8 Hz), 5.73 (1H, s), 5.65–5.59 (2H, m),
4.77–4.70 (2H, m), 3.61 (1H, dd, J=3.6, 4.1 Hz), 3.17 (1H, s), 2.18–2.02 (4H, m), 1.76–1.45 (5H, m),

J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
4323
0.97 (3H, d, J=6.5 Hz), 0.91 (3H, d, J=6.8 Hz), 0.82 (3H, d, J=6.5 Hz); 13C NMR (125 MHz, CDCl3) δ
174.7 (s), 152.3 (s), 139.2 (d), 135.2 (s), 133.1 (s), 130.2 (d), 128.6 (d), 128.5 (d), 128.5 (d), 117.8 (d),
78.7 (d), 76.9 (d), 54.6 (d), 48.9 (d), 30.9 (d), 24.2 (two allylic resonances overlapping, t), 22.3 (t), 22.2
(t), 18.9 (q), 18.3 (q), 14.1 (q); FTIR (ATR) 3500 (br s, OH), 1777 (s, C_O), 1735 (s, C_O), 1696 (s,
C_C), 1647 (s, C_C); HRMS analysis (FAB, C24H31NO4+Li=404.2413) found 404.2414 m/z.
2.3.9. Preparation of 12d
(4R,5S)-4-Methyl-5-phenyl-3((2E,4E)-1-oxo-2,4-octadienyl)-2-oxazolidin-one (11d, 500.0 mg, 1.67
mmol) was condensed with isobutyraldehyde (0.22 ml, 2.5 mmol) via the general procedure described
earlier using Bu2BOTf (0.51 ml, 2.0 mmol) and Et3N (0.33 ml, 2.3 mmol) to afford a diastereomeric
mixture of β-hydroxyoxazolidinones (520.2 mg, 84%) as an oil after flash chromatography (85:15
hexane:EtOAc): HPLC analysis (E. Merck LiChrosorb Si 60, 80:20 hexane:EtOAc, 1.0 ml/min) 5.6
(60%), 5.9 (40%); TLC analysis (3:1 hexane:EtOAc) Rf=0.40; 1H NMR (500 MHz, CDCl3) δ 7.40–7.25
(5H, m), 6.63 (0.5H, dd, J=11.3, 4.0 Hz), 6.33 (0.5H, dd, J=10.1, 5.2 Hz), 6.01 (0.5H, dd, J=13.7, 10.15
Hz), 5.94 (0.5H, t, J=10.5 Hz), 5.80–5.60 (3H, m), 4.80–4.70 (2H, m), 3.65–3.60 (1H, m), 3.10 (1H, br
s), 2.20–2.10 (2H, m), 1.75–1.68 (1H, m), 1.00–0.80 (12H, m); 13C NMR (125 MHz, CDCl3) δ 174.5
(s), 174.3 (s), 152.3 (s), 137.1 (d), 136.2 (d), 134.5 (s), 133.1 (d), 131.1 (d), 128.7 (d), 128.6 (d), 125.6
(d), 125.5 (d), 125.3 (d), 123.0 (d), 78.7 (d), 76.9 (d), 54.7 (d), 53.3 (d), 49.1 (d), 48.8 (d), 31.1 (d), 31.0
(d), 25.4 (t), 21.0 (t), 18.9 (q), 18.3 (q), 18.2 (q), 14.1 (q), 14.0 (q), 13.2 (q); FTIR (ATR) 3500 (br s,
OH), 1778 (s, C_O), 1694 (s, C_O); HRMS analysis (FAB, C22H29NO4+H=372.2175) found 372.2185
m/z.
2.3.10. Preparation of 12e
(4R,5S)-4-Methyl-5-phenyl-3-((2E,4E)-6-methyl-1-oxo-2,4-heptadienyl)-2-oxazolidinone (11e, 880.0
mg, 2.95 mmol) was condensed with isobutyraldehyde (0.40 ml, 4.4 mmol) via the general procedure
described earlier using Bu2BOTf (3.40 ml, 1.0 M in DCM, 3.40 mmol) and Et3N (0.60 ml, 4.3 mmol) to
afford the β-hydroxyoxazolidinone (920.0 mg, 82%) as a viscous oil after flash chromatography (70:30
hexane:EtOAc): HPLC analysis (E. Merck LiChrosorb Si 60, 80:20 hexane:EtOAc, 1.00 ml/min) 5.6
(99%), 7.2 (1%); TLC analysis (70:30, hexane:EtOAc) Rf=0.37; [α]D +129.5 (c 0.61, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.42–7.23 (5H, m), 6.56 (1H, dd, J=10.9, 4.0 Hz), 5.82 (1H, d, J=10.9 Hz),
5.67–5.62 (2H, m), 4.79–4.71 (2H, m), 3.63 (1H, dd, J=3.6, 3.6 Hz), 3.2 (1H, s), 1.78–1.65 (7H, m),
0.98 (3H, d, J=6.9 Hz), 0.93 (3H, d, J=6.9 Hz), 0.83 (3H, d, J=6.5 Hz); 13C NMR (125 MHz, CDCl3) δ
174.5 (s), 152.3 (s), 136.1 (s), 133.1 (s), 132.4 (d), 128.7 (d), 128.6 (d), 128.5 (d), 125.5 (d), 124.5 (d),
122.5 (d), 78.7 (d), 76.8 (d), 54.6 (d), 49.1 (d), 31.0 (d), 25.8 (q), 18.9 (q), 18.3 (q), 14.0 (q); FTIR (ATR)
3500 (br s, OH), 1776 (s, C_O), 1693 (s, C_O); HRMS analysis (FAB, C22H29NO4+Li=378.2257)
found 378.2249 m/z.
2.3.11. Preparation of 14
(4S)-4-Isopropyl-3((2E,4E)-7-cyclohexyl-1-oxo-2,4,6-heptatrienoyl)-2-oxazolidinone (13, 482.6 mg,
1.59 mmol), was condensed with isobutyraldehyde (0.21 ml, 2.3 mmol) via the general procedure
described earlier using Bu2BOTf (0.48 ml, 1.9 mmol) and Et3N (0.31 ml, 2.2 mmol) to afford the
β-hydroxyoxazolidinone (474.7 mg, 79%) as a yellow solid after flash chromatography (85:15 hex-
ane:EtOAc): HPLC analysis (E. Merck LiChrosorb Si 60, 80:20 hexane:EtOAc, 1.00 ml/min) 6.8 (100%);
TLC analysis (3:1 hexane:EtOAc) Rf=0.40; m.p. 48–50°C; [α]D −115.7 (c 0.51, CHCl3); 1H NMR (500
MHz, CDCl3) δ 6.42 (1H, dd, J=10.1, 5.2 Hz), 6.18 (1H, d, J=15.3 Hz), 6.09 (1H, dd, J=10.1, 5.2 Hz),
5.80–5.70 (2H, m), 4.80 (1H, dd, J=2.8, 6.4 Hz), 4.45–4.40 (1H, m), 4.30–4.20 (2H, m), 3.65–3.58 (1H,

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J. M. Takacs et al. / Tetrahedron: Asymmetry 9 (1998) 4313–4324
m), 3.24 (1H, d, J=2.4 Hz), 2.40–2.00 (5H, m), 1.80–1.60 (5H, m), 1.00–0.85 (12H, m); 13C NMR (125
MHz, CDCl3) δ 174.6 (s), 153.1 (s), 136.7 (d), 136.4 (d), 135.4 (s), 130.4 (d), 124.4 (d), 124.3 (d), 76.4
(d), 62.8 (t), 57.9 (d), 48.3 (d), 30.8 (d), 27.8 (d), 25.7 (t), 24.1 (t), 22.1 (t), 22.0 (t), 18.7 (q), 18.1 (q),
17.5 (q), 14.3 (q); FTIR (ATR) 3500 (br s, OH), 1770 (s, C_O), 1680 (s, C_O); HRMS analysis (FAB,
C22H33NO4+Li=382.2570) found 382.2559 m/z.
Acknowledgements
Financial support of this work by the National Institutes of Health (GM34927) is gratefully acknow-
ledged. We thank the NIH (SIG 1-S10-RR06301) for NMR instrumentation funding and the NSF (CHE-
93000831) for GC–MS instrumentation funding.
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