A highly efficient and straightforward stereoselective synthesis of novel chiral α-acetylenic ketones

Article abstract of DOI:10.1016/S0957-4166(99)00357-2

A very efficient and straightforward synthesis of novel chiral α- acetylenic ketones of type 3 has been developed. Starting from commercially available l-(-)-serine 4, and through the Garner's aldehyde 5, ethynyloxazolidine 2 was formed in good overall yi

Full text of DOI:10.1016/S0957-4166(99)00357-2

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3417–3430
A highly efficient and straightforward stereoselective synthesis of
novel chiral α-acetylenic ketones
Xavier Serrat,a Gemma Cabarrocas,a Sara Rafel,a Montserrat Ventura,a Anthony Linden b and
José M. Villalgordoa,∗
aDepartament de Química, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, E-17071 Girona, Spain
bOrganisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Received 26 July 1999; accepted 12 August 1999
Abstract
A very efficient and straightforward synthesis of novel chiral α-acetylenic ketones of type 3 has been developed.
Starting from commercially available L-(−)-serine 4, and through the Garner’s aldehyde 5, ethynyloxazolidine
2 was formed in good overall yield. Condensation of the corresponding lithium acetylide 7 with different
aliphatic and aromatic aldehydes 5 and 8a–h at low temperatures yielded the respective propargylic alcohols 9a–i.
Subsequent mild oxidation of 9a–i with 10-I-4-iodinane oxide (IBX) 12 afforded chiral α-acetylenic ketones 3a–i
almost quantitatively. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
In recent years, as demonstrated mainly by the extensive and elegant work of Obrecht et al., α-
acetylenic ketones of type 1 have been shown to be highly versatile building blocks, which are very
useful in a number of synthetic transformations. Thus, these conjugated ynones have proven to be very
suitable substrates for the synthesis of, for instance, (E)-3-acylpropenoic acids,1 flavones, styrylchromo-
nes and 3-halofurans,2 2- and 5-substituted 3-bromothiophenes3 and 3-halopyrroles,4,5 2,4-disubstituted
quinolines,6 1,2,3-triazolylacylsilanes,7 isoxazoles, isothiazoles and pyrazoles,8,9 and for the synthesis
of the natural product L-lathyrine and related analogues.10 Furthermore, when properly functionalised,
compounds of type 1 have also proven to be excellent substrates for the combinatorial and parallel syn-
thesis on solid supports of highly molecularly diverse 2,4,6-trisubstituted pyrimidines.11,12 In addition,
these α-alkynyl ketones, formally analogues of β-dicarbonyl compounds although more reactive, can
be produced readily, mainly by the reaction of alkynylzinc chlorides with acid halides,13 or by the
reaction of lithium or magnesium acetylides with aldehydes followed by subsequent oxidation with
∗
Corresponding author. Fax: +34-972418150; e-mail: dqjvs@xamba.udg.es
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00357-2

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oxalyl chloride in DMSO (Swern oxidation),14 MnO2 or with t-butyl hydroperoxide.15 Reactions of
these metallated acetylides with carboxylic anhydrides, N,N-dialkylcarboxamides or Weinreb amides,
followed by hydrolysis, have also been reported to afford compounds of type 1.2,13
2–4
In view of the strong synthetic potential of these conjugated ynones, and in connection with our
ongoing studies on the synthesis of non-proteinogenic aromatic and heteroaromatic α-amino acids in
an optically active form,16,17 we considered approaching the synthesis of a series of novel chiral α-
alkynyl ketones of type 3 containing a masked α-amino acid moiety as suitable chiral precursors in
our synthetic strategy. In this context, we focused our attention primarily on (R)-(−)-2,2-dimethyl-3-
t-butoxycarbonyl-4-ethynyloxazolidine 2 as an appropriate starting material for the synthesis of these
novel chiral conjugated ynones 3 (Fig. 1).
Figure 1.
2. Results and discussion
Recently, using naturally occurring serine 4 as the primary chiral source, the synthesis of compound
2 has been described,18–21 either by using a procedure based on a modification of the well-known, two-
step Corey–Fuchs22,23 reaction, an aldehyde–alkyne homologation of the Garner aldehyde 5, or via a
Horner–Wadsworth–Emmons reaction between diazomethyl phosphonates and 5.24–26
We proceeded by transforming L-(−)-serine 4 into the corresponding aldehyde 5 according to the
procedure described by Garner.27 The recently proposed alternative route based on a reduction–oxidation
sequence28,29 could also be followed and gave good yields of the desired aldehyde 5. Next, we attempted
the modified Corey–Fuchs procedure in order to obtain 2 from 5 as described by Reginato et al.,19 and
although compound 2 could be isolated in reasonable yields, it turned out that very careful control of
the reaction conditions was necessary in order to avoid the formation of undesired by-products with a
subsequent decrease in the yield. However, when dimethyl-1-diazo-2-oxopropylphosphonate 6, readily
available from tosyl azide and dimethyl-2-oxopropyl phosphonate,30 was allowed to react in the presence
of K2CO3 with aldehyde 5 in MeOH at rt, a very clean and efficient transformation to the enantiomerically
pure alkyne 2 took place. Furthermore, this simple and one-step procedure is ideal for large-scale
preparations. As expected, and due to the known configurational stability of 5 under strongly basic or
nucleophilic conditions,31 the alkyne 2 was isolated in enantiomerically pure form. Next, formation of
the corresponding lithium acetylide 7 by reaction of 2 with n-BuLi in THF at −100°C and condensation
with a number of different aromatic and aliphatic aldehydes, 5 and 8a–h, afforded the corresponding pure
propargyllic alcohol derivatives 9a–i in 62–96% yield, generally as a 5:1 mixture of diastereoisomers.

X. Serrat et al. / Tetrahedron: Asymmetry 10 (1999) 3417–3430
3419
No attempt was made to separate these mixtures (Scheme 1, Table 1). In marked contrast with previous
reports about the condensation of lithium acetylide 7 with other electrophiles (alkyl halides, trialkyl
silyl halides or acyl chlorides), under our reaction conditions, not even traces of enamine 10, which is a
degradation product of 2, were ever detected.18,21
Scheme 1.
The oxidation of the prepared propargyllic alcohols 9a–i to the corresponding α-acetylenic ketones
3a–i deserved some optimisation because we found that, although the reaction of 9a–i with 26 equiv.
of MnO2 in CH2Cl2 (Method A) proceeded smoothly at 0°C to give a very clean transformation with
total disappearance of the starting material, only moderate yields of the final products could be isolated,
even after extensive washing of the MnO2 filtrate with large amounts of solvent. These findings showed
that the final products 3a–i were probably adsorbed on MnO2 due to the fact that no other product was
detected from the reaction mixture. Only in the reaction of 9h with MnO2 could another compound be
identified in addition to the expected acetylenic ketone 3h. This material was obtained in a 1:1 ratio with
3h and was identified as the vinyl derivative 11. Recently, MnO2 has been reported to promote this type
of dehydrogenation reaction in certain systems32 (Scheme 2).
In view of these unsatisfactory results, we were prompted to seek another simple, mild and reliable
oxidation method that could afford our desired targets efficiently. After some experimental work, we
found that oxidation of propargyllic derivatives of type 9 to α-acetylenic ketones of type 3 could be

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Table 1
Prepared propargyllic alcohol derivatives 9a–i
cleanly accomplished in near quantitative yields by employing 10-I-4-iodinane oxide 12 (caution)†
at rt (Method B). This mild oxidising reagent offered several advantages: it is readily available from
inexpensive starting materials in one synthetic step,33 it provides operational simplicity and is easily
handled, and no rigorous drying of solvent was necessary. To our knowledge, this is the first time that such
†
Reagent 12 has been reported to cause explosion upon heavy impact and heating above 200°C.33 In our hands, using 12 at
temperatures between 20 and 70°C, no hazard has been experienced.

X. Serrat et al. / Tetrahedron: Asymmetry 10 (1999) 3417–3430
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Scheme 2.
a reagent has been employed for the successful oxidation of propargyllic alcohols to the corresponding
conjugated acetylenic ketones (Scheme 3, Table 2).
Scheme 3.
Finally, the chiral ethynyl derivative 2 was obtained in an enantiomerically pure form, as deduced by
comparing the specific rotation value with that reported in the literature.19 Under our reaction conditions
for the condensation of 7 with the aldehydes 5 and 8a–h, followed by mild oxidation to the ketones
3a–i, we did not expect that the integrity of the asymmetric centre in the oxazolidine ring could be
affected. Therefore, no attempts to check enantiomeric excesses of compounds 3a–i were made at this
stage. However, in the case of 3a we were able to grow crystals that were suitable for an X-ray crystal-
structure determination, which showed that the crystals were enantiomerically pure. It was then assumed
that they had the expected absolute configuration. This assumption was extended to the complete series
of synthesised compounds, 3a–i (Fig. 2).
In summary, we have developed an efficient procedure for the stereoselective synthesis of novel α-
acetylenic ketones which contain a latent α-amino acid lateral chain. Key steps in this strategy were
the transformation of Garner’s aldehyde 5 into the enantiomerically pure ethynyl oxazolidine 2, and the
optimised reaction conditions for the condensation of the lithium acetylide 7 with the aldehydes 5 and

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Table 2
Prepared chiral acetylenic ketones 3a–i
Figure 2. ORTEP plot34 of the molecular structure of 3a with 50% probability ellipsoids
8a–h to afford the propargyllic derivatives 9a–i. The use for the first time of hypervalent iodine reagent
12 as a mild and effective oxidising agent for the transformation of propargyllic alcohols of type 9 into
the corresponding ketones of type 3 in enantiomerically pure form proved to be an excellent alternative.
The synthetic potential of these chiral building blocks for the preparation of elaborate non-proteinogenic
aromatic and heteroaromatic α-amino acids is currently under investigation.

X. Serrat et al. / Tetrahedron: Asymmetry 10 (1999) 3417–3430
3423
3. Experimental
3.1. General methods
All commercially available chemicals were used as purchased, except that THF was dried over
Na/benzophenone prior to use. Reactions involving lithium acetylides were run under a dry N2 atmos-
phere. Melting points (capillary tube) were measured with a Gallenkamp apparatus and are uncorrected.
IR spectra were recorded on a Nicolet 205FT-IR. 1H and 13C NMR spectra were recorded at 200 and 50
MHz, respectively, on a Bruker DPX200 Advance instrument with TMS as internal standard. MS spectra
were recorded on a VG Quattro instrument in the positive ionisation FAB mode, using 3-NBA or 1-
thioglycerol as the matrix, or on a HP 5989 A for spectra in the EI mode (70 eV) or in the CI mode (using
NH3 as carrier). Elemental analyses were performed on a Carlo Erba elemental analyser 1106. X-ray
diffraction data were collected on a Rigaku AFC5R diffractometer using graphite-monochromated Mo
Kα radiation (λ=0.71069 Å) and a 12 kW rotating anode generator. Optical rotation measurements were
performed on a Perkin–Elmer 241 polarimeter. Analytical TLC was performed on precoated TLC plates,
silica gel SIL G/UV254 from Macheray–Nagel. Flash-chromatography purifications were performed on
SDS silica gel (230–400 mesh).
3.2. (R)-(−)-2,2-Dimethyl-3-t-butoxycarbonyl-4-ethynyloxazolidine 2
A solution of 5 (12.12 g, 52.9 mmol) and dimethyl-1-diazo-2-oxopropylphosphonate (15.24 g, 79.4
mmol) 6 in MeOH (291 mL) was cooled at 0°C under Ar. With vigorous stirring, K2CO3 (14.6 g, 118.4
mmol) was added in one portion. The reaction mixture was stirred at 0°C for 1 h and then 12 h at rt.
The reaction was quenched with a saturated solution of NH4Cl (190 mL), filtered through a Celite®
pad and the solvent concentrated under reduced pressure. The resulting aqueous solution was partitioned
between AcOEt (240 mL) and H2O (95 mL) and the layers separated. The aqueous layer was extracted
with AcOEt (2×240 mL) and the combined organic layers washed with H2O, dried over MgSO4 and
concentrated. Flash-chromatography (SiO2, hexanes:AcOEt 9:1) afforded pure alkyne 2 (9.34 g, 79%) as
a pale yellow oil. [α]D 88.2 (C=1.05 CHCl3); [lit.19,21 −73.5, c=1.01 and −96.5, c=1.23]. IR (film, ν):
20
3293m, 3260m, 2982m, 2937m, 2880m, 1702s, 1478m, 1459m, 1381s, 1264m, 1247m, 1211m, 1174s,
1
1150m, 1097s, 1070m, 1054m, 855m, 770m, 676m cm−1. H NMR (DMSO-d6, T=60°C), δ=4.65–4.6
(m, 1H, CH), 4.14 (dd, J=8.8 Hz, J0=6.0 Hz, 1H, CH2O), 3.98 (dd, J=8.8 Hz, J0=2.4 Hz, 1H, CH2O),
3.13 (d, J=2.2 Hz, 1H, ≡CH), 1.63 (s, 3H, C(CH3)2), 1.53 (s, 9H, C(CH3)3), 1.51 (s, 3H, C(CH3)2. 13
C
NMR (DMSO, T=60°C), δ=150.6 (s, CO), 93.2 (s, C(CH3)2), 83.1 (s, C≡CH), 79.4 (s, C(CH3)3), 71.9
(d, C≡CH), 68.1 (t, CH2), 47.7 (d, CH), 27.8 (q, C(CH3)3), 25.9 (q, C(CH3)2), 24.2 (q, C(CH3)2).
3.3. Synthesis of propargyllic alcohol derivatives 9a–i. General procedure
To a cooled (−100°C) solution of 2 (2.25 g, 10 mmol) in dry THF (30 mL), n-BuLi (2 M solution
in cyclohexane) (5.75 mL, 11.5 mmol) was added dropwise under Ar. The mixture was stirred at that
temperature for 45 min. Then, a solution of the corresponding aldehyde 5 and 8a–h (11 mmol, 1.1
equiv.) in dry THF (22 mL) was slowly added dropwise over a period of 15 min. The reaction mixture,
under Ar, was stirred at −100°C for 3 h. Pre-cooled H2O (5°C) (30 mL) was then added, and the reaction
mixture slowly warmed to rt. The organic solvent was eliminated under reduced pressure, and the residue
partitioned between AcOEt (30 mL) and H2O (20 mL). The layers were separated, and the aqueous one
extracted with AcOEt (3×30 mL). The combined organic layers were washed with sat. NaCl solution

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(50 mL) and dried over MgSO4, the solvent was evaporated and the resulting residue purified by flash-
chromatography (hexanes:AcOEt).
3.4. tert-Butyl (4R)-4-(3-hydroxy-3-phenyl-1-propynyl)-2,2-dimethyl-1,3-oxazolane-3-carboxylate 9a
According to the general procedure described above, reaction between 2 and benzaldehyde 8a afforded
3.14 g (95%) of 9a as a yellowish oil. IR (film, ν): 3420br., 2980m, 2935m, 2878m, 1701s, 1685s,
1477m, 1455m, 1378s, 1367s, 1262m, 1246m, 1170m, 1123m, 1090m, 1056m, 1011m, 861m, 847m,
806d, 769m, 698m. 1H NMR (CDCl3), δ=7.6–7.3 (m, 5H, CH arom.), 5.5 (s, br., 1H, CHOH), 4.65–4.6
(m, 1H, CH), 4.1–4.05 (m, 2H, CH2O), 2.8 (s, br., 1H, CHOH), 1.65 (s, 3H, C(CH3)2), 1.53, 1.42 (2s,
12H, [C(CH3)3+C(CH3)2]). 13C NMR (CDCl3), δ=151.5 (s, CO), 140.6 (s, C arom.), 128.4, 128.2, 126.6
(d, CH arom), 94.2 (s, C(CH3)2), 85.4 (s, C≡C), 81.9 (s, C≡C), 80.4(s, C(CH3)3), 68.6 (t, CH2O), 64.4
(d, CHOH), 48.6 (d, CH), 28.3 (q, C(CH3)3), 25.9 (q, C(CH3)2), 24.4 (q, C(CH3)2). MS (EI) m/e: 314
(M+·−17, 17), 216 (16), 214 (32), 198 (14), 172 (25), 156 (33), 128 (27), 115 (49), 114 (52), 105 (22),
85 (36), 83 (57), 79 (28), 59 (29), 58 (57), 57 (100).
3.5. tert-Butyl (4R)-4-(3-benzo[d][1,3]dioxol-5-yl-3-hydroxy-1-propynyl)-2,2-dimethyl-1,3-oxazolane-
3-carboxylate 9b
According to the general procedure described above, reaction between 2 and piperonal 8b afforded
3.6 g (96%) of 9b as a yellow oil. IR (film, ν): 3400br., 2981m, 2934m, 2884m, 1698s, 1504m, 1487m,
1443m, 1392s, 1378s, 1367s, 1247s, 1246m, 1169m, 1094m, 1040m, 1011d, 938m, 863m, 846m, 810d,
1
770m. H NMR (CDCl3), δ=7.05–6.75 (m, 3H, CH arom.), 5.96 (s, 2H, OCH2O), 5.38 (s, br., 1H,
CHOH), 4.65 (s, br., 1H, CH), 4.10 (m, 2H, CH2O), 3.46 (br., 0.5H, CHOH), 2.88 (br., 0.5H, CHOH),
1.64 (s, 3H, C(CH3)2), 1.51, 1.48 (2s, 12H, [C(CH3)3+C(CH3)2]). 13C NMR (CDCl3), δ=151.4 (s, CO),
147.8, 147.5 (s, C arom.), 134.8, 134.2 (s, C arom), 120.3, 120.2 (d, CH arom), 108.1, 107.9 (d, CH
arom), 107.4 (d, CH arom), 101.15, 101.06 (t, OCH2O), 94.0 (s, C(CH3)2), 85.3 (s, C≡C), 82.8, 80.4
(s, C≡C+C(CH3)3), 68.5 (t, CH2O), 64.2, 64.1 (d, CHOH), 48.6 (d, CH), 28.3, 28.2 (q, C(CH3)3), 26.3
(q, C(CH3)2), 24.7 (q, C(CH3)2). MS (EI) m/e: 375 (M+, 7), 319 (10), 242 (20), 200 (36), 149 (10), 57
(100).
3.6. tert-Butyl (4R)-4-[3-(2-furyl)-3-hydroxy-1-propynyl]-2,2-dimethyl-1,3-oxazolane-3-carboxylate 9c
According to the general procedure described above, reaction between 2 and furfural 8c afforded 2.98
g (93%) of 9c as a brown solid. IR (KBr, ν): 3420br., 2981m, 2934m, 2882m, 1700s, 1671s, 1503w,
1477m, 1458m, 1403s, 1388s, 1367s, 1264m, 1246m, 1156m, 1125m, 1087m, 1053m, 1011m, 846m,
1
806d, 759m, 736m, 672m. H NMR (CDCl3), δ=7.36 (m, 1H, CH arom.), 6.46 (s, br., 1H, CH arom.),
6.36 (s, br., 1H, CH arom.), 5.48 (s, br., 1H, CHOH), 4.66 (s, br., 1H, CH), 4.08 (m, 2H, CH2O), 2.75 (s,
br., 1H, CHOH), 1.65 (s, 3H, C(CH3)2), 1.53, 1.42 (2s, 12H, [C(CH3)3+C(CH3)2]). 13C NMR (CDCl3),
δ=153.0 (s, C arom), 151.5 (s, CO), 142.8, 110.3, 107.7 (d, CH arom.), 94.3 (s, C(CH3)2), 84.5 (s, C≡C),
80.5+79.6 (s, C≡C+C(CH3)3), 68.5 (t, CH2O), 58.0 (d, CHOH), 48.6 (d, CH), 28.3 (q, C(CH3)3), 26.0
(q, C(CH3)2), 24.4 (q, C(CH3)2). MS (EI) m/e: 306 (M+−15, 18), 250 (10), 206 (10), 188 (10), 146 (26),
118 (10), 57 (100).

X. Serrat et al. / Tetrahedron: Asymmetry 10 (1999) 3417–3430
3425
3.7. tert-Butyl (4R)-4-(3-hydroxy-1-pentynyl)-2,2-dimethyl-1,3-oxazolane-3-carboxylate 9d
According to the general procedure described above, reaction between 2 and propanal 8d afforded
2.09 g (74%) of 9d as a yellow oil. IR (film, ν): 3400br., 2977m, 2936m, 2878m, 1704s, 1477m, 1457m,
1391s, 1379s, 1246m, 1210m, 1172m, 1134m, 1096m, 1056m, 1031m, 970m, 861m, 844m, 807d, 770m,
1
672d. H NMR (CDCl3), δ=4.60 (m, 1H, CH), 4.34 (t, J=8.7, 1H, CHOH), 4.02 (m, 2H, CH2O), 2.39
(s, br., 1H, CHOH), 1.75 (m, 2H, CH2CH3), 1.63 (s, 3H, C(CH3)2), 1.50 (s, 9H, C(CH3)3), 1.48 (s,
3H, C(CH3)2), 1.01 (t, J=7.4, 3H, CH2CH3). 13C NMR (CDCl3), δ=151.5 (s, CO), 94.1 (s, C(CH3)2),
83.4 (s, C≡C), 80.6+80.3 (s, C≡C+C(CH3)3), 68.7 (t, CH2O), 63.4 (d, CHOH), 48.5 (d, CH), 30.8 (t,
CH2CH3), 28.3 (q, C(CH3)3), 26.3 (q, C(CH3)2), 24.8 (q, C(CH3)2), 9.34 (q, CH2CH3). MS (FAB+) m/e:
284 (M++1, 20), 228 (40), 224(50), 210 (100).
3.8. tert-Butyl (4R)-4-(3-hydroxy-1-nonyl)-2,2-dimethyl-1,3-oxazolane-3-carboxylate 9e
According to the general procedure described above, reaction between 2 and heptanal 8e afforded
2.81 g (83%) of 9e as a yellow oil. IR (film, ν): 3450br., 2979m, 2946m, 2933m, 2872m, 1704s, 1683s,
1458m, 1392s, 1367s, 1263m, 1246m, 1210m, 1172m, 1139m, 1110m, 1089m, 1057m, 862m, 844m,
807w, 770m, 672w. 1H NMR (CDCl3), δ=4.56 (m, 1H, CH), 4.32 (t, J=5.4, 1H, CHOH), 3.94 (m, 2H,
CH2O), 2.83 (s, br., 1H, CHOH), 1.75 (m, 5H, [C(CH3)2+CH2]), 1.53 (s, 12H, [C(CH3)2+C(CH3)3], 1.35
(m, 8H, CH2), 0.91 (m, 3H, (CH2)5CH3). 13C NMR (CDCl3), δ=151.4 (s, CO), 94.1 (s, C(CH3)2), 83.3
(s, C≡C), 77.6+77.0 (s, C≡C+C(CH3)3), 68.7 (t, CH2O), 62.1 (d, CHOH), 48.5 (d, CH), 37.7 (t, CH2),
31.6 (t, CH2), 28.8 (t, CH2), 28.3 (q, C(CH3)3), 26.3 (q, C(CH3)2), 25.0 (t, CH2), 24.6 (q, C(CH3)2),
22.4 (CH2), 14.0 (q, CH3). MS (FAB+) m/e: 340 (M++1, 21), 284 (34), 266 (100), 240 (39), 238 (39),
224 (54).
3.9. tert-Butyl(4R)-4-[3-hydroxy-3-(2-thienyl)-1-propynyl]-2,2-dimethyl-1,3-oxazolane-3-carboxylate
9f
According to the general procedure described above, reaction between 2 and thiophene-2-carbaldehyde
8f afforded 2.39 g (71%) of 9f as a yellow oil. IR (film, ν): 3422br., 2979m, 2934w, 2879w, 1699s, 1457w,
1379s, 1367s, 1246m, 1170m, 1116m, 1090m, 1056m, 845w, 703w. 1H NMR (CDCl3), δ=7.27 (d, 1H,
J=5Hz, CH arom.), 7.16 (d, 1H, J=3.2 Hz, CH arom.), 6.95 (dd, 1H, J=4.8 Hz, J0=1 Hz, CH arom.), 5.67
(s, br, 1H, CHOH), 4.64 (s, br., 1H, CH), 4.04 (d, 2H, J=4 Hz, CH2O), 3.66 (s, br., 0.5H, CHOH), 3.46 (s,
br., 0.5H, CHOH), 1.64 (s, 3H, C(CH3)2), 1.51, 1.48 (2s, 12H, [C(CH3)3+C(CH3)2]). 13C NMR (CDCl3),
δ=151.4 (s, CO), 144.8 (s, C arom.), 126.5 (d, CH arom.), 125.7 (d, CH arom), 125.3 (d, CH arom.),
94.3 (s, C(CH3)2), 84.6 (s, C≡C), 81.4, 80.4 (s, C(CH3)3)+C≡C), 68.5 (t, CH2O), 59.9 (d, CHOH), 48.6
(d, CH), 28.3 (q, C(CH3)3), 26.3 (q, C(CH3)2), 24.7 (q, C(CH3)2). MS (FAB+) m/e: 338 (M++1, 1), 265
(21), 264 (100), 236 (10), 234 (15), 221 (13), 206 (21), 204 (11), 162 (55).
3.10. tert-Butyl (4R)-4-{3-[(4S)-3-(tert-butyloxycarbonyl)-2,2-dimethyl-1,3-oxazolane-4-yl]-3-hydroxy-
1-propynyl}-2,2-dimethyl-1,3-oxazolane-3-carboxylate 9g
According to the general procedure described above, reaction between 2 and Garner’s aldehyde 5
afforded 2.81 g (62%) of 9g as a colourless oil. IR (film, ν): 3454br., 2979m, 1703s, 1378s, 1172m,
1
1090m. H NMR (CDCl3), δ=4.65–4.6 (m, 2H, 2 CHN), 4.05–4.0 (m, 5H, [CHOH+2CH2O]), 1.64 (s,
6H, C(CH3)2), 1.53 (s, 24H, [C(CH3)2+C(CH3)3]. 13C NMR (CDCl3), δ=154.0 (s, CO), 151.4 (s, CO),

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95.0 (s, C(CH3)2), 94.1 (s, C(CH3)2), 84.7 (s, C≡C), 81.3, 80.4 (s, C≡C+C(CH3)3), 68.6 (t, CH2O),
64.7 (t, CH2O), 63.4 (d, CHOH), 62.3 (d, CH), 48.5 (d, CH), 28.3 (q, C(CH3)3), 26.8, 24.2 (q, C(CH3)2).
MS (FAB+) m/e: 455 (M++1, 12), 440 (22), 224 (22), 57 (100).
3.11. tert-Butyl (4R)-4-(3-hydroxy-4-methyl-1-pentynyl)-2,2-dimethyl-1,3-oxazolane-3-carboxylate 9h
According to the general procedure described above, reaction between 2 and isobutyraldehyde 8g
afforded 2.31 g (78%) of 9h as a colourless oil. IR (film, ν): 3450br., 2977m, 2932m, 2873m, 1703s,
1686s, 1476m, 1458m, 1379s, 1367s, 1263m, 1247m, 1210m, 1173m, 1138m, 1111m, 1091m, 1056m,
863m, 846m, 806d, 770m, 673w. 1H NMR (CDCl3), δ=4.6–4.55 (m, 1H, CH), 4.2 (d, J=4.6, 1H,
CHOH), 4.05–4.0 (m, 2H, CH2O), 1.9–1.85 (m, 1H, CH(CH3)2), 1.64 (s, 3H, C(CH3)2), 1.51 (s, 12H,
[C(CH3)3+C(CH3)2]), 1.0–0.95 (m, 6H, CH(CH3)2). 13C NMR (CDCl3), δ=151.4 (s, CO), 94.2 (s,
C(CH3)2), 80.3 (s, C≡C), 77.6+77.0 (s, C≡C+C(CH3)3), 68.8 (t, CH2O), 67.7 (d, CHOH), 48.6 (d, CH),
34.5 (d, CH(CH3)2), 28.4 (q, C(CH3)3), 25.6 (q, C(CH3)2), 23.5 (q, C(CH3)2), 18.8 (q, CH(CH3)2), 17.3
(q, CH(CH3)2). MS (CI, NH3) m/e: 298 (M++1, 27), 242 (34), 224 (100), 182 (24), 166 (16), 57 (12).
3.12. tert-Butyl (4R)-4-[3-hydroxy-3-(3,4,5-trimethoxyphenyl)-1-propynyl]-2,2-dimethyl-1,3-oxazo-
lane-3-carboxylate 9i
According to the general procedure described above, reaction between 2 and 3,4,5-
trimethoxybenzaldehyde 8h afforded 4.04 g (96%) of 9i as a yellow oil. IR (film, ν): 3444br.,
2979m, 2937m, 2882m, 2839w, 1698s, 1594m, 1504m, 1461m, 1383s, 1332m, 1238m, 1169m, 1125s,
1096m, 1056m, 1008m, 846m, 808w, 771w, 668w, 523w. 1H NMR (CDCl3), δ=6.81 (s, 2H, CH arom.),
5.44 (s, br.,1H, CHOH), 4.66 (s, br., 1H, CH), 4.1–4.05 (m, 2H, CH2O), 3.89 (s, 6H, 2×OCH3), 3.86 (s,
3H, OCH3), 2.51 (s, br., 1H, CHOH), 1.65 (s, 3H, C(CH3)2), 1.53, 1.48 (2s, 12H, [C(CH3)3+C(CH3)2]).
13C NMR (CDCl3), δ=153.2 (s, C arom.), 151.4 (s, CO), 137.8 (s, C arom.), 136.2 (s, C arom.), 103.7
(d, CH arom), 94.1 (s, C(CH3)2), 85.4 (s, C≡C), 81.8, 80.5 (s, C(CH3)3+C≡C), 68.6 (t, CH2O), 64.5
(d, CHOH), 60.7 (q, OCH3), 56.1 (q, OCH3), 48.6 (d, CH), 28.3 (q, C(CH3)2), 26.9, 26.1 (q, C(CH3)2),
25.1, 24.3 (q, C(CH3)2). MS (EI) m/e: 421 (M+, 27), 365 (14), 288 (22), 240 (30), 57 (100).
3.13. Synthesis of α-acetylenic ketones 3a–i. General procedure
3.13.1. Method A
Over a cooled (0°C), mechanically stirred suspension of MnO2 (6.7 g, 78 mmol) in CH2Cl2 (390
mL), a solution of the corresponding propargyllic alcohol 9a–i (3 mmol) in CH2Cl2 (4.5 mL) was added
dropwise. The reaction mixture was stirred at 0°C for 1 h, and then overnight at rt. The mixture was
filtered over a MgSO4 pad and washed successively with CH2Cl2 (100 mL), AcOEt (100 mL) and MeOH
(100 mL). The solvents were removed under reduced pressure, and the residue filtered over a small SiO2
column using hexanes:AcOEt as eluent. The results are summarised in Table 2.
3.13.2. Method B
To a solution of 9a–i (5 mmol) in DMSO (18 mL), 2.1 g (7.5 mmol) of 12 were added at rt in one
portion. After 10 min of vigorous stirring, the resulting suspension becomes a solution. The reaction
mixture was stirred at rt for 4 h, then diluted with H2O (75 mL) and extracted with AcOEt (3×40
mL). The combined extracts were washed with brine (25 mL), dried over MgSO4 and the solvent

X. Serrat et al. / Tetrahedron: Asymmetry 10 (1999) 3417–3430
3427
evaporated under reduced pressure. The resulting residue was filtered through a small SiO2 column using
hexanes:AcOEt as eluent. The results are summarised in Table 2.
3.14. tert-Butyl (4R)-2,2-dimethyl-4-(3-oxo-3-phenyl-1-propynyl)-1,3-oxazolane-3-carboxylate 3a
The reaction between 9a and the oxidising reagent afforded, according to Method A, 0.87 g (88%) and,
according to Method B, 1.56 g (95%) of 3a as a colourless solid. M.p. 77–78°C. [α]D20−141.6 (c=1.11
MeOH). IR (KBr, ν): 2980m, 2932m, 2230m, 1704s, 1650s, 1598s, 1581w, 1477s, 1451m, 1377s, 1367s,
1
1314w, 1264s, 1210m, 1112m, 1090m, 1056m, 857m, 838m, 806w, 769m, 703m. H NMR (DMSO,
T=60°C), δ=8.14 (m, 2H, CH arom.), 7.85–7.65 (m, 3H, CH arom.), 5.04 (dd, J=5.8 Hz, J0=2.6 Hz, 1H,
CH), 4.35–4.2 (m, 2H, CH2O), 1.69 (s, 3H, C(CH3)2), 1.58 (s, 3H, C(CH3)2), 1.56 (s, 9H, C(CH3)3).
13C NMR (DMSO, T=60°C), δ=176.5 (s, CO), 150.5 (s, NCO), 136.1 (s, C arom.), 134.2, 128.5 (d, CH
arom.), 93.8 (s, C(CH3)2), 93.5 (s, C≡C), 79.9 (s, C(CH3)3), 79.1 (s, C≡C), 67.3 (t, CH2O), 48.1 (d,
CH), 27.7 (q, C(CH3)3), 25.9 (q, C(CH3)2), 24.0 (q, C(CH3)2). MS (EI) m/e: 214 (M+−PhCO-, 100),
105 (36), 57 (86).
3.15. tert-Butyl
3-carboxylate 3b
(4R)-4-(3-benzo[d][1,3]dioxol-5-yl-3-oxo-1-propynyl)-2,2-dimethyl-1,3-oxazolane-
The reaction between 9b and the oxidising reagent afforded, according to Method A, 0.87 g (78%)
24
and, according to Method B, 1.75 g (94%) of 3b as a colourless solid. M.p. 99–100°C. [α]D −113.1
(c=0.61 MeOH). IR (KBr, ν): 2981m, 2934m, 2220m, 1700s, 1640m, 1602m, 1504m, 1488m, 1447s,
1377s, 1367s, 1261s, 1210m, 1166m, 1098m, 1038m, 933m, 900w, 850m, 830w, 806w, 770w, 747m,
717w, 703m. 1H NMR (DMSO, T=60°C), δ=7.84 (d, J=8, 1H, CH arom.), 7.55 (s, 1H, CH arom.), 7.15
(d, J=8 Hz, 1H, CH arom.), 6.26 (s, 2H, OCH2O), 5.05–5.0 (m, 1H, CH), 4.3–4.2 (m, 2H, CH2O), 1.68
(s, 3H, C(CH3)2), 1.57 (s, 12H, C(CH3)3+C(CH3)2). 13C NMR (DMSO, T=60°C), δ=174.6 (s, CO),
152.7 (s, C arom.), 150.5 (s, NCO), 148.0 (s, C arom.), 131.1 (s, C arom.), 126.3, 108.0, 107.2 (3d, CH
arom.), 102.2 (t, OCH2O), 93.5 (s, C(CH3)2), 92.9 (s, C≡C), 80.0 (s, C(CH3)3), 79.0 (s, C≡C), 67.4 (t,
CH2O), 48.2 (d, CH), 27.7 (q, C(CH3)3), 26.1 (q, C(CH3)2), 24.1 (q, C(CH3)2). MS (EI) m/e: 373 (M+,
1), 317 (10), 259 (14), 258 (49), 149 (28), 57 (100).
3.16. tert-Butyl (4R)-2,2-dimethyl-4-[3-(2-furyl)-3-oxo-1-propynyl]-1,3-oxazolane-3-carboxylate 3c
The reaction between 9c and the oxidising reagent afforded, according to Method A, 0.73 g (77%)
20
and, according to Method B, 1.46 g (92%) of 3c as a colourless solid. M.p.: 165–166°C. [α]D −191.7
(c=0.42 MeOH). IR (KBr, ν): 3123m, 2992w, 2972m, 2886w, 2229m, 1697s, 1637s, 1561w, 1466m,
1397s, 1365m, 1336m, 1308m, 1262m, 1242m, 1175m, 1151m, 1125m, 1095m, 1061m, 1029m, 983w,
1
849m, 827w, 801m, 770w, 747w, 674w. H NMR (DMSO, T=27°C), δ=8.23 (s, 1H, CH arom.), 7.60
(s, br., 1H, CH arom.), 6.91 (t, J=1.6 Hz, 1H, CH arom.), 5.0 (t, J=4.2 Hz, 1H, CH), 4.20–4.15 (m,
2H, CH2O), 1.66 (s, 3H, C(CH3)2), 1.55 (s, br., 12H, C(CH3)2+C(CH3)3). 13C NMR (DMSO, T=27°C),
δ=163.2 (s, CO), 152.3 (s, NCO), 150.7 (s, C arom.), 150.0 (d, CH arom.), 122.2 (d, CH arom.), 113.3
(d, CH arom.), 93.8 (s, C(CH3)2), 93.5 (s, C≡C), 80.1 (s, C(CH3)3), 78.5 (s, C≡C), 67.5 (t, CH2O), 48.3
(d, CH), 28.0 (q, C(CH3)3), 26.5 (q, C(CH3)2), 24.3 (q, C(CH3)2). MS (FAB+) m/e: 320 (M++1, 10), 265
(17), 264 (100), 220 (53), 218 (22), 206 (56), 204 (55).

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3.17. tert-Butyl (4R)-2,2-dimethyl-4-(3-oxo-1-pentynyl)-1,3-oxazolane-3-carboxylate 3d
The reaction between 9d and the oxidising reagent afforded, according to Method A, 0.60 g (72%)
20
and, according to Method B, 1.29 g (92%) of 3d as a yellow oil. [α]D −63.8 (c=1.17 MeOH). IR
(film, ν): 2981m, 2938m, 2882m, 2215m, 1704s, 1682s, 1478m, 1459m, 1377s, 1367s, 1264m, 1245m,
1
1171m, 1098m, 1077m, 1058m, 970d, 859m, 842m, 807w, 770m, 672w. H NMR (DMSO, T=60°C),
δ=4.90 (dd, J=6.2 Hz, J0=2.4 Hz, 1H, CH), 4.22 (dd, J=8.8 Hz, J0=6.2 Hz, 1H, CH2O), 4.09 (dd,
J=8.8 Hz, J0=2.4 Hz, 1H, CH2O), 2.65 (q, J=7.4, 2H, CH2CH3), 1.65 (s, 3H, C(CH3)2), 1.56 (s, 12H,
[C(CH3)3+C(CH3)2]), 1.17 (t, J=7.4 Hz, 3H, CH2CH3). 13C NMR (DMSO, T=60°C), δ=187.1 (s, CO),
150.4 (s, NCO), 93.5 (s, C(CH3)2), 91.0 (s, C≡C), 80.1+79.8 (s, C≡C+C(CH3)3), 67.3 (t, CH2O), 47.9
(d, CH), 37.8 (t, CH2CH3), 27.7 (q, C(CH3)3), 25.8 (q, C(CH3)2), 24.0 (q, C(CH3)2), 7.4 (q, CH2CH3).
MS (FAB+) m/e: 282 (M++1, 8), 226 (32), 182 (52), 168 (30), 166 (35), 154 (92), 144 (48), 138 (52),
136 (100), 124 (56), 107 (59), 100 (74).
3.18. tert-Butyl (4R)-2,2-dimethyl-4-(3-oxo-1-nonyl)-1,3-oxazolane-3-carboxylate 3e
The reaction between 9e and the oxidising reagent afforded, according to Method A, 0.68 g (68%)
20
and, according to Method B, 1.56 g (93%) of 3e as an orange oil. [α]D −92.3 (c=0.95 MeOH). IR
(film, ν): 2980m, 2959m, 2933m, 2873m, 2216m, 1701s, 1678s, 1477w, 1459m, 1376s, 1366s, 1263m,
1243m, 1209w, 1171m, 1091m, 1054m, 860m, 843m, 807w, 769m. 1H NMR (DMSO, T=60°C), δ=4.89
(dd, J=6.0 Hz, J0=2.4 Hz, 1H, CH), 4.22 (dd, J=9.0 Hz, J0=6.2 Hz, 1H, CH2O), 4.08 (dd, J=9.0 Hz,
J0=2.2 Hz, 1H, CH2O), 2.62 (t, J=7.2, 2H, COCH2), 1.70–1.65 (m, 6H, 3 CH2), 1.65 (s, 3H, C(CH3)2),
1.57 (s, 9H, C(CH3)3), 1.38 (s, br., 5H, CH2+C(CH3)2), 0.97 (t, J=7.0 Hz, 3H, CH2CH3). 13C NMR
(DMSO, T=60°C), δ=186.6 (s, CO), 150.3 (s, NCO), 93.4 (s, C(CH3)2), 90.9 (s, C≡C), 80.2, 79.7 (s,
C≡C+C(CH3)3), 67.3 (t, CH2O), 47.9 (d, CH), 44.5 (t, CH2), 30.4 (t, CH2), 27.6 (t, CH2), 27.5 (q,
C(CH3)3), 25.8 (q, C(CH3)2), 24.0 (q, C(CH3)2), 23.2 (t, CH2), 21.3 (t, CH2), 13.2 (q, CH2CH3). MS
(EI) m/e: 337 (M+, 6), 236 (24), 57 (100).
3.19. tert-Butyl (4R)-2,2-dimethyl-4-[3-oxo-1-propynyl-3-thienyl]-1,3-oxazolane-3-carboxylate 3f
The reaction between 9f and the oxidising reagent afforded, according to Method A, 0.74 g (74%)
20
and, according to Method B, 1.52 g (91%) of 3f as a colourless solid. M.p.: 119–120°C. [α]D −155.2
(c=0.96, MeOH). IR (KBr, ν): 2972m, 2936m, 2884m, 2232m, 1696s, 1622s, 1514w, 1413m, 1384s,
1338w, 1283m, 1260m, 1239m, 1170m, 1148m, 1112m, 1090m, 1057m, 846w, 751m, 731w. 1H NMR
(DMSO, T=60°C), δ=8.21 (d, J=4.8 Hz, 1H,CH arom.), 8.05 (d, J=3.2 Hz, 1H, CH arom.), 7.40–7.35
(m, 1H, CH arom.), 5.00–4.95 (m, 1H, CH), 4.25–4.20 (m, 2H, CH2O), 1.68 (s, 3H, C(CH3)2 ), 1.57 (s,
br., 12H, [C(CH3)3+C(CH3)2]). 13C NMR (DMSO, T=60°C), δ=168.3 (s, CO), 150.5 (s, NCO), 143.6
(s, C arom.), 136.8 (s, C arom.), 135.4 (s, C arom.), 128.6 (s, C arom.), 93.6 (s, C≡C), 92.3 (s, C(CH3)2),
80.0 (s, C(CH3)3), 78.7 (s, C≡C), 67.4 (t, CH2O), 48.1 (d, CH), 27.7 (q, C(CH3)3), 26.1 (q, C(CH3)2),
24.1 (q, C(CH3)2). MS (FAB+) m/e: 336 (M++1, 4), 281 (20), 280 (100), 236 (73), 234 (27), 222 (90),
220 (73).

X. Serrat et al. / Tetrahedron: Asymmetry 10 (1999) 3417–3430
3429
3.20. tert-Butyl (4R)-4-{3-[(4S)-3-(tert-butyloxycarbonyl)-2,2-dimethyl-1,3-oxazolane-4-yl]-3-oxo-
1-propynyl}-2,2-dimethyl-1,3-oxazolane-3-carboxylate 3g
The reaction between 9g and the oxidising reagent afforded, according to Method A, 0.70 g (52%)
20
and, according to Method B, 1.71 g (76%) of 3g as a colourless oil. [α]D −165.1 (c=0.45 MeOH). IR
(film, ν): 2965m, 2938m, 2870m, 2214m, 1714s, 1682m, 1477w, 1470m, 1372s, 1262m, 1210m, 1175m,
1098m, 1068m, 1052m, 849m, 807d, 766m. 1H NMR (DMSO, T=60°C), δ=4.94 (dd, J=6.2 Hz, J0=2.2
Hz, 1H, CH), 4.54 (dd, J=7.4 Hz, J0=3.4 Hz, 1H, CH0), 4.30–4.25 (m, 2H, CH2O+CH2O0), 4.1–4.05 (m,
0
0
2H, CH2O+CH2O0), 1.69 (s, 3H, C(CH3)2 ), 1.62 (s, 3H, C(CH3)2), 1.57 (s, 3H, C(CH3)2 ), 1.56 (s, 9H,
C(CH3)3), 1.51 (s, 3H, C(CH3)2). 13C NMR (DMSO, T=60°C), δ=186.7 (s, CO), 150.4 (s, NCO), 94.1
(s, C(CH3)2), 93.6 (s, C≡C), 79.9 (s, C≡C), 79.8, 78.4 (s, 2 C(CH3)3), 67.2 (t, CH2O), 66.0 (d, CH0),
64.6 (t, CH2O0), 48.0 (d, CH), 27.7, 27.6 (q, 2 C(CH3)3), 25.9 (q, C(CH3)2), 23.9 (q, C(CH3)2). MS (CI,
NH3) m/e: 453 (M++1, 1), 353 (26), 298 (16), 297 (100), 239 (30), 85 (10), 83 (14), 57 (11).
3.21. tert-Butyl (4R)-2,2-dimethyl-4-(4-methyl-3-oxo-1-pentynyl)-1,3-oxazolane-3-carboxylate 3h
The reaction between 9h and the oxidising reagent afforded, according to Method A, 0.60 g (68%) of
a 1:1 mixture of 3h and 11 as a colourless oil. According to Method B, 1.22 g (83%) of 3h as colourless
oil. [α]D20 −148.9 (c=1.06 MeOH). IR (film, ν): 2977m, 2935m, 2877m, 2215m, 1705s, 1679s, 1478m,
1466m, 1377s, 1263m, 1245m, 1171m, 1092m, 1056m, 958w, 947w, 855m, 838m, 806w, 770m, 736w,
675w. 1H NMR (CDCl3 T=50°C), δ=4.75–4.70 (m, 1H, CH), 4.10–4.05 (m, 2H, CH2O), 2.65–2.60 (m,
1H, CH(CH3)2), 1.68 (s, 3H, C(CH3)2), 1.57 (s, 3H, C(CH3)2), 1.55 (s, 9H, C(CH3)3 ), 1.24 (d, J=7.0
Hz, 6H, CH(CH3)2). 13C NMR (CDCl3 T=50°C), δ=191.1 (s, CO), 151.2 (s, NCO), 94.6 (s, C(CH3)2),
91.3 (s, C≡C), 80.9 (s, C(CH3)3), 80.1 (s, C≡C), 68.0 (t, CH2O), 48.6 (d, CH), 43.0 (d, CH(CH3)2), 28.2
(q, C(CH3)3), 26.2 (q, C(CH3)2), 24.6 (q, C(CH3)2), 17.7 (q, CH(CH3)2). MS (EI) m/e: 268(5), 240(18),
222(14), 197(8), 196(100), 182(17), 180(33), 57(15).
3.21.1. Spectroscopic data for 11
1H NMR (CDCl3), δ=6.46 (s, br., 1H, C=CH2), 6.07 (s, br., 1H, C=CH2), 4.75–4.70 (m, 1H, CH),
4.15–4.10 (m, 2H, CH2O), 1.94 (s, 3H, CCH3), 1.68 (s, 3H, C(CH3)2), 1.56 (s, 3H, C(CH3)2), 1.53
(s, 9H, C(CH3)3). 13C NMR (CDCl3), δ=179.5 (s, CO), 151.1 (s, NCO), 145.1 (s, C=CH2), 130.9 (t,
C=CH2), 94.7 (s, C(CH3)2), 91.0 (s, C≡C), 80.7 (s, C(CH3)3), 79.1 (s, C≡C), 67.9 (t, CH2O), 48.6 (d,
CH), 28.3 (q, C(CH3)3), 26.4 (q, C(CH3)2), 24.6 (q, C(CH3)2), 15.9 (q, CH(CH3)2). MS (EI) m/e: 266(5),
238(9), 220(18), 195(8), 194(100), 180(9), 179(8), 178(50), 136(6), 57(30).
3.22. tert-Butyl (4R)-2,2-dimethyl-4-[3-oxo-1-propynyl-3-(3,4,5-trimethoxyphenyl)]-1,3-oxazolane-
3-carboxylate 3i
The reaction between 9i and the oxidising reagent afforded, according to Method A, 0.99 g (79%)
20
and, according to Method B, 1.96 g (94%) of 3i as a yellowish oil. [α]D −126.5 (c=0.83, MeOH). IR
(film, ν): 2979m, 2939m, 2882m, 2840w, 2223m, 1696s, 1644s, 1582s, 1503m, 1463m, 1415s, 1376s,
1332s, 1232m, 1209m, 1173m, 1128s, 1062m, 1002m, 916w, 862m, 846m, 771w, 744m, 676w. 1H NMR
(DMSO, T=60°C), δ=7.47 (s, 2H, CH arom.), 5.04 (dd, J=5.8 Hz, J0=2.6 Hz, 1H, CH), 4.25–4.20 (m,
2H, CH2O), 3.97 (s, 6H, 2×OMe), 3.92 (s, 3H, OMe), 1.69 (s, 3H, C(CH3)2), 1.59 (s, 3H, C(CH3)2), 1.55
(s, 9H, C(CH3)3). 13C NMR (DMSO, T=60°C), δ=175.3 (s, CO), 152.8 (2s, C arom.), 150.6 (s, NCO),
143.8 (s, C arom.), 131.3 (s, C arom.), 107.0 (2s, C arom.), 93.6, 93.4 (2s, C≡C+C(CH3)2), 80.0, 78.9

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X. Serrat et al. / Tetrahedron: Asymmetry 10 (1999) 3417–3430
(2s, C≡C+C(CH3)3), 67.5 (t, CH2O), 60.1 (q, OCH3), 56.1 (2q, OCH3), 48.2 (d, CH), 27.7 (q, C(CH3)3),
26.2 (q, C(CH3)2), 24.1 (q, C(CH3)2). MS (FAB+) m/e: 420 (M++1, 14), 419 (M+, 35), 365 (14), 364
(69), 363 (20), 320 (17), 306 (20), 304 (31), 195 (100).34
Acknowledgements
Generous financial support from the Ministerio de Educación y Ciencia (Spain) through project
PB94-0509, Medichem S.A. (Barcelona) and Roviall Química S.L. (Murcia) is gratefully acknowledged.
Thanks are also due to Dr. Llüisa Matas (Servei d´Anàlisi, Universitat de Girona) for recording the NMR
spectra and performing the microanalyses, to Dr. Dolors Pujol (Facultad de Farmacia, Universitat de
Barcelona), Dr. M. Maestro and Dr. J. Mahía (Servicios Xerais de Apoio á Investigación, Universidade
da Coruña) for recording the mass spectra. One of us (G.C.) thanks the Ministerio de Educación y Ciencia
(Spain) for a pre-doctoral fellowship.
References
1. Obrecht, D.; Weiss, B. Helv. Chim. Acta 1989, 72, 117.
2. Obrecht, D. Helv. Chim. Acta 1989, 72, 447.
3. Masquelin, T.; Obrecht, D. Tetrahedron Lett. 1994, 35, 9387.
4. Masquelin, T.; Obrecht, D. Synthesis 1995, 276.
5. Utimoto, K.; Miwa, H.; Nozaki, H. Tetrahedron Lett. 1981, 22, 4277.
6. Masquelin, T.; Obrecht, D. Tetrahedron 1997, 53, 641.
7. Degl’Innocenti, A.; Scafato, P.; Capperucci, A.; Bartoletti, L.; Mordini, A.; Reginato, G. Tetrahedron Lett. 1995, 36, 9031.
8. Garvey, D. S.; Wasicak, J. T.; Elliot, R. L.; Lebold, S. A.; Hettinger, A.-M.; Carrera, G. M.; Lin, N.-H.; He, Y.; Holladay,
M. W.; Anderson, D. J.; Cadman, E. D.; Raszkiewicz, J. L.; Sullivan, J. P.; Arneric, S. P. J. Med. Chem. 1994, 37, 4455.
9. Falorni, M.; Giacomelli, G.; Spanedda, A. M. Tetrahedron: Asymmetry 1998, 9, 3039.
10. Adlington, R. M.; Baldwin, J. E.; Catterick, D.; Pritchard, G. J. Chem. Commun. 1997, 1757.
11. Obrecht, D.; Abrecht, C.; Grieder, A.; Villalgordo, J. M. Helv. Chim. Acta 1997, 80, 65.
12. Chucholowski, A.; Masquelin, T.; Obrecht, D.; Stadlwieser, J.; Villalgordo, J. M. Chimia 1996, 50, 525.
13. Verkruijse, H. D.; Heus-Kloos, Y. A.; Brandsma, L. J. Organometallic Chem. 1988, 338, 289.
14. Larson, D. P.; Heathcock, C. H. J. Org. Chem. 1997, 62, 8407.
15. Palombi, L.; Arista, L.; Lattanzi, A.; Bonadies, F.; Scettri, A. Tetrahedron Lett. 1996, 37, 7849.
16. Serrat, X. PhD dissertation. University of Girona, 1999.
17. Cabarrocas, G. PhD dissertation. University of Girona, in preparation.
18. Reginato, G.; Mordini, A.; Degl’Innocenti, A.; Caracciolo, M. Tetrahedron Lett. 1995, 36, 8275.
19. Reginato, G.; Mordini, A.; Caracciolo, M. J. Org. Chem. 1997, 62, 6187.
20. Reginato, G.; Mordini, A.; Capperucci, A.; Degl’Innocenti, A.; Manganiello, S. Tetrahedron 1998, 54, 10217.
21. Meffre, P.; Gauzy, L.; Branquet, E.; Durand, P.; Goffic, F. L. Tetrahedron 1996, 52, 11215.
22. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 12, 3769.
23. Grandjean, D.; Pale, P.; Chuche, J. Tetrahedron Lett. 1994, 35, 3529.
24. Gilbert, J. C.; Weerasooriya, U. J. Org. Chem. 1982, 47, 1837.
25. Ohira, S. Synth. Commun. 1989, 19, 561.
26. Müller, S.; Liepold, B.; Roth, G. J.; Bestmann, H.-J. Synlett 1996, 521.
27. Garner, P.; Park, J. M. Org. Synth. 1991, 70, 18.
28. McKillop, A.; Taylor, R. J. K.; Watson, R. J.; Lewis, N. Synthesis 1994, 31.
29. Dondoni, A.; Perrone, D. Synthesis 1997, 527.
30. Callant, P.; D’Haenens, L.; Vandewalle, M. Synth. Commun. 1984, 14, 155.
31. Duthaler, R. O. Tetrahedron 1994, 50, 1539.
32. Aoyama, T.; Sonoda, N.; Yamauchi, M.; Toriyama, K.; Anzai, M.; Ando, A.; Shiori, T. Synlett 1998, 35.
33. Frigerio, M.; Santagostino, M.; Sputore, S.; Palmisano, G. J. Org. Chem. 1995, 60, 7272.
34. Johnson, C. K. ORTEP II. Report ORNL-5138, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 1976.