A synthetic approach to 3-hydroxy 4-substituted carboxylic acids based on the stereoselective reduction of 1-trimethylsilyl-1-alkyn-3-ones

Article abstract of DOI:10.1016/S0040-4020(00)00905-4

The oxazaborolidine-mediated reduction of chiral, 4-substituted 1-trimethylsilyl-1-alkyn-3-ones followed by hydroboration affords syn or anti 3-hydroxy 4-substituted carboxylic acids, common substructures of a number of biologically active macrolides, peptides and depsipeptides, with high control on the new C(3) stereocenter. This strategy has been applied to the synthesis of (3S,4S)-3-hydroxy-4-methylheptanoic acid and of N-Boc-statine, constituents of permentin A and pepstatin, respectively. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00905-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 9305±9312
A Synthetic Approach to 3-Hydroxy 4-Substituted Carboxylic
Acids based on the Stereoselective Reduction of
1-Trimethylsilyl-1-alkyn-3-ones
²
Carme Alemany, Jordi Bach, Jordi Garcia, Marta Lopez and Ana B. Rodrõguez
*
Â
Â
 Á  Á
Departament de Quõmica Organica, Div. III, Universitat de Barcelona, C/Martõ i Franques 1-11, 08028 Barcelona, Catalonia, Spain
Received 24 July 2000; revised 22 September 2000; accepted 28 September 2000
AbstractÐThe oxazaborolidine-mediated reduction of chiral, 4-substituted 1-trimethylsilyl-1-alkyn-3-ones followed by hydroboration
affords syn or anti 3-hydroxy 4-substituted carboxylic acids, common substructures of a number of biologically active macrolides, peptides
and depsipeptides, with high control on the new C(3) stereocenter. This strategy has been applied to the synthesis of (3S,4S)-3-hydroxy-4-
methylheptanoic acid and of N-Boc-statine, constituents of permentin A and pepstatin, respectively. q 2000 Elsevier Science Ltd. All rights
reserved.
Introduction
addition of the appropiate reagents (e.g. allyl boron
reagents7 or enolates8) to chiral a-substituted aldehydes 7,
as well as the reduction of the corresponding 3-keto esters 8.
In particular, when X are protected amino groups, the inten-
sive search for diastereoselective synthetic approaches to
such compounds carried out over the last decade, both in
academic and industrial laboratories,9 has led to a number of
useful preparations of some of these compounds in reason-
able yields and stereoselectivities.10 However, the stereo-
chemical control at the emergent stereocenter on C(3) is
Achieving stereocontrol in the construction of acyclic
systems is a challenging goal in organic synthesis. In this
connection, the incorporation of a chiral 3-hydroxy-4-
methylbutanoic acid moiety, as well as its 4-methoxy ana-
logue, to a growing framework is of great interest since they
are common structural elements of a number of biologically
active natural and synthetic macrolides of interest in pharm-
acy and veterinary (e.g. tylosin and leucomycins).1 In the
same way, structurally related 3-hydroxy 4-amino acids are
also deserving interest since relatively simple compounds as
statine (1) or cyclohexylstatine (2) became key components
of peptidomimetic protease inhibitors.2 Interestingly, the
syn (threo) relative con®guration of the amino and hydroxy
groups, which mimics the tetrahedral transition state for
peptide bond hydrolysis, has been revealed essential for
their bioactivity. However, several members of the corre-
sponding diastereomeric anti (erythro) series are also of
natural occurrence.3 Representative examples of these
substructures are isostatine (3) and (3R,4S)-3-hydroxy-4-
methylamino-5-phenylpentanoic acid (4), constituents of
the bioactive depsipeptides didemnins A±C4,5 and of hapa-
losin,6 respectively (Fig. 1).
Obvious routes to 3-hydroxy 4-substituted carboxylic acid
substructures of 1 and 2 (see 5) and of 4 (see 6) include the
Keywords: oxazaborolidines; amino acids and derivatives; hydroxy acids
and derivatives; reduction.
* Corresponding author. Tel.: 134-934021247; fax: 134-933397878;
e-mail: jgarcia@qo.ub.es
Current address: Laboratoris Almirall Prodesfarma, C/ Cardener 68-74,
²
Figure 1.
08024, Barcelona.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00905-4

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C. Alemany et al. / Tetrahedron 56 (2000) 9305±9312
Table 1. Reduction of ketones 10 with BH3:SMe2 in the presence of oxaza-
borolidines 11
not always satisfactory, specially in the mismatched cases,
and a general and uni®ed route to both, syn and anti stereo-
isomers (5 and 6, respectively), is still a challenge.
Entry
Ketones
Catalyst
Yielda (%)
12/13 Ratioa,b
1
2
3
4
5
6
7
8
9
10
(R)-11
(S)-11
(R)-11
(S)-11
(R)-11
(S)-11
(R)-11
(S)-11
(R)-11
(S)-11
97 (90)
90 (91)
75 (70)
80 (71)
74 (70)
80 (79)
85 (60)
85 (76)
55 (60)
52
24:1 (19:1)
1:24 (1:19)
49:1 (24:1)
1:49 (1:24)
32:1 (7.3:1)
1:10 (1:8)
9:1 (9:1)
By adoption of the strategy based on double-asymmetric
synthesis,11 this goal could be attained in a predictible and
controlled manner from a common precursor with the use of
a chiral reagent (or catalyst) capable of displaying such high
asymmetric induction that could override the normally
small diastereofacial selectivity of a chiral substrate (e.g.
7 or 8). In this connection, oxazaborolidine-mediated reduc-
tion of ketones could obviously accomplish that require-
ment due to the high level of enantioselectivity observed
in many cases.12
1:33.5 (1:32)
.50:1 (25:1)
16.8
a Reactions were carried out by slow addition of 10 (1.0 mmol) to a
mixture of BH3:SMe2 (1.2 mmol) and catalyst (1.0 mmol) in THF at
08C. Within parentheses values using 0.2 mmol of catalyst.
b Determined by 19F NMR analysis of the corresponding Mosher esters.
Con®guration at C(3) was determined by the Kakisawa method.19 In
addition, stereochemistry of 12a, 12d, 12e, 13a, 13d and 13e were
con®rmed by chemical correlation with the known acids (5 or 6) or
their methyl esters (see text).
Studies in our laboratory13 and others14 have demonstrated
that prochiral 1-trialkylsilyl-1-alkyn-3-ones are especially
adequate substrates for such reductions. In addition, the
highly enantioenriched propargylic alcohols obtained are
versatile building blocks for asymmetric synthesis. Based
on these studies, we report herein an alternative, stereo-
divergent route to compounds 5 and 6, which is summarized
in Scheme 1.15
contrast, reductions of 10 with NaBH4 in MeOH led to a
mixture of diastereomeric alcohols 12/13 (from 1:1.2 to
1:3.5 syn/anti ratio) in all the cases.
Preparation of a,b-acetylenic ketones
A set of representative chiral a-substituted acetylenic
ketones 10a±c were easily prepared by reaction of freshly
generated solution of lithium trimethylsilylacetylide
(1±2 equiv.) with the Weinreb amides 9a±c (86±90%
yield) which, in turn, were obtained by standard methods
from the corresponding chiral acids or methyl esters.16
Besides ketones 10, a small amount (5±8%) of desilylated
ketones were also isolated by ¯ash chromatography.17 On
the other hand, a-Boc-amino ketones 10d and 10e were also
available in a similar way following Rappoport's protocol.18
Reduction of the hexacarbonyldicobalt complexes derived
from 10 were also investigated. Ketones 10a and 10b were
easily transformed into their cobalt complexes 14a and 14b,
respectively, with octacarbonyldicobalt in pentane. Since
our previous experience indicated that oxazaborolidines
11 were inef®cient for the reduction of very crowded
ketones such as 14,13a,b we treated 14a with BH3:SMe2 in
the presence of less steric demanding oxazaborolidines 1520
in THF under Ar at 08C. As expected, the temporary trans-
formation of the acetylenic moiety in a much bulkier group
enhanced the selectivity in the reduction step leading to
propargylic alcohols 12a or 13a, in good yields and selec-
tivities after regeneration of the triple bond with the aid of
a mild oxidant like Ce(IV). Unfortunately, when we
attempted to extent this strategy to the only slightly more
crowded ketone 14b, it was sluggishly reduced under
similar conditions. In conclusion, the reduction of the Co
complexes of acetylenic ketones could give excellent
Reduction of a,b-acetylenic ketones
Reductions of 10 were performed by slow addition of the
ketone to a solution of BH3:SMe2 and (R)- or (S)-11 in THF.
To our satisfaction, the oxazaborolidine±borane system largely
overcame the intrinsic facial bias of the carbonyl group of
10 resulting in good to excellent diastereoselectivities even
in the mismatched cases, as shown in Table 1. In sharp
Scheme 1.

C. Alemany et al. / Tetrahedron 56 (2000) 9305±9312
9307
Conclusions
In summary, we have demonstrated that the tandem stereo-
selective reduction/hydroboration applied to a-substituted,
chiral trimethylsilyl acetylenic ketones constitutes an
ef®cient, alternative approach to syn or anti 3-hydroxy 4-
substituted carboxylic acids with high control on the C(3)
con®guration. Similar reduction of the corresponding Co
complexes, although highly stereoselective, has proved to
be only suitable for the less crowded ketone 10a. This
strategy has been applied to the synthesis of different
chiral b-hydroxy acids, including (3S,4S)-3-hydroxy-4-
methylheptanoic acid (5a), present in permentin A, and N-
Boc-statine (5d).
Experimental
General methods
Scheme 2.
All the solvents were distilled from an appropriate drying
agent and stored under nitrogen atmosphere. The crude
products were puri®ed by column chromatography on silica
gel of 230±400 mesh (¯ash chromatography). Thin-layer
chromatograms were performed on HF 254 silica gel plates
(using CH2Cl2, CH2Cl2/MeOH, hexane/AcOEt or CH2Cl2/
hexane as the eluents, as indicated after the Rf values). Melt-
Figure 2.
1
ing points are uncorrected. H, 13C, and 19F NMR spectra
Scheme 3.
stereoselectivities but it seems to be only suitable for
substrates with low steric requeriments (Scheme 2).14c
were obtained in CDCl3 at 200, 50.3 and 282.2 MHz,
respectively; and chemical shifts are given in ppm with
respect to internal TMS. Infrared spectra were measured
on a Perkin±Elmer 681 on NaCl plates (neat) or in KBr;
only the most signi®cant absorptions, in cm21, are indicated.
Transformation of alcohols 12 and 13 into b-hydroxy
acids
Â
Microanalyses were performed by the Serveis Cientõ®co-
Tecnics (Universitat de Barcelona). Optical rotations were
Á
Having in hand stereochemically enriched propargylic
alcohols, we undertook their transformation into b-hydroxy
acids. Accordingly, hydroboration21 of 12a with dicyclo-
hexylborane followed by oxidative workup in a basic
medium22 afforded 5a, a constituent of antibiotic depsipep-
tide permetin A,23 which was further transformed24 into its
known methyl ester derivative 16.25 In a similar way, 13a
was transformed to 6a and then into the diastereomeric anti
b-hydroxy methyl ester 17 (Fig. 2).26,27
measured at 20^28C. Chemical ionization mass spectra
(NH3) are given in m/z. HRMS (EI and FAB) were obtained
at the Centro de Apoio Cienti®co-Tecnoloxico a Investi-
Â
gacion (CACTI, Universidad de Vigo). Weinreb amides
9b,28 9c,29 9d,30 and 9e31 as well as oxazaborolidines 1113a
and 15,20 were prepared according to published procedures.
(S)-N-Methoxy-2,N-dimethylbutanamide (9). Prepared
according to a described protocol.32 To a suspension of
N,O-dimethylhydroxylamine hydrochloride (1.91 g, 19.6
mmol) in anh. CH2Cl2 (40 mL), triethylamine (4.0 mL,
Eventually, the remaining alcohols 12 and 13 showed a
similar trend and were stereoselectively converted into the
desired b-hydroxy acids 5 and 6, respectively, in good
yields (Scheme 3).
29.3 mmol),
(S)-2-methylbutanoic
acid
(0.53 mL,
4.89 mmol), a solution of 4-dimethylaminopyridine (4-
DMAP, 1.20 g, 9.8 mmol) in CH2Cl2 (5 mL), and

9308
C. Alemany et al. / Tetrahedron 56 (2000) 9305±9312
diisopropylcarbodiimide (1.53 mL, 9.8 mmol) were added
successively. After 48 h at rt, the suspension was diluted
with CH2Cl2 (60 mL). After washing with water
(4£20 mL), the organic layer was dried over MgSO4 and
the solvent removed in vacuo. The residue was puri®ed by
¯ash chromatography (CH2Cl2/MeOH, 95:5) to yield
702 mg (99%) of 9a: oil; Rf 0.38 (CH2Cl2/MeOH, 95:5);
1H NMR d 0.89 (t, Jˆ7.4 Hz, 3H), 1.11 (d, Jˆ6.4 Hz,
3H), 1.41 (m, 1H), 1.66 (m, 1H), 2.80 (m, 1H), 3.19
(s, 3H), 3.70 (s, 3H); 13C NMR d 11.8, 16.9, 26.6, 32.0,
36.5, 61.2, 178.3; IR (neat) 2980, 2940,1660;
[a]2D0ˆ134.9 (c 1.0, CHCl3); MS (NH3/CI) m/z (rel. int.)
163 (100, [M1NH41]); Anal. Calcd for C7H15NO2: C, 57.90;
H, 10.41. Found: C, 58.02; H, 10.20.
6.7 mmol) were added dropwise. The solution was stirred
for 30 min and then allowed to warm to 08C. Then, a solu-
tion of amide 9d (800 mg, 2.92 mmol) in anh. THF (3 mL)
was dropwise added and the mixture was stirred at 08C. The
progress of the reaction was monitored by TLC. After
40 min, the reaction mixture was slowly added via cannula
into pH 7 phosphate buffer (50 mL) and extracted with
CH2Cl2. The organic layer was washed with brine, dried
over MgSO4, ®ltered and concentrated in vacuo. The residue
was puri®ed by a short ¯ash chromatography (CH2Cl2) to
yield 672 mg (74%) of ketone 10d as a yellowish oil: Rf 0.54
(CH2Cl2); 1H NMR d 0.23 (s, 9H), 0.94 (d, 3H, Jˆ6.2 Hz),
0.95 (d, 3H, Jˆ2.1 Hz), 1.40 (m, 2H), 1.42 (s, 9H), 1.73
(m, 1H), 4.36 (m, 1H), 5.02 (d, 1H, Jˆ8.0 Hz); 13C NMR d
1.1, 21.5, 23.0, 24.7, 28.1, 40.5, 59.6, 79.9, 100.1, 101.6,
155.3, 187.4; IR (®lm) 3360, 2149, 1718, 1684;
[a]2D0ˆ125.5 (c 1.4, CHCl3); HRMS calcd for
C16H29NSiO3 (M1) 311.1917, found 311.1921.
General procedure for preparation of acetylenic ketones
Ketone 10a. To a stirred solution of trimethylsilylacetylene
(0.31 mL, 2.2 mmol) in anh. THF (8 mL) at 2788C, a solu-
tion of BuLi in hexanes (1.40 mL, 2.1 mmol) were added
dropwise. The solution was stirred for 30 min. Then, a solu-
tion of 290 mg (2.0 mmol) of 9a in 5 mL of anh. THF was
dropwise added and the mixture was allowed to warm to rt
The progress of the reaction was monitored by TLC. After
3 h, the reaction mixture was slowly added via cannula into
pH 7 phosphate buffer (15 mL) and the mixture was par-
titioned with diethyl ether (40 mL). The organic layer was
dried over MgSO4, ®ltered and carefully concentrated in
vacuo. The crude which was puri®ed by a short ¯ash
chromatography (CH2Cl2) to yield 317 mg (87%) of (S)-4-
methyl-1-trimethylsilylhex-1-yn-3-one, 10a,33 as a volatile
yellowish oil: Rf 0.48 (hexane/CH2Cl2 1:1); 1H NMR d 0.25
(s, 9H), 0.93 (t, 3H, Jˆ7.4 Hz), 1.17 (d, 3H, Jˆ6.8 Hz), 1.51
(m, 1H), 1.80 (m, 1H), 2.50 (m, 1H); 13C NMR d 20.8,
11.4, 15.3, 25.7, 49.7, 98.4, 101.2, 191.9; IR (®lm) 2980,
2940, 2150, 1680, 1615, 850; [a]2D0ˆ114.4 (c 1.1, CHCl3)
[lit.33 110.37 for 61% o.p.]; HRMS calcd for C10H18SiO
(M1) 182.1127, found 182.1127.
Further elution with CH2Cl2/MeOH (95:5) led to recover
120 mg (15%) of starting amide 9d.
(S)-4-(tert-Butoxycarbonylamino)-5-phenyl-1-trimethyl-
silylpent-1-yn-3-one (10e). The procedure described above
was applied to prepare 10e as a yellowish oil in 50%. Rf 0.73
1
(CH2Cl2); H NMR d 0.25 (s, 9H), 1.41 (s, 9H), 3.17 (dd,
1H, Jˆ6.3, 14.1 Hz), 3.21 (dd, 1H, Jˆ5.7, 14.1 Hz), 4.67
(m, 1H), 5.02 (broad d, NH, Jˆ4.8 Hz), 7.15±7.31 (m, 5H);
13C NMR d 20.9, 28.3, 37.3, 61.9, 79.9, 100.2, 102.6,
126.5, 127.0, 129.5, 135.5, 155.0, 186.7; IR (®lm) 3850,
2150, 1717, 1685. [a]2D0ˆ15.4 (c 0.36, CHCl3); MS
(NH3/CI) m/z (rel. int.) 346 (100, [M1H1]); HRMS calcd
for C19H27SiNO3Si (M1) 345.1760, found 345.1764.
General procedure for oxazaborolidine-mediated
reduction of acetylenic ketones
Alcohol 12a. A solution of 10a (292 mg, 1.6 mmol) in THF
(6 mL) was slowly (ca. 45 min) added to a solution of (R)-11
(1.6 mmol) and BH3:SMe2 (190 mL, 1.9 mmol) in THF
(4 mL) at 08C under Ar. Upon completion of the addition,
TLC revealed the disappearance of the starting ketone.
Reaction was cautiously quenched by addition of MeOH
(3 mL) at 08C. The solution was stirred for 2 h at rt and
then concentrated under vacuum. The residue was par-
titioned with CH2Cl2 and aq. NaHCO3. The organic layer
was dried over MgSO4, ®ltered and concentrated in vacuo.
The residue was puri®ed by ¯ash chromatography (CH2Cl2
and then CH2Cl2/MeOH 95:5 to recover the amino
alcohol derived from 11) to yield 286 mg (97%) of
(3R,4S)-4-methyl-1-trimethylsilylhex-1-yn-3-ol, 12a: oil;
(S)-5-Benzyloxy-4-methyl-1-trimethylsilylpent-1-yn-3-one
(10b). 90% Yield of a yellowish oil. Rf 0.56 (CH2Cl2); H
1
NMR d 0.28 (s, 9H), 1.25 (d, 3H, Jˆ7.0 Hz), 2.94 (m, 1H),
3.64 (dd, 1H, Jˆ5.4, 9.2 Hz), 3.81 (dd, 1H, Jˆ7.0, 9.2 Hz),
4.57 (s, 2H), 7.15±7.40 (m, 5H); 13C NMR d 20.8, 13.1, 48.9,
71.3, 73.3, 98.9, 101.1, 127.5, 127.6, 128.3, 138.1, 189.3; IR
(®lm) 2980, 2170, 1690. [a]2D0ˆ21.5 (c 1.1, CHCl3); MS
(NH3/CI) m/z (rel. int.) 292 (100, [M1NH14 ]); HRMS calcd
for C16H23SiO2 (M111) 275.1461, found 275.1456.
(S)-4-Methoxy-5-phenyl-1-trimethylsilylpent-1-yn-3-one
(10c). 86% Yield of a yellowish oil. Rf 0.54 (CH2Cl2/hexane
7:3); 1H NMR d 0.27 (s, 9H), 2.95 (dd, 1H, Jˆ8.4, 14.4 Hz),
3.12 (dd, 1H, Jˆ4.5, 14.4 Hz), 3.36 (s, 3H), 3.95 (dd, 1H,
Jˆ4.5, 8.4 Hz), 7.20±7.40 (m, 5H); 13C NMR d 20.8, 38.3,
58.6, 88.2, 100.3, 102.2, 126.7, 128.4, 129.3, 136.1, 188.2;
IR (®lm) 2980, 2161, 1680. [a]2D0ˆ212.1 (c 1.1, CHCl3);
MS (NH3/CI) m/z (rel. int.) 278 (37, [M1NH14 ]); HRMS
calcd for C15H21SiO2 (M1) 261.1311, found 261.1318.
1
Rf 0.40 (CH2Cl2); H NMR d 0.21 (s, 9H), 0.97 (t, 3H,
Jˆ7.2 Hz), 1.03 (d, 3H, Jˆ6.9 Hz), 1.30 (m, 1H), 1.65
(m, 2H), 2.0 (broad s, 1H), 4.29 (d, 1H, Jˆ4.8 Hz); 13C
NMR d 0.2, 11.6, 14.4, 24.7, 41.0, 66.9, 89.9, 106.0; IR
(neat) 3450, 2940, 2130, 1245, 825; [a]2D0ˆ15.4 (c 1.9,
CHCl3); MS (NH3/CI) m/z (rel. int.) 202 (92, [M1NH14 ]).
HRMS calcd for C10H19Si (M12H2O11) 167.1256, found
167.1255.
(S)-4-(tert-Butoxycarbonylamino)-6-methyl-1-trimethyl-
silylhept-1-yn-3-one (10d). To a stirred solution of
trimethylsilylacetylene (1.0 mL, 7.1 mmol) in anh. THF
(5 mL) at 2788C, a solution of BuLi in hexanes (4.2 mL,
An analytical sample was transformed into the correspond-
ing Mosher ester derived from Mosher's (R)-acid. H and
1

C. Alemany et al. / Tetrahedron 56 (2000) 9305±9312
9309
19F NMR analysis of the sample revealed as composition
12a/13aˆ24:1.
9.4 Hz), 3.75 (dd, 1H, Jˆ4.6, 9.4 Hz), 4.47 (d, 1H,
Jˆ6.2 Hz), 4.57 (s, 2H), 7.15±7.31 (m, 5H); 13C NMR d
20.1, 13.1, 39.4, 66.6, 73.4, 73.5, 90.0, 105.5, 127.6, 127.7,
128.4, 137.9; IR (neat) 3400, 2180; [a]2D0ˆ13.6 (c 1.0,
CHCl3); MS (NH3/CI) m/z (rel. int.) 294 (100,
[M1NH14 ]). HRMS calcd for C16H25O2Si (M111)
277.1624, found 277.1622.
In a similar way, the reduction of 1 mmol of 10a using
0.2 mmol (R)-11 and 1.1 mmol of BH3:SMe2 afforded 90
% of alcohols (12a/13a 19:1).
(3R,4S)-5-Benzyloxy-4-methyl-1-trimethylsilylpent-1-yn-3-ol
(12b). Oil; Rf 0.39 (CH2Cl2); 1H NMR d 0.18 (s, 9H), 0.92
(d, 3H, Jˆ7.2 Hz), 2.26 (m, 1H), 3.52 (m, 1H), 3.71 (m, 1H),
4.41 (dd, 1H, Jˆ3.3, 8.4 Hz), 4.50 (d, 1H, Jˆ11.8 Hz), 4.55
(d, 1H, Jˆ11.8 Hz), 7.15±7.31 (m, 5H); 13C NMR d 20.1,
12.7, 38.5, 67.0, 73.5, 73.6, 90.2, 104.9, 127.6, 127.7, 128.4,
137.7; IR (neat) 3450, 2180; [a]2D0ˆ142.3 (c 1.1, CHCl3);
MS (NH3/CI) m/z (rel. int.) 294 (100, [M1NH14 ]). HRMS
calcd for C16H25O2Si (M111) 277.1624, found 277.1623.
(3R,4S)-4-Methoxy-5-phenyl-1-trimethylsilylpent-1-yn-
3-ol (13c). Oil; Rf 0.34 (CH2Cl2); H NMR d 0.21 (s, 9H),
1
2.57 (d, OH, Jˆ6.2 Hz), 2.96 (d, 2H, Jˆ6.6 Hz), 3.36
(s, 3H), 3.50 (m, 1H), 4.41 (dd, 1H, Jˆ3.6, 6.2 Hz), 7.20±
7.40 (m, 5H); 13C NMR d 20.1, 36.3, 58.5, 63.8, 84.8, 91.6,
103.3, 126.3, 128.3, 129.2, 138.1; IR (neat) 3400, 2170;
[a]2D0ˆ170.9 (c 1.0, CHCl3); MS (NH3/CI) m/z (rel. int.)
280 (100, [M1NH14 ]). HRMS calcd for C15H21OSi
(M12H2O11) 245.1362, found 245.1364.
(3S,4S)-4-Methoxy-5-phenyl-1-trimethylsilylpent-1-yn-
3-ol (12c). Oil; Rf 0.36 (CH2Cl2); H NMR d 0.19 (s, 9H),
1
(3R,4S)-4-(tert-Butoxycarbonylamino)-6-methyl-1-trimethyl-
silylpent-1-yn-3-ol (13d). Yellowish oil; Rf 0.54 (CH2Cl2/
AcOEt 9:1); 1H NMR d 0.17 (s, 9H), 0.92 (d, 3H,
Jˆ2.7 Hz), 0.95 (d, 3H, Jˆ3.0 Hz), 1.45 (s, 9H), 1.46
(m, 2H), 1.70 (m, 1H), 3.20 (broad s, OH), 3.76 (broad s,
1H), 4.30 (m, 1H), 4.65 (d, 1H, NH, Jˆ8.7 Hz); 13C NMR d
0.2, 22.0, 23.2, 24.7, 28.3, 40.0, 53.6, 66.8, 79.9, 91.0,
103.5, 156.7; IR (®lm) 3400, 2174, 1696; [a]2D0ˆ257.0
(c 1.17, CHCl3). HRMS calcd for C16H32NSiO3 (M111)
314.2151, found 314.2150.
2.61 (d, OH, Jˆ5.6 Hz), 2.85 (dd, 1H, Jˆ7.0, 14.0 Hz), 3.00
(dd, 1H, Jˆ5.6, 14.0 Hz), 3.42 (s, 3H), 3.50 (m, 1H), 4.19
(dd, 1H, Jˆ5.8, 5.8 Hz), 7.20±7.40 (m, 5H); 13C NMR d
20.2, 37.0, 59.5, 64.2, 85.2, 90.9, 104.3, 126.3, 128.3,
129.5, 137.8; IR (neat) 3450, 2180; [a]2D0ˆ218.3 (c 1.0,
CHCl3); MS (NH3/CI) m/z (rel. int.) 280 (100,
[M1NH14 ]). HRMS calcd for C15H21OSi (M12H2O11)
245.1362, found 245.1367.
(3S,4S)-4-(tert-Butoxycarbonylamino)-6-methyl-1-trimethyl-
silylhept-1-yn-3-ol (12d). Yellowish oil; Rf 0.54 (CH2Cl2/
AcOEt 9:1); 1H NMR d 0.18 (s, 9H), 0.93 (d, 3H,
Jˆ4.2 Hz), 0.95 (d, 3H, Jˆ4.2 Hz), 1.45 (s, 9H), 1.46
(m, 2H), 1.68 (m, 1H), 3.21 (broad s, OH), 3.87 (broad d,
1H, Jˆ7.2 Hz), 4.41 (m, 1H), 4.65 (d, 1H, NH, Jˆ8.4 Hz);
13C NMR d 0.2, 21.8, 23.4, 24.8, 28.3, 39.7, 53.4, 66.0,
79.6, 90.6, 104.4, 156.3; IR (®lm) 3400, 2174, 1696;
[a]2D0ˆ241.0 (c 1.2, CHCl3). HRMS calcd for
C16H32NSiO3 (M111) 314.2151, found 314.2162.
(3R,4S)-4-(tert-Butoxycarbonylamino)-5-phenyl-1-trimethyl-
silylhept-1-yn-3-ol (13e). Viscous oil; Rf 0.17 (CH2Cl2); H
1
NMR d 0.21 (s, 9H), 1.39 (s, 9H), 2.88 (m, 2H), 4.12
(m, 1H), 4.40 (d, 1H, Jˆ3.4 Hz), 4.75 (d, 1H, NH,
Jˆ4.7 Hz), 7.15±7.31 (m, 5H); 13C NMR d 0.7, 28.1,
37.6, 56.8, 64.1, 76.4, 79.9, 126.4, 128.5, 129.0, 135.5,
158.0; IR (KBr) 3250, 2185, 1700; [a]2D0ˆ213.7 (c 3.5,
CHCl3); HRMS calcd for C19H30NSiO3 (M111)
348.1995, found 348.2003.
(3S,4S)-4-(tert-Butoxycarbonylamino)-5-phenyl-1-trimethyl-
silylpent-1-yn-3-ol (12e). Mpˆ73±58C; Rf 0.17 (CH2Cl2);
1H NMR d 0.17 (s, 9H), 1.33 (s, 9H), 2.81 (m, 1H), 2.95 (dd,
1H, Jˆ3.4, 12.0 Hz), 3.85 (m, 1H), 4.33 (d, 1H, Jˆ3.4 Hz),
4.78 (d, 1H, NH, Jˆ6.0 Hz), 7.20±7.31 (m, 5H); 13C NMR
d 20.8, 28.1, 37.0, 56.4, 68.2, 76.4, 79.9, 126.3, 128.3,
129.3, 135.5, 158.0; IR (KBr) 3250, 1700, 2185;
[a]2D0ˆ16.8 (c 5.1, CHCl3) for a mixture 12e/13e 6.8:1;
HRMS calcd for C19H30NSiO3 (M111) 348.1995, found
348.2002.
General procedure for conversion of propargylic
alcohols into b-hydroxy acids
Preparation of 16 and 17. To a solution of cyclohexene
(0.18 mL, 1.78 mmol) in anh. THF (2 mL), BH3:SMe2
(80 mL, 0.80 mmol) were added at 08C under Ar. When
the stirred solution was allowed to warm to rt a white
suspension of dicyclohexylborane was observed. After
3 h, the mixture was cooled again to 08C and a solution of
12a (184 mg, 0.30 mmol) in anh. THF (2 mL) were added
via cannula. After 1.5 h of stirring at rt, TLC (98:2 CH2Cl2/
MeOH) revealed the disappearance of the starting alcohol.
The reaction ¯ask was then quenched by addition of saturated
aq. NaHCO3 (2 mL) and H2O2 (aq. 30%, 0.5 mL) under
vigorous stirring and allowed overnight at rt Afterwards,
most of solvent were removed under vacuo and aq. 2 M
NaOH was added to pHˆ9. The mixture was washed
with diethyl ether and the aqueous layer was acidi®ed
with HCl until pHˆ2. It was then carefully extracted with
CH2Cl2, dried (MgSO4) and the volatiles were eliminated in
vacuo. The residue was ®ltered through a pad of silica gel
(CH2Cl2/MeOH 95:5) to yield 36 mg (82%) of crude acid 5a
[Rf 0.10 (CH2Cl2/MeOH 95:5)] which was then dissolved
in anh. DMF (1 mL). To the solution, NaHCO3 (50 mg,
(3S,4S)-4-Methyl-1-trimethylsilylhex-1-yn-3-ol (13a). Oil;
Rf 0.40 (CH2Cl2); H NMR d 0.21 (s, 9H), 0.95 (t, 3H,
1
Jˆ7.4 Hz), 1.01 (d, 3H, Jˆ6.6 Hz), 1.30 (m, 1H), 1.65
(m, 2H), 2.1 (broad s, 1H), 4.28 (d, 1H, Jˆ4.8 Hz); 13C
NMR d 0.2, 11.5, 14.1, 25.3, 40.8, 67.0, 90.2, 105.4; IR
(neat) 3460, 2930, 2140, 1245, 830; [a]2D0ˆ21.41 (c 1.0,
CHCl3); MS (NH3/CI) m/z (rel. int.) 202 (90, [M1NH14 ]).
HRMS calcd for C10H19Si (M12H2O11) 167.1256, found
167.1254.
(3S,4S)-5-Benzyloxy-4-methyl-1-trimethylsilylpent-1-yn-
3-ol (13b). Oil; Rf 0.22 (CH2Cl2); H NMR d 0.22 (s, 9H),
1
1.10 (d, 3H, Jˆ7.0 Hz), 2.13 (m, 1H), 3.52 (dd, 1H, Jˆ6.8,

9310
C. Alemany et al. / Tetrahedron 56 (2000) 9305±9312
0.5 mmol) and methyl iodide (50 mL, 0.8 mmol) were
added and the mixture was stirred at rt for 4 h. The reaction
was quenched by addition of water (1 mL) and extracted
with CH2Cl2. The organic layer was dried over MgSO4,
®ltered and carefully concentrated in vacuo. The residue
was puri®ed by ¯ash chromatography (CH2Cl2/MeOH
95:5) to yield methyl (3S,4S)-3-hydroxy-4-methylhexano-
ate, 16, (20 mg, 62%) as a very volatile liquid. Rf 0.50
(3S,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-5-phenyl-
pentanoic acid (5e). Mp 149±1508C [lit.35 148±148.58C];
Rf 0.40 (CH2Cl2/MeOH/AcOH 95:5:1); H NMR (CD3OD,
200 MHz) d 1.34 (s, 9H), 2.43 (m, 2H), 2.69 (dd, 1H, Jˆ9.0,
13.5 Hz), 2.86 (dd, 1H, Jˆ5.8, 14.0 Hz), 3.77 (m, 1H), 4.05
(m, 1H), 6.25 (broad d, Jˆ8.7 Hz, NH), 7.20±7.35 (m, 5H);
13C NMR (CD3OD, 50.3 MHz) d 28.7, 38.8, 40.1, 57.3,
69.9, 79.5, 127.2, 128.5, 129.3, 140.1, 158.2, 182.4; IR
(KBr) 3360, 2927, 1711, 1690. [a]2D0ˆ239.0 (c 1.4,
MeOH) [lit.35 237.0, lit.36 239.0].
1
1
(CH2Cl2/MeOH 95:5); H NMR d 0.91 (t, 3H, Jˆ6.8 Hz),
0.92 (d, 3H, Jˆ7.1 Hz), 1.15 (m, 1H), 1.40 (m, 2H), 2.46
(dd, 1H, Jˆ10.0, 16.3 Hz), 2.47 (dd, 1H, Jˆ2.2, 16.3 Hz),
3.01 (broad s, OH), 3.71 (s, 3H), 3.95 (m, 1H); 13C NMR d
11.7, 13.8, 25.9, 37.7, 39.8, 51.8, 71.6, 174.0; IR (neat)
3400±3000, 2980, 2920, 1740; [a]2D0ˆ232.8 (c 1.0,
CHCl3) [lit.26 233.0]; MS (NH3/CI) m/z (rel. int.) 178
(100, [M1NH14 ]).
(3R,4S)-5-Benzyloxy-3-hydroxy-4-methylpentanoic acid
(6b).37 Oil; Rf 0.13 (CH2Cl2/MeOH 95:5); 1H NMR d
0.93 (d, 3H, Jˆ6.9 Hz), 1.95 (m, 1H), 2.47 (dd, 1H,
Jˆ8.7, 15.9 Hz), 2.58 (dd, 1H, Jˆ3.3, 15.9 Hz), 3.51 (dd,
1H, Jˆ6.9, 9.3 Hz), 3.57 (dd, 1H, Jˆ5.1, 9.3 Hz), 4.00
(m, 1H), 4.52 (s, 2H), 6.40 (broad s, 2H, OH), 7.20±7.40
(m, 5H); 13C NMR d 13.6, 38.1, 39.2, 71.8, 73.4, 73.9,
127.6, 127.7, 128.4, 137.6, 175.4; IR (neat) 3400±3000,
1725, 1452; [a]2D0ˆ117.8 (c 1.1, CHCl3); MS (NH3/CI)
m/z (rel. int.) 256 (100, [M1NH14 ]). HRMS calcd for
C13H19O4 (M111) 239.1283, found 239.1288.
In a similar way, hydroboration of alcohol 13a with dicyclo-
hexylborane followed by treatment with saturated aq.
NaHCO3 and 30% H2O2 gave 82% yield of crude (3R,4S)-
3-hydroxy-4-methylhexanoic acid which was then trans-
formed without puri®cation into its methyl ester
(NaHCO3/MeI/DMF, 50%), methyl (3R,4S)-3-hydroxy-4-
methylhexanoate, 17:26 oil; Rf 0.50 (CH2Cl2/MeOH 95:5);
1H NMR d 0.89 (t, 3H, Jˆ7.1 Hz), 0.92 (d, 3H, Jˆ7.1 Hz),
1.20 (m, 1H), 1.50 (m, 2H), 2.41 (dd, 1H, Jˆ10.0, 16.3 Hz),
2.49 (dd, 1H, Jˆ2.2, 16.3 Hz), 3.01 (broad s, OH), 3.71
(s, 3H), 3.87 (m, 1H); 13C NMR d 11.4, 14.4, 24.9, 37.7,
39.8, 51.8, 71.6, 174.0; IR (neat) 3400±3000, 2980, 2920,
1740; [a]2D0ˆ134.8 (c 0.5, CHCl3) [lit.25 132.37]; MS
(NH3/CI) m/z (rel. int.) 178 (100, [M1NH14 ]).
(3R,4S)-4-Methoxy-5-phenylpentanoic acid (6c). Oil; Rf
0.10 (CH2Cl2/MeOH 95:5); 1H NMR d 2.59 (dd, 1H,
Jˆ8.7, 16.5 Hz), 2.69 (dd, 1H, Jˆ3.3, 16.5 Hz), 2.85 (d,
2H, Jˆ6.3 Hz), 3.31 (s, 3H), 3.44 (m, 1H), 4.00 (m, 1H),
7.15±7.30 (m, 5H); 13C NMR d 36.2, 36.7, 58.6, 69.0, 84.5,
126.4, 128.4, 129.4, 138.0, 178.0; IR (neat) 3400±3300,
1730; [a]2D0ˆ19.1 (c 0.9, CHCl3); MS (NH3/CI) m/z (rel.
int.) 242 (100, [M1NH14 ]). HRMS calcd for C12H17O4
(M111) 225.1127, found 225.1122.
(3S,4S)-5-Benzyloxy-3-hydroxy-4-methylpentanoic acid
(5b). Oil; Rf 0.13 (CH2Cl2/MeOH 95:5); H NMR d 0.97
1
(3R,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-6-methyl-
heptanoic acid (6d). Mp 132±1348C [lit.34 135±1368C]; Rf
0.07 (CH2Cl2/MeOH 95:5); 1H NMR d 0.91 (d, 3H,
Jˆ6.6 Hz), 0.94 (d, 3H, Jˆ6.6 Hz), 1.32 (m, 2H), 1.45
(s, 9H), 1.66 (m, 1H), 2.59 (m, 2H), 3.70 (m, 1H), 4.01
(broad s, 1H), 4.72 (d, 1H, Jˆ8.1 Hz, NH), 5.90 (broad s,
1H, OH); 13C NMR d 21.5, 23.5, 24.7, 28.3, 37.2, 38.8, 53.0,
71.4, 80.1, 156.6, 175.8; IR (KBr) 3340, 1716, 1686;
[a]2D0ˆ225.3 (c 0.2, MeOH) [lit.34 227.6].
(d, 3H, Jˆ6.9 Hz), 1.99 (m, 1H), 2.46 (dd, 1H, Jˆ3.6,
16.2 Hz), 2.56 (dd, 1H, Jˆ9.6, 16.2 Hz), 3.50 (dd, 1H,
Jˆ6.9, 9.3 Hz), 3.56 (dd, 1H, Jˆ4.5, 9.3 Hz), 4.22
(m, 1H), 4.50 (d, 1H, Jˆ12.0 Hz), 4.54 (d, 1H,
Jˆ12.0 Hz), 7.20±7.40 (m, 5H); 13C NMR d 11.2, 37.6,
38.3, 70.3, 73.5, 73.7, 127.6, 127.8, 128.5, 137.6, 175.4;
IR (neat) 3400±3000, 1715, 1455, 1180; [a]2D0ˆ28.8
(c 1.8, CHCl3); MS (NH3/CI) m/z (rel. int.) 256 (100,
[M1NH14 ]). HRMS calcd for C13H19O4 (M111)
239.1283, found 239.1278.
(3R,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-5-phenyl-
pentanoic acid (6e). Mp 183±1858C [lit.35 187.58C]; Rf
0.33 (CH2Cl2/MeOH/AcOH 95:5:1); 1H NMR (CD3OD,
200 MHz) d 1.18 (s, 9H), 2.36 (dd, 1H, Jˆ9.3, 15.6 Hz),
2.54 (m, 2H), 3.07 (dd, 1H, Jˆ3.3, 13.9 Hz), 3.61 (m, 1H),
3.90 (m, 1H), 6.40 (broad d, Jˆ10.9 Hz, NH), 7.10±7.25
(m, 5H); 13C NMR (CD3OD, 50.3 MHz) d 28.7, 37.7, 40.2,
58.0, 72.0, 79.9, 127.1, 129.2, 130.4, 140.2, 153.9, 175.7; IR
(KBr) 3355, 3000, 1700, 1680; [a]2D0ˆ217.2 (c 1.4, MeOH)
[lit.35 216.1]; HRMS calcd for C16H24NO5 (M111)
310.1654, found 310.1647.
(3S,4S)-4-Methoxy-5-phenylpentanoic acid (5c). Oil; Rf
0.10 (CH2Cl2/MeOH 95:5); 1H NMR d 2.53 (dd, 1H,
Jˆ4.2, 16.0 Hz), 2.65 (dd, 1H, Jˆ8.2, 16.0 Hz), 2.89 (m,
2H), 3.32 (s, 3H), 3.33 (m, 1H), 3.98 (m, 1H), 7.15±7.35 (m,
5H); 13C NMR d 36.1, 38.2, 58.6, 68.2, 84.3, 126.3, 128.4,
129.4, 137.9, 176.8; IR (neat) 3400±3300, 1730;
[a]2D0ˆ13.2 (c 1.7, CHCl3); MS (NH3/CI) m/z (rel. int.)
242 (100, [M1NH14 ]). HRMS calcd for C12H17O4
(M111) 225.1127, found 225.1120.
(3S,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-6-methyl-
heptanoic acid (5d). Mp 115±1168C [lit.34 117±1188C]; Rf
0.13 (CH2Cl2/AcOEt 9:1); 1H NMR d 0.92 (d, 6H,
Jˆ6.2 Hz), 1.25 (m, 2H), 1.46 (s, 9H), 1.72 (m, 1H), 2.53
(m, 2H), 3.65 (m, 1H), 4.01 (broad s, 1H), 4.83 (d, 1H,
Jˆ8.7 Hz, NH); 13C NMR d 22.1, 23.0, 24.7, 28.3, 39.7,
41.4, 52.1, 69.8, 79.6, 156.4, 177.8; IR (KBr) 3340, 1716,
1686; [a]2D0ˆ238.4 (c 1.0, MeOH) [lit.34 239.6].
Representative procedure for reduction of cobalt
complexes
Reduction of 14a with BH3:SMe2 catalysed by 15. To a
solution of of Co2(CO)8 (250 mg, 0.66 mmol) in anh. pen-
tane (2 mL) under Ar at rt, a solution of ketone 10a (115 mg,
0.63 mmol) in anh. pentane (1 mL) was added via cannula.
The dark red solution was stirred at rt After 2 h, TLC

C. Alemany et al. / Tetrahedron 56 (2000) 9305±9312
9311
3. Aoyagi, Y.; Williams, R. M. Tetrahedron 1998, 54, 10419±
10433 (and references therein).
revealed the disappearance of the starting ketone. Concen-
tration and column chromatography (hexane/CH2Cl2 4:6)
afforded of 14a (268 mg, 91%) as a red oil which was stored
under Ar until the reduction step: Rf 0.52 (CH2Cl2/hexane
1:1); H NMR d 0.36 (s, 9H), 0.93 (t, 3H, Jˆ7.4 Hz), 1.23
4. (a) Hossain, H. B.; van der Helm, D.; Antel, J.; Sheldrick, G. M.;
Sanduja, S. K.; Weinheimer, A. J. Proc. Natl. Acad. Sci. USA 1988,
85, 4118±4122. (b) Banaigs, B.; Jeanty, G.; Francisco, C.; Jouin,
 Â
P.; Poncet, J.; Heitz, A.; Cave, A.; Prome, J. C.; Wahl, M.;
Lafargue, F. Tetrahedron 1989, 45, 181±190.
1
(d, 3H, Jˆ7.0 Hz), 1.56 (m, 1H), 1.80 (m, 1H), 2.77 (m,
1H); 13C NMR d 0.7, 12.0, 17.9, 25.7, 49.5, 111.3, 112.3,
199.6, 205.9; IR (®lm) 2980, 2940, 2040, 1680, 1260, 840.
A solution of ketone 14a (240 mg, 0.51 mmol) in THF
(2 mL) was added dropwise over ~50 min to a solution of
BH3:SMe2 (61 mL, 0.61 mmol) and (4R,5S)-15 (0.56 mmol,
from a toluene solution after removing the solvent under
vacuum) in THF (1 mL), at 08C under Ar. After 90 min,
TLC revealed the disappearance of the starting ketone.
The reaction was then cautiously quenched by adding
1 mL of MeOH, allowed to warm to rt, and stirred for
additional 30 min. The mixture was carried to dryness
under vacuum and the residue was ®ltered through a pad
of silica gel (hexane/CH2Cl2, 3:7) to afford after removing
the solvent under vacuo, besides recovered ketone 14a
(19 mg, 8%), the hexacarbonyldicobalt complex of
the propargylic alcohol 13a (204 mg, 85%): Rf 0.42
5. For nordidemnin B, a closely-related natural product, see:
Jouin, P.; Poncet, J.; Dufour, M.; Pantaloni, A.; Castro, B. J. Org.
Chem. 1989, 54, 617±627.
6. Stratmann, K.; Burgoyne, D. L.; Moore, R. E.; Patterson,
G. M. L. J. Org. Chem. 1994, 59, 7219±7226.
7. Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207±2293.
8. (a) Braun, M. Angew. Chem., Int. Ed. Engl. 1987, 26, 24±37.
(b) Arya, P.; Qin, H. Tetrahedron 2000, 56, 917±947.
9. (a) Cardillo, G.; Tomasini, C. Chem. Soc. Rev. 1996, 117±128.
For a discussion of the synthetic approaches to 3-hydroxy 4-amino
 Á
acids, see: (b) Castejon, P.; Moyano, A; Pericas, M. A.; Riera, A.
Â
Tetrahedron 1996, 52, 7063±7086. See also: (c) Pasto, M.;
Á
Moyano, A.; Pericas, M. A.; Riera, A. Tetrahedron: Asymmetry
1996, 7, 243±262.
10. For example, see: (a) Merino, P.; Castillo, E.; Franco, S.;
Â
Merchan, F. L.; Tejero, T. Tetrahedron 1998, 54, 12301±12322.
1
(CH2Cl2/hexane 1:1); H NMR d 0.34 (s, 9H), 0.96 (t, 3H,
Jˆ7.2 Hz), 1.05 (d, 3H, Jˆ7.0 Hz), 1.56 (m, 2H), 1.80
(m, 1H), 4.51 (broad m, 1H); 13C NMR d 1.1, 11.0, 16.4,
24.4, 42.6, 77.4, 114.9, 115.2, 199.0, 205.9; IR (®lm) 3450,
2980, 2000, 1580, 1250, 840. To a solution of the crude
complex (168 mg, 0.36 mmol) in MeOH (4 mL), CAN
(987 mg, 1.8 mmol) were added at rt A vigorous gas release
was observed. After 1 h (TLC monitoring), the volatiles
were eliminated under vacuo and the residue was partitioned
with CH2Cl2 and saturated aqueous NaCl. The organic
phase was dried over MgSO4. Evaporation of the solvent
and puri®cation by column chromatography (CH2Cl2)
yielded 62 mg (0.34 mmol, 94%) of 13a. An analytical
sample of 13a was transformed into the corresponding
(b) Jost, S.; Gimbert, Y.; Greene, A. E.; Fotiadu, F. J. J. Org. Chem.
1997, 62, 6672±6677. In particular, several groups have reported
the reduction of suitable chiral a-amino ketones to obtain 5 or 6
(Xˆprotected amine group), with modest to good diastereoselec-
tivities for a number of amine protecting groups and achiral redu-
cing agents, the anti isomer generally prevailing. See: (c) Hoffman,
R. V.; Tao, J. J. Org. Chem. 1997, 62, 2292±2297 and references
therein.
11. Masamune, S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew.
Chem., Int. Ed. Engl. 1985, 24, 1±76.
12. For recent reviews, see: (a) Corey, E. J.; Helal, C. H. Angew.
Chem., Int. Ed. Engl. 1998, 37, 1986±2012. (b) Deloux, L.;
Srebnik, M. Chem. Rev. 1993, 93, 763±784. (c) C. J. Wallbaum,
S.; Martens, J. Tetrahedron: Asymmetry 1992, 3, 1475±1504.
13. (a) Bach, J.; Berenguer, R.; Garcia, J.; Loscertales, T.;
Vilarrasa, J. J. Org. Chem. 1996, 61, 9021±9025. (b) Bach, J.;
Berenguer, R.; Garcia, J.; Loscertales, T.; Manzanal, J.; Vilarrasa,
J. Tetrahedron Lett. 1997, 38, 1091±1094. (c) Bach, J.;
1
Mosher ester derived from Mosher's (R)-acid. H and 19F
NMR analysis of the sample revealed 97% d.e.
A similar reduction of 14a was performed with BH3:SMe2
(1.2 equiv.) and (4S,5R)-15 (1.1 equiv.) to afford 12a in
82% yield and 97% d.e.
Â
Galobardes, M.; Garcia, J.; Romea, R.; Tey, C.; Urpõ, F.; Vilarrasa,
J. Tetrahedron Lett. 1998, 39, 6765±6768. (d) Garcia, J.;
Â
Lopez, M.; Romeu, J. Synlett 1999, 429±431. (e) Garcia, J.;
Â
Lopez, M.; Romeu, J. Tetrahedron: Asymmetry 1999, 10, 2617±
2626.
Acknowledgements
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Tetrahedron Lett. 1997, 38, 7511±7514. For reduction of other
acetylenic ketones using oxazaborolidine reagents, see: (c) Helal,
C. H.; Corey, E. J. Tetrahedron Lett. 1995, 36, 9153±9156.
(d) Morita, S.; Otsubo, K.; Matsubara, J.; Ohtani, T.; Uchida, M.
Tetrahedron: Asymmetry 1995, 6, 245±254. (e) Parker, K. A.;
Ledeboer, M. W. J. Org. Chem. 1996, 61, 3214±3217. (f) Hung,
D. T.; Nerenberg, J. B.; Schreiber, S. L. J. Am. Chem. Soc. 1996,
118, 11054±11080. For general reviews on enantioselective reduc-
tions of ketones, see: (g) Brown, H. C.; Cho, B. T.; Park, W. S.;
Ramachandran, P. V. J. Org. Chem. 1987, 52, 5406±5412.
(h) Singh, V. K. Synthesis 1992, 605±617. (i) Brown, H. C.;
Ramachandran, P. V. Acc. Chem. Res. 1992, 25, 16±24.
(j) Midland, M. M.; Morrell, L. A. In Houben-Weyl Methods of
Organic Chemistry Helmchen, G.; Hoffmann, R. W.; Mulzer, J.;
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This work has been supported by the Ministerio de Edu-
Â
cacion y Cultura [PM95-0061 (DGICYT) and PM98-1272
(DGESIC)] and Direccio General de Recerca, Generalitat de
Â
Catalunya (1996SGR00102). We also thank to Universitat
de Barcelona for a doctorate studentship to M. L. and
Professor J. Vilarrasa for reading the draft.
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