Synthesis of enantiopure β- and γ-amino alcohols from homochiral α- and β-aminoacylsilanes as stable synthetic equivalents of α- and β-amino aldehydes

Article abstract of DOI:10.1002/(SICI)1099-0690(199902)1999:2<437::AID-EJOC437>3.0.CO;2-V

A practical route is described for the synthesis of enantiopure β- and γ-amino alcohols with two stereocenters, starting from homochiral α- (1 and 5) and β- (13 and 16) -aminoacylsilanes, and involving stereoselective addition of allylmetal compounds and subsequent stereospecific protiodesilylation of the adducts. The degree of diastereoselectivity achieved in the nucleophilic addition step depends on both the nitrogen- protecting group and the reagents used. Diastereomeric excess (de) values equal to or higher than 98% were obtained in the TiCl₄-promoted allylation of the N-Pht aminoacylsilanes 1 and 13 and of the N-Ts-aminoacylsilane 5 with allyltrimethylsilane. Lower de values were obtained in the Sc(OTf)₃- catalyzed anylation of 5 with tetraallyltin and in the additions of both allyltrimethylsilane and tetraallyltin to the N-Ts-β-aminoacylsilane 16. Protiodesilylation of the adducts, leading to the β- and γ-amino alcohols, was accomplished with TBAF, except in the case of the adducts obtained from 5. For these, a preliminary removal of the tosyl group was necessary, which was accomplished with simultaneous desilylation by treatment with Na in liquid ammonia.

Full text of DOI:10.1002/(SICI)1099-0690(199902)1999:2<437::AID-EJOC437>3.0.CO;2-V

FULL PAPER
Synthesis of Enantiopure β- and γ-Amino Alcohols from Homochiral
α- and β-Aminoacylsilanes as Stable Synthetic Equivalents
of α- and β-Amino Aldehydes
Bianca Flavia Bonini,[a] Mauro Comes-Franchini,[a] Mariafrancesca Fochi,[a]
Jacek Gawronski,[b] Germana Mazzanti,*[a] Alfredo Ricci,[a] and Greta Varchi[a]
Keywords: Aminoacylsilanes / Amino aldehydes / Amino alcohols / Allylation
aminoacylsilanes 1 and 13 and of the N-Ts-aminoacylsilane
A practical route is described for the synthesis of enantiopure
β- and γ-amino alcohols with two stereocenters, starting from
homochiral α- (1 and 5) and β- (13 and 16) -aminoacylsilanes,
and involving stereoselective addition of allylmetal
compounds and subsequent stereospecific protiodesilylation
of the adducts. The degree of diastereoselectivity achieved in
the nucleophilic addition step depends on both the nitrogen-
protecting group and the reagents used. Diastereomeric
excess (de) values equal to or higher than 98% were
obtained in the TiCl4-promoted allylation of the N-Pht-
5 with allyltrimethylsilane. Lower de values were obtained
in the Sc(OTf)3-catalyzed allylation of 5 with tetraallyltin and
in the additions of both allyltrimethylsilane and tetraallyltin
to the N-Ts-β-aminoacylsilane 16. Protiodesilylation of the
adducts, leading to the β- and γ-amino alcohols, was
accomplished with TBAF, except in the case of the adducts
obtained from 5. For these, a preliminary removal of the tosyl
group was necessary, which was accomplished with
simultaneous desilylation by treatment with Na in liquid
ammonia.
Much effort has been directed towards the synthesis of or of heterocycles such as 2-isoxazolines.[19] To the best of
enantiopure β-amino alcohols with two stereocenters due our knowledge, a synthetic protocol analogous to that used
to their numerous and important applications as peptidomi- for β-amino alcohols, starting in this case from β-amino
metics,[1,2] as building blocks in the synthesis of pharma- aldehydes, has never been reported, probably because of the
ceuticals,[1,3] and as ligands for asymmetric catalysis.[4Ϫ7] highly unstable nature of these precursors.[20]
One of the most straightforward methodologies for the syn-
We have previously reported[21] that homochiral α- and
thesis of optically active β-amino alcohols involves the dia- β-aminoacylsilanes, obtained from natural α-amino acids,
stereoselective addition of organometallic reagents to N- can be used as stable synthetic equivalents of α- and β-
protected α-amino aldehydes, which, in turn, are accessible amino aldehydes in the diastereoselective synthesis of op-
from the corresponding α-amino acids.[1,8Ϫ11] However, it is tically active β- and γ-amino alcohols, respectively. This ap-
well known[1] that most N-protected α-amino aldehydes are proach is based on the possibility of stereospecifically re-
relatively unstable, both chemically and configurationally, placing the silyl group with a proton in the initially formed
and must be used immediately after their preparation. An- α-hydroxysilanes. Moreover, the use of acylsilanes as syn-
other problem is the low degree of stereoselectivity often thetic equivalents of the corresponding aldehydes has the
associated with the addition step.[1,12] Specific variations of advantage of increasing the degree of stereoselectivity in the
the protecting groups and reagents have been partly suc- nucleophilic addition step, due to the bulkiness of the silyl
cessful in overcoming these problems.[9,10]
group.[22Ϫ24]
Enantiopure γ-amino alcohols containing two stereocen-
In this paper we wish to report the results of a more
ters, a structural motif quite commonly encountered in extensive study on the synthesis of β- and γ-amino alcohols
natural products,[13,14] are important compounds in the by the reaction of homochiral α- and β-aminoacylsilanes
pharmacological field[15,16] and have recently found wide- bearing different protecting groups at the nitrogen atom
spread use as chiral catalysts.[17] Many methods are known with allylmetal compounds, which, among the various or-
for their synthesis. The most commonly used procedure in- ganometallics, have a prominent position due to the various
volves the reduction of β-amino carbonyl compounds[13,18] possibilities for further transformation of the homoallylic
function.[25]
[a]
`
Dipartimento di Chimica Organica “A. Mangini”, Universita,
Viale Risorgimento 4, I-40136 Bologna, Italy
Fax: (internat.) ϩ 39(0)51/6443654
Results and Discussion
E-mail: mazzanti@ms.fci.unibo.it
[b]
Department of Chemistry, Adam Mickiewicz University,
Grunwaldzka 6, PL-60 780 Poznan, Poland
Fax: (internat.) ϩ 48(0)61/8658008
Synthesis of β-Amino Alcohols
E-mail: gawronsk@amu.edu.pl
The α-aminoacylsilanes selected for study were (S)-di-
methyl(phenyl)(3-phenyl-2-phthalimidopropanoyl)silane
(1)[26] and (S)-dimethyl(phenyl)(3-phenyl-2-tosylamidopro-
Supporting information for this article is available on the
WWW under http://www.wiley-vch.de/home/eurjoc or from
the author.
Eur. J. Org. Chem. 1999, 437Ϫ445
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0202Ϫ0437 $ 17.50ϩ.50/0
437

G. Mazzanti et al.
FULL PAPER
panoyl)silane (5), both of which are stable compounds that 5-hexen-3-ol (6b) was obtained in 88% yield (Scheme 2,
can be purified and stored. In our preliminary communi- path a).
cation[21] we reported the allylation of 1 by treatment with
allyltrimethylsilane in the presence of 1 equiv. of titanium
tetrachloride in CH2Cl2 for 24 h at Ϫ78°C. Under these
conditions, the allylated α-hydroxysilane 2 was obtained in
1
75% yield. The H- and 13C-NMR spectra of 2 showed the
Scheme 2. a) tetraallyltin (0.5 equiv.), Sc(OTf)3 (7 mol-%), 20°C,
90 min, 6a/6b ϭ 75:25, 88%; b) allyltrimethylsilane (2 equiv.), TiCl4
(1 equiv.), Ϫ78°C, 8 h, only 6a, 60%
presence of a single diastereoisomer, thus suggesting de val-
ues equal to or higher than 98% (see General in the Exper-
imental Section) (Scheme 1).
Compounds 6a and 6b were separated on silica gel plates
(eluent: CH2Cl2) and were assigned the syn (2S,3R) and the
anti (2S,3S) relative configurations, respectively, with the
aid of NOE techniques (see Experimental Section).
Allylation of the same acylsilane 5 with allyltrimethyl-
silane in the presence of 1 equiv. of TiCl4 for 8 h at Ϫ78°C
gave the syn adduct 6a in 60% yield as a single diastereoiso-
mer, as was apparent from analysis of its NMR spectra,
thus suggesting a de value equal to or higher than 98%
(Scheme 2, path b). The high syn selectivity observed in this
reaction can be attributed, in terms of a “Cram chelating
model”, to the presence of TiCl4, which is known to give
very constrained chelated transition states.[9] The lower dia-
stereoselectivity observed in the reaction of 5 with tetraal-
lyltin and Sc(OTf)3 can probably be attributed to a reduced
chelation ability of this Lewis acid owing to both its greater
size and the lower charge on scandium, which allows an
increase in the degrees of freedom.
In order to complete our protocol for the synthesis of β-
amino alcohols, the replacement of the silyl group by a pro-
ton was investigated. Treatment of 6a with TBAF in THF
led to 1-phenyl-4-hexen-3-one (7) in 30% yield, besides
other unidentified products, rather than to the expected de-
silylated amino alcohol. The formation of this compound
can be rationalized in terms of a facile β-elimination reac-
tion, favoured by the good leaving group ability of tosyl-
amido, occurring in the initial intermediate formed by at-
tack of the fluoride ion on the silicon atom, followed by
isomerization (Scheme 3).
Scheme 1. Synthesis of (2S,3S)-1-phenyl-2-phthalimido-5-hexen-3-
ol 3 and its conversion into the benzoyl derivative 4
Subsequent protiodesilylation of 2 with tetrabutylam-
monium fluoride (TBAF) in THF gave stereospecifically
the syn-amino alcohol, viz. (2S,3S)-1-phenyl-2-phthal-
imido-5-hexen-3-ol (3), in 60% yield (Scheme 1). The (S)
configuration at C-3 was determined, after conversion to
(4S,5S)-4-benzoyloxy-6-phenyl-5-phthalimido-1-hexene (4)
(Scheme 1), from the sign of the exciton Cotton effect re-
sulting from the coupling of the π-π* transitions of the
phthalimide and benzoate chromophores (see Supporting
Information).
Having established that the syn-amino alcohol 3 had been
formed, we tentatively assigned the syn configuration to
compound 2 as well. In fact, it is known[22] that TBAF-
induced protiodesilylation of α-hydroxysilanes, derived
from acylsilanes bearing an α-chiral carbon atom, proceeds
with retention of configuration. Moreover, the presence of
TiCl4 should favour a chelation-controlled addition[9] lead-
ing to the syn diastereoisomer.
Next, we attempted the scandium triflate catalyzed al-
lylation of acylsilane 1 with tetraallyltin according to the
Kobayashi methodology,[27] but in the case at hand the pro-
cedure failed and 1 was recovered almost quantitatively.
Since this protocol has proved to be successful in the al-
lylation of aliphatic and aromatic acylsilanes,[28] we inferred
that its failure might have been due to some incompatibility
between the Lewis acid and the phthaloyl protecting group
in 1. Indeed, a change of the N-protecting group from
phthaloyl to tosyl allowed successful allylation using both
of the aforementioned methodologies.
Scheme 3. Reaction of 6a with TBAF
The reaction of acylsilane 5 with tetraallyltin (0.5 equiv.)
Removal of the tosyl group prior to desilylation was
in the presence of Sc(OTf)3 (7 mol-%) was investigated with therefore investigated. Treatment of compound 6a with Na
regard to the optimal conditions of temperature and time. in liquid ammonia led to both deprotection of the amino
From these experiments, it was established that the best re- group and to desilylation, with the formation of the anti-
sults were achieved at 20°C with a reaction time of 90 min. amino alcohol (2S,3R)-2-amino-1-phenyl-5-hexen-3-ol (8)
Under these conditions, a 75:25 mixture of (2S,3R)-3-di- as a single diastereoisomer in 50% yield. The anti relative
methylphenylsilyl-1-phenyl-2-tosylamido-5-hexen-3-ol (6a) stereochemistry in 8 was assigned through its conversion to
and (2S,3S)-3-dimethylphenylsilyl-1-phenyl-2-tosylamido- the N-phthaloyl derivative 9, which turned out to be the
438
Eur. J. Org. Chem. 1999, 437Ϫ445

Enantiopure β- and γ-Amino Alcohols from Homochiral α- and β-Aminoacylsilanes
FULL PAPER
diastereoisomer of the corresponding syn derivative 3
(Scheme 4).
Scheme 6. a) TsCl, THF/H2O, r.t., 9 h, 98%; b) Ph3P, I2, imidazole,
CH3CN, 95Ϫ100°C, 1 h, 90%; c) Bu4NCN, CH3CN, 70°C, 4 h,
65%; d) H2SO4, CH3COOH, H2O, 110°C, 9 h, 70%; e) SOCl2,
55Ϫ60°C, 6 h, 95%; f) (PhMe2Si)2CuCN(Li)2, Ϫ78°C, 1 h, 50%
Scheme 4. Deprotection and desilylation of 6a and 6b, followed by
transformation of 8 and 10 into the phthaloyl derivatives 9 and 3
Analogous treatment with Na in liquid ammonia of the
anti-α-hydroxysilane 6b gave the syn-(2S,3S)-amino alcohol
10 in 60% yield, and indeed, its reaction with phthalic anhy-
dride gave the syn derivative 3 (Scheme 4). Under these
basic conditions, the desilylation of 6a and 6b most prob-
ably occurs by a Brook rearrangement[29] with inversion of
configuration at C-3, followed by hydrolysis.
THF gave stereospecifically the (4R,6R)-7-phenyl-6-phthal-
imido-1-hepten-4-ol (18) in 72% yield (Scheme 7). In this
case, the absolute stereochemistry of the newly formed ster-
eogenic center (C-4) was assigned using the Mosher
method,[31] as already reported in our preliminary com-
munication.[21]
Synthesis of γ-Amino Alcohols
As starting β-aminoacylsilanes, we used homologues of 1
and 5, specifically (S)-dimethyl(phenyl)(4-phenyl-3-phthal-
imidobutanoyl)silane (13) and (S)-dimethyl(phenyl)(4-
phenyl-3-tosylamidobutanoyl)silane (16), both of which
were derived from -phenylalanine.
For the synthesis of 13, N-Pht--phenylalanine[30] (11)
was homologated by means of the ArndtϪEistert reaction
to give (S)-4-phenyl-3-phthalimidobutanoic acid (12), from
which 13 was obtained following sequential chlorinationϪ
silylcupration[21] (Scheme 5).
Scheme 7. Synthesis of (4R,5R)-7-phenyl-6-phthalimido-1-hepten-
4-ol 18
When the β-aminoacylsilane 16 was allylated under the
same conditions, the α-hydroxysilane 19 was obtained in
62% yield and with 64% de (Scheme 8, path a). The al-
lylation of 16 was also performed with 0.5 equiv. of tetraal-
lyltin in the presence of 7 mol-% Sc(OTf)3 by reaction at
20°C for 24 h, which afforded 19 in 96% yield and with
50% de (Scheme 8, path b).
Scheme 5. a) ref.[30], 90%; b) CH2N2, Et2O/THF, r.t., 1 h, 94%; c)
Ag2O, MeOH, 50°C, 40 min, 87%; d) HCl, H2O, aceton, reflux,
150 min, 81%; e) SOCl2, 55°C, 4 h, 93%; f) (PhMe2Si)2CuCN(Li)2,
Ϫ78°C, 1 h, 55%
For the synthesis of 16, we started from commercially
available -phenylalaninol (14), derived from -phenylala-
nine, which, by tosylation, iodination, cyanide displace-
ment, and hydrolysis, was converted to (S)-4-phenyl-3-tosyl-
amidobutanoic acid (15). Sequential chlorinationϪsilyl-
cupration was again used to convert 15 to 16 (Scheme 6).
The N-Ts-β-aminoacylsilane 16, as well as the corre-
Scheme 8. a) allyltrimethylsilane, TiCl4 (1 equiv.), Ϫ78°C, 24 h, de
64%, 62%; b) tetraallyltin (0.5 equiv), Sc(OTf)3 (7 mol-%), 20°C,
24 h, de 50%, 96%; c) TBAF, THF, r.t., 72 h, starting from 19 de
50%, 72%
The α-hydroxysilane 19 (de 50%) was subsequently
sponding N-Pht derivative 13, proved to be stable com- treated with TBAF in THF, giving a 75:25 mixture of the
pounds.[21] As previously reported,[21] the TiCl4-mediated two diastereoisomers (4R,6R)-7-phenyl-6-tosylamido-1-
addition of allyltrimethylsilane to the β-aminoacylsilane 13 hepten-4-ol (20a) and (4S,6R)-7-phenyl-6-tosylamido-1-
by reaction at Ϫ78°C for 24 h gave the α-hydroxysilane 17 hepten-4-ol (20b) in 72% yield (Scheme 8, path c). The iso-
in 80% yield and with a de value equal to or higher than mers 20a and 20b were separated on silica gel plates (eluent:
98%. Subsequent protiodesilylation of 17 with TBAF in dichloromethane/light petroleum ether, 5:1). The absolute
Eur. J. Org. Chem. 1999, 437Ϫ445
439

G. Mazzanti et al.
FULL PAPER
septum techniques. THF was distilled immediately prior to use
from sodium/benzophenone ketyl under Ar. CH2Cl2 was passed
through basic alumina and distilled from CaH2 prior to use. Other
solvents were purified by standard procedures. Light petroleum
ether refers to the fraction with b.p. 40Ϫ60°C. The reactions were
monitored by TLC on Baker-flex IB2-F silica gel plates. Column
chromatography was performed with Merck 70Ϫ230 mesh silica gel
60. Preparative TLC was carried out on glass plates using a 1 mm
layer of Merck silica gel Pf254. Ϫ (S)-Dimethyl(phenyl)(3-phenyl-2-
phthalimidopropanoyl)silane (1) was obtained as described pre-
viously.[26] Ϫ The diastereoisomer ratios of the diastereomeric mix-
tures were determined from the 1H-NMR spectra of the crude
products by integration of well-separated signals. In cases where
the NMR spectra were indicative of the presence of a single dia-
stereoisomer (2, 3, 6a obtained from 5 and allyltrimethylsilane/
TiCl4, 17 and 18), the de values were estimated from a measure of
the signal-to-noise ratio of the NMR spectra of the crude products.
stereochemistry of the newly formed stereogenic center (C-
4) was determined for the major diastereoisomer 20a by 1H-
NMR analysis of the corresponding esters of the MosherЈs
acids (R)-MTPA and (S)-MTPA. From the differences in
the chemical shifts, the configuration at C-4 could be as-
signed as R[31] (Table 1).
Table 1. Determination of the absolute configuration of 20a
δH C(1) δH C(3) δH C(5) δH C(7)
(R)-MTPA ester of 20a
(S)-MTPA ester of 20a
∆δH ϭ δ(R)Ϫδ(S)
4.862
4.966
5.508
5.625
1.816
1.746
2.709
2.591
Ϫ0.104 Ϫ0.117 ϩ0.070 ϩ0.118
Reaction of 1 with Allyltrimethylsilane: To a stirred solution of the
acylsilane 1 (0.40 g, 0.97 mmol) in CH2Cl2 (1.5 mL) at Ϫ78°C,
allyltrimethylsilane (0.22 g, 1.94 mmol) was added, followed by a
1.0  solution of TiCl4 (0.97 mL, 0.97 mmol) in CH2Cl2. The reac-
tion mixture was stirred under Ar at Ϫ78°C until the starting mate-
rial 1 was no longer detectable by TLC analysis (24 h). Saturated
aqueous NH4Cl solution (10 mL) and CH2Cl2 (10 mL) were then
added and the mixture was allowed to warm to room temperature
(r.t.). The organic layer was separated, washed with saturated aque-
Concluding Remarks
The results reported herein illustrate a means of ob-
taining enantiopure β- and γ-amino alcohol units, starting
from the α-amino acids of the chiral pool, that avoids the
problems associated with the use of α- and β-amino alde-
hydes. In fact, the α-aminoacylsilanes 1 and 5 and the β-
aminoacylsilanes 13 and 16 used as precursors are stable
compounds that can be purified, handled, and stored with- ous NH4Cl solution, and dried with MgSO4. After removal of the
solvent in vacuo, the crude residue was submitted to 1H- and 13C-
out any problems. The degree of stereoselectivity achieved
NMR analysis, which showed the presence of a single diastereoiso-
in the addition step is strongly dependent on both the type
mer. The product was then purified by column chromatography on
of protecting groups and the reagents, as previously re-
silica gel (light petroleum ether/Et2O, 3:1), affording 0.35 g (75%
ported by Reetz[9] for the reactions of α-amino aldehydes.
In fact, with the bulky phthaloyl N-protecting group, a very
high diastereoselectivity is obtained with both the α- and β-
aminoacylsilanes 1 and 13.
With the tosyl group, a high degree of diastereoselectivity
is achieved only under conditions which allow the forma-
yield) of pure (2S,3R)-3-(dimethylphenylsilyl)-1-phenyl-2-phthal-
imido-5-hexen-3-ol (2) as
a
white crystalline solid; m.p.
128Ϫ130°C. Ϫ [α]D ϭ Ϫ7.3 (c ϭ 2.14, C6H6). Ϫ 1H NMR (200
MHz, CDCl3): δ ϭ 7.87Ϫ7.39 (m, 9 H), 7.10Ϫ6.86 (m, 5 H),
5.80Ϫ5.60 (m, 1 H), 4.90Ϫ4.70 (m, 3 H), 4.45 (s, 1 H), 3.29 (dd,
J ϭ 13.9, 11.7 Hz, 1 H), 2.94 (dd, J ϭ 13.9, 3.9 Hz, 1 H), 2.55Ϫ2.23
tion of a constrained five-membered ring chelate, as in the (m, 2 H), 0.55 (s, 6 H). Ϫ 13C NMR (50.3 MHz, CDCl3): δ ϭ
171.76, 167.58, 137.74, 137.32, 134.73, 134.08, 133.91, 133.16,
131.21, 129.35, 128.82, 128.12, 127.82, 126.83, 123.27, 123.16,
117.64, 70.97, 59.58, 43.73, 34.97, Ϫ3.50, Ϫ3.91. Ϫ IR (CCl4): ν˜ ϭ
3440 cmϪ1, 1770, 1715. Ϫ MS; m/z: 455 [Mϩ], 440, 414, 364, 308,
135. Ϫ C28H29NO3Si (455.63): calcd. C 73.82, H 6.42, N 3.08;
found C 73.41, H 6.39, N 3.05.
reaction of the α-aminoacylsilane 13 with allyltrimethyl-
silane in the presence of TiCl4. In other cases, mixtures of
two diastereoisomers are formed, which can be separated
either at the α-hydroxysilane stage, with subsequent stereo-
specific protiodesilylation of the two isomers, or at the stage
of the protiodesilylated compounds, thereby furnishing en-
antiopure syn- and anti-β- and -γ-amino alcohols.
(2S,3S)-1-Phenyl-2-phthalimido-5-hexen-3-ol (3): To a stirred solu-
tion of the α-hydroxysilane 2 (100 mg, 0.22 mmol) in dry THF (3
mL) at r.t. was added a 1.0  solution of TBAF (0.24 mL, 0.24
mmol) in THF and the reaction mixture was stirred under Ar at
r.t. for 72 h. A saturated aqueous NH4Cl solution (5 mL) followed
by Et2O (20 mL) was then added. The organic layer was separated,
washed three times with water, and dried with MgSO4. After evap-
oration of the solvent in vacuo, the crude residue was submitted to
1H-NMR analysis, which showed the presence of a single dia-
stereoisomer. The product was then purified by column chromatog-
raphy on silica gel (light petroleum ether/Et2O, 3:1), affording 42
mg (60%) of pure 3 as a white crystalline product; m.p. 110Ϫ112°C.
Ϫ [α]D ϭ Ϫ37.8 (c ϭ 1.14, CH2Cl2). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 7.80Ϫ7.60 (m, 4 H), 7.15Ϫ7.05 (m, 5 H), 5.90Ϫ5.70
(m, 1 H), 5.05Ϫ4.95 (m, 2 H), 4.60Ϫ4.50 (m, 1 H), 4.02Ϫ3.95 (m,
1 H), 3.65 (br. d, J ϭ 9.4 Hz, 1 H), 3.20 (dd, J ϭ 7.9, 3.1 Hz, 2
H), 2.20 (t, J ϭ 6.9 Hz, 2 H). Ϫ 13C NMR (75.4 MHz, CDCl3):
δ ϭ 169.53, 137.35, 134.18, 133.79, 131.45, 129.07, 128.44, 126.63,
123.42, 117.96, 71.09, 57.47, 39.82, 35.44. Ϫ IR (CCl4): ν˜ ϭ 3460
Experimental Section
General: Melting points, determined using a capillary apparatus,
are uncorrected. Ϫ 1H- and 13C-NMR spectra were recorded using
CDCl3 solutions at 200 and 50.3 MHz, respectively, with a Varian
Gemini 200, or at 300 and 75.4 MHz, respectively, with a Varian
Gemini 300. Chemical shifts are reported in ppm relative to CHCl3
1
(δ ϭ 7.23 for H and δ ϭ 77.0 for 13C). Ϫ IR spectra were recorded
with a Perkin-Elmer 257 spectrometer. Ϫ Mass spectra were ob-
tained with a VG 7070E spectrometer at an ionizing voltage of 70
eV. Ϫ [α]D values were determined with a Jasco Dip-360 polari-
meter. Ϫ UV spectra were recorded with a Shimadzu 160 spectro-
photometer. Ϫ CD spectra were obtained with a Jobin-Yvon
dichrograph III. Ϫ Moisture-sensitive reactions were carried out
in oven-dried (120°C) glassware under Ar. Transfers of anhydrous
solvents or of mixtures were accomplished using standard syringe/
440
Eur. J. Org. Chem. 1999, 437Ϫ445

Enantiopure β- and γ-Amino Alcohols from Homochiral α- and β-Aminoacylsilanes
FULL PAPER
cmϪ1, 1775, 1745, 1705. Ϫ MS; (m/z): 321 [Mϩ], 280, 262, 133. Ϫ
C20H19NO3 (321.38): calcd. C 74.73, H 5.96, N 4.36; found C
74.38, H 5.92, N 4.33.
MHz, CDCl3): δ ϭ 142.42, 136.64, 136.20, 135.70, 135.60, 134.98,
134.57, 129.34, 129.10, 128.37, 127.84, 125.56, 125.68, 117.14,
69.85, 62.72, 38.46, 37.61, 21.26, Ϫ3.89, Ϫ2.92. Ϫ IR (CCl4): ν˜ ϭ
3470 cmϪ1, 3720, 1430, 1175. Ϫ MS; m/z: 479 [Mϩ], 438, 309, 274,
230, 217, 155, 135, 91. Ϫ C27H33NO3SSi (479.71): calcd. C 67.61,
H 6.94, N 2.92; found C 67.20, H 6.75, N 2.80.
(4S,5S)-4-Benzoyloxy-6-phenyl-5-phthalimido-1-hexene (4): Alcohol
3 (20 mg, 0.06 mmol) was dissolved in dichloromethane (0.8 mL)
and treated with benzoyl chloride (0.02 mL), pyridine (0.1 mL),
and 4-(dimethylamino)pyridine (5 mg). After 4 h at room tempera-
ture, the mixture was diluted with ethyl acetate and extracted with
2  aq. HCl, 1  aq. Na2CO3 solution, and water. The organic
phase was dried (MgSO4), the solvent was evaporated, and the resi-
due was purified by short-column chromatography (hexane/di-
chloromethane, 1:1) to give 21 mg (79%) of the benzoate 4 as a
white crystalline product; m.p. 113Ϫ114°C (from MeOH). Ϫ 1H
NMR (CDCl3): δ ϭ 8.00Ϫ7.05 (m, 14 H), 6.00Ϫ5.80 (m, 2 H),
5.30Ϫ5.10 (m, 2 H), 4.84 (ddd, J ϭ 12.1, 8.2, 4.9 Hz, 1 H), 3.55
(dd, 1 H, J ϭ 13.7, 11.8 Hz), 3.19 (dd, J ϭ 13.7, 4.8 Hz, 1 H),
2.77Ϫ2.70 (m, 1 H), 2.55Ϫ2.50 (m, 1 H). Ϫ CD (MeCN): ∆e ϭ
Ϫ1.6 (241 nm), ϩ2.8 (230 nm), Ϫ12.6 (218 nm). Ϫ UV (MeCN):
λmax (ε) ϭ 220 nm (45200).
6b: Minor isomer; m.p. 45Ϫ50°C. Ϫ [α]D ϭ 11.0 (c ϭ 2.78, CHCl3).
Ϫ
1H NMR (300 MHz, CDCl3): δ ϭ 7.75Ϫ7.65 (m, 2 H),
7.50Ϫ7.40 (m, 3 H), 7.05Ϫ6.80 (m, 7 H), 6.50Ϫ6.40 (m, 2 H),
6.20Ϫ6.00 (m, 1 H), 5.25Ϫ5.05 (m, 2 H), 4.00 (d, J ϭ 7.5 Hz, 1 H),
3.57 (s, 1 H), 3.45Ϫ3.35 (m, 1 H), 2.78Ϫ2.65 (m, 2 H), 2.40Ϫ2.25 (s
ϩ m, 4 H), 1.85 (dd, J ϭ 13.1, 11.2 Hz, 1 H), 0.60 (s, 3 H), 0.45
(s, 3 H). Ϫ 13C NMR (75.4 MHz, CDCl3): δ ϭ 142.60, 137.40,
136.84, 134.12, 132.99, 129.75, 129.26, 128.26, 126.99, 126.67,
126.08, 118.29, 71.37, 63.77, 40.50, 37.48, 21.36, Ϫ3.46. Ϫ IR
(CCl4): ν˜ ϭ 3470 cmϪ1, 3720, 1430, 1175. Ϫ MS; m/z: 479 [Mϩ],
438, 309, 274, 230, 217, 155, 135, 91. Ϫ C27H33NO3SSi (mol.
mass?): calcd. C 67.61, H 6.94, N 2.92; found C 67.30, H 6.80,
N 2.78.
The relative configurations of 6a and 6b were elucidated from NOE
experiments: In the major isomer 6a, saturation of the signals of
the two methyl groups bonded to the silicon atom at δ ϭ 0.42 and
δ ϭ 0.48 produced an increase in the intensity of the 5-H signal at
δ ϭ 3.45Ϫ3.30 (3.5%) and no increase in the intensity of the NH
signal at δ ϭ 4.45. In the minor isomer 6b, saturation of the signals
of the two methyl groups bonded to the silicon atom at δ ϭ 0.45
and δ ϭ 0.60 produced an increase in the intensity of the NH signal
at δ ϭ 4.00 (2.8%) and no increase in the intensity of the 5-H signal
at δ ϭ 3.45Ϫ3.35.
(S)-Dimethyl(phenyl)(3-phenyl-2-tosylamidopropanoyl)silane (5): To
a 0.4  solution of bis(dimethylphenylsilyl)lithium cyanocuprate[32]
(11.5 mL, 4.6 mmol) in THF at Ϫ78°C was added a solution of
N-tosyl--phenylalanyl chloride[33] (1.55 g, 4.6 mmol) in THF (9
mL). The reaction mixture was stirred under Ar at Ϫ78°C for 1 h.
Saturated aqueous NH4Cl solution (10 mL) was then added, the
mixture was allowed to warm to r.t., whereupon it was extracted
three times with diethyl ether. The combined organic extracts were
dried with Na2SO4. After removal of the solvent in vacuo, the crude
residue was purified by column chromatography on silica gel (light
petroleum ether/Et2O, 5:1), affording 0.96 g (48%) of pure 5 as a
pale-yellow solid; m.p. 107Ϫ109°C. Ϫ [α]D ϭ 93.6 (c ϭ 1.79,
CHCl3). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 7.50Ϫ7.40 (m, 8 H),
7.15Ϫ7.00 (m, 4 H), 6.70Ϫ6.60 (m, 2 H), 5.25 (d, J ϭ 7.6 Hz, 1
H), 4.25Ϫ4.15 (m, 1 H), 2.75 (dd, J ϭ 15.2, 4.8 Hz, 1 H), 2.40Ϫ2.25
(m ϩ s, 4 H), 0.42 (s, 3 H), 0.34 (s, 3 H). Ϫ 13C NMR (50.3 MHz,
Reaction of 5 with Allyltrimethylsilane: The reaction was performed
under the same conditions as used for the reaction of acylsilane 1,
starting from acylsilane 5 (0.44 g, 1 mmol) in CH2Cl2 (1.5 mL),
allyltrimethylsilane (0.23 g, 2 mmol), and a 1.0  solution of TiCl4
(1 mL, 1.0 mmol) in CH2Cl2. The crude product was submitted to
1H- and 13C-NMR analysis, which showed the presence of a single
diastereoisomer. The material was then purified on a silica gel col-
umn (eluent: light petroleum ether/Et2O, 5:1) affording 0.24 g
(60%) of pure 6a.
CDCl3):
δ
ϭ
240.59, 170.30, 143.19, 134.98, 134.16,
126.75Ϫ130.38, 65.97, 36.24, 21.44, Ϫ4.6. Ϫ IR (CCl4): ν˜ ϭ 3300
cmϪ1, 1650, 1350, 1175. Ϫ MS; m/z: 437 [Mϩ], 422, 274, 135, 91.
Ϫ C24H27NO3SSi (437.15): calcd. C 65.88, H 6.22, N 3.20; found
C 65.10, H 6.05, N 3.12.
Attempted Protiodesilylation of 6a with TBAF: To a stirred solution
of 6a (0.23 g, 0.48 mmol) in THF (3 mL) at r.t., a 1  solution of
TBAF (0.53 mL, 0.53 mmol) in THF was added. After 16 h, satu-
rated aqueous NH4Cl solution (5 mL) and Et2O (10 mL) were ad-
ded. The organic layer was separated, washed with water, and dried
with MgSO4. After removal of the solvent in vacuo, the crude resi-
due was purified by preparative TLC on silica gel plates (ethyl ace-
tate/Et2O, 1:1), giving 25 mg (30%) of 1-phenyl-4-hexen-3-one (7)
Reaction of Acylsilane 5 with Tetraallyltin: To a stirred suspension
of scandium(III) triflate (7.9 mg, 0.016 mmol) and tetraallyltin (33
mg, 0.115 mmol) in CH2Cl2 (3 mL) at r.t. was added a solution of
5 (100 mg, 0.23 mmol) in CH2Cl2. After 90 min, saturated aqueous
NH4Cl solution (10 mL) was added and the mixture was extracted
three times with diethyl ether. The combined organic extracts were
dried with Na2SO4 and the solvent was evaporated in vacuo. The
crude residue was submitted to 1H-NMR analysis, which showed
the presence of both the syn and the anti isomer 6a and 6b in a
75:25 ratio. The two isomers were separated on silica gel plates
(CH2Cl2 as eluent) giving, as the slower moving compound, 73 mg
(67%) of (2S,3R)-3-[dimethyl(phenyl)silyl]-1-phenyl-2-tosylamido-
5-hexen-3-ol (6a), and, as the faster moving compound, 23 mg
(21%) of (2S,3S)-3-[dimethyl(phenyl)silyl]-4-phenyl-2-tosylamido-
5-hexen-3-ol (6b).
1
as a colorless oil. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 7.37Ϫ7.15
(m, 5 H), 6.95Ϫ6.75 (m, 1 H), 6.20Ϫ6.06 (m, 1 H), 3.01Ϫ2.80 (m,
4 H), 1.95Ϫ1.88 (m, 3 H). Ϫ IR (CCl4): ν˜ ϭ 2960 cmϪ1, 1660. Ϫ
MS; m/z: 174 [Mϩ], 159, 105, 69.
(2S,3R)-2-Amino-1-phenyl-5-hexen-3-ol (8): A solution of 6a (0.479
g, 1 mmol) in THF (5 mL) was added with stirring to liquid am-
monia (30 mL) at Ϫ78°C. Stirring was continued and clean sodium
was added in small pieces until the blue color, which developed
on dissolution of the metal and disappeared during the reaction,
persisted for about 1 min. Approximately 0.14 g (6 mmol) of so-
6a: Major isomer; light-yellow oil. Ϫ [α]D ϭ Ϫ44.0 (c ϭ 2.78,
CHCl3). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 7.75Ϫ7.65 (m, 2 dium was required. Ethanol was then added and the ammonia was
H), 7.50Ϫ7.35 (m, 3 H), 7.00Ϫ6.90 (m, 3 H), 6.89Ϫ6.70 (m, 4 H),
allowed to evaporate at r.t. The residual ammonia and the THF
6.30Ϫ6.10 (m, 3 H), 5.25Ϫ5.15 (m, 2 H), 4.45 (d, J ϭ 8.5 Hz, 1 were removed in vacuo. The residue was then purified on a silica
H), 3.65 (s, 1 H), 3.45Ϫ3.30 (m, 1 H), 2.70Ϫ2.65 (dd, J ϭ 13.6, 2.7
gel column (CHCl3/MeOH, 2:1) giving 96 mg (50%) of 8 as a color-
Hz, 1 H), 2.55Ϫ2.40 (m, 2 H), 2.30 (s, 3 H), 2.15Ϫ2.05 (dd, J ϭ less oil. Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 7.35Ϫ7.00 (m, 5
13.6, 10.2 Hz, 1 H), 0.48 (s, 3 H), 0.42 (s, 3 H). Ϫ 13C NMR (75.4 H), 5.95Ϫ5.40 (m, 4 H), 5.20Ϫ4.90 (m, 2 H), 4.00Ϫ3.95 (m, 1 H),
Eur. J. Org. Chem. 1999, 437Ϫ445
441

G. Mazzanti et al.
FULL PAPER
3.50Ϫ3.35 (m, 1 H), 3.10Ϫ2.70 (m, 2 H), 3.15Ϫ2.25 (m, 2 H). Ϫ 4.30. Ϫ A suspension of methyl (S)-4-phenyl-3-phthalimidobutano-
13C NMR (75.4 MHz, CDCl3): δ ϭ 136.46, 133.95, 129.35, 128.82,
127.08, 118.03, 70.02, 57.07, 37.17, 33.55. Ϫ IR (CCl4): ν˜ ϭ
3650Ϫ3200 (br.) cmϪ1. Ϫ MS; m/z: 181 [Mϩ], 150, 120, 91.
ate (1.0 g, 3.1 mmol) in acetone (13 mL), water (10 mL), and con-
centrated hydrochloric acid (4 mL) was heated under reflux for 3
h. The reaction mixture was then concentrated to dryness in vacuo.
The residue was dissolved in 12% aqueous potassium hydrogen car-
bonate solution, the solution was filtered to eliminate impurities,
and then acidified with hydrochloric acid. The resulting precipitate
was filtered off and crystallized from MeOH/H2O, giving 0.77 g
(81%) of 12 as a white solid; m.p. 123Ϫ125°C. Ϫ [α]D ϭ Ϫ118.2
(c ϭ 1.01, CHCl3). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 7.81Ϫ7.62
(m, 4 H), 7.25Ϫ7.12 (m, 5 H), 5.00Ϫ4.85 (m, 1 H), 3.40Ϫ3.08 (m,
3 H), 2.98Ϫ2.82 (dd, J ϭ 17.5, 5.0 Hz, 1 H). Ϫ 13C NMR (50.3
MHz, CDCl3): δ ϭ 176.53, 168.01, 136.99, 133.89, 131.40, 128.92,
128.48, 126.77, 123.18, 48.78, 38.34, 35.98. Ϫ IR (CCl4): ν˜ ϭ 3500
cmϪ1, 1780, 1720. Ϫ MS; m/z: 309 [Mϩ], 291, 218, 200, 162. Ϫ
C18H15NO4 (309.10): calcd. C 69.89, H 4.89, N 4.53; found C
69.80, H 4.86, N 4.50.
(2S,3R)-1-Phenyl-2-phthalimido-5-hexen-3-ol (9): A mixture of 8 (50
mg, 0.26 mmol) and phthalic anhydride (46 mg, 0.31 mmol) was
stirred at 150°C for 30 min. After cooling to r.t., the reaction mix-
ture was extracted with CHCl3. After removal of the solvent in
vacuo from the combined organic extracts, the residue was chroma-
tographed on silica gel plates giving 59 mg (70%) of pure 9 as a
white solid; m.p. 71Ϫ72°C. Ϫ [α]D ϭ Ϫ64.5 (c ϭ 0.69, CHCl3). Ϫ
1H NMR (300 MHz, CDCl3): δ ϭ 7.80Ϫ7.60 (m, 4 H), 5.90Ϫ5.75
(m, 1 H), 5.20Ϫ5.15 (m, 2 H), 4.65Ϫ4.45 (m, 1 H), 4.30Ϫ4.20 (m,
1 H), 3.39Ϫ3.20 (m, 3 H), 2.45Ϫ2.30 (m, 2 H). Ϫ 13C NMR (75.4
MHz, CDCl3): δ ϭ 168.45, 137.85, 131.37, 134.09, 133.96, 128.94,
128.38, 126.47, 123.31, 118.69, 71.94, 57.40, 39.20, 33.08. Ϫ IR
(CCl4): ν˜ ϭ 3460 cmϪ1, 1770, 1750, 1705. Ϫ MS; m/z: 321 [Mϩ],
280, 262, 133. Ϫ C20H19NO3 (321.38): calcd. C 74.75, H 5.96, N
4.36; found C 74.09, H 5.88, N 4.28.
(S)-(4-Phenyl-3-phthalimidobutanoyl)dimethylphenylsilane (13):
A
mixture of the acid 12 (2.0 g, 6.4 mmol) and SOCl2 (20 mL) was
warmed to 55Ϫ60°C for 6 h. After work-up according to the stand-
ard procedures, 1.96 g (93%) of (S)-4-phenyl-3-phthalimidobu-
tanoyl chloride was obtained as a white solid, which was used in
the next step without further purification; m.p. 93Ϫ95°C. Ϫ 1H
NMR (200 MHz, CDCl3): δ ϭ 7.84Ϫ7.65 (m, 4 H), 7.30Ϫ7.15 (m,
5 H), 5.05Ϫ4.90 (m, 1 H), 3.92 (dd, J ϭ 17.5, 10 Hz, 1 H),
3.45Ϫ3.05 (m, 3 H). Ϫ IR (CCl4): ν˜ ϭ 1800 cmϪ1, 1780, 1720. Ϫ
MS; m/z: 327 [Mϩ], 292, 250. Ϫ Compound 13 was prepared using
the same procedure as that described for acylsilane 5, by reaction
of a 0.4  solution of bis(dimethylphenylsilyl)lithium cyanocu-
prate[32] (7.5 mL, 3 mmol) in THF with (S)-4-phenyl-3-phthalimi-
dobutanoyl chloride (1.0 g, 3 mmol) in THF (10 mL). The crude
product was purified on a silica gel column (eluent: light petroleum
ether/Et2O, 10:1), giving 0.72 g (55%) of pure 13 as a white solid;
m.p. 60Ϫ61°C. Ϫ [α]D ϭ Ϫ45.2 (c ϭ 2.76, C6H6). Ϫ 1H NMR (200
MHz, CDCl3): δ ϭ 7.80Ϫ7.10 (m, 14 H), 5.05Ϫ4.95 (m, 1 H), 3.52
(dd, 1 H, J ϭ 17.5, 7.5 Hz), 3.20Ϫ3.05 (m, 2 H), 2.95 (dd, J ϭ
17.5, 6.0 Hz, 1 H), 0.48 (s, 3 H), 0.43 (s, 3 H). Ϫ 13C NMR (50.3
MHz, CDCl3): δ ϭ 243.47, 168.07, 137.49, 134.95, 133.97, 133.71,
131.55, 129.99, 128.94, 128.37, 128.20, 126.58, 123.04, 50.07, 47.48,
38.84, Ϫ4.69, Ϫ4.05. Ϫ IR (CCl4): ν˜ ϭ 1780 cmϪ1, 1720, 1650,
1250. Ϫ MS; m/z: 427 [Mϩ], 399, 336, 292, 135. Ϫ C26H25NO3Si
(427.57): calcd. C 73.04, H 5.89, N 3.28; found C 72.75, H 5.85,
N 3.26.
(2S,3S)-2-Amino-1-phenyl-5-hexen-3-ol (10): The reaction was per-
formed under the same conditions as used for 6a, starting from 6b
(0.14 g, 0.29 mmol), liquid ammonia (9 mL), and sodium (40 mg,
1.74 mmol). Chromatography of the crude product on silica gel
1
plates (CHCl3/MeOH, 2:1) gave 33 mg (60%) of 10. Ϫ H NMR
(200 MHz, CDCl3): δ ϭ 7.50Ϫ7.20 (m, 5 H), 6.10Ϫ5.70 (m, 4 H),
5.30Ϫ5.10 (m, 2 H), 3.95Ϫ3.80 (m, 1 H), 3.45Ϫ3.40 (m, 1 H),
3.30Ϫ2.90 (m, 2 H), 2.40Ϫ2.00 (m, 2 H). Ϫ 13C NMR (75.4 MHz,
CDCl3): δ ϭ 137.60, 133.63, 129.75, 129.05, 127.15, 118.39, 69.17,
56.92, 36.36, 29.68. Ϫ IR (CCl4): ν˜ ϭ 3690Ϫ3220 (br.) cmϪ1. Ϫ
MS; m/z: 150 [Mϩ Ϫ 41], 120, 100, 91, 77. Ϫ Compound 10 was
N-protected with phthalic anhydride (29.6 mg, 0.2 mmol) under
the same conditions as used for the protection of 8, giving 48 mg
(86%) of (2S,3S)-1-phenyl-2-phthalimido-5-hexen-3-ol (3).
(S)-4-Phenyl-3-phthalimidobutanoic Acid (12): To a stirred 0.3 
solution of diazomethane (90 mL, 27 mmol) in diethyl ether at 0°C,
was added a solution of N-phthaloyl--phenylalanyl chloride[30]
(2.5 g, 8 mmol) in THF (10 mL). After 1 h, the excess diazometh-
ane was removed by bubbling Ar through the solution. Concen-
tration of the reaction mixture under reduced pressure gave 2.4 g
(94%) of (S)-1-diazo-3-phthalimido-4-phenyl-2-butanone; m.p.
129Ϫ131°C (dec.). Ϫ [α]D ϭ Ϫ210.8 (c ϭ 0.66, CHCl3). Ϫ 1H
NMR (200 MHz, CDCl3): δ ϭ 7.85Ϫ7.60 (m, 4 H), 7.05Ϫ7.10 (m,
5 H), 5.35 (s, 1 H), 5.10 (dd, J ϭ 9.3, 5.8 Hz, 1 H), 3.55Ϫ3.45 (m,
2 H). Ϫ 13C NMR (50.3 MHz, CDCl3): δ ϭ 189.27, 167.55, 136.64,
134.27, 131.34, 128.80, 128.57, 126.83, 123.51, 58.29, 54.23, 33.89.
Ϫ IR (CCl4): ν˜ ϭ 2113 cmϪ1, 1775, 1715, 1650. Ϫ MS; m/z: 291
Reaction of 13 with Allyltrimethylsilane: The reaction was per-
formed under the same conditions as used for the reaction of acyl-
silane 1, starting from 13 (0.49 g, 1.15 mmol) in CH2Cl2 (4 mL),
allyltrimethylsilane (0.26 g, 2.3 mmol), and a 1.0  solution of
[Mϩ Ϫ N2], 250, 200. Ϫ To a stirred solution of (S)-1-diazo-3- TiCl4 (1.15 mL, 1.15 mmol) in CH2Cl2. The crude product was
phthalimido-4-phenyl-2-butanone (3.19 g, 10 mmol) in methanol
submitted to 1H- and 13C-NMR analysis, which showed the pres-
(90 mL) was added silver oxide (0.28 g, 1.2 mmol) and the mixture ence of a single diastereoisomer. The material was then purified on
was warmed to 50°C for 40 min. After cooling to r.t., the reaction
mixture was filtered through Celite and the filtrate was concen-
trated in vacuo. The crude residue was purified on a silica gel col-
umn (eluent: light petroleum ether/diethyl ether, 1:2) giving 2.8 g
(87%) of methyl(S)-4-phenyl-3-phthalimidobutanoate; m.p.
a silica gel column (eluent: light petroleum ether/Et2O, 5:1), afford-
ing 0.43 g (80%) of pure (S)-4-(dimethylphenylsilyl)-7-phenyl-6-
phthalimido-1-hepten-4-ol (17) as a colorless oil. Ϫ [α]D ϭ Ϫ63.3
1
(c ϭ 1.98, C6H6). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 7.75Ϫ7.58
(m, 6 H), 7.45Ϫ7.35 (m, 3 H), 7.20Ϫ7.05 (m, 5 H), 5.70Ϫ5.50 (m,
73Ϫ75°C. Ϫ [α]D ϭ Ϫ1.3 (c ϭ 1.00, CHCl3). Ϫ 1H NMR (200 1 H), 5.15Ϫ4.95 (m, 2 H), 4.85Ϫ4.65 (m, 1 H), 3.28 (dd, J ϭ 14.1,
MHz, CDCl3): δ ϭ 7.85Ϫ7.63 (m, 4 H), 7.28Ϫ7.15 (m, 5 H),
9.8 Hz, 1 H), 3.04 (dd, J ϭ 14.1, 6.5 Hz, 1 H), 2.75 (dd, J ϭ 15.2,
5.15Ϫ4.95 (m, 1 H), 3.62 (s, 3 H), 3.40Ϫ3.13 (m, 3 H), 2.95Ϫ2.80 9.8 Hz, 1 H), 2.48Ϫ2.35 (m, 2 H), 1.85 (dd, J ϭ 15.2, 2.6 Hz, 1
(dd, J ϭ 15.8, 5.3 Hz, 1 H). Ϫ 13C NMR (50.3 MHz, CDCl3): H), 1.09 (s, 1 H), 0.39 (s, 6 H). Ϫ 13C NMR (50.3 MHz, CDCl3):
δ ϭ 170.15, 168.01, 137.55, 134.03, 131.98, 129.13, 128.66, 126.92,
123.31, 51.98, 49.02, 38.56, 36.22. Ϫ IR (CCl4): ν˜ ϭ 1770 cmϪ1
δ ϭ 168.62, 138.01, 134.59, 133.83, 133.67, 133.53, 131.88, 129.40,
,
128.94, 128.34, 127.85, 126.43, 122.91, 118.75, 68.01, 48.37, 41.81,
1720, 1745. Ϫ MS; m/z: 323 [Mϩ], 292, 250, 176. Ϫ C19H17NO4 39.87, 36.34, Ϫ4.68, Ϫ4.98. Ϫ IR (CCl4): ν˜ ϭ 3571 cmϪ1, 1770,
(323.35): calcd. C 70.58, H 5.30, N 4.33; found C 70.30, H 5.26, N
442
1708. Ϫ MS; m/z: 469 [Mϩ], 428, 378, 321, 135. Ϫ C29H31NO3Si
Eur. J. Org. Chem. 1999, 437Ϫ445

Enantiopure β- and γ-Amino Alcohols from Homochiral α- and β-Aminoacylsilanes
FULL PAPER
(469.21): calcd. C 74.16, H 6.65, N 2.98; found C 73.85, H 6.61,
N 2.26.
46.10, H 4.20, N 3.31. Ϫ A mixture of (S)-1-iodo-3-phenyl-2-tosyl-
amidopropane (6.5 g, 15.7 mmol), tetrabutylammonium cyanide
(10 g, 37.3 mmol, previously dried in vacuo over P2O5), and dry
CH3CN (35 mL), was stirred at 70°C for 4 h. The solvent was then
removed under reduced pressure and the residue was extracted with
chloroform. The combined organic phases were washed with water,
dried with MgSO4, and concentrated in vacuo. The residue was
purified on a silica gel column (eluent: CHCl3), affording 3.2 g
(65%) of (S)-3-phenyl-2-tosylamido-1-butanonitrile as a light-yel-
low oil. Ϫ [α]D ϭ ϩ58.6 (c ϭ 4.00, CHCl3). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 7.60Ϫ7.50 (m, 2 H), 7.20Ϫ7.10 (m, 5 H), 7.00Ϫ6.90
(m, 2 H), 5.35 (d, J ϭ 6.5 Hz, 1 H), 3.60 (m, 1 H), 2.85 (dd, J ϭ
14.1, 6.4 Hz, 1 H), 2.75 (dd, J ϭ 14.1, 7.7 Hz, 1 H), 2.65 (dd, J ϭ
16.7, 5.4 Hz, 1 H), 2.50 (dd, J ϭ 16.7, 3.85 Hz, 1 H) 2.40 (s, 3 H). Ϫ
13C NMR (75.4 MHz, CDCl3): δ ϭ 143.04, 136.01, 135.02, 129.26,
128.48, 128.25, 126.52, 126.30, 116.70, 51.18, 39.16, 23.84, 20.97.
Ϫ IR (CCl4): ν˜ ϭ 3310 cmϪ1, 1660, 1175. Ϫ MS; m/z: 314 [Mϩ],
274, 223, 155, 91. Ϫ C17H18N2O2Si (314.11): calcd. C 64.95, H
5.78, N 8.92; found C 64.81, H 5.60, N 8.64. Ϫ A mixture of (S)-
3-phenyl-2-tosylamido-1-butanonitrile (3.14 g, 10 mmol), glacial
acetic acid (10 mL), water (10 mL), and concentrated sulfuric acid
(10 mL) was stirred at 110°C for 9 h. After cooling, the reaction
mixture was poured into iced water and the precipitated solid was
washed with water until a neutral pH was reached. The residue was
dissolved in a 20% aqueous potassium hydrogen carbonate solution
and the resulting solution was filtered in order to eliminate impurit-
ies. Acidification with concentrated hydrochloric acid led to cloud-
ing of the solution, which was then extracted three times with di-
ethyl ether. The combined organic phases were dried with MgSO4
and the solvent was evaporated in vacuo, leaving 2.3 g (70%) of 15
as a white solid (MeOH/H2O, 1:1); m.p. 91Ϫ93°C. Ϫ 1H NMR
(300 MHz, CDCl3): δ ϭ 10.0 (br. s, 1 H), 7.70Ϫ7.50 (m, 2 H),
7.30Ϫ7.10 (m, 5 H), 7.10Ϫ6.90 (m, 2 H), 5.90Ϫ5.70 (m, 1 H),
3.90Ϫ3.70 (m, 1 H), 2.90Ϫ2.70 (m, 2 H), 2.60Ϫ2.45 (m, 2 H), 2.40
(s, 3 H). Ϫ 13C NMR (75.4 MHz, CDCl3): δ ϭ 176.12, 143.17,
136.95, 136.64, 129.48, 129.08, 128.42, 126.76, 126.57, 51.76, 40.48,
38.13, 21.30. Ϫ IR (CCl4): ν˜ ϭ 3480 cmϪ1, 3380, 1720, 1175. Ϫ
MS; m/z: 333 [Mϩ], 274, 242, 155, 91. Ϫ C17H19NO4S (333.10):
calcd. C 61.24, H 5.75, N 4.20; found C 61.00, H 5.64, N 4.01.
(4R,6R)-7-Phenyl-6-phthalimido-1-hepten-4-ol (18): Prepared using
the same procedure as that used for compound 3, starting from 17
(80 mg, 0.17 mmol) in THF (3 mL) and 0.19 mL (0.19 mmol) of
1
a 1.0  solution of TBAF in THF. H- and 13C-NMR analysis of
the crude product showed the presence of a single diastereoisomer.
Subsequent purification on a silica gel column (eluent: light petro-
leum ether/Et2O, 3:1) gave 41 mg (72%) of pure 18 as a colorless
oil. Ϫ [α]D ϭ Ϫ57.3 (c ϭ 1.74, C6H6). Ϫ 1H NMR (200 MHz,
CDCl3): δ ϭ 7.80Ϫ7.65 (m, 4 H), 7.25Ϫ7.10 (m, 5 H), 5.85Ϫ5.75
(m, 1 H), 5.15Ϫ5.05 (m, 2 H), 4.90Ϫ4.70 (m, 1 H), 3.50Ϫ3.35 (m,
1 H), 3.15Ϫ3.05 (dd, J ϭ 13.8, 5.75 Hz, 1 H), 2.48Ϫ2.35 (m, 1 H),
2.28Ϫ2.15 (m, 3 H), 1.85Ϫ1.70 (m, 1 H). Ϫ 13C NMR (50.3 MHz,
CDCl3): δ ϭ 168.84, 137.88, 134.42, 133.92, 131.52, 128.84, 128.44,
126.51, 123.18, 118.08, 67.46, 50.80, 41.77, 39.06, 38.58. Ϫ IR
(CCl4): ν˜ ϭ 3515 cmϪ1, 1770, 1715. Ϫ MS; m/z: 335 [Mϩ], 317,
294, 250, 244. Ϫ C21H21NO3 (335.40): calcd. C 75.20, H 6.31, N
4.18; found C 74.91, H 6.27, N 4.15.
MTPA Esters of Alcohol 18: These esters were obtained under
standard conditions (see ref.[31]).
(R)-MTPA Ester of 18: Purified by preparative TLC (eluent: light
1
petroleum ether/Et2O, 3.1). Ϫ H NMR (300 MHz, CDCl3): δ ϭ
8.20Ϫ6.90 (m, 14 H), 5.46Ϫ5.30 (m, 1 H), 5.05Ϫ4.90 (m, 3 H), 4.52
(m, 1 H), 3.60 (s, 3 H), 3.20 (dd, 1 H), 2.97 (dd, 1 H), 2.66Ϫ2.50 (m,
1 H), 2.29Ϫ2.25 (m, 2 H), 1.98 (m, 1 H).
(S)-MTPA Ester of 18: Purified as in the case of the (R)-MTPA
1
ester. Ϫ H NMR (300 MHz, CDCl3): δ ϭ 8.10Ϫ7.00 (m, 14 H),
5.62 (m, 1 H), 5.10Ϫ4.90 (m, 3 H), 4.44Ϫ4.40 (m, 1 H), 3.60 (s, 3
H), 3.18 (dd, 1 H), 2.95 (dd, 1 H), 2.65Ϫ2.60 (m, 1 H), 2.42Ϫ2.38
(m, 2 H), 1.96Ϫ1.85 (m, 1 H).
(S)-4-Phenyl-3-tosylamidobutanoic Acid (15): A mixture of -phen-
ylalaninol (7.6 g, 0.05 mol), p-toluenesulfonyl chloride (11 g, 0.06
mol), water (50 mL), and THF (75 mL) was stirred at r.t. for 9 h,
then extracted with diethyl ether. The organic phase was washed
with water, dried with MgSO4, and the solvent was evaporated in
vacuo. The crude residue was purified by chromatography on a
silica gel column (eluent: light petroleum ether/diethyl ether, 1:2),
giving 15 g (98%) of N-tosyl--phenylalaninol as a white product; (S)-(4-Phenyl-3-tosylamidobutanoyl)dimethylphenylsilane (16):
A
m.p. 28Ϫ30°C. Ϫ [α]D ϭ Ϫ32.5 (c ϭ 5.38, CHCl3). Ϫ 1H NMR
(200 MHz, CDCl3): δ ϭ 7.65Ϫ7.60 (m, 2 H), 7.30Ϫ7.10 (m, 5 H),
mixture of the acid 15 (2.0 g, 6.0 mmol) and SOCl2 (20 mL) was
warmed to 55Ϫ60°C for 6 h. After work-up according to standard
7.10Ϫ6.95 (m, 2 H), 5.90 (d, J ϭ 7.8 Hz, 1 H), 3.80Ϫ3.40 (m, 4 procedures, 2.0 g (95%) of (S)-4-phenyl-3-tosylamidobutanoyl chlo-
H), 2.90Ϫ2.60 (m, 2 H), 2.40 (s, 3 H). Ϫ IR (CCl4): ν˜ ϭ 3500 cmϪ1
ride was obtained as a light-yellow solid, which was used in the
3260, 1160. Ϫ MS; m/z: 305 [Mϩ], 274, 242, 155. Ϫ C16H19NO3S next step without further purification; m.p. 84Ϫ86°C. Ϫ [α]D
,
ϭ
(305.39): calcd. C 62.93, H 6.27, N 4.59; found C 62.86, H 6.22, N
4.56. Ϫ To a stirred solution of N-tosyl--phenylalaninol (10 g, 33
Ϫ36.0 (c ϭ 2.43, CHCl3). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ
7.60Ϫ7.50 (m, 2 H), 7.30Ϫ7.10 (m, 5 H), 7.00Ϫ6.90 (m, 2 H), 4.80
mmol) in dry CH3CN (135 mL), were added triphenylphosphane (d, J ϭ 7.5 Hz, 1 H), 3.75 (m, 1 H), 3.15Ϫ3.00 (m, 2 H), 2.80Ϫ2.60
(13 g, 49.5 mmol), imidazole (3.3 g, 49.5 mmol), and iodine (12.6 (m, 2 H), 2.40 (s, 3 H). Ϫ IR (CCl4): ν˜ ϭ 3260 cmϪ1, 1800, 1175.
g, 49.5 mmol) and the mixture was warmed to 95Ϫ100°C for 2 h.
After cooling to r.t., the excess iodine was removed by the addition
of a 40% aqueous sodium thiosulfate solution. The reaction mix-
ture was then extracted with diethyl ether, the combined organic
Ϫ Compound 16 was prepared using the same procedure as that
described for 5, by reaction of a 0.4  solution of bis(dimethylphen-
ylsilyl)lithium cyanocuprate[32] (14.25 mL, 5.7 mmol) in THF with
(S)-4-phenyl-3-tosylamidobutanoyl chloride (2.0 g, 5.7 mmol) in
phases were washed with water, dried with MgSO4, and concen- THF (12 mL). The crude product was purified on a silica gel col-
trated in vacuo. The residue was purified on a silica gel column
(eluent: light petroleum ether/Et2O, 2:1) giving 12.2 g (90%) of (S)-
1-iodo-3-phenyl-2-tosylamidopropane as a white product; m.p.
umn (eluent: light petroleum ether/Et2O, 3:1), giving 1.28 g (50%)
of pure 16 as a colorless oil. Ϫ [α]D ϭ Ϫ21.0 (c ϭ 3.00, CHCl3).
Ϫ
1H NMR (300 MHz, CDCl3): δ ϭ 7.60Ϫ7.55 (m, 2 H),
86Ϫ87°C. Ϫ [α]D ϭ Ϫ11.0 (c ϭ 4.81, CHCl3). Ϫ 1H NMR (300 7.50Ϫ7.30 (m, 5 H), 7.20Ϫ7.00 (m, 5 H), 7.75Ϫ7.70 (m, 2 H), 5.10
MHz, CDCl3): δ ϭ 7.70Ϫ7.60 (m, 2 H), 7.20Ϫ7.10 (m, 5 H),
7.10Ϫ7.00 (m, 2 H), 5.25 (d, J ϭ 7.8 Hz, 1 H), 3.30Ϫ3.10 (m, 3
(d, J ϭ 8.2 Hz, 1 H), 3.70Ϫ3.55 (m, 1 H), 2.75 (dd, J ϭ 18.2, 4.1
Hz, 1 H), 2.65Ϫ2.50 (m, 3 H), 2.40 (s, 3 H), 0.40 (s, 6 H). Ϫ 13C
H), 2.85 (dd, J ϭ 14.2, 6.8 Hz, 1 H), 2.70 (dd, J ϭ 14.3, 6.4 Hz, 1 NMR (75.4 MHz, CDCl3): δ ϭ 245.59, 143.06, 137.55, 137.17,
H), 2.40 (s, 3 H). Ϫ MS: m/z: 415 [Mϩ], 324, 288, 274, 155, 91. Ϫ 133.92, 130.10, 129.54, 129.02, 128.51, 128.26, 127.98, 126.90,
C16H18NIO2S (415.01): calcd. C 46.26, H 4.37, N 3.37; found C
126.55, 51.11, 50.59, 40.29, 21.46, Ϫ5.20. Ϫ IR (CCl4): ν˜ ϭ 3300
Eur. J. Org. Chem. 1999, 437Ϫ445
443

G. Mazzanti et al.
cmϪ1, 1650, 1175. Ϫ MS; m/z: 451 [Mϩ], 360, 274, 155, 135, 91. Ϫ H), 7.58Ϫ7.52 (m, 2 H), 7.50Ϫ7.40 (m, 3 H), 7.30Ϫ7.15 (m, 5 H),
FULL PAPER
C25H29NO3SSi (451.16): calcd. C 66.49, H 6.48, N 3.10; found C
66.49, H 6.31, N 2.90.
6.98Ϫ6.90 (m, 2 H), 5.53Ϫ5.39 (m, 1 H), 5.18Ϫ5.06 (m, 1 H),
4.94Ϫ4.82 (m, 2 H), 4.78 (d, J ϭ 7.5 Hz, 1 H), 3.60Ϫ3.44 (m, 1
H), 3.42 (s, 3 H), 2.71Ϫ2.52 (m, 2 H), 2.39 (s, 3 H), 2.22Ϫ2.17 (m,
2 H), 1.82Ϫ1.55 (m, 2 H).
Reaction of 16 with Allyltrimethylsilane: The reaction was per-
formed under the same conditions as used for the reaction of acyl-
silane 1, starting from acylsilane 16 (0.3 g, 0.66 mmol) in CH2Cl2
(1.5 mL), allyltrimethylsilane (0.15 g, 1.32 mmol), and a 1.0  solu-
tion of TiCl4 (0.66 mL, 0.66 mmol) in CH2Cl2. (S)-4-[Dimethyl-
(phenyl)silyl]-7-phenyl-6-tosylamido-1-hepten-4-ol (19) was ob-
tained as an 82:18 mixture of two diastereoisomers. Purification of
the crude product on a silica gel column (eluent: light petroleum
ether/CH2Cl2, 1:5) gave 0.2 g (62%) of pure 19 as a light-yellow oil
containing both diastereoisomers in the same 82:18 ratio. Ϫ 1H
NMR (200 MHz, CDCl3): major stereoisomer: δ ϭ 0.231 (s, 3 H),
0.243 (s, 3 H); minor stereoisomer: δ ϭ 0.098 (s, 3 H), 0.185 (s, 3
H). Ϫ 13C NMR (50.3 MHz, CDCl3): major stereoisomer: δ ϭ
Ϫ5.12 (CH3Si); minor stereoisomer: δ ϭ Ϫ4.98 (CH3Si). Ϫ IR
(S)-MTPA Ester of 20a: Purified as in the case of the (R)-MTPA
ester. Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ 7.63Ϫ7.60 (m, 2 H),
7.56Ϫ7.48 (m, 2 H), 7.42Ϫ7.37 (m, 2 H), 7.28Ϫ7.15 (m, 6 H),
6.90Ϫ6.80 (m, 2 H), 5.65Ϫ5.51 (m, 1 H), 5.05Ϫ4.90 (m, 2 H),
3.53Ϫ3.40 (s ϩ m, 3 H), 2.59Ϫ2.40 (m, 2 H), 2.39 (s, 3 H),
1.75Ϫ1.49 (m, 2 H), 0.97Ϫ0.81 (m, 2 H).
Acknowledgments
This work was supported by Progetto Strategico, Tecnologie Chi-
miche Innovative (CNR, Italy) and by the University of Bologna
(“Funds For Selected Research Topics, 1996Ϫ1998”).
(CCl4): ν
˜ ϭ 3520 cmϪ1, 3280, 1350, 1175. Ϫ MS; m/z: 493 [Mϩ],
478, 452.
[1]
Reaction of 16 with Tetraallyltin: The reaction was performed under
the same conditions as used in the reaction of 5, starting from
acylsilane 16 (180 mg, 0.4 mmol) in CH2Cl2 (2.0 mL), tetraallyltin
(57 mg, 0.2 mmol), and Sc(OTf)3 (14 mg, 0.028 mmol) in CH2Cl2
(1.0 mL). Compound 19 was obtained as a 75:25 mixture of two
diastereoisomers, the ratio of which was maintained after purifi-
cation on a silica gel column, which furnished 188 mg (96%) of
pure 19.
J. Jurczak, A. Golebiowski, Chem. Rev. 1989, 89, 149Ϫ164 and
references therein.
[2]
D. H. Rich, “Peptidase Inhibitors” in Comprehensive Medicinal
Chemistry (Ed.: P. G. Sammes), Pergamon Press, Oxford, 1990,
vol. 2, p. 391Ϫ441 and references therein.
[3]
K. C. Nicolaou, W. Dai, R. K. Guy, Angew. Chem. Int. Ed.
Engl. 1994, 33, 15Ϫ44.
[4]
Z. X. Shen, J. Lu, Q. Zhang, Y. W. Zhang, Tetrahedron: Asym-
metry 1997, 8, 2287Ϫ2289.
[5]
J. Wilken, M. Kossenjans, H. Groger, J. Martens, Tetrahedron:
Asymmetry 1997, 8, 2007Ϫ2015.
(4R,6R)- (20a) and (4S,6R)-7-Phenyl-6-tosylamido-1-hepten-4-ol
(20b): Prepared using the same procedure as that used for com-
pound 3, starting from 19 (0.1 g, 0.2 mmol, 75:25 mixture of two
diastereoisomers) in THF (4 mL) and 0.28 mL (0.28 mmol) of a
1.0  solution of TBAF in THF. The crude product was submitted
to 1H-NMR analysis, which showed the presence of 20a and 20b
in a 75:25 ratio. The two isomers were separated on silica gel plates.
A double elution with CH2Cl2/light petroleum ether, 5:1, gave, as
the slower moving product, 39 mg (54%) of 20a and, as the faster
moving product, 13 mg (18%) of 20b.
[6]
W. Trentmann, T. Mehler, J. Martens, Tetrahedron: Asymmetry
1997, 8, 2033Ϫ2043.
[7]
M. Andres, Y. Martin, R. Pedrosa, A. Perez-Encabo, Tetra-
hedron 1997, 53, 3787Ϫ3794.
[8]
F. DЈAniello, A. Mann, D. Mattii, M. Taddei, J. Org. Chem.
1994, 59, 3762Ϫ3768 and references therein.
[9]
M. T. Reetz, Angew. Chem. Int. Ed. Engl. 1991, 30, 1531Ϫ1546;
M. T. Reetz, M. W. Drewes, A. Schmitz, Angew. Chem. Int. Ed.
Engl. 1987, 26, 1141Ϫ1143.
[10]
A. Dondoni, D. Perrone, P. Merino, J. Org. Chem. 1995, 60,
8074Ϫ8080; A. Dondoni, D. Perrone, T. Semola, Synthesis
1995, 181Ϫ186.
[11]
1
J. V. N. V. Prasad, D. H. Rich, Tetrahedron Lett. 1990, 31,
20a (major): [α]D ϭ 8.1 (c ϭ 2.5, CHCl3). Ϫ H NMR (200 MHz,
1803Ϫ1806; J. V. N. V. Prasad, D. H. Rich, Tetrahedron Lett.
1991, 32, 5857Ϫ5860.
CDCl3): δ ϭ 7.70Ϫ7.60 (m, 2 H), 7.29Ϫ7.15 (m, 5 H), 6.95Ϫ6.85
(m, 2 H), 5.82Ϫ5.60 (m, 1 H), 5.07Ϫ4.88 (m, 3 H), 4.00Ϫ3.81 (m,
1 H), 3.78Ϫ3.61 (m, 1 H), 2.68Ϫ2.49 (m, 3 H), 2.40 (s, 3 H),
2.15Ϫ2.03 (m, 2 H), 1.55Ϫ1.30 (m, 2 H). Ϫ 13C NMR (50.3 MHz,
CDCl3): δ ϭ 143.29, 137.70, 136.89, 134.57, 129.69, 128.52, 126.95,
126.58, 117.80, 66.89, 52.20, 41.72, 41.53, 40.72, 21.51. Ϫ IR
(CCl4): ν˜ ϭ 3510 cmϪ1, 3280, 1175. Ϫ MS; m/z: 359 [Mϩ], 318,
268, 198, 155, 91. Ϫ C20H25NO3S (359.48): calcd. C 66.82, H 7.02,
N 3.90; found C 66.58, H 6.88, N 3.77.
[12]
D. Gryko, Z. Urbanczyk-Lipkowska, J. Jurczak, Tetrahedron:
Asymmetry 1997, 8, 4059Ϫ4067.
[13]
J. Barluenga, A. L. Viado, E. Aguilar, S. Fustero, B. Olano, J.
Org. Chem. 1993, 58, 5972Ϫ5975 and references therein.
[14]
V. Jäger, W. Schwab, V. Buss, Angew. Chem. Int. Ed. Engl. 1981,
20, 601Ϫ603.
[15]
A. Pohland, H. R. Sullivan, J. Am. Chem. Soc. 1953, 75,
4458Ϫ4461; A. Pohland, H. R. Sullivan, J. Am. Chem. Soc.
1955, 77, 3400Ϫ3401.
[16]
R. Carlier, K. M. Lo, M. M. C. Lo, I. D. Williams, J. Org.
20b (minor): [α]D ϭ Ϫ4.5 (c ϭ 0.81, CHCl3). Ϫ 1H NMR (300
MHz, CDCl3): δ ϭ 7.71Ϫ7.62 (m, 2 H), 7.29Ϫ7.10 (m, 5 H),
7.05Ϫ6.98 (m, 2 H), 5.69Ϫ5.58 (m, 1 H), 5.38 (d, J ϭ 7.0 Hz, 1
H), 5.12Ϫ4.98 (m, 2 H), 3.50Ϫ3.38 (m, 2 H), 2.85 (dd, J ϭ 14.0,
5.0 Hz, 1 H), 2.65 (dd, J ϭ 14.0, 6.5 Hz, 1 H), 2.40 (s, 3 H),
2.19Ϫ1.92 (m, 3 H), 1.60Ϫ1.40 (m, 2 H). Ϫ 13C NMR (50.3 MHz,
CDCl3): δ ϭ 143.17, 137.32, 133.68, 128.49, 128.40, 127.92, 127.22,
127.14, 126.56, 119.05, 69.08, 54.49, 42.34, 41.96, 39.99, 21.54. Ϫ
Chem. 1995, 60, 7511Ϫ7517.
[17]
S. Chicchi, S. Crea, A. Goti, A. Brandi, Tetrahedron: Asym-
metry 1997, 8, 293Ϫ301; B. T. Cho, N. Kim, Tetrahedron Lett.
1994, 35, 4115Ϫ4118.
[18]
J. Barluenga, B. Olano, S. Fastero, J. Org. Chem. 1985, 50,
4052Ϫ4056; G. Bartoli, C. Cimarelli, E. Marcantoni, G. Pal-
mieri, M. Petrini, J. Org. Chem. 1994, 59, 5328Ϫ5335.
[19]
V. Jäger, V. Buss, Liebigs Ann. Chem. 1980, 101Ϫ121; V. Jäger,
V. Buss, W. Schwab, Liebigs Ann. Chem. 1980, 122Ϫ139; R.
Annunziata, M. Cinquini, F. Cozzi, A. Gilardi, A. Rastelli, J.
IR (CCl4): ν ϭ 3510 cmϪ1, 3280, 1175. Ϫ MS; m/z: 359 [Mϩ], 318,
˜
Chem. Soc., Perkin Trans. 1 1985, 2289Ϫ2292.
[20]
`
I. E. Marko, A. Chesney, Synlett 1992, 275; S. G. Davis, T. D.
268, 198, 155, 91. Ϫ C20H25NO3S (359.48): calcd. C 66.82, H 7.02,
N 3.90; found C 66.78, H 6.94, N 3.78.
McCarthy, Synlett 1995, 700Ϫ702.
[21]
[22]
[23]
B. F. Bonini, M. Comes-Franchini, G. Mazzanti, A. Ricci, M.
Sala, J. Org. Chem. 1996, 61, 7242Ϫ7243.
M. Nakada, Y. Urano, S. Kobayashi, M. Ohno, J. Am. Chem.
Soc. 1988, 110, 4826Ϫ4827.
MTPA Esters of Alcohol (20a): These esters were obtained under
standard conditions (see ref.[31]).
(R)-MTPA Ester of 20a: Purified by preparative TLC (CH2Cl2/
M. Nakada, Y. Urano, S. Kobayashi, M. Ohno, Tetrahedron
Lett. 1994, 35, 741Ϫ744.
1
Et2O, 1:1). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 7.62Ϫ7.60 (m, 2
444
Eur. J. Org. Chem. 1999, 437Ϫ445

Enantiopure β- and γ-Amino Alcohols from Homochiral α- and β-Aminoacylsilanes
FULL PAPER
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
M. Cherest, H. Felkin, N. Prudent, Tetrahedron Lett. 1968,
2199Ϫ2204.
C. Sheehan, D. W. Chapman, R. W. Roth, J. Am. Chem. Soc.
1952, 74, 3822Ϫ3825.
J. A. Dale, H. S. Mosher, J. Am. Chem. Soc. 1973, 95, 512Ϫ519;
I. Ohtani, I. Kasumi, Y. Kashman, H. Kakisawa, J. Am. Chem.
Soc. 1991, 113, 4092Ϫ4096.
I. Fleming, T. W. Newton, F. Roessler, J. Chem. Soc., Perkin
Trans. 1 1981, 2527Ϫ2532.
E. A. Popenoe, V. du Vigneaud, J. Am. Chem. Soc. 1954, 76,
6202Ϫ6203.
Y. Yamamoto, Acc. Chem. Res. 1987, 20, 243Ϫ249 and refer-
ences therein.
B. F. Bonini, M. Comes-Franchini, G. Mazzanti, U. Passa-
monti, A. Ricci, P. Zani, Synthesis 1995, 92Ϫ96.
I. Hachiya, S. Kobayashi, J. Org. Chem. 1993, 58, 6958Ϫ6960;
S. Kobayashi, Synlett 1994, 689Ϫ701.
B. F. Bonini, M. Comes-Franchini, M. Fochi, G. Mazzanti, C.
Nanni, A. Ricci, Tetrahedron Lett. 1998, 6737Ϫ6740.
A. G. Brook, Acc. Chem. Res. 1974, 7, 77Ϫ84.
[32]
[33]
Received July 23, 1998
[O98342]
Eur. J. Org. Chem. 1999, 437Ϫ445
445