Stereoselective Three-Carbon and Two-Carbon Elongation of the Carbon Chain in N-Boc-Protected α-Aminoacylsilanes: An Entry to Functionalized β-Amino Alcohols and to Statine Analogues

Full text of DOI:10.1021/jo982501x

8008
J . Org. Chem. 1999, 64, 8008-8013
tension of this previous work to differently protected R-
Ster eoselective Th r ee-Ca r bon a n d
and â-aminoacylsilanes obtained from L-phenylalanine
indicated that stereoselectivity in the addition step is
strongly dependent on the type of protecting group as well
as on the nature of the allylating reagent.8 Moreover, the
robustness of the protecting groups so far employed (N-
Pht and N-Ts) have caused some problems in the depro-
tection-desilylation steps of the allylated adducts, re-
quiring harsh conditions.
These observations prompted us to extend our previous
study to the synthesis of N-Boc aminoacylsilanes, since
the Boc group has proven9 highly serviceable in organic
synthesis as an amine protecting group. Here we report
the synthesis of the new N-Boc R-aminoacylsilanes
derived from L-phenylalanine and L-isoleucine and their
utility in a series of nucleophilic additions and aldol
condensations with the aim of devising a new entry to
functionalized molecules bearing the â-amino alcohol
moiety.
The methodology previously used for the synthesis of
aminoacylsilanes, based on the nucleophilic silylation of
an acyl chloride,7 was not applicable to the case of the
N-Boc-protected amino acids due to formation of the
corresponding oxazolone through spontaneous intramo-
lecular cyclization.10 On the other hand, attempts to use
the Weinreb amides11 from N-Boc-protected L-phenyla-
lanine and L-isoleucine failed in the silylcupration reac-
tion and led either to recovery of the starting materials
or to intractable mixtures of products. The established
usefulness and versatility of acylimidazolides,12 also
supported by our recent investigation directed at the
synthesis of R-aminoketones,13 prompted us to perform
the silylcupration of these more activated forms of the
amino acids. N-Boc L-phenylalanine (1) and N-Boc L-
isoleucine (2) were converted (Scheme 1) into the corre-
sponding R-aminoacylsilanes 5 and 6 in moderate yields
via 3 and 4 by reaction with carbonyldiimidazole (CDI),
followed by treatment with (Me2PhSi)2CuCNLi2. These
new compounds were purified by column chromatography
on silica gel (see Experimental Section) and stored in a
refrigerator for long periods without chemical degrada-
tion or racemization, thus proving their chemical and
optical stability.7,8
Tw o-Ca r bon Elon ga tion of th e Ca r bon
Ch a in in N-Boc-P r otected
r-Am in oa cylsila n es: An En tr y to
F u n ction a lized â-Am in o Alcoh ols a n d to
Sta tin e An a logu es
Bianca Flavia Bonini,† Mauro Comes-Franchini,†
Mariafrancesca Fochi,† Fre´deric Laboroi,‡
Germana Mazzanti,† Alfredo Ricci,*,† and Greta Varchi†
Dipartimento di Chimica Organica “A. Mangini”,
Universita` di Bologna, Via Risorgimento No. 4, I-40136,
Bologna, Italy, and ESCOM, 13, boulevard de l’ Hautil,
F-95092, Cergy Pontoise
Received December 23, 1998
The synthesis of enantiopure â-amino alcohols is
currently a subject of enormous interest mainly due to
their applications as peptidomimetics,1 as building blocks
for pharmaceuticals2 and also as ligands for asymmetric
catalysis.3 Diastereoselective addition to R-amino alde-
hydes has emerged as one of the most efficient and
versatile methods available for preparing functionalized
â-amino alcohols.4 However, N-protected R-amino alde-
hydes have some recurring drawbacks, since most of
them are relatively unstable both chemically and con-
figurationally, and low diastereoselectivity can be ob-
served5 in a number of addition reactions.
A simple conceptual approach to solve these problems,
bypassing amino aldehydes, would be to consider amino
acid-derived acylsilanes which mimic them and offer
increased stability and higher diastereofacial selectivity
induced by the presence of the bulky R3Si moiety.6
We have previously reported7 the synthesis of N-Pht-
protected R- and â-aminoacylsilanes derived from L-
phenylalanine and shown that the allylation occurs with
good chemical yields and high diastereoselectivity. Ex-
* Corresponding author. Tel: 0039-51-2093635. Fax: 0039-51-
2093654. e-mail: ricci@ms.fci.unibo.it.
† Universita` di Bologna.
‡ ESCOM.
(1) (a) J urczak, J .; Gobielowsky, A. Chem. Rev. 1989, 89, 149-164.
(b) Ibuka, T.; Habashita, H.; Otaka, A.; Fujii, N.; Oguchi, Y.; Uyehara,
T.; Yamamoto, Y. J . Org. Chem. 1991, 56, 4370-4382. (c) Huff, J . R.
J . Med. Chem. 1991, 34, 2305-2314. (d) Reetz, M. T.; Kanand, J .;
Griebenow, N.; Harms, K. Angew. Chem., Int. Ed. Engl. 1992, 31,
1626-1629 and references therein. (e) Hagihara, M.; Schreiber, S. L.
J . Am. Chem. Soc. 1992, 114, 6570-6571.
The synthetic equivalence of 5 and 6 to R-amino
aldehydes, which have been widely used in the synthesis
of amino sugars14 and other natural products,1a,4a allows
(2) Nicolau, K. C., Dai, W.; Guy, R. K. Angew. Chem., Int. Ed. Engl.
1994, 33, 15-44.
(8) Bonini, B. F.; Comes-Franchini, M.; Fochi, M.; Gawronsky, J .;
Mazzanti, G.; Ricci, A.; Varchi, G. Eur. J . Org. Chem. 1999, 437-445.
(9) Kocienski, P. J . In Protecting Groups; Georg Thieme Verlag:
Stuttgart, New York, 1994; Chapter 6, pp 192-195.
(10) Carpino, L. A.; Beyermann, M.; Wenschuh, H.; Bienert, M. Acc.
Chem. Res. 1996, 29, 268-274.
(11) (a) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815-
3818. (b) Levin, I. J .; Turos, E.; Weinreb, S. M. Synth. Commun. 1982,
12, 989-993.
(3) (a) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991,
30, 49-69. (b) Ajer, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev.
(Washington D. C.) 1996, 96, 835-875. (c) Shen, Z. X.; Lu, J .; Zhang,
Q.; Zhang, Y. W. Tetrahedron: Asymmetry 1997, 8, 2287-2289. (d)
Wilken, J .; Kossenjans, M.; Groger, H.; Martens, J . Ibid. 1997, 8, 2007-
2015. (e) Trentmann, W.; Mehler, T.; Martens, J . Ibid. 1997, 8, 2033-
2043. (f) Andres, M.; Martin, Y.; Pedrosa, A.; Perez-Encabo, A.
Tetrahedron 1997, 53, 3787-3794.
(4) (a) Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1991, 30, 1531-
1546. (b) D′Aniello, F.; Mann, A.; Matii, M.; Taddei, M. J . Org. Chem.
1994, 59, 3762-3768 and references therein. (c) Dondoni, A.; Perrone,
D.; Merino, P. J . Org. Chem. 1995, 60, 8074-8080.
(12) (a) Mitchell, R. H.; Iyer, V. S. Tetrahedron Lett. 1993, 34, 3683-
3686. (b) Nimitz, J . S.; Mosher, H. S. J . Org. Chem. 1981, 46, 211-
213. (c) Bhattacharya, A.; Williams, J . M.; Amato, J . S.; Dolling, U.
H.; Grabowsky, E. J . J . Synth. Commun. 1990, 30, 2683-2690.
(13) Bonini, B. F.; Comes-Franchini, M.; Fochi, M.; Mazzanti, G.;
Ricci, A.; Varchi, G. Synlett 1998, 1013-1015.
(14) (a) Dondoni, A. In Modern Synthetic Methods; Scheffold, R., Ed.;
Verlag Helvetica Chimica Acta: Basel, 1992; p 377. (b) J urzac, J .;
Golebiowsky, A. In Antibiotics and Antiviral Compounds. Chemical
Synthesis and Modification; Kroh, K., Kirst, H., Maag, H., Eds.; VCH:
Weinheim 1993; p 343.
(5) Gryko, D.; Urbanczyk-Lipkowska, Z.; J urczak, J . Tetrahedron:
Asymmetry 1997, 24, 4059-4067.
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Soc. 1988, 110, 4826-4827. (b) Nakada, M.; Urano, Y.; Kobayashi, S.;
Ohno, M. Tetrahedron Lett. 1994, 35, 741-744.
(7) Bonini, B. F.; Comes-Franchini, M.; Mazzanti, G.; Ricci, A.; Sala,
M. J . Org. Chem. 1996, 61, 7242-7243.
10.1021/jo982501x CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/21/1999

Notes
J . Org. Chem., Vol. 64, No. 21, 1999 8009
Sch em e 1a
N-Boc group took place under normal conditions affording
the isomerically pure amino alcohols 10a ,b and 13 in
high yields. After their transformation into the corre-
sponding oxazolidinone derivatives 11a ,b and 14, their
relative stereochemistry at C2 and C3 was determined by
measuring the coupling constants (J H4-J H5) and observ-
ing the NOE cross-peak between the H-4 and H-5
protons20 (Scheme 2). These results suggested that the
absolute configuration of the carbon bearing the hydroxy
group is R in products 7a and 8, and S in product 7b.
The significant differences in diastereoselectivities in
Table 1 appear related to the structure of the starting
amino acid. The observation that under the same ally-
lation conditions only derivative 6 leads to very high syn
selectivity suggests that factors other than chelation are
likely to play a major role in driving the stereochemical
outcome. Based on the Felkin-Ahn model, we propose
that these reactions proceed via conformers A and B.
a
(a) CDI, THF, rt, 45 min, 97% (for 3), 98% (for 4); (b)
(PhMe2Si)2CuCNLi2, -78 °C, 1 h, 50% (for 5), 55% (for 6).
Ta ble 1. Asym m etr ic Allyla tion of 5 a n d 6
The increase in the level of syn amino alcohol, which
accompanies the R-branching of the side chain as in 6,
can be concisely rationalized in terms of increased
adoption of conformer A in order to minimize steric
interaction of R with the Lewis acid- or In-coordinated21
carbonyl group. Chelation might also be operational in
stabilizing this conformer. As the spatial demand of R is
reduced as in the case of 5, conformer B would be favored
and anti selectivity materializes. In this case, however,
the differences in the product ratios are modest, indicat-
ing a small energy difference between the two pathways.
In the SnCl4-promoted reaction of 5 the diastereoselec-
tivity is biased in the syn direction as a consequence of a
chelation22 of the Lewis acid by both the oxygen atoms
of the Boc and carbonyl moieties thus favoring A.
Stereoselective two-carbon elongation of the carbon
skeleton of aminoacylsilanes 5 and 6 was performed by
introducing an acetic acid moiety. The aldol reaction of
O-ethyl-O-tert-butyldimethylsilyl ketene acetal with 5
and 6 proceeded smoothly (Scheme 3) in the presence of
BF3‚Et2O to give the expected addition products 15a ,b
and 17 in good yields and with high diastereoselectivity
in favor of the syn adduct. The highly preferred syn
selectivities can be accounted for by a preferential attack
a
Conditions A: 0.5 equiv of tetraallyltin, Sc(OTf)3 (7 mol %),
CH2Cl2, rt, 24 h; B: 2 equiv of allyl bromide, 1 equiv of In, THF,
rt, 15 h; C: 3 equiv of allyltrimethylsilane, 2 equiv of SnCl4,
CH2Cl2, -78 °C, 12 h. Yields of isolated products.
b
consideration of these new compounds as versatile chiral
synthons with potential use in asymmetric synthesis. For
this reason we embarked on a systematic three-carbon
and two-carbon stereoselective elongation of the carbon
skeleton of 5 and 6 via allylation and aldol reactions,
respectively.
The results of the addition of the allyl moiety to the
carbonyl group of 5 and 6 are shown in Table 1. Since
the allylation under Hosomi-Sakurai conditions15 led to
extensive decomposition of the starting materials because
of the incompatibility of TiCl4 with the N-Boc moiety, we
turned our attention to Sc(OTf)3-catalyzed16 allylation
with tetraallyltin and In-mediated allylation with allyl
bromide under Barbier conditions.17 Both these reactions
afforded the expected homoallylic alcohols in satisfactory
to good yields.
Allylation of 5 under both conditions, A and B (entries
1 and 2), yielded a mixture of diastereoisomers, 7a and
7b, while similar additions to 6 afforded (entries 4 and
5) a single diastereoisomer 8 selectively. The choice of
the allylating systems was made avoiding the use of more
basic allylic metals to prevent racemization at the C2
carbon in 5 and 6.18 To determine the configuration of
the monoprotected diastereoisomeric adducts, 7a and 7b,
separated by silica gel chromatography, and 8 were
subjected to stereospecific protiodesilylation with TBAF,
which can be assumed to proceed with complete retention
of configuration,6,19 to give the enantiopure â-amino
alcohols 9a ,b and 12.18 Subsequent deprotection of the
(18) The enantiomeric purity of 5 and 6 during synthesis or reaction
was a major concern. However, in the case of 6, only one diastereoi-
somer was observed in the allylation reaction (de > 98% for 8) within
the limits of detection in the 1H and 13C NMR spectra of the crude.
Moreover, in the case of 5, the optical purity of the amino alcohols 9a
and 9b was proved by converting them into the corresponding Mosher
esters. On these grounds, significant racemization in 5 and 6 could be
ruled out.
(19) Hudrlik, P. F.; Hudrlik, A. M.; Kulkarni, A. K. J . Am. Chem.
Soc. 1982, 104, 6809-6811.
(20) (a) Futagawa, S.; Inui, T.; Shiba, T. Bull. Chem. Soc. J pn. 1973,
46, 3308-3310. (b) Wagner, B.; Buegelmans, R., Zhu, J . Tetrahedron
Lett. 1996, 37, 6557-6560. (c) La¨ıb, T.; Chastanet, J .; Zhu, J . J . Org.
Chem. 1998, 63, 1709-1713.
(21) Paquette, L.; Mitzel, T. M.; Isaac, M. B.; Crasto, C. F.; Schomer,
W. W. J . Org. Chem. 1997, 62, 4293-4301.
(22) (a)Santelli, M.; Pons, J .-M. In Lewis Acids and Selectivity in
Organic Synthesis; CRC Press: New York, 1996; p 135. (b) Reetz, M.
T.; Kessler, K.; Yung, A. Tetrahedron Lett. 1984, 25, 729-732.
(15) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 16, 1295-1298.
(16) Kobayashi, S. Synlett 1994, 689-701, and references therein.
(17) Chan, T. H.; Li, C. J .; Lee, M. C.; Wei, Z. Y. Can. J . Chem.
1994, 72, 1181-1192.

8010 J . Org. Chem., Vol. 64, No. 21, 1999
Notes
Sch em e 2a
a
(a) TBAF, THF, rt, 24 h; (b) 4 N HCl/dioxane, 1 h, rt, (c) CDI, DMAP (12% mol), THF, rt, 24 h.
Sch em e 3a
come with this procedure, which nicely complements the
more recent reports27 on the preparation of this class of
compounds.
The methodology outlined herein based on the three-
carbon and two-carbon elongation of the carbon chain of
several new N-Boc-protected R-aminoacylsilanes via nu-
cleophilic addition to the carbonyl moiety constitutes a
convenient and reliable means for the stereoselective
synthesis of functionalized amino alcohol units frequently
found as key structural units in bioactive compounds.
Extension to other two-carbon elongation procedures calls
for further studies now in progress in our laboratory.
Exp er im en ta l Section
Gen er a l. Capillary mp are uncorrected. NMR spectra were
recorded as follows: 1H NMR (200 and 300 MHz; CDCl3, δ )
7.23 ppm) and 13C NMR (50.3 and 75.46 MHz, δ ) 77.0 ppm).
Mass spectra were recorded at an ionizing voltage of 70 eV.
Infrared spectra were taken in CCl4. Optical rotations were
determined as solutions in a 1-dm cell. Combustion analyses
were performed by the analysis service of the University of
Florence. Moisture sensitive reactions were carried out in oven-
dried (120 °C) glassware under an Ar atmosphere. Transfer of
anhydrous solvents or mixtures was accomplished with the
standard syringe/septum technique. THF was distilled im-
mediately prior to use from benzophenone ketyl under Ar. CH2-
Cl2 was passed through basic alumina and distilled from CaH2
just prior to use. Other solvents were purified by standard
procedures. Petroleum ether refers to the fraction bp 40-60 °C.
The reactions were monitored by TLC on silica gel plates.
Column chromatography was performed with 70-230 mesh
silica gel 60. Preparative TLC was carried out on glass plates
using a 1 mm layer. The ratios between the diastereoisomers of
the diastereomeric mixtures were determined from the 1H NMR
spectra of the crude products by integration of well-separated
signals. In the case of compounds whose NMR spectra indicate
the presence of a single diastereoisomer (8, 12-14, 17, 18) the
estimate of the de values derives from a measure of the signal-
to-noise ratio of the 1H NMR spectra of the crude products.
P r ep a r a tion of Im id a zolid es: Typ ica l P r oced u r e. To a
solution of N-(tert-butoxycarbonyl)-L-phenylalanine 1 (1.59 g, 6.0
mmol) in THF (6.0 mL) was added 1.07 g (6.6 mmol) of N,N′-
carbonyldiimidazole at room temperature. The reaction mixture
was stirred at the same temperature for 30 min, diluted with
Et2O, and quenched with water. The organic layer was washed
twice with distilled water, dried over MgSO4, filtered, and
concentrated in vacuo giving 1.84 g (97%) of (2S)-2-[N-(ter t-
a
Conditions: (a) BF3‚Et2O, CH2Cl2, -78 °C, 48 h for 5, 10 h
for 6; (b) TBAF, THF, rt, 24 h.
on the less hindered Si face23 of the starting acylsilanes
in which the BF3‚Et2O predominantly coordinates the
carbonyl oxygen.
The stereochemistry of 15a ,b and 17 was determined
after desilylation of the compounds with TBAF by
comparison of the spectroscopic data of 16a ,b and 18 with
the literature data.24 The syn:anti ratios in Scheme 3
appear slightly higher with respect to those obtained with
the same Lewis acid in the diastereoselective addition
of silyl ketene acetals to N-protected R-amino aldehydes,25
providing further support to the assumption that a
beneficial effect can be exerted by the R3Si moiety on the
diastereofacial selectivity. A set of important biologically
active statine analogues with natural configurations
(3S,4S) can be prepared by this four-step highly syn-
diastereoselective sequence. The difficulties due to low
diastereoselectivities with the presence of the incorrect
3R,4S and the severe reaction conditions26 can be over-
(23) Masamune, S.; Choy, W.; Petersen, J . S.; Sita, L. R. Angew.
Chem., Int. Ed. Engl. 1985, 24, 1-30.
(24) For phenylalanine: (a) Parkes, K.; Bushnell, D.; Crackett, P.;
Dunsdon, S. J . Org. Chem. 1994, 59, 3656-3664. (b) Holmes, D. S.;
Bethell, R. C.; Commack, N.; Clemens, I. R.; Kitchin, J .; McMeekin,
P.; Mo, C. L.; Orr, D. C.; Patel, B.; Paternoster, I. L.; Storer, R. J . Med.
Chem. 1993, 36, 3129-3136. (c) Nishi, T.; Morisawa, Y. Heterocycles
1989, 29, 1835-1842. For isoleucine: (d) Rinehart, L.; Sakai, R.;
Kishore, V.; Sullins, D. W., Li, K. J . Org. Chem. 1992, 57, 3007-3013.
(e) Hamada, Y.; Kondo, Y.; Shibata, M.; Shioiri, T. J . Am. Chem. Soc.
1989, 111, 669-673.
(26) (a) Harris, B. D.; Bhat, K. L.; J ouille`, M. M. Tetrahedron. Lett.
1987, 25, 2837-2840. (b) Maibaum, J .; Rich, D. H. J . Org. Chem. 1988,
53, 869-873. (c) Kessler, H.; Schudok, M. Synthesis 1990, 457-458.
(27) Hoffmann, R. V.; Tao, J . J . Org. Chem. 1997, 62, 2292-2297.
(25) Takemoto, Y.; Matsumoto T.; Ito, Y.; Terashima, S. Tetrahedron
Lett. 1990, 31, 217-218.

Notes
J . Org. Chem., Vol. 64, No. 21, 1999 8011
Bu toxyca r bon yl)a m in o]-1-im id a zol-1-yl-3-p h en ylp r op a n -
1-on e (3). White solid, mp 110 °C; [R]24D +33.1° (c 2.00, CHCl3);
IR: 3440, 1740, 1720 cm-1; MS (EI) m/z 248 (M+- C3H3N2), 192,
δ 0.45 (s, 6H), 1.00 (br s, 1H), 1.20 (s, 9H), 2.25-2.45 (m, 2H),
2.55 (dd, 1H, J ) 14.3, 6.5 Hz), 2.90 (d, 1H, J ) 12.3 Hz), 3.90
(td, 1H, J ) 11.0, 2.3 Hz), 4.10 (d, 1H, J ) 8.7 Hz), 5.00-5.20
(m, 2H), 5.85-6.10 (m, 1H), 6.90-7.05 (m, 2H), 7.10-7.15 (m,
3H), 7.30-7.45 (m, 3H), 7.60-7.70 (m, 2H); 13C NMR (50.3 MHz)
δ -3.2, -3.6, 28.1, 37.3, 41.4, 58.7, 72.5, 79.4, 118.5, 126.2, 128.0,
128.2, 128.9, 129.4, 133.4, 134.5, 137.5, 138.5, 156.77. Anal.
Calcd for C25H35NO3Si: C, 70.55; H, 8.30; N, 3.29. Found: C,
70.49; H, 8.26; N, 3.25.
1
164, 120; H NMR (200 MHz) δ 1.40 (s, 9H), 3.06 (dd, 1H, J )
13.9, 6.2 Hz), 5.15 (m, 1H), 5.33 (d, 1H, J ) 7.5 Hz), 7.06 (s,
1H), 7.10-7.35 (m, 5H), 7.45 (s, 1H), 8.15 (s, 1H); 13C NMR (50.3
MHz) δ 28.1, 38.9, 54.7, 80.3, 116.0, 127.5, 128.8, 129.1, 131.2,
134.7, 136.4, 169.1.
(2S,3S)-2-[N-(ter t-Bu toxyca r bon yl)a m in o]-1-im id a zol-1-
yl-3-m eth ylp en ta n -1-on e (4). Colorless oil (1.65 g, 98%), [R]24
a n ti-7b: [R]24 -23.9 (c 2.00, CHCl3); IR: 3430, 1730, 1250
D
D
+34.8° (c 3.59, CHCl3); IR 3460, 1745, 1725 cm-1; MS (EI) m/z
cm-1; MS (EI) m/z 425 (M+), 308, 135, 120, 91, 57; 1H NMR (200
MHz) δ 0.48 (s, 6H), 1.20 (br s, 1H), 1.41 (s, 9H), 2.35-2.40 (m,
2H), 2.60-2.70 (m, 1H), 2.95 (dd, 1H, J ) 14.0, 2.7 Hz), 3.80-
3.90 (m, 1H), 4.45 (d, 1H, J ) 9.3 Hz), 5.20-5.40 (m, 2H), 5.80-
6.20 (m, 1H), 7.00-7.10 (m, 2H), 7.15-7.25 (m, 3H), 7.30-7.40
(m, 3H), 7.60-7.72 (m, 2H); 13C NMR (50.3 MHz) δ -3.6, -3.8,
28.2 34.8, 41.0, 57.9 72.0, 79.4 118.2, 126.1 127.8, 128.2 129.1
134.0, 134.6 137.4, 138.6, 156.1. Anal. Calcd for C25H35NO3Si:
C, 70.55; H, 8.30; N, 3.29. Found: C, 70.51; H, 8.26; N, 3.27.
In d iu m -Med ia ted Allyla tion of 5. Allyl bromide (2.05
mmol, 0.177 mL) was added to a mixture of 5 (335 mg, 0.87
mmol) and indium powder (110 mg, 0.96 mmol) in 3 mL of THF
at room temperature. After stirring at the same temperature
under nitrogen atmosphere for 15 h, the reaction mixture was
poured into 5% aqueous Na2CO3. The organic layer was ex-
tracted with Et2O, dried over Na2SO4, and concentrated in vacuo.
Purification by column chromatography on silica gel afforded
355 mg (96%) of the two diastereoisomers, syn-7a and anti-7b,
in a 35:65 ratio. When the reaction was carried out in 3 mL of
THF:H2O 2:1 for 70 h, 270 mg (73%) of the two stereoisomers
were obtained in the same ratio.
1
214 (M+ - C3H3N2), 158, 130; H NMR (200 MHz) δ 0.85-1.05
(m, 6H), 1.10-2.00 (m, 12H), 4.82 (m, 1H), 5.38-5.42 (m, 1H),
7.13 (s, 1H), 7.55 (s, 1H), 8.30 (s, 1H); 13C NMR (50.3 MHz) δ
11.5, 16.2, 24.6, 28.6, 38.1, 58.5, 80.9, 116.8, 131.5, 137.0, 156.1,
170.4.
Syn t h esis of r-Am in oa cylsila n es: Typ ica l P r oced u r e.
Phenyl dimethylsilyllithium28 (0.85 M, 35.5 mL, 30.17 mmol)
was added to a suspension of CuCN (1.25 g, 15.07 mmol) in THF
(70 mL) at 0 °C. The reaction mixture was stirred for 20 min
under Ar atmosphere and then was slowly transferred by
cannula to a suspension of 3 (4.31 g, 13.7 mmol) in THF (90
mL) at -78 °C. Stirring was continued at this temperature for
further 30 min. Saturated aqueous NH4Cl was then added to
the solution, and the mixture was allowed to warm to room
temperature and extracted three times with Et2O (3 × 30 mL).
The organic extracts were dried over Na2SO4 and concentrated
in vacuo. The crude was purified by column chromatography on
silica gel (petroleum ether: Et2O ) 4:1), affording 2.62 g (50%)
of
(2S)-3-P h en yl-2-[N-(ter t-bu toxyca r bon yl)a m in o]p r o-
p a n oyld im eth ylp h en ylsila n e (5) as a light yellow oil. [R]24
D
+19.3 (c 2.00, CHCl3); IR: 3420, 1715, 1650, 1240 cm-1; MS (EI)-
Sn Cl4-Med ia ted Allyla tion of 5. A 100 mg (0.26 mmol)
amount of 5 was mixed with 0.12 mL (0.78 mmol) of allyltrim-
ethylsilane in 3 mL of CH2Cl2 at room temperature, and a 1 M
solution of SnCl4 in CH2Cl2 (0.52 mmol) was added to the
solution at -78 °C. The reaction mixture was quenched after
12 h at -78 °C with saturated aqueous NaHCO3 and extracted
three times with Et2O (3 × 10 mL), dried over Na2SO4, and
concentrated in vacuo. The crude was purified with preparative
silica gel plates affording 67 mg of the two diastereostereoiso-
mers, syn-7a and anti-7b, in a 65:35 ratio.
m/z 383 (M+), 298, 221, 164, 135, 91, 57; H NMR (200 MHz) δ
1
0.55 (s, 6H), 1.40 (s, 9H), 2.50 (dd, 1H, J ) 14.0, 7.4 Hz), 2.95
(dd, 1H, J ) 14.0, 5.8 Hz), 4.70 (bq, 1H, J ) 7.6 Hz), 4.95 (d,
1H, J ) 9.9 Hz), 6.80-6.95 (m, 2H), 7.20-7.80 (m, 8H); 13C NMR
(50.3 MHz) δ -4.6, -4.4, 28.2, 35.6, 64.2, 79.5, 126.5, 128.3,
128.3, 129.3, 130.1, 134.0, 134.1, 136.0, 154.8, 241.6. Anal. Calcd
for C22H29NO3Si: C, 68.90; H, 7.63; N, 3.65. Found: C, 68.82;
H, 7.58; N, 3.61.
(2S,3S)-3-Meth yl-2-[N-(ter t-bu toxyca r bon yl)a m in o]p en -
ta n oyld im eth ylp h en ylsila n e (6). The title compound was
prepared by the procedure as described for compound 5, using
4 (4.2 g, 15.0 mmol) and 16.5 mmol of phenyl dimethylsilyl-
lithium cyanocuprate. Column chromatography on silica gel
(petroleum ether: Et2O ) 6:1) gave 2.88 g (55%) of 6 as a pale
(2S,3S)-1-P h en yl-2-[N-(ter t-b u t oxyca r b on yl)a m in o]-5-
h exen -3-ol (9a ). To a stirred solution of R-hydroxysilane 7a (500
mg, 1.18 mmol) in dry THF (15 mL) was added a 1.0 M solution
of TBAF (1.30 mL, 1.30 mmol) in THF at room temperature.
The reaction mixture was stirred under Ar atmosphere at the
same temperature for 24 h, and saturated aqueous NH4Cl and
then Et2O (50 mL) were added to the solution. The organic layer
was washed three times with water and dried over MgSO4. After
evaporation of the solvent in vacuo, the crude was submitted to
1H NMR analysis which showed the presence of a single
diastereoisomer. The crude was then purified by column chro-
matography on silica gel (petroleum ether: Et2O ) 2:1), affording
247 mg (72%) of 9a as a white crystalline product. Mp ) 138-
yellow oil. [R]24 +62.6 (c 2.00, CHCl3); IR: 3440, 1730, 1650,
D
1240 cm-1; MS (EI) m/z 349 (M+), 232, 220, 186, 135, 86, 57; 1H
NMR (300 MHz) δ 0.48-0.87 (m, 12H), 1.45-1.85 (m, 12H), 4.50
(dd, 1H, J ) 8.9, 3.2 Hz), 5.05 (bd, 1H, J ) 8.3 Hz), 7.30-7.60
(m, 5H); 13C NMR (50.3 MHz) δ - 4.4, 11.3, 16.4, 23.0, 28.3,
34.8, 68.7, 79.3, 128.2, 130.0, 132.9, 133.9, 155.8, 243.0. Anal.
Calcd for C19H31NO3Si: C, 65.29; H, 8.95; N, 4.01. Found: C,
65.27; H, 8.93; N, 4.00.
140 °C; [R]24 -16.8 (c 1.00, CHCl3); IR: 3600, 3460 cm-1; MS
Sc(OTf)3-Ca ta lyzed Allyla tion of 5. To a stirred suspension
of scandium(III) triflate (172.0 mg, 0.35 mmol) and tetraallyltin
(0.61 mL, 716 mg, 2.53 mmol) in CH2Cl2 (20 mL) was added a
solution of 5 (1.94 g, 5.07 mmol) in CH2Cl2 (40 mL) at room
temperature. After 24 h, saturated aqueous NH4Cl was added
to the solution, and the mixture was extracted three times with
Et2O. The organic extracts were dried over Na2SO4 and concen-
trated in vacuo. The 1H NMR spectrum of the crude, showed
the presence of both syn -(2S,3R)-2-[N-(ter t-bu toxyca r bon yl)-
a m in o]-3-d im eth ylp h en ylsilyl-1-p h en yl-5-h exen -3-ol (7a )
and a n ti-(2S,3S)-2-[N-(ter t-bu toxyca r bon yl)a m in o]-3-[d im -
eth yl(p h en yl)silyl]-1-p h en yl-5-h exen -3-ol (7b) isomers in a
20:80 ratio. The two isomers were separated by column chro-
matography on silica gel (CH2Cl2 as eluant) giving 1.03 g (48%)
of 7b as the less retained compound and 0.28 g (13%) of 7a as
the more retained compound, as pale yellow oils.
D
(EI) m/z 291 (M+), 200, 100, 57; H NMR (200 MHz) δ 1.31 (s,
1
9H), 2.15-2.40 (m, 2H), 2.50 (bs, 1H), 2.70-2.80 (m, 1H), 2.91
(dd, 1H, J ) 14.1, 4.2 Hz), 3.60-3.71 (m, 1H), 3.73-3.85 (m,
1H), 4.62 (d, 1H, J ) 8.2 Hz), 5.10-5.20 (m, 2H), 5.75-5.90 (m,
1H), 7.10-7.30 (m, 5H); 13C NMR (75.46 MHz) δ 28.2, 35.3, 38.4
55.8, 72.7 79.5, 118.2 126.3 128.3, 129.3, 134.7 138.1, 156.0. Anal.
Calcd for C17H25NO3: C, 70.06; H, 8.65; N, 4.81. Found: C, 70.01;
H, 8.61; N, 4.79. MTPA ester of alcohol 9a : (R)-(-)-R-methoxy-
R-(trifluoromethyl)phenylacetyl chloride (50 mg, 0.19 mmol) was
added to a solution of 9a (20 mg, 0.069 mmol) in CH2Cl2 (3 mL)
and DIMAP (18 mg, 0.14 mmol). The solution was stirred at
room temperature for 36 h, diluted with 2 mL of CH2Cl2, and
washed with saturated aqueous NH4Cl. The water phase was
extracted three times with Et2O (3 × 10 mL) and dried over
MgSO4. Purification with preparative silica gel plates of the
crude (CH2Cl2:petroleum ether ) 1:1) afforded 32 mg (97%) of
(R)-MPTA ester of 9a as a pale yellow oil. 1H NMR (300 MHz)
δ: 1.30 (s, 9H), 2.18 (dd, J ) 14.3, 10.4 Hz, 1H), 2.33-2.54 (m,
2H), 2.77 (dd, 1H, J ) 14.3, 4.1 Hz), 3.58 (s, 3H), 3.90-4.12 (m,
2H), 5.05-5.18 (m, 2H), 5.35-5.45 (m, 1H), 5.68-5.85 (m, 1H),
6.90-7.00 (m, 2H), 7.10-7.30 (m, 3H), 7.35-7.48 (m, 3H), 7.52-
7.62 (m, 2H).
syn -7a : [R]24 -11.1 (c 2.00, CHCl3); IR: 3420, 1740 cm-1
;
D
MS (EI) m/z 425 (M+), 308, 135, 120, 91, 57; 1H NMR (200 MHz)
(28) (a) Fleming, I.; Newton, T. W.; Roessler, F. J . Chem. Soc., Perkin
Trans. 1 1981, 2527. (b) Harwood: L. M.; Moodie, C. J . Organocopper
Reagents; Taylor, J . K., Ed.; Oxford University Press: New York, 1994;
pp 260-261.

8012 J . Org. Chem., Vol. 64, No. 21, 1999
Notes
(2S,3S)-2-Am in o-1-p h en yl-5-h exen -3-ol (10a ). A solution
of 9a (110 mg, 0.38 mmol) in 4 N HCl/dioxane (2/1) solution (12
mL) was stirred under Ar atmosphere for 1 h at room temper-
ature and concentrated in vacuo. The solution was adjusted to
pH ) 9 with NH4OH, and extracted three times with EtOAc.
The organic extracts were dried over Na2SO4, filtered and
concentrated in vacuo giving 62 mg (85%) of pure 10a as a thick
oil. [R]24D +31.2 (c 1.00, MeOH); MS (EI) m/z 191 (M+), 176, 150,
120, 91; 1H NMR (200 MHz) δ 1.55-2.20 (bs, 3H), 2.25-2.55
(m, 3H), 2.85-3.20 (m, 2H), 3.50-3.70 (bs, 1H), 5.05-5.25 (m,
2H), 5.80-6.00 (m, 1H), 7.10-7.35 (m, 5H); 13C NMR (75.46
MHz) δ 37.2, 38.2, 56.2, 73.1, 117.7, 126.4, 128.5, 129.2, 135.1,
139.2.
(4S,5S)-4-Ben zyl-5-(1-pr open yl)-1,3-oxazolidin -2-on e (11a).
To 60 mg (0.32 mmol) of 10a in THF (1.6 mL) were added
carbonyldiimidazole (73 mg, 0.45 mmol) and a catalytic amount
of DMAP (5.0 mg, 0.04 mmol, 12% mol) at room temperature.
After being stirred at the same temperature for 24 h, the reaction
mixture was diluted with saturated aqueous NH4Cl. The aque-
ous phase was extracted with EtOAc, and the organic extracts
were washed with brine, dried over Na2SO4 and concentrated
in vacuo. Purification with preparative silica gel plates (petro-
leum ether:EtOAc ) 2:1) afforded 65 mg (93%) of 11a as a pale
yellow oil. IR: 3480, 1750 cm-1; MS (EI) m/z 217 (M+), 175, 126,
91; 1H NMR (200 MHz) δ 2.35-2.70 (m, 3H), 2.80-3.00 (m, 1H),
3.90-4.05 (m, 1H), 4.60-4.75 (m, 1H), 5.15-5.25 (m, 2H), 5.65
(bs, 1H), 5.70-5.90 (m, 1H), 7.00-7.35 (m, 5H); 13C NMR (75.46
MHz) δ 33.6, 36.2, 56.6, 78.8, 118.6, 127.2, 128.9, 129.1, 132.4,
136.5, 158.3.
0.336 mmol) in CH2Cl2 (64 mL) under the same conditions used
in the reaction of 5. H NMR spectrum of the crude showed the
1
presence of a single diastereoisomer which was purified by
column chromatography on silica gel (petroleum ether:Et2O )
6:1) to give 1.13 g (60%) of pure (4R,5S,6S)-5-[N-(ter t-bu toxy-
ca r b on yl)a m in o]-4-[d im e t h yl(p h e n yl)silyl]-6-m e t h yl-1-
octen -4-ol (8) as a pale yellow oil. [R]24 -7.00 (c 2.15, CHCl3);
D
IR: 3600, 3460, 1700, 1240 cm-1; MS (EI) m/z 391 (M+), 274,
245, 186, 135, 86, 57; 1H NMR (300 MHz) δ 0.381 (s, 3H), 0.406
(s, 3H), 0.55 (t, 3H, J ) 7.0 Hz), 0.75-0.90 (m, 5H), 1.39 (s, 9H),
1.60-1.90 (m, 2H), 2.24 (dd, 1H, J ) 13.9, 8.2 Hz), 2.42 (dd, 1H,
J ) 13.9, 7.2 Hz), 3.66 (dd, 1H, J ) 10.2, 2.1 Hz), 4.68 (d, 1H, J
) 10.2 Hz), 4.90-5.10 (m, 2H), 5.70-5.90 (m, 1H), 7.25-7.40
(m, 3H), 7.55-7.65 (m, 2H); 13C NMR (75.46 MHz) δ -3.5, -3.4,
11.3, 18.2, 23.5, 28.3, 37.9, 42.6, 59.4, 73.6, 78.8, 118.9, 127.7,
129.1, 133.5, 134.6, 137.5, 154.6. Anal. Calcd for C22H37NO3Si:
C, 67.48; H, 9.53; N, 3.58. Found: C, 67.45; H, 9.50; N, 3.56.
In d iu m -Med ia ted Allyla tion of 6. The reaction was per-
formed as described for 5, starting from 6 (349 mg, 1.0 mmol),
allyl bromide (0.20 mL, 2.34 mmol), and In (126 mg, 1.1 mmol)
in 3 mL of THF. Column chromatography on silica gel gave 371
mg of 8 (95%). When the same reaction was carried out in THF/
H2O (2:1) as a solvent, a 53% yield was obtained in 12 h.
(4S,5S,6S)-6-Meth yl-5-[N-(ter t-bu toxyca r bon yl)a m in o]-
1-octen -4-ol (12). This compound was prepared with the same
procedure used for 9a starting from 8 (1.12 g, 2.86 mmol) in
THF (48 mL) and 3.18 mL (3.18 mmol) of a 1.0 M solution of
1
TBAF in THF. H and 13C NMR spectrum of the crude showed
the presence of a single diastereoisomer. Subsequent purification
by column chromatography on silica gel (petroleum ether:Et2O
) 3:1) gave 680 mg (92%) of pure 12 as a white solid. Mp )
(2S,3R)-1-P h en yl-2-[N-(ter t-b u t oxyca r b on yl)a m in o]-5-
h exen -3-ol (9b). The title compound was obtained as previously
described for 9a , starting from 7b (250 mg, 0.59 mmol) in THF
(8 mL) with TBAF (0.65 mL, 0.65 mmol). Column chromatog-
raphy on silica gel (petroleum ether:Et2O ) 4:1) gave 118 mg
117-119 °C; [R]24 +34.2 (c 1.40, MeOH); IR: 3600, 3470, 1760
D
cm-1; MS (EI) m/z 257 (M+), 200, 186, 130, 86, 57; 1H NMR (300
MHz) δ 0.75-0.90 (m, 6H), 0.95-1.20 (m, 2H), 1.40 (s, 9H),
1.41-1.60 (m, 1H), 2.00 (bs, 1H), 2.10-2.38 (m, 2H), 3.10-3.25
(m, 1H), 3.70-3.83 (m, 1H), 4.80 (d, 1H, J ) 9.9 Hz), 5.05-5.20
(m, 2H), 5.70-5.90 (m, 1H); 13C NMR (75.46 MHz) δ 11.3, 15.8,
25.5, 28.3, 36.6, 39.7, 57.9, 69.6, 78.9, 118.4, 134.7, 156.4. Anal.
Calcd for C14H27NO3: C, 65.32; H, 10.58; N, 5.44. Found: C,
65.2; H, 10.55; N, 5.41.
(69%) of 9b as an oil. [R]24 -22.3 (c 1.00, CHCl3); IR: 3600,
D
3470 cm-1; MS (EI) m/z 291 (M+), 200, 100, 57; 1H NMR (200
MHz) δ 1.35 (s, 9H), 2.15-2.55 (m, 3H), 2.75-2.90 (m, 2H), 3.53
(td, 1H, J ) 6.9, 1.9 Hz), 3.70 (bq, 1H, J ) 8.3 Hz), 4.90 (d, 1H,
J ) 8.8 Hz), 5.03-5.10 (m, 2H), 5.60-5.80 (m, 1H), 7.10-7.30
(m, 5H); 13C NMR (75.46 MHz) δ 28.3, 38.8, 39.3, 55.2, 70.1,
79.3, 118.4, 126.3, 128.4, 129.32, 134.4, 138.4, 156.0. Anal. Calcd
for C17H25NO3: C, 70.06; H, 8.65; N, 4.81. Found: C, 70.04; H,
8.63; N, 4.80. MTPA ester of alcohol 9b: prepared as described
for compound 9a , starting from 9b (26 mg, 0.089 mmol), (R)-
(-)-R-methoxy-R-(trifluoromethyl)phenylacetyl chloride (50 mg,
0.19 mmol) and DIMAP (21 mg, 0.17 mmol) in CH2Cl2 (3 mL).
Purification with preparative silica gel plates of the crude (CH2-
Cl2:petroleum ether ) 1:1) afforded 40 mg (94%) of (R)-MPTA
ester of 9b as a pale yellow oil. 1H NMR (300 MHz) δ 1.30 (s,
9H), 2.30 (dd, J ) 14.0, 9.1 Hz, 1H), 2.30-2.60 (m, 2H), 2.90
(dd, 1H, J ) 14.0, 4.9 Hz), 3.60 (s, 3H), 3.85-4.18 (m, 2H), 5.00-
5.20 (m, 2H), 5.22-5.35 (m, 1H), 5.60-5.82 (m, 1H), 6.80-6.90
(m, 2H), 7.10-7.50 (m, 6H), 7.50-7.70 (m, 2H).
(4S,5S,6S)-5-Am in o-6-m eth yl-1-octen -4-ol (13). The title
compound was prepared as for 10a , using 12 (108 mg, 0.42
mmol), in 4 N HCl/dioxane (2/1) solution (15 mL). After the usual
workup, 53 mg (80%) of 13 was obtained as a pale yellow oil.
[R]24 +6.5 (c 1.00, MeOH), MS (EI) m/z 157 (M+), 116, 100, 86;
D
1H NMR (200 MHz) δ 0.75-1.00 (m, 8H), 1.20 (s, 1H), 1.30-1.50
(m, 3H), 1.85-2.50 (m, 3H), 3.45-3.55 (m, 1H), 4.95-5.15 (m, 2H),
5.75-5.95 (m, 1H); 13C NMR (75.46 MHz) δ 11.4, 14.0, 24.7, 29.7,
39.7, 60.8, 78.8, 119.5, 131.5.
(4S,5S)-5-(1-P r op en yl)-4-[2(S)]-m eth ylp r op yl]-1,3-oxa zo-
lid in -2-on e (14). The title compound was synthesized according
to the procedure reported for 11a , starting from 13 (30 mg, 0.19
mmol), CDI (42 mg, 0.26 mmol), and DMAP (3.0 mg, 0.025
mmol). Purification with preparative silica gel plates (petroleum
ether:AcOEt ) 4:1) gave 22 mg (63%) of 14 as a pale yellow oil.
MS (EI) m/z 183 (M+), 142, 126, 57; 1H NMR (200 MHz) δ 0.70-
0.90 (m, 6H), 1.00-1.50 (m, 3H), 2.30-2.40 (m, 2H), 3.30 (t, 1H,
J ) 4.8 Hz), 4.20-4.35 (m, 1H), 5.00-5.20 (m, 2H), 5.60-5.90
(m, 2H); 13C NMR (75.46 MHz) δ 11.1, 14.0, 24.7, 38.9, 39.7,
60.9, 78.8, 119.5, 131.5, 156.8.
(2S,3R)-2-Am in o-1-p h en yl-5-h exen -3-ol (10b). The title
compound was prepared as described for 10a , using 9b (100 mg,
0.34 mmol) in 4 N HCl/dioxane (2/1) solution (15 mL). After the
standard workup, 59 mg (90%) of 10b were obtained as a thick
oil. [R]24D -20.3 (c 1.00, MeOH); MS (EI) m/z 191 (M+), 176, 150,
120, 100, 91, 77; 1H NMR (200 MHz) δ 1.70-2.20 (bs, 3H), 2.40
(d, 2H, J ) 6.2 Hz), 2.56 (dd, 1H, J ) 9.4, 4.2 Hz), 2.80-3.05
(bs, 2H), 3.45 (bs, 1H), 5.05-5.20 (m, 2H), 5.75-5.95 (m, 1H),
7.10-7.35 (m, 5H); 13C NMR (75.46 MHz) δ 39.1, 41.1, 56.0, 72.4,
117.5, 126.4, 128.6, 129.2, 134.8, 138.6.
Eth yl (3R,4S)-4-[N-(ter t-Bu toxyca r bon yl)a m in o]-3-[d im -
eth yl(p h en yl)silyl]-3-h yd r oxy-5-p h en ylp en ta n oa te (15). To
a solution of 5 (1.32 g, 3.45 mmol) and tert-butyl(dimethyl)silyl
1-ethoxyvinyl ether (836 mg, 4.14 mmol) in CH2Cl2 (7.0 mL) was
added dropwise BF3‚Et2O (0.49 mL, 3.85 mmol) at -78 °C under
Ar atmosphere. After being stirred for 48 h at the same
temperature, the reaction mixture was diluted with CH2Cl2, and
the organic layer was washed with aqueous NaHCO3 and water,
dried over Na2SO4, and concentrated in vacuo. 1H NMR spec-
trum of the crude showed the presence of two diastereoisomers
15a ,b in a 95:5 ratio. This ratio was maintained after purifica-
tion by column chromatography on silica gel (petroleum ether:
Et2O ) 5:1) which gave 991 mg (61%) of 15a and 15b. 15a : MS
(EI) m/z 471 (M+), 398, 370, 354, 276, 164, 135, 120, 91; 1H NMR
(200 MHz) δ 0.40 (s, 3H), 0.50 (s, 3H), 1.10-1.30 (m, 12H), 2.50-
2.65 (m, 3H), 2.96 (dd, 1H, J ) 13.7, 3.1 Hz), 3.90-4.10 (m, 3H),
(4S,5R)-4-Ben zyl-5(1-pr open yl)-1,3-oxazolidin -2-on e (11b).
The title compound was prepared as described for 11a , using
10b (54 mg, 0.28 mmol), CDI (66 mg, 0.41 mmol), DMAP (4 mg,
0.03 mmol, 12%), and THF (1.5 mL). Purification with silica gel
plates (petroleum ether:EtOAc ) 2:1) gave 58 mg (95%) of 11b
as a pale yellow oil. IR: 3480, 1750 cm-1; MS (EI) m/z 217 (M+),
1
175, 126, 91; H NMR (300 MHz) δ 2.20-2.40 (m, 2H), 2.80 (d,
2H, J ) 7.4 Hz), 3.70 (q, 1H, J ) 6.0 Hz), 4.32 (q, 1H, J ) 5.1
Hz), 5.05-5.20 (m, 2H), 5.60-5.95 (m + bs, 2H), 7.05-7.35 (m,
5H); 13C NMR (75.46 MHz) δ 38.5, 41.6, 58.1, 80.8, 119.4, 121.9,
127.2, 128.9, 129.0, 131.2, 158.6.
Sc(OTf)3-Ca ta lyzed Allyla tion of 6. The reaction was
performed starting from 6 (1.69 g, 4.8 mmol) in CH2Cl2 (40 mL),
tetraallyltin (0.58 mL, 679 mg, 2.4 mmol), and Sc(OTf)3 (165 mg,
4.45 (bd, 1H, J ) 11.1 Hz), 4.73 (s, 1H), 6.90-7.70 (m, 10H); 13
C

Notes
J . Org. Chem., Vol. 64, No. 21, 1999 8013
NMR (75.46 MHz) δ -4.4, -3.7, 13.94, 28.1, 37.9, 38.8, 58.2,
60.8, 70.3, 78.9, 126.1, 127.9, 128.1, 129.2, 129.5, 134.6, 136.4,
138.6, 155.4, 174.5.
3580, 3420; 1250 cm-1; MS (EI) m/z 437 (M+), 320, 291, 251,
157, 57; H NMR (300 MHz) δ 0.36 (s, 3H), 0.40 (s, 3H), 0.50-
1
0.85 (m, 6H), 1.15 (t, 3H, J ) 6.7 Hz), 1.40-1.80 (m, 12H), 2.45
(s, 2H), 3.45 (d, 1H, J ) 11.2 Hz), 3.92 (q, 2H, J ) 6.7 Hz), 4.60
(bs, 1H), 4.83 (d, 1H, J ) 11.2 Hz), 7.30-7.65 (m, 5H); 13C NMR
(75.46 MHz) δ -4.0, -4.1, 11.3, 13.9, 18.1, 23.3, 28.3, 38.1, 38.4,
60.7, 60.8, 72.6, 78.9, 127.7, 129.3, 134.5, 136.8, 156.4, 175.3.
Anal. Calcd for C23H39NO5Si: C, 68.10; H, 9.70; N, 3.46. Found:
C, 68.01; H, 9.65; N, 3.38.
A mixture of 15a and 15b was reacted with TBAF (2.3 mL,
2.3 mmol, 1.1 equiv) in THF (30 mL) for 24 h affording two
stereoisomers in a 95:5 ratio. Purification by column chroma-
tography on silica gel (petroleum ether:Et2O ) 6:1) gave 423
mg (60%) of eth yl (3S,4S)-4-[N-(ter t-bu toxycar bon yl)am in o]-
3-h yd r oxy-5-p h en ylp en ta n oa te (16a ) and 22 mg (3%) of
eth yl (3R,4S)-4-[N-(ter t-bu toxycar bon yl)am in o]-3-h ydr oxy-
5 p h en ylp en ta n oa te (16b), whose spectral data were consis-
tent with those reported in the literature.24a-c
Eth yl (3S,4S,5S)-4-[N-(ter t-Bu toxyca r bon yl)a m in o]-3-h y-
d r oxy-5-m eth ylh ep ta n oa te (18). The title compound was
prepared as described for 16, using 17 (190 mg, 0.43 mmol) and
TBAF (0.47 mL, 0.47 mmol) in THF (8 mL). Purification with
preparative silica gel plates gave 85 mg (65%) of 18, whose
spectral data well matched24d,e with those reported in the
literature. (18): [R]24D +26.7 (c 0.5, MeOH); 1H NMR (300 MHz)
δ: 0.87 (t, J ) 7.0 Hz, 3H), 0.93 (d, J ) 6.0 Hz, 3H), 1.28 (t, J
) 7.0 Hz, 3H), 1.43 (s, 9H), 0.70-1.90 (m, 3H), 2.50-2.58 (m,
2H), 2.70 (brs, 1H), 3.25-3.35 (m, 1H), 4.21 (q, J ) 7.0 Hz, 2H),
3.90-4.42 (m, 1H), 4.81 (d, J ) 9.3 Hz, 1H).
(16a ): [R]20D -36.3 (c 1.0, MeOH); 1H NMR (200 MHz) δ: 1.24
(t, J ) 7.0 Hz, 3H), 1.41 (s, 9H), 2.37 (dd, J ) 16.8, 2.6 Hz, 1H),
2.59 (dd, J ) 16.8, 9.9 Hz, 1H), 2.91 (d, J ) 7.7 Hz, 2H), 3.46
(bd, J ) 2.6 Hz,1H), 3.70-3.75 (m, 1H), 3.91-3.98 (m, 1H), 4.13
(q, J ) 7.0 Hz, 2H), 4.90-4.95 (m, 1H), 7-10-7.35 (m, 5H).
(16b): [R]20 -14.4 (c 1.0 MeOH); 1H NMR (200 MHz) δ: δ:
1.29 (t, J ) 7.0 Hz, 3H), 1.34 (s, 9H), 2.41-2.64 (m, 2H), 2.80-
3.00 (m, 2H), 3.59 (bs, 1H), 3.86 (bs, 1H), 3.99 (m, 1H), 4.19 (q,
J ) 7.0 Hz, 2H), 4.50-4.60 (m, 1H), 7-15-7.45 (m, 5H).
E t h yl (3R,4S,5S)-4-[N-(ter t-Bu t oxyca r b on yl)a m in o]-3-
[dim eth yl(ph en yl)silyl]-3-h ydr oxy-5-m eth ylh eptan oate (17).
The title compound was prepared as described for 15, starting
from 6 (385 mg, 1.1 mmol), O-ethyl-O-tert-butyldimethylsilyl
ketene acetal (244 mg, 1.2 mmol) in CH2Cl2 (2.0 mL), and BF3‚
Et2O (0.155 mL, 1.23 mmol). Column chromatography on silica
gel of the crude (petroleum ether:Et2O ) 15:1) afforded 322 mg
(67%) of 17 as a pale yellow oil. [R]24D -6.76 (c 0.94, CHCl3); IR:
Ack n ow led gm en t. This work has been supported
by University of Bologna (Funds for Selected Research
Topics, A.A. 1995-97) and by the National Project
Stereoselezione in Sintesi Organica, Metodologie ed
Applicazioni.
J O982501X