Vinylsulfones versus alkylsulfones in the addition to chiral imines. Synthesis of N-(tert-butoxycarbonyl)-L-homophenylalanine

Article abstract of DOI:10.1016/j.tet.2005.09.046

A study of the addition of vinylsulfones versus alkylsufones has been done, and applied to the synthesis of N-(tert-butoxycarbonyl)-L-homophenylalanine.

Full text of DOI:10.1016/j.tet.2005.09.046

Tetrahedron 61 (2005) 11641–11648
Vinylsulfones versus alkylsulfones in the addition to chiral imines.
Synthesis of N-(tert-butoxycarbonyl)-L-homophenylalanine
a,
David Dıez, Pilar Garcıa, Isidro S. Marcos, Pilar Basabe, Narciso M. Garrido,
a
a
a
a
*
´
´
H. B. Broughtonb and Julio G. Uronesa
a
´ ´ ´
Departamento de Quımica Organica, Universidad de Salamanca, Plaza de los Caıdos 1-5, 37008 Salamanca, Spain
bLilly, S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid
Received 4 August 2005; revised 12 September 2005; accepted 15 September 2005
Available online 6 October 2005
Abstract—A study of the addition of vinylsulfones versus alkylsufones has been done, and applied to the synthesis of N-(tert-
butoxycarbonyl)-L-homophenylalanine.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
inhibitors, for example, Cilazapril3 and Enalapril4 among
others (Fig. 2). To the best of our knowledge there is no
report of a synthesis applying this approach to L-homo-
phenylalanine, although this molecule has been synthesized
several times in both enantiomeric forms.5 Initially, we
decided to study the addition of sulfone 2 to the chiral imine
1 (Scheme 1).
The addition of organometallics to imines derived from (R)-
2,3-diprotected-D-glyceraldehyde, has been the subject of
numerous papers, in particular related to the synthesis of
natural and unnatural aminoacids.1 Recently we have
published the addition of a cyclopropylvinylsulfone to the
benzylimine of (R)-2,3-O-isopropylidene-D-glyceraldehyde
1, for the synthesis of unnatural aminoacids.2 (Fig. 1).
Figure 2. Some ACE inhibitors containing the L-HPA moiety.
2. Results and discussion
Figure 1. Addition of cyclopropylvinylsulfone to imine 1, and transform-
ation into an unnatural protected aminoacid.
When sulfone 2 was treated with n-BuLi in THF and made
to react with imine 1, several compounds 3 (45%) 4–6
(21%) and 7 (30%) were obtained, which were isolated by
column chromatography. Compound 3 was hydrogenated in
presence of Boc2O, giving a 48% yield of derivative 8,
In order to extend this approach to other systems we decided
to study the addition of phenylsulfones to the chiral imine 1.
In this manner the synthesis of one of the more interesting
unnatural aminoacids, L-homophenylalanine, could be
achieved. This amino acid is found in several pharmaceu-
ticals such as the angiotensin converting enzyme (ACE)
which was then transformed into D-homophenylalanine
`
6
using Pericas methodology. Thus, deprotection of the
acetonide and oxidation with RuCl3 and sodium periodate
led to N-Boc-D-homophenylalanine7 10 in 59% yield from
8, hence establishing the stereochemistry for 8.
Keywords: Alkyl and vinyl sulfones; Aminoacids; Chiral imines; Hydride
transfer.
*
Corresponding author. Tel.: C34 923294474; fax: C34 923294574;
e-mail: ddm@usal.es
The other three compounds 4, 5 and 6 were debenzylated
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.046

´
D. Dıez et al. / Tetrahedron 61 (2005) 11641–11648
11642
Scheme 1. Reagents: (a) n-BuLi, THF, K78/0 8C, 5 h (3:45%, 4–6:21%, 7:30%); (b) H2, Boc2O, Pd(OH)2, EtOAc, rt, 24 h; (c) CF3COOH, MeOH/H2O 3:1,
rt, 7 h; (d) RuCl3–H2O, NaIO4, MeCN/CCl4/H2O 2:2:3, rt, 1 h; (e) Na–Hg, MeOH, 1–2 h.
under the same conditions as 3, and N-Boc derivatives 11,
12, and 13 were obtained in 69% yield in a 1:2:1 ratio. In
order to establish the stereochemistry of these compounds,
they were desulfonylated with sodium amalgam. Derivative
11 gave a 3:7 mixture of the olefin 14, via a Julia type
reaction,8 and the N-Boc compound 8, in nearly quantitative
yield. Compounds 12 and 13, when similarly treated,
separately gave the same desulfonylated compound 15 in
quantitative yield, along with 14. This compound 15 has
already been described and the spectroscopic properties and
rotation were coincident with those taken from the
literature.9 The stereochemistry of the sulfone carbon C-2
was tentatively determined for 11, 12 and 13 by extensive
NOE and comparative NMR studies. We felt sufficiently
confident of this assignment for the purposes of this study,
particularly since this stereocentre was in any event going to
be removed.
In order to further study the stereoselectivity of the sulfone
addition, we decided to examine the behaviour of the more
rigid phenylstyrylsulfone 16 in a similar manner, in the
expectation that we might find changes in the stereo-
selectivity that would help determine the causes of that
selectivity. The reaction of the anion of 16 (generated by
treatment with n-BuLi in THF) with imine 1 gave
compounds 17, 18, 19 and 20 in an excellent 93% yield
and with complete stereoselectivity, as will be demonstrated
below (Scheme 2).
The stereoselectivity obtained has been explained for
analogous systems in terms of a-chelate controlled
addition1b,12 but, while the Cram, Cram-chelate, and
Felkin-Anh models have all been applied to the addition
of nucleophiles to imines,1c the substrate 1 provides a
particularly complex case. As mentioned above, the
stereochemical outcome of additions to 1 is known to
depend upon the nucleophile used, with a complete reversal
of the (nearly complete) stereoselectivity on changing, for
example, from PhMgBr to PhCH2MgCl11—this has been
postulated to be due to changes in the preferred chelate
formed (with the a or b oxygen of the acetonide unit). In any
event, this means that the classical models provide no
guidance in this context as to possible outcomes prior to
Thus, in this case, the addition of an anion stabilised by an
alkyl sulfone to the imine proceeded with moderate
stereoselectivity (3:1 ratio), following a course similar to
´
that found by Dıaz-de-Villegas and Galvez et al for the
addition of benzylmagnesium chloride to imine 1,10 and in
contrast to the addition of other organometalics to the same
imine observed by these authors.11

´
D. Dıez et al. / Tetrahedron 61 (2005) 11641–11648
11643
synthesis, since there is no a priori way to decide, which of
the chelated forms will predominate for a particular
nucleophile. Therefore, we undertook a molecular modeling
study to determine what might be controlling the
stereoselective addition of our anions to imine 1. Our
objective in undertaking such a study was to provide an
approximate model that could be generated in a practical
amount of time, rather than to do a full investigation of the
many chelated and/or solvated forms of every possible
conformation of each possible intermediate or transition
state. While the result is necessarily approximate, this is a
characteristic of many useful models, such as are indeed the
Cram or Felkin–Anh models; our hope was to find a model
that was consistent with the observed results, and which
might serve as a guide to predict the outcome of related
reactions, with a minimal increase in complexity over the
classical Cram chelate model.
Given the dependence of the stereochemical outcome of
these additions on the nucleophile, we considered the
possibility that the addition might proceed through a late
transition state, or that the addition might be reversible;
under either of these circumstances, the relative stability of
the possible diastereoisomeric products might serve as a
model to explain the stereoselectivity of the reaction.
Therefore, the addition product of 16 to 1, with a hydrogen
atom on the amine nitrogen, was sketched in Maestro
(v. 7.0.113)13 and subjected to Monte Carlo multiple
minimum/low mode conformational search with Macro-
model (v. 9.0.016)13 using up to 5000 iterations of TNCG
minimization of each conformer with the MMFFs force-
field, with all other parameters selected using the automatic
setup options within Maestro. The result of a conformational
search with 1000 attempts to find new conformers suggested
that the more stable product should be the S,S stereoisomer
Figure 3. Top panel: lowest-energy conformation of the S,S addition
product of 1 and 16. Bottom panel: lowest-energy conformation of the S,R
addition product.
(MMFF94s energy 429.88 kJ/mol versus S,R isomer
434.64 kJ/mol; the S stereocentre is that in the dioxolane
ring, the other is the new stereocentre, with nitrogen, created
by the reaction). This difference is in the right direction and
probably would be sufficient to explain the modest
stereoselectivity of the related reaction of 1 with the anion
of 2, and hence this simple model may serve as a rough
guide to the stereochemical outcome of these reactions.
However, given the small energetic difference, it seems that
Scheme 2. Reagents: (a) n-BuLi, THF, K78/0 8C, 7 h (17 and 20:42%, 18:33%, 19:18%); (b) Silica gel (quantitative); (c) Boc2O, THF, rt, overnight;
(d) Na–Hg, MeOH, 1–2 h.

´
D. Dıez et al. / Tetrahedron 61 (2005) 11641–11648
11644
the hypothesis that the stability of the intermediates (or
nearby transition states) corresponding to the structures in
Figure 3 might only be a partial explanation for the total
stereoselectivity observed for the reaction of 1 with the
anion of 16, even allowing for the approximations—such as
the use of the amine rather than the lithium amide-used.
VG-TS 250 spectrometer at 70 eV ionising voltage. Mass
spectra are presented as m/z (% rel int.). HRMS were
recorded on a VG Platform (Fisons) spectrometer using
chemical ionization (ammonia as gas) or Fast Atom
Bombardment (FAB) technique. For some of the samples,
QSTAR XL spectrometer was employed for electrospray
ionization (ESI). Optical rotations were determined on a
Perkin-Elmer 241 polarimeter in 1 dm cells. Diethyl ether
and THF were distilled from sodium, and dichloromethane
was distilled from calcium hydride under Argon
atmosphere.
Compounds 17 and 20 are the result of addition to the imine
followed by hydride transfer to the resulting vinylsulfone.
This hydride transfer has been observed previously by us
with the cyclopropylvinylsulfone of Figure 1.2 Hydride
transfer may further enhance the stereoselectivity of the
reaction in the vinylsulfone case, as the conformation shown
in the top panel of Figure 3 (S,S stereochemistry) is also
ideally set up for the this process to take place via a chair
like transition state, and rapid, irreversible hydride transfer
(rapid transfer is supported by the absence of any of the
immediate product of addition in the product mixture)
would hence result in a trapping of this intermediate and
greater stereoselectivity.
Imine 1 was prepared from (R)-2,3-O-isopropylidene-D-
glyceraldehyde and benzylamine in the presence of
anhydrous magnesium sulphate according to the literature
procedure.14
Numbering of compounds in the experimental part
corresponds with Schemes in the discussion and not with
the name, for spectral interpretation and comparison
purposes.
Amines 18 and 19 are the result of the hydrolysis of
derivatives 17 and 20, respectively (Scheme 2). Compound
19 has the same stereochemistry at C-3 as 18 but the
opposite at C-2. The stereochemistry of these four
compounds was established as follows. Imine 17 was
hydrolyzed on silica gel to give compound 18 quantitat-
ively. Compounds 18 and 19 were transformed separately
into their N-Boc-protected derivatives 21 and 11. The
stereochemistry of 11 has been determined previously.
When compound 21 was submitted to desulfonylation,
compounds 8 and 14 were obtained in a similar ratio as was
the case with 11, so the stereochemistry of compound 21,
and hence of 18, is the same at C-3 and different at C-2.
4.1.1. Reaction of 2 with imine 1. n-BuLi 1.6 M (0.80 mL,
1.29 mmol) was added to a solution of 2 (264 mg,
1.07 mmol) in THF (5 mL) at K78 8C under Ar atmosphere.
After 15 min, imine 1 (350 mg, 1.60 mmol) was added to
the reaction flask via cannula as a solution in THF (5 mL).
The reaction mixture was left to stir for 5 h at K78/0 8C
under Ar before addition of saturated ammonium chloride
solution (3 mL). The product was extracted into EtOAc (3!).
The organic extracts were combined, washed with brine,
dried over anhydrous Na2SO4, filtered and removed the
solvent in vacuo. The resultant oil was submitted to flash
silica column chromatography (hexane/EtOAc, 95:5) to
yield 156 mg (0.48 mmol, 45%) of 3, 104 mg (0.22 mmol,
21%) of the mixture 4–6 and 98 mg (0.32 mmol, 30%) of 7.
Compound 3. [a]2D2 K50.0 (c 1.2, CHCl3). IR: 3330, 2985,
2934, 1495, 1454, 1371, 1213, 1146, 1067, 852, 748,
697 cmK1. 1H NMR (200 MHz, CDCl3) d 1.35 and 1.36 (3H
each, 2s, Me2C), 3.17–3.33 (1H, m, H-3), 3.68 and 3.95 (1H
each, 2d, JZ13.6 Hz, NHCH2Ph), 3.86 (1H, dd, JZ5.4,
8.4 Hz, HA-5), 3.91–3.94 (1H, m, HB-5), 4.10–4.20 (1H, m,
H-4), 6.03 (1H, dd, JZ8.8, 16.0 Hz, H-2), 6.59 (1H, d, JZ
16.0 Hz, H-1), 7.26–7.43 (10H, m, Ar). 13C NMR (50 MHz,
CDCl3) d 25.7 and 27.2 (Me2C), 51.0 (NHCH2Ph), 64.0
(C-3), 67.0 (C-5), 78.3 (C-4), 110.0 (Me2C), 126.8 (Cmeta
Ph), 127.3 (Cpara NHCH2Ph), 128.0 (C-2), 128.2 (Cpara Ph),
128.5 (Cmeta NHCH2Ph), 128.7 (Cortho NHCH2Ph), 128.9
(Cortho Ph), 134.8 (C-1), 136.6 (Cipso NHCH2Ph), 140.0
(Cipso Ph). MS: 324 [MCH]C, 279, 217, 159, 149, 117.
HRMS: calcd for C21H26NO2 [MCH]C: 324.1964, found:
324.1928.
3. Conclusions
The addition of the phenylstyrylsulfone to the imine 1 was
thus completely stereoselective, an improvement upon the
addition of the alkylsulfone. The hydride transfer previously
reported is also confirmed as a somewhat general
phenomenon by this work, and its synthetic utility is being
investigated. This methodology constitutes an alternative
procedure for the synthesis of L-homophenyalanine, and
opens a new methodology for the synthesis of unnatural
aminoacids.
4. Experimental
4.1. General
Unless otherwise stated, all chemicals were purchased as the
highest purity commercially available and were used
without further purification. IR spectra were recorded on a
BOMEM 100 FT-IR or an AVATAR 370 FT-IR Thermo
Nicolet spectrophotometers. 1H and 13C NMR spectra were
performed in CDCl3 and referenced to the residual peak of
CHCl3 at d 7.26 and 77.0 ppm, for 1H and 13C, respectively,
using Varian 200 VX and Bruker DRX 400 instruments.
Chemical shifts are reported in d ppm and coupling
constants (J) are given in Hz. MS were performed at a
Compounds 4–6. IR: 3525, 3355, 2985, 2933, 1447, 1371,
1
1305, 1214, 1149, 1084, 1029, 743, 699, 609 cmK1. H
NMR (200 MHz, CDCl3) d 1.21 and 1.34 (3H each, 2s,
Me2C), 3.01–3.42, 3.59–3.86, 3.93–4.21, 4.45–4.55 and
4.76–4.84 (9H, series of 5m, H-1, H-2, H-3, H-4, H-5 and
NHCH2Ph), 6.79–7.97 (15H, series of m, Ar). 13C NMR
(50 MHz, CDCl3) d 25.6 and 26.9 (Me2C), 28.9 and 30.9
(C-1), 52.8 and 57.7 (NHCH2Ph), 58.5 (C-3), 66.2 (C-2),
69.5 (C-5), 76.9 (C-4), 109.5 (Me2C), 126.9–129.6 (14C
Ar), 133.7 and 134.1 (Cpara SO2Ph), 137.5, 137.7, 139.2,

´
D. Dıez et al. / Tetrahedron 61 (2005) 11641–11648
11645
139.5 and 140.3 (3Cipso Ar). MS: 466 [MCH]C, 408, 279.
HRMS: calcd for C27H32NO4S [MCH]C: 466.2052, found:
466.2018.
(CO2C(CH3)3). MS: 318 [MCNa]C, 296 [MCH]C, 240,
196. HRMS: calcd for C16H26NO4 [MCH]C: 296.1862,
found: 296.1843.
Compound 7. IR: 3600–3300, 3063, 2980, 2936, 1447,
4.1.4. (2R)-(tert-butoxycarbonylamino)-4-phenyl buta-
noic acid 10. To a solution of 9 (61 mg, 0.21 mmol) in
MeCN/CCl4/H2O 2:2:3 (4 mL) was slowly added NaIO4
(178 mg, 0.83 mmol). The mixture was vigorously stirred
for 5 min before addition of RuCl3–H2O (2 mg, 0.01 mmol).
It was then left to stir at room temperature for 1 h. CH2Cl2
was then added and the product extracted with NaHCO3
1 M aqueous solution (3!). The aqueous extracts were
combined, washed with Et2O, and slowly acidulated with
solid KHSO4 until pHZ3. Product was then extracted with
Et2O, dried over anhydrous Na2SO4, filtered and removed
the solvent in vacuo. It was purified by flash chromato-
graphy (hexane/EtOAc, 1:1) to provide 41 mg (0.15 mmol,
71%) of 10. [a]2D2 K5.2 (c 1.1, EtOH). Lit.7 value for (2S)-
(tert-butoxycarbonylamino)-4-phenylbutanoic acid: [a]D22
C5.8 (c 1, EtOH). IR: 3450–3100, 2978, 1717, 1498,
1
1381, 1292, 1197, 1140, 1081, 746, 689, 610 cmK1. H
NMR (200 MHz, CDCl3) d 1.33 and 1.67 (3H each, 2s,
Me2C), 3.04 (1H, dd, JZ5.4, 15.8 Hz, HA-1), 3.19 (1H, dd,
JZ7.0, 15.8 Hz, HB-1), 3.72 (1H, dd, JZ5.4, 7.0 Hz, H-2),
4.63 (1H, br s, OH), 6.76–6.81 (2H, m, Hortho Ph), 7.03–7.07
(3H, m, Hmeta and Hpara Ph), 7.33–7.41 (2H, m, Hmeta
SO2Ph), 7.48–7.55 (1H, m, Hpara SO2Ph), 7.62–7.66 (2H,
m, Hortho SO2Ph). 13C NMR (50 MHz, CDCl3) d 26.5 and
30.3 (Me2C), 33.5 (C-1), 74.2 (C-3), 75.5 (C-2), 126.8 (Cpara
Ph), 128.1 (Cmeta Ph), 128.6 (Cortho SO2Ph and Cortho Ph),
129.2 (Cmeta SO2Ph), 133.6 (Cpara SO2Ph), 137.9 (Cipso Ph),
140.4 (Cipso SO2Ph).
4.1.2. (1R,40S)-N-tert-butoxycarbonyl-1-2020-dimethyl
[10,30]-dioxolan-40-yl-3-phenylpropylamine, 8. To a
solution of 3 (67 mg, 0.21 mmol) and di-tert-butyl
dicarbonate (68 mg, 0.31 mmol) in dry EtOAc (2.5 mL)
was added 55 mg (0.10 mmol) of 20% wt Pd(OH)2, and the
mixture was hydrogenated with H2 at atmospheric pressure
by stirring at room temperature for 24 h. After completion
the reaction mixture was filtered and concentrated in vacuo
to afford a crude product, which was purified by flash
chromatography (hexane/EtOAc, 9:1) to provide 34 mg
(0.10 mmol, 48%) of 8 as a white solid. [a]2D2 C23.2 (c 1.10,
CHCl3). IR: 3450, 3358, 2981, 2932, 1715, 1498, 1367,
1169, 1057, 700 cmK1. 1H NMR (200 MHz, CDCl3) d 1.33
and 1.43 (3H each, 2s, Me2C), 1.46 (9H, s, CO2C(CH3)3),
1.78–1.91 (2H, m, H-2), 2.58–2.79 (2H, m, H-1), 3.66 (1H,
dd, JZ7.4, 7.8 Hz, HA-5), 3.67–3.77 (1H, m, H-3), 3.98
(1H, dd, JZ6.8, 7.8 Hz, HB-5), 4.11–4.18 (1H, m, H-4),
4.71 (1H, d, JZ9.8 Hz, NH), 7.18–7.32 (5H, m, Ph). 13C
NMR (50 MHz, CDCl3) d 25.3 and 26.5 (Me2C), 28.6
(CO2C(CH3)3), 32.7 (C-2), 35.8 (C-1), 50.5 (C-3), 66.6
(C-5), 77.7 (C-4), 79.7 (CO2C(CH3)3), 109.3 (Me2C), 126.1
(Cpara Ph), 128.6 (Cortho and Cmeta Ph), 141.9 (Cipso Ph),
156.4 (CO2C(CH3)3). MS: m/z (%) 336 (10) [MCH]C, 280
(15), 222 (65), 117 (25), 91 (55). HRMS: calcd for
C19H30NO4 [MCH]C: 336.2175, found: 336.2153.
1
1406, 1368, 1248, 1166, 700 cmK1. H NMR (200 MHz,
CDCl3) d 1.46 (9H, s, CO2C(CH3)3), 1.94–2.30 (2H, m,
H-2), 2.73 (2H, t, JZ7.8 Hz, H-1), 4.28–4.43 (1H, m, H-3),
5.10 (1H, d, JZ7.4 Hz, NH), 7.18–7.32 (5H, m, Ar), 10.6
(1H, br s, COOH). 13C NMR (50 MHz, CDCl3) d 28.5
(CO2C(CH3)3), 31.8 (C-2), 34.3 (C-1), 53.4 (C-3), 80.5
(CO2C(CH3)3), 126.4 (Cpara Ph), 128.7 (Cortho and Cmeta
Ph), 140.9 (Cipso, Ph), 155.8 (CO2C(CH3)3), 177.6 (COOH).
MS: 302 [MCNa]C, 280 [MCH]C, 224, 180, 134, 117.
HRMS: calcd for C15H22NO4 [MCH]C: 280.1549, found:
280.1540.
4.1.5. N-tert-butoxycarbonyl-1-2020-dimethyl-[10,30]-
dioxolan-40-yl-3-phenyl-2-(phenylsulfonyl)
propyl
amines 11, 12 and 13. To a solution of 4–6 (94 mg,
0.20 mmol) and di-tert-butyl dicarbonate (68 mg,
0.31 mmol) in dry EtOAc (2.5 mL) was added 53 mg
(0.10 mmol) of 20% wt Pd(OH)2, and the mixture was
hydrogenated with H2 at atmospheric pressure by stirring at
room temperature for 24 h. After completion the reaction
mixture was filtered and concentrated in vacuo to afford a
crude product, which was purified by flash chromatography
(hexane/EtOAc, 95:5) to provide 15 mg (0.03 mmol, 16%)
of 11, 32 mg (0.07 mmol, 34%) of 12 and 18 mg
(0.04 mmol, 19%) of 13. Compound 11. [a]2D2 K17.0 (c
0.9, CHCl3). IR: 3442, 2981, 2935, 1713, 1495, 1448, 1369,
1305, 1233, 1147, 1082, 918, 862, 734, 690, 666 cmK1. 1H
NMR (200 MHz, CDCl3) d 1.34 (9H, s, CO2C(CH3)3), 1.39
and 1.43 (3H each, 2s, Me2C), 3.13 (1H, dd, JZ5.6,
14.8 Hz, HA-1), 3.25 (1H, dd, JZ7.6, 14.8 Hz, HB-1), 3.58
(1H, dd, JZ7.0, 8.0 Hz, HA-5), 3.74–3.82 (1H, m, H-2),
4.08 (1H, dd, JZ7.0, 8.0 Hz, HB-5), 4.42 (1H, dt, JZ2.6,
2.6, 9.0 Hz, H-3), 4.78–4.87 (2H, m, H-4 and NH), 6.93–
6.98 (2H, m, Hortho Ph), 7.08–7.16 (3H, m, Hmeta and Hpara
Ph), 7.42–7.61 (3H, m, Hmeta and Hpara SO2Ph), 7.80–7.83
(2H, m, Hortho SO2Ph). 13C NMR (50 MHz, CDCl3) d 25.4
and 26.5 (Me2C), 28.4 (CO2C(CH3)3), 31.5 (C-1), 50.1
(C-3), 67.4 (C-2 and C-5), 74.5 (C-4), 80.0 (CO2C(CH3)3),
110.2 (Me2C), 126.8 (Cpara Ph), 128.6 (Cortho SO2Ph), 128.7
(Cmeta and Cortho Ph), 129.4 (Cmeta SO2Ph), 133.9 (Cpara
SO2Ph), 138.1 (Cipso Ph), 139.3 (Cipso SO2Ph), 155.2
(CO2C(CH3)3). MS: 498 [MCNa]C, 476 [MCH]C, 420,
4.1.3. (2S,3R)-3-(tert-butoxycarbonylamino)-5-phenyl-1,
2-pentanediol, 9. To a solution of 8 (93 mg, 0.28 mmol) in
MeOH/H2O 3:1 (1.5 mL), CF3COOH (12 mL, 0.15 mmol)
was added and the mixture was left to stir for 7 h. The
solution was then poured into a separting funnel, extracted
with CH2Cl2 (3!), washed with brine (1!), dried over
anhydrous Na2SO4, filtered and removed the solvent. The
product was purified by flash silica column chromatography
(hexane/EtOAc 6:4) to yield 68 mg (0.23 mmol, 83%) of 9
as a white solid. [a]D22 C15.9 (c 1.1, CHCl3). IR: 3600–
3100, 2977, 2932, 1682, 1513, 1455, 1392, 1366, 1250,
1169, 1053, 872, 751, 700 cmK1 1H NMR (200 MHz,
.
CDCl3) d 1.45 (9H, s, CO2C(CH3)3), 1.76–1.93 (2H, m,
H-2), 2.64–2.74 (2H, m, H-1), 3.10 (2H, br s, 2OH), 3.48–
3.76 (4H, m, H-3, H-4 and H-5), 4.89 (1H, d, JZ9.2 Hz,
NH), 7.15–7.31 (5H, m, Ar). 13C NMR (50 MHz, CDCl3) d
28.6 (CO2C(CH3)3), 32.8 (C-2), 34.1 (C-1), 51.2 (C-3), 63.9
(C-5), 73.6 (C-4), 80.2 (CO2C(CH3)3), 126.2 (Cpara Ph),
128.7 (Cortho and Cmeta Ph), 141.7 (Cipso Ph), 157.4

´
D. Dıez et al. / Tetrahedron 61 (2005) 11641–11648
11646
376, 362. HRMS: calcd for C25H34NO6S [MCH]C:
476.2107, found: 476.2112.
159, 143, 117. HRMS: calcd for C14H18O2Na [MCNa]C:
241.1204, found: 241.1193.
Compound 12. [a]2D2 C7.5 (c 1.2, CHCl3). IR: 3368, 2982,
2934, 1716, 1498, 1448, 1370, 1307, 1243, 1150, 1078,
4.1.7. Reaction of 12 with Na amalgam: synthesis of (1S,
40S)-N-tert-butoxycarbonyl-1-2020-dimethyl [10,30]dioxo-
lan-40-yl-3-phenylpropylamine 15. A solution of 12
(43 mg, 0.09 mmol) in dry MeOH (1.5 mL) was added to
Na–Hg 5% amalgam (200 mg) via cannula. The reaction
mixture was left to stir for 1 h at room temperature under Ar.
The residue was filtered and diluted with EtOAc. The
mixture was washed with H2O and brine, dried over
anhydrous Na2SO4, filtered and removed the solvent. The
crude product was submitted to flash silica column
chromatography (hexane/EtOAc 95:5) to yield 4 mg
(0.02 mmol, 22%) of 14 and 17 mg (0.05 mmol, 56%) of
15. Compound 15. [a]D22 K21.3 (c 1.0, CHCl3). Lit.9 [a]D
1
1058, 734, 691 cmK1. H NMR (200 MHz, CDCl3) d 1.21
(6H, s, Me2C), 1.45 (9H, s, CO2C(CH3)3), 3.12 (1H, dd, JZ
8.8, 14.6 Hz, HA-1), 3.38 (1H, dd, JZ5.2, 14.6 Hz, HB-1),
3.70–3.91 (4H, m, H-2, H-3 and H-5), 4.16–4.27 (1H, m,
H-4), 5.04 (1H, d, JZ9.8 Hz, NH), 7.12–7.25 (5H, m, Ph),
7.48–7.62 (3H, m, Hmeta and Hpara SO2Ph), 7.88–7.92 (2H,
m, Hortho SO2Ph). 13C NMR (50 MHz, CDCl3) d 25.6 and
26.6 (Me2C), 28.5 (CO2C(CH3)3), 30.8 (C-1), 52.2 (C-3),
66.3 (C-2), 68.0 (C-5), 75.8 (C-4), 80.4 (CO2C(CH3)3),
110.2 (Me2C), 127.3 (Cpara Ph), 129.0 (Cortho SO2Ph), 129.2
(Cortho and Cmeta Ph), 129.4 (Cmeta SO2Ph), 134.0 (Cpara
SO2Ph), 137.0 (Cipso Ph), 138.4 (Cipso SO2Ph), 155.4
(CO2C(CH3)3). MS: 476 [MCH]C, 420, 376, 362.
HRMS: calcd for C25H34NO6S [MCH]C: 476.2107,
found: 476.2094.
1
K22.3 (c 1, CHCl3). H NMR (200 MHz, CDCl3) d 1.32
and 1.38 (3H each, 2s, Me2C), 1.46 (9H, s, CO2C(CH3)3),
1.54–1.73 and 1.87–2.08 (1H each, 2m, H-2), 2.55–2.85
(2H, m, H-1), 3.61–3.80 (2H, m, H-3 and HA-5), 3.96–4.05
(2H, m, H-4 and HB-5), 4.51 (1H, d, JZ10.0 Hz, NH). 7.14–
7.32 (5H, m, Ph). This compound 15 has already been
described and the spectroscopic properties and rotation were
coincident with those taken from literature.9
Compound 13. [a]2D2 C6.2 (c 1.0, CHCl3). IR: 3392, 2982,
2929, 1716, 1506, 1448, 1370, 1306, 1237, 1153, 1074,
666 cmK1. 1H NMR (200 MHz, CDCl3) d 0.76 and 1.17 (3H
each, 2s, Me2C), 1.50 (9H, s, CO2C(CH3)3), 2.89 (1H, dd,
JZ10.6, 13.8 Hz, HA-1), 3.03 (1H, dd, JZ3.2, 13.8 Hz,
HB-1), 3.79 (1H, dd, JZ3.8, 8.8 Hz, HA-5), 3.86–4.05 (3H,
m, H-2, H-3 and HB-5), 4.45–4.54 (1H, m, H-4), 5.61 (1H, d,
JZ10.6 Hz, NH), 7.00–7.04 (2H, m, Hortho Ph), 7.16–7.22
(3H, m, Hmeta and Hpara Ph), 7.56–7.70 (3H, m, Hmeta and
Hpara SO2Ph), 7.90–7.98 (2H, m, Hortho SO2Ph). 13C NMR
(50 MHz, CDCl3) d 25.6 and 26.4 (Me2C), 28.5
(CO2C(CH3)3), 33.4 (C-1), 52.9 (C-3), 65.6 (C-2), 67.6
(C-5), 76.1 (C-4), 80.4 (CO2C(CH3)3), 110.0 (Me2C), 127.2
(Cpara Ph), 128.5 (Cortho SO2Ph), 128.9 (Cmeta Ph), 129.6
(Cmeta SO2Ph and Cortho Ph), 134.2 (Cpara SO2Ph), 136.7
(Cipso Ph), 139.7 (Cipso SO2Ph), 156.1 (CO2C(CH3)3).
MS:476 [MCH]C, 420, 376, 362. HRMS: calcd for
C25H34NO6S [MCH]C: 476.2107, found: 476.2076.
4.1.8. Reaction of 13 with Na amalgam: synthesis of (1S,
40S)-N-tert-butoxycarbonyl-1-2020-dimethyl [10,30]dioxo-
lan-40-yl-3-phenylpropylamine 15. A solution of 13
(23 mg, 0.05 mmol) in dry MeOH (1.5 mL) was added to
Na–Hg 5% amalgam (150 mg) via cannula. The reaction
mixture was left to stir for 1 h at room temperature under Ar.
The residue was filtered and diluted with EtOAc. The
mixture was washed with H2O and brine, dried over
anhydrous Na2SO4, filtered and removed the solvent. The
crude product was submitted to flash silica column
chromatography (hexane/EtOAc 95:5) to yield 3.3 mg
(0.015 mmol, 31%) of 14 and 6 mg (0.02 mmol, 35%) of 15.
4.1.9. Reaction of 16 with imine 1. n-BuLi 1.6 M (1.4 mL,
2.24 mmol) was added to a solution of 16 (500 mg,
2.05 mmol) in THF (10 mL) at K78 8C under Ar
atmosphere. After 15 min, imine 1 (685 mg, 3.12 mmol)
was added to the reaction flask via cannula as a solution in
THF (15 mL). The reaction mixture was left to stir for 7 h at
K78/0 8C under Ar before addition of saturated
ammonium chloride solution (4 mL). The product was
extracted into EtOAc (3!). The organic extracts were
combined, washed with brine, dried over anhydrous
Na2SO4, filtered and removed the solvent in vacuo. The
resultant oil was submitted to flash silica column chroma-
tography (hexane/EtOAc, 95:5) to yield 255 mg
(0.55 mmol, 27%) of 17, 142 mg (0.31 mmol, 15%) of the
mixture 17 and 20, 254 mg (0.68 mmol, 33%) of 18 and
139 mg (0.37 mmol, 18%) of 19. Compound 17. [a]D22
K85.1 (c 1.0, CHCl3). IR: 3063, 2986, 2936, 2876, 1643,
4.1.6. Reaction of 11 with Na amalgam: synthesis of (1R,
40S)-N-tert-butoxycarbonyl-1-2020-dimethyl [10,30]dioxo-
lan-40-yl-3-phenylpropylamine 8. A solution of 11 (53 mg,
0.11 mmol) in dry MeOH (1.5 mL) was added to Na–Hg 5%
amalgam (250 mg) via cannula. The reaction mixture was
left to stir for 1 h at room temperature under Ar. The residue
was filtered and diluted with EtOAc. The mixture was
washed with H2O and brine, dried over anhydrous Na2SO4,
filtered and removed the solvent. The crude product was
submitted to flash silica column chromatography (hexane/
EtOAc 9:1) to yield 6 mg (0.03 mmol, 24%) of 14 and
27 mg (0.08 mmol, 72%) of 8. Compound 14. [a]2D2 C31.6
(c 0.2, CHCl3). IR: 2986, 2928, 2856, 1451, 1371, 1156,
1
1061, 968, 862, 665 cmK1. H NMR (400 MHz, CDCl3) d
1.38 and 1.42 (3H each, s, Me2C), 3.40 (2H, d, JZ6.8 Hz,
H-1), 3.58 (1H, dd, JZ7.6, 8.4 Hz, HA-5), 4.07 (1H, dd, JZ
6.4, 8.4 Hz, HB-5), 4.48–4.53 (1H, m, H-4), 5.51 (1H, dd,
JZ7.6, 15.2 Hz, H-3), 5.95 (1H, dt, JZ6.8, 6.8, 15.2 Hz,
H-2), 7.16–7.22 (2H, m, Hortho Ph), 7.26–7.31 (3H, m, Hmeta
and Hpara Ph). 13C NMR (100 MHz, CDCl3) d 25.8 and 26.7
(Me2C), 38.6 (C-1), 69.4 (C-5), 77.0 (C-4), 109.1 (Me2C),
126.1 (Cpara Ph), 128.4 (Cmeta Ph), 128.5 (Cortho Ph), 128.7
(C-2), 134.0 (C-3), 139.5 (Cipso Ph). MS: 241 [MCNa]C,
1447, 1381, 1306, 1217, 1148, 1071, 841, 746, 692 cmK1
.
1H NMR (200 MHz, CDCl3) d 1.13 and 1.32 (3H each, 2s,
Me2C), 3.27–3.60 (5H, m, H-1, H-2 and H-5), 3.68–3.78
(1H, m, H-4), 4.08 (1H, d, JZ8.2 Hz, H-3), 7.23–7.26,
7.37–7.49, 7.68–7.72 and 7.79–7.83 (15H, 4m, Ar), 8.22
(1H, s, N]CHPh). 13C NMR (50 MHz, CDCl3) d 25.6 and
26.8 (Me2C), 31.0 (C-1), 66.4 (C-5), 69.4 (C-2), 70.3 (C-3),
76.4 (C-4), 110.0 (Me2C), 127.1 (Cpara Ph), 128.6 (Cortho

´
D. Dıez et al. / Tetrahedron 61 (2005) 11641–11648
11647
SO2Ph), 128.9 (Cortho and Cmeta Ph), 129.2 (Cmeta SO2Ph),
129.4 (Cortho and Cmeta N]CHPh), 131.2 (Cpara
N]CHPh), 133.8 (Cpara SO2Ph), 136.2 (Cipso N]CHPh),
138.3 (Cipso Ph), 138.5 (Cipso SO2Ph), 164.6 (N]CHPh).
MS: m/z (%) 464 (5) [MCH]C, 89 (30). HRMS: calcd for
C27H30NO4S [MCH]C: 464.1896, found: 464.1902.
7.6 Hz, HB-5), 4.42–4.48 (2H, m, H-3 and H-4), 4.73 (1H, d,
JZ10.0 Hz, NH), 7.04–7.07 (2H, m, Hortho Ph), 7.12–7.22
(3H, m, Hmeta and Hpara Ph), 7.49–7.53 (2H, m, Hmeta
SO2Ph), 7.59–7.63 (1H, m, Hpara SO2Ph), 7.89–7.91 (2H,
m, Hortho SO2Ph). 13C NMR (100 MHz, CDCl3) d 24.8 and
25.9 (Me2C), 28.2 (CO2C(CH3)3), 32.1 (C-1), 49.9 (C-3),
66.4 (C-5), 67.7 (C-2) 76.9 (C-4), 79.9 (CO2C(CH3)3),
109.4 (Me2C), 126.6 (Cpara Ph), 128.5 (Cortho SO2Ph, Cmeta
Ph and Cortho Ph), 129.1 (Cmeta SO2Ph), 133.7 (Cpara
SO2Ph), 137.7 (Cipso Ph), 138.2 (Cipso SO2Ph), 155.5
(CO2C(CH3)3). MS: m/z (%) 498 (20) [MCNa]C, 476 (5)
[MCH]C, 420 (10), 362 (70), 154 (30), 91 (50). HRMS:
calcd for C25H34NO6S [MCH]C: 476.2107, found:
476.2117.
Compound 18. [a]2D2 K3.7 (c 1.4, CHCl3). IR: 3395, 2986,
2936, 2880, 1674, 1497, 1447, 1371, 1304, 1215, 1148,
1067, 914, 845, 743, 691 cmK1 1H NMR (400 MHz,
.
CDCl3) d 1.22 and 1.31 (3H each, 2s, Me2C), 2.11 (2H, br s,
NH2), 3.15 (1H, dd, JZ5.2, 14.8 Hz, HA-1), 3.23–3.27 (1H,
m, H-2), 3.41 (1H, dd, JZ6.8, 14.8 Hz, HB-1), 3.49 (1H, dd,
JZ6.8, 7.6 Hz, HA-5), 3.60–3.63 (2H, m, HB-5 and H-3),
3.79 (1H, q, JZ6.8 Hz, H-4), 7.02–7.04 (2H, m, Hortho Ph),
7.13–7.20 (3H, m, Hmeta and Hpara Ph), 7.49–7.55 (2H, m,
Hmeta SO2Ph), 7.60–7.64 (1H, m, Hpara SO2Ph), 7.84–7.86
(2H, m, Hortho SO2Ph). 13C NMR (100 MHz, CDCl3) d 25.3
and 26.4 (Me2C), 28.6 (C-1), 51.9 (C-3), 66.5 (C-5), 68.9
(C-2), 77.9 (C-4), 109.7 (Me2C), 126.7 (Cpara Ph), 128.6
(Cortho SO2Ph and Cmeta Ph), 128.7 (Cortho Ph), 129.3 (Cmeta
SO2Ph), 133.8 (Cpara SO2Ph), 138.0 (Cipso SO2Ph), 138.2
(Cipso Ph). MS: m/z 376 (75) [MCH]C, 318 (15), 274 (20),
154 (30), 91 (100). HRMS: calcd for C20H26NO4 [MCH]C:
376.1583, found: 376.1560.
To a solution of 19 (114 mg, 0.30 mmol) in THF (1.5 mL)
was added Boc2O (110 mg, 0.50 mmol) as a solution in THF
(1.5 mL). The mixture was left to stir for 15 h before
addition of 5% NaHCO3 solution (1 mL). The product was
extracted into EtOAc (3!). The organic extracts were
combined, washed with brine, dried over anhydrous
Na2SO4, filtered and removed the solvent in vacuo. The
resultant oil was purified by flash silica column chroma-
tography (hexane/EtOAc, 9:1) to yield 114 mg (0.24 mmol,
80%) of 11.
Compound 19. [a]2D2 K8.9 (c 1.2, CHCl3). IR: 3399, 2986,
2936, 2886, 1497, 1449, 1371, 1304, 1254, 1215, 1146,
4.1.11. Reaction of 21 with Na amalgam: synthesis of 8. A
solution of 21 (205 mg, 0.43 mmol) in dry MeOH (3 mL)
was added to Na–Hg 5% amalgam (600 mg) via cannula.
The reaction mixture was left to stir for 30 min at room
temperature under Ar. The residue was filtered and diluted
with EtOAc. The mixture was washed with H2O and brine,
dried over anhydrous Na2SO4, filtered and removed the
solvent. The crude product was submitted to flash silica
column chromatography (hexane/EtOAc 95:5) to yield
20 mg (0.09 mmol, 21%) of 14 and 94 mg (0.28 mmol,
65%) of 8.
1
1067, 849, 731, 691 cmK1. H NMR (200 MHz, CDCl3) d
1.32 (6H, s, Me2C), 2.17 (2H, br s, NH2), 3.00 (1H, dd, JZ
4.8, 14.4 Hz, HA-1), 3.28 (1H, dd, JZ8.8, 14.4 Hz, HB-1),
3.28–3.31 (2H, m, H-2 and H-3), 3.50 (1H, dd, JZ7.2,
8.0 Hz, HA-5), 4.09 (1H, dd, JZ6.4, 8.0 Hz, HB-5), 4.64–
4.73 (1H, m, H-4), 6.95-7.02 (2H, m, Hortho Ph), 7.12–7.19
(3H, m, Hmeta and Hpara Ph), 7.46–7.66 (3H, m, Hmeta and
Hpara SO2Ph), 7.82–7.87 (2H, m, Hortho SO2Ph). 13C NMR
(50 MHz, CDCl3) d 25.4 and 26.7 (Me2C), 32.5 (C-1), 53.3
(C-3), 67.0 (C-5), 71.5 (C-2), 76.5 (C-4), 109.6 (Me2C),
127.1 (Cpara Ph), 128.7 (Cortho SO2Ph), 128.8 (Cmeta Ph),
129.0 (Cortho Ph), 129.4 (Cmeta SO2Ph), 134.0 (Cpara
SO2Ph), 137.3 (Cipso Ph), 139.3 (Cipso SO2Ph). MS: m/z
(%) 376 (30) [MCH]C, 274 (10), 154 (100), 91 (45).
HRMS: calcd for C20H26NO4S [MCH]C: 376.1583, found:
376.1578.
Acknowledgements
The authors are gratefully acknowledged to Dra. A. Lithgow
and Dr. C. Raposo, from the NMR and Mass Spectrometry
Services, respectively, of Universidad de Salamanca and to
the CICYT for financial support. P. G. is grateful to
Universidad de Salamanca for a fellowship.
4.1.10. N-tert-butoxycarbonyl-1-2020-dimethyl-[10,30]-
dioxolan-40-yl-3-phenyl-2-(phenylsulfonyl)-propyl-
amines 21 and 11. To a solution of 18 (250 mg, 0.67 mmol)
in THF (2.5 mL) was added Boc2O (230 mg, 1.05 mmol) as
a solution in THF (2 mL). The mixture was left to stir for
20 h before addition of 5% NaHCO3 solution (2 mL). The
product was extracted into EtOAc (3!). The organic
extracts were combined, washed with brine, dried over
anhydrous Na2SO4, filtered and removed the solvent in
vacuo. The resultant oil was purified by flash silica column
chromatography (hexane/EtOAc, 9:1) to yield 249 mg
(0.52 mmol, 78%) of 21. [a]2D2 K16.9 (c 1.3, CHCl3). IR:
3443, 3375, 2981, 2932, 1716, 1497, 1369, 1306, 1247,
References and notes
´
1. (a) Badorrey, R.; Cativiela, C.; Dıaz-de-Villegas, M. D.;
´
Galvez, J. A. Synthesis 1997, 747. (b) Badorrey, R.; Cativiela,
´
´
C.; Dıaz-de-Villegas, M. D.; Galvez, J. A. Tetrahedron 1997,
53, 1411. (c) For a review of this kind of reactions see: Bloch,
R. Chem Rev. 1998, 98, 1407.
´
´
2. Dıez, D.; Garcıa, P.; Moro, R. F.; Marcos, I. S.; Basabe, P.;
Garrido, N. M.; Broughton, H. B.; Urones, J. G. Synthesis
2005, in press.
1150, 1072, 748, 691, 666 cmK1 1H NMR (400 MHz,
.
CDCl3) d 1.26 and 1.28 (3H each, 2s, Me2C), 1.43 (9H, s,
CO2C(CH3)3), 2.94 (1H, dd, JZ7.6, 14.8 Hz, HA-1), 3.21
(1H, dd, JZ4.0, 14.8 Hz, HB-1), 3.60 (1H, dd, JZ6.8,
7.6 Hz, HA-5), 3.71–3.74 (1H, m, H-2), 3.99 (1H, t, JZ
¨
3. (a) Attwood, M. R.; Hassall, C. H.; Krohn, A.; Lawton, G.;
Redshaw, S. J. Chem. Soc., Perkin Trans. 1 1986, 1011. (b)
Mancini, G. B. J. Am. J. Med. 1998, 105, 40S.

´
D. Dıez et al. / Tetrahedron 61 (2005) 11641–11648
11648
´ `
6. Poch, M.; Alcon, M.; Moyano, A.; Pericas, M. A.; Riera, A.
4. (a) Wyvratt, M. J.; Tristram, E. W.; Ikeler, T. J.; Lohr, N. S.;
Joshua, H.; Springer, J. P.; Arison, B. H.; Patchett, A. A.
J. Org. Chem. 1984, 49, 2816. (b) Blacklock, T. J.; Shuman,
R. R.; Butcher, J. W.; Shearin, W. E., Jr.; Budavari, J.; Grenda,
V. J. J. Org. Chem. 1988, 53, 836. (c) Huffmann, M. A.;
Reider, P. J. Tetrahedron Lett. 1999, 40, 831. (d) Palomo, C.;
Ganboa, I.; Oiarbide, M.; Sciano, G. T.; Miranda, J. I.
ARKIVOC 2002, v, 8.
Tetrahedron Lett. 1993, 34, 7781.
7. Chandrasekhar, S.; Raza, A.; Takhi, M. Tetrahedron:
Asymmetry 2002, 13, 423.
8. (a) Julia, M.; Paris, J.-M. Tetrahedron Lett. 1973, 14, 4833. (b)
Carretero, J. C.; Arrayas, R. G. J. Org. Chem. 1998, 63, 2993.
(c) Kocienski, P. J. Phosphorus and Sulfur 1985, 24, 97.
´ `
9. Alcon, M.; Poch, M.; Moyano, A.; Pericas, M. A.; Riera, A.
Tetrahedron: Asymmetry 1997, 8, 2967.
´
5. (a) Regla, I.; Luna, H.; Perez, H. I.; Demare, P.; Bustos-
´
Jaimes, I.; Zaldivar, V.; Calcagno, M. L. Tetrahedron:
´ ´
10. Badorrey, R.; Cativiela, C.; Dıaz-de-Villegas, M. D.; Galvez,
J. A. Tetrahedron 2002, 58, 341.
Asymmetry 2004, 15, 1285. (b) Hu, Q.; Wang, G.; Wang, X.;
Wu, T.; Pan, X.; Chan, A. S.; Yang, T. Tetrahedron:
Asymmetry 2000, 11, 2309. (c) Williams, R. M.; Sinclair,
P. J.; Zhai, D. G.; Chen, D. M. J. Am. Chem. Soc. 1988, 110,
1547. (d) Ben-Ishal, D.; Moshenberg, R. Tetrahedron 1977,
33, 1533. (e) Pulley, S. R.; Hegedus, L. S. J. Am. Chem. Soc.
1993, 115, 9037. (f) Corey, E. J.; Link, J. O. J. Org. Chem.
1992, 114, 1906. (g) Hashimoto, C.; Potier, P. Tetrahedron
Lett. 1987, 28, 6062. (h) Chistine, M.; Serreqi, A. N.; Huang,
Q.; Kazlauscas, R. J. J. Org. Chem. 1994, 59, 2075.
´ ´
11. Badorrey, R.; Cativiela, C.; Dıaz-de-Villegas, M. D.; Dıez, R.;
´
Galvez, J. A. Eur. J. Org. Chem. 2003, 2268.
¨
12. Flogel, O.; Amombo, M. G. O.; Reissig, H.-U.; Zahn, G.;
Bru¨dgam, I.; Hartl, H. Chem. Eur. J. 2003, 9, 1405.
¨
13. Schrodinger, LLC, Poland, OR.
14. (a) Wagle, D. R.; Garai, C.; Chiang, J.; Monteleone, M. G.;
Kurys, B. E.; Strohmeyer, T. W.; Hedge, V. R.; Manhas, M. S.;
Bose, A. K. J. Org. Chem. 1988, 53, 4227. (b) Cativiela, C.;
´ ´
Dıaz-de-Villegas, M. D.; Galvez, J. A. Tetrahedron:
Asymmetry 1996, 7, 529.