3-benzoyl-2-isopropyl-4-alkyloxazolidin-5-ones as efficient and inexpensive sources of enantiopure α,α-dialkyl α-amino acids and α,β-dialkyl α,β-diaminopropionic acids

Article abstract of DOI:10.3987/COM-04-10214

It is shown that the 3-benzoyl-2-isopropyl-4-alkyloxazolidin-5-ones (12), derived from isobutyraldehyde and α-amino acids are as efficient as, but more economical than, the corresponding tert-butyl compounds (9), as sources of enantiopure α,α-dialkylated

Full text of DOI:10.3987/COM-04-10214

HETEROCYCLES, Vol. 65, No. 1, 2005
59
HETEROCYCLES, Vol. 65, No. 1, 2005, pp. 59 - 75
Received, 31st August, 2004, Accepted, 1st November, 2004, Published online, 2nd November, 2004
3-BENZOYL-2-ISOPROPYL-4-ALKYLOXAZOLIDIN-5-ONES AS
EFFICIENT AND INEXPENSIVE SOURCES OF ENANTIOPURE
α,α-DIALKYL α-AMINO ACIDS AND α,β-DIALKYL
α,β-DIAMINOPROPIONIC ACIDS
Susana Rojas-Lima,* Omar Téllez-Zenteno, Heraclio López-Ruiz, Lizeth
Loubet-González, and Alejandro Alvarez-Hernandez
Chemical Research Center (CIQ), Autonomous University of Hidalgo (UAEH)
University City, Pachuca-Tulancingo road Km 4.5, Pachuca de Soto, Hidalgo,
México, CP 42076. address: *corresponding author: lima@uaeh.edu.mx
Abstract - It is shown that the 3-benzoyl-2-isopropyl-4-alkyloxazolidin-5-ones
(12), derived from isobutyraldehyde and α-amino acids are as efficient as, but
more economical than, the corresponding tert-butyl compounds (9), as sources of
enantiopure α,α-dialkylated α-amino acids (e.g., 21-23). In the absence of
alkylating agents, the anions of (2R,4S)-12 and its enantiomer undergo a
fragmentation-recombination process to generate (1S,2’R,4’S)-N-[1-(3-benzoyl-
2-isopropyl-4-methyl-5-oxo-oxazolidin-4-yl)-2-methylpropyl]benzamide
((1S,
2’R,4’S)-20), and its enantiomer. Acidic methanolysis of these condensation
products provides access to α,β-dialkylated α,β-diaminopropionic acids [e.g.,
(2S,3S)-2,3-bisbenzoylamino-2,4-dimethylpentanoic
((2S,3S)-24)).
acid
methyl
ester
1. INTRODUCTION
In recent years the preparation of enantiopure α,α-dialkylated α-amino acids has received substantial
attention owing to the interesting chemical and biological properties exhibited by these compounds.1-5 It
can be anticipated that α,β-diaminopropionic acids will also possess interesting properties.6 Furthermore,
peptides incorporating such geminally-branched amino acids will likely show unusual conformations.7,8

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HETEROCYCLES, Vol. 65, No. 1, 2005
Because of their potential roles in physiological processes, α,β-diaminopropionic acids (1) are especially
interesting objects for study and several enantioselective synthetic routes thereto have recently been
reported. For example, they have been prepared by the alkylation of the chiral benzodiazepinone (2) by
Juaristi and coworkers9 and the catalytic asymmetric hydrogenation of the enamines (4) by Robinson et
al.10 In addition, Jones11 prepared such compounds through the alkylation of the phenyl substituted
oxazolidinones (5) and Jorgensen12 prepared α,β-diaminopropionic acids by a Mannich type reaction of
the glycine derivatives (6) with imines (7) (Scheme 1).
CH3
O
O
Ph
N
Br
N
+
N
O
O
CH3
2
3
O
R´
NH
CO2R
O
R
O
HO
O
NH2
O
*
N
Bz
H2N
R"
N
R
Ph
H
4
1
5
Ph
N
CO2CH3
R
N
+
Ts
Ph
6
7
Scheme 1
In addition to 5, other oxazolidinones such as 2-tert-butyloxazolidinones (9), which are derived form
α-amino acids, have been used to prepare α,α-disubstituted α-amino acids13 (10a-d) (Scheme 2). Due to
the steric interaction with the incoming electrophile, the tert-butyl group in the oxazolidinone (9) directs
alkylation of the enolates to the opposite side of the ring. The required pivalaldehyde, however, is
O
CO2H
CO2H
R'
O
N
1) t-C4H9CHO
H2N
H
R
H2N
2) BzCl
R
R
Bz
10
8a R = -CH3
8b
8c R = -CH2C6H5
R = -CH(CH3)2
8e R = -CH(CH3)CH2CH3
9
R = -CH2CH(CH3)2
8d
Scheme 2

HETEROCYCLES, Vol. 65, No. 1, 2005
61
expensive and we reasoned that incorporation of the inexpensive isobutyraldehyde into this heterocyclic
system would probably afford equally high levels of diastereoselection upon alkylation of the enolates. In
the present paper we describe a convenient preparation of enantiopure α,α-dialkylated α-amino acids and
α,β-diaminopropionic acid derivatives starting from the readily available and inexpensive
2-isopropyloxazolidinone derivatives (12) derived from isobutyraldehyde and α-amino acids.
2. RESULTS AND DISCUSSION
2.1. Preparation of the chiral oxazolidinones(12-a-e) and configurational assignments.
The sodium salts of the amino acids (S)-alanine, (S)-leucine, (S)-phenylalanine, (S)-valine and
(S)-isoleucine (8a-e) were condensed with isobutyraldehyde14 to give the corresponding Schiff bases
(11a-e) wich were treated with benzoyl chloride to provide a trans/cis mixture of the α-alkylated
2-isopropyloxazolidinones (12a-e) (Scheme 3). After chromatographic separation of the isomers, their
structures were assigned by comparison of the chemical shifts of H-2 and H-4 with those of the
corresponding cis- and trans- 2-tert-butyloxazolidinones (9). The absolute configuration of all these
compounds was further confirmed by X-Ray analysis of several of the oxazolidinones.15 (See Figure 1).
O
R
O
R
CO2H
O
N
CO2H
O
2
BzCl
1) NaOH
N
H
R
H2N
H
R
4
+
2) (CH3)2CHCHO
N
Bz
Bz
trans-12
cis-12
11a-e
12a R = -CH3 (3:1)
12b
8a R = -CH3
8b
8c R = -CH2C6H5
R = -CH(CH3)2
8e R = -CH(CH3)CH2CH3
R = -CH2CH(CH3)2 (2:1)
12c R = -CH2C6H5 (3:1)
R = -CH(CH3)2 (5:1)
R = -CH2CH(CH3)2
12d
12e R = -CH(CH3)CH2CH3 (5:1)
8d
Scheme 3
2.2. Stereoselectivity of alkylation of (2R,4S)-12a and (2R,4S)-12c
The lithium enolates of oxazolidinones ((2R,4S)-12a) and ((2R,4S)-12c), generated with lithium
bis(trimethylsilyl)amide (LiHMDS) in THF, were alkylated with benzyl bromide, allyl bromide and ethyl
bromoacetate at –78°C to afford the trans disubstituted oxazolidinones (13-17) exclusively (the minor
diastereomer could not be detected by 1H NMR spectroscopy 16) and in good yields. (Table 1). The X-Ray
data for (2R,4S)-13, (2R,4R)-16 and (2R,4S)-17 (Figure 2) show that alkylation took place from the side
of the ring opposite to the isopropyl group.15

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HETEROCYCLES, Vol. 65, No. 1, 2005
63

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HETEROCYCLES, Vol. 65, No. 1, 2005
Interestingly, addition of the lithium salt of oxazolidinone ((2R,4S)-12a) to benzylbenzylideneamine (18)
.
catalyzed by BF3 O(C2H5)2 lead to the formation of the amide ((1S,2’R,4’S)-20) instead of the expected
amine (19) (Scheme 4). Compound ((1S,2’R,4’S)-20) was fully characterized by spectroscopic means,
including an X-Ray crystal structure determination (Figure 3).15 The formation of compound
((1S,2’R,4’S)-20) is explained, in part, as self addition of the enolate of (2R)-12a-Li. Repetition of the
experiment in the absence of benzylbenzylideneamine (18) gave (1S,2’R,4’S)-20 in considerably better
yield (Scheme 4) . Similarly, (2S,4S)-12a gave the enantiomeric product ent-20 (Scheme 5).
O
O
(2R, 4S)-12a
N
CH3
Bz
LiHMDS
THF, - 78 °C
18
O
Ph
O
OLi
O
BnN
O
O
BF3O(C2H5)2
CH3
CH3
N
N
N
NHBn
CH3
BF3O(C2H5)2
Bz
Bz
Bz
HN
Ph
Ph
O
(2R)-12a Li
(1S,2'R,4'S)-20
19
Scheme 4
O
O
O
O
N
LiHMDS
CH3
THF, - 78 °C
N
CH3
Bz
Bz
HN
O
Ph
ent-20
(2S,4S)-12a
Scheme 5
We propose a fragmentation-recombination process as a rationale for the formation of the unexpected
product (1S,2’R,4’S)-20. The steric repulsion between the phenyl ring of benzamide and the substituent at
C-2 on unreacted (2R,4S)-12a drives the opening of the oxazolidinone ring to form a pseudo iminium ion
A which alkylates enolate (2R)-12a-Li to form intermediate B. Then B undergoes a LiHMDS-promoted
fragmentation to lithium acrylate and the anion C, from which the observed product (1S,2’R,4’S)-20 is
obtained upon quenching of the reaction mixture. (Scheme 6). The steric repulsion in the oxazolidinone
ring that drives its fragmentation to pseudo-iminium ion A is evident in the crystal structure of
(2R,4S)-12a (Figure 1). This structure shows that the crowding between the benzoyl group and the
substituent at C-2 is partially aleviated by distortion of the dihedral angles N-CO-Ph (N1-C8-C9-C10 =46.3o
and N1-C8-C9-C14 = -136.4o) which avoids the planarity and the stabilization of this benzamide moeity.

HETEROCYCLES, Vol. 65, No. 1, 2005
65
δ
O
O
OLi
O
N
Bz
O
O
N
O
+
Base
N
CH3
CH3
δ
Bz
Bz
N
H
(2R)-12a
A
O
OLi
O
O
O
O
N
B
N
Bz
H2O
Bz
O
N
O
NH
elimination
β−
-
LiO2C-CH=CH2
C
(1S,2'R,4'S)-20
Base: LiHMDS
Scheme 6
(1S,2’R,4’S)-20
Figure 3. X-Ray structure and solid-state conformation of (1S,2’R,4’S)-20 (numbers in structur refer to
X-Ray coodinates as deposited CCDC).
2.3. Methanolysis of oxazolidinones (13-15 and 20). Production of enantiopure α,α-dialkylated
α-amino acids and α,β-dialkylated α,β-diamino acids.
Methanolysis of the alkylated heterocycles ((2R,4S)-13-15) was achieved by treatment with 2M
CF3CO2H in CH3OH (130oC, 72 h). The N-benzoylated amino esters ((S)-21-23) thus obtained were

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HETEROCYCLES, Vol. 65, No. 1, 2005
purified by flash chromatography. Oxazolidinone ((1S,2’R,4’S)-20) was converted into the
di-N-benzoyl-α,β-diamino acid methyl ester ((2S,3S)-24) in the same manner (Table 2).
Table 2. Methanolysis of the products ((2R,4S)-13-15) to give N-benzoylated amino acid esters
((2S)-21-23) and ((1S,2’R,4’S)-20) to give di-N-benzoyl-α,β-diamino acid methyl ester
((2S,3S)-24)
O
O
O
H3CO
2M CF3CO2H
CH3OH, 130oC
72 h
CH3
CH3
N
HN
Bz
R
R
Bz
20
D
R
Product
Yield (%)
α
[ ]
-CH2C6H5
(2S)-21
(2S)-22
(2S)-23
+ 77.5°
+ 9.74°
+4.84°
97
87
85
-CH2CH=CH2
-CH2COOCH3
HN
O
(2S,3S)-24
-55.4°
95
Ph
In summary, inexpensive isobutyraldehyde and (S)-amino acids, were converted to enantiopure
oxazolidinones ((2R,4S)-12a-e) which were then alkylated with high stereoselectivity with various alkyl
halides to give the products (13-17) of trans addition. Methanolysis of the alkylated derivatives was
accomplished under acidic conditions to afford enantiopure α,α-dialkyl α-amino acids methyl esters
(21-23). Methanolysis of oxazolidinone (20) afforded α,β-dialkylated α,β-diaminopropionic acid methyl
esters derivatives ((2S,3S)-24). The present synthetic protocol constitutes a useful application of the so
called “self-regeneration of stereogenic centers” concept.18
3. EXPERIMENTAL
Flasks, stirring bars, and glass syringes used for the generation and reactions of organolithium reagents
were dried for ca. 12 h at 120oC and allowed to cool in a desiccator over anhydrous CaSO4. Anhydrous
solvents were obtained by distillation from benzophenone ketyl.19 TLC was performed on Merck-DC-F254
plates, detection was made by shining UV light. Flash column chromatography20 was performed using
Merck silica gel (230-240 mesh). All melting points are uncorrected. 1H NMR spectra were recorded on a
13
JEOL Eclipse+400 (400 MHz) spectrometer. C NMR spectra were recorded on a JEOL Eclipse+400
(100 MHz) spectrometer. Chemical shifts (δ) are indicated in ppm downfield from internal TMS reference;
the coupling constants (J) are given in Hz. Optical rotation were measured in a Perkin-Elmer Model 341

HETEROCYCLES, Vol. 65, No. 1, 2005
67
Polarimeter, using the sodium D-line (586 nm). Elemental analyses were performed on a Perkin-Elmer
Serie II CHNS/O Analyzer 2400.
3.1. General procedure for the preparation of oxazolidinones (12a-e)
In a 500 mL round-bottom flask was placed (1.0 equiv) of amino acid in 200 mL of dry C2H5OH. NaOH
(1.2 equiv.) was added, and the resulting solution was stirred at rt until complete dissolution of the amino
acid (ca. 30 min.). After evaporation, the sodium salt of the amino acid was dried under high vacuum and
then suspended in 150 mL of CH2Cl2. This suspension was treated with (1.1 equiv.) of isobutyraldehyde
and heated to reflux for 8 h with simultaneous removal of the generated H2O (Dean-Stark trap). The
reaction flask was cooled in an ice-water bath before addition of benzoyl chloride (1.0 equiv.). The
reaction mixture was stirred at rt overnight, washed once with 2 x 200 mL of aq. 5% NaHCO3 and once
with water. The organic phase was dried (Na2SO4), filtered and concentrated at reduced pressure.
3.1.2. (2R,4S) and (2S,4S)-3-Benzoyl-2-isopropyl-4-methyloxazolidin-5-one (12a)
The general procedure was followed using 3.0 g (33.7 mmol) of (S)-alanine (8a), 1.62 g (40.4 mmol) of
NaOH, 3.3 mL (37.1 mmol) of isobutyraldehyde and 3.8 mL (33.7 mmol) of benzoyl chloride to give 6.9
g (83 %) of the crude product as a 3:1 (trans/cis) mixture, which was purified by flash column
chromatography (hexane-ethyl acetate; 98:2) to afford 2.7 g (37 %) of (2R,4S)-12a as white crystals
(recrystallization solvent CH2Cl2-hexane), mp 112-114oC,
= + 170o (c = 2.0, CHCl3) and 1.0 g
20
D
α
[ ]
(14 %) of (2S,4S)-12a as a colorless oil,
= + 8.72o (c = 1.0, CHCl3).
20
D
α
[ ]
1
3.1.2.1. (2R,4S)-12a, H NMR (CDCl3) δ 7.6-7.4 (m, 5H), 5.98 (s, 1H), 4.46 (q, J = 6.6 Hz, 1H), 2.94
13
(br, 1H), 1.25 (br, 3H), 1.02 (d, J = 7.0 Hz, 1H), 0.89 (d, J = 7.0 Hz, 1H). C NMR (CDCl3) δ 172.6,
169.1, 135.7, 131.5, 129.0, 127.0, 93.5, 53.5, 31.4, 18.1, 17.5, 13.3. Anal. Calcd for C14H17NO3: C, 68.00;
H, 6.93, N, 5.66. Found: C, 68.37; H, 6.84, N, 5.34.
1
3.1.2.2. (2S,4S)-12a H NMR (CDCl3; 60oC) δ 7.55-7.38 (m, 5H) 5.88 (d, J = 5.9 Hz, 1H), 4.21 (q, J =
7.0 Hz, 1H), 2.05 (m, 1H), 1.41 (d, J = 7.0Hz, 3H), 0.98 (d, J = 6.76 Hz, 3H), 0.97 (d, J = 7.0 Hz, 3H).
13C NMR (CDCl3; 60oC) δ 172.6, 171.0, 135.5, 130.5, 128.8, 126.4, 93.8, 53.1, 34.0, 19.1, 17.7, 16.1.
Anal. Calcd for C14H17NO3: C, 68.00; H, 6.93, N,5.66. Found: C, 68.04; H, 6.66, N, 5.39.
3.1.3. (2R,4S) and (2S,4S)-3-Benzoyl-4-isobutyl-2-isopropyloxazolidin-5-one (12b)
The general procedure was followed using 3.0 g (22.9 mmol) of (S)-leucine (8b), 1.1 g (27.5 mmol) of

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HETEROCYCLES, Vol. 65, No. 1, 2005
NaOH, 2.3 mL (25.2 mmol) of isobutyraldehyde and 3.4 mL (33.7 mmol) of benzoyl chloride to give 6.5
g (98%) of the crude product as a 5:1 (trans/cis) mixture, which was purified by flash column
chromatography (hexane-ethyl acetate; 98:2) to afford 3.0 g (45%) of (2R,4S)-12b as white crystals,
(recrystallization solvent CH2Cl2-hexane), mp 124-126oC,
+ 155.3o (c = 1.0, CHCl3) and 1.0 g
20
D
α
[ ]
(14 %) of (2S,4S)-12b as white crystals, (recrystallization solvent CH2Cl2-hexane), mp 91-93oC,
20
D
α
[ ]
= + 49.4o (c = 1.0, CHCl3).
3.1.3.1. (2R,4S)-12b, 1H NMR (CDCl3; 60oC) δ 7.48 (m, 5H), 5.92 (s, 1H), 4.47 (dd, J = 8.0 Hz, J = 7.7
Hz, 1H), 2.35 (br, 1H), 1.73 (br, 1H), 1.51 (br, 2H), 1.02 (d, J= 6.6 Hz, 3H), 0.86 (d, J= 7.0 Hz, 3H), 0.76
(d, J = 7.0 Hz, 3H), 0.72 (d, J = 7.0 Hz, 3H). 13C NMR (CDCl3; 60oC) δ 172.2, 169.1, 135.7, 131.5, 129.0,
127.1, 93.7, 56.3, 40.0, 30.9, 23.9, 23.4, 21.4,17.6,13.0. Anal. Calcd for C17H23NO3: C, 70.56; H, 8.01, N,
4.84. Found: C, 70.30; H, 8.18, N, 4.63.
3.1.3.2. (2S,4S)-12b, 1H NMR (CDCl3) δ 7. 36-7. 48 (m, 5-H), 5.86 (d, J= 7.0 Hz, 1H), 4.20 (d, J= 6.6 Hz,
1H), 2.03 (m, 1H), 1.84 (m, 1H), 1.76 (m,1H), 1.52 (m, 1H), 1.02 (d, J= 6.6 Hz, 3H), 1.00 (d, 7.0 Hz, 3H),
0.81 (d, J = 6.6 Hz, 3H), 0.61 (d, J= 6.2 Hz, 3H). 13C NMR (CDCl3) δ 172.3, 171.2, 135.3, 130.6, 128.9,
126.4, 93.8, 55.1, 43.5, 34.7, 24.5, 23.2, 21.0, 17.9, 16.9. C17H23NO3: C, 70.56; H, 8.01, N, 4.84. Found: C,
70.44; H, 8.00, N, 4.86.
3.1.4. (2R,4S) and (2S,4S)-3-Benzoyl-4-benzyl-2-isopropyloxazolidin-5-one (12c)
The general procedure was followed using 3.0 g (18.2 mmol) of (S)-phenylalanine (8c), 0.87 g (21.8
mmol) of NaOH, 1.8 mL (20.0 mmol) of isobutyraldehyde and 2.1 mL (18.2 mmol) of benzoyl chloride to
give 5.23 g (89 %) of the crude product as a 3:1 (trans/cis) mixture, which was purified by flash column
chromatography (hexane-ethyl acetate; 98:2) to afford 2.5 g (42.5 %) of (2R,4S)-12c as white crystals,
(recrystallization solvent CH2Cl2-hexane), mp 161-163oC,
= + 230.4o (c = 1.0, CHCl3) and 1.5 g
20
D
α
[ ]
(26 %) of (2S,4S)-12c as white crystals, (recrystallization solvent CH2Cl2-hexane), mp 126-128oC,
20
D
α
[ ]
= + 75.9o (c = 1.0, CHCl3).
3.1.4.1. (2R,4S)-12c, 1H NMR (CDCl3) δ7.50-7.00 (m, 10H), 5.18 (s, 1H), 4.83 (dd, J= 4.0 Hz, J= 3.3 Hz,
13
1H), 3.14 (br, 2H), 1.63 (br, 6H), 0.76 (br, 6H). C NMR (CDCl3) δ 171.5, 168.6, 135.5, 134.8, 131.5,
129.8, 129.1, 128.7, 127.6, 127.0, 94.1, 58.8, 36.0, 31.0, 17.4, 12.7. Anal. Calcd for C20H21NO3: C, 74.28;
H, 6.55, N, 4.33. Found: C, 73.98; H, 6.47, N 4.51
3.1.4.2. (2S,4S)-12c, 1H NMR (CDCl3; 60oC) δ 7.00-7.50 (m, 10H), 5.79 (d, J = 7.3 Hz, 1H), 4.51 (dd, J=
7.0 Hz, J = 5.0 Hz 1H), 3.13 (dd, J = 14.0 Hz, J = 5.0 Hz, 1H), 3.07 (dd, J= 14.0 Hz, J= 7.0 Hz, 1H), 1.28
(m, 1H), 0.88 (d, J = 7.0 Hz, 3H), 0.86 (d, J = 7.0 Hz, 3H). 13C NMR (CDCl3, 60oC) δ 171.4, 171.3, 135.5,

HETEROCYCLES, Vol. 65, No. 1, 2005
69
135.4, 130.3, 129.7, 128.9, 128.7, 127.4, 126.3 94.1, 59.0, 39.1, 34.4, 18.0, 16.7. Anal. Calcd for
C20H21NO3: C, 74.28; H, 6.55, N, 4.33. Found: C, 74.19; H, 6.61, N 4.45
3.1.5. (2R,4S) and (2S,4S)-3-Benzoyl-2,4-diisopropyloxazolidin-5-one (12d)
The general procedure was followed using 3.0 g (25.6 mmol) of (S)-valine (8d), 1.23 g (30.7 mmol) of
NaOH, 2.5 mL (28.2 mmol) of isobutyraldehyde and 3.0 mL (25.6 mmol) of benzoyl chloride to give 6.33
g (90 %) of the crude product as a 5:1 (trans/cis) mixture, which was purified by flash column
chromatography (hexane-ethyl acetate; 98:2) to afford 5.0 g (71 %) of (2R,4S)-12d as white crystals,
(recrystallization solvent CH2Cl2-hexane), mp 129-131oC,
= + 108.2o (c = 1.0, CHCl3) and 1.0 g
20
D
α
[ ]
(14 %) of (2S,4S)-12d as white crystals, (recrystallization solvent CH2Cl2-hexane), mp 69-71oC,
=
20
D
α
[ ]
+ 46.1o (c = 1.0, CHCl3).
3.1.5.1. (2R,4S)-12d, 1H NMR (DMSO-d6; 120oC) δ7. 46-7. 71 (m, 5-H), 5.98 (s, 1H), 4.65 (d, J = 3.3 Hz,
1H), 2.17 (br, 1H), 1.99 (br, 1H), 0.96 (d, J=7.0 Hz, 3H), 0.95 (d, J= 7.0 Hz, 3H), 0.85 (d, J= 7.0 Hz, 3H),
13
0.81 (d, J = 7.0 Hz, 3H). C NMR (DMSO-d6; 120oC) δ 170.7, 168.7, 136.1, 131.9, 129.4, 127.5, 94.0,
62.5, 61.7, 31.1, 30.9, 18.0, 17.9, 16.4, 13.3. Anal. Calcd for C16H21NO3: C, 69.79; H, 7.69, N, 5.09 Found:
C, 69.77; H, 7.59, N, 4.96.
3.1.5.2. (2S,4S)-12d 1H NMR (CDCl3; 60oC) δ 7. 30-7. 47 (m, 5H), 5.62 (d, J = 7.7 Hz, 1H), 4.24 (d, J =
8.1 Hz, 1H), 1.98 (m, 1H), 1.91 (m, 1H), 1.10 (d, J = 7.0 Hz, 3H), 1.01 (d, J = 7.0 Hz, 3H), 0.96 (d, J= 7.0
13
Hz, 3H), 0.94 (d, J = 7.0 Hz, 3H). C NMR (CDCl3; 60oC) δ 172.0, 171.2, 135.6, 130.2, 128.7, 126.6,
94.3, 61.6, 35.3, 32.6, 19.9, 18.6, 18.2, 17.5. Anal. Calcd for C16H21NO3: C, 69.79; H, 7.69, N, 5.09 Found:
C, 69.74; H, 7.69, N, 5.06.
3.1.6. (2R,4S) and (2S,4S)-3-Benzoyl-4-sec-butyl-2-isopropyloxazolidin-5-one (12e)
The general procedure was followed using 3.0 g (22.9 mmol) of (S)-isoleucine (8e), 1.1 g (27.5 mmol) of
NaOH, 2.3 mL (25.2 mmol) of isobutyraldehyde and 2.7 mL (22.9 mmol) of benzoyl chloride to give 6.5g
(98 %) of the crude product as a 5:1 (trans/cis) mixture, which was purified by flash column
chromatography (hexane-ethyl acetate; 98:2) to afford 5.0 g (76 %) of (2R,4S)-12e as white crystals,
(recrystallization solvent CH2Cl2-hexane), mp 131-133oC,
= + 202.3o (c = 1.0, CHCl3) and 1.0 g
20
D
α
[ ]
(15 %) of (2S,4S)-12e as white crystals, (recrystallization solvent CH2Cl2-hexane), mp 88-90oC,
=
20
D
α
[ ]
+ 65.2o (c = 1.0, CHCl3).

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HETEROCYCLES, Vol. 65, No. 1, 2005
3.1.6.1. (2R,4S)-12e, 1H NMR (DMSO-d6; 120oC) δ7.10-7.50 (m, 5H), 5.97 (d, J= 2.0 Hz, 1H), 4.72 (d, J
= 3.3 Hz, 1H), 2.24 (br, 1H), 1.68 (br, 1H), 1.49 (m, 1H), 1.26 (m, 1H), 0.96 (d, J= 7.0 Hz, 3H), 0.93 (d, J
13
= 7.3 Hz, 3H), 0.82 (d, J = 7.3 Hz, 3H, H-13), 0.68 (t, J = 7.3 Hz, 3H). C NMR (DMSO-d6; 120oC) δ
170.8, 168.6, 132.0, 129.5, 127.6, 127.4, 94.0, 61.1, 38.0, 31.0, 25.2 18.0, 17.9, 14.2, 13.5, 11.9, 11.8.
Anal. Calcd for C17H23NO3: C, 70.56; H, 8.01, N, 4.84 Found: C, 70.40; H, 8.03, N, 4.94.
3.1.6.2. (2S,4S)-12e 1H NMR (CDCl3) δ 7.30-7.50 (m, 5H), 5.66 (d, J = 8.0 Hz, 1H), 4.27 (d, J = 7.4 Hz,
1H), 1.92 (m, 1H), 1.68 (m, 1H), 1.53 (m, 1H), 1.14 (m, 1H), 1.05 (d, J = 7.0 Hz, 3H), 1.10 (d, J = 7.0 Hz,
13
3H), 0.95 (d, J = 7.0 Hz, 3H), 0.69 (t, J = 7.0 Hz, 3H). C NMR (CDCl3) δ 172.4, 171.2, 135.5, 130.3,
128.8, 126.4, 94.2, 60.8, 38.9, 35.4, 26.1 18.1, 17.7, 15.2, 11.4. Anal. Calcd for C17H23NO3: C, 70.56; H,
8.01, N, 4.84.Found: C, 70.64; H, 8.19, N, 4.62.
3.2. General procedure for the reaction of oxazolidinones enolates ((2R,4S)-Li-12a) and
((2R,4S)-Li-12c) with electrophiles
In a 25 mL round-bottom flask fitted with a magnetic bar was placed 500 mg (2.02 mmol) of ((2R,4S)-12a
or (2R,4S)-12c in 15 mL of dry THF under nitrogen. The flask was cooled in a dry ice-acetone bath (-78
oC) and 1.2 equiv. of 1.0 M LiHMDS was added via syringe. The resulting solution was allowed to react
for 30 min before the addition of electrophile (dropwise addition). The reaction mixture was then stirred at
-78 oC for 2 h then it was allowed to warm up to rt and stirring was continued overnight. The reaction was
quenched with 5 mL of saturated aq. NH4Cl, and the product was extracted with CH2Cl2 (3 X50 mL). The
combined extracts were dried over anhydrous Na2SO4, and concentrated. Final purification was
accomplished by flash chromatography
3.2.1. (2R,4S)-3-Benzoyl-4-benzyl-2-isopropyl-4-methyloxazolidin-5-one ((2R,4S)-13)
The general procedure was followed using 0.5 g (2.02 mmol) of (2R,4S)-12a in 15 mL of THF, 2.5 mL
(2.5 mmol) of LiHMDS and 0.5 mL (4.20 mmol) of benzyl bromide. Purification of the crude product by
flash chromatography (n-hexane:ethyl acetate 8:2) afforded 0.62 g (91% yield) of (2R,4S)-13 as white
= +174.40o ( c = 1.0,
20
D
crystals, (recrystallization solvent CH2Cl2-hexane), mp. 117.2-117.4 °C.
α
[ ]
CHCl3).
1
(2R,4S)-13 H NMR (CDCl3) δ 7.40-6.95 (m, 10H), 4.87 (s, 1H), 3.85 (d, J = 13.5 Hz, 1H), 3.22 (d, J =
13
13.5 Hz, 1H), 1.96 (s, 3H), 1.07 (m, 1H), 0.68 (d, J = 6.6 Hz, 3H), 0.58 (d, J= 7.0 Hz, 3H). C NMR
(CDCl3) δ 175.2, 168.1, 136.4, 130.6, 129.9, 128.9, 127.7, 125.8, 93.3, 65.6, 41.0, 31.0, 23.8, 17.6, 13.1.
Anal. Calcd for C21H23NO3: C, 74.75; H, 6.87, N, 4.15. Found: C 74.65, H, 6.88, N,.4.28.

HETEROCYCLES, Vol. 65, No. 1, 2005
71
3.2.2. (2R,4S)-4-Allyl-3-benzoyl-2-isopropyl-4-methyloxazolidin-5-one ((2R,4S)-14)
The general procedure was followed using 0.5 g (2.02 mmol) of (2R,4S)-12a in 15 mL of THF, 2.5 mL
(2.5 mmol) of LiHMDS and 0.35 mL (4.16 mmol) of allyl bromide. Purification of the crude product by
flash chromatography (n-hexane:ethyl acetate 8:2) afforded 0.46 g (79 % yield) of (2R,4S)-13 as white
o
20
D
crystals, (recrystallization solvent CH2Cl2-hexane), mp 63.8-65.9 °C.
= + 15.45 ( c = 1.0,
α
[ ]
CHCl3).
1
(2R,4S)-13 H NMR (CDCl3) δ 7.55-7.46 (m, 5H), 5.82 (d, J = 2.6 Hz, 1H), 5.75 (m, 1H), 5.27 (d, J=
10.2 Hz, 1H), 5.15 (d, J = 17.2 Hz, 1H), 3.0 (br, 1H), 2.47 (dd, J = 14.3 Hz, J = 6.6 Hz 1H), 1.69 (s, 3H),
1.60 (m, 1H), 0.79 (d, J = 7.0 Hz), 0.78 (d, J = 6.6 Hz). 13C NMR (CDCl3) δ 174.6, 168.9, 136.6, 131.3,
130.5, 128.7, 126.4, 131.3, 121.1, 93.4, 63.7, 40.2, 31.5, 24.1, 17.7, 13.6. Anal. Calcd for C17H21NO3: C,
71.06; H, 7.37, N, 4.87. Found: C 71.01, H, 7.60, N, 4.73.
3.2.3. [(2R,4S)-3-Benzoyl-2-isopropyl-4-methyl-5-oxo-oxazolidin-4-yl]acetic acid ethyl ester
((2R,4S)-15)
The general procedure was followed using 0.5 g (2.02 mmol) of (2R,4S)-12a in 15 mL of THF, 2.5 mL
(2.43 mmol) of LiHMDS and 0.5 mL (4.04 mmol) of ethyl bromoacetate. Purification of the crude product
by flash chromatography (n-hexane:ethyl acetate 8:2) afforded 0.53 g (85% yield) of (2R,4S)-13 as a
= + 75.91o ( c = 1.0, CHCl3).
20
D
viscous oil.
α
[ ]
(2R,4S)-13 1H NMR (CDCl3) δ 7.33-7.26 (m, 5H), 5.79 (d, J = 2.2 Hz, 1H), 4.02 (q, J = 7.1 Hz, 2H), 3.5
(br, 1H), 2.77 (d, J= 17.9 Hz, 1H), 1.63 (s, 3H), 1.09 (t, J = 7.1 Hz, 3H), 0.69 (d, J= 7.0 Hz, 6H). 13C NMR
(CDCl3) δ 174.0, 170.3, 168.3, 136.5, 130.5, 128.8, 126.1, 93.9, 60.9, 60.5, 39.3, 30.8, 24.0, 17.7, 13.9,
13.6. anal. Calcd for C18H23NO5: C, 64.85; H, 6.95, N, 4.20. Found: C 64.52, H, 7.16 N, 4.13.
3.2.4. (2R,4R)-4-Allyl-3-benzoyl-4-benzyl-2-isopropyloxazolidin-5-one ((2R,4R)-16)
The general procedure was followed using 0.2 g (0.62 mmol) of (2R,4S)-12c in 15 mL of THF, 0.7 mL
(0.74 mmol) of LiHMDS and 0.11 mL (1.27 mmol) of allyl bromide. Purification of the crude product by
flash chromatography (n-hexane:ethyl acetate 8:2) afforded 0.12 g (53 % yield) of (2R,4R)-16 as white
o
20
D
crystals, (recrystallization solvent CH2Cl2-hexane), mp 104.7-105.8 °C.
= - 86.39 ( c = 1.0,
α
[ ]
CHCl3).
1
(2R,4R)-16 H NMR (CDCl3) δ 7.53-7.18 (m, 10H), 5.84 (m, 1H), 5.41 (d, J = 3.7 Hz, 1H), 5.35 (d, J =
16.5 Hz, 1H), 5.34 (d, J = 11.4 Hz, 1H), 3.88 (d, J = 13.2 Hz, 1H), 3.47 (t, J = 11.4 Hz, 1H), 3.36 (d, J =
13.5 Hz, 1H), 2.67 (dd, J = 5.9 Hz, J = 13.9 Hz, 1H), 0.58 (m, 1H), 0.40 (d, J = 7.0 Hz, 3H), -0.18 (d, J =
13
6.6 Hz, 3H). C NMR (CDCl3) δ 173.4, 169.2, 137.0, 136.1, 131.3, 130.7, 130.3, 128.8, 128.5, 127.4,
126.1, 121.7, 93.7, 69.7, 42.0, 39.7, 31.6, 18.5, 12.4. Anal. Calcd for C23H25NO3: C, 76.01; H, 6.93, N,

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HETEROCYCLES, Vol. 65, No. 1, 2005
3.85. Found: C 75.99, H, 7.23, N, 3.65.
3.2.5. [(2R,4S)-3-Benzoyl-4-benzyl-2-isopropyl-5-oxo-oxazolidin-4-yl]acetic acid ethyl ester
((2R,4S)-17)
The general procedure was followed using 0.51 g (1.58 mmol) of (2R,4S)-12c in 15 mL of THF, 1.9 mL
(1.9 mmol) of LiHMDS and 0.35 mL (3.15 mmol) of ethyl bromoacetate. Purification of the crude product
by flash chromatography (n-hexane:ethyl acetate 8:2) afforded 0.51 g (79% yield) of (2R,4R)-16 as white
= + 6.67 o ( c= 1.0, CHCl3).
20
D
crystals, (recrystallization solvent CH2Cl2-hexane), mp 107.2-108.1 °C.
α
[ ]
(2R,4R)-16 1H NMR (CDCl3) δ 7.59-7.39 (m, 10H), 5.78 (d, J= 3.7 Hz, 1H), 4.16 (q, J= 5.1 Hz, 2H), 3.87
(d, J = 16.8 Hz, 1H), 3.70 (d, J = 13.6 Hz, 1H), 3.37 (d, J = 13.6 Hz, 1H) 2.95 (d, J = 17.6 Hz, 1H) 1.24 (t,
J = 7.1 Hz, 3H), 0.70 (m, 1H), 0.48 (d, J = 7.0 Hz, 3H) 0.03 (d, J= 6.6 Hz, 3H). 13C NMR (CDCl3) δ173.2,
170.8, 169.2, 136.6, 135.0, 130.9, 130.6, 128.9, 128.7, 127.8, 126.2, 94.4, 66.0, 61.3, 42.6, 38.7, 31.2, 18.8,
14.1, 13.0. Anal. Calcd for C24H27NO5: C, 70.40; H, 6.65. N, 3.42 Found: C 70.26, H, 6.75, N, 3.57.
3.2.6. (1S,2’R,4’S)-N-[1-(3-Benzoyl-2-isopropyl-4-methyl-5-oxo-oxazolidin-4-yl)-2-methylpropyl]ben-
zamide ((1S,2’R,4’S)-20)
The general procedure was followed using 0.2 g (0.81 mmol) of (2R,4S)-12c in 15 mL of THF, 0.89 mL
(0.89 mmol) of LiHMDS without electrofile. Purification of the crude product by flash chromatography
(n-hexane:ethyl acetate 8:2) afforded 0.08 g (47% yield) of (1S,2’R,4’S)-20 as white crystals,
= + 31.15 o ( c = 0.5, CHCl3).
20
D
(recrystallization solvent CH2Cl2-hexane), mp 200-202 °C.
α
[ ]
(1S,2’R,4’S)-20 1H NMR (CDCl3) δ 7.50-7.44 (m, 10H) 5.83 (d, J = 2.9 Hz, 1H), 4.76 (d, J = 8.0 Hz, 1H),
1.88 (m, 1H,), 1.74 (s, 1H), 1.37 (m, 1H), 1.10 (d, J= 7.0 Hz, 1H), 1.05 (d, J= 7.0 Hz, 1H), 0.80 (d, J= 7.0
Hz, 1H), 0.78 (d, J = 7.0 Hz, 1H). 13C NMR (CDCl3) δ 173.5, 170.4, 166.9, 135.8, 134.09, 131.6, 131.3,
129.5, 128.7, 127.2, 125.6, 93.3, 66.2, 60.4, 31.4, 21.5, 20.9, 20.0, 18.0, 14.1. Anal. Calcd for C25H30N2O4:
C, 71.07; H, 7.16, N, 6.63. Found: C, 71.25, H, 7.32, N, 6.40.
3.3. General procedure for the methanolysis of (2R,4S)-13-15 and (1S,2’R,4’S)-20
A solution of 1 mmol of adduct in 10 mL of methanolic 2M CF3CO2H was heated in a sealed ampule at
130oC for 72 h. The solution was then allowed to cool to rt, and was concentrated in a rotary evaporator.
The residue was dissolved in 200 mL of CH2Cl2, washed three times with H2O, dried over anh. Na2SO4
and concentrated in the rotary evaporator to afford the crude product that was purified by flash
chromatography (hexane: ethyl acetate, 8:2).
3.3.1. (2S)-2-Benzylamino-2-methyl-3-phenylpropionic acid methyl ester ((2S)-21)

HETEROCYCLES, Vol. 65, No. 1, 2005
73
Derivative ((2R,4S)-13) (100 mg, 0.30 mmol) was hydrolyzed according to the general procedure to afford
85 mg (95 % yield) of (2S)-21 as white crystals, (recrystallization solvent CH2Cl2-hexane), mp 112-114 °C.
o
1
20
D
= + 78.53 ( c = 1.0, CHCl3). H NMR (CDCl3) δ 7.67-7.06 (m, 10H), 6.82 (s, 1H), 3.81 (s, 3H),
α
[ ]
3.71 (d, J = 13.6 Hz, 1H), 3.29 (d, J = 13.6 Hz, 1H), 1.79 (s, 3H). 13C NMR (CDCl3) δ 174.6, 167.0, 136.5,
135.0, 131.6, 129.9, 128.6, 128.4, 127.0, 126.9, 61.7, 52.8, 41.2, 23.5. Anal. Calcd for C18H19NO3: C,
72.71; H, 6.44, N, 4.71. Found: C, 72.49, H, 6.57, N, 4.63.
3.3.2. (2S)-2-Benzylamino-2-methylpent-4-enoic acid methyl ester ((2S)-22)
Derivative ((2R,4S)-14) (77 mg, 0.27 mmol) was hydrolyzed according to the general procedure to afford
58 mg (87 % yield) of (2S)-22 as white crystals, (recrystallization solvent CH2Cl2-hexane), mp 67-68 °C.
= + 9.74 o ( c = 1.0, CHCl3). 1H NMR (CDCl3) δ 7.76-7.39 (m, 5H), 6.94 (s, 1H), 5.68 (m, 1H), 5.12
20
D
α
[ ]
(d, J = 19.0 Hz, 1H), 5.10 (d, J = 9.2 Hz, 1H), 3.80 (s, 3H) 3.08 (dd, J = 13.18 Hz, J = 7.32 Hz, 1H), 2.66
(dd, J = 13.55 Hz, J = 7.32 Hz, 1H), 1.71 (s, 3H). 13C NMR (CDCl3) δ 174.7, 166.5, 134.8, 132.5, 131.6,
128.6, 126.9, 119.6, 60.3, 52.9, 40.8, 22.9. Anal. Calcd for C14H17NO3: C, 68.00; H, 6.93, N, 5.66. Found:
C, 67.90, H, 7.16, N, 5.49.
3.3.3. (2S)-2-Benzylamino-2-methyl-succinic acid dimethyl ester ((2S)-23)
Derivative ((2R,4S)-15) (112 mg, 0.34 mmol) was hydrolyzed according to the general procedure to
o
1
20
D
afford 70 mg (79 % yield) of (2S)-24 as a viscous oil.
= + 4.84 ( c = 1.0, CHCl3). H NMR
α
[ ]
(CDCl3) δ 7.78-7.35 (m, 5H), 3.81 (s, 3H), 3.61 (d, J = 16.5 Hz, 1H), 3.61 (s, 3H), 3.04 (d, J = 16.5 Hz,
13
1H), 1.74 (s, 3H). C NMR (CDCl3) δ 174.2, 171.3, 166.6, 134.5, 131.7, 128.6, 127.1, 58.1, 53.2, 51.9,
40.0, 23.30. Anal. Calcd for C14H17NO4: C, 63.87; H, 6.51, N, 5.32. Found: C, 63.78, H, 6.76, N, 5.53.
3.3.4. (2S,3S)-2,3-Bisbenzoylamino-2,4-dimethylpentanoic acid methyl ester ((2S,3S)-24)
Derivative ((1S,2’R,4’S)-20) (100 mg, 0.24 mmol) was hydrolyzed according to the general procedure to
afford 79 mg (88 % yield) of (2S,3S)-23 as white crystals, (recrystallization solvent CH2Cl2-hexane), mp
1
= -55.4 o ( c = 0.5, CHCl3). H NMR (CDCl3) δ 8.06-7.46 (m, 10H) 4.81 (dd, J = 9.7
20
D
188-190 °C.
α
[ ]
Hz, J = 8.0 Hz, 1H), 3.90 (s, 1H), 1.75 (m, 1H), 1.62 (s, 1H), 0.94 (d, J= 7.0 Hz, 1H), 0.90 (d, J= 7.0 Hz,
1H). 13C NMR (CDCl3) δ 175.8, 167.9, 167.3, 134.3, 134.4, 132.1, 131.5, 128.9, 128.7, 127.3, 127.1, 64.0,
58.9, 53.7, 31.3, 22.0, 20.5, 19.6. Anal. Calcd for C22H26N2O4: C, 69.09; H, 6.85, N, 7.32. Found: C 68.99,
H 6.61, N, 7.16

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HETEROCYCLES, Vol. 65, No. 1, 2005
ACKNOWLEDGEMENTS
We are indebted to Dr. Joseph M. Muchowski for many friendly discussions and to CONACyT for
financial support via grant (J37412E)
REFERENCES AND NOTES
1. α,α-Dialkylated derivatives of proteinogenic amino acids have proven to be efficient inhibitors of those
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Ballesteros, G. C. Trigo, and C. Avendaño, J. Med. Chem., 1983, 26, 1374.
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Org. Chem., 1975, 40, 953.
5. The preparation of enantiopure α,α-dialkylated α-amino acids has recently attracted considerable
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Synthesis: Construction of Chiral Molecules Using Amino Acid, Wiley: New York, 1987, p.20, 78, 267.
[e] R. M. Williams, Synthesis of Optically Active α-amino acids; Pergamon Press, London, 1989; p. 1,
34, 62, 87, 208. [f] Y. Ohfune, S. H. Moon, and M. Horikawa, Pure and Appl. Chem., 1996, 68, 645.
[g] D. Obrecht , C. Abrecht, M. Altorfer, U. Bohdal, A. Grieder, and K. Pfyffer, Helv. Chim. Acta,
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T. Wirth, Angew. Chem., Int. Ed. Engl., 1997, 36, 225. [j] G. Porzi, and S. Sandri, Tetrahedron:
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12468. [l] E. Juaristi, M. Balderas, H. López-Ruiz, V. M. Jiménez-Pérez, M. L. Kaiser-Carril, and Y.
Ramírez-Quirós, Tetrahedron: Asymmetry, 1999, 10, 3493.
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Lanaspa, F. L. Merchan, and T. Tejero, Tetrahedron: Asymmetry, 1998, 9, 629. [c] Y. Aoyagi, M. S.
Chorghade, A. A.Padmapriya, H. Suguna, and S. M. Hecht, J. Org. Chem., 1990, 55, 6291. [d] M.

HETEROCYCLES, Vol. 65, No. 1, 2005
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Otsuka, A. Kittaka, T. Iimori, H. Yamashita, S. Kobayashi, and M. Ohno, Chem. Pharm. Bull., 1985,
33, 509.
7. [a] D. Seebach and J. L. Matthews, Chem. Commun., 1997, 20015. and references cited therein. [b] S.
H. Gellman, Acc. Chem. Res., 1998, 31, 173.
8. For reviews of enantioselective synthesis of β-amino acids see: [a] E. Juaristi; D. Quintana, and J.
Escalante, Aldrichimica Acta, 1994, 27, 3. [c] D. C. Cole, Tetrahedron, 1994, 50, 5917. [d] G.
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14. Owing to the high price of pivaldehyde (100 mL, $ 348.00 USD from Aldrich), have been substituted
this aldehyde with isobutyraldehyde (1.0 L, $13.80 USD from Aldrich) in the synthesis of some chiral
analogues of imidazolidinones: E. Juaristi, H. López-Ruiz, D. Madrigal, Y. Ramírez-Quirós and J.
Escalante, J. Org. Chem., 1998, 63, 4706.
15. Crystallographic data (excluding structure factors) for the structures in this paper have been deposited
with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC
243395 (12a), CCDC 243394 (12b), CCDC 243396 (12c), CCDC 243397 (13), CCDC243398 (16),
CCDC243393 (17), CCDC 243399 (20). Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union, Cambridge CB2 IEZ [fax: +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk].
1
16. A single product was detected by both H and 13C NMR Spectroscopy (400 and 100 MHz,
Respectively).
17. Compare [a] E. Juaristi, D. Quintana, B. Lamatsch, and D. Seebach, J. Org. Chem., 1991, 56, 2553.
[b] D. Seebach, B. Lamatsch, R. Amstutz, A. K. Beck, M. Dobler, M. Egli, R. Fitzi, M. Gautschi, B.
Herradón, P. C. Hidber, J. J. Irwin, R. Locher, M. Maestro, T. Maetzke, A. Mouriño, E. Pfammatter,
D. A. Plattner, C. Schickli, W. B. Schweizer, P. Seiler, G. Stucky, W. Petter, J. Escalante, E. Juaristi,
D. Quintana, C. Miravitlles, and E. Molins, Helv. Chim. Acta, 1992, 75, 913.
18. D. Seebach, A. Sting, and M. Hoffmann, Angew. Chem., Int. Ed. Engl., 1996, 35, 2708.
19. H. C. Brown, G. W. Kramer, A. B. Levy, and M. M. Midland, Organic Synthesis via Boranes; Wiley,
New York, 1975; p. 256.
20. W. C. Still, M. Kahn, and A. Mitra, J. Org. Chem., 1978, 43, 2923.