Enantioselective syntheses of α-phenylalkanamines via intermediate addition of Grignard reagents to chiral hydrazones derived from (R)-(-)-2- aminobutan-1-ol

Article abstract of DOI:10.1016/S0957-4166(98)00217-1

The hydrazine (R)-(-)-28 was obtained in four steps from 2-aminobutan- 1-ol (R)-(-)-11, and reacted with benzaldehyde to give the hydrazone (R)-(- )-29. Nucleophilic addition of various alkyl Grignard reagents to the latter yielded the corresponding trisubstituted hydrazines (R,R)-30a-g in 70-89% yields and having d.e.s=100% (¹H and ¹³C NMR). Catalytic hydrogenolysis of these hydrazines afforded the corresponding (R)(+)-α-phenylalkanamines (R)- (+)-31a-g having e.e.s=90-92% (chiral GPC).

Full text of DOI:10.1016/S0957-4166(98)00217-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2181–2192
Enantioselective syntheses of α-phenylalkanamines via
intermediate addition of Grignard reagents to chiral hydrazones
derived from (R)-(−)-2-aminobutan-1-ol
Patricia Bataille, Michel Paterne and Eric Brown ∗
Laboratoire de Synthèse Organique (ESA-CNRS 6011), Faculté des Sciences, Avenue Messiaen, F-72085 Le Mans Cedex 9,
France
Received 5 May 1998; accepted 26 May 1998
Abstract
The hydrazine (R)-(−)-28 was obtained in four steps from 2-aminobutan-1-ol (R)-(−)-11, and reacted with
benzaldehyde to give the hydrazone (R)-(−)-29. Nucleophilic addition of various alkyl Grignard reagents
to the latter yielded the corresponding trisubstituted hydrazines (R,R)-30a–g in 70–89% yields and having
d.e.s=100% (1H and 13C NMR). Catalytic hydrogenolysis of these hydrazines afforded the corresponding (R)-
(+)-α-phenylalkanamines (R)-(+)-31a–g having e.e.s=90–92% (chiral GPC). © 1998 Elsevier Science Ltd. All
rights reserved.
1. Introduction
The enantioselective addition of organometallic reagents to chiral hydrazones, followed by hy-
drogenolytic cleavage of the N–N bond of the resulting hydrazine, constitutes an attractive method for
the preparation of optically active amines. The general synthetic strategy disclosed by Takahashi and
his coworkers1 as early as 1979 is still in use: the chiral hydrazones are most generally derived from an
enantiopure secondary amine, by N-nitrosation followed by reduction of the NO group into a NH2 group
and reaction with an appropriate aldehyde. Thus, the hydrazone derived from (−)-N-aminoephedrine
and benzaldehyde reacted with organolithium or Grignard reagents to give chiral hydrazines having
diastereomeric excesses (d.e.s) near 100%. Hydrogenolysis of the hydrazines yielded the corresponding
(R)-α-phenylalkanamines in good enantiomeric purity despite the fact that some degree of racemization
presumably occurred during the hydrogenolysis step. By this procedure, Takahashi and his coworkers
obtained the amines 1–4 (Scheme 1), which were characterized as their crystalline N-salicylidene
∗
Corresponding author. E-mail: lso@lola.univ-lemans.fr
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00217-1

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derivatives, the latter having e.e.s=97.6, 96, 76 and 40%, respectively.1 Along similar lines, the same
group used the hydrazine derived from (S)-N-methylvalinol and obtained poor yields of the amines (S)-1
and (S)-2, whose crystalline salicylidene derivatives had e.e.s=99–100%.2
Scheme 1.
Starting from (S)-proline, Enders and coworkers3 obtained the hydrazine 5 (SAMP reagent) via a
4–5 step sequence and prepared the corresponding hydrazones from diversified aromatic and aliphatic
aldehydes. Addition of various organometallic (including alkyllithium) reagents to the above hydrazones,
followed by hydrogenolysis using H2/Raney nickel, afforded chiral amines whose e.e.s were within
the range 81–94%. In the course of parallel studies, Denmark and coworkers4 described the addition
of organocerium reagents to the hydrazones derived from (S)-6 and various aldehydes. The addition
proceeded in good yields (67–81%) and with high d.e.s (>86%). Trapping the intermediate N-metallated
hydrazine with methyl chloroformate gave carbamates whose N–N bonds were smoothly cleaved by
lithium in liquid ammonia, thus affording the desired product 7 with no loss of enantiomeric purity. In
1996, Kim and Choi5 reported the synthesis of the chiral SAMI reagent (S)-8 in four steps from (S)-
indoline-2-carboxylic acid. The hydrazones (S)-9 derived from (S)-8 and benzaldehyde or butanal were
treated with three equivalents of an organolithium reagent (such as n-BuLi or PhLi) at −78°C and this
afforded the corresponding hydrazines 10 in good yields (77–88%) and with high d.e.s (94–98%). The
N–N bond of two trisubstituted hydrazines (amongst all those prepared) was cleaved by hydrogenation at
room temperature under atmosphere using a Pd(OH)2–C catalyst, in DME/H2O containing hydrochloric
acid. No racemization was observed in either of these cases.
2. Results and discussion
For some time now, we have considered using simple derivatives of (S)-(+) or (R)-(−)-2-aminobutan-
1-ol 11 (Scheme 2) as new chirality transfer reagents in asymmetric synthesis.6 Indeed, racemic amino-
butanol 11 is a cheap chemical which can be easily resolved into both its enantiomers on the industrial
scale.7 The present study is devoted to the asymmetric synthesis of chiral amines from hydrazines
derived from (R)-(−)-2-aminobutan-1-ol (R)-(−)-11, using the general strategy disclosed in the early
works of Takahashi and coworkers.1 Firstly, the known morpholine (R)-(+)-138 was obtained by N-
alkylation of aminobutan-1-ol (R)-(−)-11 by 2-bromoethanol, followed by acid catalyzed intramolecular
dehydration of the intermediate diol (R)-(−)-12. Treatment of (R)-(+)-13 with sodium nitrite in aqueous
hydrochloric acid gave the N-nitrosoamine (R)-(−)-14 (98.8%), which was next transformed into the
hydrazine (R)-(−)-15 (94%) upon reduction with LiAlH4 in ether. The hydrazones 16–18 were prepared
in 52.8–97.7% yields by reaction of (R)-(−)-15 with 4-nitrobenzaldehyde, 2-methoxybenzaldehyde and
heptanal, respectively, in the presence of anhydrous MgSO4 in dry dichloromethane at room temperature

P. Bataille et al. / Tetrahedron: Asymmetry 9 (1998) 2181–2192
2183
for 18 hours. However, all attempts failed to obtain the required trisubstituted hydrazines upon treatment
of the above hydrazones 16–18 with excess organolithium or Grignard reagents.
Scheme 2.
In the following study, N-trifluoroethyl aminobutanol (R)-(−)-196c was similarly transformed into
the hydrazine (R)-(−)-21 via intermediate formation of the N-nitrosoamine (R)-(−)-20. The hydrazone
(R)-(−)-22 derived from (R)-(−)-21 and benzaldehyde was obtained in 72.5% yield using the technique
mentioned above. The hydrazone (R)-(−)-22 reacted with 10 equivalents of n-pentylmagnesium bromide
in refluxing ether and gave the desired hydrazine (+)-23 in 79% yield. Addition of other Grignard reagents
RMgX (where R=Et, n-Pr, n-Bu, n-hexyl) to the hydrazone (R)-(−)-22 similarly gave the corresponding
trisubstituted hydrazines analogous to (+)-23, in yields ranging from 55 to 78%. Examination of the high
1
resolution H and 13C NMR spectra of these five hydrazines revealed that they were diastereomerically
pure (d.e.=100%).9 However, all attempts failed to cleave the N–N bond of (+)-23 and its analogues under
a wide array of hydrogenolytic procedures. These failures might be due to steric hindrance and/or to
strong, stabilizing hydrogen bonding between a fluorine atom and the nitrogen-bound hydrogen atom.10
Reaction of the hydrazine (R)-(−)-21 with aliphatic aldehydes RCHO afforded the heterocyclic
compounds 24 rather than the requisite hydrazones. Reaction of compounds of type 24 with alkyl
Grignard reagents led to degradation products.9 Starting from the O-methyl derivative of aminobutanol
(R)-(−)-11, the O-methyl hydrazone 25 was prepared in the usual way. However, this compound did not
react with n-BuMgBr or n-BuLi/CeCl3 in a variety of experimental conditions.9 Therefore, it seems that
the presence of a free hydroxy group is necessary here for the nucleophilic addition to occur.
Considering the above results, we finally extended our study to the N-methyl derivative (R)-(−)-266a
of aminobutanol (R)-(−)-11 (Scheme 3). N-Nitrosation gave (R)-(+)-27 (74.7%). Reduction of the latter
with LiAlH4 led to the hydrazine (R)-(−)-28 (88%), which was transformed into the hydrazone (R)-(−)-
29 (76.4%) upon reaction with benzaldehyde in the presence of anhydrous MgSO4 in dichloromethane.
The hydrazone 29 was next treated with a tenfold molar excess of various n-alkyl Grignard reagents in

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refluxing ether for 15 hours. This led to the corresponding seven trisubstituted liquid hydrazines (R,R)-
30a–g in yields ranging between 70 and 89% in all cases but one. Using smaller quantities of Grignard
reagents (i.e. fivefold molar excess) gave mixtures of starting hydrazone 29 and trisubstituted hydrazine
1
30, the latter having rather average d.e.s. Examination of the high resolution H and 13C NMR spectra
of the hydrazines 30a–g (prepared with a tenfold excess of Grignard reagents) revealed that they were
diastereomerically pure (d.e.=100% in all cases). The absolute (R,R) configuration of the hydrazines
30a–g was assigned on the basis of the tentative mechanism depicted in Scheme 3.
Scheme 3.
Being rather unstable, the hydrazines 30a–g were used directly in the following step without purifi-
cation. Thus hydrogenolysis of the crude colourless hydrazines 30a–g was carried out in the presence
of concentrated hydrochloric acid and 10% Pd–C catalyst under hydrogen (6 bar) at ca. 60°C for 16
hours. This afforded the crude amines (R)-31a–g which were purified by chromatography over silica
gel in the presence of triethylamine in order to avoid racemization.11 The amines (R)-(+)-31a,12 (S)-
(−)-31b13 and (S)-(−)-31c14 are known compounds, which enabled us to confirm the (R,R) absolute
configuration allotted to the starting hydrazines 30. We assume that the other amines 30d–g also have the
(R) configuration. The latter amines were described in racemic form only.15 Gas chromatography using
a chiral column revealed that the e.e.s of the amines 31a,c–g were in the range 90–92%, which implies
that some racemization must have occurred during the final hydrogenolysis step.1a
3. Experimental section
3.1. General
1
IR spectra were recorded with Nicolet 5DX and Genesis (Mattson) spectrophotometers. H NMR
(400 MHz) and 13C NMR (100 MHz) spectra were recorded with a Bruker AC 400 spectrometer, using
Me4Si as an internal standard. Melting points were determined with a Reichert microscope. Optical
rotations were measured at 26°C with a Perkin–Elmer 241 micropolarimeter. Elemental analyses were

P. Bataille et al. / Tetrahedron: Asymmetry 9 (1998) 2181–2192
2185
carried out at the I.C.S.N. (C.N.R.S., Gif-sur-Yvette). Chiral CPG experiments were carried out with
a Hewlett Packard HP 6890 chromatograph equipped with a Restek beta DEX-sm 30 m column. (R)-
(−)-2-Aminobutan-1-ol, [α]D −10.0 (neat), was kindly provided by SmithKline Beecham Laboratories
(Mayenne).
3.2. (R)-(−)-2-[(2-Hydroxyethyl)amino]-butan-1-ol (R)-(−)-12
2-Bromoethanol (15.6 g; 125 mmol) in toluene (45 ml) was added dropwise to (R)-(−)-2-aminobutan-
1-ol (R)-(−)-11 (11.12 g; 125 mmol) in toluene (45 ml). After heating under reflux for 18 h, solid Na2CO3
(26.5 g; 250 mmol) was added. After refluxing for a further 18 h, the mixture was filtered through Celite,
the solid material was extracted with dichloromethane and the combined organic phases were evaporated
under reduced pressure. Vacuum distillation of the residue gave the diol (R)-(−)-12 as a very viscous
colourless oil (8.70 g; 52.4%), b.p.0.5=110–120°C and [α]D −25.0 (c 1.2, MeOH). Lit.8 [α]D −17.85 (c
2.8, MeOH). 1H NMR (CDCl3) δ: 0.92 (t, 3H); 1.30–1.60 (m, 2H); 2.52–2.58 (m, 1H); 2.67–2.86 (m,
2H); 3.34–3.42 (dd, 1H); 3.63–3.70 (m, 3H). 13C NMR (CDCl3) δ: 9.94 (q), 23.35 (t), 48.07 (t), 59.96
(d), 60.66 (t), 62.42 (t).
3.3. (R)-(+)-3-Ethylmorpholine (R)-(+)-13
Concentrated sulphuric acid (8.9 mmol) was slowly added to the diol (R)-(−)-12 (12.12 g; 91 mmol)
at 0°C (ice bath). After heating at 160°C for 5 h, the mixture was cooled, diluted with a little water
and made basic by cautious addition of sodium hydroxide pellets. The crude morpholine was recovered
by continuous extraction with ether. Distillation gave the purified morpholine (R)-(+)-13 as a colourless
1
oil (7.90 g; 75.8%), b.p.10=50–55°C and [α]D +9.8 (c 0.87, MeOH). Lit.8 [α]D −2.8 (neat). H NMR
(CDCl3) δ: 0.92 (t, 3H); 1.10–1.40 (m, 2H); 1.70 (s, 1H); 2.68 (m, 1H); 2.80–3.00 (m, 2H); 3.13 (t, 1H);
3.45–3.52 (m, 1H); 3.80 (d, 2H). 13C NMR (CDCl3) δ: 10.57 (q), 26.03 (t), 46.87 (t), 56.87 (d), 68.20
(t), 73.18 (t).
3.4. (R)-(−)-3-Ethyl-4-nitrosomorpholine (R)-(−)-14
Sodium nitrite (18.78 g; 0.27 mol) in water (20 ml) was added dropwise to a mixture of 3-ethyl-
morpholine (R)-(+)-13,8 [α]D +9.8 (c 0.87, MeOH) (10.45g; 90 mmol), concentrated hydrochloric acid
(14 ml) and crushed ice (17 g). After stirring for a further 14 h at room temperature, dichloromethane (40
ml) was added, and the separated aqueous phase was extracted three more times with dichloromethane
(3×20 ml). The combined organic extracts were dried (MgSO4), filtered and evaporated under reduced
pressure, thus giving the nitrosomorpholine (R)-(−)-14 (12.97 g; 98.8%) as a yellow oil, [α]D −116.7
(c 0.98, MeOH) which was directly used in the next reduction step, without further purification. This
compound was pure enough to give satisfactory microanalytical data. Anal. calc. for C6H12N2O2: C,
1
49.99; H, 8.39; N, 19.43. Found: C, 49.78; H, 8.17; N, 19.06. IR (film): 1444 (NO) cm−1. H NMR
(CDCl3) δ: major conformer, 0.96 (t, 3H); 1.40–2.10 (m, 2H); 3.08–3.15 (m, 1H); 3.37–4.62 (m, 6H);
minor conformer, 0.84 (t, 3H); 1.40–2.10 (m, 2H); 3.37–4.62 (m, 6H); 4.90–4.93 (m, 1H). 13C NMR
(CDCl3) δ: major conformer, 9.82 (q), 22.24 (t), 36.84 (t), 60.34 (d), 65.53 (t), 69.60 (t); minor conformer,
9.92 (q), 21.04 (t), 46.34 (t), 49.96 (d), 66.93 (t), 67.82 (t).

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3.5. (R)-(−)-4-Amino-3-ethylmorpholine (R)-(−)-15
A suspension of LiAlH4 (0.790 g; 20.8 mmol) in dry ether (150 ml) was cooled down to −10°C
and treated with dropwise addition of the nitrosoamine (R)-(−)-14 (1.0 g; 6.9 mmol) in dry ether (25
ml). After stirring at room temperature for 6 h, the mixture was quenched with methanol (2.1 ml) and
water (4.1 ml). The suspension was filtered and the filtrate was dried (MgSO4) and evaporated under
reduced pressure, thus giving the hydrazine (R)-(−)-15 as a colourless oil (0.843 g; 94%), [α]D −44 (c
1
1.12, MeOH) which was directly used in the next step without further purification. H NMR (CDCl3) δ:
0.90 (t, 3H); 1.11–1.41 (m, 1H); 1.82–2.0 (m, 1H); 2.03–2.10 (m, 1H); 2.43 (dt, 1H); 2.99–3.0 (dt, 3H);
3.24–3.29 (dd, 1H); 3.63–3.68 (dt, 1H); 3.80–3.87 (m, 2H). 13C NMR (CDCl3) δ: 9.96 (q); 21.43 (t);
59.68 (t); 67.25 (t); 67.70 (d); 70.61 (t).
3.6. General procedure for the preparation of hydrazones derived from (R)-(−)-15
A mixture of hydrazine (R)-(−)-15 (1–4 mmol), aldehyde (1 equiv.) and anhydrous MgSO4 (1 molar
equiv.) in dry dichloromethane (5 ml) was stirred overnight at room temperature. The suspension was
filtered and the filtrate was treated with aqueous saturated sodium bisulphite solution for 2 h under
stirring. The hydrazone was extracted with dichloromethane and the crude product was purified by
column chromatography on silica gel (eluent: cyclohexane/ether 9/1 and elution gradient).
3.7. Hydrazone (R)-(−)-16 derived from 4-nitrobenzaldehyde
Yellow crystals (52.8% yield), m.p.=74–76°C and [α]D −45.3 (c 1.0, MeOH). Anal. calc. for
C13H17N3O3: C, 59.34; H, 6.51. Found: C, 59.47; H, 6.69. IR (Nujol): 3106–3079 (CH_); 1594 (C_N)
cm−1. 1H NMR (CDCl3) δ: 0.98 (t, 3H); 1.70–1.90 (m, 2H); 3.10–3.16 (m, 1H); 3.26–3.31 (sext, 1H);
3.32–3.38 (m, 1H); 3.71–3.75 (dd, 1H); 3.84–3.94 (m, 3H); 7.44 (s, 1H); 7.68 (d, 2H); 8.18 (d, 2H).
3.8. Hydrazone (R)-(−)-17 derived from 2-methoxybenzaldehyde
Pale yellow oil (74% yield), [α]D −6.9 (c 1.0, MeOH). Anal. calc. for C14H20N2O2: C, 67.72; H, 8.12;
1
N, 11.28. Found: C, 67.81; H, 8.33; N, 11.14. IR (film): 3106–3079 (CH_) cm−1. H NMR (CDCl3)
δ: 0.96 (t, 3H); 1.64–1.96 (m, 2H); 2.97–3.03 (quint, 1H); 3.10–3.14 (m, 1H); 3.28–3.34 (quint, 1H);
3.64–3.69 (dd, 1H); 3.84 (s, 3H); 3.85–3.90 (m, 3H); 6.86–6.88 (d, 1H); 6.94 (t, 1H); 7.24 (m, 1H);
7.87–7.89 (dd, 1H); 7.93 (s, 1H).
3.9. Hydrazone (R)-(+)-18 derived from heptanal
Orange oil (97.7% yield), [α]D +143 (c 1.70, MeOH). Anal. calc. for C13H26N2O: N, 12.38. Found:
1
N, 12.21. IR (film): 1654 (C_N) cm−1. H NMR (CDCl3) δ: 0.88 (t, 3H); 0.90 (t, 3H); 1.25–1.80 (m,
10H); 2.22–2.28 (dt, 2H); 2.75–2.81 (m, 1H); 2.84–2.89 (m, 1H); 2.94–2.99 (m, 1H); 3.54–3.59 (dd,
1H); 3.81–3.86 (m, 3H); 7.07 (t, 1H).
3.10. (R)-(−)-N-Nitroso-N-(2,2,2-trifluoroethyl)-2-aminobutanol-1-ol (R)-(−)-20
Sodium nitrite (1.84 g; 27 mmol) in water (2 ml) was added dropwise at 0°C and under vigorous
stirring to a mixture of trifluoroethylamine (R)-(−)-19,6c [α]D −10.2 (c 1.02, MeOH) (1.52 g; 9.0

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2187
mmol), concentrated hydrochloric acid (1.3 ml) and crushed ice (5 g). After stirring overnight at
room temperature, dichloromethane (10 ml) was added, and the separated aqueous phase was extracted
twice more with dichloromethane (2×10 ml). The combined organic extracts were dried (MgSO4),
filtered and evaporated under reduced pressure. Chromatography of the residue over silica gel (eluent:
cyclohexane/ether 9/1 and elution gradient) gave the N-nitrosamine (R)-(−)-20 as a yellow oil (1.70 g;
94.4%), [α]D −37.6 (c 2.7, MeOH). Anal. calc. for C6H11F3N2O2: C, 36.00; H, 5.54; N, 14.00. Found:
C, 35.79; H, 5.48; N, 13.91. IR (film): 3300 (OH) and 1444 (N_O) cm−1. 1H NMR (CDCl3) δ: 0.99 (t,
3H); 1.80–2.05 (m, 2H); 2.54 (t, 1H); 3.90–4.05 (m, 2H); 4.10 (dq, 1H); 4.26–4.32 (m, 1H); 4.50 (dq,
1H). 19F NMR (CDCl3) δ: −70.16 (conformer A, 11.75%); −68.01 (conformer B, 88.25%).
3.11. (R)-(−)-2-[1-(2,2,2)-Trifluoroethyl)hydrazino]butan-1-ol (R)-(−)-21
A suspension of LiAlH4 (4.0 g; 105 mmol) in dry ether (150 ml) was cooled to 0°C and treated
dropwise by the N-nitrosoamine (R)-(−)-20 (6.0 g; 30 mmol) in dry ether (150 ml). After stirring at room
temperature for 6 h, the mixture was quenched at −10°C by methanol, followed by water (4 ml), 15%
NaOH solution (4 ml) and finally water (12 ml). The suspension was filtered and the filtrate was dried
(MgSO4) and evaporated under reduced pressure. The residual orange oil was distilled under atmospheric
pressure, thus giving the hydrazine (R)-(−)-21 (3.60 g; 64.5%), b.p.=98–103°C and [α]D −3.8 (c 1.3,
1
MeOH). IR (film): 3357 (OH and NH2) cm−1. H NMR (CDCl3) δ: 0.96 (t, 3H); 1.40–1.54 (m, 2H);
2.60–2.68 (m, 1H); 3.29 (q, 2H); 3.63 (dd, 1H); 3.71 (dd, 1H). 13C NMR (CDCl3) δ: 11.06 (q); 18.29 (t);
60.87 (t); 62.91 (t); 69.40 (d); 126.64 (s). 19F NMR (CDCl3) δ: −71.00 ppm.
3.12. Benzenecarbaldehyde N-[(1R)-1-(hydroxymethyl)propyl]-N-(2,2,2-trifluoroethyl)hydrazone
(R)-(−)-22
A mixture of hydrazine (R)-(−)-21 (2.55 g; 13.7 mmol), benzaldehyde (1.67 g; 15.7 mmol) and
anhydrous MgSO4 (1.60 g; 15.7 mmol) in dry dichloromethane (50 ml) was stirred overnight at room
temperature. The mixture was then filtered and evaporated under reduced pressure. The oily residue was
chromatographed over silica gel (eluent: cyclohexane/ether=9/1 and elution gradient), thus affording the
hydrazone (R)-(−)-22 as a colourless viscous oil (72.5%), [α]D −135 (c 0.8, MeOH). Anal. calc. for
C13H17F3N2O: N, 10.21. Found: N, 10.29. MS calc. for C13H17F3N2O: M, 274.1292. Found: 274.1292.
1
IR (film): 3407 (OH), 3062 (CH_) and 1594–1569 (C_N) cm−1. H NMR (CDCl3) δ: 0.96 (t, 3H);
1.60–1.85 (2 sept., 2H); 2.47 (s, 1H); 3.20 (dq, 1H); 3.80–4.0 (m, 4H); 7.24–7.35 (m, 3H); 7.45 (s, 1H);
7.52 (d, 2H). 13C NMR (CDCl3) δ: 10.27 (q); 22.95 (t); 53.52 (t); 64.58 (t); 70.38 (d); 124.15 (s); 125.93
(d); 128.16 (d); 128.63 (d); 133.31 (d); 135.95 (s). 19F NMR (CDCl3) δ: −70.15 ppm.
3.13. 2-[2-(1-Phenylhexyl)-1-(2,2,2-trifluoroethyl)hydrazino]butan-1-ol (+)-23 : a typical procedure for
the addition of alkyl Grignard reagents to the hydrazone (R)-(−)-22
1-Bromopentane (1.36 ml; 10.9 mmol) in dry ether (15 ml) was added to magnesium chips (0.266 g;
10.9 mmol) under an inert atmosphere. After refluxing for 3 h, the mixture was cooled to 0°C and treated
dropwise by the hydrazone (R)-(−)-22 (0.300 g; 1.09 mmol) in dry ether (10 ml). The mixture was then
refluxed for 17 h. After cooling to −10°C, water was added and the resulting medium was filtered through
Celite. The aqueous phase was separated, saturated with NaCl and extracted once more with ether. The
organic extracts were pooled, dried (MgSO4) and evaporated under reduced pressure. The residual orange
oil was chromatographed over silica gel (eluent: cyclohexane/ether=9/1 and elution gradient), thus giving

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the hydrazine (+)-23 as a pale yellow oil (0.300 g; 79%), [α]D +8.14 (c 1.29, MeOH) and d.e.=100%
1
(13C and 19F NMR). MS calc. for C18H29F3N2O: M, 346.2318. Found: 346.2238. H NMR (CDCl3)
δ: 0.81–0.86 (m, 6H); 1.0–1.6 (m, 10H); 1.90–2.0 (m, 1H); 2.50–2.70 (m, 1H); 3.18–3.24 (dd, 1H);
3.33–3.39 (dd, 1H); 3.54–3.59 (dd, 1H); 3.69–3.76 (m, 2H); 7.10–7.31 (m, 5H). 13C NMR (CDCl3) δ:
10.76 (q), 13.57 (q), 17.23 (t), 22.11 (t), 25.29 (t), 31.40 (t), 33.73 (t), 55.46 (t), 62.67 (t), 63.00 (d), 66.76
(d), 127.02 (s), 125.26 (d), 127.55 (d), 128.115 (d), 142.07 (s) (single diastereomer). 19F NMR (CDCl3)
δ: −70.268 (single diastereomer).
3.14. (R)-(+)-N-Methyl-N-nitroso-2-aminobutan-1-ol (R)-(+)-27
Sodium nitrite (10.1 g; 147 mmol) in water (20 ml) was added dropwise at 0°C to a mixture of amine
(R)-(−)-26,6a [α]D −31.7 (c 3.9, MeOH) (5.0 g; 49.0 mmol), concentrated hydrochloric acid (7 ml)
and crushed ice (27 g). After stirring overnight at room temperature, the mixture was extracted with
dichloromethane. The organic phase was dried (MgSO4), evaporated under reduced pressure and the oily
residue was chromatographed over silica gel (eluent: cyclohexane/ether=7/3 and elution gradient), thus
giving the N-nitrosoamine (R)-(+)-27 as a yellow liquid (4.83 g; 74.7%), [α]D +19.9 (c 1.65, MeOH).
Anal. calc. for C5H12N2O2: C, 45.44; H, 9.15; N, 21.2. Found: C, 45.44; H, 9.17; N, 21.17. IR (film):
3421 (OH) and 1461–1430 (N_O) cm−1. 1H NMR (CDCl3) δ: 0.92 (t, 3H); 1.60–1.80 (m, 2H); 3.02 (s,
3H); 3.70–3.80 (m, 2H); 4.40–4.50 (m, 1H) 13C NMR (CDCl3) δ: 10.46 (q), 22.07 (t), 29.38 (q), 62.91
(t), 67.46 (d).
3.15. (R)-(−)-2-(1-Methylhydrazino)butan-1-ol (R)-(−)-28
A suspension of LiAlH4 (1.33 g; 35 mmol) in dry ether (100 ml) was cooled to 0°C and treated drop-
wise with the N-nitrosoamine (R)-(+)-27 (1.32 g; 10 mmol) in dry ether (20 ml). After stirring overnight
at room temperature, the excess hydride was destroyed by addition of methanol (4 ml) and water (7
ml). The suspension was filtered and the solids were extracted several times with dichloromethane. The
combined organic extracts were dried (MgSO4) and evaporated under reduced pressure thus affording the
hydrazine (R)-(−)-28 as a colourless oil (1.04 g; 88%), [α]D −21.6 (c 1.1, MeOH), which was used in the
1
next step without further purification. H NMR (CDCl3) δ: 0.92 (t, 3H); 1.20–1.40 (m, 2H); 2.30–2.40
(m, 1H); 2.56 (s, 3H); 3.0–3.50 (m, 2H); 3.59–3.64 (dd, 1H); 3.70–3.74 (dd, 1H). 13C NMR (CDCl3) δ:
10.71 (q), 17.36 (t), 47.38 (q), 63.77 (t), 68.12 (d).
3.16. Benzenecarbaldehyde N-[1-hydroxymethyl)propyl]-N-methylhydrazone (R)-(−)-29
Anhydrous magnesium sulphate (1.7 g; 16.9 mmol) was added to a solution of hydrazine (R)-(−)-28
(2.0 g; 16.9 mmol) and benzaldehyde (1.7 ml; 16.9 mmol) in dichloromethane (10 ml) and the mixture
was stirred overnight at room temperature. After filtration and evaporation of the solvent, the residue
was stirred for 2 h with aqueous saturated sodium hydrogen sulphite solution. The hydrazone was
next extracted with dichloromethane. The crude product was chromatographed over silica gel (eluent:
cyclohexane/ether=9/1), thus giving the hydrazone (R)-(−)-29 as a colourless oil (2.66 g; 76.4%), [α]D
−25.4 (c 1.04, MeOH). Anal. calc. for C12H18N2O: C, 69.87; H, 8.79; N, 13.58. Found C, 69.85; H,
1
8.73; N, 13.61. IR (film): 3316 (OH) and 1585–1556 (C_N) cm−1. H NMR (CDCl3) δ: 0.93 (t, 3H);
1.50–1.80 (m, 2H); 2.97 (s, 3H); 3.10–3.30 (m, 1H); 3.80–3.90 (m, 2H); 7.19–7.33 (m, 4H); 7.51 (d, 2H).
13C NMR (CDCl3) δ: 11.03 (q); 22.13 (t), 37.04 (q), 63.86 (t), 69.66 (d), 125.36 (2d), 127.18 (d), 128.54
(2d), 131.04 (d), 136.92 (s).

P. Bataille et al. / Tetrahedron: Asymmetry 9 (1998) 2181–2192
2189
3.17. General procedure for the addition of alkyl Grignard reagents to the hydrazone (R)-(−)-29:
preparation of the hydrazines 30a–g
Magnesium chips (10 equiv.) were added to an alkyl bromide (10 equiv.) in dry ether. After refluxing
for 3 h, the mixture was cooled to −10°C and treated dropwise by the hydrazone (R)-(−)-29 (1 equiv.)
in dry ether. After stirring under reflux for 16 h, the mixture was cooled to −10°C and hydrolyzed with
brine. After filtration through Celite, the aqueous phase was decanted and extracted three times more
with ether. The organic extracts were pooled and evaporated under reduced pressure. The residue was
treated with aqueous 50% hydrochloric acid solution. The mixture was washed three times with pentane,
then made basic with 32% aqueous ammonia and finally extracted three times with ether. The combined
ether extracts were dried (MgSO4) and evaporated under reduced pressure, thus leading to the required
hydrazine 30 which was used directly in the next hydrogenolysis step, without further purification. The
hydrazines 30a–g are unstable colourless oils.
3.18. (R,R)-(+)-2-[1-Methyl-2-(1-phenylpropyl)hydrazono]butan-1-ol (R,R)-(+)-30a
Starting from magnesium (0.471 g), bromoethane (1.45 ml) in ether (20 ml) and the hydrazone (R)-
(−)-29 (0.40 g; 1.94 mmol) in ether (5 ml), the above procedure led to the hydrazine (R,R)-(+)-30a (0.408
g; 89%), [α]D +10.0 (c 1.15, MeOH) and d.e.=100% (1H and 13C NMR). 1H NMR (CDCl3) δ: 0.77 (t,
3H); 0.84 (t, 3H); 1.20–2.0 (m, 4H); 2.40 (s, 3H); 2.40–2.50 (m, 1H); 2.80–3.0 (m, 2H); 3.37–3.46 (dd,
1H); 3.60–3.66 (dd, 1H); 3.65–3.72 (dd, 1H); 7.25–7.36. 13C NMR (CDCl3) δ: 11.03 (q), 11.38 (q),
17.76 (t), 28.26 (t), 40.67 (q), 63.51 (t), 64.78 (d), 68.63 (d), 128.08 (d), 128.27 (2d), 128.51 (2d), 144.76
(s).
3.19. (R,R)-(+)-2-[1-Methyl-2-(1-phenylbutyl)hydrazono]butan-1-ol (R,R)-(+)-30b
Starting from magnesium (0.236 g), 1-bromopropane (0.882 ml) in ether (10 ml) and the hydrazone
(R)-(−)-29 (0.200 g; 0.97 mmol) in ether (2 ml), the above procedure led to the hydrazine (R,R)-(+)-30b
1
(0.172 g; 70.8%), [α]D +6.8 (c 1.33, MeOH) and d.e.=100% (1H and 13C NMR). H NMR (CDCl3)
δ: 0.84 (t, 3H); 0.87 (t, 3H); 1.0–1.80 (m, 6H); 2.44 (s, 3H); 2.44–2.50 (m, 1H); 3.20–3.33 (m, 1H);
3.38–3.42 (dd, 1H); 3.61–3.65 (dd, 1H); 3.76–3.79 (dd, 1H); 7.10–7.40 (m, 5H). 13C NMR (CDCl3) δ:
10.74 (q), 13.96 (q), 17.97 (t), 19.33 (t), 36.57 (t), 39.48 (q), 62.61 (t), 62.92 (d), 67.52 (d), 127.66 (d),
127.94 (2d), 128.40 (2d), 141.36 (s).
3.20. (R,R)-(+)-2-[1-Methyl-2-(1-phenylpentyl)hydrozono]butan-1-ol (R,R)-(+)-30c
Starting from magnesium (0.471 g), 1-bromobutane (2.08 ml) in ether (20 ml), and the hydrazone
(R)-(−)-29 (0.400 g; 1.94 mmol) in ether (5 ml), the above procedure led to the hydrazine (R,R)-(+)-30c
1
(0.360 g; 70.3%), [α]D +5.0 (c 1.08, MeOH) and d.e.=100% (1H and 13C NMR). H NMR (CDCl3)
δ: 0.83 (t, 3H); 0.84 (t, 3H); 1.0–1.80 (m, 8H); 2.44 (s, 3H); 2.30–2.50 (m, 1H); 3.38–3.42 (dd, 1H);
3.61–3.64 (dd, 1H); 3.74–3.77 (dd, 1H), 7.10–7.40 (m, 5H). 13C NMR (CDCl3) δ: 10.91 (q), 13.95 (q),
17.41 (t), 22.72 (t), 28.42 (t), 34.70 (t), 40.15 (q), 62.86 (d), 63.08 (t), 68.20 (d), 127.25 (d), 127.76 (2d),
128.25 (2d), 143.05 (s).

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P. Bataille et al. / Tetrahedron: Asymmetry 9 (1998) 2181–2192
3.21. (R,R)-(−)-2-[1-Methyl-2-(1-phenylhexyl)hydrazono]butan-1-ol (R,R)-(−)-30d
Starting from magnesium (0.471 g), 1-bromopentane (2.4 ml) in ether (20 ml), and the hydrazone
(R)-(−)-29 (0.400 g; 1.94 mmol) in ether (5 ml), the above procedure led to the hydrazine (R,R)-(−)-30d
(0.44 g; 81.4%), [α]D −0.8 (c 1.2, MeOH) and d.e.=100% (1H and 13C NMR). 1H NMR (CDCl3) δ: 0.82
(t, 3H); 0.83 (t, 3H); 1.0–1.80 (m, 10H); 2.43 (s, 3H); 2.47–2.50 (m, 1H); 3.34–3.44 (dd, 1H); 3.59–3.66
(dd, 1H); 3.72–3.79 (dd, 1H); 7.20–7.40 (m, 5H). 13C NMR (CDCl3) δ: 10.89 (q), 13.95 (q), 17.38 (t);
22.47 (t), 25.89 (t), 31.84 (t), 34.92 (t), 40.16 (q), 62.86 (d), 63.08 (t), 68.17 (d), 127.24 (d), 127.75 (2d),
128.24 (2d), 143.02 (s).
3.22. (R,R)-(−)-2-[1-Methyl-2-(1-phenylheptyl)hydrazono]butan-1-ol (R,R)-(−)-30e
Starting from magnesium (0.238 g), 1-bromohexane (1.36 ml) in ether (10 ml), and the hydrazone
(R)-(−)-29 (0.200 g; 0.97 mmol) in ether (2 ml), the above procedure led to the hydrazine (R,R)-(−)-30e
(0.128 g; 45.2%), [α]D −4.3 (c 0.8, MeOH) and d.e.=100% (1H and 13C NMR). 1H NMR (CDCl3) δ:
0.82–0.86 (m, 6H); 1.10–2.0 (m, 12H); 2.43 (s, 3H); 2.40–2.50 (m, 1H); 3.37–3.41 (dd, 1H); 3.61–3.64
(dd, 1H); 3.74–3.77 (dd, 1H); 7.10–7.40 (m, 5H). 13C NMR (CDCl3) δ: 10.39 (q), 13.48 (q), 16.92 (t),
22.02 (t), 25.70 (t), 28.81 (t), 34.47 (t), 39.65 (q), 62.38 (d), 62.58 (t), 69.12 (d), 126.76 (d), 127.25 (2d),
127.75 (2d), 143.27 (s).
3.23. (R,R)-(−)-2-[1-Methyl-2-(1-phenyloctyl)hydrazono]butan-1-ol (R,R)-(−)-30f
Starting from magnesium (0.238 g), 1-bromoheptane (1.35 ml) in ether (10 ml), and the hydrazone
(R)-(−)-29 (0.200 g; 0.97 mmol) in ether (2 ml), the above procedure led to the hydrazine (R,R)-(−)-30f
1
(0.208 g; 70%), [α]D −2.8 (c 1.07, MeOH) and d.e.=100% (1H and 13C NMR). H NMR (CDCl3) δ:
0.83 (t, 3H); 0.85 (t, 3H); 1.10–1.90 (m, 14H); 2.43 (s, 3H); 2.40–2.50 (m, 1H); 3.37–3.41 (dd, 1H);
3.61–3.64 (dd, 1H); 3.74–3.77 (dd, 1H); 7.10–7.40 (m, 5H). 13C NMR (CDCl3) δ: 10.91 (q), 14.03 (q),
17.44 (t), 22.57 (t), 26.27 (t), 29.15 (t), 29.64 (t), 31.75 (t), 35.00 (t), 40.18 (q), 62.90 (d), 62.96 (t), 68.22
(d), 127.27 (d), 127.78 (2d), 128.27 (2d), 143.06 (s).
3.24. (R,R)-(−)-2-[1-Methyl-2-(1-phenylnonyl)hydrazono]butan-1-ol (R,R)-(−)-30g
Starting from magnesium (0.471 g), 1-bromooctane (3.35 ml) in ether (20 ml), and the hydrazone (R)-
(−)-29 (0.400 g; 1.94 mmol) in ether (5 ml), the above procedure led to the hydrazine (R,R)-(−)-30g
(0.437 g; 70.4%), [α]D −2.8 (c 1.1, MeOH) and d.e.=100% (1H and 13C NMR). 1H NMR (CDCl3) δ:
0.84 (t, 3H); 0.86 (t, 3H); 1.10–1.90 (m, 16H); 2.43 (s, 3H); 2.40–2.50 (m, 1H); 3.37–3.41 (dd, 1H);
3.61–3.64 (dd, 1H); 3.74–3.77 (dd, 1H); 7.10–7.40 (m, 5H). 13C NMR (CDCl3) δ: 10.33 (q), 13.47 (q),
16.82 (t), 22.00 (t), 25.67 (t), 28.60 (t), 28.84 (t), 29.07 (t), 31.19 (t), 34.40 (t), 39.59 (q), 62.90 (d), 62.53
(t), 67.63 (d), 127.68 (d), 127.78 (2d), 127.87 (2d), 143.11 (s).
3.25. General procedure for the hydrogenolysis of the hydrazines 30: preparation of the (R)-1-phenyl-
1-alkanamines (R)-31
The trisubstituted hydrazine 30a–g in ethanol was hydrogenolyzed in the presence of conc. HCl and
10% Pd–C under hydrogen (6 bar) at 55–65°C for 16 h. After filtration and evaporation, the residue
was treated with 32% aqueous ammonia solution until basic, and the mixture was extracted three times

P. Bataille et al. / Tetrahedron: Asymmetry 9 (1998) 2181–2192
2191
with ether. The ethereal solutions were pooled, dried (MgSO4), filtered and evaporated, thus affording
the crude amine 31 which was chromatographed over silica gel in the presence of triethylamine (eluent:
cyclohexane/ether=9/1 and elution gradient).
3.26. (R)-(+)-1-Phenyl-1-propanamine (R)-(+)-31a
Starting from the hydrazine (R,R)-(+)-30a, [α]D +10.0 (c 1.15, MeOH) (0.330 g; 1.39 mmol) in ethanol
(26 ml), conc. HCl (0.3 ml) and 10% Pd–C (0.106 g), the above procedure led to the pure amine (R)-(+)-
30
31a (0.066 g; 35.4%), [α]D +26 (c 1.6, EtOH) and e.e.=90.5% (chiral GPC). Lit.12 [α]D +6.6 (c 1.49,
EtOH). 1H NMR (CDCl3) δ: 0.86 (t, 3H); 1.69 (quint, 2H); 1.95 (s, 2H); 3.79 (t, 1H); 7.10–7.30 (m, 5H).
3.27. (R)-(+)-1-Phenyl-1-butanamine (R)-(+)-31b
Starting from the hydrazine (R,R)-(+)-30b, [α]D +6.8 (c 1.33, MeOH) (0.321 g; 1.28 mmol) in ethanol
(25 ml), conc. HCl (0.3 ml) and 10% Pd–C (0.1 g), the above procedure led to the pure amine (R)-(+)-31b
(0.130 g; 68.4%), [α]D +22.7 (c 1.1, CHCl3) and [α]D +14.5 (c 1, EtOH), which could not be resolved
1
by chiral GPC. Lit.13 [α]D −21.3 (c 1.3, CHCl3) for the (S) enantiomer. H NMR (CDCl3) δ: 0.90 (t,
3H); 1.10–1.80 (m, 6H); 3.89 (t, 1H); 7.10–7.30 (m, 5H).
3.28. (R)-(+)-1-Phenyl-1-pentanamine (R)-(+)-31c
Starting from the hydrazine (R,R)-(+)-30c, [α]D +5.0 (c 1.08, MeOH) (0.100 g; 0.38 mmol) in ethanol
(10 ml), conc. HCl (0.08 ml) and 10% Pd–C (0.029 g), the above procedure led to the pure amine (R)-
(+)-31c (0.048 g; 77.4%), [α]D +11.7 (c 1.0, CHCl3) and e.e.=92% (chiral GPC). Lit.14 [α]D −12.7 (c
2.50, CHCl3) for the (S) enantiomer. 1H NMR (CDCl3) δ: 0.86 (t, 3H); 1.10–1.80 (m, 8H); 3.86 (t, 1H);
7.10–7.30 (m, 5H).
3.29. (R)-(+)-1-Phenyl-1-hexanamine (R)-(+)-31d
Starting from the hydrazine (R,R)-(−)-30d, [α]D −0.8 (c 1.2, MeOH) (0.400 g; 1.44 mmol) in ethanol
(30 ml), conc. HCl (0.30 ml) and 10% Pd–C (0.111 g), the above procedure led to the pure amine (R)-
(+)-31d (0.140 g; 54.9%), [α]D +4.3 (c 1.6, EtOH) and e.e.=90.2% (chiral GPC). Lit.15 (racemic form).
1H NMR (CDCl3) δ: 0.85 (t, 3H); 1.10–1.80 (m, 10H); 3.86 (t, 1H); 7.10–7.30 (m, 5H).
3.30. (R)-(+)-1-Phenyl-1-heptanamine (R)-(+)-31e
Starting from the hydrazine (R,R)-(−)-30e, [α]D −4.3 (c 0.8, MeOH) (0.100 g; 0.34 mmol) in ethanol
(10 ml), conc. HCl (0.08 ml) and 10% Pd–C (0.026 g), the above procedure led to the pure amine (R)-
(+)-31e (0.046 g; 70.6%), [α]D +9.2 (c 0.6, EtOH) and e.e.=91.3% (chiral GPC). Lit.15 (racemic form).
1H NMR (CDCl3) δ: 0.85 (t, 3H); 1.10–1.80 (m, 12H); 3.89 (t, 1H); 7.10–7.40 (m, 5H).
3.31. (R)-(+)-1-Phenyl-1-octanamine (R)-(+)-31f
Starting from the hydrazine (R,R)-(−)-30f, [α]D −2.8 (c 1.07, MeOH) (0.170 g; 0.55 mmol) in ethanol
(16 ml), conc. HCl (0.12 ml) and 10% Pd–C (0.043 g), the above procedure led to the pure amine (R)-

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P. Bataille et al. / Tetrahedron: Asymmetry 9 (1998) 2181–2192
(+)-31f (0.055 g; 49.1%), [α]D +4.0 (c 1, EtOH) and e.e.=90% (chiral GPC). Lit.15 (racemic form). 1H
NMR (CDCl3) δ: 0.86 (t, 3H); 1.10–1.80 (m, 14H); 3.86 (t, 1H); 7.10–7.40 (m, 5H).
3.32. (R)-(+)-1-Phenyl-1-nonamine (R)-(+)-31g
Starting from the hydrazine (R,R)-(−)-30g, [α]D −2.8 (c 1.1, MeOH) (0.330 g; 1.04 mmol) in ethanol
(20 ml), conc. HCl (0.22 ml) and 10% Pd–C (0.080 g), the above procedure led to the pure amine (R)-
(+)-31g (0.110 g; 48.2%), [α]D +2.3 (c 4.5, EtOH) and e.e.=91% (chiral GPC). Lit.15 (racemic form). 1H
NMR (CDCl3) δ: 0.86 (t, 3H); 1.10–1.80 (m, 16H); 3.89 (t, 1H); 7.20–7.40 (m, 5H).
References
1. (a) Takahashi, H.; Tomita, K.; Otomasu, H. J. Chem. Soc., Chem. Commun. 1979, 668–669; (b) Takahashi, H.; Tomita,
K.; Noguchi, H. Chem. Pharm. Bull. 1981, 29, 3387–3391; (c) Takahashi, H.; Inagaki, H. Chem. Pharm. Bull. 1982, 30,
922–926.
2. Takahashi, H.; Suzuki, Y. Chem. Pharm. Bull. 1983, 31, 4295–4299.
3. (a) Enders, D.; Schubert, H.; Nübling, C. Angew. Chem. 1986, 98, 1118–1119; (b) Enders, D.; Reinhold, U. Tetrahedron:
Asymmetry 1997, 8, 1895–1946; (c) Enders, D.; Nübling, C.; Schubert, H. Liebigs Ann./Recueil 1997, 1089–1100.
4. (a) Denmark, S. E.; Weber, T.; Piotrowski, D. W. J. Am. Chem. Soc. 1987, 109, 2224–2225; (b) Denmark, S. E.; Nicaise,
O.; Edwards, J. P. J. Org. Chem. 1990, 55, 6219–6223.
5. Kim, Y. H.; Choi, J. Y. Tetrahedron Lett. 1996, 37, 5543–5546.
6. (a) Touet, J.; Baudouin, S.; Brown, E. Tetrahedron: Asymmetry 1992, 3, 587–590; (b) Brown, E.; Lézé, A.; Touet, J.
Tetrahedron: Asymmetry 1992, 3, 841–844; (c) Touet, J.; Le Grumelec, C.; Huet, F.; Brown, E. Tetrahedron: Asymmetry
1993, 4, 1469–1472.
7. Le Goff, J. P. Personal communication.
8. Bettoni, G.; Franchini, C.; Perrone, R.; Tortorella, V. Tetrahedron 1980, 36, 409–415.
9. Bataille, P.; Paterne, M.; Brown, E. Unpublished results.
10. Mackey, M. D.; Goodman, J. M. J. Chem. Soc., Chem. Commun. 1997, 2383–2384.
11. Alexakis, A.; Lensen, N.; Mangeney, P. Synlett 1991, 625–626.
12. Nohira, H.; Nohira, M.; Yoshida, S.; Osaka, A.; Terunuma, D. Bull. Chem. Soc., Jpn 1988, 61, 1395–1396.
13. Tanaka, H.; Inoue, K.; Pokorski, U.; Taniguchi, M.; Torii, S. Tetrahedron Lett. 1990, 31, 3023–3026.
14. Yang, T. K.; Chen.; R. Y.; Lee, D. S.; Peng, W. S.; Jiang, Y. Z. J. Org. Chem. 1994, 59, 914–921.
15. de Roocker, A.; de Radzitzky, P. Bull. Soc. Chim. Belg. 1963, 72, 202–207.