Camphordisulfonamides: Good chiral ligands for the addition of dialkylzinc to aliphatic aldehydes

Article abstract of DOI:10.1016/S0957-4166(00)00100-2

The preparation of several disulfonamides derived from camphor and their use in the titanium tetraisopropoxide-promoted enantioselective addition of dialkylzinc to aldehydes is described. The enantiomeric ratio is up to 98:2, the best results being obtained for aliphatic aldehydes. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00100-2

Tetrahedron: Asymmetry 11 (2000) 1629±1644
Camphordisulfonamides: good chiral ligands for the addition
of dialkylzinc to aliphatic aldehydes
Oscar Prieto, Diego J. Ramon and Miguel Yus*
Â
Departamento de Quõmica Organica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, E-03080-Alicante, Spain
Â
Received 29 February 2000; accepted 13 March 2000
Abstract
The preparation of several disulfonamides derived from camphor and their use in the titanium tetra-
isopropoxide-promoted enantioselective addition of dialkylzinc to aldehydes is described. The enantio-
meric ratio is up to 98:2, the best results being obtained for aliphatic aldehydes. # 2000 Elsevier Science
Ltd. All rights reserved.
1. Introduction
The di€erence in biological activity between two enantiomers, the necessity of homochiral
compounds for the total synthesis of natural products, and the questions of regulatory agencies
about data of fate and e€ects of both enantiomers of a chiral pharmaceutical compound in the
course of registration, focuses interest on enantioselective reactions.1 Among them, the nucleo-
philic addition to carbonyl compounds is of paramount importance in synthetic organic chem-
istry, as a useful tool for enantioselective carbon±carbon bond formation. Concerning this
subject, the addition of diethylzinc to benzaldehyde has become a prototype for the evaluation of
any new chiral ligand.
The use of titanium2 tetraalkoxide as a Lewis acid in the promotion of the aforementioned
reaction has been quite popular although the use of diols, such as TADDOL3 and BINOL4 and
their corresponding polymeric5,6 and dendritic7,8 derivatives, as chiral ligands is constantly
increasing. One of the most expansive classes of chiral ligands are disulfonamide derivatives 1±7.
Originally,9 ligand 1 has been used in the addition of functionalised dialkylzinc reagents10 to
aldehydes in the presence of titanium tetraisopropoxide and it has been, probably, the most
studied.11 A similar ligand has been used as co-monomer in the preparation of the corresponding
polymer 2,12 the enantioselection being quite similar to that found in the homogeneous phase.
Instead of using chiral trans-1,2-cyclohexyldiamine as starting material, it is possible to use the
* Corresponding author. Tel: +34-965 903548; fax: +34-965 903549; URL: www.ua.es/dept.quimorg. E-mail:
yus@ua.es
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00100-2

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racemic mixture: its reaction with chiral camphorsulfonyl chloride, followed by separation of
both diastereomers, yielded the chiral ligand 3, which shows a lower enantioselection compared
to ligand 1.13 The corresponding tetradentate ligands 414 and 515 have also been developed, which
show a di€erent level of enantioselection depending on the nature of the aldehyde. Other ligands
with 1,4- and 1,5-disulfonamide moieties (structures 616 and 717) have been used as alternative
chiral ligands for the aforementioned reaction. A general characteristic behaviour of this reaction
is that the enantioselection is better for aromatic aldehydes than for aliphatic ones.2 On the other
hand, the ample amount of chiral disulfonamides used successfully as ligands for the above
mentioned enantioselective addition, together with the unusual properties of hydroxysulfonamide
8, which is the only ligand able to promote the enantioselective addition of dialkylzinc reagents to
aldehydes18 and ketones,19 in the presence of titanium tetraisopropoxide, prompted us to prepare
chiral disulfonamide ligands with the structure of camphor20 and to study their use as chiral
ligands in the enantioselective alkylation of aldehydes.
2. Results and discussion
2.1. Preparation of chiral disulfonamide ligands
Disulfonamide ligands 12 and 13 were ®rst prepared from the commercially available d-(+)-
10-camphorsulfonyl chloride 9. Its reaction with isobutylamine or benzylamine (2 equiv.), cata-
lysed by 4-dimethylaminopyridine (DMAP, 0.2 equiv.), at 0ꢀC gave after 3 h the expected camphor-
sulfonamides 10 with good yields. The corresponding reaction of these ketones with an excess of
hydroxylammonium chloride (2.5 equiv.) and triethylamine (2 equiv.) in re¯uxing ethanol21 gave
the expected oximes 11 with good yields and as a single diastereoisomer. The ®nal step was the
reduction of oximes 11 to the corresponding amines and, for that purpose, several methods were
tested (Table 1). However, due to the problems in their isolation, the crude mixture of amines
were directly transformed into the corresponding mesylated derivatives 12 and 13 or the pivaloyl-
amide derivative 12c by reaction with methanesulfonyl chloride22 or pivaloyl chloride, respectively,
in the presence of triethylamine (Scheme 1). In this way, the isolation of exo-12 and endo-13
epimers was easily achieved.

O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
1631
Table 1
Reduction of oximes 11 and preparation of bidentate ligands
ꢀ
.
Scheme 1. Reagents and conditions: i, RCH2NH2, DMAP, CH3CN, 0 C; ii, H2O; iii, NH2OH HCl, Et3N, EtOH,
80ꢀC; iv, CH3CO2NH4, NaBH3CN, MeOH, 70ꢀC; v, R0Cl, Et3N, CH3CN, 0 to 25ꢀC; vi, CH3CO2NH4, NaBH3CN,
TiCl3, MeOH, 0 to 25ꢀC
The di€erent strong reduction methods used for oximes 11, such as lithium aluminium
hydride23 or borane24 both in re¯uxing THF, gave, after mesylation, a low yield of the corre-
sponding mesylamide, the diastereomeric ratio also being poor (Table 1, entries 2 and 3). Other
mild reduction methods, such as sodium borohydride in the presence of nickel(II) chloride,25
sodium cyanoborohydride in the presence of diphenyldisul®de and triethylphosphine,26 sodium
borohydride in the presence of titanium(IV) chloride,27 or sodium borohydride in the presence of
titanium(III) chloride and sodium acetate,28 gave very poor yields or diastereomeric ratios of
nearly 1:1 (Table 1, entries 4±7). However, the reduction using sodium borohydride in the presence
of titanium(III) chloride and ammonium acetate29 yielded the expected amines with a reasonable

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O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
yield and diastereomeric ratio, independently either of the starting camphorsulfonamide (entries 1
and 8) or of the isolation procedure (chromatography or recrystallisation; compare entries 8 and
9 in Table 1). Nevertheless, the results of this former procedure were inconsistent in the scaling-
up process.
On the other hand, the corresponding reductive amination of camphorsulfonamide 10b, using
ammonium acetate and sodium cyanoborohydride in the presence of 4 A molecular sieves in
re¯uxing methanol,30 gave the expected amines. Their transformation into the corresponding
mesylamide derivatives, as has been mentioned previously, gave an isolable mixture of both epi-
mers 12b and 13b with a 10% yield for both epimers.
The aforementioned problems made us turn to another way to prepare these ligands. The
starting material was 10,2-camphorsultam 14, which was easily prepared from the corresponding
camphorsulfonyl chloride 9 by a two step process:31 monodeprotonation of sultam 14 at low
temperature, followed by a reaction with various sulfonyl chloride derivatives, gave the corre-
sponding sultams 15 in good yields. The nucleophilic opening32 of heterocycles 15 using various
lithium amides yielded the expected ligands 12 (Scheme 2 and Table 2).
Scheme 2. Reagents and conditions: i, NH4OH, 1,4-dioxane, 25 to 110ꢀC; ii, NaBH4, MeOH/H2O, 0 to 25ꢀC; iii,
H2SO4 (4 M); iv, BunLi, THF, ^78ꢀC; v, R0Cl, ^78 to 25ꢀC; vi, H2O; vii, RCH2NH2/BunLi, THF, ^78 to 25ꢀC.
Table 2
Preparation of ligands 12 by nucleophilic opening
2.2. Asymmetric addition of dialkylzinc to aldehydes
Once the ligands 12 had been prepared, we studied ®rst the in¯uence of the temperature taking
the ligand 12b as standard for the reaction of diethylzinc and benzaldehyde using 20 mol% of
ligand, 120 mol% of titanium isopropoxide and 180 mol% of the organometallic compound
in toluene (Scheme 3 and Fig. 1). The maximum enantiomeric ratio was found at ^20ꢀC, and in
all cases, the yield was higher than 95% after 4 h at the selected temperature, except in the case of

O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
1633
Scheme 3.
Figure 1. Eyring's diagram for ligand 12b
performing the reaction at ^50ꢀC after 120 h, in which only 70% yield was obtained. The Eyring
diagram33 shown in Fig. 1 probably indicates the existence of several reaction mechanisms in
competition.
Once the optimal temperature had been found, other parameters such as solvent and bulkiness
of titanium alkoxide were tested. Thus, the addition of diethylzinc (1.8 equiv.) to benzaldehyde
(1 equiv.) in di€erent solvents was studied using the chiral ligand 12b, ®nding that the enantio-
selectivity of the reaction dropped down to nearly zero giving a racemic mixture when THF or
dichloromethane were used (Table 3, entries 1 and 2). However, when toluene was used as solvent
the enantiomeric ratio was 82:18 (Table 3, entry 3). This important in¯uence of the solvent in the
enantioselection was not present in the related ligand 8 (see above).18
The ligand 12g was used as standard for studying the in¯uence of the nature of titanium alkoxide.
In the case of using the corresponding titanium ethoxide or propoxide derivatives, the enantio-
meric ratio was lower than in the case of using titanium tetraisopropoxide (Table 4, compare
entries 1±3). However, when the reaction was performed under similar conditions but using a
more crowded derivative, such as titanium tetra-tert-butoxide, the reaction time was longer and
the enantioselection was similar to those obtained using the less crowded titanium derivatives
(Table 4, entry 4).
After verifying that toluene and titanium tetraisopropoxide were the best options for the con-
ditions tested, we tried to ®nd the best ligand for the aforementioned enantioselective reaction.
Firstly we studied the in¯uence of substitution of a 10-sulfonamide moiety (R3), ®nding that the
presence of an aromatic ring improved the enantioselection (Table 5, entries 1, 3 and 4). However,
in the case of using a more crowded aromatic ring derivative, such as naphthyl, the enantiomeric
ratio dropped. In the case of ligand 12a, the in¯uence of the temperature was also tested, and, as

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O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
Table 3
Table 4
in the previous case, the best temperature seemed to be ^20ꢀC, the enantiomeric ratio being
worse; even the main enantiomer was di€erent performing the reaction at ^30ꢀC (Table 5, entry 2).
The in¯uence of substitution of a 2-sulfonamide moiety (R1) and its nature was studied: mesyl-
amide derivative gave the best results (Table 5, entry 3), better than the more acidic tri¯amide
derivative (Table 5, entry 6) or the more hindered tosylamide derivative (Table 5, entry 7). When
the reaction was performed using the corresponding pivaloylamide (Table 5, entry 8) a nearly
racemic mixture of alcohol 16 was obtained. The relative position of mesylamide is also very
important, since the modi®cation from exo-position to endo-position (see compounds 12b and
13b; Table 5, entries 3 and 9) changed the enantioselection down to lead to a racemic mixture; a
similar behaviour was found with the corresponding hydroxysulfonamide derivatives 9.18 Finally,

O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
1635
Table 5
no enantioselection was found when the reaction was carried out using the oxime 11a as chiral
ligand (Table 5, entry 10).
Once the best ligand 12b had been found for the enantioselective addition of diethylzinc to
benzaldehyde, we tested the in¯uence of dialkylzinc reagents and aldehydes, these results being
included in Table 6. In all cases, the reactions were ®nished after 2 h and yields were greater than
95%. As was pointed out previously, for other disulfonamide ligands,11i,34 the reaction with
dimethylzinc gave a lower enantiomeric ratio than the corresponding diethylzinc reagent (Table 6,
entry 1). The enantioselective addition carried out using benzadehyde derivatives gave a worse
result in comparison with benzaldehyde (Table 5, entry 3 and Table 6, entries 2 and 3); the more
basic the functionality present on the benzaldehyde derivative is, the lower the enantiomeric ratio, even
the main enantiomer being changed. Surprisingly, the best enantioselection was found when the
reaction was carried out using aliphatic aldehydes, independently of their steric hindrance (Table 6,
entries 4, 6 and 7). Also in these cases of high enantioselection, the presence of an extra basic
atom in the ligand 12 decreased the e.r. as in the previous case of benzaldehyde derivatives (Table 6,
entries 4 and 5). Finally, the enantiomeric ratio was very low when the reaction was performed
using alkenyl- or alkynylaldehydes (Table 6, entries 8±10). These results emphasize the special
properties of this ligand in which the in¯uence of the electronic aspects of the aldehyde is the major
contribution in the enantioselectivity, giving the best results for the less reactive aliphatic aldehydes.
The main enantiomer obtained with the here described disulfonamide derivatives is usually R.
However, in the case of using the corresponding hydroxysulfonamide 9, the main enantiomer
had S con®guration,18 in both cases the absolute con®guration of the ligand being the same,
which indicates that small changes in the structure of the chiral auxiliary may produce major
consequences in the enantioselection.

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O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
Table 6
3. Conclusion
In conclusion, we have described here new disulfonamide ligands, which can be easily prepared
from chiral camphorsulfonyl chloride and can be successfully used in the enantioselective addition
of dialkyzinc reagents to aldehydes. It is worthy of note that the enantioselection is higher for aliphatic
aldehydes than for aromatic derivatives, this behaviour being unusual for this type of reaction.
4. Experimental
4.1. General
Melting points were obtained with a Reichert Thermovar apparatus. Distillation for puri®cation
of the alcohol products was performed in a Buchi GKR-51 bulb to bulb distillation apparatus;
boiling points correspond to the air bath temperature. [ꢀ]D values were recorded at room
temperature (ca. 25ꢀC) in a DIP-1000 Jasco polarimeter (p.a. solvents, Panreac). FT-IR spectra were
obtained on a Nicolet Impact 400D spectrophotometer. NMR spectra were recorded on a Bruker
AC-300 (300 MHz for 1H and 75 MHz for 13C) using CDCl3 as solvent (unless otherwise stated)

O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
1637
and TMS as internal standard; chemical shifts are given in ꢁ (ppm) and coupling constants (J) in Hz.
NOESY and NOE experiments for assignation of relative con®guration in ligands 12 and 13 were
1
performed in a Bruker Avance DRX-500 (500 MHz for H and 125 MHz for 13C). Mass spectra
(EI) were obtained at 70 eV on a Shimadzu QP-5000 spectrometer, giving fragment ions in m/z
with relative intensities (%) in parentheses. High resolution mass spectra and elemental analyses
were performed by the corresponding Mass Spectrometry and Microanalysis Service at the Uni-
versity of Alicante. The purity of volatile products and the chromatographic analyses (GLC) were
determined with a Hewlett±Packard HP-5890 instrument equipped with a ¯ame ionisation
detector and 12 m HP-1 capillary column (0.2 mm diameter, 0.33 mm ®lm thickness, OV-1
stationary phase), using nitrogen (2 ml/min) as carrier gas, Tinjector=275ꢀC, Tdetector=300ꢀC,
Tcolumn=60ꢀC (3 min) and 60±270ꢀC (15ꢀC/min), P=40 kPa; tR values are given in min under
these conditions. The enantiomeric ratios (e.r.) were determined with the aforementioned appar-
atus and a 50 m WCOT fused silica capillary column (0.25 mm diameter, 0.25 mm ®lm thickness,
CP-cyclodextrin-b-2,3,6-M-19), using nitrogen as carrier gas, Tinjector=250ꢀC, Tdetector=260ꢀC;
A conditions: Tcolumn=60ꢀC (10 min) and 220ꢀC (0.3ꢀC/min), P=130 kPa; B conditions:
Tcolumn=80ꢀC (20 min) and 220ꢀC (0.6ꢀC/min), P=120 kPa; C conditions: Tcolumn=80ꢀC (5 min)
and 220ꢀC (0.5ꢀC/min), P=120 kPa; or with a WCOT fused silica capillary column (0.25 mm
diameter, 0.25 mm ®lm thickness, FS-Lipodex-E) g-CD, Tinjector=250ꢀC, Tdetector=260ꢀC; D
conditions: Tcolumn=75ꢀC (20 min) and 210ꢀC (0.1ꢀC/min), P=120 kPa; tR(R) and tR(S) values
are given in min under these four conditions. In the cases of alcohols 20, 21 and 22, for achieving
a good resolution in the GLC-analyses it was necessary to transform them in their tri¯uoroacetate
derivatives (TFA) by reaction of the corresponding alcohol (5 mg) in CH2Cl2 (0.5 ml) at 25ꢀC
with tri¯uoroacetic anhydride (ca. 0.25 ml); after 30 min of stirring, nitrogen gas was passed
through for several minutes and the obtained sample was used directly.35 In the case of alcohols
24 and 25, previously to the GLC-analyses, they were hydrogenated in methanol by hydrogen
22
(1 atm) using palladium on activated carbon under standard conditions,
to give alcohol 21.
Thin layer chromatography (TLC) was carried out on Schleicher and Schuell F1400/LS 254
plates coated with a 0.2 mm layer of silica gel; detection by UV254 light, staining with phospho-
.
molybdic acid (25 g phosphomolybdic acid, 10 g Ce(SO4)2 4H2O, 60 ml concentrated H2SO4 and
940 ml H2O) or with I2; Rf values are given under these conditions. Column chromatography was
performed using silica gel 60 of 35±70 mesh. 10,2-Camphorsultam 14 was prepared from d-(+)-
camphorsulfonyl chloride by a two step process with a 65% overall yield;31 other reagents were
commercially available (Acros, Aldrich, Strem) and were used as received. Solvents were dried by
standard procedures.36
4.2. Preparation of ligands
4.2.1. Preparation of camphorsulfonamides 10. General procedure
To a solution of the corresponding alkylamine (21 mmol) and dimethylaminopyridine (2.0 mmol,
0.235 g) in acetonitrile (20 ml) at 0ꢀC was slowly added (ca. 1 h) a solution of d-(+)-10-camphor-
sulfonyl chloride 9 (10 mmol) in acetonitrile (20 ml). After one additional hour the mixture was
hydrolysed with water (10 ml) and the obtained mixture was extracted with ethyl acetate (3Â25 ml)
and the organic layer was dried over Na2SO4.The solvents were removed under reduced pressure
(15 torr), obtaining the pure title compound 10 in yields indicated in Scheme 1. Compound 10b was
already described by us and was characterised by comparison of its physical and spectroscopic
data with those reported in the literature.18 Spectroscopic, physical and analytical data follow.

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O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
4.2.1.1. (1S,4S)-N-2-Methylpropyl-10-camphorsulfonamide 10a. White solid, tR 17.1, Rf 0.12
(hexane/ethyl acetate: 1/1); mp 78±79ꢀC (ethyl acetate/hexane); [ꢀ]D +1.85 [c=1.4 (Me2CO)]; ꢂ
(melted) 3397, 2950 (NH), 1723 (CO), 1394 cm^1 (SO2); ꢁH 0.92, 1.03 [3 and 3H, respectively, 2s,
C(CH3)2], 1.4±2.45 [8H, m, (CH2)2CHCH2CO, CH(CH3)2], 2.91, 3.39 (2H, 2d, J=15.2, CH2S),
2.95±3.15 (2H, m, CH2N), 5.30 (1H, t, J=5.4, NH); ꢁC 19.4, 19.8, 19.9, 26.5 (2C), 27.0, 42.7, 42.8
(2C), 48.7, 49.1, 50.9, 59.15, 216.9; m/z 288 (M++1, <1%), 244 (14), 215 (61), 151 (26), 123 (31),
115 (23), 109 (64), 108 (14), 107 (27), 95 (12), 93 (26), 91 (13), 81 (66), 79 (24), 77 (12), 72 (37), 69
(13), 67 (49), 60 (29), 57 (20), 55 (34), 53 (22), 43 (49), 41 (100), 40 (13) (found: C, 58.45; H, 8.82;
N, 4.90. C14H25NO3S requires: C, 58.50; H, 8.77; N, 4.87%).
4.2.2. Preparation of camphoroximes 11. General procedure21
To a solution of corresponding camphorsulfonamide 10 (8.4 mmol) in ethanol (50 ml) were
added hydroxylammonium chloride (50.5 mmol, 3.5 g) and triethylamine (38.5 mmol, 4.7 ml).
The resulting mixture was re¯uxed over 24 h. Then the solvent was removed under reduced
pressure (15 torr) and the residue was suspended in water (10 ml). The aforementioned suspen-
sion was extracted with ethyl acetate (3Â25 ml) and the organic layer was dried over Na2SO4. The
solvents were removed under reduced pressure (15 torr) yielding a residue which was then puri®ed
by ¯ash chromatography (silica gel, hexane/ethyl acetate) to a€ord the expected oxime as a single
isomer. Yields are indicated in Scheme 1. Spectroscopic, physical and analytical data follow.
4.2.2.1. (1S,4S)-N-(2-Methylpropyl)-2-hydroxyimino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethane-
sulfonamide 11a. White solid, tR (decompose), Rf 0.60 (hexane/ethyl acetate: 1/1); mp 113±115ꢀC
(ethyl acetate/hexane); [ꢀ]D +7.25 [c=1.50 (Me2CO)]; ꢂ (melted) 3423 (OH), 3311 (NH), 1609
(CˆN), 1311 cm^1 (SO2); ꢁH 0.86, 0.97 [3 and 3H, respectively, 2s, C(CH3)2], 0.95 [6H, t, J=4.2,
CH(CH3)2], 1.25±2.65 [8H, m, (CH2)2CHCH2CˆN, CH(CH3)2], 2.80±2.95 (2H, m, NHCH2),
3.01, 3.41 (1 and 1H, respectively, 2d, J=15.2, CH2S), 5.80 (1H, dd, J=5.5, 2, NH); ꢁC 14.1, 19.5,
20.0, 27.3, 28.75 (2C), 29.55 (2C), 30.05, 43.0, 50.9, 51.1, 52.8, 168.55; m/z 306 (M++4, 1%), 134
(20), 109 (42), 108 (82), 107 (12), 94 (15), 93 (100), 91 (30), 82 (35), 81 (17) (found: C, 55.65; H,
8.40; N, 9.16; S, 10.47. C14H26N2O3S requires: C, 55.60; H, 8.34; N, 9.26; S, 10.60%).
4.2.2.2. (1S,4S)-N-Benzyl-2-hydroxyimino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide
11b. White solid, tR (decompose), Rf 0.58 (hexane/ethyl acetate: 1/1); mp 129±131ꢀC (ethyl
acetate/hexane); [ꢀ]D ^7.25 [c=1.37 (CHCl3)]; ꢂ (melted) 3424 (OH), 2947 (NH), 1609 (CˆN),
1327 cm^1 (SO2); ꢁH 0.70, 0.89 (3 and 3H, respectively, 2s, 2ÂCH3), 1.20±2.60 [7H, m,
(CH2)2CHCH2CˆN], 2.95, 3.21 (1 and 1H, respectively, 2d, J=15.0, CH2S), 4.22, 4.34 (1 and 1H,
respectively, 2d, J=14.0, CH2N), 6.4, 7.11 (1 and 1H, respectively, 2s, NH, OH), 7.10±7.40 (5H,
m, Ph); ꢁc 18.8, 19.45, 27.3, 29.85, 32.95, 42.95, 47.85, 50.7, 53.0, 53.9, 127.75, 128.35 (2C), 128.7
(2C), 138.1, 168.35; m/z 304 (M+^NOH, <1%), 153 (28), 149 (12), 135 (32), 134 (13), 127 (20),
109 (34), 108 (42), 106 (32), 105 (15), 93 (46), 91 (61), 83 (16), 82 (12), 79 (41), 78 (12), 77 (13), 67
(34), 65 (36), 55 (20), 53 (16), 51 (20), 48 (20), 44 (100), 42 (13), 41 (46) (found: C, 60.78; H, 7.14;
N, 8.29; S, 9.48. C17H24N2O3S requires: C, 60.69; H, 7.19; N, 8.33; S, 9.53%).
4.2.3. Preparation and isolation of ligands 12 and 13. General procedure
To a solution of corresponding camphoroxime 11 (4.5 mmol) in methanol (45 ml) at 0ꢀC were
added ammonium acetate (58.0 mmol, 4.5 g) and sodium cyanoborohydride (18.0 mmol, 1.15 g).
Then, a solution of titanium trichloride (13.5 mmol, 12 ml, 15%) was slowly added (ca. 1 h) to the

O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
1639
above mixture and the resulting dark brown mixture was stirred overnight allowing the tem-
perature to rise to 25ꢀC.29 Then, the resulting mixture was quenched by addition of a saturated
NaHCO3 solution (25 ml) and ®ltered through Celite. The colourless solution was extracted with
ethyl acetate (3Â25 ml) and the organic layer was dried over Na2SO4. The solvents were removed
under reduced pressure (15 torr) yielding a residue which was dissolved in acetonitrile (40 ml). To
the resulting mixture at 0ꢀC was added triethylamine (18 mmol, 2.5 ml) and then the corre-
sponding sulfonyl22 or alkanoyl chloride (9 mmol) was slowly added during 1 h. After one addi-
tional hour a solution of saturated NH4Cl solution (10 ml) was added and the resulting mixture
was extracted with ethyl acetate (3Â25 ml) and the organic layer was dried over Na2SO4. The
solvents were removed under reduced pressure (15 torr), yielding a residue which was then pur-
i®ed by ¯ash chromatography (silica gel, hexane/ethyl acetate) to a€ord the expected ligands
12a,b and 13b. The ligand 12c was puri®ed by crystallisation from a mixture of ethyl acetate and
hexane. Yields are included in Table 1. Spectroscopic, physical and analytical data follow.
4.2.3.1. (1S,2R,4S)-N-(2-Methylpropyl)-2-methylsulfonylamino-7,7-dimethylbicyclo[2.2.1]hept-
1-ylmethanesulfonamide 12a. Pale yellow syrup, tR 22.2, Rf 0.30 (hexane/ethyl acetate: 1/1); [ꢀ]D
^17.1 [c=1.60 (CHCl3)]; ꢂ (®lm) 3299, 2942 (NH), 1320 cm^1 (SO2); ꢁH 0.94, 0.97 [3 and 3H,
respectively, 2s, C(CH3)], 0.96, 0.98 [3 and 3H, respectively, 2s, CH(CH3)2], 1.25±2.15 [7H, m,
(CH2)2CHCH2], 2.30±2.45 (1H, m, CHCH3), 2.90±2.95 (2H, m, NHCH2), 3.00 (3H, s, SO2CH3),
3.13, 3.17 (2H, d, J=3.6, CH2S), 3.80±3.85 (1H, m, CHN), 4.86 (1H, t, J=6.4, NHCH2), 5.78
(1H, d, J=4.2, CHNH); ꢁC 18.95, 19.8, 19.9, 25.2, 28.0, 29.0, 38.2, 40.65, 43.1, 44.2, 50.4, 50.7, 54.85,
57.65, 68.1; m/z 325 (M+^41, <1%), 230 (65), 223 (22), 136 (16), 135 (100), 94 (11), 93 (38), 91
(16), 81 (12), 79 (41), 74 (12), 67 (27), 57 (12), 55 (19), 44 (12), 43 (33), 41 (47) (found: C, 47.54; H,
.
8.29; N, 7.34; S, 17.40. C15H30N2O4S2 2/3H2O requires: C, 47.59; H, 8.34; N, 7.40; S, 16.94%).
4.2.3.2. (1S,2R,4S)-N-Benzyl-2-methylsulfonylamino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethane-
sulfonamide 12b. Pale yellow syrup, tR 26.1, Rf 0.38 (hexane/ethyl acetate: 1/1); [ꢀ]D ^34.3
[c=2.02 (CHCl3)]; ꢂ (®lm) 3297, 2957 (NH), 3031 (CHˆC), 1328 cm^1 (SO2); ꢁH 0.74, 0.92 [3 and
3H, respectively, 2s, C(CH3)2], 1.10±2.20 [7H, m, (CH2)2CHCH2], 2.70, 3.22 (1 and 1H, respec-
tively, 2d, J=14.6, CH2S), 2.96 (3H, s, SO2CH3), 3.55±3.65 (1H, m, CHN), 4.32 (2H, d, J=6.1,
CH2N), 4.99 (1H, d, J=4.9, CHNH), 5.19 (1H, t, J=6.1, NHCH2), 7.25±7.55 (5H, m, Ph); ꢁC
20.15, 20.4, 27.05, 32.65, 39.25, 39.3, 44.6, 46.15, 47.25, 50.1, 52.5, 59.2, 128.05, 128.25 (2C), 128.9
(2C), 136.9; m/z 281 (M+^119, <1%), 139 (12), 111 (31), 101 (14), 95 (14) (found: C, 52.28; H,
.
6.93; N, 6.76; S, 14.99. C18H28N2O4S2 1/3H2O requires: C, 53.18; H, 7.11; N, 6.89; S, 15.77%).
4.2.3.3. (1S,2R,4S)-N-Benzyl-2-pivaloylamino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide
12c. White solid, tR 23.7, Rf 0.5 (hexane/ethyl acetate: 1/1); mp 143±146ꢀC (ethyl acetate/hexane);
[ꢀ]D ^32.8 [c=1.13 (CHCl3)]; ꢂ (melted) 3433, 2966 (NH), 2656, 2333, 1659 (CˆO), 1322 cm^1
(SO2); ꢁH 0.86, 0.92 [3 and 3H, respectively, 2s, C(CH3)2], 1.16 [9H, s, C(CH3)3], 1.20±2.10 [7H,
m, (CH2)2CHCH2], 2.94, 3.16 (1 and 1H, respectively, 2d, J=14.3, CH2S), 4.00±4.20 (1H, m,
CHN), 4.30±4.35 (2H, m, CH2N), 5.65 (1H, t, J=5.8, NHCH2), 5.78 (1H, d, J=7.9, CHNH),
7.10±7.40 (5H, m, Ph); ꢁC 20.15, 20.6, 27.0, 27.5(3C), 31.5, 38.7, 39.7, 43.3, 46.6, 49.25, 49.5, 52.95,
55.05, 127.65, 127.85 (2C), 128.6 (2C), 137.6, 178.1; m/z 343 (M+^63, <1%), 237 (12), 236 (26),
157 (72), 156 (59), 141 (16), 135 (38), 109 (13), 108 (10), 107 (18), 106 (32), 102 (37), 93 (18), 91
.
(24), 79 (20), 67 (12), 57 (100) (found: C, 63.23; H, 8.42; N, 6.77; S, 7.42. C22H34N2O3S 2/3H2O
requires: C, 63.13; H, 8.51; N, 6.70; S, 7.66%.

1640
O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
4.2.3.4. (1S,2S,4S)-N-Benzyl-2-methylsulfonylamino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethane-
sulfonamide 13a. Pale yellow syrup, tR 21.8, Rf 0.31 (hexane/ethyl acetate: 1/1); [ꢀ]D +26.2
[c=1.61 (CHCl3)]; ꢂ (®lm) 3297, 2957 (NH), 3031 (CHˆC), 1328 cm^1 (SO2); ꢁH 0.81, 0.82 [3 and
3H, respectively, C(CH3)2], 0.75^2.4 [7H, m, (CH2)2CHCH2], 2.92 (2H, s, CH2S), 2.97 (3H, s,
SO2CH3), 3.70±3.75 (1H, m, CHN), 4.30 (2H, s, CH2N), 5.40±5.45 (1H, m, NHCH2), 5.77 (1H, d,
J=4.3, CHNH), 7.25±7.45 (5H, m, Ph); ꢁC 18.7, 19.7, 25.1, 28.1, 38.15, 40.65, 44.0, 47.2, 50.35
(2C), 56.25, 57.45, 128.0, 128.3 (2C), 128.8 (2C), 136.85; m/z 305 (M+^95, <1%), 91 (100), 79
(13), 77 (10), 65 (14), 64 (12), 44 (69), 43 (22), 42 (11), 41 (21) (found: C, 52.61; H, 6.95; N, 6.51; S,
.
15.41. C18H28N2O4S2 3/5H2O requires: C, 52.56; H, 7.15; N, 6.81; S, 15.59%).
4.2.4. Preparation and isolation of ligands 12. General procedure
To a solution of (1S,2R,4S)-methylsulfonyl-10,2-camphorsultam 14 (20 mmol, 4.23 g) in THF
at ^78ꢀC was added butyllithium (25.6 mmol, 16 ml, 1.6 M), allowing the temperature to rise to
0ꢀC during 30 min. Then, the resulting solution was cooled down to ^78ꢀC and the corre-
sponding sulfonyl chloride (26 mmol) was slowly added (ca. 10 min), allowing the temperature to
rise to 25ꢀC overnight. The resulting mixture was hydrolysed by successive addition of methanol
(2 ml) and saturated NH4Cl solution (20 ml), extracted with ethyl acetate (3Â50 ml) and the
organic layer was dried over Na2SO4. The solvents were removed under reduced pressure
(15 torr) yielding a residue. In the case of compound 15a, it was puri®ed by crystallisation from a
mixture of chloroform and hexane. Yield is included in Scheme 2. Spectroscopic, physical and
analytical data follow for (1S,2R,4S)-N-methylsulfonyl-10,2-camphorsultam 15a: white solid,
tR (descompose), Rf 0.30 (hexane/ethyl acetate: 1/1); mp 162^164ꢀC (chloroform/hexane); [ꢀ]D
^74.45 [c=1.6 (CHCl3)]; ꢂ (melted) 1328 cm^1 (SO2); ꢁH 0.97, 1.23 (3 and 3H, respectively, 2s,
CH3), 1.30±2.00 [7H, m, (CH2)2CHCH2], 3.19 (3H, s, SO2CH3), 3.39, 3.46 (1 and 1H, respec-
tively, 2d, J=13.7, CH2S), 3.65±3.70 (1H, m, CHN); ꢁC 19.8, 20.4, 26.5, 32.8, 37.45, 39.1,
44.65, 48.0, 49.5, 52.45, 66.5; m/z 292 (M+^1, <1%), 158 (12), 157 (100), 154 (11), 141 (22), 135
(21), 134 (19), 109 (31), 108 (51), 107 (17), 93 (26), 67 (19), 55 (16), 43 (15), 41 (34) (found: C,
.
43.67; H, 6.41; N, 4.66; S, 21.00. C11H19NO4S2 1/2H2O requires: C, 43.69; H, 6.67; N, 4.63;
S, 21.20%). The aforementioned residue was dissolved in THF and to the resulting solution at
^78ꢀC was added a THF solution (60 ml) which contained the corresponding lithium alkylamide
prepared from alkylamine (120 mmol) and butyllithium (80 mmol, 50 ml, 1.6 M) at ^78ꢀC. The
resulting mixture was stirred overnight, allowing temperature to rise to 25ꢀC. The reaction
was hydrolysed with water (40 ml) and the resulting mixture was extracted with ethyl acetate
(3Â50 ml) and the organic layer was dried over Na2SO4. The solvents were removed under
reduced pressure (15 torr) yielding a residue which was then puri®ed by ¯ash chromatography
(silica gel, hexane/ethyl acetate) to a€ord the expected ligands 12b,d±h. Ligand 12b has been
described above. Yields are included in Table 2. Spectroscopic, physical and analytical data
follow.
4.2.4.1. (1S,2R,4S)-N-Benzyl-2-trifluoromethylsulfonylamino-7,7-dimethylbicyclo[2.2.1]hept-1-
ylmethanesulfonamide 12d. Yellow syrup, tR 20.4, Rf 0.70 (hexane/ethyl acetate: 1/1); [ꢀ]D ^25.6
[c=1.04 (CHCl3)]; ꢂ (®lm) 3342, 2949 (NH), 1384 (SO2), 1187 cm^1 (CF); ꢁH 0.68, 0.83 (3 and
3H, respectively, 2s, 2ÂCH3), 1.20±2.10 [7H, m, (CH2)2CHCH2], 2.51, 2.56 (1 and, 1H, respec-
tively, 2d, J=6.7, CH2S), 3.85±3.95 (1H, m, CHN), 4.37 (2H, s, CH2N), 5.68 (2H, s, 2ÂNH),
7.25±7.40 (5H, m, Ph); ꢁC 19.55, 20.0, 26.85, 32.75, 38.15, 44.3, 47.05, 49.45, 50.3, 52.95, 60.05,
121.45, 127.9 (2C), 128.25 (2C), 128.85, 137.2; m/z 390 (M+^64, <1%), 135 (16), 108 (22), 107

O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
1641
(48), 106 (100), 93 (18), 91 (39), 79 (15), 67 (10), 43 (12), 41 (16) (found: C, 47.45; H, 5.42; N, 6.99;
S, 13.81. C18H25F3N2O4S2 requires: C, 47.56; H, 5.54; N, 6.16; S, 14.11%).
4.2.4.2. (1S,2R,4S)-N-Benzyl-2-[(4-methylphenyl)sulfonylamino]-7,7-dimethylbicyclo[2.2.1]-
hept-1-ylmethanesulfonamide 12e. Yellow solid, tR 27.9, Rf 0.65 (hexane/ethyl acetate: 1/1); mp
64±66ꢀC (ethyl acetate/hexane); [ꢀ]D ^30.1 [c=1.29 (CHCl3)]; ꢂ (melted) 3288, 2952 (NH), 1328
cm^1 (SO2); ꢁH 0.68, 0.92 [3 and 3H, respectively, 2s, CC(CH3)2], 1.00±2.20 [7H, m,
(CH2)2CHCH2], 2.39 (3H, s, CH3CCH), 2.65, 3.24 (1 and 1H, respectively, 2d, J=14.6, CH2S),
2.69±3.20 (1H, m, CHN), 2.96, 4.28 (2H, d, J=6.1, CH2N), 5.50±5.70 (2H, m, 2ÂNH), 7.29, 7.74
(2 and 2H, respectively, 2d, J=7.9, SC6H4), 7.25±7.40 (5H, m, Ph); ꢁC 19.85, 20.4, 21.45, 26.9,
32.3, 36.0, 44.4, 47.05, 49.45, 50.2, 52.55, 59.1, 127.55 (2C), 127.75, 128.2 (2C), 128.65 (2C), 129.6
(2C), 135.75, 137.0, 143.55; m/z 452 (M+^23, <1%), 126 (15), 113 (75), 98 (14), 85 (19), 84 (14),
71 (24), 70 (42), 56 (22), 55 (43), 44 (95), 43 (100), 42 (20), 41 (43), 40 (83) (found: C, 57.84; H,
.
6.74; N, 5.99; S, 13.75. C24H32N2O4S2 1/3H2O requires: C, 57.87; H, 6.77; N, 6.13; S, 14.04%).
4.2.4.3. (1S,2R,4S)-N-(4-Methoxyphenyl)methyl-2-methylsulfonylamino-7,7-dimethylbicyclo[2.2.1]-
hept-1-ylmethanesulfonamide 12f. White solid, tR 23.3, Rf 0.30 (hexane/ethyl acetate: 1/1); mp
156±158ꢀC (ethyl acetate/hexane); [ꢀ]D ^32.7 [c=1.33 (CHCl3)]; ꢂ (melted) 3294, 2950 (NH), 1321
(SO2), 1149 cm^1 (CO); ꢁH 0.74, 0.92 [3 and 3H, respectively, s, C(CH3)2], 1.10±2.20 [7H, m,
(CH2)2CHCH2], 2.67, 3.15 (1 and 1H, respectively, 2d, J=14.5, CH2S), 2.95 (3H, s, SO2CH3),
3.55±3.60 (1H, m, CHN), 3.79 (3H, s, OCH3) 4.24 (2H, d, J=3.7, CH2N), 5.11, 5.33 (1 and 1H,
respectively, 2ÂNH), 6.89, 7.29 (2 and 2H, respectively, 2d, J=8.4, OC6H4); ꢁC 20.1, 20.35, 27.05,
32.6, 39.1, 39.15, 44.55, 46.7, 49.45, 50.05, 52.35, 55.25, 59.1, 114.15 (2C), 128.9, 129.65 (2C),
159.35; m/z 430 (M+, <1%), 157 (31), 156 (25), 137 (47), 136 (100), 135 (32), 121 (32), 109 (18),
108 (14), 107 (14), 106 (14), 93 (16), 79 (17), 67 (14), 43 (12), 41 (17) (found: C, 53.12; H, 7.07; N,
.
6.06; S, 14.09. C19H30N2O5S2 1/3AcOEt requires: C, 53.10; H, 7.16; N, 6.09; S, 13.99%).
4.2.4.4. (1S,2R,4S)-N-(2-Phenylethyl)-2-methylsulfonylamino-7,7-dimethylbicyclo[2.2.1]hept-1-
ylmethanesulfonamide 12g. Pale yellow syrup, tR 29.0, Rf 0.31 (hexane/ethyl acetate: 1/1); [ꢀ]D
^30.4 [c=1.43 (CHCl3)]; ꢂ (®lm) 3298, 2949 (NH), 1320 cm^1 (SO2); ꢁH 0.80, 0.97 [3 and 3H,
respectively, 2s, C(CH3)2], 1.55±2.40 [7H, m, (CH2)2CHCH2], 2.73, 3.23 (1 and 1H, respectively,
2d, J=14.6, CH2S), 2.86 (2H, t, J=17.3, CH2Ph), 2.90 (3H, s, SO2CH3), 3.30±3.45 (2H, m,
NCH2), 3.50±3.60 (1H, m, CHN), 5.02 (1H, t, J=6.1, NHCH2), 5.19 (1H, d, J=4.9, CHNH),
7.15±7.35 (5H, m, Ph); ꢁC 20.25, 20.5, 27.05, 32.55, 36.55, 39.25, 39.45, 44.45, 44.55, 44.65, 49.55,
51.55, 59.2, 128.8 (2C), 128.85, 128.95 (2C), 137.95; m/z 326 (M+^88, <1%), 323 (22), 259 (43), 230
(66), 136 (15), 135 (100), 119 (13), 109 (49), 108 (23), 107 (33), 230 (60), 136 (15), 135 (100), 105 (18),
93 (40), 91 (50), 81 (14), 79 (42), 77(14), 67 (29), 65 (16), 55 (19), 44 (23), 43 (27), 41 (40) (found: C,
53.88; H, 6.93; N, 6.66; S, 15.99. C18H28N2O4S2 requires: C, 53.97; H, 7.05; N, 6.99; S, 16.01%).
4.2.4.5. (1S,2R,4S)-N-(Naphth-1-ylmethyl)-2-methylsulfonylamino-7,7-dimethylbicyclo[2.2.1]-
hept-1-ylmethanesulfonamide 12h. Yellow solid, tR 15.7, Rf 0.42 (hexane/ethyl acetate: 1/1); mp
117±119ꢀC (ethyl acetate/hexane); [ꢀ]D ^15.3 [c=1.35 (CHCl3)]; ꢂ (melted) 3299 (NH), 3046
(CHˆC), 1318 cm^1 (SO2); ꢁH 0.60, 0.84 [3 and 3H, respectively, 2s, C(CH3)2], 1.60±1.90 [7H, m,
(CH2)2CHCH2], 2.64, 3.11 (1 and 1H, respectively, 2d, J=14.6, CH2S), 2.95 (3H, s, SO2CH3),
3.45±3.60 (1H, m, CHN), 4.78 (2H, d, J=2.4, CH2Ph), 4.83, 5.02 (1 and 1H, respectively, 2s,
2ÂNH), 7.40±7.65 (7H, m, ArH); ꢁC 21.1, 20.3, 27.05, 32.65, 39.25, 40.75, 44.6, 45.2, 49.45, 50.05,

1642
O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
52.25, 59.2, 125.35, 125.45, 126.15, 126.2, 126.85, 127.35, 128.85, 128.9, 129.1, 129.15; m/z 321
(M+^129, <1%), 235 (22), 156 (16), 155 (59), 154 (100), 141 (20), 135 (14), 129 (22), 128 (19), 127
(23), 115 (12), 109 (11), 108 (13), 107 (32), 106 (52), 93 (11), 91 (18), 79 (16), 77 (17), 44 (26), 41
(13) (found: C, 58.69; H, 6.62; N, 5.34; S, 14.44. C22H30N2O4S2 requires: C, 58.64; H, 6.71; N,
6.22; S, 14.23%).
4.3. Enantioselective addition of dialkylzinc to aldehydes in the presence of ligands 12 or 13 and
titanium tetraisopropoxide. General procedure
To a solution of corresponding ligand 12 or 13 (1 mmol) in toluene (5 ml) under nitrogen
atmosphere was added the corresponding solution of dialkylzinc reagent (9 mmol, 4.5 ml, ca. 2 M)
at ^20ꢀC. After 10 min, titanium tetraisopropoxide (6.5 mmol, 2 ml) was added to the above
solution and after an additional 10 min the corresponding aldehyde (5 mmol) was successively
added. The resulting mixture was stirred at the same temperature for 2 h. Then, methanol (ca. 1
ml) and saturated NH4Cl solution (ca. 20 ml) were successively added, the mixture was ®ltered
through Celite, extracted with ethyl acetate (3Â50 ml) and the organic layer was dried over
Na2SO4. The solvents were removed under reduced pressure (15 torr) and the residue was distilled
bulb to bulb to yield the expected alcohols. Yields and enantiomeric ratios (e.r.) are included in
Tables 3±6. Compounds 16±20 were already described by us and were characterised by compar-
ison of their physical and spectroscopic data with those reported in the literature.18 Spectroscopic
and physical data, as well as literature references, follow.
4.3.1. 3-Nonanol 2018
tR (S-TFA-20) 54.44, tR (R-TFA-20) 54.88 (A conditions); [ꢀ]D=+9.2 [c=7.06, CHCl3; e.r.
(R/S) 98.0:2.0].
4.3.2. 1-Phenylpentan-3-ol 2137
Colourless oil, bp 140±145ꢀC (0.1 torr), tR 7.8; tR (R±TFA-21) 117.92, tR (S-TFA-21) 119.61
(D conditions); Rf 0.75 (hexane/ethyl acetate: 1/1); [ꢀ]D ^21.2 [c=7.72 (EtOH), e.r. (R/S)
97.0:3.0]; ꢂ (®lm) 3404 (OH), 1629 (CHˆC) cm^1; ꢁH 0.93 (3H, q, J=5.8, CH3), 1.40±1.60 (2H,
m, CH2CH3), 1.65±1.89 (2H, m, CH2CH2Ph), 2.60±2.75 (2H, m, CH2Ph), 2.75±2.80 (1H, m,
CHO), 3.53 (1H, s, OH), 7.15±7.30 (5H, m, Ph); ꢁC 9.75, 30.15, 32.0, 34.15, 72.5, 125.65 (2C),
128.3 (3C), 142.15; m/z 165 (M++1, <1%), 164 (M+, 3), 146 (29), 117 (54), 104 (27), 92 (34), 91
(100), 78 (16), 65 (16), 59 (17), 44 (22), 43 (15), 41 (12).
4.3.3. 1-Cyclohexy-1-propanol 2237
Colourless oil, bp 105±110ꢀC (0.1 torr), tR 5.1; tR (S-TFA-22) 37.20, tR (R-TFA-22) 37.50 (B
conditions); Rf 090 (hexane/ethyl acetate: 1/1); [ꢀ]D +7.7 [c=1.63 (CHCl3); e.r. (R/S) 96.0:4.0]; ꢂ
(®lm) 3369 cm^1 (OH); ꢁH 0.95 (3H, t, J=7.3, CH3), 1.00±1.85 (13H, m, 6ÂCH2, OH), 3.20±3.35
(1H, m, CHO); ꢁC 10.15, 26.15, 26.35, 26.5, 26.75, 27.7, 29.25, 43.1, 77.55; m/z 141 (M+^1,
<1%), 113 (37), 95 (85), 83 (11), 82 (26), 81 (14), 69 (11), 67 (43), 59 (100), 58 (47), 57 (15), 56
(13), 55 (51), 54 (11), 43 (25), 41 (66).
4.3.4. (E)-4-Hexen-3-ol 2337
Colourless oil, bp 30ꢀC (760 torr), tR 2.0; tR (R-23) 12.82, tR (S-23) 13.13 (C conditions); Rf
0.59 (hexane/ethyl acetate: 1/1); [ꢀ]D +0.15 [c=0.45 (CHCl3); e.r. (R/S) 57.0:43.0]; ꢂ (®lm) 3403

O. Prieto et al. / Tetrahedron: Asymmetry 11 (2000) 1629±1644
1643
(OH), 3034, 1663, 1638 cm^1 (HCˆC); ꢁH 0.83 (3H, t, J=7.3 CH2CH3), 1.35±1.55 (2H, m,
CH2CH3), 1.60±1.65 (3H, m, CH3CH), 3.85±3.95 (1H, m, CHCH2), 5.35±5.55 (1H, m,
CHCHCH), 5.55±5.65 (1H, m, CHCH3); ꢁC 9.75, 17.65, 25.55, 30.1, 126.9, 134.0; m/z 100 (M+,
<1%), 92 (45), 91 (79), 71 (26), 65 (12), 45 (21), 44 (45), 43 (100), 41 (19).
4.3.5. (E)-1-Phenyl-1-penten-3-ol 2437
Colourless oil, bp 140±145ꢀC (0.1 torr), tR 8.49; tR (R-H2-TFA-24R-TFA-21) 117.92, tR (S-
H2-TFA-24S-TFA-21) 119.61 (D conditions); Rf 0.73 (hexane/ethyl acetate: 1/1); [ꢀ]D +0.75
[c=2.14 (CHCl3); e.r. (R/S) 56.0/44.0]; ꢂ (®lm) 3381 (OH), 3090, 1590 cm^1 (CHˆC); ꢁH 0.94
(3H, t, J=7.4, CH3), 1.60±1.70 (2H, m, CH2), 2.28 (1H, s, OH), 4.15±4.30 (1H, m, CH2O), 6.15±
6.25 (1H, m, CHPh), 6.25±6.55 (1H, m, CHCHO), 7.20±7.40 (5H, m, Ph); ꢁC 9.65, 30.1, 74.25,
126.35 (2C), 127.45, 128.45 (2C), 130.25, 132.15, 136.65; m/z 163 (M++1, 2%), 162 (M+, 21),
144 (39), 143 (12), 134 (13), 133 (81), 131 (14), 129 (100), 128 (56), 127 (16), 115 (59), 92 (16), 91
(58), 79 (20), 78 (25), 77 (50), 71 (15), 65 (20).
4.3.6. 1-Phenyl-1-pentin-3-ol 2537
Colourless oil, bp 145±150ꢀC (0.1 torr), tR 8.28; tR (R-H2-TFA-25R-TFA-21) 117.92, tR (S-
H2-TFA-25S-TFA-21) 119.61 (D conditions); Rf 0.69 (hexane/ethyl acetate: 1/1); [ꢀ]D +7.8
[c=2.12 (Et2O); e.r. (R/S) 69.0:31.0]; ꢂ (®lm) 3374 (OH), 2192 (CꢁC), 1595 cm^1 (Ph); ꢁH 1.05
(3H, t, J=7.3, CH3), 1.70±1.90 (2H, m, CH2), 2.73 (1H, s, OH), 4.54 (1H, t, J=6.4, CHO), 7.25±
7.45 (5H, m, Ph); ꢁC 9.4, 30.85, 64.0, 84.75, 89.95, 128.15 (2C), 128.2, 131.55 (3C); m/z 161 (M++1,
<1%), 132 (16), 131 (100), 103 (33), 102 (14), 77 (34), 51 (20), 44 (33), 43 (14).
Acknowledgements
This work was ®nancially supported by the DGICYT (Project PB97-0133) from the Spanish
Ministerio de Educacion y Cultura and Generalitat Valenciana (Project GVDOC99-2-4).
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