Chiral lithium amido sulfide ligands for asymmetric addition reactions of alkyllithium reagents to aldehydes

Article abstract of DOI:10.1016/S0957-4166(02)00864-9

Six chiral amino sulfides have been synthesised from the amino acids phenylalanine, phenylglycine and valine. These amino sulfides were used as chiral ligands in the asymmetric addition of n-butyllithium and metyllithium to various aldehydes at low temperatures. The highest stereoselectivities were obtained with benzaldehyde, resulting in 1-phenyl-1-pentanol and 1-phenyl-1-ethanol in enantiomeric excesses of >98.5 and 95%, respectively. These stereoselectivities were significantly higher than those induced by the ether analogues.

Full text of DOI:10.1016/S0957-4166(02)00864-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 439–447
Chiral lithium amido sulfide ligands for asymmetric addition
reactions of alkyllithium reagents to aldehydes
Johan Granander, Richard Sott and Go¨ran Hilmersson*
Department of Chemistry, Organic Chemistry, Go¨teborg University, S-412 96 Go¨teborg, Sweden
Received 12 November 2002; revised 13 December 2002; accepted 16 December 2002
Abstract—Six chiral amino sulfides have been synthesised from the amino acids phenylalanine, phenylglycine and valine. These
amino sulfides were used as chiral ligands in the asymmetric addition of n-butyllithium and metyllithium to various aldehydes at
low temperatures. The highest stereoselectivities were obtained with benzaldehyde, resulting in 1-phenyl-1-pentanol and 1-phenyl-
1-ethanol in enantiomeric excesses of >98.5 and 95%, respectively. These stereoselectivities were significantly higher than those
induced by the ether analogues. © 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
organic synthesis.7 We have previously reported the
selectivities and solution structures of a number of
chiral lithium amides2g–i,8 with internal coordinating
oxygen and nitrogen atoms, used in the asymmetric
addition of different organolithium compounds to alde-
hydes. In the work reported herein, we have developed
a number of chiral amino sulfides from the amino acids
phenylalanine, phenylglycine, and valine. These amino
sulfides have been used in the asymmetric addition of
methyllithium (MeLi) and n-butyllithium (n-BuLi) to
various aldehydes at low temperatures and their asym-
metric induction properties have been compared to
those of their amino ether analogues.
Synthesis using organometallic reagents is a highly ver-
satile way to create new carbonꢀcarbon bonds while at
the same time introducing a stereogenic center. Exten-
sive research has been directed toward the development
of chiral ligands that bind non-covalently to the
organometallic reagent to allow asymmetric synthesis.1
Chiral lithium amides with an internal coordinating
group, such as an amine or ether, have been shown to
be effective ligands in the enantioselective addition of
alkyllithium reagents to aldehydes2 as well as the enan-
tioselective deprotonation of epoxides.3 Chiral amides
containing a chelating sulfur atom have proven very
successful in asymmetric reactions such as the addition
of diethylzinc to aromatic aldehydes,4 palladium-
catalysed allylic substitutions,5 and copper-catalysed
conjugate addition of Grignard reagents to enones.6
Sulfur is more polarizable than oxygen and nitrogen
and exhibits a higher affinity for transition metals but it
is not clear how it would coordinate to the smaller and
harder lithium atom. To the best of our knowledge
there has only been one report where a chiral lithium
amide containing a sulfur atom has been used as a
ligand.4e A lithium amide thiolate was used as a ligand
in the asymmetric addition of diethylzinc to benzalde-
hyde yielding the corresponding alcohol in 76% enan-
tiomeric excess (ee). However the acidity of the
a-protons of sulfides is utilized in the generation of
a-lithiated sulfides which are common nucleophiles in
2. Results and discussion
The amino sulfides 7a–f were easily synthesised from
the enantiomerically pure amino acids phenylalanine,
phenylglycine and valine in good yields (Scheme 1). The
amino acids 1 were reduced to the corresponding amino
alcohols 2 using lithium aluminium hydride and the
amino group transformed into an amide group using
di-tert-butyl dicarbonate. This was necessary in order
to avoid an internal substitution reaction when the
hydroxyl group is changed into a sulfonyloxy group in
the next step. The amido alcohols 3 were subsequently
reacted with methanesulfonyl chloride resulting in the
amido sulfonates 4. The methylsulfonyloxy group was
substituted by the appropriate thiolate anion, yielding
the amido sulfides 5. The tert-butyl carbonate group
was removed using concentrated hydrochloric acid and
* Corresponding author. Fax: (+46) 31 7723840; e-mail: hilmers@
organic.gu.se
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00864-9

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J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
Scheme 1. Synthesis of the chiral amino sulfides.
MeLi and n-BuLi to benzaldehyde are presented below
(Table 1).
the resulting primary amino sulfides 6 were condensed
with acetone to afford the corresponding imines, which
were subsequently reduced cleanly with sodium borohy-
dride to the desired secondary amino sulfides 7.
The lithium amido sulfides achieve moderate to excel-
lent stereoselectivity in the asymmetric addition reac-
tions. In the addition of MeLi to benzaldehyde the
highest stereoselectivity, 95% ee (entry 2), was obtained
with ligand 7a in a Et2O/THF mixture at −116°C. All
ligands gave high stereoselectivity at −116°C in a mix-
ture of Et2O/THF, none lower than 71% ee, with
conversions around 70%. At higher temperatures
(−78°C) the stereoselectivity was slightly lower while
the conversions were similar. However, changing the
solvent to pure Et2O drastically reduced both the
stereoselectivities and the conversions. When n-BuLi
was used as the organolithium reagent the stereoselec-
tivity induced by the chiral amido sulfides was even
higher. The highest stereoselectivity obtained, >98.5%
ee (entry 14), was again with ligand 7a in a Et2O/THF
mixture at −116°C, while ligands 7b, 7e, and 7f induced
high stereoselectivities (>90% ee) under the same reac-
tion conditions. The conversions of the reactions were
around 85%. The stereoselectivity of the reaction was
reduced by some 10% when the reactions were per-
formed at −78°C while the conversions were largely
The amino sulfides were then used as chiral ligands in
the addition of MeLi and n-BuLi to aldehydes (Scheme
2) to evaluate their ability to induce asymmetry in these
reactions.
The ligand was dissolved in diethyl ether (Et2O) or a
1:1 mixture of tetrahydrofuran (THF) and Et2O and
the solution was cooled to −78°C prior to the addition
of the alkyllithium reagent. This was done to avoid the
possibility of deprotonation of an a-proton of the
sulfide by the base, which is known to proceed rapidly
at room temperature. Ligands with a phenyl group
attached to the sulfur atom are especially prone to
undergo deprotonation. However, quenching experi-
ments with CH3OD performed at −78°C did not indi-
cate any deprotonation of the a-proton of the sulfide.
Benzaldehyde was added slowly as a solution in tolu-
ene. In some of the experiments the solution was fur-
ther cooled to −116°C before benzaldehyde was added.
The results of the asymmetric addition reactions of
Scheme 2. Asymmetric addition of alkyllithium reagents to aldehydes.

J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
441
Table 1. Asymmetric alkylation of benzaldehyde (1.0 equiv.) with MeLi or n-BuLi (14.5 equiv.) in the presence of the chiral
amines 7a–f (10.0 equiv.). The ees and conversions of the product alcohols, 1-phenyl-1-ethanola 9a and 1-phenyl-1-pentanolb
9b were determined by chiral stationary phase GC analysis
Entry
Ligand
Organolithium reagent
Temp. (°C)
Et2O/THF
Conv. (%)
Et2O
Conv. (%)
ee (%)
ee (%)
1
2
3
4
5
6
7
8
(S)-7a
(R)-7a
(S)-7b
(S)-7b
(S)-7c
(S)-7c
(S)-7d
(S)-7d
(R)-7e
(R)-7e
(S)-7f
(S)-7f
(S)-7a
(R)-7a
(S)-7b
(S)-7b
(S)-7c
(S)-7c
(S)-7d
(S)-7d
(R)-7e
(S)-7e
(S)-7f
(S)-7f
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
−78
−116
88 (R)
95 (S)
85 (R)
84 (R)
66 (R)
71 (R)
75 (R)
83 (R)
78 (S)
92 (S)
78 (R)
92 (R)
90 (R)
\98.5 (S)
85 (R)
94 (R)
57 (R)
68 (R)
68 (R)
81 (R)
84 (S)
97 (R)
82 (R)
91 (R)
65
67
69
62
70
74
72
86
69
77
78
89
79
82
82
84
81
87
87
92
74
80
90
72
–
–
22
–
22
–
59
–
53
–
32
–
56
80
82
83
90
75
87
83
88
46
70
87
91
34 (S)
–
12 (R)
–
29 (R)
–
25 (R)
–
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2 (S)
–
27 (R)
79 (R)
97 (S)
61 (R)
83 (R)
46 (R)
70 (R)
25 (R)
58 (R)
41 (S)
87 (R)
32 (R)
71 (R)
a Absolute configuration determined by preparing an authentic sample of (S)-9a.
b Absolute configuration determined by comparing the specific rotation with the literature value.2b
unaffected. The stereoselectivity was generally lower in
Et2O, but ligand 7a still gave 97% ee at −116°C. The
conversions were largely unaffected by the change of
solvents. In all reactions the product obtained had the
opposite configuration to the ligand itself. A relatively
large excess of both the ligand and the alkyllithium
reagent, compared to the aldehyde substrate, was used
to ensure a high conversion and that only alkyllithium
reagent coordinated to the ligand would react with the
substrate. No attempt to systematically determine the
optimum ratios between ligand/reagent/substrate was
made but earlier studies show that both more substrate
and less ligand can be used without deteriorating either
the conversion or stereoselectivities of the reactions.2h
a lower stereoselectivity. Perhaps a strong chelate com-
plex is not as important, as previously argued when
comparing lithium amides of amino ethers and
Scheme 3. The chiral amino ethers 10a–c.
Table 2. Asymmetric alkylation of benzaldehyde (1.0
equiv.) with n-BuLi (14.5 equiv.) in the presence of the
chiral amines 7b, 7d, 7f, and 10a–c (10.0 equiv.) at
−116°C. The ees of the product 1-phenyl-1-pentanola 9b
were determined by chiral stationary phase GC analysis
In previous studies by our group several chiral amino
ethers have been synthesised and used as ligands in the
asymmetric addition of n-BuLi to benzaldehyde. Three
of the previously studied amines,2i 10a–c, are the ether
analogues of the amino sulfides with an ethyl group
attached to the sulfur atom (Scheme 3). The asymmet-
ric induction properties of the sulfide and ether ana-
logues in the addition of n-BuLi to benzaldehyde at
−116°C are presented below (Table 2).
Entry
Ligand
Et2O/THF ee (%)
Et2O ee (%)
1
(S)-7b
(S)-10a
(S)-7d
(S)-10b
(S)-7f
94 (R)
79 (R)
81 (R)
69 (R)
91 (R)
74 (R)
83 (R)
60 (R)
58 (R)
41 (R)
16 (R)
44 (R)
2b
3
4b
5
It is clear that the amido sulfides are superior to their
oxygen analogues in this reaction. These results came as
a bit of a surprise since we expected that the sulfur
would coordinate more weakly to the lithium atom
than oxygen and thus make a less rigid chelate yielding
6b
(S)-10c
a Absolute configuration determined by comparing the specific rota-
tion with the literature value.2b
b Ref. 2i.

442
J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
diamines, to achieve a high degree of stereoselectivity.
It is also interesting to note that both kinds of amides
yield the product with configuration opposite to that of
the ligand, indicating that the two transition states are
similar.
3. Conclusion
In conclusion, six novel chiral amino sulfides have been
synthesised and characterised. The amido sulfides have
been used in the asymmetric addition of MeLi and
n-BuLi to different aldehydes. The addition products
1-phenyl-1-ethanol, 1-phenyl-1-pentanol, 1-(o-tolyl)-1-
ethanol, 1-(o-tolyl)-1-pentanol and 1-cyclohexyl-1-pen-
tanol were obtained in 95, >98.5, 87, 96 and 93% ee,
respectively, at −116°C using ligand 7a. The selectivities
were only affected slightly by carrying out the reaction
at −78°C. These results represent the most successful
additions of alkyllithium reagents to aldehydes, in
terms of stereoselectivity, reported. In comparison with
their ether analogues they give far better selectivity.
NMR studies of the lithium amido sulfide complexes in
solution will be reported separately. These studies indi-
cate that the species present in these reactions are the
same as those present in the reactions mediated by
lithium amido ethers.
The amido sulfides were also tested as chiral inducers in
other addition reactions. The most successful ligand,
7a, was used in the addition of MeLi and n-BuLi to
o-tolualdehyde 8c and cyclohexanecarboxaldehyde 8e
at various temperatures and Et2O/THF as solvent mix-
ture (Table 3).
The results show that ligand 7a gives very good to
excellent stereoselectivities in all of the addition reac-
tions tested with stereoselectivities exceeding 86%
throughout the study, even at −78°C. In general, how-
ever, the ligand is slightly more effective with n-BuLi
than with MeLi. Ligand 7a was also used in the addi-
tion of MeLi to cyclohexanecarboxaldehyde but base-
line separation of the product enantiomers could not be
achieved on the chiral GC. Analysis of the chro-
matogram for the reaction performed at −116°C
showed only one peak, while at −78°C a small peak
overlapping with a much larger peak was discernible,
indicating that the higher temperature reaction also
occurred with high stereoselectivity.
4. Experimental
4.1. General
NMR spectra were recorded on a Varian 400 MHz
spectrometer using CDCl3 as solvent. Optical rotations
were measured using a Perkin–Elmer 341 LC polarime-
ter. IR spectra were recorded on a Perkin–Elmer 1600
Series FTIR spectrometer. Melting points were deter-
mined using a Bu¨chi Melting Point B-545 and are
uncorrected. HRMS (FAB) spectra were recorded on a
VG ZabSpec using a beam of Cs atoms as ionization
source and glycerol was used to dissolve the sample.
GC analyses were carried out using a Varian Star 3400
CX gas chromatograph equipped with a chiral station-
ary phase column (CP-Chirasil-DEX CB, 25 m, 0.32
It is difficult to explain the higher stereoselectivity of
the sulfides compared to that of the ethers. However,
there is a significant structural difference between a
chelate with oxygen and a chelate with sulfur. The LiꢀS
9
,
bond (ꢀ2.5 A) is considerably longer than the LiꢀO
10
,
bond (ꢀ2.0 A) which affects the geometry of the
chelate. This small, structural difference may at least
partially explain the enhancement of the stereoselectiv-
ity in the alkylation reactions with the sulfides com-
pared to those with the ethers.
Table 3. Asymmetric alkylation of aldehydes 8a, 8c, and 8e (1.0 equiv.) with MeLi or n-BuLi (14.5 equiv.) in the presence
of the chiral amine 7a (10.0 equiv.) in a Et2O/THF solvent mixture. The ees and conversions of the products 9aa, 9bb, 9cc,
9dd, and 9ed were determined by chiral stationary phase GC analysis
Entry
Ligand
Organolithium reagent
Aldehyde
Temp. (°C)
ee (%)
Conv. (%)
1
2
3
4
5
6
7
8
(S)-7a
(R)-7a
(S)-7a
(R)-7a
(S)-7a
(S)-7a
(S)-7a
(S)-7a
(S)-7a
(S)-7a
MeLi
MeLi
n-BuLi
n-BuLi
MeLi
8a
8a
8a
8a
8c
8c
8c
8c
8e
8e
−78
−116
−78
−116
−78
−116
−78
−116
−78
88 (R)
95 (S)
90 (R)
\98.5 (S)
91 (R)
87 (R)
95
96
86
93
65
67
79
82
69
73
87
88
88
74
MeLi
n-BuLi
n-BuLi
n-BuLi
n-BuLi
9
10
−116
a Absolute configuration determined by preparing an authentic sample of (S)-9a.
b Absolute configuration determined by comparing the specific rotation with the literature value.2b
c Absolute configuration determined by preparing an authentic sample of (S)-9c.
d Absolute configuration not yet determined.

J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
443
mm) from Chrompack. Analyses were done using He
(1.5 mL min−1) as carrier gas (injector 225°C, detector
250°C). Dried solvents were distilled from sodium/
benzophenone.
128.7 (Ar), 129.2 (Ar), 129.6 (Ar), 129.8 (Ar), 136.3 (Ar),
137.7 (Ar), 155.3 (CꢁO); HRMS (FAB): MH+, found
344.1682. C20H26NO2S requires 344.1684.14,15
4.2.4.
(S)-N-t-BOC-2-Amino-3-phenyl-1-thioethyl-
4.2. Synthesis
propane, (S)-5d. Preparation identical to that of (S)-5a
except that ethanethiol was used instead of thiophenol.
Yield 97% as a slightly yellowish solid. The crude product
was recrystallized from hexane yielding white needle-
shaped crystals. Spectral data consistent with those
reported in the literature.16
The starting materials, the chiral amino acids, 1, were
purchased from Sigma-Aldrich and their reduction to the
corresponding amino alcohols,2i,11 2, protection as t-
BOC-amido alcohols,12 3, and conversion to methanesul-
fonates,12d,13 4, were made according to literature
procedures.
4.2.5.
(S)-N-t-BOC-2-Amino-3-methyl-1-thiophenyl-
butane, (S)-5e. Preparation identical to that of (S)-5a.
Yield 81% as a yellow oil. Spectral data consistent with
those reported in the literature.5e,14
4.2.1.
(S)-N-t-BOC-2-Amino-2-phenyl-1-thiophenyl-
ethane, (S)-5a. Thiophenol (7.51 g, 6.97 mL, 68.2 mmol,
1.1 equiv.) was added slowly to an ice cooled suspension
of sodium hydride (60% in mineral oil, 2.73 g, 68.2 mmol,
1.1 equiv.) in dry THF (150 mL). The mixture was allowed
to slowly reach room temperature and after one hour a
solution of crude (S)-4a (19.55 g, 62.0 mmol, 1.0 equiv.)
in dry THF (150 mL) was added slowly over 30 min. The
mixture was stirred at room temperature over night (12
h). Water (100 mL) was added, the mixture concentrated
under reduced pressure and the residue extracted with
CH2Cl2 (3×100 mL). The combined organic extract was
dried over Na2SO4 and the solvent evaporated under
reduced pressure yielding a clear yellow oil which slowly
crystallized (20.43 g, 100%). The crude product was
recrystallized from ethyl acetate:hexane yielding white
needle-shaped crystals. Spectral data were consistent with
those reported in the literature.14
4.2.6.
(S)-N-t-BOC-2-Amino-3-methyl-1-thioethyl-
butane, (S)-5f. Preparation identical to that of (S)-5a
except that ethanethiol was used instead of thiophenol.
Yield 70% as a yellow oil. Mp=65°C; [h]2D0=+19.3 (c 1.09,
CH2Cl2); wmax (KBr) 3318, 2977, 1639, 1538, 1452, 1367,
1304, 1251, 1176, 1015 cm−1; 1H NMR (400 MHz, CDCl3)
l 0.90 (d, J=7.3 Hz, 3H, C(CH3)3), 0.95 (d, J=7.3 Hz,
3H, C(CH3)3), 1.3 (t, J=7.5 Hz, 3H, CH2CH3), 1.45 (s,
9H, C(CH3)3), 1.90 (m, 1H, (CH3)2CH), 2.55 (q, J=7.5
Hz, 2H (SCH2CH3), 2.70 (m, 1H, SCH2CH), 3.6 (m, 1H,
CH(NHCO2)), 4.6(m, 1H, CONH);13CNMR(100MHz,
CDCl3) l 15.0 (CH(CH3)2), 17.9 (CH(CH3)2), 19.8
(CH2CH3), 26.7 (CH(CH3)2), 28.6 (C(CH3)3), 30.9
(CH2CH3), 35.0 (CHCH2S), 55.1 (CHCH2); HRMS
(FAB): MH+, found 248.1661. C12H26NO2S requires
248.1684.
4.2.2.
(S)-N-t-BOC-2-Amino-2-phenyl-1-thioethyl-
ethane, (S)-5b. Preparation identical to that of (S)-5a
except that ethanethiol was used instead of thiophenol.
Yield 96% of the crude product as a white solid which
was recrystallized from hexane yielding white needle-
shaped crystals. Mp=93–94°C; [h]2D0=+44.9 (c 1.01,
CH2Cl2); wmax (KBr) 3384, 2974, 1680, 1522, 1176, 731,
700 cm−1; 1H NMR (400 MHz, CDCl3) l 1.21 (t, J=7.4
Hz, 3H, SCH2CH3), 1.43 (s, 9H, (CH3)3CO), 2.44 (q,
J=7.4 Hz, 2H, SCH2CH3), 2.93 (d, J=6.0 Hz, 2H,
PhCHCH2), 4.84 (s (br), 1H, PhCHCH2), 5.18 (s (br), 1H,
CONHC), 7.26–7.37 (m, 5H, Ph); 13C NMR (100 MHz,
CDCl3) l 14.9 (SCH2CH3), 26.6 (SCH2CH3), 28.5
((CH3)3C), 38.5 (PhCHCH2), 54.1 (PhCHCH2), 79.9
((CH3)3C), 126.5 (o-Ph), 127.7 (p-Ph), 128.8 (m-Ph),
141.6 (i-Ph), 155.4 (OCONH); HRMS (FAB): MH+,
found 282.1527. C15H24NO2S requires 282.1528.
4.2.7. (S)-2-Amino-2-phenyl-1-thiophenyl-ethane, (S)-6a.
Crude (S)-5a (20.43 g, 62.0 mmol, 1.0 equiv.) was
dissolved in ethyl acetate (400 mL) and concentrated
hydrochloric acid (62.8 g, 53.2 mL, 0.62 mol, 10 equiv.)
added slowly. The mixture was stirred at room temper-
ature for 2 h. Water (200 mL) was added and the aqueous
layer separated. The organic layer was extracted with
aqueous hydrochloric acid (3×50 mL, 10%). The com-
bined aqueous extract was basified with aqueous sodium
hydroxide (800 mL, 5 M) and extracted with CH2Cl2
(4×100 mL). The combined organic extract was dried over
Na2SO4 and the solvent evaporated under reduced pres-
sure yielding a clear, slightly yellowish oil which quickly
crystallized (8.92 g, 63%). Spectral data consistent with
those reported in the literature.5e,17
4.2.8. (S)-2-Amino-2-phenyl-1-thioethyl-ethane, (S)-6b.
Preparation identical to that of (S)-6a. Yield 63% as a
clear, slightly yellowish oil. [h]2D0=+29.7 (c 1.33, CH2Cl2);
wmax (thin film) 3364, 3288, 2966, 1604, 1452, 700 cm−1;
1H NMR (400 MHz, CDCl3) l 1.26 (t, J=7.4 Hz, 3H,
SCH2CH3), 2.54 (q, J=7.4 Hz, 2H, SCH2CH3), 2.67 (dd,
J=9.4, 13.4 Hz, 1H, PhCHCH2), 2.90 (dd, J=4.2, 13.4
Hz, 1H, PhCHCH2), 4.10 (dd, J=4.2, 13.4 Hz, 1H,
PhCHCH2), 7.20–7.40 (m, 5H, Ph); 13C NMR (100 MHz,
CDCl3) l 15.1 (SCH2CH3), 26.5 (SCH2CH3), 42.0
(PhCHCH2), 55.2 (PhCHCH2), 126.6 (o-Ph), 127.6 (p-
Ph), 128.7 (m-Ph), 144.9 (i-Ph); HRMS (FAB): MH+,
found 182.0993. C10H16NS requires 182.1003.
4.2.3.
(S)-N-t-BOC-2-Amino-3-phenyl-1-thiophenyl-
propane, (S)-5c. Preparation identical to that of (S)-5a.
Yield 100% as a white solid which was recrystallized from
ethyl acetate:hexane yielding white needle-shaped crys-
tals. Mp=86°C; [h]D20=+21.9 (c 1.05, CH2Cl2); wmax (KBr)
3372, 2974, 1693, 1680, 1526, 1173, 737, 702, 698 cm−1;
1H NMR (400 MHz, CDCl3) l 1.40 (s, 9H, C(CH3)3), 2.92
(d, J=6.8 Hz, 2H, PhCH2), 3.04 (d, J=5.6 Hz, 2H,
CH2SPh), 4.06 (s (br), 1H, CH(NHCO2)), 4.67 (s (br),
1H, CONH), 7.17–7.37 (m, 10H, Ar); 13C (100 MHz,
CDCl3) l 28.5 (C(CH3)3), 38.0 (PhCH), 39.7 (CHCH2S),
51.5 (CHCH2), 79.6 (C(CH3)3), 126.5 (Ar), 126.8 (Ar),

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J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
4.2.9. (S)-2-Amino-3-phenyl-1-thiophenyl-propane, (S)-
6c. Preparation identical to that of (S)-6a. Yield 53% as
a clear, slightly yellowish oil. Spectral data consistent
with those reported in the literature.17
The product was purified by Kugelrohr distillation
(80°C, 0.040 mbar) followed by column chromatogra-
phy (aluminium oxide, dichloromethane) yielding a
clear, colourless oil. Yield 61%. [h]2D0=+90.0 (c 1.12,
CH2Cl2); wmax (thin film) 3296, 2960, 1600, 1452, 1167,
700 cm−1; 1H NMR (400 MHz, CDCl3) l 1.01 (d,
J=6.2 Hz, 3H, (CH3)2CHN), 1.10 (d, J=6.2 Hz, 3H,
(CH3)2CH), 1.25 (t, J=7.4 Hz, 3H, SCH2CH3), 2.52 (q,
J=7.4, 2H, SCH2CH3), 2.64 (sept., J=6.2 Hz, 1H,
(CH3)2CH), 2.68 (dd, J=9.0, 13.1 Hz, 1H, PhCHCH2),
2.84 (dd, J=4.5, 13.1 Hz, 1H, PhCHCH2), 3.81 (dd,
J=4.5, 9.0 Hz, 1H, PhCHCH2), 7.25–7.40 (m, 5H, Ph);
13C NMR (100 MHz, CDCl3) l 15.0 (SCH2CH3), 22.2
((CH3)2CHN), 24.5 ((CH3)2CHN), 26.3 (SCH2CH3),
4.2.10. (S)-2-Amino-3-phenyl-1-thioethyl-propane, (S)-
6d. Preparation identical to that of (S)-6a. Yield 97% as
a clear, slightly yellowish oil. Spectral data consistent
with those reported in the literature.16
4.2.11. (S)-2-Amino-3-methyl-1-thiophenyl-butane, (S)-
6e. Preparation identical to that of (S)-6a except that
ethanol saturated with HCl was used instead of conc.
HCl. Yield 95% as a yellow oil. Spectral data consistent
with those reported in the literature.5e,17
40.7
(PhCHCH2),
46.1
((CH3)2CHN),
59.3
(PhCHCH2), 127.3 (o-Ph), 127.4 (p-Ph), 128.6 (m-Ph),
143.9 (i-Ph); HRMS (FAB): MH+, found 224.1487.
C13H22NS requires 224.1473.
4.2.12. (S)-2-Amino-3-methyl-1-thioethyl-butane, (S)-6f.
Preparation identical to that of (S)-6a except that etha-
nol saturated with HCl was used instead of conc. HCl.
Yield 95% as a yellow oil. [h]2D0=+78.4 (c 1.02,
CH2Cl2); wmax (thin film) 3367, 2959, 1463, 1060 cm−1;
1H NMR (400 MHz, CDCl3) l 0.89 (d, J=7.1 Hz, 3H,
C(CH3)3), 0.91 (d, J=7.1 Hz, 3H, C(CH3)3), 1.23 (t,
J=7.5 Hz, 3H, CH2CH3), 1.65 (m, 1H, (CH3)2CH),
2.30 (m, 1H, SCH2CH), 2.50 (q, J=7.5 Hz, 2H
(SCH2CH3), 2.62 (m, 1H, CHNH), 2.72 (m, 1H,
SCH2CH); 13C NMR (100 MHz, CDCl3) l 15.0
(CH(CH3)2), 17.8 (CH(CH3)2), 19.4 (CH2CH3), 26.2
(NCH(CH3)2), 33.1 (CH2CH3), 38.0 (CHCH2S), 55.7
(CHCH2)); HRMS (FAB): MH+, found 148.1130.
C7H18NS requires 148.1160.
4.2.15. (S)-N-Isopropyl-2-amino-3-phenyl-1-thiophenyl-
propane, (S)-7c. Preparation identical to that of (S)-7a.
The crude product was purified by column chromatog-
raphy (aluminium oxide, dichloromethane) yielding a
clear, colourless oil. Yield 73%. [h]2D0=+5.3 (c 1.22,
CH2Cl2); wmax (thin film) 3312, 2961, 1583, 1480, 1173,
1
738, 700 cm−1; H NMR (400 MHz, CDCl3) l 0.98 (d,
J=6.4 Hz, 3H, NCH(CH3)2), 1.00 (d, J=6.4 Hz, 3H,
NCH(CH3)2), 2.86 (d, J=6.4 Hz, 2H, PhCH2), 2.88
(sept., J=6.4 Hz, 1H, NCH(CH3)2), 2.92 (dd, J=5.6,
12.9 Hz, 1H, CH2SPh), 3.03 (dd, J=5.4, 12.9 Hz, 1H,
CH2SPh), 3.06 (m, 1H, CHCH2), 7.17–7.35 (m, 10H,
Ar); 13C (100 MHz, CDCl3) l 23.4 (NCH(CH3)2), 23.5
(NCH(CH3)2, 38.3 (PhCH2), 40.6 (CHCH2), 46.0
(NCH(CH3)2, 55.6 (CHCH2), 126.1 (Ar), 126.5 (Ar),
128.6 (Ar), 129.0 (Ar), 129.4 (Ar), 129.6 (Ar), 136.7
(Ar), 138.9 (Ar); HRMS (FAB): MH+, found 286.1625.
C18H24NS requires 286.1629.
4.2.13. (S)-N-Isopropyl-2-amino-2-phenyl-1-thiophenyl-
ethane, (S)-7a. Acetone (11.3 g, 14.3 mL, 0.19 mol, 5.0
equiv.) and crude (S)-6a (8.92 g, 38.9 mmol, 1.0 equiv.)
were dissolved in dry benzene (300 mL) and the mixture
refluxed over night (14 h) with a Dean–Stark trap to
collect the water formed. The mixture was allowed to
cool to room temperature and then concentrated under
reduced pressure. The residue was dissolved in dry
ethanol (250 mL), NaBH4 (2.94 g, 77.8 mmol, 2.0
equiv.) added and the mixture stirred at room tempera-
ture for 8 h. Water (100 mL) was added and the
mixture concentrated under reduced pressure. The
residue was extracted with CH2Cl2 (3×100 mL), the
combined extracts dried over Na2SO4, and the solvent
evaporated under reduced pressure yielding a white
solid (10.61 g, 100%). Mp 59–60°C; [h]2D0=+7.8 (c 1.03,
CH2Cl2); wmax (KBr) 3289, 2961, 1577, 1480, 1086, 744
4.2.16.
(S)-N-Isopropyl-2-amino-3-phenyl-1-thioethyl-
propane, (S)-7d. Preparation identical to that of (S)-7a.
The crude product was purified by distillation under
reduced pressure yielding a clear, colourless oil. The
product was further purified by column chromatogra-
phy (aluminium oxide, dichloromethane) yielding a
clear, colourless oil. Yield 35%. Bp=93°C, 0.10 mbar;
[h]2D0=+18.9 (c 1.14, CH2Cl2); wmax (thin film) 3298,
1
2961, 1600, 1452, 1173, 700 cm−1; H NMR (400 MHz,
1
cm−1; H NMR (400 MHz, CDCl3) l 0.91 (t, J=6.1
CDCl3) l 1.00 (d, J=6.3 Hz, 3H, NCH(CH3)2), 1.07
(d, J=6.3 Hz, 3H, NCH(CH3)2), 1.22 (t, J=7.4 Hz,
3H, SCH2CH3), 2.49 (dd, J=6.2, 12.9 Hz, 1H,
CHCH2S), 2.51 (q, J=6.3 Hz, 2H, SCH2CH3), 2.61
(dd, J=8.4 Hz, 1H, CHCH2S), 2.77 (dd, J=7.4, 13.5
Hz, 1H, PhCH2), 2.82 (dd, J=6.0, 13.5 Hz, 1H,
PhCH2), 2.92 (sept., J=6.3 Hz, 1H, NCH(CH3)2), 3.02
(dddd, J=6.0, 6.2, 7.4, 8.4 Hz, 1H, CHCH2), 7.20–7.32
Hz, 6H, (CH3)2CHN), 2.52 (sept., J=6.1 Hz, 1H,
(CH3)2CHN), 2.97 (dd, J=9.2, 13.2 Hz, 1H,
PhCHCH2), 3.15 (dd, J=4.6, 13.2 Hz, 1H, PhCHCH2),
3.77 (dd, J=4.6, 9.2 Hz, 1H, PhCHCH2), 7.11–7.32 (m,
10H, Ph); 13C NMR (100 MHz, CDCl3) l 22.29
((CH3)2CHN), 24.54 ((CH3)2CHN), 42.89 (PhCHCH2),
46.24 ((CH3)2CHN), 126.55 (p-Ar), 127.31 (Ar), 127.59
(p-Ar), 128.69 (Ar), 129.15 (Ar), 130.13 (Ar), 135.91
(i-ArS), 143.59 (i-Ar); HRMS (FAB): MH+, found
272.1430. C17H22NS requires 272.1473.
(m, 5H, Ar); 13C (100 MHz, CDCl3)
l 15.1
(SCH2CH3), 23.4 (NCH(CH3)2), 23.5 (NCH(CH3)2),
26.8 (SCH2CH3), 36.6 (CHCH2S), 40.7 (PhCH2), 45.9
(NCH(CH3)2), 55.8 (CHCH2), 126.4 (Ar), 128.6 (Ar),
129.5 (Ar), 139.1 (Ar); HRMS (FAB): MH+, found
238.1629. C14H24NS requires 238.1629.
4.2.14.
(S)-N-Isopropyl-2-amino-2-phenyl-1-thioethyl-
ethane, (S)-7b. Preparation identical to that of (S)-7a.

J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
445
4.2.17. (S)-N-Isopropyl-2-amino-3-methyl-1-thiophenyl-
butane, (S)-7e. Preparation identical to that of (S)-7a
except that chloroform was used as solvent and a
reversed Dean–Stark trap was used to collect the water
formed. Yield 82%. [h]2D0=+30.0 (c 0.96, CH2Cl2); wmax
GC: 100°C for 5 min then temperature was raised to
125°C, 14.7 (S) and 15.4 (R) min.
4.2.21. ( )-1-(o-Tolyl)-1-ethanol, 9c. Preparation identi-
cal to that of ( )-9a except that 8c was used instead of
8a. Yield 66% as a clear, slightly yellowish oil. Spectral
properties consistent with those reported in the litera-
ture.19 Retention times on chiral stationary phase GC:
100°C for 6 min then temperature was raised to 120°C,
15.0 (R) and 18.1 (S) min.
1
(thin film) 3324, 2929, 1480, 1236, 737, 690 cm−1; H
NMR (400 MHz, CDCl3) l 0.93 (d, J=6.8 Hz, 3H,
CH(CH3)2), 1.01 (d, J=6.4 Hz, 3H, NCH(CH3)2), 1.94
(m, 1H, CH(CH3)2), 2.59 (dd, 1H, CHCH2S), 2.82 (m,
1H, NCH(CH3)2), 2.60 (dd, J=4.1 Hz, 1H, CHCH2S),
2.83 (dd, J=6.2 Hz, 1H, CHCH2S), 2.88 (dd, J=6.8
Hz, 1H, CHCH2S), 3.01 (dd, J=5.2 Hz, 1H, CHCH2S),
7.15–7.37 (m, 5H, Ar); 13C NMR (100 MHz, CDCl3) l
18.4, (2C, CH(CH3)2), 23.6 ((CH3)2CHN), 23.7
((CH3)2CHN), 30.3 ((CH3)2CHN), 36.6 (CH2CH), 46.5
((CH3)2CHCH), 59.1 (CHCH2), 126.0 (Ar), 129.0 (Ar),
129.5 (Ar), 137.2 (Ar); HRMS (FAB): MH+, found
238.1675. C14H24NS requires 238.1629.
4.2.22. ( )-1-(o-Tolyl)-1-pentanol, 9d. Preparation iden-
tical to that of ( )-9a except that n-BuLi was used
instead of MeLi and 8c was used instead of 8a. Yield
89% as a clear, colourless oil. Spectral properties con-
sistent with those reported in the literature.2d–f Reten-
tion times on chiral stationary phase GC: 125°C for 6
min then temperature was raised to 125°C, 27.5 and
28.9 min.
4.2.18.
(S)-N-Isopropyl-2-amino-3-methyl-1-thioethyl-
butane, (S)-7f. Preparation identical to that of (S)-7a
except that chloroform was used as solvent and a
reversed Dean–Stark trap was used to collect the water
formed. Yield 60%. [h]2D0=+38.5 (c 0.96, CH21Cl2); wmax
(thin film) 3297, 2958, 1462, 1173, 724 cm−1; H NMR
4.2.23. ( )-1-Cyclohexyl-1-pentanol, 9e. Preparation
identical to that of ( )-9a except that n-BuLi was used
instead of MeLi and 8e was used instead of 8a. Yield
59% as a clear, colourless oil. Spectral properties con-
sistent with those reported in the literature.2h Retention
times on chiral stationary phase GC: 100°C for 5 min
then temperature was raised to 125°C, 16.1 and 16.6
min.
(400 MHz, CDCl3)
l 0.88 (d, J=6.9 Hz, 3H,
CH(CH3)2), 1.03 (d, J=7.2 Hz, 3H, NCH(CH3)2), 1.25
(t, J=7.4 Hz, 3H, SCH2CH3), 1.87 (m, 1H, CH(CH3)2),
2.46 (m, 1H CHCH2S), 2.52 (q, J=7.2 Hz, 2H,
SCH2CH3), 2.60 (dd, J=4.1 Hz, 1H, CHCH2S), 2.83
(dd, J=6.2 Hz, 1H, NCH(CH3)2); 13C NMR (100
MHz, CDCl3) l 15.0 (CH3CH2), 18.2 ((CH3)2CH), 18.4
((CH3)2CH), 23.6 ((CH3)2CHN), 23.8 ((CH3)2CHN),
26.7 ((CH3)2CH), 30.2 ((CH3)2CH), 34.3 (CH2CH),
46.6 ((CH3)2CHN), 59.3 (CHCH2); HRMS (FAB):
MH+, found 190.1627. C10H24NS requires 190.1629.
4.2.24. (S)-1-Phenyl-1-ethanol, (S)-9a. Dimethylzinc
(2.28 mL, 2.0 M in toluene, 4.56 mmol, 1.1 equiv.) was
added slowly to an ice cooled suspension of sodium
hydride (60% dispersion in mineral oil, 0.183 g, 4.56
mmol, 1.1 equiv.) in dry THF (15 mL). The mixture
was stirred at this temperature for 1 h. (R)-Styrene
oxide (0.50 g, 0.48 mL, 4.2 mmol, 1.0 equiv.) dissolved
in dry THF (5 mL) was added slowly. The mixture was
allowed to reach room temperature and was stirred
over night (22 h). The mixture was concentrated in
vacuo and the residue dissolved in saturated aqueous
NH4Cl (50 mL) and extracted with dichloromethane
(3×50 mL). The combined organic extract was dried
over Na2SO4 and the solvent removed in vacuo yielding
the crude product. The crude product was purified
using column chromatography (silica, ethyl ace-
tate:hexane 1:3) yielding the pure product as a clear,
colourless oil (0.305 g, 59%). [h]2D0=−56.0 (c 1.22,
CHCl3). Other spectral properties identical to the
racemic material.
4.2.19. ( )-1-Phenyl-1-ethanol, 9a. MeLi (0.92 mL, 1.6
M in Et2O, 1.48 mmol, 1.5 equiv.) was added to dry
THF (20 mL) and the resulting mixture cooled to
−78°C over a Et2O/dry ice cooling bath. Compound 8a
(0.104 g, 0.98 mmol, 1.0 equiv.) was added slowly and
the mixture was stirred for 2 h while its temperature
slowly reached room temperature. Methanol (5.0 mL)
was added to quench the excess MeLi reagent and the
mixture was concentrated in vacuo. The residue was
dissolved in diluted hydrochloric acid (5.0 mL, 5%) and
the
resulting
mixture
was
extracted
with
dichloromethane (3×5 mL). The combined organic
extract was dried over Na2SO4 and the solvent removed
under reduced pressure. The resulting crude product, a
clear, yellowish oil, was purified using column chro-
matography (silica, ethyl acetate:hexane 20:80) yielding
the product as a clear colourless oil (0.090 g, 75%).
Spectral properties consistent with those reported in the
literature.18 Retention times on chiral stationary phase
GC: 100°C, 14.3 (R) and 16.3 (S) min.
4.2.25. (S)-1-(o-Tolyl)-1-ethanol, (S)-9c. (S)-9a (0.42 g,
3.4 mmol, 1.0 equiv.) was dissolved in dry Et2O (15
mL) and cooled to −78°C over a dry ice/acetone cool-
ing bath. t-Butyllithium (4.0 mL, 1.7 M in pentane, 6.8
mmol, 2.0 equiv.) was added slowly and the mixture
stirred for 2 h after which it was allowed to slowly
reach room temperature over a period of 2 h. The
orange solution was cooled to −78°C again and methyl
iodide added slowly. The mixture was stirred at this
temperature for 2 h after which it was allowed to slowly
reach room temperature and was stirred further over
night (17 h). Methanol (2.0 mL) was added to quench
any remaining t-butyllithium. Aqueous HCl (20 mL,
4.2.20. ( )-1-Phenyl-1-pentanol, 9b. Preparation identi-
cal to that of (rac)-9a except that n-BuLi was used
instead of MeLi. Yield 76% as a clear, colourless oil.
Spectral properties consistent with those reported in the
literature.2h Retention times on chiral stationary phase

446
J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
5%) was added and the mixture extracted with Et2O
(3×20 mL). The organic extract was dried over Na2SO4
and the solvent removed under reduced pressure. The
resulting yellowed oil was purified using column chro-
matography (silica, ethyl acetate:hexane 1:3) yielding a
clear slightly yellowish oil (0.399 g). The oil consisted of
70% of the desired product and 30% of the starting
material.
2002, 58, 4707–4716; (g) Arvidsson, P. I.; Hilmersson,
8
G.; Davidsson, O. Chem. Eur. J. 1999, 6, 2348–2355;
8
(h) Arvidsson, P. I.; Davidsson, O.; Hilmersson, G.
Tetrahedron: Asymmetry 1999, 10, 527–534; (i) Granan-
der, J.; Sott, R.; Hilmersson, G. Tetrahedron 2002, 58,
4717–4725.
3. (a) Cox, P. J.; Simpkins, N. S. Tetrahedron: Asymmetry
1991, 2, 1–26; (b) O’Brien, P. J. Chem. Soc., Perkin
Trans. 1 1998, 1439–1457.
4.3. General procedure for the alkylation of aldehydes
4. (a) Hof, R. P.; Poelert, M. A.; Peper, N. C. M. W.;
Kellogg, R. M. Tetrahedron: Asymmetry 1994, 5, 31–34;
(b) Kang, J.; Lee, J. W.; Kim, J. I. J. Chem. Soc.,
Chem. Commun. 1994, 2009–2010; (c) Rijnberg, E.;
Jastrzebski, J. T. B. H.; Janssen, M. D.; Boersma, J.;
van Koten, G. Tetrahedron Lett. 1994, 35, 6521–6524;
(d) Nakano, H.; Kumagai, N.; Matsuzaki, H.; Kabuto,
C.; Hongo, H. Tetrahedron: Asymmetry 1997, 8, 1391–
1401; (e) Anderson, J. C.; Cubbon, R.; Harding, M.;
James, D. S. Tetrahedron: Asymmetry 1998, 9, 3461–
3490.
5. (a) Frost, C. G.; Williams, J. M. J. Tetrahedron Lett.
1993, 34, 2015–2018; (b) Frost, C. G.; Williams, J. M.
J. Tetrahedron: Asymmetry 1993, 4, 1785–1788; (c)
Dawson, G. J.; Frost, C. G.; Martin, C. J.; Williams, J.
M. J. Tetrahedron Lett. 1993, 34, 7793–7796; (d)
Chesney, A.; Bryce, M. R.; Chubb, R. W. J.; Batsanov,
A. S.; Howard, J. A. K. Tetrahedron: Asymmetry 1997,
8, 2337–2346; (e) Adams, H.; Anderson, J. C.; Cubbon,
R.; James, D. S.; Mathias, J. P. J. Org. Chem. 1999,
64, 8256–8262.
6. (a) Zhou, Q.-L.; Pfaltz, A. Tetrahedron 1994, 50, 4467–
4478; (b) Lambert, F.; Knotter, D. M.; Janssen, M. D.;
van Klaveren, M.; Boersma, J.; van Koten, G. Tetra-
hedron: Asymmetry 1991, 2, 1097–1100; (c) Cran, G. A.;
Gibson, C. L.; Handa, S.; Kennedy, A. R. Tetrahedron:
Asymmetry 1996, 7, 2511–2514; (d) Nakagawa, Y.;
Kanai, M.; Nagaoka, Y.; Tomioka, K. Tetrahedron
Lett. 1996, 37, 7805–7808; (e) Dieter, R. K.; Tokles, M.
J. Am. Chem. Soc. 1987, 109, 2040–2046.
Inside a glovebox: dry solvent, either Et2O (2.0 mL) or
a mixture of THF (1.0 mL) and Et2O (1.0 mL), and the
amino sulfide (0.22 mmol, 10.0 equiv.) were added to a
reaction vessel, which was sealed with a septum. The
vessel was taken out of the glovebox, fitted with a
nitrogen inlet, and cooled to −78°C over a Et2O/dry ice
cooling bath. The alkyllithium solution (0.32 mmol,
14.5 equiv.), either MeLi (1.6 M in Et2O) or n-BuLi
(2.5 M in hexanes), was added slowly using a gas-tight
syringe. The mixture was stirred for 30 min and was in
some experiments cooled to −116°C over a Et2O /liquid
nitrogen cooling bath before the aldehyde solution
(6.25 vol% in toluene, 0.022 mmol, 1.0 equiv.) was
added slowly and the mixture stirred for 15 min before
being quenched with methanol (1.0 mL). The mixture
was allowed to reach room temperature and was aci-
dified by adding diluted hydrochloric acid (5%, 1.0
mL). The mixture was extracted with Et2O (2.5 mL)
and the organic phase dried over Na2SO4 and analysed
using chiral GC.
Acknowledgements
Financial support from the Swedish Research Council
(Vetenskapsra˚det) is gratefully acknowledged. We are
particularly indebted to Dr. Gunnar Stenhagen for his
invaluable help in getting the high resolution mass
spectrometer up running. Anna Sivenga˚rd is also
acknowledged for preliminary but encouraging results
on these chiral thio-amides as ligands in the asymmetric
alkylation reactions.
7. Boche, G. Angew. Chem., Int. Ed. Engl. 1989, 28, 277–
297.
8
8. (a) Hilmersson, G.; Davidsson, O. J. Org. Chem. 1995,
8
60, 7660–7669; (b) Hilmersson, G.; Davidsson, O. J.
Organomet. Chem. 1995, 489, 175–179; (c) Hilmersson,
8
G.; Arvidsson, P. I.; Davidsson, O.; Ha˚kansson, M. J.
Am. Chem. Soc. 1998, 120, 8143–8149; (d) Hilmersson,
G.; Malmros, B. Chem. Eur. J. 2001, 7, 337–341.
9. Olmstead, M. M.; Power, P. P. J. Am. Chem. Soc.
1990, 112, 8008–8014.
References
1. (a) Noyori, R. Asymmetric Catalysis in Organic Synthe-
sis; John Wiley & Sons: New York, 1994; (b) Compre-
hensive Asymmetric Catalysis; Jacobsen, E. N.; Pfaltz,
A.; Yamamoto, H., Eds.; Springer: Berlin, 1999.
10. Setzer, W. N.; Schleyer, P.v. R Adv. Organomet. Chem.
1985, 24, 352–451.
11. (a) Hsiao, Y.; Hegedus, L. S. J. Org. Chem. 1997, 62,
3586–3591; (b) Garc´ıa Ruano, J. L.; Alcudia, A.; del
Prado, M.; Barros, D.; Maestro, M. C.; Ferna´ndez, I.
J. Org. Chem. 2000, 65, 2856–2862; (c) Welch, J. T.;
Seper, K. W. J. Org. Chem. 1988, 53, 2991–2999.
12. (a) Cox, G. G.; Harwood, L. M. Tetrahedron: Asymme-
try 1994, 5, 1669–1672; (b) Hamada, Y.; Shibata, M.;
Sugiura, T.; Kato, S.; Shioiri, T. J. Org. Chem. 1987,
52, 1252–1255; (c) Luly, J. R.; Dellaria, J. F.; Plattner,
J. J.; Soderquist, J. L.; Yi, N. J. Org. Chem. 1987, 52,
1487–1492; (d) Moree, W. J.; van der Marel, G. A.;
Liskamp, R. J. J. Org. Chem. 1995, 60, 5157–5169.
2. (a) Kozaki, H.; Aratani, T.; Toraya, T. Tetrahedron
Lett. 1968, 9, 4097–4098; (b) Mukaiyama, T.; Soai, K.;
Sato, T.; Shimizu, H.; Suzuki, K. J. Am. Chem. Soc.
1979, 101, 1455–1460; (c) Mazaleyrat, J.-P.; Cram, D.
J. J. Am. Chem. Soc. 1981, 103, 4585–4586; (d) Cor-
ruble, A.; Valnot, J.-Y.; Maddaluno, J.; Prigent, Y.;
Davoust, D.; Duhamel, P. J. Am. Chem. Soc. 1997,
119, 10042–10048; (e) Corruble, A.; Valnot, J.-Y.; Mad-
daluno, J.; Duhamel, P. J. Org. Chem. 1998, 63, 8266–
8275; (f) Flinois, K.; Yuan, Y.; Bastide, C.;
Harrison-Marchand, A.; Maddaluno, J. Tetrahedron

J. Granander et al. / Tetrahedron: Asymmetry 14 (2003) 439–447
13. Higashiura, K.; Morino, H.; Matsuura, H.; Toyomaki,
1027.
447
17. Ishibashi, H.; Uegaki, M.; Sakai, M.; Takeda, Y. Tetra-
Y.; Ienaga, K. J. Chem. Soc., Perkin Trans. 1 1989,
1479–1481.
hedron 2001, 57, 2115–2120.
18. Imuta, M.; Kawai, K.; Ziffer, H. J. Org. Chem. 1980, 45,
3352–3355.
19. Carter, M. B.; Schiøtt, B.; Gutie´rrez, A.; Buchwald, S. L.
J. Am. Chem. Soc. 1994, 116, 11667–11670.
14. Siedlecka, R.; Skarzewski, J. Synlett 1996, 757–758.
15. Kano, S.; Yokomatsu, T.; Shibuya, S. J. Org. Chem.
1989, 54, 513–515.
16. Christoffers, J.; Mann, A. Chem. Eur. J. 2001, 7, 1014–