The regioisomeric triphenylaminoethanols - Comparison of their efficiency in enantioselective catalysis

Article abstract of DOI:10.1002/adsc.200303178

Both enantiomers of the novel amino alcohol (R)- and (S)-2 are prepared from the corresponding enantiomer of the mandelic acid-derived ethanediol 3. The regioisomeric amino alcohols 1 and 2 are converted into the imines 7 and 8, respectively. Titanium com

Full text of DOI:10.1002/adsc.200303178

FULL PAPERS
The Regioisomeric Triphenylaminoethanols Comparison of
their Efficiency in Enantioselective Catalysis
¬
Manfred Braun,* Ralf Fleischer, Brigitte Mai, Marc-Andre Schneider,
Stefan Lachenicht
Institut f¸r Organische Chemie und Makromolekulare Chemie, Universit‰t D¸sseldorf, 40225 D¸sseldorf, Germany
Fax: ( ‡ 49)-211-811-5079, e-mail: braunm@uni-duesseldorf.de
Received: October 16, 2003; Accepted: February 10, 2004
Abstract: Both enantiomers of the novel amino cyclization reaction of the diketone 16 togive the
alcohol (R)- and (S)-2 are prepared from the corre- estrone derivative 17. In both reactions titanium
sponding enantiomer of the mandelic acid-derived complexes 10 and 15 derived of the novel amino
ethanediol 3. The regioisomeric amino alcohols 1 and alcohol 2 give higher enantioselectivities than the
2 are converted into the imines 7 and 8, respectively. complexes 9 and 14 that are based on the regioiso-
Titanium complexes 9 and 10 derived therefrom are meric amino alcohol 1.
used as catalysts for the addition of diethylzinc to
benzaldehyde and yield the alcohol 11 in up to92%
Keywords: amino alcohols; asymmetric catalysis;
ee. On the other hand, the chloro-substituted titanium cyclization; N,O ligands; nucleophilic addition; tita-
complexes 14 and 15 are able to mediate the Torgov nium
Introduction
new amino alcohols (R)- and (S)-2, which contain as a
structural unit the diphenylaminomethyl moiety,[13]
In various asymmetric syntheses, the diarylhydroxy- might be suitable reagents for stereoselective conver-
methyl group has turned out to play a key role. Although sions,[14] an efficient synthesis of (R)- and (S)-2 had tobe
not a stereogenic unit at least not a permanent one it developed first.[15] Subsequently, alkoxy-imine-titanium
proved itself tobe crucial and led toan enhancement of
complexes derived of the regioisomeric amino alcohols
stereoselectivity in many cases.[1] Among the chiral 1 and 2 were generated and tested in twocases of
reagents containing the diarylhydroxymethyl group are enantioselective catalysis.
fairly well known representatives like the TADDOLs,[2]
triphenyl-glycol-derived carboxylic esters,[3] cyclic sul-
fides,[4] and the so-called CBS-catalysts.[5,6] In these and
various other cases,[7] the diarylhydroxymethyl group,
which may occur either in its free or deprotonated or
protected from, is essential for sufficient stereoselectiv-
ity. The key role of this moiety has been studied
intensively and the way its acts as a temporary stereo-
genic unit has been made plausible by transition state
models based on crystal structure parameters of inter-
mediates[8] and calculations.[9]
The diphenylhydroxymethyl group was introduced in
chiral amino alcohols as early as in the first part of the
last century, when McKenzie and Wills were able to
obtain 2-amino-1,1,2-triphenylethanol (1) from phenyl-
glycinate.[10] This readily available chiral compound has
been used in recent years for enantioselective reduc-
tions of ketones[11] and allylic oxidations.[12] On the other
hand, 2-amino-1,2,2-triphenylethanol (2), a regioisomer
of McKenzie×s amino alcohol, has neither been pre-
pared in enantiomerically pure form nor used as a chiral
auxiliary reagent (Scheme 1). Wondering whether the Scheme 1. The regioisomeric triphenylaminoethanols 1 and 2.
474
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/adsc.200303178
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The Regioisomeric Triphenylaminoethanols
FULL PAPERS
Results and Discussion
The readily accessible mandelic-acid derived reagents
(R)- and (S)-triphenylglycol 3,[16] both commercially
available, were chosen as starting materials for the
synthesis of the corresponding enantiomer of the amino
alcohol 2. Thus, (R)-diol 3 was first treated with thionyl
chloride in the presence of triethylamine to afford the
diastereomeric sulfites 4a and 4b that were formed in a
ratioof90:10. [17] The diastereomericmixture of 4a/b was
used in the following step without separation. Treatment
with triflic acid in acetonitrile furnished the oxazoline
(R)-5, a conversion that is obviously a hitherto unknown
variant of the Ritter reaction.[18] Finally, the amino
alcohol (R)-2 was prepared from the oxazoline (R)-5 by
sulfuric acid-mediated methanolysis. Following the
same protocol, (S)-2 was prepared from (S)-3 (Scheme
2). Racemic amino alcohol 2 is accessible by 1,3-dipolar
cycloadditions of various benzhydrylisonitrile ylides
and benzaldehyde.[19] After the synthesis of (R)- and
(S)-2 starting from the corresponding enantiomer of
triphenylglycol 3 had been communicated,[15] an alter-
native access tonon-racemic 2 based on an asymmetric
epoxidation was reported.[20]
Scheme 2. Synthesis of (R)- and (S)-2-amino-1,2,2-tripheny-
lethanol 2.
The major compound of the sulfites 4a and 4b could be
isolated, and its configuration, [Rc,Ss]-4a, was deter- enantiomeric ligands to the Si face. This result was
mined by chemical correlation[17] as well as by a crystal obtained with both regioisomeric reagents. However,
structure analysis.[21] It turned out that in the diaster- only moderate enantioselectivities were provided by the
eomer 4a the phenyl residue at the stereogenic carbon imines 7 that are derived from the amino alcohol 1
atom and the exocyclic oxygen atom are oriented in a (entries 1 and 2). When, on the other hand, regioiso-
trans configuration. Diastereomerically pure sulfite 4a meric imines 8 were incorporated in the corresponding
has been used as starting material for syntheses of titanium complexes, distinctly higher enantioselectiv-
enantiomerically pure sulfoxides.[17]
ities could be obtained (entries 3 6). A t-butyl sub-
The imines 7a,b were prepared from the amino stituent in the ortho position to the phenol residue
alcohol (R)-1 by condensation with ortho-formylphe- turned out to be crucial for stereoselectivity (entries 1
nols 6a,basdescribedpreviously.[22] In an analogous way, vs. 2, 3 vs. 4). Being aware of the fact that, in asymmetric
the reaction of (R)-2 with the aldehydes 6a c led tothe
syntheses, enantioselectivity is not only determined by
imines 8a c, whereas the aldehydes 6d f[23] were the sterical hindrance of substituents but might also by
condensed with the enantiomeric amino alcohol (S)-2 influenced by their electronic properties,[25] electron-
togive the imines ( S)-8d f. Both regioisomeric struc- donating and -withdrawing substituents were intro-
tures 7 and 8 served us as tridentate ligands in mono- and duced intothe para position to the phenolic moiety.
bis-chelated titanium(IV) complexes. The mono-che- Thus the performance of the titanium complexes 10d f,
lated titanium complexes 9 and 10 were usually not which were generated in situ from the corresponding
isolated but generated in situ by treatment of the imines imines 8d f, in the diethylzinc addition protocol was
7 or 8 with titanium tetraisopropoxide and subsequent studied. It turned out that the presence of electron-
evaporation of 2-propanol (Scheme 3). Nevertheless, donating substituents (NMe2 and OMe) enhanced the
several examples of the titanium complexes 9 and 10 enantioselectivity (entries 6 and 7), the optimum result
were isolated and characterized by their NMR spec- being obtained with the titanium complex having
tra.[22]
methoxy-substituted imine 8d as a chelating ligand
First, they were used as catalysts in enantioselecitve (entry 6). The introduction of the electron-withdrawing
additions of diethylzinc to benzaldehyde[24] (Scheme 4). nitro group, on the other hand, leads to a slightly
As shown in Table 1, efficient conversions were feasible reduced enantioselectivity (entry 8). As a result of the
with all of the titanium complexes as far as the chemical comparison between the regioisomeric imines 7 and 8, it
yield was concerned. In all cases, an lk topicity was is more efficient to have a stereogenic center bearing the
observed in that sense that R configurated imine ligands hydroxy than the amino group. In all cases, (R)-1-
directed the addition of diethylzinc predominantly to phenylpropanol 11 was obtained from the (R) enan-
the Re face of the aldehyde and, accordingly the tiomers of the imines (R)-7a, b and (R)-8a c. Accord-
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Table 1. Addition of diethylzinc to benzaldehyde, catalyzed
by imines 7/8 and Ti(Oi-Pr)4.
Entry
Imine
11
Yield [%]
ee [%]
Configuration
1
2
3
4
5
6
7
8
(R)-7a[a]
(R)-7b[a]
(R)-8a[a]
(R)-8b[a]
(R)-8c[b]
(S)-8d[b]
(S)-8e[b]
(S)-8f[a]
87
73
96
100
100
100
100
95
21
58
42
82
79
92
87
84
R
R
R
R
R
S
S
S
[a]
20 mol % imine/Ti(Oi-Pr)4, 08C, 16 24 h.
10 mol % imine/Ti(Oi-Pr)4, À 208C ! À 108C, 12 15 h.
[b]
derived titanium complexes as potential catalysts with
higher Lewis acidity, the chloro complexes were gen-
erated. It turned out that the optimal access to these
Lewis acids was provided by the bis-chelated complexes
12 and 13, which were easily obtained when imines 7b
and 8c were reacted with titanium tetraisopropoxide in a
molar ratio of 2:1. They proved themselves to be
compounds that are stable towards air, moisture, and
protic solvents, could be purified by column chromatog-
raphy, and their structures were elucidated.[22] Although
a series of diastereomers could form from a combination
of the tridentate ligands 7 or 8 with titanium in an
octahedral arrangement, usually one diastereomer
arose in excess or even exclusively, depending on the
substitution pattern. Either the diastereomerically pure
bis-chelated complexes 12 and 13 or the mixture of
diastereomers were converted into the chloro com-
plexes 14 and 15 by treatment with titanium tetrachlor-
ide (Scheme 5).
Looking for an application of the novel halo com-
plexes as Lewis-acidic chiral catalysts, we turned tothe
cyclization of methyl secone 16, the key step of the well-
known Torgov synthesis,[26] which, undoubtedly, ™be-
longs to the simplest conceivable strategies for the
synthesis of steroids with estrane ... skeleton.∫[27] The
Scheme 3. Imines 7, 8 and monochelated titanium complexes
9, 10 derived from the regioisomeric amino alcohols 1 and 2,
respectively.
ingly, (S)-11 was formed when the ligands (S)-8d f were conversion of methyl secone 16 intothe tetracyclic
used. product 17, a valuable precursor of estrone, is the
Titanium complexes like 9 and 10 carrying alkoxy chirogenic step of the reaction sequence. Among the
ligands are relatively weak Lewis acids compared to the attempts for the enantioselective syntheses of estrone,
corresponding halides. Thus, in order to obtain imine- the dissymetrization of the diketone 16 has turned out to
be very efficient.[28] Nevertheless, the additional reduc-
tion step can be avoided if the secone 16 is converted
directly intothe tetracyclic product 17 by means of an
enantioselectively catalyzed cyclization (Scheme 6). So
far, only one attempt has been made in order to realize
this concept, and the Torgov diene product 17 was
obtained in a maximum of 70% ee. For this purpose, an
estrane-based titanium complex had to be used as a
chiral Lewis acid.[29] Another problem this protocol
Scheme 4. Enantioselective addition of diethylzinc to benzal-
dehyde mediated by the imines 7 or 8 and titanium
tetraisopropoxide.
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The Regioisomeric Triphenylaminoethanols
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Scheme 6. Cyclization of meso-diene 16 to Torgov diene 17,
mediated by Lewis acids generated from titanium complexes
12 or 13.
titanium complex (14 vs. 15). Remarkably, here again,
the ligands that are based on the amino alcohol (S)-2 are
superior to those generated from phenylglycine-derived
(S)-1. Thus, compared to the low enantioselectivity
obtained by means of the titanium complex 14, the
catalyst 15 provided an enhancement of the enantio-
meric excess.
Scheme 5. Synthesis of bis-chelated titanium complexes 12,
13 and generation of dichloro complexes 14, 15.
encounters is the formation of a carbinol 18 as a by-
product that arises with lower enantiomeric purity (30
36% ee).
Conclusions
In order to bring about enantioselective Torgov In two cases of enantioselective catalysis, titanium
cyclizations of the secone 16, the bis-chelated complexes complexes that are generated from the novel amino
12 and 13 were first converted into the dichloro alcohol 2 proved themselves to be superior to those
complexes 14 and 15 by treatment with equimolar derived of the regioisomeric amino alcohol 1. As both
amounts of titanium tetrachloride in dichloromethane enantiomers of 2 are accessible from the corresponding
or toluene in the presence of molecular sieves 4 ä. The mandelic acid derivative 3, a novel amino alcohol has
Lewis acids 14 and 15, thus generated in situ and used in become available, which could serve as a chiral building
a ratio of 0.2 molar equivalents, were able to mediate the block or reagent in various other transformations. Aside
cyclization of the diketone 16. Remarkably, the carbinol from the two cases of asymmetric catalysis outlined
18 did not form at all and the diene 17, a useful above, triphenylaminoethanols (R)- and (S)-2 also
intermediate in estrone synthesis,[28,30] was the only provided an access to new chiral dopants, which here
product. It turned out that this compound was obtained again were more efficient than those derived of the
in the desired (S)-configuration, when those titanium amino alcohol 1. This new application of the regioiso-
complexes 14 and 15 were used that are based on the (S)- meric triphenylethanol that will be published elsewhere
enantiomer of the amino alcohols 1 and 2. However, the seems to meet some commercial interest.[31]
enantiomeric excesses obtained were moderate: The
enantioselectivity was only 17% ee when the reaction
was mediated by chlorotitanate 14 (toluene) and 38% ee
in the case of 15 (dichloromethane). Nevertheless, there
is a substantial influence on the enantioselectivity
exhibited by the tridentate ligand of the corresponding
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layers were dried with MgSO4 and concentrated under vacuum
to give light yellow, viscous crude 5, which contained about 5%
of benzhydryl phenyl ketone, but was sufficiently pure to be
used in the following reaction.
Experimental Section
General Remarks
Analytically pure samples of 5 were obtained by column
chromatography to give white, crystalline material; yield:
11.3 g (64%); mp 58.5 60.08C; Rf ˆ 0.5 (n-hexane/ethyl ace-
tate, 3.5:1). IR (KBr): n ˆ 3070, 3060, 3030, 2360, 1660, 1600,
Melting points (uncorrected) were determined with a B¸chi
melting point apparatus 540. Specific rotations were deter-
mined with a Perkin-Elmer 341 polarimeter. IR spectra:
Bruker Vector 22. Mass spectra: Varian MAT 311 A. NMR
spectra: Varian VXR 200 and VXR 300 and DRX 500. The
spectra were recorded in CDCl3 with TMS as internal standard.
TLC: Silica gel 60 F254 (Merck). Column chromatography:
Macherey-Nagel-Kieselgel 60 and Merck Kieselgel 60, mesh
size 0.04 0.063. All titanium-mediated reactions were per-
formed under an atmosphere of dry nitrogen or argon.
Reactions at temperatures below À 208C were monitored by
a thermocouple connected to a resistance thermometer
(Ebro). General remarks concerning the handling of mois-
ture-sensitive compounds are given in Ref.[32]
1
1495, 1445, 1385, 1250, 1210, 975 cmÀ1; H NMR (300 MHz):
d ˆ 2.25 (s, 3H, CH3), 6.24 (s, 1H, 5-H), 6.91 7.07 (m, 10H,
aromatic H); 13C NMR (75 MHz): d ˆ 14.2 (CH3), 83.5 (C-4),
89.8 (C-5), 126.2 128.4 (aromatic C), 137.5, 141.9, 146.6
‡
(aromatic ipso-C), 163.7 (C-2); MS (EI): m/z ˆ 314 (M ‡ 1,
‡
1%), 313 (M , 4%), 260 (10%), 208 (46%), 207 (100%), 167
(21%), 166 (75%), 165 (69%); anal. calcd. for C22H19NO: C
84.31, H 6.11, N 4.47; found: C 84.35, H 5.94, N 4.23; (R)-5: [a]2D0:
‡ 231 (c 1, CHCl3).
(S)-5 was prepared analogously from ent-4a/b: [a]2D0: À 233
(c 1, CHCl3).
(2S,5R)- and (2R,5R)-4,4,5-Triphenyl-1,3,2-
dioxathiolane-2-oxide (4a and 4b)
(R)-2-Amino-1,2,2-triphenylethanol (2)
A solution of (R)-5 (10.9 g, 34.8 mmol) in absolute methanol
(300 mL) was stirred in a 1-L two-necked flask equipped with a
magnetic stirrer, a pressure-equalizing dropping funnel, which
was closed with a stopper and reflux condenser with a drying
tube. The mixture was cooled under stirring to 08C and
concentrated H2SO4 (37 mL) was added within 30 min. The
cooling bath was removed, the dropping funnel was replaced
by a stopper, and the mixture was refluxed for 10 d. After
cooling to 258C, the mixture was diluted with water (250 mL),
methanol was removed in a rotary evaporator and the
remaining aqueous mixture was further concentrated to about
half of its volume. The precipitate (benzhydryl phenyl ketone)
formed thereby was removed by filtration and the filtrate was
washed twice with Et2O. The aqueous layer (containing the
hydrogen sulfate of 2) was cooled to 0 8C and treated with 2.5 M
NaOH (300 mL), which was added slowly. Thereby, a white
suspension formed. After the addition of CH2Cl2 (150 mL) and
stirring for 10 min, the precipitate had dissolved completely.
The organic layer was separated, and the aqueous phase was
extracted with CH2Cl2 (2 Â 100 mL). The combined organic
layers were washed with brine, dried with MgSO4 and
concentrated in a rotary evaporator to give a colorless solid.
Recrystallization from toluene gave white crystalline 2; yield:
8.87 g (88%); mp 152.0 153.58C [Ref.[19a]: 141 1428 (rac-2);
Ref.[19b]: 143 1448C (rac-2)]. IR (KBr): n ˆ 3380, 3100, 3080,
3040, 2900, 1600, 1500, 1450, 1195, 1060, 1040, 1030, 960, 890,
Prepared according to Ref.[17] as a mixture of diastereomers in
88% yield. The crude product, obtained from (R)-diol 3 (22.3 g,
76.9 mmol) as an oil was purified by chromatography on a short
column (approximately 15 cm), which was protected against
light. The yellowish eluate was concentrated, the oily residue
was treated with 50 mL of n-hexane and stirred vigorously. The
white precipitate thus formed was filtered through a sinter,
washed with n-hexane and dried in an oil-pump vacuum
(0.05 mbar, 408C, light protection). The diastereomeric mix-
ture of 4a and 4b thus obtained in 88% yield (22.8 g) was kept
at À 188C. For analytical and spectroscopic data, see Ref.[17]
In an analogous way, a mixture of (2R,5S)-ent-4a and
(2S,5S)-ent-4b was prepared from (S)-diol 3.
(R)-2-Methyl-4,4,5-triphenyl-4,5-dihydrooxazole (5)
Under argon, a solution of 4a, b (19 g, 56.5 mmol) in 90 mL of
absolute acetonitrile was stirred in a 250-mL three-necked
flask equipped with a magnetic stirrer, a pressure-equalizing
dropping funnel, a septum and a connection to the combined
argon/vacuum line. The solution was cooled to À 108C the
temperature being monitored by an electronic resistance
thermometer the thermocouple of which was introduced
through the septum. The dropping funnel was charged with
trifluoromethanesulfonic acid (10 mL, 113 mmol) while a
stream of argon was maintained. The acid was added dropwise
within 1 h, and the temperature was not allowed to exceed
À 58C. The thermocouple was removed (to avoid corrosion)
and the mixture was stirred at À 108C fo r 16 h.
1
835 cmÀ1; H NMR (500 MHz): d ˆ 1.90 (broad s, 2H, NH2),
3.25 (broad s, 1H, OH), 5.58 (s, 1H, 1-H), 6.86 6.88 (m, 1H,
aromatic H), 7.02 7.32 (m, 11H, aromatic H), 7.55 À 7.57 (m,
2H, aromatic H); 13C NMR (75 MHz): d ˆ 65.6 (C-2), 77.4 (C-
1), 126.4 128.2 (aromatic C), 139.7, 145.3, 145.8 (aromatic
‡
‡
A slight precipitate consisting of benzhydryl phenyl ketone
was filtered and washed with n-hexane (50 mL). The combined
filtrates were diluted with H2O (100 mL) and brought to pH ˆ
8 by the addition of 2.5 M NaOH under vigorous stirring and
cooling. The mixture was concentrated in a rotary evaporator
in order to remove n-hexane and acetonitrile. The residue was
treated with CH2Cl2 (150 mL) and stirred vigorously for
10 min. The phases were separated and the aqueous layer
was extracted with CH2Cl2 (2 Â 50 mL). The combined organic
ipso-C); MS (FAB; NAB): m/z ˆ 290 (M ‡ 1, 9%), 289 (M ,
2%), 274 (22%), 273 (44%), 195 (20%), 183 (17%), 182 (100%),
167 (25%), 165 (18%), 1107 (17%), 105 (24%), 104 (26%); anal.
calcd. for C20H19NO: C 83.01, H 6.62, N 4.84; found: C 83.16, H
6.7, N 4.69.
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and the residue was purified by column chromatography to
give the yellow to orange products. According to this proce-
dure, the following compounds were obtained:
2-Hydroxy-3-(1,1-dimethylethyl)-5-nitrobenzaldehyde
(6f)
A solution of 6b (5.0 g, 2.80 mmol) in acetic acid (8 mL) was
stirred in an ice bath at 58C. Fuming nitric acid (2.8 mL,
68 mmol) was added slowly by means of a dropping funnel at
such a rate that the temperature did not exceed 108C. The
cooling bath was removed and the mixture was stirred at 258C
for 1 h. Then, the solution was poured into ice/water (250 mL)
under vigorous stirring. The orange precipitate formed thereby
was filtered through a sinter, washed with water (50 mL),
recrystallized twice from ethanol and dried in oil-pump
vacuum togive 6f; yield: 4.3 g (68%), mp 90.4 91.08C.
1H NMR (500 MHz): d ˆ 1.47 [s, 9H, C(CH3)3], 8.41 (d, J ˆ
2.9 Hz, 1H, 4-H or 6-H), 8.42 (d, J ˆ 2.9 Hz, 1H, 6-H or 4-H),
9.98 (s, 1H, CHO), 12.44 (s, 1H, OH).
(R)-1-{[(2-Hydroxy-1,1,2-triphenylethyl)imino]methyl}-2-
naphthol (8a): Prepared from (R)-2 (4.0 mmol) and 6a
(4.0 mmol); reaction conditions: 20 h, 608C. Rf ˆ 0.6 (CHCl3/
ethyl acetate, 10:1); yield: 0.97 g (55%); mp 110 1128C
(decomp.), [a]2D0: ‡ 109 (c 1, CHCl3). IR (KBr): n ˆ 3415,
3060, 3030, 1620, 1580, 1545, 1495, 1445, 1350, 1180, 835 cmÀ1;
1H NMR (500 MHz): d ˆ 2.88 [d, J ˆ 2.1 Hz, 1H, PhCH(OH)],
5.71 [d, J ˆ 2.1 Hz, 1H, PhCH(OH)], 6.74 6.75 (m, 1H, phenyl
H), 6.92 (d, J ˆ 9.3 Hz, 1H, 3-H), 7.05 7.20 (m, 9H, aromatic
H), 7.26 (dt, Jd ˆ 1.4 Hz, Jt ˆ 8.2 Hz, 1H, 7-H), 7.35 7.39 (m,
3H, aromatic H), 7.47 (d, J ˆ 8.2 Hz, 1H, 8-H), 7.53 7.58 (m,
3H, aromatic H), 7.67 (d, J ˆ 9.3 Hz, 1H, 4-H), 8.71 (d, J ˆ
3
ˆ
ˆ À
8.5 Hz, 1H, Ph2CN CHC C OH, J ˆ due tochelation with
ArOH), 15.37 (d, J ˆ 8.5 Hz, 1H, ArOH); 13C NMR
(125 MHz): d ˆ 75.0 [Ph2C(N)], 78.3 [PhCH(OH)], 107.1 (C-
1), 118.1 (C-8), 122.8 (C-6), 124.8 (C-3), 126 (C-10), 127.4 130
(aromatic C), 134.1 (C-9), 137.5 (C-4), 138.8, 141.6, 142.1
(aromatic ipso-C), 159.3 (NCHAr), 176.1 (C-2); MS (FAB;
2-Hydroxy-5-(dimethylamino)-3-(1,1-
dimethylethyl)benzaldehyde (6e)
In a hydrogenation apparatus, a mixture of 6f (1.50 g,
6.72 mmol), ethanol (40 mL), aqueous formaldehyde solution
(37%, 4.5 mL) and palladium on charcoal (10%, 0.17 g) was
hydrogenated at normal pressure for 12 h under stirring. The
red-brownish mixture was filtered through celite in a sinter and
the residue was washed three times with ethanol (10 mL). The
combined filtrates were concentrated in a rotary evaporator,
the residue was dissolved in the minimum amount of CH2Cl2
and submitted to column chromatography (n-hexane/ethyl
acetate, 5:1) togive crystalline 6e; yield: 0.50 g (34%); mp
133.7 1348C; Rf ˆ 0.4 (n-hexane/ethyl acetate, 5:1). IR
(KBr): n ˆ 3450, 3000, 2950, 1715, 1650, 1610, 1490, 1460,
‡
‡
NBA, NaI): m/z ˆ 467 (M ‡ 1 ‡ Na, 28%), 466 (M ‡ Na,
68%), 337 (43%), 336 (100%), 167 (66%), 165 (93%), 152 (39%),
139 (21%).
(R)-2-(1,1-Dimethylethyl)-6-{[(2-hydroxy-1,1,2-triphenyl-
ethyl)imino]methyl}phenol (8b): Prepared from (R)-2
(4.0 mmol) and 6b (4.0 mmol); reaction conditions: 8 h, 608C.
Rf ˆ 0.5 (n-hexane/ethyl acetate, 5:1);yield: 0.96 g(54%); [a]2D0:
‡ 58 (c 1, CHCl3). IR (KBr): n ˆ 3440, 3070, 3030, 3000, 2960,
2910, 1620, 1495, 1435, 1270, 1200, 1145, 1090, 855 cmÀ1;
1H NMR (500 MHz): d ˆ 1.48 [s, 9H, C(CH3)3], 2.26 [d, J ˆ
3.8 Hz, 1H, PhCH(OH)], 5.60 [d, J ˆ 3.8 Hz, 1H, PhCH(OH)],
6.73 6.75 (m, 2H, aromatic H), 6.77 (t, J ˆ 7.7 Hz, 1H, 4-H),
6.98 (dd, J ˆ 7.7 Hz, J ˆ 1.6 Hz, 1H, 3-H or 5-H), 7.03 7.41 (m,
14H, aromatic H), 8.05 (s, 1H, NCHAr), 14.08 (s, 1H, ArOH);
13C NMR (125 MHz): d ˆ 29.3 [C(CH3)3], 34.9 [C(CH3)3], 77.8
[Ph2C(N)], 78.5 [PhCH(OH)], 117.7 (C-4), 118.8 (C-6), 127.0
130.3 (aromatic C), 130.9 (C-3 or C-5), 137.5, 139.6, 142.7, 143.5
(aromatic ipso-C), 160.5 (C-1),167.8 (NCHAr); MS (FAB;
1435, 1355, 1265, 1180, 995, 880, 830, 710 cmÀ1 1H NMR
;
(500 MHz): d ˆ 1.43 [s, 9H, C(CH3)3], 2.89 [s, 6H, N(CH3)2],
6.72 (d, J ˆ 3.2 Hz, 1H, 4-H or 6-H), 7.15 (d, J ˆ 3.2 Hz, 1H, 6-H
or 4-H), 9.85 (s, 1H, CHO), 11.28 (s, 1H, OH); 13C NMR
(125 MHz): d ˆ 29.2 [C(CH3)3], 35.1 [C(CH3)3], 41.9
[N(CH3)2], 114.7 (C-4 or C-6), 120.3 (C-1), 122.8 (C-6 or C-
4), 138.9 (C-5), 144.3 (C-3), 154.2 (C-2), 197.3 (CHO); MS (CI;
‡
NBA): m/z ˆ 450 (M ‡ 1, 5%), 343 (36%), 342 (100%), 326
‡
‡
NH3): m/z ˆ 238 (M ‡ NH3, 32%), 222 (M ‡ 1, 15%), 221
(12%), 178 (14%), 167 (20%), 165 (30%); anal. calcd. for
C31H31NO2: C 82.82, H 6.95, N 3.12; found: C 82.63, H 7.09,
N,3.25.
‡
(M , 100%); anal. calcd. for C13H19NO2: C 70.56, H 8.65, N 6.33;
found: C 70.48, H 8.48, N 6.60.
Imines 7a, b were prepared as described in Ref.[22]
(R)-2,4-Bis(1,1-dimethylethyl)-6-{[(2-hydroxy-1,1,2-triphe-
nylethyl)imino]methyl}phenol (8c): Prepared from (R)-2
(4.0 mmol) and 6c (4.0 mmol); reaction conditions: 12 h reflux;
Rf ˆ 0.4 (n-hexane/EtOAc, 7:1); yield: 1.07 g (53%); [a]2D0:
‡ 92 (c 1, CHCl3). IR (KBr): n ˆ 3595, 3445, 3060, 3030, 2955,
2855, 2890, 2860, 1625, 1495, 1470, 1440, 1360, 1275, 1275, 1250,
Preparation of Imines 8a f; General Procedure
A 100-mL two-necked flask was equipped with a magnetic
stirrer, a reflux condenser, a septum, and a connection to the
combined argon/vacuum line and charged with (R)- or (S)-2
(1.15 g, 4.0 mmol) and dry Na2SO4 (1.2 g, 8.5 mmol). In the
case of the preparation of the imine 8d, molecular sieve 3 ä,
which had been crushed with a pistil and mortar, was used
instead of Na2SO4. The air in the flask was replaced with argon,
and absolute CH3OH (10 mL) and CH2Cl2 (10 mL) were
injected by syringe. In case of the imine 8d, methanol was used
exclusively. A solution of the corresponding 2-formylphenol 6
in absolute CH3OH (15 mL) was added dropwise to the stirred
suspension at 258C. Stirring was continued under the con-
ditions given below. The drying agent was removed by suction
filtration, the filtrate was concentrated in a rotary evaporator
1
1170, 1025, 840 cmÀ1; H NMR (500 MHz): d ˆ 1.27 [s, 9H,
C(CH3)3], 1.49 [s, 9H, C(CH3)3], 2.28 [d, J ˆ 3.8 Hz, 1H,
PhCH(OH)], 6.76 6.77 (m, 2H, aromatic H), 6.97 (d, J ˆ
2.5 Hz, 1H, 3-H or 5-H), 7.04 7.43 (m, 14H, aromatic H),
8.08 (s, 1H, NCHAr), 13.92 (s, 1H, ArOH); 13C NMR
(125 MHz): d ˆ 29.4 and 31.5 [C(CH3)3], 34.2 and 35.1
[C[CH3)3], 77.7 [Ph2C(N)], 78.5 [PhCH(OH)], 118.0 (C-6),
126.9 130.3 (aromatic C), 136.8, 139.6, 140.0, 142.9, 143.6
(aromatic ipso-C), 158.2 (C-1), 168.2 (NCHAr); MS (FAB;
‡
‡
NBA): m/z ˆ 506 (M ‡ 1, 10%), 505 (M , 3%), 400 (24%), 399
(100%), 398 (30%), 382 (19%), 342 (17%), 234 (20%); anal.
calcd. for C35H39NO2: C 82.72, H 7.96, N 2.84; found: C 82.97, H
8.08, N 2.64.
Adv. Synth. Catal. 2004, 346, 474 482
asc.wiley-vch.de
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479

Manfred Braun et al.
FULL PAPERS
(S)-2-(1,1-Dimethylethyl)-6-[(2-hydroxy-1,1,2-triphenyle-
thyl)imino]methyl-4-methoxyphenol (8d): Prepared from (S)-
2 (3.5 mmol) and 6d (3.33 mmol); reaction conditions: 48 h,
À 208C to ‡ 258C. The product 8d could not be obtained
completely free of aldehyde 6d by column chromatography.
Therefore, the eluate was concentrated and the residue was
treatedwith n-pentane (3 mL), stirred vigorously and cooled to
À 188C. The solvent was removed by decantation. The
procedure was repeated twice. The remaining solvent was
removed in an oil pump vacuum to give solid 8d, which is
recommended to be kept at À 188C. Rf ˆ 0.6 (CHCl3); yield:
0.31 g (19%); [a]2D0: ‡ 74 (c 0.75, CHCl3). IR (KBr): n ˆ 3450,
3060, 3030, 3000, 2955, 1630, 1590, 1450, 1430, 1335, 1150,
1060 cmÀ1; 1H NMR (500 MHz): d ˆ 1.47 [s, 9H, C(CH3)3], 2.28
[d, J ˆ 3.8 Hz, 1H, PhCH(OH)], 3.72 (s, 3H, OCH3), 5.64 [d,
J ˆ 3.8 Hz, 1H, PhCH(OH)], 6.50 (d, J ˆ 3.1 Hz, 1 H, 3-H or 5-
H), 6.73 6.75 (m, 2H, aromatic H), 7.01 (d, J ˆ 3.1 Hz, 1H, 5-H
or 3-H), 7.04 7.45 (m, 13H, aromatic H), 8.05 (s, 1H, NCHAr),
13.68 (s, 1H, ArOH); 13C NMR (75 MHz): d ˆ 29.2 [C(CH3)3],
35.1 [C(CH3)3], 55.8 (OCH3), 77.8 [PhC(N)], 78.5
[PhCH(OH)], 112.1 (C-3 or C-5), 118.0 (C-6), 119.0 (C-5 or
C-3), 127.0 127.3 (aromatic C), 139.2, 139.6, 142.9, 143.5
(aromatic ipso-C), 151.1 (C-4), 155.1 (C-1), 167.7 (NCHAr);
and stirring of the yellow solution was continued for 3 h. By
means of the combined argon/vacuum line, the solvent was
removed, the remaining bright yellow solid was exposed to
high vacuum for 3 h and dissolved in toluene (3 mL). Benzal-
dehyde (0.17 mL, 1.7 mmol) was injected and the solution was
cooled to À 788C. A 1.1 M solution of Et2Zn in toluene
(3.1 mL, 3.4 mmol) was added slowly drop by drop by means of
a syringe. Stirring was continued for 15 h at À 20 to0 8C. A
saturated aqueous solution of NH4Cl (10 mL) was added, the
mixture was stirred for 30 min at 258C, and filtered through
celite, which was subsequently washed with toluene (10 mL).
The layers of the combined filtrates were separated, and the
aqueous phase was extracted with Et2O (3 Â 10 mL). The
combined organic layers were washed with brine, dried with
MgSO4 and evaporated. The viscous residue was purified by a
short-path distillation; bp 628C/0.2 mbar; Rf ˆ 0.6 (CHCl3/
ethyl acetate, 5:1). The 1H NMR spectrum corresponds to that
of a commercial sample; ee values given in Table 1 were
determined: a) based on the optical rotation:[33] (S)-11: [a]D20:
À 47.6 (c 6.11, CHCl3); 98% ee; b) from the 1H NMR spectra of
the corresponding MTPA ester (Mosher×s ester): 1'-phenyl-
propyl-2-methoxy-2-trifluoromethyl-2-phenylacetate.[34]
(1'R,2S): d ˆ 0.93 (t, J ˆ 7.6 Hz, 3H, 3'-H), 1.84 2.07 (m, 2H,
2'-H), 3.54 (m, 3H, OCH3), 5.82 (dd, J ˆ 5.7 Hz, J ˆ 7.6 Hz, 1H,
‡
‡
MS (FAB; NBA): m/z ˆ 480 (M ‡ 1, 6%), 479 (M , 3%), 374
(11%), 373 (48%), 372 (100%), 167 (21%), 165 (14%), 105
(26%).
1
1'-H), 7.28 7.42 (m, 10H, aromatic H). (1'S, 2S): H NMR
ˆ
differs in: d ˆ 0.84 (t, J 7.6 Hz), 5.89 (dd, J ˆ 5.7 Hz, J ˆ
(S)-4-(Dimethylamino)-2-(1,1-dimethylethyl)-6-{[(2-hy-
droxy-1,1,2-triphenylethyl)imino]methyl}phenol (8e): Pre-
pared from (S)-2 (1.8 mmol) and 6e (1.8 mmol); reaction
conditions: 72 h, 608C. Rf ˆ 0.2 (n-hexane/ethyl acetate, 3.5:1);
yield: 0.25 g (28%). The product could not be obtained in
7.6 Hz).
Bis-Chelated Titanium Complex 12
Obtained according to Ref.[22]
1
analytically pure form. H NMR (500 MHz): d ˆ 1.49 [s, 1H,
C(CH3)3], 2.41 [s, 1H, PhCH(OH)], 2.78 [s, 6H, N(CH3)2], 5.60
[s, 1H, PhCH(OH)], 6.42 (d, J ˆ 2.9 Hz, 1H, 3-H or 5-H), 6.73
6.75 (m, 3H, aromatic H), 7.42 7.43 (m, 2H, aromatic H), 8.06
(s, 1H, NCHAr), 13.50 (s, 1H, ArOH).
[OC-6-22'-(C),(S),(S)]-Bis-{2,4-Bis-(1,1-
(S)-2-(1,1-Dimethylethyl)-6-{[(2-hydroxy-1,1,2-triphenyle-
thyl)imino]methyl}-4-nitrophenol (8f): Prepared from (S)-2 dimethylethyl)-6-{[(2-hydroxy-1,2,2-triphenylethyl)
(1.8 mmol) and 6f (1.8 mmol); reaction conditions: 8 h reflux.
Rf ˆ 0.3 (CHCl3), yield: 0.65 g (73%); [a]2D0: À 55 (c ,1 CHCl3).
1H NMR (300 MHz): d ˆ 1.48 [s, 9H, C(CH3)3], 2.30 [d, J ˆ
2.8 Hz, 1H, PhCH(OH)], 5.66 [d, J ˆ 2.8 Hz, 1H, PhCH(OH)],
6.69 (d, J ˆ 7.3 Hz, 2H, aromatic H), 7.13 7.43 (m, 13H,
aromatic H), 8.01 (d, J ˆ 2.8 Hz, 1H, 3-H or 5-H), 8.09 (d, J ˆ
2.2 Hz, 1H, NCHAr), 8.23 (d, J ˆ 2.5 Hz, 1H, 5-H or 3-H),
15.70 (d, J ˆ 2.2 Hz, 1H, ArOH); 13C NMR (125 MHz): d ˆ
28.9 [C(CH3)3], 35.9 [C(CH3)3], 77.8 [Ph2CN], 78.1
[PhCH(OH)], 116.9 (C-6), 125.2 130.1 (aromatic C), 138.3
142.3 (aromatic ipso-C), 166.8 (C-1), 168.5 (NCHAr); MS
imino]methyl}phenolato (2-)-N,O,O']titanium (13)
A solution of the imine 8c (1.21 g, 2.39 mmol) in dry CH2Cl2
(6 mL) was stirred under argon in a 50-mL two-necked flask
equipped with a magnetic stirrer, a reflux condenser, a
connection to the combined argon/vacuum line, and a septum.
Ti(Oi-Pr)4 (0.35 mL, 1.19 mmol) was injected by syringe, and
the solution was refluxed for 7 h. The solvent was removed in a
rotary evaporator, and the orange residue was purified by
column chromatography to give the main diastereomer in 23%
yield (0.45 g); Rf ˆ 0.4 (CHCl3/n-hexane, 3:2); [a]2D0: À 94.3 (c
1
1, CHCl3). H NMR (300 MHz): d ˆ 1.18 [s, 18H, C(CH3)3],
‡
(FAB; NBA): m/z ˆ 495 (M ‡ 1, 1%), 388 (100%), 387 (81%),
1.25 [s, 18H, C(CH3)3], 6.65 6.68 (m, 4H, aromatic H), 6.78 [s,
2H, PhCH(O)], 6.92 7.19 (m, 18H, aromatic H), 7.22 7.25
(m, 6H, aromatic H), 7.47 (d, J ˆ 2.5 Hz, 3-H or 5-H), 7.61
371 (22%), 182 (17%), 167 (28%), 165 (12%).
7.64 (m, 4H, aromatic H), 8.25 (s, 2H, N CH); 13C NMR
ˆ
(75 MHz): d ˆ 29.1, 31.6 [C(CH3)3], 34.5, 34.8 [C(CH3)3], 88.4
[PhCH(N)], 90.4 [Ph2C(OH)], 120.6 (C-6), 125.5 126.9 (ar-
omatic C), 127.8 (C-3 or C-5), 128.0 128.4 (aromatic C), 130.7
(C-5 or C-3), 131.0 (aromatic C), 136.5, 139.6, 141.4, 144.2,
148.2 (aromatic ipso-C, C-2, C-4), 161.8 (C-1), 162.0
Addition of Diethyl Zinc to Benzaldehyde; General
Procedure
A 25-mL-two-necked flask was equipped with a magnetic
stirrer and a connection to the combined argon/vacuum line,
charged with the imine 7 or 8 (0.358 mmol) and closed with a
septum. The air in the flask was carefully replaced by argon and
absolute toluene (4.5 mL) was injected by syringe. Under
stirring at 258C, Ti(Oi-Pr)4 (0.1 mL, 0.342 mmol) was injected,
‡
[(N)CHAr]; MS (FAB; NBA): m/z ˆ 1056(M ‡ 1, 9%), 1055
‡
(M , 14%), 950 (76%), 949 (100%), 842 (70%), 398 (56%), 279
(53%), 253 (46%); anal. calcd. for C70H74N2O4Ti: C 79.68, H
7.14, N 2.64; found: C 79.54, H 7.27, N 2.52.
480
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 474 482

The Regioisomeric Triphenylaminoethanols
FULL PAPERS
Two minor diastereomers separated by column chromatog-
raphy differ in: d 1.19 (s) and 1.33 (s); 1.20 (s) and 1.25 (s); 1.31
and 1.42 (s).
[7] D. Enders, V. Bhushan, Tetrahedron Lett. 1988, 29, 2437;
K. Soai, A. Ookawa, T. Kaba, K. Ogawa, J. Am. Chem.
Soc. 1987, 109, 7111; S. Wassmann, J. Wilken, J. Martens,
Tetrahedron: Asymmetry 1999, 10, 4437; K. R. K. Prasad,
N. N. Joshi, J. Org. Chem. 1997, 62, 3770; H. Brunner, C.
Henrichs, Tetrahedron: Asymmetry 1995, 6, 653; M.
Watanabe, M. Komota, M. Nishimura, S. Araki, Y.
Butsugan, J. Chem. Soc. Perkin Trans. 1 1993, 2193; C.
ˆ
Torgov-Cyclization of Secone 16; General Procedure
Under argon, a mixture of the corresponding bis-chelated
titanium complex 13 (0.106 g, 0.10 mmol), molecular sieves
4 ä (0.50 g) and dry CH2Cl2 (2 mL) was stirred at À 788C. A
0.25 M solution of TiCl4 in CH2Cl2 (0.4 mL, 0.10 mmol),
generated under argon as well, was added dropwise by a
syringe below À 758C. The mixture was allowed to reach
À 228C within 3 h, and a solution of 16 (0.298 g, 1.0 mmol) in
dry CH2Cl2 (3 mL) was added. Subsequently, the mixture was
stirred for 3 d at À 228C under argon. A 20% solution of
Na2CO3 was added, the layers were separated, and the aqueous
layer was extracted with CH2Cl2 or toluene (3 Â 20 mL). The
combined organic layers were dried with Na2SO4, concentrated
in a rotary evaporator, and the residue was submitted to
column chromatography to give 17 as a colorless solid
compound; Rf ˆ 0.55 (n-hexane/ethyl acetate, 3:1). The enan-
tiomeric excess was determined by comparison of the optical
rotation: [a]D20: À 39 (c 0.1, tetrahydrofuran); Ref.[29]: [a]D20:
À 102 (c 0.1, tetrahydrofuran) and by HPLC (Chiracel OJ;
Diacel Chemical Industries; n-hexane/2-propanol, 96:4):
(S)-17: tR ˆ 29.3 min; (R)-19: tR ˆ 52.4 min The spectroscopic
data correspond to these described in the literature[28] for 17.
Anal. calcd. for C19H22O3: C 81.42, H 7.17; found: C 81.37,
H 7.11.
¬
ƒ
Bolm, K. Muniz Fernandez, A. Seger G. Raabe, Synlett
1997, 1051; P. I. Dosa, J. C. Ruble, G. C. Fu, J. Org.
Chem. 1997, 62, 444; R. Annunziata, M. Benaglia, M.
Cinquini, F. Cozzi, P. Giaroni, J. Org. Chem. 1992, 57,
782; T. Hintermann, D. Seebach, Helv. Chim. Acta 1998,
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2001, 66, 3059.
¬
[8] Y. N. Ito, X. Ariza, A. K. Beck, A. Bohac, C. Ganter, R.
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[9] D. K. Jones, D. C. Liotta, I. Shinkai, D. J. Mathre, J. Org.
Chem. 1993, 58, 799; V. Nevalainen, R. Uggla, M. R.
Sundberg, Tetrahedron: Asymmetry 1995, 6, 1431.
[10] A. McKenzie, G. O. Wills, J. Chem. Soc. 1925, 127, 283.
[11] R. Berenguer, J. Garcia, J. Vilarrasa, Tetrahedron:
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Tetrahedron: Asymmetry 1996, 7, 3147.
[12] G. Sekar, A. DattaGupta, V. K. Singh, J. Org. Chem.
1998, 63, 2961.
[13] The diarylaminomethyl moiety is also present in several
chiral 1,2-diamines, recently used as co-ligands in hydro-
genation catalysts, cf: T. Ohkuma, M. Koizumi, H.
Doucet, T. Pham, M. Kozawa, K. Murata, E. Katayama,
T. Yokozawa, T. Ikariya, R. Noyori, J. Am. Chem. Soc.
1998, 120, 13529; R. Noyori, T. Ohkuma, Angew. Chem.
2001, 113, 40; Angew. Chem. Int. Ed. 2001, 40, 40.
[14] For a review on the application of b-amino alcohols and
heterocyclic compounds derived therefrom in asymmet-
ric syntheses, see: D. J. Ager, I. Prakash, D. R. Schaad,
Chem. Rev. 1996, 96, 835.
[15] Preliminary communication: R. Fleischer, M. Braun,
Synlett 1998, 1441.
[16] M. Braun, S. Gr‰f, S. Herzog, Org. Synth. 1993, 72, 32.
[17] R. Fleischer, D. Galle, M. Braun, Liebigs Ann./Recueil
1997, 1189.
[18] J. J. Ritter, P. P. Minieri, J. Am. Chem. Soc. 1948, 70,
4045; L. I. Krimen, D. J. Cota, Org. React. 1969, 17, 213;
for a Ritter reaction mediated by triflic acid, see: C. H.
Senanayake, R. D. Larsen, L. M. DiMichele, J. Liu, P. H.
Toma, R. G. Ball, T. R. Verhoeven, P. J. Reider, Tetrahe-
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[19] a) G. Bittner, H. Witte, G. Hesse, Justus Liebigs Ann.
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Chem. 1983, 57, 67.
Acknowledgements
This work was supported by the Deutsche Forschungsgemein-
schaft and the Fonds der Chemischen Industrie. Grants to R. F.
were provided by the Graduiertenfˆrderung des Landes Nord-
rhein-Westfalen and the Dr. Jost Henkel-Stiftung
References and Notes
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Int. Ed. Engl. 1996, 35, 519.
[2] D. Seebach, A. K. Beck, A. Heckel, Angew. Chem. 2001,
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[6] E. J. Corey, C. J. Helal, Angew. Chem. 1998, 110, 2092;
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Adv. Synth. Catal. 2004, 346, 474 482
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
481

Manfred Braun et al.
FULL PAPERS
[23] The aldehydes 6a and 6c are commercially available. The
compounds 6b and 6d were prepared according to the
following references: 6b: M. Hayashi, H. Kaneda, N.
Oguni, Tetrahedron: Asymmetry 1995, 6, 2511; 6d: J. F.
Larrow, E. N. Jacobsen, J. Org. Chem. 1994, 59, 1939; for
the syntheses of 6e and 6f, see: experimental section.
[24] For reviews on enantioselective additions of diethylzinc
to aldehydes, see: a) R. Noyori, Asymmetric Catalysis in
Organic Synthesis, John Wiley and Sons, New York 1994,
pp. 255 297; b) K. Soai, S. Niwa, Chem. Rev. 1992, 92,
833; c) L. Pu, H. B. Yu, Chem. Rev. 2001, 101, 757.
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[30] For recent syntheses of non-racemic Torgov diene 17,
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37, 7403; K. Tanaka, H. Nakashima, T. Taniguchi, K.
Ogasawara, Org. Lett. 2000, 2, 1915.
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[32] R. Devant, U. Mahler, M. Braun, Chem. Ber. 1988, 121,
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[34] J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969,
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