Acetals as chiral ligands for organomagnesium and organolithium compounds

Article abstract of DOI:10.1007/PL00013503

Five 2-alkoxyoctahydro-7,8,8-trimethyl-4,7-methanobenzofurans were tested as additives for the enantioselective addition of butyllithium and butylmagnesium bromide to benzaldehyde. The selectivity of the reaction was determined by GC, HPLC, and by measurement of the optical rotation of the obtained 1-phenyl-1-pentanol, and the stability of the ligands under the given reaction conditions was investigated. Upon reaction with benzaldehyde, the addition of octahydro-7,8,8-trimethyl-2-(2-(phenylmethoxy)ethoxy)-4,7-methanobenzofuran to butylmagnesium bromide yielded (R)-1-phenyl-1-pentanol with 47% ee.

Full text of DOI:10.1007/PL00013503

Monatshefte fuÈr Chemie 129, 953±959 (1998)
Acetals as Chiral Ligands for
Organomagnesium and Organolithium
Compounds
Ã
È
Max KnollmuÈller , Peter Gartner, and Martin Letschnig
È
Institut fuÈr Organische Chemie, Technische Universitat Wien, A-1060 Wien, Austria
Summary. Five 2-alkoxyoctahydro-7,8,8-trimethyl-4,7-methanobenzofurans were tested as addi-
tives for the enantioselective addition of butyllithium and butylmagnesium bromide to benzaldehyde.
The selectivity of the reaction was determined by GC, HPLC, and by measurement of the optical
rotation of the obtained 1-phenyl-1-pentanol, and the stability of the ligands under the given reaction
conditions was investigated. Upon reaction with benzaldehyde, the addition of octahydro-7,8,8-
trimethyl-2-(2-(phenylmethoxy)ethoxy)-4,7-methanobenzofuran to butylmagnesium bromide
yielded (R)-1-phenyl-1-pentanol with 47% ee.
Keywords: Acetals; Ligands, chiral; Carbonyl addition, stereoselective.
Acetale als chirale Liganden fuÈr organische Magnesium- und Lithiumverbindungen
Zusammenfassung. FuÈnf 2-Alkoxyoctahydro-7,8,8-trimethyl-4,7-methanobenzofurane wurden als
Additive fuÈr die enantioselektive Addition von Butyllithium bzw. Butylmagnesiumbromid an
È
Benzaldehyd getestet. Die Selektivitat der Reaktion wurde mittels GC, HPLC und Messung der
È
È
optischen Aktivitat des erhaltenen 1-Phenyl-1-pentanols bestimmt. Die Stabilitat der Liganden unter
den gegebenen Reaktionsbedingungen wurde untersucht. Die Addition von Octahydro-7,8,8-
trimethyl-2-(2-(phenylmethoxy)ethoxy)-4,7-methanobenzofuran an Butylmagnesiumbromid lieferte
nach der Reaktion mit Benzaldehyd (R)-1-Phenyl-1-pentanol mit 47% ee.
Introduction
One of the fundamental methods to establish a carbon±carbon bond is the addition
of organometallic reagents to compounds with a carbonyl functionality, e.g. a
Grignard reaction. In most cases, a new stereogenic center is formed in this
reaction. Therefore, attempts to perform this addition enantioselectively have been
carried out early [1]. Since then, numerous approaches have been directed towards
the synthesis of chiral non-racemic ligands for organometallic compounds, and
their usefulness has been investigated. Some of them displayed high enantio-
selectivities, as e.g. zinc [2] and titanium [3] derivatives, but in general, applicability
Ã
Corresponding author

954
M. KnollmuÈller et al.
was limited to a few examples. For a recent overview of this topic, see Ref. [4] and
literature quoted therein.
In the case of Grignard reagents, only the addition to ketones can be performed
with high enantioselectivity in the presence of ꢀ,ꢀ,ꢀ0,ꢀ0-tetraaryl-1,3-dioxolan-
4,5-dimethanols [5]. Some other ligands have been used for the addition to
aldehydes with selectivities up to 75% ee [6]. One of these ligands, which showed
some selectivity, was derived from carbohydrates [7].
This prompted us to test acetals of type 2 as additives. They had been used in
stereoselective synthesis in a broad range of applications and had shown promising
results in previous investigations, in which the acetal was a covalently bound part
of the molecule which reacted with a Grignard reagent [8]. This type of acetals had
never been tested as additives. For this reason we investigated the reaction of
benzaldehyde (3) with butylmagnesium bromide (1b) and butyllithium (1a), resp.,
which were complexed with acetals 2. These metals were chosen because of the
very broad ®eld of application and ready availability of their organic derivatives.
Moreover, the highest selectivity reported for the Grignard reaction without
modi®cation, e.g. transmetalation, was 39% ee [9, 10].
Results and Discussion
For the sake of comparability we used the same conditions as were found in the
literature dealing with this kind of experiments [9]. In detail, a solution of the
acetal 2a-e in THF and diethyl ether, resp., was cooled to 0ꢀC before one
equivalent of the organometallic component 1a,b was added. The mixture was
Scheme 1. Principle reaction pathway of the selectivity experiments and by-products 5±7 obtained
from 2b and 2c, resp., upon reaction with BuLi in THF

Chiral Ligands in Grignard Reactions
955
stirred for 30 min to complete complex formation, cooled to ꢁ78ꢀC, and a solution
of a quarter equivalent of 3 in the corresponding solvent was added dropwise. It
was stirred for exactly 1 h keeping the temperature between ꢁ84 and ꢁ72ꢀC,
quenched with water, and worked up by extraction to give a mixture of recovered
acetal 2a-e, 1-phenyl-1-pentanol (4), and sometimes unreacted 3 and degradation
products of the additive 5±7, resp., which were all separated by chromatography.
The enantiomeric excess of 4 was determined by GC, HPLC, and measurement
of ‰ꢀŠ2D5. The gaschromatographic analyses were carried out directly with 4 on
derivatized cyclodextrines. For HPLC, substituted cellulose was used as stationary
phase.
One experiment only (2b, Et2O, BuMgBr) out of 20 (5 ligands, 2 solvents, 2
organometallics) showed a considerable enantioselectivity; the (R)-enantiomer was
formed with 47% ee. The reaction was very sensitive with regard to conditions;
both the change from Et2O (47% ee) to THF (1% ee) and from BuMgBr (47% ee)
to BuLi (0% ee in Et2O, 1% ee in THF) led to a complete loss of selectivity. The
fact that with BuLi as organometallic compound no selectivity was observed may
be attributed, on the one hand, to the degradation of 2b by BuLi (vide infra), and,
on the other hand, to the higher reactivity of BuLi.
Further evidence that Et2O is essential for the observed enantioselectivity arises
from an experiment carried out in toluene which is unable to coordinate to the
organometallic species and in which the obtained alcohol showed only 9% ee. In
all other investigated cases the selectivity was lower than 5% ee.
As far as the stability of the acetals was concerned, they were recovered in high
yield (74 ±100%) in most of the experiments, which shows that they were stable
under these reaction conditions. However, 2b and 2c gave some degradation
products (about 40%) when used with BuLi. These products were identi®ed as 5
and 6, which can be formed by ꢁ-elimination, and 7, which is the product of a base
induced [1,2]-Wittig rearrangement of 2c [11]. For more detailed information on
yield, recovered ligand, and enantioselectivity see Table 1 in the experimental
section.
Eventually, the different methods for determination of enantioselectivity used
within this paper were compared. Considering the time necessary to conduct the
analysis and from the separation factor point of view as well, HPLC was the
method of choice. Unfortunately, especially in cases in which by-products
originating from the ligand were observed, results from HPLC were not reliable,
because by-products and product under investigation showed nearly the same
retention time. Thus, it was obvious that measuring the optical rotation of products
puri®ed by chromatography would also give incorrect results. Taking all this into
account we had to conclude that GC analysis was the most appropriate method in
our study, although the separation factor was not as good and the analysis time was
much longer than with HPLC.
Conclusion
Acetals of type 2 only exhibit a signi®cant enantioselectivity as ligand for the
addition of butylmagnesium bromide to benzaldehyde, if a further heteroatom is
available for complex formation, i.e. if chelat formation is possible. The achieved

956
M. KnollmuÈller et al.
selectivity is still rather low compared with other reaction systems, but somewhat
higher than the highest value reported so far for Grignard reagents [9,10].
Experimental
General techniques
All reactions were carried out under a nitrogen atmosphere in dry, freshly distilled solvents under
anhydrous conditions unless otherwise stated. Tetrahydrofuran (THF) and diethyl ether (Et2O) were
distilled from sodium/benzophenone. Magnesium chippings were dried in a desiccator at 60 ꢀC
before use. Butyllithium was purchased from Aldrich as a 2.5 M solution in n-hexane and used
immediately. All other reagents were purchased in standard commercial quality unless otherwise
stated. Reactions were monitored by TLC carried out on 0.25 mm Merck silica gel plates (60F-254)
using UV light as visualizing agent and 5% ethanolic phosphomolybdatic acid solution and heat as
developing agents. For vacuum ¯ash chromatography (VFC) and column chromatography (CC), the
amount of silica gel 60 (Merck, 0.2±0.5 mm mesh size) and the eluent is given. Melting points were
recorded according to Ko¯er and are uncorrected. Microanalyses were performed at the Institute of
Physical Chemistry, University of Vienna, under the supervision of Mag. J. Theiner; their results
agreed with the calculated values within experimental error. NMR spectra were recorded on a Bruker
AC 200 instrument and calibrated using the solvent as internal standard. Optical rotations were
recorded on a Perkin Elmer 241 polarimeter, and optical purity was based on the highest value of
25
speci®c rotation ꢂ‰ꢀŠ ˆ 37:6 ꢂc ˆ 3; benzene)) [12]. HPLC separations of 1-phenyl-1-pentanol
D
were performed on a Shimadzu system (LC-8A pump and SPD-6AV detector) using a Daicel column
(Chiralcel OD) and 1% 2-propanol in n-hexane as eluent. UV light (254 nm) was used for detection.
The signals were recorded and integrated with a DP 700 from Carlo Erba. GC analyses of 1-phenyl-
1-pentanol were performed on a Carlo Erba HR-GC 5300 Mega Series using a 50 m Macherey-Nagel
fused silica capillary column (FS-Lipodex/E) with an ID of 0.25 mm. Helium 5.0 was used as carrier
gas with a ¯ow rate of 4.3 ml/min (column pre-pessure: 210 kPa). The injector was heated to 220ꢀC,
and injected samples were splitted in a ratio of 1/73. The column was held at 100ꢀC for 50 min; then
the temperature was raised to 140ꢀC in a rate of 1ꢀC/min. Signals were detected with a FID (260ꢀC),
and chromatograms were recorded on a Carlo Erba SP4270 integrator and processed with LABNET2
software from Spectra Physics.
n-Butylmagnesium bromide (1b) was prepared in the appropriate solvent (Et2O or THF, resp.)
immediately before use. Compounds 2a,d,e were prepared as described in Ref. [13].
(2R-(2ꢀ,3aꢀ,4ꢁ,7ꢁ,7aꢀ))-Octahydro-7,8,8-trimethyl-2-(2-(phenylmethoxy)ethoxy)-
4,7-methanobenzofuran (2b; C21H30O3)
A solution of 4.0 g (11.5 mmol) of (2S,20S-(2ꢀ,20ꢀ,3aꢀ,3a0ꢀ,4ꢁ,40ꢁ,7ꢁ,70ꢁ,7aꢀ,7a0ꢀ))-2,20-oxybis-
(octahydro-7,8,8-trimethyl-4,7-methanobenzofuran) (MBE)2O), 6.5 g (42.7 mmol) of 2-(phenyl-
methoxy)ethanol, and 0.2 g (1.05 mmol) of 4-methylbenzenesulfonic acid monohydrate in 50 ml
CH2Cl2 was stirred for 30 min. 2 g Na2SO4 were added, and stirring was continued for further
90 min. The mixture was washed with a saturated NaHCO3 solution, dried over Na2SO4, and the
solvent was evaporated. VFC (200 g, petroleum ether (PE)/Et2O (20:1)) and Kugelrohr distillation
gave 4.0 g (59%) of 2b as a colorless oil.
25
D
1
B.p.: 70ꢀC/1.3 Pa (Kugelrohr); ‰ꢀŠ ˆ ꢁ46:6 ꢂc ˆ 3, benzene); H NMR (200 MHz, ꢂ, CDCl3):
7.42±7.22 (m, 5H, Ph-H), 5.16 (dd, 1H, 2-H), 4.58 (s, 2H, Ph-CH2-O), 3.90 (d, J ˆ 6.6 Hz, 1H, 7a-H),
3.86±3.50 (m, 4H, O-CH2-CH2-O), 2.4±0.8 (m, 17H, aliphatic H, therein: 1.00, 0.98, and 0.80 (3s;
9H, 3 CH3) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 138.4 (s, C(ph)- 1), 128.3 (d, C(ph)-3, C(ph)-5),
127.6 (d, C(ph)-2, C(ph)-6), 127.5 (d, C(ph)-4), 105.1 (d, C-2), 91.1 (d, C-7a), 73.0 (t, Ph-CH2-O),

Chiral Ligands in Grignard Reactions
957
69.4 (t, Ph-CH2-O-CH2), 65.8 (t, O-CH-O-CH2), 48.4 (d, C-4), 47.5 (s, C-7), 47.0 (s, C-8), 45.9 (d,
C-3a), 38.6 (t, C-3), 32.4 (t, C-6), 28.9 (t, C-5), 22.9, 20.4, and 11.6 (3q, 3 CH3) ppm.
(2R-(2ꢀ,3aꢀ,4ꢁ,7ꢁ,7aꢀ))-Octahydro-2-((2-(methoxy)phenyl)methoxy)-7,8,8-trimethyl-
4,7-methanobenzofuran (2c; C20H28O3)
Prepared analogously to 2b from 4.49 g (12.9 mmol) of (MBE)2O and 3.57 g (25.8 mmol) of 2-
methoxybenzenemethanol [14]; yield after VFC (220 g, PE/Et2O (50:1)) and Kugelrohr distillation:
4.75 g (58%) of 2c as a colorless oil.
25
D
1
B.p.: 80ꢀC/1.1 Pa (Kugelrohr); ‰ꢀŠ ˆ ꢁ90:8 ꢂc ˆ 1, CH2Cl2); H NMR (200 MHz, ꢂ, CDCl3):
7.42±7.18, and 7.01±6.82 (2m, 4H, Ph-H), 5.25 (dd, 1H, 2-H), 4.71 and 4.51 (2d, J ˆ 13 Hz, 2 H, Ph-
CH2-O) 3.97 (d, J ˆ 6.6 Hz, 1H, 7a-H), 3.80 (s, 3H, OCH3), 2.4±0.8 (m, 17H, aliphatic H, therein:
1.01, 0.98, and 0.80 (3s; 9H, 3 CH3)) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 157.1 (s, C(ph)- 2), 128.7,
128.3 (2d, C(ph)-3, C(ph)-5), 127.1 (s, C(ph)-1), 120.3 (d, C(ph)-4), 110.2 (d, C(ph)-6), 104.5 (d, C-
2), 91.1 (d, C-7a), 63.2 (t, Ph-CH2-O), 55.3 (q, CH3-OPh), 48.5 (d, C-4), 47.6 (s, C-7), 47.0 (s, C-8),
46.0 (d, C-3a), 38.6 (t, C-3), 32.5 (t, C-6), 28.9 (t, C-5), 22.9, 20.5, and 11.6 (3q, 3 CH3) ppm.
General procedure of selectivity experiments
To a solution of 4 mmol of 2a±e in 18 ml of anhydrous Et2O and THF, resp., a solution of 4 mmol of
the organometallic compound (BuMgBr and BuLi, resp.) was added at 0ꢀC within 10 min. The
mixture was stirred for 30 min, cooled to ꢁ78ꢀC, a solution of 0.106 g (1 mmol) of benzaldehyde in
the corresponding solvent was added within 10 min, and the mixture was stirred for 1 h. After adding
5 ml of water the mixture was allowed to reach room temp. When THF was used as solvent, the
mixture was concentrated in vacuo and diluted with a mixture of Et2O and water. If BuMgBr was
used as organometallic component, ammonium chloride was added to dissolve the magnesium salts.
The aqueous phase was separated and extracted twice with Et2O. The combined organic layers were
dried with sodium sulfate, and the solvent was evaporated. VFC (20±30 g, PE/Et2O (50:1±4:1)) and
CC (150±300 g, PE/Et2O (20:1±4:1)), resp., yielded 1-phenyl-1-pentanol (4) and recovered 2a-e
which could be reused after Kugelrohr distillation. Additionally in experiments 5 and 6 (2b, BuLi,
THF) and 10 (2c, BuLi, THF) larger amounts (about 40%) of by-products were obtained which were
identi®ed as enolether 5, vinylacetal 6, and alcohol 7.
(3aS-(3aꢀ,4ꢁ,7ꢁ,7aꢀ))-3a,4,5,6,7,7a-Hexahydro-7,8,8-trimethyl-4,7-methanobenzofuran
(5; C12H18O)[15]
Colorless oil; 1H NMR (200 MHz, ꢂ, CDCl3): 6.10±6.02 (m, 1H, 2-H), 5.15±5.05 (m, 1H, 3-H), 4.35
(d, J ˆ 9.9 Hz, 1H, 7a-H), 2.86±2.74 (m, 1H, 3a-H), 1.8±0.75 (m, 14H, aliphatic H, therein: 1.11,
1.05, and 0.83 (3s, 9H, 3 CH3)) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 146.6 (d, C-2), 105.6 (d,C-3),
93.6 (d, C-7a), 52.5 (d, C-3a), 48.6 (d, C-4), 47.6 (s, C-7), 46.1 (s, C-8), 32.6 (t, C-6), 28.1 (t, C-5),
‡
23.3, 18.9, and 11.2 (3q, 3 CH3) ppm; MS: m/z ˆ 178 [M ].
(2R-(2ꢀ,3aꢀ, 4ꢁ, 7ꢁ, 7aꢀ))-2-(Ethenyloxy)-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran
(6; C14H22O2)
25
D
Colorless oil; ‰ꢀŠ ˆ ꢁ103:3 ꢂc ˆ 1, CH2Cl2); 1H NMR (200 MHz, ꢂ, CDCl3): 6.43 (dd, J1 ˆ 20 Hz,
J2 ˆ 6.6 Hz, 1H, O-CH=CH2), 5.40 (dd, 1H, 2-H), 4.41 (d, J ˆ 20 Hz, 1H, O-CH=CH2 trans), 4.09 (d,
J ˆ 6.6 Hz, 1H, O-CH=CH2 cis), 3.98 (d, J ˆ 6.6 Hz, 1H, 7a-H), 2.4±0.75 (m, 17H, aliphatic H,
therein: 0.99, 0.96, and 0.80 (3s, 9H, 3 CH3)) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 148.9 (d, O-
CH=CH2), 104.7 (d, C-2), 91.8 (d, C-7a), 90.5 (t, O-CH=CH2), 48.4 (d, C-4), 47.6 (s, C-7), 47.0 (s,
C-8), 45.5 (d, C-3a), 38.3 (t, C-3), 32.3 (t, C-6), 28.8 (t, C-5), 22.9, 20.4, and 11.5 (3q, 3 CH3) ppm.

958
M. KnollmuÈller et al.
Ã
(2R-(2ꢀ(R ),3aꢀ,4ꢁ,7ꢁ,7aꢀ))-Octahydro-ꢀ-(2-methoxyphenyl)-7,8,8-trimethyl-
Ã
Octahydro-ꢀ-(2-methoxyphenyl)-7,8,8-trimethyl-4,7-methanobenzofuran-2-methanol
(7b; C20H28O3); mixture (3/2) [16]
4,7-methanobenzofuran-2-methanol (7a; C20H28O3) and (2R-(2ꢀ(S †,3aꢀ,4ꢁ,7ꢁ,7aꢀ))-
1
Colorless crystals; m.p.: 73±90ꢀC; H NMR (200 MHz, ꢂ, CDCl3): 7.47±7.36 and 7.30±7.18 (2m,
2H, 3(ph)-H, 5(ph)-H), 7.03±6.91 (m, 1H, 4(ph)-H), 6.87 (d, 0.6H, 6(ph)-H, 7a), 6.83 (d, 0.4H,
6(ph)-H, 7b), 5.07 (d, J ˆ 4.4 Hz, 0.4H, CHOH, 7b), 4.84 (d, J ˆ 9.6 Hz, 0.6H CHOH, 7a), 4.48±4.37
(m, 0.4H, 2-H, 7b), 4.21±4.08 (m, 0.6H, 2-H, 7a), 4.01 (d, J ˆ 7 Hz, 0.4H, 7a-H, 7b), 3.97 (d,
J ˆ 7 Hz, 0.6H, 7a-H, 7a), 3.83 (s, 3H, OCH3), 2.4±2.1 (m, 1H, 3a-H), 1.9±0.75 (m, 16H, aliphatic
H, therein: 1.0, 0.95, and 0.8 (3s, 9H, 3 CH3) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 157.0 (s, C(ph)-2,
7a), 156.2 (s, C(ph)-2, 7b), 129.3 (s, C(ph)-1, 7b), 128.8 (s, C(ph)-1, 7a), 128.6, 128.2, and 127.3
(3d, C(ph)-3, C(ph)-5), 120.9 (d, C(ph)-4, 7a), 120.5 (d, C(ph)-4, 7b), 110.5 (d, C(ph)-6, 7a), 110.1
(d, C(ph)-6, 7b), 93.8 (d, C-7a, 7b), 91.1 (d, C-7a, 7a), 84.7 (d, C-2, 7a), 82.5 (d, C-2, 7b), 73.1 (d,
CHOH, 7b), 68.4 (d, CHOH, 7a), 55.4 (q, OCH3, 7a), 55.1 (q, OCH3, 7b), 49.2 (d, C-4, 7b), 48.9 (d,
C-4, 7a), 48.7 (d, C-3a, 7b), 48.4 (s, C-7, 7b), 48.2 (s, C-7, 7a), 47.9 (d, C-3a, 7a), 46.8 (s, C-8, 7a),
Table 1. Summary of the selectivity experiments: yield of 4 (% based on 3), amount of recovered 2a-e
(% of added acetal), and enantiomeric excess (% ee) determined by different methods (GC, HPLC,
‰ꢀŠ2D5) for different additives, solvents, and organometallic compounds
b
Exp. Nr Add.
Solv.
Organometallic Yield of
Rec. Add.
(%)
%ee
Component
4 (%)
25
D
GC
HPLC
‰ꢀŠ
1
2a
2a
2a
2a
2b
2ba
2b
2b
2b
2b
2c
2c
2c
2c
2d
2d
2d
2d
2e
2e
2e
2e
THF
THF
Et2O
Et2O
THF
THF
THF
Et2O
Et2O
BuLi
84
86
93
98
93
46
51
80
45
83
-
1
1
±
5
1
4
1
0
47
9
1
1
5
1
1
1
1
1
2
1
1
1
4
1
±
3
±
±
1
±
44
±
±
2
4
2
4
4
5
5
2
3
1
3
2
2
BuMgBr
BuLi
77
79
93
6
2
0
3
±
±
1
±
45
±
±
0
4
0
±
1
1
2
±
1
0
1
3
4
BuMgBr
BuLi
5
6
BuLi
30
81
94
36
98
18
72
88
85
80
66
91
82
89
85
97
42
7
BuMgBr
BuLi
8
9
BuMgBr
10
11
12
13
14
15
16
17
18
19
20
21
22
toluene BuMgBr
THF
THF
Et2O
Et2O
THF
THF
Et2O
Et2O
THF
THF
Et2O
Et2O
BuLi
52
100
89
97
95
97
100
98
78
74
94
83
BuMgBr
BuLi
BuMgBr
BuLi
BuMgBr
BuLi
BuMgBr
BuLi
BuMgBr
BuLi
BuMgBr
a In alteration to the general procedure, in this experiment the complex formation between 1a and 2b
was carried out at ꢁ46ꢀC because the yield was very low under usual reaction conditions (see
b
experiment 5); & main product 4b (S-enantiomer), & main product 4a (R-enantiomer)

Chiral Ligands in Grignard Reactions
959
46.5 (s, C-8, 7b), 32.5 (t, C-3, 7a), 32.4 (t, C-3, 7b), 32.3 (t, C-6, 7a), 31.2 (t, C-6, 7b), 28.8 (t, C-5,
7a), 28.7 (t, C-5, 7b), 22.7, 20.5, 20.2, and 11.7 (4q, 3 CH3) ppm.
References
[1] Cohen HL, Wright GF (1953) J Org Chem 18: 432
[2] Noyori R, Kitamura M (1991) Angew Chem 103: 34; Angew Chem Int Ed Engl 30: 49; Knochel
P (1995) Synlett 393; Vidalferran A, Moyano A, Pericas MA, Riera A (1997) J Org Chem 62:
4970; Lutz C, Knochel P (1997) J Org Chem 62: 7895; Bolm C, Fernandez KM, Seger A, Raabe
G (1997) Synlett 1051; Hayase T, Sugiyama T, Suzuki M, Shibata T, Soai K (1997) J Fluorine
Chem 84: 1; Shibata T, Hayase T, Aiba Y, Tabira H, Soai K (1997) Heterocycles 46: 235; Asami
M, Inoue S (1997) Bull Chem Soc Jap 70: 1687; Chan TH, Zheng GZ (1997) Can J Org Chem 75:
629; Nakano H, Iwasa K, Hongo H (1997) Heterocycles 46: 267; Rijnberg E, Hovestad NJ, Kleij
AW, Jastrzebski JTBH, Boersma J, Janssen MD, Spek AL, van Koten G (1997) Organometallics
16: 2847; Prasad KRK, Joshi NN (1997) J Org Chem 62: 3770; Nakano H, Kumagai N,
Matsuzaki H, Kabuto C, Hongo H (1997) Tetrahedron-Asymmetry 8: 1391; Beliczey J, Giffels G,
Kragl U, Wandrey C (1997) Tetrahedron-Asymmetry 8: 1529; Genov M, Kostova K, Dimitrov V
(1997) Tetrahedron-Asymmetry 8: 1869; Trentmann W, Mehler T, Martens J (1997) Tetrahe-
dron-Asymmetry 8: 2033; Wilken J, Groger H, Kossenjans M, Martens J (1997) Tetrahedron-
Asymmetry 8: 2761; Anderson JC, Harding M (1998) Chem Commun 393; Dosa PI, Fu GC
(1998) J Amer Chem Soc 120: 445
[3] Seebach D, Weidmann B, Widler L (1983) In: Scheffold R (ed) Modern Synthetic Methods, vol
È
3. Salle & Sauerlander, Aarau, p 217; Reetz MT (1986) Organotitanium Reagents in Organic
Synthesis. Springer, Berlin Heidelberg; Duthaler RO, Hafner A (1992) Chem Rev 92: 807;
Ramon DJ, Yus M (1997) Tetrahedron-Asymmetry 8: 2479; Zhang FY, Chan ASC (1997)
Tetrahedron-Asymmetry 8: 3651; Chan ASC, Zhang FY, Yip CW (1997) J Amer Chem Soc 119:
4080; Guo C, Qiu J, Zhang XM, Verdugo D, Larter ML, Christie R, Kenney P, Walsh PJ (1997)
Tetrahedron 53: 4145; Ramon DJ, Yus M (1998) Tetrahedron Lett 39: 1239
[4] Devant RM, Radunz H-E (1995) In: Helmchen G, Mulzer J, Hoffmann RW, Schaumann E (eds)
Methoden der organischen Chemie (Houben-Weyl), 4th edn, vol E21b. Thieme, Stuttgart, p 1297
[5] Weber B, Seebach D, (1994) Tetrahedron 50: 6117
[6] Tomioka K, Nakajima M, Koga K (1987) Chem Lett 65
[7] Inch TD, Lewis GJ, Sainsbury GL, Sellers DJ (1969) Tetrahedron Lett 3657
È
È
[8] Noe CR, KnollmuÈller M, Ettmayer P, Gartner P, Letschnig M (1990) Osterr Chem Z 36
[9] Mukaiyama T, Soai K, Sato T, Shimizu H, Suzuki K (1979) J Amer Chem Soc 101: 1455
[10] The optical purity reported in Ref. [9] (47% ee) was based upon a maximum rotation of
‰ꢀŠ ˆ 31:3 ꢂc ˆ 3:0; benzene), but this value represents only 83.3% optically pure material.
D
25
Their ee values were corrected to a maximum of ‰ꢀŠ ˆ 37:6 ꢂc ˆ 3:0; benzene) see Mazaleyrat
D
J-P, Cram DJ (1981) J Amer Chem Soc 103: 4585
[11] Tomooka K, Yamamoto H, Nakai T (1996) J Amer Chem Soc 118: 3317
[12] Horeau A, Guette J-P, Weidmann R (1966) Bull Soc Chim Fr 3513
È
[13] Noe CR, KnollmuÈller M, Steinbauer G, Jangg E, Vollenkle H (1988) Chem Ber 121: 1231
[14] Obtained by LiAlH4 reduction of the corresponding acid. - bp 60ꢀC/13 Pa (Nielsen AT, Haseltine
S (1968) J Org Chem 33: 3264, 3271 bp 68±70ꢀC/13 Pa)
[15] Letschnig M (1987) Diploma thesis, Vienna University of Technology, p 50
[16] Assignment of 7a and 7b was performed tentatively
Received March 19, 1998. Accepted (revised) April 27, 1998