Optimisation, scope and limitations of enantioselective aldol reactions of an S-ketene silyl acetal with aliphatic aldehydes under (R)-BINOL-titanium(IV) catalysis conditions

Article abstract of DOI:10.1002/1099-0690(200210)2002:20<3419::AID-EJOC3419>3.0.CO;2-F

The Mukaiyama aldol reaction between the functionalised aldehydes 5 and the S-ketene silyl acetal 2 catalysed by 1,1'-binaphthyl-derived chiral titanium(IV) complex 4 afforded the corresponding aldol products 6 in good yields and with good to excellent enantioselectivities. The chemical yield could further be enhanced, without loss of stereoselection, by addition of phenol and/or molecular sieves. The presented aldol reactions with aluminium, boron and ytterbium-BINOL catalysts demonstrate that only low chiral induction can be achieved. Aldol product 6a was converted into an α-lipoic acid precursor 8, thus providing a formal synthesis of this biologically active compound. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).

Full text of DOI:10.1002/1099-0690(200210)2002:20<3419::AID-EJOC3419>3.0.CO;2-F

FULL PAPER
Optimisation, Scope and Limitations of Enantioselective Aldol Reactions of an
S-Ketene Silyl Acetal with Aliphatic Aldehydes under (R)-BINOL-
Titanium(IV) Catalysis Conditions
Reinhold Zimmer,*[a] Anke Peritz,[b] Regina Czerwonka,[b] Luise Schefzig,[a] and
Hans-Ulrich Reißig[a]
Dedicated to Dr. Maximilian A. Grassberger on the occasion of his 65th birthday
Keywords: Aldehydes / Aldol reaction / Asymmetric catalysis / Ketene silyl acetal / Titanium
The Mukaiyama aldol reaction between the functionalised
aldehydes 5 and the S-ketene silyl acetal 2 catalysed by 1,1Ј-
binaphthyl-derived chiral titanium(IV) complex 4 afforded
the corresponding aldol products 6 in good yields and with
good to excellent enantioselectivities. The chemical yield
could further be enhanced, without loss of stereoselection, by
aldol reactions with aluminium, boron and ytterbium-BINOL
catalysts demonstrate that only low chiral induction can be
achieved. Aldol product 6a was converted into an α-lipoic
acid precursor 8, thus providing a formal synthesis of this bio-
logically active compound.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
addition of phenol and/or molecular sieves. The presented 2002)
Introduction
aldehydes Ϫ was required. In recent years, considerable suc-
cess has been achieved in enhancing the yields and stereo-
selectivities of aldol reactions, ultimately resulting in prac-
tical procedures with very useful levels of enantioselectiv-
ity.[6] One of the most popular ligands for a variety of
metal-mediated enantioselective carbon-carbon bond-for-
ming reactions is C2-symmetric 1,1Ј-binaphthyl-2,2Ј-diol (4,
abbreviated as BINOL).[7] The use of chiral ligands is not
restricted to BINOL 4 and its derivatives: several other
highly effective ligands have successfully been employed in
enantioselective reactions.[8] We decided to examine BINOL
4 because it is relatively cheap and, more importantly, com-
mercially available in both its R and S forms. The first BI-
NOL/titanium-catalysed aldol reactions with S-ketene silyl
acetal 2 were carried out in the mid-1990s, in particular by
Keck[9a] and Mikami.[10aϪ10c] In general, they obtained the
resulting aldol products in reasonable yields and with good
enantioselectivities (up to 97% ee). Most of these experi-
ments were performed with benzaldehyde or unfunc-
tionalised aldehydes; only a few examples involving func-
tionalised substrates, such as α-benzyloxy- and α-chloro-
substituted aldehydes[8d,9,10] and 2,2,2-trifluoroethanal,[11]
were reported. We have therefore investigated a broad vari-
ety of aliphatic functionalised aldehydes as substrates in a
series of BINOL/metal-catalysed aldol reactions. The op-
timisation and the scope and limitations of the enantioselec-
tive aldol reaction with S-ketene silyl acetal 2 as nucleo-
philic component in the presence of 4 and titanium() are
reported here (Scheme 1).
Because of the recent interest in (R)-α-lipoic acid (1), a
pharmacologically important compound,[1] reliable and effi-
cient methods for its asymmetric synthesis are required. A
variety of stereoselective approaches to compound 1 have
so far been reported. Enzyme-catalysed reactions of key in-
termediates[2] have frequently been utilised, but ‘‘chemical’’
routes, such as the iron-mediated method developed by
[3]
´
Gree or the Sharpless asymmetric dihydroxylation reac-
tion, have also been employed.[4] We have recently success-
fully employed asymmetric allylation to prepare enantio-
pure homoallyl alcohols that can serve as useful interme-
diates in the synthesis of 1.[5]
As part of our research into the preparation of enantio-
pure sec-alcohols, an efficient procedure for enantioselective
aldol reactions Ϫ in particular with aliphatic functionalised
[a]
Institut für Chemie Ϫ Organische Chemie, Freie Universität
Berlin,
Takustrasse 3, 14195 Berlin, Germany
Fax: (internat.) ϩ 49-(0)30/83855367
E-mail: rzimmer@chemie.fu-berlin.de
[b]
Institut für Organische Chemie, Technische Universität
Dresden,
01062 Dresden, Germany
Eur. J. Org. Chem. 2002, 3419Ϫ3428  2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1020Ϫ3419 $ 20.00ϩ.50/0
3419

R. Zimmer, A. Peritz, R. Czerwonka, L. Schefzig, H.-U. Reißig
FULL PAPER
yield and stereoselectivity (entry 4, Table 1). The reaction
mixture was routinely worked up by addition of 2  HCl
solution, although the workups of the initial experiments
were done by addition of saturated aqueous NH4Cl solu-
tion instead of acid, resulting in isolation of the corres-
ponding O-silylated product 7 as a second component (ent-
ries 2, 3 and 6 in Table 1; further examples see Table 2).
Scheme 1
Scheme 2
Results and Discussion
Starting with easily accessible model substrates me-
Combinations of BINOL or its derivatives with achiral
thoxycarbonyl- and n-propoxycarbonyl-substituted alde- and chiral activators were very useful in a variety of asym-
hydes 5a and 5b (which may actually serve as intermediates metric transformations. These additives may enhance en-
for the synthesis of 1), enantioselective aldol reactions were antioselectivity as well as chemical yield.[14Ϫ19] Molecular
performed with 1.5 equivalents of S-ketene silyl acetal 2 sieves are a simple and efficient additive for enantioselective
(Scheme 2). Variations of reaction conditions were system- CϪC bond-forming reactions.[10c] The aldol reaction be-
atically examined, and typical results are compiled in tween model compound 5a and 2 in the presence of 5 mol %
˚
Table 1. The first experiments were carried out according to of catalyst 4a and finely powdered 4 A molecular sieves
a procedure described by Keck and Krishnamurthy.[9] (R)- (activated by heating to 150 °C, 5 h, 0.15 mbar) afforded 6a
BINOL-Ti catalyst 4a[12] was generated in situ by mixing in higher yield and with excellent enantioselectivity (cf. ent-
(R)-BINOL 4 and Ti(OiPr)4 in diethyl ether at room tem- ries 4 and 5, Table 1). Another favourable additive is
perature.[13] Our initial efforts focused on reduction of the phenol,[10b][14b,18] which strongly promoted the aldol addi-
quantity of premixed catalyst from 10 to 7.5 and 5 mol % tion between 5a and 2 to afford 6a in better yield and with
(entries 1, 3 and 4, Table 1). It turned out that the enantio- an enantioselectivity of Ͼ 97% ee (cf. entries 4 and 8,
selectivity and yield of the aldol reaction were strongly Table 1). An excellent level of enantioselectivity and the
˚
dependent on the amount of catalyst. Use of 10 mol % and best yield of 6a could be attained by use of both 4 A mo-
also of 7.5 mol % of (R)-BINOL-Ti catalyst 4a provided lecular sieves and phenol as additives (entry 11, Table 1).
alcohol 6a in good yields and with excellent enantioselectiv- Reduction of the ratio of catalyst 4a/phenol from 1:5 to 1:1
ities (93% and Ͼ 97% ee); however, reduction of the quant- gave no significant difference in the efficiency of the aldol
ity of catalyst 4a to 5 mol % dramatically decreased both addition of 5b and 2 (cf. entries 6 and 7, Table 1).
Table 1. Aldol reactions of aldehydes 5a and 5b with S-ketene silyl acetal 2 under conditions of Ti(OiPr)4/(R)-BINOL 4a catalysis
(Scheme 2)
Entry
Aldehyde 5
Amount of catalyst
Additive
Product 6
Yield of 6
ee
1
2
3
4
5
6
7
8
9
10
11
12
13
5a
5b
5a
5a
5a
5b
5b
5a
5a
5a
5a
5a
5a
10 mol %
10 mol %
7.5 mol %
5 mol %
Ϫ
Ϫ
Ϫ
Ϫ
6a
6b
6a
6a
6a
6b
6b
6a
6a
6a
6a
6a
6a
66%
Ն 97%
96%
93%
41%
Ն 97%
96%
96%
Ն 97%
90%
48%[a][b]
50%[b][c]
27%
˚
5 mol %
mol. sieves (4 A)
64%
10 mol %
10 mol %
5 mol %
2.5 mol %
1.25 mol %
10 mol %
10 mol %
10 mol %
phenol (50 mol %)
phenol (10 mol %)
phenol (50 mol %)
phenol (12.5 mol %)
phenol (6.3 mol %)
phenol (50 mol %) mol. sieves (4 A)
Me3SiCl (40 mol %)
39%[b][d]
65%
70%
61%
21%
76%
39%
24%
32%
˚
Ն 97%
Ն 97%
91%
2-tert-butylphenol (20 mol %)
[a]
[b]
In addition, O-silylated product 7b was isolated in 20% yield.
Workup with sat. aq. NH4Cl soln. instead of 2  HCl soln.; see Exp.
[c]
[d]
Sect. In addition, O-silylated product 7a was isolated in 24% yield. In addition, O-silylated product 7b was isolated in 17% yield.
3420 Eur. J. Org. Chem. 2002, 3419Ϫ3428

Enantioselective Aldol Reactions of an S-Ketene Silyl Acetal with Aliphatic Aldehydes
FULL PAPER
Table 2. Aldol reactions between aldehydes 5cϪ5q and S-ketene silyl acetal 2 under conditions of Ti(OiPr)4/(R)-BINOL 4a catalysis
(Schemes 3Ϫ5)
Entry
Aldehyde 5
Amount of catalyst
Additive
Product 6
Yield of 6
ee
1
2
3
4
5
6
7
8
9
10
11
12
13
5c
5c
5d
5e
5e
5f
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
5 mol %
Ϫ
6c
6c
6d
6e
6e
6f
71%
76%
52%
36%
58%
65%
71%
68%
73%
50%
85%
56%
43%[a][b]
82%
93%
38%
46%
53%
95%
96%
97%
96%
94%
92%
92%
94%
phenol (50 mol %)
Ϫ
Ϫ
phenol (50 mol %)
Ϫ
phenol (50 mol %)
Ϫ
phenol (50 mol %)
Ϫ
phenol (50 mol %)
phenol (25 mol %)
phenol (25 mol %)
5f
6f
5g
5g
5h
5h
5h
5h
6g
6g
6h
6h
6h
6h
5 mol %
˚
mol. sieves (4 A)
14
15
16
17
18
19
20
21
22
23
24
5i
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
Ϫ
6i
23%
90%
95%
71%
63%
62%
5i
phenol (20 mol %)
Ϫ
phenol (20 mol %)
Ϫ
6i
22%[b][c]
[b][d]
5j
5j
6j
6j
26%
65%
23%
5k
5l
5m
5n
5o
5p
5q
6k
6l
6m
10
6o
6p
6q
Ϫ
76%[b][e]
31%[f]
40%[h]
0%
95%
[g]
phenol (50 mol %)
[g]
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
0%
0%
[a]
[b]
In addition, desilylated product 7h was isolated in 31% yield. Workup with sat. aq. NH4Cl soln. instead of 2  HCl soln.; see Exp.
[c]
[d]
[e]
Sect. In addition, desilylated product 9 was isolated in 48% yield. In addition, O-silylated product 7j was isolated in 2% yield. In
addition, O-silylated product 7l was isolated in 11% yield. Mixture of two diastereomers (64:36). [g] Not determined. [h] Mixture of cis/
[f]
trans diastereomers (55:45).
To demonstrate the scope and limitations of the above
optimisation we applied (R)-BINOL-Ti catalyst 4a to a
We next studied the effect of reducing the amount of
catalyst in the presence of phenol. Interestingly, the catalyst
loading could be reduced to 2.5 mol % of 4a with almost
no negative effect, except that the ee was decreased slightly
(entries 8 and 9, Table 1). On the other hand, use of only
1.25 mol % of catalyst 4a and 6.3 mol % of phenol resulted
in poor selectivity (32% ee) and a low yield (21%) of 6a
(entry 10). Aldol reactions in the presence of sterically
bulky phenols, such as 2-tert-butylphenol (entry 13) and
chlorotrimethylsilane (entry 12), furnished 6a with good to
excellent enantioselectivities, but the yields were only mod-
erate.
At this point it should be mentioned that reduction of
the thioester unit of enantiopure compounds 6a and 6b
with sodium borohydride directly affords key intermediates
for the synthesis of enantiopure (R)-α-lipoic acid (1). Treat-
ment of aldol product 6a afforded the 1,3-diol 8 in 61%
yield. The conversion of the methyl ester analogue of 8 into
(R)-α-lipoic acid (1) has already been reported.[20] A short
and enantioselective formal total synthesis of (R)-1 with an
asymmetric aldol reaction as a crucial step has thus been
established as shown in Equation (1).
variety
of
(mostly)
aliphatic
aldehydes
5cϪq
(Schemes 3Ϫ5). The results are summarised in Table 2. In
general, use of phenol as additive has effects similar to
those found for the corresponding reactions of 5a and 5b.
Addition of phenol increased the yields of aldol products
6, while enantioselectivities were similar or even slightly
higher. Good to excellent results could be obtained with
most of the aldehydes employed (e.g., 5c, 5fϪi, 5l, see
Table 2). On the other hand, only moderate enantioselectiv-
ities were observed with aldehydes 5d (38% ee), 5e (53% ee)
and functionalised precursors 5j (71% ee) and 5k (62% ee).
Remarkably, the steric hindrance of an isopropyl group
seems to have less influence on the stereoselectivity under
the reaction conditions applied. With elongation of the
chain from n ϭ 0 to n ϭ 1, the enantioselectivity of aldol
products increased slightly from 38% to 46% ee (cf. entries
3 and 4, Table 2). Nitro-substituted and methoxycarbonyl-
substituted aldehydes 5m and 5n[21] gave the expected aldol
products only in moderate yields (entries 20 and 21,
Table 2). In the latter aldol reaction, the intermediate 6n
could only be obtained as crude product, since it completely
cyclised to the γ-lactone 10 during purification by chroma-
tography.[22] Chiral aldehydes 5m and 5n were used in ra-
cemic form, and mixtures of diastereomers with ratios of
64:36 and 55:45, respectively, were therefore obtained. De-
(1)
Eur. J. Org. Chem. 2002, 3419Ϫ3428
3421

R. Zimmer, A. Peritz, R. Czerwonka, L. Schefzig, H.-U. Reißig
FULL PAPER
Scheme 3. a) (R)-BINOL-Ti 4a, Et2O, (phenol), 0 °C, 5 h, then 0
°C to room temp., 16 h
Scheme 5. a) (R)-BINOL-Ti 4a, Et2O, (phenol), 0 °C, 5 h, then 0
°C to room temp., 16 h
dol reactions were observed with aldehydes 5oϪq as pre-
cursors under the conditions developed above for catalyst
4a (entries 22Ϫ24, Table 2, Scheme 5). In these cases only
starting material was recovered.
The enantiomeric purities of the resulting aldol products
6 were unambiguously established by 1H and 13C NMR
spectroscopy on the corresponding MPTA esters prepared
with (S)-configured Mosher’s acid chloride.[23] The assign-
ment of the predominating configuration at the newly gen-
erated stereocentre of compounds 6 as depicted in the
Schemes is based on comparison with the signs of specific
rotation of known compounds (6d, 6f, 6h and 6l) or by ana-
logy if closely related products had been described in the
literature (6a, 6b, 6c, 6i, 6j and 6k). In good accordance
with Keck’s and Mikami’s results, (R)-BINOL-titanium
catalyst 4a promotes the preferential attack of 2 to the Re
face of the aldehydes investigated. A mechanistic interpreta-
tion will be provided in connection with quantum mechan-
ical calculations performed for the asymmetric aldol addi-
tion.[24]
Not only the isopropoxy-substituted (R)-BINOL-Ti cata-
lyst 4a, but also the ethoxy-substituted (R)-BINOL-Ti cata-
lyst 4b may efficiently be used. Catalyst 4b gave a compar-
ably good result with model compound 5a (Scheme 6), as
Scheme 4. a) (R)-BINOL-Ti 4a, Et2O, (phenol), 0 °C, 5 h, then 0
°C to room temp., 16 h
termination of the ee values of products 6m and 10 was not observed with the use of catalyst 4a. The tert-butoxy ligand
possible, because the diastereomers could not be completely (catalyst 4c) is apparently not suitable for the
separated by column chromatography or by HPLC. No al- carbonϪcarbon bond formation, due to a dramatic de-
3422
Eur. J. Org. Chem. 2002, 3419Ϫ3428

Enantioselective Aldol Reactions of an S-Ketene Silyl Acetal with Aliphatic Aldehydes
FULL PAPER
crease of the Lewis acidity of the titanium species.[25] Aldol of these additions are compiled in Table 3. Unfortunately,
reactions of 5a and 5f with 2 in the presence of catalyst 4c the chemical yields for alcohol 6a and its silylated derivative
afforded the desired alcohols 6a and 6f, respectively, with 7a were generally low, independently of the solvent used.
negligible enantioselectivities and in low yields (Scheme 6). When the reaction was performed in diethyl ether (entry 3,
Furthermore, the reaction between 2 and 5a resulted in the Table 3) the best result in terms of the enantiomeric excess
formation of α,β-unsaturated thioester 11 as a by-product.
(24% ee) was obtained. However, aldol products 6a/7a were
inevitably accompanied in all cases by 1,3,5-trioxane deriv-
ative 12 as the major component. This main component
arises from Lewis acid-catalysed cyclotrimerisation of alde-
hyde 5a.[28]
Scheme 7
Finally, the use of aluminium, boron and ytterbium as
central atoms in BINOL complexes should briefly be dis-
cussed. On treatment of (R)-BINOL 4 with AlMe3 at room
temperature for 0.5 h (R)-BINOL-Al catalyst 4f was
obtained.[29] This catalyst was used for the aldol reaction
Scheme 6. a) Et2O, 0 °C, 5 h, then 0 °C to room temp., 16 h
In analogy with the preparation of a tosylated titanium- between 5a and 2. With dichloromethane as solvent and
TADDOLate catalyst by mixing of (R,R)-TADDOL and (R)-BINOL-Al catalyst 4f (reaction conditions: Ϫ20 or
Ti(OiPr)2(OTs)2, generated in situ,[26] we applied this pro- Ϫ78 °C; 2Ϫ18 h; 0.20:0.10 equiv. of AlMe3/(R)-4), aldol
cedure to the generation of tosyl-substituted catalyst 4d by products 6a/7a were observed in 38% yield and with ee
mixing of (R)-BINOL 4 with Ti(OiPr)2(OTs)2 (reaction values only of up to 18%. A change of solvent from dichlor-
time 30 min at room temp.). Application of this new catalyst omethane to hexane or toluene resulted in strong decreases
4d to the model addition between 2 and 5a under standard in the yield and enantioselectivity of 6a (11Ϫ14% yield,
˚
conditions (Scheme 6) provided the aldol products 6a and 2Ϫ4% ee). Notably, addition of 4-A molecular sieves did
7a in 17% and 18% yields, respectively. However, the re- not affect the ee value (38% yield of 6a, 16% ee).
sulting ee value of 6a was disappointingly low (3% ee).
Furthermore, the known boron catalysts [(R)-BI-
We also investigated aldol reactions with catalyst 4e, pre- NOL]2BH 4g[30] and (R)-BINOL-BOPh 4h[31] were used in
pared from (R)-BINOL 4 and TiF4 according to a proced- the aldol addition between 2 and 5a under standard reac-
ure described by Carreira et al. (Scheme 7).[27] The results tion conditions (see Scheme 2). The reaction promoted by
Table 3. Aldol addition between 5a and 2 in the presence of (R)-BINOL/TiF4 (4e)
Entry
Solvent
Temperature
Time
Yield of 6a, 7a and 12
ee[a]
1
2
3
CH2Cl2
MeCN
Et2O
Ϫ78 °C to room temp.
Ϫ40 °C to room temp.
a) Ϫ78 °C to room temp.
b) room temp.
a) Ϫ78 °C to room temp.
b) room temp.
14 h
12 h
4, 0 and 72%
16, 17 and 34%
11, 0 and 41%
14% (ϩ)
7% (Ϫ)
24% (ϩ)
a) 16 h
b) 24 h
a) 16 h
b) 24 h
a) 10 h
b) 24 h
4
5
Toluene/MeCN
Benzotrifluoride
0, 8 and 11%
8, 13 and 77%
10% (ϩ)
16% (ϩ)
a) Ϫ20 °C to room temp.
b) room temp.
[a]
The sense of the optical rotation of the product is given in parentheses.
Eur. J. Org. Chem. 2002, 3419Ϫ3428
3423

R. Zimmer, A. Peritz, R. Czerwonka, L. Schefzig, H.-U. Reißig
FULL PAPER
procedure described by Keck (method D).[9b] A mixture of Ti(OR)4
(R ϭ iPr, tBu, Et or Ts) and (R)-BINOL 4 in diethyl ether (5 mL/
mmol of 5) was stirred for 1.5 h at room temp. The solution was
cooled to 0 °C, the corresponding aldehyde 5 (1.0 equiv.) was ad-
ded, and the mixture was stirred for 10 min. A solution of S-ketene
silyl acetal 2 (1.5 equiv.) in diethyl ether (5 mL/mmol of 5) was then
added. The reaction mixture was stirred for 5 h at 0 °C and was
then allowed to warm up to room temp. over 16 h. The reaction
was quenched by addition of 2  HCl solution (5 mL/mmol of 5)
and the mixture was stirred for 30 min at room temp. The aqueous
layer was extracted three times with diethyl ether (5 mL/mmol of
5), and the combined organic phases were dried over Na2SO4 and
concentrated. The crude product was purified by column chroma-
tography (neutral alumina, n-hexane/EtOAc, 3:1 or 4:1). Amounts
of catalyst and additives, yields and enantioselectivities are given
in Table 1 and 2.
catalyst 4g furnished aldol products 6a and 7a in 20% and
7% yields, respectively, product 6a being formed with an
enantioselectivity of only 30%. Catalyst 4h did not afford
the desired aldol product 6a (or 7a) under the reaction con-
ditions applied. The catalyst (R)-BINOL-Yb 4i was gener-
ated by mixing of (R)-BINOL 4 with Yb(OTf)3 in a 1:1
stoichiometry, similarly to the generation of 4a described
above. This catalyst promoted the formation of alcohol 6a
in 47% yield, but unfortunately with very low enantioselec-
tivity (9% ee).
Conclusions
The results reported here highlight the use of func-
tionalised aliphatic aldehydes as substrates in enantioselec-
tive aldol reactions with S-ketene silyl acetal 2 to obtain
chiral aliphatic sec-alcohols in good yields and with high to
excellent enantioselectivities. In particular, catalysts 4a and
4b are highly efficient for the preparation of the key com-
pounds 6a and 6b, which are key intermediates in the syn-
thesis of (R)-α-lipoic acid (1). For the first time, the crucial
stereogenic centre of a precursor of this biological active
compound has been generated simply by an asymmetric
catalysed aldol reaction.[5] Preliminary experiments with
aluminium, boron and ytterbium-BINOL catalysts demon-
In a few experiments the workup was performed by addition of
satd. aqueous NH4Cl (5 mL/mmol of 5) instead of 2  HCl (entries
2, 3 and 6 in Table 1; entries 13, 16 and 19 in Table 2; entries 2, 4
and 5 in Table 3).
˚
In cases in which molecular sieves were used, these (4 A, 600 mg/
mmol of 5) were added during the generation of the catalyst.
Reactions with (R)-BINOL-Met (Met ϭ B, Yb) were also per-
formed according to the typical procedure.
Typical Procedure for Desilylation of Aldol Derivatives 7: A mixture
of the corresponding silylated thioester 7 and HCl solution (2 ,
strated that only inferior chiral induction could be achieved 1 mL/mmol of 7) in THF (10 mL/mmol of 7) was stirred for 3 h at
room temp. The reaction was then quenched by addition of satd.
aqueous NaHCO3 solution (2 mL/mmol of 7). The aqueous layer
was extracted with diethyl ether (3 ϫ 5 mL/mmol of 7), and the
combined organic phases were dried over Na2SO4 and concen-
trated. The crude product 6 was purified by column chromato-
graphy (neutral alumina, n-hexane/EtOAc, 4:1 or 3:1).
under the reaction conditions employed. Related aldol reac-
tions employing substituted BINOL derivatives will be re-
ported in a forthcoming paper.[32]
Experimental Section
Analytical and Spectroscopic Data of Compounds Prepared
General Remarks: All reactions were performed under argon atmo-
sphere in flame-dried flasks, and the components were added by
syringe. All solvents were dried by standard methods. IR spectra
were measured with Beckman IR Acculab 4, Beckman IR 5A,
PerkinϪElmer IR 1420 or PerkinϪElmer FT-IR spectrometer Nic-
olet 5 SXC. Mass spectra were recorded with a Varian MAT 711
spectrometer. 1H and 13C NMR spectra were recorded in CDCl3
solution on Bruker instruments (AC 500, WM 300, WH 270, AC
250). The chemical shifts are relative to TMS or to the CDCl3 sig-
nal (δH ϭ 7.27 ppm, δC ϭ 77.0 ppm). Higher order NMR spectra
were approximately interpreted as first-order spectra if possible.
Missing signals of minor isomers are hidden by signals of major
isomers, or they could not be unambiguously identified due to low
intensity. Neutral alumina (activity III, Fa. Merck) was used for
column chromatography. Melting points (uncorrected) were meas-
ured with an apparatus from Büchi (SMP-20). Optical rotations
were determined in a 1 mL cell with a path length of 10 cm on a
PerkinϪElmer 241 polarimeter (NaD line). The [α]D values are
given in 10Ϫ1 deg cm2 gϪ1 and the concentrations are given in g/
100 cm3.
n-Propyl (6S)-7-(tert-Butylsulfanylcarbonyl)-6-hydroxyheptanoate
(6a): Colourless oil, [α]2D3 ϭ ϩ14.5 (c ϭ 1.1, CHCl3) (Ͼ 97% ee).
1H NMR (CDCl3, 300 MHz): δ ϭ 4.03 (mc, 3 H, 6-H, OCH2), 2.64
(dd, J ϭ 3.4, 15.7 Hz, 1 H, 7-H), 2.56 (dd, J ϭ 8.4, 15.7 Hz, 1 H,
7-H), 2.32 (t, J ϭ 7.5 Hz, 2 H, 2-H), 1.68Ϫ1.38 (m, 9 H, 3-H, 4-
H, 5-H, CH2, OH), 1.47 (s, 9 H, SϪtBu), 0.94 (t, J ϭ 7.5 Hz, 3 H,
CH3) ppm. 13C NMR (CDCl3, 75.5 MHz): δ ϭ 200.1 (s, COS),
173.6 (s, C-1), 68.3 (d, C-6), 65.7 (t, OCH2), 50.9 (t, C-7), 48.3,
29.6 (s, q, tBu), 36.0, 34.1, 24.8, 24.6, 21.9 (5 t, C-2, C-3, C-4, C-5,
CH2), 10.3 (q, CH3) ppm. IR (neat): ν˜ ϭ 3600Ϫ3180 cmϪ1 (OϪH),
3020Ϫ2800 (CϪH), 1735, 1680 (CϭO). C15H28O4S (304.5): calcd.
C 59.18, H 9.27, S 10.53; found C 58.87, H 9.42, S 10.59.
n-Propyl (6S)-7-(tert-Butylsulfanylcarbonyl)-6-(trimethylsiloxy)hep-
tanoate (7a): Colourless oil. 1H NMR (CDCl3, 200 MHz): δ ϭ 4.11
(mc, 1 H, 6-H), 4.02 (t, J ϭ 7 Hz, 2 H, OCH2), 2.62 (dd, J ϭ 7,
14.5 Hz, 1 H, 7-H), 2.49 (dd, J ϭ 5.5, 14.5 Hz, 1 H, 7-H), 2.30 (t,
J ϭ 7 Hz, 2 H, 2-H), 1.76Ϫ1.48 (m, 8 H, 3-H, 4-H, 5-H, CH2),
1.45 (s, 9 H, SϪtBu), 0.93 (t, J ϭ 7.5 Hz, 3 H, CH3), 0.10 (s, 9 H,
OSiMe3) ppm. 13C NMR (CDCl3, 75.5 MHz): δ ϭ 200.0 (s, COS),
174.1 (s, C-1), 69.9 (d, C-6), 65.6 (t, OCH2), 52.5 (t, C-7), 48.3,
29.6 (s, q, tBu), 36.1, 33.5, 24.7, 24.6, 21.4 (5 t, C-2, C-3, C-4, C-
5, CH2), 10.3 (q, CH3), 0.05 (q, SiMe3) ppm. IR (neat): ν˜ ϭ
2950Ϫ2820 cmϪ1 (CϪH), 1745, 1735 (CϭO). MS (EI, 80 eV): m/z
(%) ϭ 376 (1) [Mϩ], 361 (2) [Mϩ Ϫ Me], 317 (5) [Mϩ Ϫ nPrO],
Starting materials 2,[33] 5a and 5b[34] 5i,[35] 5k,[36] 5l,[37] 5m,[38] 5n,[21]
5o[39] and 5p[40] were prepared by literature procedures. All other
chemicals were commercially available and were used as received.
Typical Procedure for Enantioselective Aldol Reaction with (R)-BI-
NOL-Ti Catalyst: The (R)-BINOL-Ti catalyst was prepared by a 287 (30) [Mϩ Ϫ SϪtBu], 215 (23), 186 (16), 173 (27), 155 (33), 137
3424
Eur. J. Org. Chem. 2002, 3419Ϫ3428

Enantioselective Aldol Reactions of an S-Ketene Silyl Acetal with Aliphatic Aldehydes
(59), 113 (62), 85 (11), 73 (40), 57 (tBuϩ, 100), 43 (29), 41 (33), 39 2.89 (dd, J ϭ 8.7, 15.8 Hz, 1 H, 2-H), 2.82 (dd, J ϭ 3.9, 15.8 Hz,
FULL PAPER
(19). HRMS (80 eV): calcd. for C18H36O4SSi 376.2104; found
376.2136.
1 H, 2-H), 1.47 (s, 9 H, SϪtBu) ppm.
S-tert-Butyl (3R)-3-Phenyl-3-(trimethylsiloxy)propanethioate
Methyl
(6b): Colourless oil, [α]2D3 ϭ ϩ13.7 (c ϭ 1.0, CHCl3) (96% ee). H
NMR (CDCl3, 300 MHz): δ ϭ 3.92 (mc, 1 H, 6-H), 3.56 (s, 3 H, (dd, J ϭ 9.3, 14.4 Hz, 1 H, 2-H), 2.61 (dd, J ϭ 3.8, 14.4 Hz, 1 H,
(6S)-7-(tert-Butylsulfanylcarbonyl)-6-hydroxyheptanoate (7f):[42] Colourless oil. 1H NMR (CDCl3, 300 MHz):
δ ϭ
1
7.36Ϫ7.19 (m, 5 H, Ph), 5.14 (dd, J ϭ 3.8, 9.3 Hz, 1 H, 3-H), 2.84
OMe), 2.80 (br. d, J ϭ 4 Hz, 1 H, OH), 2.53 (dd, J ϭ 3.7, 15.7 Hz,
1 H, 7-H), 2.46 (dd, J ϭ 5.4, 15.7 Hz, 1 H, 7-H), 2.24Ϫ2.17,
1.57Ϫ1.14 (2 m, 2 H, 6 H, 2-H, 3-H, 4-H, 5-H), 1.36 (s, 9 H,
SϪtBu) ppm. 13C NMR (CDCl3, 75.5 MHz): δ ϭ 200.2 (s, COS),
173.4 (s, C-1), 68.0 (d, C-6), 51.5 (q, OMe), 50.7 (t, C-7), 48.2, 29.6
(s, q, tBu), 36.3, 34.1, 24.7, 24.6 (4 t, C-2, C-3, C-4, C-5) ppm. IR
(neat): ν˜ ϭ 3550Ϫ3400 cmϪ1 (OϪH), 2980Ϫ2850 (CϪH), 1745,
1735 (CϭO). C13H24O4S (276.4): calcd. C 56.49, H 8.75, S 11.60;
found C 56.27, H 8.70, S 11.20.
2-H), 1.44 (s, 9 H, SϪtBu), 0.03 (s, 9 H, SiMe3) ppm.
S-tert-Butyl (3S)-3-Hydroxy-4-phenylbutanethioate (6g): Pale yel-
low oil, [α]2D3 ϭ ϩ15.9 (c ϭ 1.15, CHCl3) (97% ee). 1H NMR
(CDCl3, 300 MHz): δ ϭ 7.34Ϫ7.18 (m, 5 H, Ph), 4.27 (mc, 1 H, 3-
H), 2.86Ϫ2.55 (m, 5 H, 2-H, 4-H, OH), 1.46 (s, 9 H, SϪtBu) ppm.
13C NMR (CDCl3, 75.5 MHz): δ ϭ 198.8 (s, C-1), 141.7, 128.4,
128.1, 126.0 (s, 3 d, Ph), 69.7 (d, C-3), 51.6 (t, C-2), 48.0, 29.8 (s,
q, tBu), 40.5 (t, C-4) ppm. IR (neat): ν˜ ϭ 3600Ϫ3150 cmϪ1 (OϪH),
3085Ϫ2865 (ϭCH, CϪH), 1680 (CϭO). C14H20O2S (252.4): calcd.
C 66.63, H 7.99, S 12.71; found C 66.84, H 8.20, S 12.37.
Methyl (6S)-7-(tert-Butylsulfanylcarbonyl)-6-(trimethylsiloxy)hep-
tanoate (7b): Colourless oil. 1H NMR (CDCl3, 300 MHz): δ ϭ 4.10
(mc, 1 H, 6-H), 3.64 (s, 3 H, OMe), 2.50 (dd, J ϭ 5.4, 14.5 Hz, 1
H, 7-H), 2.49 (dd, J ϭ 7.2, 14.5 Hz, 1 H, 7-H), 2.30 (t, J ϭ 7.5 Hz,
2 H, 2-H), 1.65Ϫ1.15 (m, 6 H, 3-H, 4-H, 5-H), 1.44 (s, 9 H,
S-tert-Butyl (3S)-3-Hydroxy-5-phenylpentanethioate (6h):[9,43] Col-
ourless oil, [α]2D3 ϭ Ϫ4.3 (c ϭ 1.85, CHCl3) (94% ee). 1H NMR
(CDCl3, 300 MHz): δ ϭ 7.32Ϫ7.16 (m, 5 H, Ph), 4.04 (mc, 1 H, 3-
H), 2.85Ϫ2.56, 1.88Ϫ1.67 (2 m, 5 H, 2 H, 2-H, 4-H, 5-H, OH),
1.46 (s, 9 H, SϪtBu) ppm. 13C NMR (CDCl3, 62.9 MHz): δ ϭ
198.3 (s, C-1), 141.7, 128.4, 128.3, 125.8 (s, 3 d, Ph), 67.9 (d, C-3),
50.9 (t, C-2), 48.5, 29.7 (s, q, tBu), 38.0, 31.6 (2 t, C-4, C-5) ppm.
SϪtBu), 0.09 (s,
9
H, OSiMe3) ppm. 13C NMR (CDCl3,
75.5 MHz): δ ϭ 198.1 (s, COS), 173.8 (s, C-1), 69.1 (d, C-6), 52.3
(t, C-7), 51.2 (q, OMe), 48.0, 29.4 (s, q, tBu), 36.9, 33.8, 24.7, 24.6
(4 t, C-2, C-3, C-4, C-5), 0.03 (q, SiMe3) ppm. IR (neat): ν˜ ϭ
2970Ϫ2870 cmϪ1 (CϪH), 1740, 1735 (CϭO).
S-tert-Butyl (3S)-5-Phenyl-3-(trimethylsiloxy)pentanethioate (7h):
1
Colourless oil. H NMR (CDCl3, 300 MHz): δ ϭ 7.17Ϫ7.02 (m, 5
S-tert-Butyl (3S)-3-Hydroxynonanethioate (6c): Colourless oil,
[α]2D3 ϭ ϩ20.8 (c ϭ 1.15, CHCl3) (93% ee). 1H NMR (CDCl3,
300 MHz): δ ϭ 4.01 (mc, 1 H, 3-H), 2.77 (br. s, 1 H, OH), 2.66
(dd, J ϭ 3.3, 15.8 Hz, 1 H, 2-H), 2.55 (dd, J ϭ 8.5, 15.8 Hz, 1 H,
2-H), 1.68Ϫ1.24 (m, 10 H, 4-H to 8-H), 1.47 (s, 9 H, SϪtBu), 0.88
(t, J ϭ 7 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3, 62.9 MHz): δ ϭ
200.6 (s, C-1), 68.7 (d, C-3), 50.9 (t, C-2), 48.4, 29.7 (s, q, tBu),
36.5, 31.7, 29.1, 25.3, 22.6 (5 t, C-4, C-5, C-6, C-7, C-8), 14.0 (q,
C-9) ppm. IR (neat): ν˜ ϭ 3650Ϫ3180 cmϪ1 (OϪH), 2960Ϫ2860
(CϪH), 1680 (CϭO). C13H25O2S (245.4): calcd. C 63.63, H 10.27,
S 13.06; found C 63.28, H 10.01, S 13.80.
H, Ph), 4.07 (mc, 1 H, 3-H), 2.63Ϫ2.41, 1.79Ϫ1.52 (2 m, 4 H, 2 H,
2-H, 4-H, 5-H), 1.33 (s, 9 H, SϪtBu), 0.01 (s, 9 H, OSiMe3) ppm.
13C NMR (CDCl3, 75.5 MHz): δ ϭ 198.2 (s, C-1), 141.9, 128.4,
128.3, 125.8 (s, 3 d, Ph), 69.1 (d, C-3), 52.3 (t, C-2), 48.1, 29.8 (s,
q, tBu), 39.2, 31.7 (2 t, C-4, C-5), 0.3 (q, OSiMe3) ppm. IR (neat):
ν˜ ϭ 3090Ϫ2870 cmϪ1 (ϭCH, CϪH), 1685 (CϭO). C18H30O2SSi
(338.6): calcd. C 63.85, H 8.93, S 9.47; found C 63.49, H 9.17,
S 9.25.
S-tert-Butyl
(3S)-8-[tert-Butyl(dimethyl)siloxy]-3-hydroxyoctane-
thioate (6i): Pale yellow oil, [α]2D3 ϭ ϩ11.9 (c ϭ 1.2, CHCl3) (95%
ee). 1H NMR (CDCl3, 300 MHz): δ ϭ 4.02 (mc, 1 H, 3-H), 3.59 (t,
J ϭ 6.5 Hz, 2 H, 8-H), 2.77 (d, J ϭ 4 Hz, 1 H, OH), 2.68 (dd, J ϭ
3.3, 15.6 Hz, 1 H, 2-H), 2.52 (dd, J ϭ 8.5, 15.6 Hz, 1 H, 2-H),
1.63Ϫ1.25 (m, 8 H, 4-H, 5-H, 6-H, 7-H), 1.47 (s, 9 H, SϪtBu), 0.89
(s, 9 H, SiϪtBu), 0.04 (s, 6 H, SiMe2) ppm. 13C NMR (CDCl3,
75.5 MHz): δ ϭ 199.6 (s, C-1), 68.6 (d, C-3), 63.1 (t, C-8), 50.9 (t,
C-2), 48.4, 29.7 (s, q, tBu), 36.5, 32.7, 25.7, 25.2 (4 t, C-4, C-5, C-
6, C-7), 25.9, 18.3 (s, q, SiϪtBu), Ϫ3.6 (q, SiMe2) ppm. IR (neat):
ν˜ ϭ 3600Ϫ3200 cmϪ1 (OϪH), 2995Ϫ2850 (CϪH), 1680 (CϭO).
MS (EI, 80 eV): m/z (%) ϭ 347 (1) [Mϩ], 305 (17) [Mϩ Ϫ tBu], 249
(14), 231 (17), 215 (26), 197 (22), 173 (55), 171 (42), 131
S-tert-Butyl (3R)-3-Hydroxy-4-methylpentanethioate (6d):[41] Col-
ourless oil that slowly crystallised during storage (mp, 34Ϫ37 °C),
[α]2D3 ϭ ϩ12.4 (c ϭ 1.24, CHCl3) (38% ee). 1H NMR (CDCl3,
300 MHz): δ ϭ 3.80 (mc, 1 H, 3-H), 2.74 (br. s, 1 H, OH), 2.64
(dd, J ϭ 3, 15.5 Hz, 1 H, 2-H), 2.53 (dd, J ϭ 9, 15.5 Hz, 1 H, 2-
H), 1.74Ϫ1.64 (m, 1 H, 4-H), 1.47 (s, 9 H, SϪtBu), 0.93, 091 (2 d,
J ϭ 6.8 Hz, 3 H each, 5-H, 4-CH3) ppm. 13C NMR (CDCl3,
62.9 MHz): δ ϭ 198.0 (s, C-1), 73.3 (d, C-3), 48.3, 29.7 (s, q, tBu),
48.1 (t, C-2), 33.2 (d, C-4), 18.3, 17.5 (2 q, C-5, 4-CH3) ppm.
S-tert-Butyl (3S)-3-Hydroxy-5-methylhexanethioate (6e): Colourless
oil, [α]2D3 ϭ ϩ8.2 (c ϭ 0.92, CHCl3) (53% ee). 1H NMR (CDCl3, (OSiϪtBuMe2ϩ, 24), 123 (26), 115 (11) [SiϪtBuMe2ϩ], 99 (26), 95
300 MHz): δ ϭ 4.10 (mc, 1 H, 3-H), 2.75 (br. s, 1 H, OH), 2.64 (31), 81 (33), 75 (83), 57 (100) [tBuϩ], 41 (23), 29 (13). C18H38O3SSi
(dd, J ϭ 3.3, 15.8 Hz, 1 H, 2-H), 2.54 (dd, J ϭ 8.3, 15.8 Hz, 1 H, (362.6): calcd. C 59.62, H 10.56, S 8.85; found C 59.85, H 10.91,
2-H), 1.84Ϫ1.60, 1.46Ϫ1.12 (2 m, 1 H, 2 H, 4-H, 5-H), 1.47 (s, 9
H, SϪtBu), 0.91 (t, J ϭ 6.5 Hz, 6 H, 6-H, 5-CH3) ppm. 13C NMR
(CDCl3, 75.5 MHz): δ ϭ 198.5 (s, C-1), 67.0 (d, C-3), 51.4 (t, C-
2), 48.5, 29.8 (s, q, tBu), 45.7 (t, C-4), 24.5 (d, C-5), 23.2, 22.0
(2 q, C-6, 5-CH3) ppm. IR (neat): ν˜ ϭ 3650Ϫ3100 cmϪ1 (OϪH),
2995Ϫ2870 (CϪH), 1680 (CϭO). C11H23O2S (218.4): calcd. C
60.50, H 10.15, S 14.69; found C 60.70, H 10.58, S 15.12.
S 8.87.
S-tert-Butyl (3S)-3,8-Dihydroxyoctanethioate (9): Colourless oil,
[α]2D3 ϭ ϩ17.5 (c ϭ 0.04, CHCl3). 1H NMR (CDCl3, 300 MHz):
δ ϭ 4.03 (mc, 1 H, 3-H), 3.62 (t, J ϭ 6.5 Hz, 2 H, 8-H), 2.63 (dd,
J ϭ 3.6, 15.6 Hz, 1 H, 2-H), 2.55 (dd, J ϭ 8.2, 15.6 Hz, 1 H, 2-H),
1.62Ϫ1.36 (m, 10 H, 4-H, 5-H, 6-H, 7-H, OH), 1.47 (s, 9 H, SϪtBu)
ppm. 13C NMR (CDCl3, 62.9 MHz): δ ϭ 200.4 (s, C-1), 68.5 (d,
C-3), 62.6 (t, C-8), 51.0 (t, C-2), 48.4, 29.7 (s, q, tBu), 36.4, 32.5,
S-tert-Butyl (3R)-3-Hydroxy-3-phenylpropanethioate (6f):[41] Col-
ourless solid, m.p. 41Ϫ43 °C, [α]2D3 ϭ ϩ35.3 (c ϭ 1.23, CHCl3) 25.5, 25.1 (4 t, C-4, C-5, C-6, C-7) ppm. IR (neat): ν˜ ϭ 3600Ϫ3100
(96% ee). 1H NMR (CDCl3, 300 MHz): δ ϭ 7.37Ϫ7.26 (m, 5 H,
cmϪ1 (OϪH), 3070Ϫ2890 (CϪH), 1690 (CϭO). C12H24O3S
Ph), 5.15 (dd, J ϭ 3.9, 8.7 Hz, 1 H, 3-H), 3.18 (br. s, 1 H, OH), (248.4): calcd. C 58.02, H 9.74; found C 57.69, H 9.37.
Eur. J. Org. Chem. 2002, 3419Ϫ3428
3425

R. Zimmer, A. Peritz, R. Czerwonka, L. Schefzig, H.-U. Reißig
Ethyl (3R)-3-(tert-Butylsulfanylcarbonyl)-2-hydroxypropanoate (6j): 300 MHz): δ ϭ 4.66Ϫ4.55 (m, 1 H, 3-H), 4.12Ϫ3.95, 3.10Ϫ2.95 (2
FULL PAPER
Pale yellow oil (b.p., 100 °C/0.01 mbar), [α]2D3 ϭ ϩ14.9 (c ϭ 1.1,
m, 1 H each, 6-H, OH), 2.68Ϫ2.52 (m, 2 H, 2-H), 2.20Ϫ1.58 (m,
CHCl3) (71% ee). 1H NMR (CDCl3, 300 MHz): δ ϭ 4.46 (mc, 1 4 H, 4-H, 5-H), 1.54 (d, J ϭ 6.7 Hz, 3 H, 7-H), 1.47 (s, 9 H, SϪtBu)
H, 2-H), 4.31Ϫ4.21 (m, 2 H, OCH2), 3.15 (br. s, 1 H, OH), 2.97 ppm. 13C NMR (CDCl3, 75.5 MHz): δ ϭ 200.5 (s, C-1), 83.6, 82.9*
(dd, J ϭ 4.4, 15.9 Hz, 1 H, 3-H), 2.89 (dd, J ϭ 6.3, 15.9 Hz, 1 H, (2 d, C-6), 68.1, 67.4* (2 d, C-3), 48.7, 30.0 (s, q, tBu), 50.6,
3-H), 1.46 (s, 9 H, SϪtBu), 1.19 (t, J ϭ 7 Hz, 3 H, CH3) ppm. 13C
50.5*, 32.5, 31.9*, 31.4, 30.7* (6 t, C-2, C-4, C-5), 19.5, 19.2* (2 q,
NMR (CDCl3, 62.9 MHz): δ ϭ 197.0 (s, COS), 173.3 (s, C-1), 67.4 CH3) ppm; * signals of the minor isomer. IR (neat): ν˜
ϭ
(d, C-2), 61.9, 14.0 (t, q, OCH2CH3), 48.6 (t, C-3), 48.6, 29.6 (s, q,
3430Ϫ3500 cmϪ1 (OϪH), 2995Ϫ2920 (CϪH), 1720 (CϭO), 1675
tBu) ppm. IR (neat): ν˜ ϭ 3650Ϫ3100 cmϪ1 (OϪH), 3000Ϫ2870 (NO2). C11H21NO4S (263.4): calcd. C 50.17, H 8.04, N 5.32; found
(CϪH), 1740, 1685 (CϭO). MS (EI, 80 eV): m/z (%) ϭ 234 (5) C 50.38, H 8.17, N 5.51.
[Mϩ], 161 (4) [Mϩ Ϫ CO2Et], 145 (43) [Mϩ Ϫ SϪtBu], 117 (37),
5-[(tert-Butylsulfanylcarbonyl)methyl]-4,5-dihydro-4-methyl-2(3H)-
89 (17) [SϪtBuϩ], 71 (35), 57 (100) [tBuϩ], 41 (19), 29 (30). HRMS
(80 eV): calcd. for C10H18O4S 234.0926; found 234.0943.
1
furanone (10): Colourless oil, cis-10:trans-10 ϭ 55:45. H NMR
(CDCl3, 300 MHz): δ ϭ 5.03 (td, J ϭ 6, 7.5 Hz, 0.55 H, cis-5-H),
4.57 (td, J ϭ 5.5, 7 Hz, 0.45 H, trans-5-H), 3.05Ϫ2.75, 2.46Ϫ2.27
(2 m, 4 H, 1 H, 3-H, 4-H, 5-CH2), 1.58 (s, 9 H, SϪtBu), 1.26 (d,
J ϭ 6.5 Hz, 1.65 H, cis-4-CH3), 1.12 (d, J ϭ 7.2 Hz, 1.35 H, trans-
4-CH3) ppm. 13C NMR (CDCl3, 75.5 MHz): Major diastereomer:
δ ϭ 196.2 (s, COSϪtBu), 175.9 (s, CϭO), 78.8 (d, C-5), 48.7, 29.7
(s, q, tBu), 48.0, 37.0 (2 t, 2 CH2), 32.7 (d, C-4), 14.2 (q, 4-CH3)
ppm. Minor diastereomer: δ ϭ 196.0 (s, COSϪtBu), 175.6 (s,
CϭO), 82.4 (d, C-5), 48.8, 29.6 (s, q, tBu), 44.3, 36.5 (2 t, 2 CH2),
35.7 (d, C-4), 17.3 (q, 4-CH3) ppm. IR (neat): ν˜ ϭ 2990Ϫ2850 cmϪ1
(CϪH), 1780, 1720 (CϭO). C11H18O3S (230.3): calcd. C 57.36, H
7.88; found C 56.98, H 8.27.
Ethyl
(3R)-3-(tert-Butylsulfanylcarbonyl)-2-(trimethylsiloxy)pro-
panoate (7j): Pale yellow oil. 1H NMR (CDCl3, 300 MHz): δ ϭ
4.64 (dd, J ϭ 4.4, 8.4 Hz, 1 H, 2-H), 4.23Ϫ4.10 (m, 2 H, OCH2),
2.67 (dd, J ϭ 4.4, 15.1 Hz, 1 H, 3-H), 2.82 (dd, J ϭ 8.4, 15.1 Hz,
1 H, 3-H), 1.46 (s, 9 H, SϪtBu), 1.27 (t, J ϭ 7 Hz, 3 H, CH3), 0.13
(s, 9 H, SiMe3) ppm.
S-tert-Butyl (3S)-3-Hydroxy-4-(2-methyl-1,3-dioxolan-2-yl)butane-
thioate (6k): Yellow oil, [α]2D3 ϭ Ϫ3.8 (c ϭ 1.28, CHCl3) (62% ee).
1H NMR (CDCl3, 300 MHz): δ ϭ 4.36 (mc, 1 H, 3-H), 4.04Ϫ3.98
(m, 4 H, OCH2CH2O), 2.73 (br. s, 1 H, OH), 2.69 (dd, J ϭ 7.7,
14.9 Hz, 1 H, 2-H), 2.56 (dd, J ϭ 5.1, 14.9 Hz, 1 H, 2-H),
1.96Ϫ1.85 (m, 2 H, 4-H), 1.52 (s, 3 H, Me), 1.47 (s, 9 H, SϪtBu)
ppm. 13C NMR (CDCl3, 62.9 MHz): δ ϭ 199.1 (s, C-1), 107.5 (s,
OϪCϪO), 65.4 (d, C-3), 64.8, 63.7 (2 t, 2 OCH2), 50.1, 49.0 (2 t,
C-2, C-4), 48.6, 29.8 (s, q, tBu), 24.2 (q, CH3) ppm. IR (neat): ν˜ ϭ
3600Ϫ3050 cmϪ1 (OϪH), 2950Ϫ2860 (CϪH), 1680 (CϭO). MS
(EI, 80 eV): m/z (%) ϭ 247 (1) [Mϩ Ϫ CH3], 229 (1) [Mϩ Ϫ CH3
Ϫ H2O], 175 (3) [Mϩ Ϫ C4H7O2], 173 (5) [Mϩ Ϫ SϪtBu], 131
(22), 129 (37), 115 (16), 111 (44), 87 (95), 57 (48) [tBuϩ], 43 (100)
[CH3COϩ], 41 (16), 29 (11). HRMS (80 eV): calcd. for C11H19O4S
(Mϩ Ϫ CH3) 247.1004; found 247.1033.
n-Propyl 7-(tert-Butylsulfanylcarbonyl)hept-6-enoate (11): Pale yel-
low oil. 1H NMR (CDCl3, 300 MHz): δ ϭ 6.94 (td, J ϭ 7, 15.5 Hz,
1 H, 6-H), 6.16 (td, J ϭ 1.5, 15.5 Hz, 1 H, 7-H), 4.18 (t, J ϭ 6.8 Hz,
2 H, OCH2), 2.46 (t, J ϭ 7.2 Hz, 2 H, 2-H), 2.33 (dq, J ϭ 1.5,
7 Hz, 2 H, 5-H), 1.85Ϫ1.68 (m, 6 H, 3-H, 4-H, CH2), 1.64 (s, 9 H,
SϪtBu), 1.09 (t, J ϭ 7.4 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3,
62.9 MHz): δ ϭ 192.5 (s, COS), 173.4 (s, C-1), 143.3, 129.6 (2 d,
C-6, C-7), 65.9 (t, OCH2), 48.2, 29.9 (s, q, SϪtBu), 34.0, 31.8, 27.5,
24.4, 21.9 (5 t, C-2, C-3, C-4, C-5, CH2), 10.3 (q, CH3) ppm. IR
(neat): ν˜ ϭ 3050Ϫ2800 cmϪ1 (ϭCH, CϪH), 1735, 1660 (CϭO).
MS (EI, 80 eV): m/z (%) ϭ 286 (3) [Mϩ], 197 (11) [Mϩ Ϫ SϪtBu],
171 (10), 170 (17), 137 (15), 127 (16), 110 (17), 81 (10), 57 (100)
[tBuϩ], 41 (21), 29 (10). HRMS (80 eV): calcd. for C15H26O3S
286.1603; found 286.1635.
S-tert-Butyl (3R)-3-Hydroxy-3-(2-styryloxazol-4-yl)propanethioate
(6l):[44] Colourless crystals, m.p. 105Ϫ107 °C, [α]2D3 ϭ ϩ38.1 (c ϭ
1.1, C6H6) (95% ee). 1H NMR (CDCl3, 250 MHz): δ ϭ 7.55 (d,
J ϭ 1 Hz, 1 H, ϭCH), 7.55Ϫ7.30 (m, 6 H, ϭCH, Ph), 6.90 (d, J ϭ
16.5 Hz, 1 H, ϭCH), 5.20 (dddd, J ϭ 1, 4, 5, 8.5 Hz, 1 H, 3-H),
3.55 (d, J ϭ 5 Hz, 1 H, OH), 3.05 (dd, J ϭ 4, 16 Hz, 1 H, 2-H),
2.95 (d, J ϭ 8.5, 16 Hz, 1 H, 2-H), 1.46 (s, 9 H, SϪtBu) ppm. 13C
NMR (CDCl3, 75.5 MHz): δ ϭ 199.2 (s, C-1), 161.6, 153.5 (2 s,
ϭCN, CϭCH), 136.5, 135.3, 134.2, 129.1, 128.8, 127.2 (d, s, 4 d, 2
ϭCH, Ph), 113.6 (d, ϭCH), 64.3 (d, C-3), 50.0 (t, C-2), 48.5, 29.7
(s, q, tBu) ppm. MS (EI, 80 eV): m/z (%) ϭ 331 (22) [Mϩ], 274 (13)
2,4,6-Tris(4-n-propoxycarbonylbutyl)-1,3,5-trioxane (12): Colourless
oil. 1H NMR (CDCl3, 300 MHz): δ ϭ 4.84 (t, J ϭ 5.2 Hz, 3 H,
OCHO), 4.03 (t, J ϭ 7.3 Hz, 6 H, OCH2), 2.31 (t, J ϭ 7.4 Hz, 6
H, CH2CϭO), 1.71Ϫ1.59, 1.49Ϫ1.39 (2 m, 18 H, 6 H, CH2), 0.94
(t, J ϭ 7.3 Hz, 9 H, CH3) ppm. 13C NMR (CDCl3, 75.5 MHz):
δ ϭ 173.6 (s, CϭO), 101.2 (d, OCH), 65.8 (t, OCH2), 34.1, 33.9,
24.7, 23.0, 21.9 (5 t, CH2), 10.3 (q, CH3) ppm. IR (neat): ν˜ ϭ
2920Ϫ2810 cmϪ1 (CϪH), 1730 (CϭO). MS (FD, 70 eV): m/z (%) ϭ
517 (4) [Mϩ], 406 (38) [Mϩ Ϫ 2 OϪnPr], 189 (62), 145 (79), 144
(75), 42 (100). C27H48O9 (516.7): calcd. C 62.77, H 9.36; found C
62.91, H 9.43.
[Mϩ Ϫ tBu], 242 (47) [Mϩ Ϫ SϪtBu], 224 (27), 214 (48) [Mϩ
Ϫ
COSϪtBu], 200 (100) [Mϩ Ϫ CH2COSϪtBu], 198 (30), 147 (11),
146 (11), 131 (24) [CH2COSϪtBuϩ], 130 (15), 115 (25), 103 (21),
77 (14), 57 (53) [tBuϩ], 41 (19), 29 (16).
S-tert-Butyl
(3R)-3-(2-Styryloxazol-4-yl)-3-(trimethylsiloxy)pro-
n-Propyl (6S)-6,8-Dihydroxyoctanoate (8): Sodium borohydride
(0.085 g, 2.24 mmol) was added in portions at 0 °C to a solution
of 6a (0.173 g, 0.569 mmol; Ͼ 97% ee) in 1-propanol (5 mL). After
5 h at 0 °C the solution was allowed to warm up to room temp.
overnight. The solution was then concentrated in vacuo and the
residue was dissolved in ethyl acetate (20 mL). The organic phase
was washed with sat. aqueous NH4Cl solution (5 mL), the aqueous
layer was extracted with ethyl acetate (3 ϫ 5 mL), and the com-
bined organic phases were dried over Na2SO4. Purification of the
crude product by column chromatography (EtOAc/n-hexane ϭ 1:1
to 1:0) afforded the 1,3-diol 8 (0.075 g, 61%) as a slightly yellow
panethioate (7l): Pale yellow crystals, m.p. 77Ϫ79 °C. 1H NMR
(CDCl3, 250 MHz): δ ϭ 7.55Ϫ7.30 (m, 7 H, 2 ϭCH, Ph), 6.89 (d,
J ϭ 16 Hz, 1 H, ϭCH), 5.24 (dd, J ϭ 4.5, 8 Hz, 1 H, 3-H), 2.94
(dd, J ϭ 4.5, 16 Hz, 1 H, 2-H), 2.88 (dd, J ϭ 8, 16 Hz, 1 H, 2-H),
1.45 (s, 9 H, SϪtBu), 0.21 (s, 9 H, SiMe3) ppm. 13C NMR (CDCl3,
62.9 MHz): δ ϭ 197.3 (s, C-1), 161.5, 145.1 (2 s, ϭCN, CϭCH),
136.2, 135.5, 134.3, 129.2, 128.9, 127.2 (d, s, 4 d, ϭCH, Ph), 113.9
(d, ϭCH), 65.5 (d, C-3), 52.1 (t, C-2), 48.1, 29.8 (s, q, tBu), 0.1
(q, SiMe3).
S-tert-Butyl 3-Hydroxy-6-nitroheptanethioate (6m): Pale yellow oil,
mixture of two diastereomers
1
ϭ
64:36. 1H NMR (CDCl3,
oil. [α]2D5 ϭ Ϫ2.5 (c ϭ 0.9, CHCl3). H NMR (CDCl3, 300 MHz):
3426
Eur. J. Org. Chem. 2002, 3419Ϫ3428

Enantioselective Aldol Reactions of an S-Ketene Silyl Acetal with Aliphatic Aldehydes
FULL PAPER
istry, 4th ed. Thieme Verlag: Stuttgart, 1995, Vol. E 21/b,
¸
δ ϭ 4.00 (t, J ϭ 6.8 Hz, 2 H, OCH2), 3.94Ϫ3.59 (m, 3 H, 6-H, 8-
H), 2.85 (br. s, 2 H, OH), 2.30 (t, J ϭ 7.3 Hz, 2 H, 2-H), 1.70Ϫ1.25
(m, 10 H, 3-H, 4-H, 5-H, 7-H, CH2), 0.91 (t, J ϭ 7.5 Hz, 3 H,
CH3) ppm. 13C NMR (CDCl3, 75.5 MHz): δ ϭ 173.8 (s, C-1), 71.7
(d, C-6), 65.9 (t, OCH2), 61.6 (t, C-8), 38.3, 37.3, 34.2, 25.0, 24.8,
22.0 (6 t, C-2, C-3, C-4, C-5, C-7, CH2), 10.3 (q, CH3) ppm. IR
(neat): ν˜ ϭ 3620Ϫ3150 cmϪ1 (OϪH), 3040Ϫ2840 (CϪH), 1730
(CϭO). C11H22O4 (218.3): calcd. C 60.52, H 10.16; found C 59.99,
H 10.03. Because of the sensitivity of this compound, no better
elemental analysis could be obtained.
p. 1603Ϫ1666.
[7]
[7a]
Reviews:
Y. Yamamoto, N. Asao, Chem. Rev. 1993, 93,
[7b]
2207Ϫ2293.
T. Bach, Angew. Chem. 1994, 106, 433Ϫ435;
[7c]
Angew. Chem. Int. Ed. Engl. 1994, 33, 417.
A. Hoveyda, P.
Morken, Angew. Chem. 1996, 108, 1378Ϫ1401; Angew. Chem.
[7d]
Int. Ed. Engl. 1996, 35, 1262.
P. G. Cozzi, E. Tagliavini, A.
[7e]
Umani-Ronchi, Gazz. Chim. Ital. 1997, 127, 247Ϫ254.
R.
Zimmer, J. Suhrbier, J. Prakt. Chem. 1997, 339, 758Ϫ762.
[8] [8a]
M. Sodeoka, R. Tokunoh, F. Miyazaki, E. Hagiwara, M.
[8b]
Shibasaki, Synlett 1997, 463Ϫ466.
ibe, Chem. Eur. J. 1997, 3, 1472Ϫ1481.
Furuta, T. Hayashi, M. Hishijima, K. Hanada, J. Am. Chem.
Soc. 1998, 120, 908Ϫ919.
J. A. Murry, C. S. Burgey, K. R. Campos, B. T. Connell, R. J.
Staples, J. Am. Chem. Soc. 1999, 121, 669Ϫ685.
S. Kobayashi, M. Hor-
[8c]
S. Kobayashi, T.
General Procedure for the Transformation of Alcohols 6 into the
Corresponding Mosher’s Esters by Treatment with Mosher’s Acyl
Chloride: (S)-Mosher’s acyl chloride (1.4 equiv.) was added to a
solution of the corresponding alcohol 6 (1.0 equiv.) in CH2Cl2 and
dry pyridine (each 5.5 mL/mmol of 6) and the reaction mixture was
stirred for 40 h at room temp. The mixture was then diluted with
CH2Cl2 (50 mL/mmol of 6) and washed successively with 2  HCl
solution, satd. aqueous NaHCO3 solution and H2O (each 15 mL/
mmol of 6). The organic layer was dried (Na2SO4) and the solvent
was evaporated to afford the crude product, which was pure by
TLC analysis. The de value of the resulting ester was determined
[8d]
D. A. Evans, M. C. Kozlowski,
[8e]
D. A. Ev-
ans, C. S. Burgey, M. C. Kozlowski, S. W. Tregay, J. Am. Chem.
Soc. 1999, 121, 686Ϫ699. [8f] Y. Yamashita, H. Ishitani, H. Shi-
mizu, S. Kobayashi, J. Am. Chem. Soc. 2002, 124, 3292Ϫ3302.
[9] [9a]
G. E. Keck, D. Krishnamurthy, J. Am. Chem. Soc. 1995,
[9b]
117, 2363Ϫ2364.
G. E. Keck, D. Krishnamurthy, M. C.
Grier, J. Org. Chem. 1993, 58, 6543Ϫ6544.
[10] [10a]
K. Mikami, S. Matsukawa, J. Am. Chem. Soc. 1994, 116,
[10b]
4077Ϫ4078.
S. Matsukawa, K. Mikami, Tetrahedron:
1
by H and 13C NMR.
[10c]
Asymmetry 1995, 6, 2571Ϫ2574.
K. Mikami, S. Matsu-
kawa, E. Sawa, A. Harada, N. Koga, Tetrahedron Lett. 1997,
38, 1951Ϫ1954. [10d] H. Matsunaga, Y. Yamada, T. Ide, T. Ishi-
zuka, T. Kunieda, Tetrahedron: Asymmetry 1999, 10,
3095Ϫ3098.
Acknowledgments
[11] [11a]
K. Mikami, T. Takasaki, S. Matsukawa, M. Maruta, Syn-
lett 1995, 1057Ϫ1058. [11b] K. Mikami, T. Yajima, T. Takasaki,
S. Matsukawa, M. Terada, T. Uchimaru, M. Maruta, Tetrahed-
ron 1996, 52, 85Ϫ98.
We are most grateful for generous support of this work by the Arz-
neimittelwerk Dresden (BMBF grant No. FKZ: 03D00497). We
thank the Fonds der Chemischen Industrie for general support,
Hannes Helmboldt (Technische Universität Dresden) for his ex-
perimental help and Prof. K. Krohn (Universität Paderborn) for
the donation of dialdehyde 5q.
[12]
It should be mentioned that the actual structure of (R)-BI-
NOL-MetXn (e.g., 4a) is more complicated than described by
a simple 1:1-stoichiometric version. However, on mixing the
components the structure of the catalyst depends on a variety
of factors (e.g., stoichiometry of the reaction partners, temper-
[1] [1a]
[1b]
L. J. Reed, Acc. Chem. Res. 1974, 7, 40Ϫ46.
H. Sigel,
ature, additives and solvent play a crucial role). See for ex-
Angew. Chem. 1982, 94, 421Ϫ432; Angew. Chem. Int. Ed. Engl.
[12a]
ample:
M. Mori, T. Nakai, Tetrahedron Lett. 1997, 38,
1982, 21, 389. [1c] C. V. Natraj, V. M. Gandhi, K. K. G. Menon,
[12b]
6233Ϫ6236.
M. Terada, Y. Matsumoto, Y. Nakamura, K.
[1d]
J. Biosci. 1984, 6, 37Ϫ46.
A. Kleemann, H. O. Borbe, H.
[12c]
Mikami, Inorg. Chim. Acta 1999, 296, 267Ϫ272.
Charrette, A. Gagnon, Tetrahedron: Asymmetry 1999, 10,
1961Ϫ1968.
67, 2831Ϫ2836.
A. B.
Ulrich, in Thioctsäure, H. O. Borbe, H. Ulrich, Eds., PMI-Ver-
lag, Frankfurt a. M., 1989, p. 11. [1e]L. Packer, E. H. Witt, H.
J. Tritschler, Free Rad. Biol. Med. 1995, 19, 227Ϫ250.
[12d]
X. Feng, L. Shu, Y. Shi, J. Org. Chem. 2002,
[2] [2a]
A. S. Gopalan, H. K. Jacobs, J. Chem. Soc., Perkin Trans.
[13]
[14]
[2b]
The generation of the catalyst was performed according to
method D as described in ref.[9] with 2 equiv. of (R)-BINOL 4
and 1 equiv. of Ti(OiPr)4. Methods A to C as reported in ref.[9]
were also examined in this study; we obtained results very sim-
ilar to those with method D (e.g., yield of 6a: 58%, ee Ͼ 97%).
Ene reactions: with molecular sieves: [14a] M. Terada, Y. Matsu-
1 1990, 1897Ϫ1900.
1994, 50, 4137Ϫ4148.
McCague, S. Pedragosa-Moreau, S. M. Roberts, R. Villa, P. W.
D. Basavaiah, S. B. Raju, Tetrahedron
[2c]
B. Adger, M. T. Bes, G. Grogan, R.
H. Wan, A. J. Willetts, J. Chem. Soc., Chem. Commun. 1995,
[2d]
1563Ϫ1564.
K. Matsumoto, M. Shimojo, H. Kitajima, M.
Hatanaka, Synlett 1996, 1085Ϫ1086. [2e] Y. R. Santosh Laxmi,
D. S. Iyengar, Synthesis 1996, 594Ϫ596.
Bes, G. Grogan, R. McCague, S. Pedragosa-Moreau, S. M. Ro-
[2f]
moto, Y. Nakamura, K. Mikami, Chem. Commun. 1997,
B. Adger, M. T.
[14b]
281Ϫ282. See also ref.[10c]. Biphenols:
M. Chavarot, J. J.
´
Byrne, P. Y. Chavant, J. Pardillos-Guindet, Y. Vallee, Tetrahed-
ron: Asymmetry 1998, 9, 3889Ϫ3894. Chiral activators:
berts, R. Villa, P. W. H. Wan, A. J. Willetts, Bioorg. Chem. Lett.
[14c]
[2g]
K.
1997, 5, 253Ϫ261.
N. W. Fadnavis, R. L. Babu, S. K. Vadi-
Mikami, S. Matsukawa, T. Volk, M. Terada, Angew. Chem.
1997, 109, 2936Ϫ2939; Angew. Chem. Int. Ed. Engl. 1997, 36,
2768.
vel, A. A. Deshpande, U. T. Bhalerao, Tetrahedron: Asymmetry
1998, 9, 4109Ϫ4112.
C. Crevisy, B. Herbage, M.-L. Marrel, L. Toupet, R. Gree, Eur.
J. Org. Chem. 1998, 1949Ϫ1954.
T. T. Upadhya, M. D. Nikalje, A. Sudalai, Tetrahedron Lett.
2001, 42, 4891Ϫ4893.
R. Zimmer, U. Hain, M. Berndt, R. Gewald, H.-U. Reißig,
[3]
[4]
[5]
[6]
´
´
DielsϪAlder reactions: [15a] K. Mikami, Y. Motoyama, M. Ter-
[15]
[16]
ada, J. Am. Chem. Soc. 1994, 116, 2812Ϫ2820. With chiral ac-
[15b]
tivators:
S. Matsukawa, K. Mikami, Tetrahedron: Asym-
metry 1997, 8, 815Ϫ816.
[16a]
Tetrahedron: Asymmetry 2000, 11, 879Ϫ887.
Allylation reactions:
C.-M. Yu, H.-S. Choi, W.-H. Jung,
[6a]
Reviews:
S. G. Nelson, Tetrahedron: Asymmetry 1998, 9,
H.-J. Kim, J. Shin, Chem. Commun. 1997, 761Ϫ762. [16b] S. Kii,
[16c]
357Ϫ389. [6b] P. Arya, H. Qin, Tetrahedron 2000, 56, 917Ϫ947.
T. D. Machajewski, C.-H. Wong, Angew. Chem. 2000, 112,
1407Ϫ1430; Angew. Chem. Int. Ed. 2000, 39, 1352.
K. Maruoka, Tetrahedron Lett. 2001, 42, 1935Ϫ1939.
H.
[6c]
Hanawa, S. Kii, K. Maruoka, Adv. Synth. Catal. 2001, 343,
[6d]
[16d]
C. Pal-
57Ϫ60. Alkylation reactions:
F.-Y. Zhang, C.-W. Yip, R.
omo, M. Oiarbide, J. M. Garcia, Chem. Eur. J. 2002, 8, 36Ϫ44.
For the ‘‘auxiliary-based’’ concept, see: [6e] Braun, M. Stereose-
lective Synthesis In Houben-Weyl, Methods of Organic Chem-
Cao, A. S. C. Chan, Tetrahedron: Asymmetry 1997, 8,
[16e]
585Ϫ589. Prop-2-ynylation reactions:
C.-M. Yu, S.-K.
Yoon, K. Baek, Chem. Commun. 1997, 763Ϫ764.
Eur. J. Org. Chem. 2002, 3419Ϫ3428
3427

R. Zimmer, A. Peritz, R. Czerwonka, L. Schefzig, H.-U. Reißig
FULL PAPER
[17]
[30]
Mukaiyama reactions: with phenols: see ref.[10b]. With molecu-
K. Ishihara, M. Miyata, K. Hattori, T. Tada, H. Yamamoto,
J. Am. Chem. Soc. 1994, 116, 10520Ϫ10524.
R. Lock, H. Waldmann, Chem. Eur. J. 1997, 3, 143Ϫ151.
R. Zimmer, A. Peritz, R. Czerwonka, H.-U. Reißig, manuscript
in preparation.
lar sieves: see ref.[10c]. With alcohols: [17a] H. Ishitani, Y. Yama-
shita, H. Shimizu, S. Kobayashi, J. Am. Chem. Soc. 2000, 122,
5403Ϫ5404. With chiral activators:
[31]
[32]
[17b]
A. Ishii, J. Kojima, K.
Mikami, Org. Lett. 1999, 1, 2013Ϫ2016.
[18]
[33]
[34]
[35]
Strecker synthesis: J. J. Byrne, M. Chavarot, P.-Y. Chavant, Y.
H. Gerlach, P. Künzler, Helv. Chim. Acta 1978, 61, 2503Ϫ2509.
´
Vallee, Tetrahedron Lett. 2000, 41, 873Ϫ876.
S. L. Schreiber, R. E. Claus, Org. Synth. 1986, 64, 150Ϫ156.
[35a]
[19] [19a] T. Mukaiyama, A. Inubushi, S. Suda, R. Hara, S. Kobaya-
shi, Chem. Lett. 1990, 1015Ϫ1018. [19b] S. Orlandi, A. Mandoli,
D. Pini, P. Salvatori, Angew. Chem. 2001, 113, 2587Ϫ2589; An-
gew. Chem. Int. Ed. 2001, 40, 2519.
From ε-caprolactone:
T. Murata, T. Kumagai, M. Ishi-
kawa, K.-i. Tadano, S. Ogawa, Bull. Chem. Soc. Jpn. 1996, 69,
3551Ϫ3561. Silylation of the resulting alcohol with TBDMSCl:
[35b]
E. J. Corey, A. Venkateswarlu, J. Am. Chem. Soc. 1972,
[20]
R. B. Menon, M. A. Kumar, T. Ravindranathan, Tetrahedron
94, 6190Ϫ6191.
[36]
Lett. 1987, 28, 5313Ϫ5316.
P. Langer, I. Freifeld, Synlett 2001, 523Ϫ525.
[21] [21a]
[37] [37a]
E. Kunkel, I. Reichelt, H.-U. Reißig, Liebigs Ann. Chem.
J. S. Panek, R. T. Beresis, J. Org. Chem. 1996, 61,
[21b]
1984, 802Ϫ819.
H.-U. Reißig, I. Reichelt, T. Kunz, Org.
6496Ϫ6497. [37b] D. A. Evans, D. M. Fitch, Angew. Chem. 2000,
112, 2636Ϫ2640; Angew. Chem. Int. Ed. 2000, 39, 2536.
R. Ballini, M. Petrini, Synthesis 1986, 1024Ϫ1026.
M. T. Reetz, M. W. Drewes, A. Schmitz, Angew. Chem. 1987,
99, 1186Ϫ1188; Angew. Chem. Int. Ed. Engl. 1987, 26, 1141.
J. Schallenberg, E. Meyer, Z. Naturforsch., Teil B 1983, 38,
108Ϫ112.
C. Gennari, A. Vulpetti, G. Pain, Tetrahedron 1997, 53,
5909Ϫ5924.
D. Kitamoto, H. Imma, T. Nakai, Tetrahedron Lett. 1995, 36,
1861Ϫ1864.
Synth. 1992, 71, 189Ϫ199.
[22] [22a]
[38]
[39]
H. Angert, T. Kunz, H.-U. Reißig, Tetrahedron 1992, 48,
5681Ϫ5690. [22b] H. Angert, R. Czerwonka, H.-U. Reißig, Lie-
[22c]
bigs Ann. 1996, 259Ϫ263.
U. Reißig, Chem. Ber. 1996, 129, 227Ϫ232.
Czerwonka, H.-U. Reißig, Liebigs Ann./Recueil 1997,
H. Angert, R. Schumacher, H.-
[22d]
[40]
[41]
[42]
H. Angert, R.
2215Ϫ2220.
[23]
[24]
J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969, 34,
2543Ϫ2549.
G. Fischer, J. Fabian, Technische Universität Dresden, unpub-
lished results.
S. Weigand, R. Brückner, Chem. Eur. J. 1996, 2, 1077Ϫ1084.
K. V. Gothelf, I. Thomsen, K. A. Jorgensen, J. Am. Chem. Soc.
1996, 118, 59Ϫ64.
D. R. Gauthier Jr., E. M. Carreira, Angew. Chem. 1996, 108,
2521Ϫ2523; Angew. Chem. Int. Ed. Engl. 1996, 35, 2363.
Y.-S. Hon, C.-F. Lee, Tetrahedron 2001, 57, 6181Ϫ6188.
T. Ooi, M. Takahashi, K. Maruoka, J. Am. Chem. Soc. 1996,
118, 11307Ϫ11308.
[43] [43a]
C. Gennari, D. Moresca, S. Vieth, A. Vulpetti, Angew.
Chem. 1993, 105, 1717Ϫ1719; Angew. Chem. Int. Ed. Engl.
[25]
[26]
[43b]
1993, 32, 1618.
S. Kobayashi, H. Uchiro, Y. Fujishita, I.
Shiima, T. Mukaiyama, J. Am. Chem. Soc. 1991, 113,
[27]
4247Ϫ4252.
[44]
D. A. Evans, D. M. Fitch, T. E. Smith, V. J. Cee, J. Am. Chem.
Soc. 2000, 122, 10033Ϫ10046.
Receveived May 6, 2002
[28]
[29]
[O02244]
3428
Eur. J. Org. Chem. 2002, 3419Ϫ3428