Enantioselective intramolecular cyclopropanation of allyl 2-diazo-3-silanyloxybut-3-enoates

Article abstract of DOI:10.1016/j.tetasy.2005.04.006

The performance of the [Rh₂{(S)-ntt}₄]-catalyst in comparison to [Rh₂{(S)-pttl}₄] and [Rh₂{(S)- dosp}₄] has been examined with allyl 2-diazo-3-silanyloxybut-3- enoates. The best results were obtained with [Rh₂{(S)-pttl} ₄], where enantioselectivity culminated at 89% ee at -78°C. [Rh₂{(S)-ntt}₄] was slightly less selective, while [Rh₂{(S)-dosp}₄] was found less suitable for these substrates. However, even the results obtained with [Rh₂{(S)-pttl} ₄] are much less satisfactory than those for the intramolecular cyclopropanation of allyl diazoacetates in the presence of [Rh ₂{(S)-mepy}₄].

Full text of DOI:10.1016/j.tetasy.2005.04.006

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 2007–2013
Enantioselective intramolecular cyclopropanation of allyl
2-diazo-3-silanyloxybut-3-enoates
*
Paul Muller, Yves F. Allenbach and Stefane Grass
¨
´
Department of Organic Chemistry, University of Geneva, 30, Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland
Received 21 March 2005; accepted 11 April 2005
Available online 23 May 2005
Abstract—The performance of the [Rh2{(S)-ntt}4]-catalyst in comparison to [Rh2{(S)-pttl}4] and [Rh2{(S)-dosp}4] has been exam-
ined with allyl 2-diazo-3-silanyloxybut-3-enoates. The best results were obtained with [Rh2{(S)-pttl}4], where enantioselectivity cul-
minated at 89% ee at ꢀ78 ꢀC. [Rh2{(S)-ntt}4] was slightly less selective, while [Rh2{(S)-dosp}4] was found less suitable for these
substrates. However, even the results obtained with [Rh2{(S)-pttl}4] are much less satisfactory than those for the intramolecular
cyclopropanation of allyl diazoacetates in the presence of [Rh2{(S)-mepy}4].
ꢁ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
(Silanyloxyvinyl)diazoacetates have been used in enan-
tioselective olefin cyclopropanations in the presence of
[Rh2{(S)-dosp}4] with limited success.8 However, we
have recently observed, that Rh(II) carboxylate-cata-
lysts having 1,8-naphthanoyl protected tert-leucin as
ligand, dirhodium tetrakis (S)-N-1,8-naphthanoyl tert-
leucinate, [Rh2{(S)-nttl}4],9 are particularly suited for
these diazo precursors. Indeed, the cyclopropanation
of styrene with methyl (silanyloxyvinyl)diazoacetate in
the presence of [Rh2{(S)-nttl}4] afforded the correspond-
ing cyclopropane in up to 98% ee and 95% de.10 In view
of this positive result, we herein report the suitability of
our [Rh2{(S)-nttl}4]-catalyst for enantioselective intra-
molecular cyclopropanations of allyl 2-diazo-3-silanyl-
oxy-but-3-enoates 3a–c.
The intramolecular cyclopropanation of allyl diazoace-
tate esters in the presence of chiral, non-racemic
Rh(II)-carboxamidate catalysts, such as [Rh2{(S)-
mepy}4], represents the first conclusive demonstration
of the exceptional selectivity of this class of catalysts.1
Subsequently, these catalysts were found to be efficient
for a variety of other enantioselective carbene transfer
reactions.2,3 Among the various diazoacetates of inter-
est, those stabilized by aryl or vinyl groups occupy a
prominent position. Their reactions often occur with
almost perfect enantioselectivities with Rh(II) prolinate-
catalysts, such as [Rh2{(S)-tbsp}4]4 or [Rh2{(S)-
dosp}4].5 In contrast, the intramolecular cyclopropana-
tion of phenyl and vinyl diazoacetates results in disap-
pointingly low enantioselectivities. Thus Doyle
reported an ee of only 25–50% for the decomposition
of allyl phenyldiazoacetates in the presence of
[Rh2{(S)-tbsp}4]. With [Rh2{(S)-meaz}4] as catalyst,
the enantioselectivity increased significantly to 68%.6
The enantioselectivity for allyl styryl-diazoacetates with
[Rh2{(S)-dosp}4] varied from 2% to 87% depending on
the substituents of the allylic moiety. An exceptional
intramolecular cyclopropanation of a substituted allyl
vinyldiazoacetate with 93% ee (at ꢀ78 ꢀC) has already
been reported by Davies, and applied to an enantioselec-
tive synthesis of 5-epitremulenolide.7
2. Results and discussion
The diazo precursors were synthesized by straight-
forward methods. Commercial allylaceto-acetate 1a
was subjected to diazo transfer with p-acetamidoben-
zenesulfonyl azide in the presence of Et3N to afford allyl
2-diazoacetoacetate 2a,11 which was silylated with tris-
isopropylsilyl triflate (TIPSOTf) and Et3N to give 3a
(see Experimental).12 The same sequence was applied
to 1b1 and 1c, which, in turn, were accessible via acid-
catalyzed ester exchange of methyl acetoacetate and
cinnamyl alcohol and (E,E)-hexa-2,4-dienol, respec-
tively. The diazo decompositions were carried out in
PhCH3 at 0 ꢀC, and in a few cases, at ꢀ78 ꢀC. The
results are summarized in Table 1. With 1a, the expected
*
Corresponding author. Tel.: +41 22 702 6527; fax: +41 22 328
7396; e-mail: paul.muller@chiorg.unige.ch
0957-4166/$ - see front matter ꢁ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.04.006

2008
P. Mu¨ller et al. / Tetrahedron: Asymmetry 16 (2005) 2007–2013
cyclopropane 4a was isolated in 57–81% yield (Scheme 1
and Table 1).
þ58.8 for 47% ee. Comparison with the literature value
25
D
of ½aꢁ ¼ ꢀ163.8 (c 1.32, CH2Cl2) for (1S,5R)-616 leads
to a (1R,5S) configuration for 6 and 4a. Lactone 6 has
also been synthesized by the diazo decomposition of al-
lyl methyl diazomalonate with [Rh2{(S)-meaz}4] as cat-
alyst in 30% yield and 57% ee,15 and with 11% ee with a
Cu-bisoxazoline catalyst.17 The tert-butyl analogue of 6,
in turn, has been obtained by the intramolecular cyclo-
propanation of allyl tert-butyl malonate in up to 84%
ee.18
Table 1. Yield and enantioselectivity for intramolecular cyclopropa-
nation of substituted allyl 2-diazo-3-silanyloxybut-3-enoates 3a–c in
a
PhCH3
Compd
R
Ligand
Yield (%)
Ee (%)
3a
3a
3a
3a
3b
3b
3b
3b
3c
3c
3c
3c
H
{(S)-nttl}
{(S)-pttl}
{(S)-pttl}b
{(S)-dosp}
{(S)-nttl}
{(S)-pttl}
{(S)-pttl}b
{(S)-dosp}
{(S)-nttl}
{(S)-pttl}
{(S)-pttl}b
{(S)-dosp}
4a 81
4a 75
4a 57
4a 73
4b 77
4b 93
4b 66
4b 69
10 77
10 81
10 71
10 65
47c
50c
70c
05c
73d
77d
89d
05d
67e
60e
68e
02e
H
H
H
Ph
The structure of the cyclization product of 3b was as-
signed by comparison of the NMR data with the data
of 7, available in the literature (Scheme 2). The exo ori-
entation of the phenyl substituent at C(6) in 4b is a con-
sequence of the well established stereoselectivity of the
intramolecular cyclopropanation of allyl diazoace-
tates.1,7,8 For the diazo decomposition of 3b, [Rh2{(S)-
pttl}4] was again the most selective catalyst leading to
an ee of 77% at 0 ꢀC, and 89% at ꢀ78 ꢀC. [Rh2{(S)-
nttl}4] was almost as efficient, however, with 74% ee at
0 ꢀC. These results are remarkable in light of the fact
that the intramolecular cyclopropanation of the parent
Ph
Ph
Ph
(E)-CH@CHMe
(E)-CH@CHMe
(E)-CH@CHMe
(E)-CH@CHMe
a At 0 ꢀC.
b At ꢀ78 ꢀC.
c (1R,5S).
d (1S,5R,6S).
e (3aR,6R).
trans-cinnamyl diazoacetate proceeds to
7
with
[Rh2{(S)-mepy}4] with only 68% ee.1 The absolute con-
figuration of (ꢀ)-4b was tentatively assigned on the
grounds of comparison of its circular dichroism with
that of the structurally related 8 of known absolute con-
figuration.10 For compounds of the same absolute con-
figuration, the Cotton effects occur at the same
wavelength and have the same sign (Fig. 1).19
The structure of 4a was established by its conversion to
lactone 6, which is a known compound.13 Lactone 4a
was subjected to ozonolysis to yield 5a, which was not
characterized, but directly converted to methyl ester 6
by reaction with MeOH in the presence of p-toluenesulf-
onic acid. The enantioselectivity of the reaction of 3a
varied between 5 (with [Rh2{(S)-dosp}4]) and 50% ee
(with [Rh2{(S)-pttl}4]14) at 0 ꢀC, and increased to 70%
ee at ꢀ78 ꢀC. This is much lower than the enantioselec-
tivity for the cyclopropanation of allyl diazoacetate with
[Rh2{(S)-mepy}4], which reaches 95%.1 It is noteworthy,
however, that [Rh2{(S)-mepy}4] is generally not suitable
for the decomposition of diazo esters having a second
substituent at the diazo carbon.15 The absolute
configuration of (+)-4a was determined after its trans-
As Table 2 shows, the CD spectra of 4b and 8 are super-
imposable at the wavelengths k1–k5. An exception
occurs at k1, where 8 exhibits a positive Cotton effect,
which is absent in 4b. Accordingly, 4b should have the
(1S,5R,6S) absolute configuration. Thus the sense of
asymmetric induction is inverted in going from 3a to
3b. Similar changes have been reported for other intra-
molecular cyclopropanations of substituted allylic dia-
zoacetates.7,20 Cyclopropane 4c resulting from the
diazo decomposition of 3c was not isolable, but under-
went a spontaneous Cope rearrangement to afford 9.
formation to 6 as described above. A sample of 6
¼
23
D
prepared from 3a with [Rh2{(S)-nttl}4] had ½aꢁ
O
O
OTIPS
O
O
O
O
O
O
O
O
N2
R
N2
R
O
R
3a R = H
1a R = H
2a R = H
3b R = Ph
1b R = Ph
2b R = Ph
3c R = t-CH=CHMe
1c R = t-CH=CHMe
2c R = t-CH=CHMe
OTIPS
OMe
O
OTIPS
O
O
[Rh2L*4]
O
O
3a
O
H
O
O
H
H
(1R,5S)-4a
(1S,5S)-5a
(1R,5S)-6
Scheme 1.

P. Mu¨ller et al. / Tetrahedron: Asymmetry 16 (2005) 2007–2013
2009
H
H
OTIPS
O
3b
OTIPS
Ph
O
O
O
O
[Rh2L*4]
N2
R
Ph
O
H
H
(1S,5R,6R)-7
(1S,5R,6S)-4b
3b R = Ph
3c R = t-CH=CHMe
[Rh2L*4]
OTIPS
3c
O
RO
H
Me
H
Me
H
O
O
O
O
RO
H
O
OTIPS
(1S,5R,6R)-8
(R)-10 R = H
(R)-11 R = Me
(3aR,6R)-9
Scheme 2.
Table 2. Cotton effect of cyclopropanes 4b and 8
Compd
Solvent [M] · 108
k1 (nm)
k2 (nm)
k3 (nm)
k4 (nm)
k5 (nm)
De · 10ꢀ7
[Mꢀ1 cmꢀ1
De · 10ꢀ7
[Mꢀ1 cmꢀ1
De · 10ꢀ7
[Mꢀ1 cmꢀ1
De · 10ꢀ7
[Mꢀ1 cmꢀ1
De · 10ꢀ7
]
]
]
]
[Mꢀ1 cmꢀ1
]
8
4b
8
C6H12
6.4
222
+2.3
—
210
ꢀ2.2
213
261
ꢀ2.8
261
268
ꢀ4.3
268
274
ꢀ4.6
275
C6H12
6.3
ꢀ2.6
207
ꢀ2.0
261
ꢀ2.3
267
ꢀ2.0
274
MeCN
6.1
223
+1.6
—
ꢀ4.0
208
ꢀ2.8
262
ꢀ3.2
268
ꢀ2.0
275
4b
MeCN
6.6
ꢀ3.8
ꢀ1.8
ꢀ1.9
ꢀ1.6
Mechanistic considerations require that the methyl
group at C(6) and the hydrogen at C(3a) are in a trans
orientation,21 and this has been experimentally con-
firmed.7 The yield and enantioselectivity of the cyclo-
propanation/Cope rearrangement of 3c are also
included in Table 1. [Rh2{(S)-nttl}4] was slightly supe-
rior over [Rh2{(S)-pttl}4] and afforded an ee of 67% at
0 ꢀC. The enantioselectivities reached 89% with 3c (at
ꢀ78 ꢀC). Ozonolysis of (ꢀ)-9 of 67% ee afforded 2-meth-
ylsuccinic acid, which was transformed to dimethyl ester
10. Comparison of the GC retention time of 10 with that
of a sample of commercial (R)-10, allowed the assign-
ment of a (R)-configuration to the major component
of the degradation product with 65% ee (from reaction
with [Rh2{(S)-nttl}4]). Accordingly, the sense of induc-
tion of 3c is identical to that (supposed) of 3b, but oppo-
site to that of 3a (Fig. 1).
3. Conclusion
Among the catalysts examined in the present investiga-
tion, [Rh2{(S)-pttl}4] is best suited for the intramolecu-
lar cyclopropanation of allyl 2-diazo-3-silanyloxybut-3-
COOMe
O
O
COOMe
N
H
N
H
[Rh2{(4S)-meaz}4]
[Rh2{(2S)-mepy}4]
O
S
O
O
N
R
N
H
H
HOOC
COOH
O
R = C12H25 [Rh2{(S)-dosp}4]
R = t-Bu [Rh2{(S)-tbsp)4]
[Rh2{(S)-pttl}4]
R
OTIPS
OTIPS
H
O
O
R
COOH
S
O
O
O
N
Ph
O
S
Ph
H
S
H
[Rh2{(S)-nttl}4]
(1S,5R,6S)-4b
Figure 1. Configurational relationship between 4b and 8.
(1R,2S)-8
Figure 2. Ligands L H and abbreviations of Rh(II)-catalysts.
*

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P. Mu¨ller et al. / Tetrahedron: Asymmetry 16 (2005) 2007–2013
enoates, followed by [Rh2{(S)-ntt}4] while [Rh2{(S)-
dosp}4] is less suitable for these substrates. The excep-
tional selectivity exhibited by [Rh2{(S)-nttl}4] in the
intermolecular cyclopropanation of styrene with alkyl
2-diazo-3-silanyloxybut-3-enoates was not observed in
the intramolecular cyclopropanation. In addition, even
the results obtained with [Rh2{(S)-pttl}4] are much less
satisfactory than those for intramolecular cyclopropana-
tion of allyl diazoacetates in the presence of [Rh2{(S)-
mepy}4] (Fig. 2).
4.2.3. Allyl 2-diazo-3-oxo-butyrate 2a.1 To allyl aceto-
acetate (2.00 g, 14.1 mmol) and p-acetamidobenzene-
sulfonyl azide (p-ABSA, 3.71 g, 15.5 mmol) in aceto-
nitrile (70 mL) was added, at 0 ꢀC, Et3N (2.84 g,
28.2 mmol) dropwise. After the addition, stirring was
continued at rt for 3 h. The solvent was evaporated
and the residue suspended in Et2O (100 mL). p-Acetam-
idobenzenesulfonamide was separated by filtration, and
then washed with Et2O (2 · 100 mL). After evaporation
of the solvent, the residue was purified by flash chroma-
tography (SiO2, EtOAc/pentane 20:80) to afford 2a as a
yellow liquid (2.15 g, 90%). 1H NMR (400 MHz,
CDCl3): 2.50 (s, 3H); 4.74–4.77 (m, 2H); 5.31–5.41 (m,
2H); 5.92–6.01 (m, 1H). 13C NMR (100 MHz, CDCl3):
28.3 (q); 65.9 (t); 119.2 (t); 131.5 (d); 161.1 (s); 190.1 (s).
4. Experimental
4.1. General
See Ref. 22. The CD spectra were measured on a Jasco
J-715 instrument; the wavelengths k are indicated in
nanometer, and the ellipticity in terms of [De].
4.2.4. (E)-(3-Phenylallyl)-2-diazo-3-oxo-butyrate 2b.1
To p-ABSA (2.41 g, 10.1 mmol) and acetoacetate 1b
(2.10 g, 9.2 mmol) in acetonitrile (45.0 mL) was added,
dropwise, Et3N (1.7 g, 16.8 mmol) at 0 ꢀC. After stirring
for 3 h at rt, the solid precipitate was eliminated by fil-
tration and washed with Et2O (2 · 50 mL). The solvent
was evaporated, and the residue purified by flash chro-
matography (EtOAc/pentane 30:70) to yield a yellow
oil (1.59 g, 70%). IR (film): 3030w, 2144s, 1697s,
1645s, 1492w, 1452w, 1385m, 1365m, 1315s, 1279m,
4.2. Synthesis of allyl 3-silanyloxy-2-diazobut-3-enoates
3a–c
4.2.1. (E)-(3-Phenylallyl) 3-oxo-butyrate 1b.1 (E)-
Cinnamyl alcohol (5.20 g, 38.8 mmol) and methyl aceto-
acetate (8.60 g, 74.1 mmol) was heated in the presence of
Dowex 50W · 8 resin (94 mg) to 150 ꢀC until distillation
of MeOH ceased. Excess methyl acetoacetate was elim-
inated by evaporation under reduced pressure, and the
residue distilled (0.08 Torr, T = 107–110 ꢀC) to give 1b
as colorless oil (5.90 g, 69%). IR (film): 3028w, 1740s,
1714s, 1645w, 1578w, 1494w, 1448w, 1313m, 1259m,
1
1248s, 1157s, 1028m, 973s, 744s. H NMR (500 MHz,
CDCl3): 2.57 (s, 3H); 4.96 (dd, J = 1.1, 6.6, 2H); 6.37
(dt, J = 6.6, 15.9, 1H); 6.66 (d, J = 15.9, 1H); 7.33–7.37
(m, 1H); 7.39–7.43 (m, 2H); 7.47–7.48 (m, 2H). 13C
NMR (125 MHz, CDCl3): 28.3 (q); 65.9 (t); 122.3 (d);
126.7 (d); 128.4 (d); 128.7 (d); 135.4 (d); 135.8 (s);
161.3 (s); 190.1 (s). MS: 244 (M+; <1), 216 (6), 133
(46), 132 (15), 131 (13), 129 (10), 118 (13), 117 (100),
116 (14), 115 (41), 91 (24), 83 (10), 77 (12), 51 (10).
HR MS: 244.0824 (C13H12O3N2+; calcd 244.0848).
1
1145s, 1065w, 1027w, 963s, 744s. H NMR (500 MHz,
CDCl3): 2.31 (s, 3H); 3.52 (s, 2H); 4.82 (dd, J = 1.1,
6.5, 1H); 6.30 (dt, J = 6.5, 15.9, 1H); 6.70 (d, J = 15.9,
1H); 7.28–7.31 (m, 1H); 7.34–7.37 (m, 2H); 7.41–7.43
(m, 2H). 13C NMR (125 MHz, CDCl3): 30.2 (q); 50.1
(t); 65.9 (t); 122.4 (d); 126.7 (d); 128.2 (d); 128.7 (d);
134.9 (d); 136.0 (s); 166.9 (s); 200.4 (s). MS: 218 (M+;
<1), 194 (3), 119 (13), 118 (100), 104 (67), 103 (13),
102 (23), 93 (60), 82 (28), 81 (27), 69 (12), 49 (12). HR
MS: 218.0943 (C13H14O3+; calcd 218.0943).
4.2.5.
(E,E)-(Hexa-2,4-dienyl)-2-diazo-3-oxo-butyrate
2c. To the ketoester 1c (1.00 g, 5.49 mmol) and p-
ABSA (1.45 g, 6.04 mmol) in acetonitrile (40 mL) was
added dropwise, at 0 ꢀC, Et3N (1.00 g, 9.96 mmol) and
the mixture stirred at rt for 3 h. The solvent was evapo-
rated and the residue dissolved in Et2O (40 mL). The
solid precipitate was removed by filtration and washed
with Et2O (2 · 40 mL). After evaporation, the residue
was purified by flash chromatography (SiO2, EtOAc/
pentane 20:80) to yield 1c (1.05 g, 91%) as a yellow
semi-solid. IR (film): 3025w, 2938w, 2136s, 1710s,
1655s, 1444w, 1363s, 1305s, 1245s, 1148s, 1103w,
1056s, 987s, 964m, 915w, 742s, 635s. 1H NMR
(500 MHz, CDCl3): 1.77 (d, J = 6.8, 3H); 2.47 (s, 3H);
4.72 (d, J = 6.8, 2H); 5.60–5.66 (m, 1H); 5.76–5.82 (m,
1H); 6.03–6.09 (m, 1H), 6.28 (dd, J = 10.4, 15.3, 1H).
13C NMR (125 MHz, CDCl3): 18.1 (q); 28.2 (q); 65.8
(t); 122.7 (d); 130.1 (d); 132.2 (d); 135.9 (d); 161.2 (s);
190.1 (s). MS: 208 (M+; <1), 97 (40), 83 (12), 81 (100),
79 (21), 53 (19). HR MS: 208.0852 (C10H12O3N2+; calcd
208.0848).
4.2.2. (E,E)-(Hexa-2,4-dienyl) 3-oxo-butyrate 1c.23
Methyl acetoacetate (8.56 g, 73.8 mmol) and (E,E)-2,4-
hexadien-1-ol (3.62 g, 36.9 mmol) were heated in the
presence of a catalytic amount of DOWEX 50W · 8 re-
sin (100 mg) to 150 ꢀC, until distillation of MeOH
ceased. Excess methyl acetoacetate was removed by dis-
tillation in vacuo. Compound 1c was isolated upon dis-
tillation (p = 0.08 Torr, T = 117 ꢀC) as colorless oil
(4.01 g, 59%). IR (film): 3025w, 2934w, 1739s, 1714s,
1661w, 1444w, 1410w, 1360w, 1312m, 1266m, 1146s,
1027w, 988s, 958m, 925w. 1H NMR (500 MHz, CDCl3):
1.77 (d, J = 6.8, 3H); 2.27 (s, 3H); 3.46 (s, 2H); 4.63–4.65
(m, 2H); 5.54–5.66 (m, 1H); 5.73–5.81 (m, 1H); 6.03–
6.08 (m, 1H); 6.23–6.30 (m, 1H). 13C NMR (125 MHz,
CDCl3): 18.1 (q); 30.1 (q); 50.1 (t); 65.7 (t); 122.8 (d);
130.2 (d); 131.8 (d); 135.6 (d); 166.9 (s); 200.5 (s). MS:
182 (M+; 11), 98 (29), 97 (99), 85 (36), 81 (100), 80
(27), 79 (52), 69 (13), 58 (11), 53 (21). HR MS:
182.0932 (C10H14O3+; calcd 182.0943).
4.2.6. Allyl 2-diazo-3-[tri(isopropyl)silanyl-oxy]-but-3-
enoate 3a. To diazoester 2a (625 mg, 3.72 mmol) in
CH2Cl2 (15.0 mL) was added, at 0 ꢀC, Et3N (414 mg,
4.1 mmol) dropwise. Triisopropylsilyl trifluorosulfonate

P. Mu¨ller et al. / Tetrahedron: Asymmetry 16 (2005) 2007–2013
2011
(TIPSSOTf, 1.141 g, 3.73 mmol) in CH2Cl2 was added,
and the mixture stirred at 0 ꢀC for 1 h. After dilution
with hexane (40 mL), it was washed with aq 5% NaH-
CO3 (20 mL), followed by satd NaCl (20 mL), dried
over MgSO4, and evaporated to give an orange oil
(1.20 g, 99%). IR (film): 2946m, 2893w, 2868m, 2101s,
1710s, 1648w, 1601m, 1463m, 1371m, 1338s, 1271m,
1217w, 1160w, 1105m, 1067s, 1010s, 920w, 881m,
rated and the residue purified by flash chromatography
(SiO2, Et2O/pentane 15:85) to afford a colorless oil.
4.3.2.
oxa-bicyclo[3.1.0]hexan-2-one
(1R,5S)-1-[1-Tri(isopropyl)silanyloxy-vinyl]-3-
4a. Yield 113.1 mg
20
D
(81%); ½aꢁ ¼ þ49 (c 1.17, CHCl3, for 47% ee). IR (film):
2945m, 2867m, 1770s, 1626m, 1464m, 1370m, 1319s,
1257m, 1190s, 1111w, 1079s, 1031s, 1017s, 992s, 919w,
881s, 823m. 1H NMR (400 MHz, CDCl3): 1.10 (d,
J = 7.1, 18H); 1.20–1.29 (m, 3H); 1.82 (dd, J = 4.5, 7.8,
1H); 2.48 (dt, J = 4.8, 7.8, 1H); 4.19 (d, J = 9.1, 1H);
4.33 (dd, J = 4.8, 9.4, 1H); 4.41 (d, J = 1.8, 1H); 4.95
(d, J = 1.8, 1H). 13C NMR (125 MHz, CDCl3): 12.6
(d); 17.6 (t); 18.1 (q); 24.1 (d); 30.9 (s); 67.5 (t); 91.3
(t); 149.8 (s); 174.3 (s). MS: 296 (M+; <1); 255 (6), 254
(20), 253 (100), 209 (12), 167 (14), 139 (31), 125 (10),
103 (38), 85 (10), 79 (14), 77 (21), 75 (75), 61 (47), 59
(25). HR SM: 296.1843 (C16H28O3Si+; calcd 296.1808).
Enantiomer separation by GC (TAKEO-methyl, iso-
thermal at 130 ꢀC): s1 = 15.7 min [(1S,5R)-3a] minor;
s2 = 17.1 min [(1R,5S)-3a] major.
1
802m. H NMR (300 MHz, CDCl3): 1.13 (d, J = 7.0,
18H); 1.22–1.34 (m, 3H); 4.30 (d, J = 2.1, 1H); 4.74–
4.75 (m, 2H); 5.03 (d, J = 2.1, 1H); 5.27–5.39 (m, 2H);
5.91–6.00 (m, 1H). 13C NMR (75 MHz, CDCl3): 12.7
(d); 18.0 (q); 65.2 (t); 89.8 (t); 118.2 (t); 132.1 (d);
140.9 (s); 164.0 (s). MS: 324 (M+; 4), 281 (8), 253 (5),
225 (9), 170 (29), 157 (18), 129 (11), 115 (44), 113 (10),
101 (16), 99 (12), 87 (46), 85 (12), 75 (23), 73 (62), 61
(19), 59 (100). HR MS: 324.1839 (C16H28O3N2Si+; calcd
324.1869).
4.2.7. (E)-(3-Phenylallyl)-2-diazo-3-[tri(isopropyl)silanyl-
oxy]-but-3-enoate 3b. Same procedure with 2b, yield
99%, orange oil. IR (film): 2945m, 2867m, 2100s,
1707s, 1637w, 1600w, 1495w, 1463m, 1383m, 1342s,
1271s, 1216w, 1062s, 1010m, 964m, 881m, 803m. 1H
NMR (500 MHz, CDCl3): 1.11 (d, J = 7.4, 18 H);
1.22–1.32 (m, 3H); 4.29 (d, J = 2.2, 1H); 4.87 (dd,
J = 1.0, 6.5, 2H); 5.02 (d, J = 2.2, 1H); 6.32 (dt,
J = 6.5, 15.8, 1H); 6.67 (d, J = 15.8, 1H); 7.26–7.29 (m,
1H); 7.32–7.35 (m, 2H); 7.40–7.42 (m, 2H). 13C NMR
(125 MHz, CDCl3): 12.7 (d); 17.9 (q); 65.2 (t); 98.7 (t);
123.1 (d); 126.7 (d); 128.1 (d); 128.6 (d); 134.4 (d);
136.1 (s); 140.9 (s); 164.1 (s). MS: 400 (M+; <1), 372
(11), 330 (22), 329 (85), 281 (19), 225 (11), 157 (56),
155 (12), 131 (31), 129 (17), 128 (10), 117 (53), 116
(12), 115 (86), 103 (59), 101 (13), 91 (67), 88 (13), 87
(47), 77 (11), 75 (71), 73 (57), 61 (43), 59 (100), 45
(16). HR MS: 400.2165 (C22H32N2O3Si+; calcd
400.2182).
4.3.3. (1S,5R,6S)-6-Phenyl-1-[1-tri(isopropyl)-silanyl-
oxyviny]-3-oxa-bicyclo[3.1.0]hexan-2-one 4b. Colorless
20
D
oil. For yield and ee: see Table 1. ½aꢁ ¼ ꢀ17 (c 0.58,
20
CHCl3, for 61% ee); ½aꢁ ¼ ꢀ26 (c 0.67, CHCl3, for
D
89% ee). IR (film): 2944w, 2866w, 1770s, 1627w,
1463w, 1370m, 1311w, 1262m, 1240w, 1181m, 1094m,
1054s, 1013s, 955s, 956w, 881m. H NMR (500 MHz,
1
CDCl3): 0.96 (d, J = 7.4, 9H); 0.97 (d, J = 7.3, 9H);
1.06–1.15 (m, 3H); 2.53 (d, J = 4.9, 1H); 2.92 (t,
J = 4.8, 1H); 4.29 (d, J = 1.8, 1H); 4.34 (d, J = 9.1,
1H); 4.39 (d, J = 1.8, 1H); 4.45 (dd, J = 4.8, 9.2, 1H);
7.16–7.28 (m, 5H). 13C NMR (125 MHz, CDCl3): 12.4
(d); 18.9 (q); 27.1 (d); 34.9 (d); 39.9 (s); 67.9 (t); 95.7
(t); 127.2 (d); 128.0 (d); 128.2 (d); 133.9 (s); 147.6 (s);
174.0 (s). MS: 329 (M+; 94), 155 (12), 115 (15), 103
(25), 91 (100), 75 (45), 61 (27), 59 (21). HR MS:
329.1590 (C19H25O3Si+; calcd 329.1573). Enantiomer
separation by HPLC (OD-H, i-PrOH/hexane 1:9,
0.5 mL/min): s1 = 15.5 min [(1S,5R,6R)-4b] major;
s2 = 17.3 min [(1R,5S,6S)-4b] minor; or SFC (OD-H,
2% MeOH): s1 = 9.9 min (major); s2 = 11.0 min (minor).
4.2.8. (E,E)-(Hexa-2,4-dienyl)-2-diazo-3-[tri-(isopropyl)-
silanyloxy]-but-3-enoate 3c. Same procedure with 2c.
Yield 96%, orange oil. IR (film): 2945w, 2868w, 2100s,
1708s, 1663w, 1637w, 1600w, 1463w, 1383m, 1342s,
1270w, 1217w, 1155w, 1102m, 1062s, 1009m, 986s,
1
919w, 881m, 802m, 683s. H NMR (400 MHz, CDCl3):
4.3.4. (3aR,6R)-6-Methyl-8-[tri(isopropyl)-silanyloxy]-
3,3a,6,7-tetrahydrocyclohepta[c]-furan-1-one 9. Color-
1.01 (d, J = 7.1, 18H); 1.13–1.21 (m, 3H); 1.70 (d,
J = 6.0, 3H); 4.18 (d, J = 2.2, 1H); 4.62 (d, J = 6.6,
1H); 4.92 (d, J = 2.1, 1H); 5.53–5.61 (m, 1H); 5.65–
5.76 (m, 1H); 5.95–6.02 (m, 1H); 6.15–6.25 (m, 1H).
13C NMR (100 MHz, CDCl3): 12.7 (d); 18.0 (q); 65.1
(t); 89.7 (t); 123.7 (d); 130.4 (d); 131.5 (d); 135.1 (d);
140.9 (s); 164.2 (s). MS: 364 (M+; <1), 157 (21), 155
(36), 87 (28), 81 (100), 73 (34), 59 (39). HR MS:
364.2154 (C19H32O3N2Si+; calcd 364.2182).
20
D
less oil. For yield and ee: see Table 1. ½aꢁ ¼ ꢀ40 (c
1.04, CHCl3, for 67% ee). IR (film): 2944w, 2891w,
2866w, 1750s, 1632s, 1462w, 1368w, 1353w, 1310w,
1250w, 1174s, 1152s, 1122w, 1069w, 1031m, 986m,
1
918w, 880m, 800m. H NMR (400 MHz, CDCl3): 1.11
(d, J = 7.1, 18H); 1.23–1.35 (m, 3H); 2.10 (ddd,
J = 16.7, 10.3, 2.5, 1H); 2.52 (dt, J = 16.7, 3.3, 1H);
2.63–2.71 (m, 1H); 3.77 (dd, J = 9.1, 8.3, 1H); 3.92–
3.98 (m, 1H); 4.38 (dd, J = 9.8, 8.3, 1H); 5.46 (ddd,
J = 10.2, 2.8, 1.8, 1H); 5.56 (ddd, J = 10.2, 5.6, 2.8,
1H). 13C NMR (100 MHz, CDCl3): 13.6 (d); 18.0 (q);
18.1 (q); 20.8 (q); 29.6 (d); 36.2 (d); 42.3 (t); 69.7 (t);
106.1 (s); 129.8 (d); 137.2 (d); 163.6 (s); 168.6 (s). MS:
294 (23), 293 (Mꢀ43+; 100), 103 (19), 75 (29), 61 (16),
59 (15). HR MS: 293.1589 (C16H25O3Si+; calcd
293.1573). Enantiomer separation by HPLC (OD-H,
4.3. Diazo decomposition of allyl 3-silanyloxy-2-diazobut-
3-enoates 3a–c
4.3.1.
Sample
run. [Rh2{(S)-nttl}4]
(13.9 mg,
0.01 mmol) was activated by heating in vacuo, dissolved
in toluene and cooled to 0 ꢀC. Diazoacetate 3a
(152.4 mg, 0.47 mmol) in toluene (1.0 mL) was added
dropwise. After 1 h of stirring, the solvent was evapo-

2012
P. Mu¨ller et al. / Tetrahedron: Asymmetry 16 (2005) 2007–2013
1423–1424; (b) Doyle, M. P.; Austin, R. E.; Bailey, A. S.;
Dwyer, M. P.; Dyatkin, A. B.; Kalinin, A. V.; Kwan, M.
M.; Liraqs, S.; Oalman, C. J.; Pieters, R. J.; Protopopova,
M. N.; Raab, C. E.; Roos, G. H. P.; Zjou, Q.; Martin, S.
F. J. Am. Chem. Soc. 1995, 117, 5763–5775.
i-PrOH/hexane 1:9, 0.25 mL/min): s1 = 18.9 min [(3aS,
6S)-9] minor; s2 = 19.8 min [(3aR,6R)] major.
4.4. Ozonolysis of 4a; methyl (1R,5S)-2-oxo-3-oxabicy-
clo[3.1.0]hexanecarboxylate 6
2. (a) Muller, P.; Polleux, P. Helv. Chim. Acta 1994, 77, 645–
¨
654; (b) Doyle, M. P.; Dyatkin, A. B.; Roos, G. H. P.;
Can˜as, F.; Pierson, D. A.; van Basten, A.; Muller, P.;
¨
Lactone 4a (375 mg, 1.27 mmol) was ozonized in
CH2Cl2 (30 mL) at ꢀ78 ꢀC for 10 min, until the blue
color persisted. The mixture was purged with oxygen,
then treated with Me2S (470 lL, 6 mmol) and allowed
to reach room temperature within 24 h. It was washed
with satd NaHCO3 (2 · 20 mL), then H2O (2 · 20 mL),
dried, and evaporated to afford crude 5a (306 mg,
81%), which was transesterified by refluxing with
p-toluenesulfonic acid (30.5 mg) in MeOH (16 mL)
overnight. After the addition of solid NaHCO3, the
mixture was concentrated and extracted with Et2O
(20 mL). Work-up afforded 99.6 mg (61%) of 6. Mp
Polleux, P. J. Am. Chem. Soc. 1994, 116, 4507–4508.
3. (a) Doyle, M. P. Aldrichim. Acta 1996, 29, 3–11; Doyle, M.
P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds: From Cyclo-
propanes to Ylides; Wiley-Interscience: New York, 1998,
pp 112–162; (b) Doyle, M. P. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed., 2nd ed.; Wiley: New York, 2000,
Chapter 5.
4. Kennedy, M.; Mc Kervey, M. A.; Maguire, A. R.; Roos,
G. H. P. J. Chem. Soc., Chem. Commun. 1990, 361–
362.
5. (a) Davies, H. M. L. Aldrichim. Acta 1997, 30, 107–114;
(b) Davies, H. L. M. Eur. J. Org. Chem. 1999, 2459; (c)
Davies, H. M. L.; Antoulinakis, E. G. Org. React. 2001,
57, 1–326; (d) Davies, H. L. M.; Hutcheson, D. K.
Tetrahedron Lett. 1993, 34, 7243–7247; (e) Davies, H. L.
M.; Bruzinski, P. R.; Lake, D. H.; Kone, N.; Fall, M. J. J.
Am. Chem. Soc. 1996, 118, 6897–6907.
6. Doyle, M. P.; Hu, W.; Weathers, T. M., Jr. Chirality 2003,
15, 369–373.
7. (a) Davies, H. M. L.; Doan, B. D. J. Org. Chem. 1999, 64,
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8. Davies, H. M. L.; Ahmed, G.; Calvo, R. L.; Churchill, M.
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69–72 ꢀC, lit.24 68–72 ꢀC; lit.16 46–47 ꢀC. [a]D = +58.8
25
(c 1.23, CH2Cl2) for 48% ee. Lit.16 ½aꢁ ¼ ꢀ163.9 (c
D
1.32, CHCl3) for (1S,5R)-6. Enantiomer separation by
GC (Lipodex E), 10 min at 100 ꢀC, then 1 ꢀC/min to
150 ꢀC, 10 min at 150 ꢀC. s1 = 27.6 min (1R,5S), major;
s2 = 29.8 min (1S,5R), minor.
4.5. Ozonolysis of 9; dimethyl (R)-methylsuccinate (R)-11
Lactone 9 (90 mg, 0.27 mmol) with 68% ee was ozonized
in MeOH (12 mL) at ꢀ78 ꢀC, and then treated at room
temperature with formic acid (1.5 mL) and H2O2 (30%,
0.8 mL). After 30 min of stirring at room temperature,
the mixture was heated to reflux for 30 min, cooled, treat-
ed with formic acid (1.0 mL), and heated again to reflux
for 30 min. When all peroxides were decomposed, H2O
(4.0 mL) was added, and the mixture extracted with
AcOEt (3 · 10 mL). After the evaporation of the sol-
vent, the residue was recrystallized from AcOEt/pen-
tane, and gave 10 mg (28%) of (R)-2-methylsuccinic
acid (R)-10, which was converted in 42% yield to the di-
methyl ester (R)-11 by treatment with MeOH and p-tol-
uenesulfonic acid. Enantiomer separation by GC: (FS-
Hydrodex b-6-TBDMS): s1 = 40.4 min (R)-11, major;
s2 = 41.5 min (S)-11, minor, by comparison with com-
mercial sample; ee 65%.
10. Muller, P.; Bernardinelli, G.; Allenbach, Y. F.; Ferri, M.;
¨
Flack, H. D. Org. Lett. 2004, 6, 1725–1728.
11. Julia, S.; Cannic, G.; Linstrumelle, G. C.R. Acad. Sci.,
Ser. C: Sci. Chim. 1967, 264, 1890–1892.
12. Ueda, Y.; Roberge, G.; Vinet, V. Can. J. Chem. 1984, 62,
2936–2940.
13. (a) Kitaori, K.; Mikami, M.; Furukawa, Y.; Yoshimoto,
H.; Otera, J. Synlett 1998, 499; (b) Inoue, T.; Kitagama,
O.; Ochiai, O.; Taguchi, T. Tetrahedron: Asymmetry 1995,
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Commun. 1991, 21, 1429–1432.
14. (a) Hashimoto, S. I.; Watanabe, N.; Ikegami, S. Tetrahe-
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Watanabe, N.; Sato, T.; Shiro, M.; Ikegami, S. Tetrahe-
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Acknowledgements
This work was supported by the Swiss National Science
Foundation (Projects No. 20-52581.97 and 2027-
048156). Support and sponsorship concerted by COST
Action D24 ÔSustainable Chemical Processes: Stereose-
lective Transition Metal-Catalyzed ReactionsÕ are kindly
acknowledged. The authors are indebted to S. Matile
and N. Sakai for the interpretation of the CD spectra,
to A. Pinto and J.-P. Saulnier for the NMR spectra,
and D. Klink for the mass spectra.
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1145–1147; (b) Doyle, M. P.; Hu, W. ARKIVOC 2003,
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483–494; (c) Muller, P.; Bolea, C. Synlett 2000, 826–828;
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(d) Bolea, C. Ph.D. Thesis, Thesis No. 3251, University of
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