Rhodium(II)-catalyzed enantioselective intramolecular CH insertion with alkyl diazo(trialkylsilyl) acetates

Article abstract of DOI:10.1016/S0957-4166(03)00208-8

The decomposition of cyclohexyl diazo(triethylsilyl)acetate 2a and the t-butyl derivatives 3a,b with [Rh₂{(S)-nttl}₄] and similar chiral Rh(II)-catalysts proceeds in toluene at room temperature to produce silylated lactones in up to 90% yield. The reaction is highly stereoselective. Enantioselectivities of up to 79% have been observed.

Full text of DOI:10.1016/S0957-4166(03)00208-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 1503–1510
Rhodium(II)-catalyzed enantioselective intramolecular CH
insertion with alkyl diazo(trialkylsilyl) acetates
Paul Mu¨ller,* Fabienne Lacrampe and Ge´rald Bernardinelli
Department of Organic Chemistry, University of Geneva, 30, Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland
Received 7 February 2003; accepted 27 February 2003
Abstract—The decomposition of cyclohexyl diazo(triethylsilyl)acetate 2a and the t-butyl derivatives 3a,b with [Rh2{(S)-nttl}4] and
similar chiral Rh(II)-catalysts proceeds in toluene at room temperature to produce silylated lactones in up to 90% yield. The
reaction is highly stereoselective. Enantioselectivities of up to 79% have been observed. © 2003 Elsevier Science Ltd. All rights
reserved.
1. Introduction
the sterically less congested stereoisomer was
observed.12 Subsequently, the stereoselectivity of methyl
diazoacetates having different trialkylsilyl groups was
The intra-1 and intermolecular2 carbonꢀhydrogen bond
insertion of diazoacetate esters in the presence of chiral,
non-racemic catalysts proceeds with very high enan-
tioselectivities. Attractive applications based on this
methodology have been described with alkyl diazoac-
etate, alkyl vinyl- or alkyl phenyldiazoacetate esters.3
examined
with
[Cu(OTf)],
[Rh2(OAc)4]
and
[Ru(CO)4(m-OAc)2]n and the predominance of the less
congested diastereomer was confirmed.13
Recent investigations of Marsden et al. revealed that
silylated diazoacetate esters undergo intramolecular CH
insertions in the presence of [Rh2(OAc)4] to afford
silylated lactones,14 or oxasilacyclopentanes,15 respec-
tively, in a highly diastereoselective manner. The obser-
vations of Marsden et al. combined with our own
results on enantioselective olefin cyclopropanation with
trimethylsilyldiazomethane suggested the possibility of
carrying out enantioselective intramolecular CH inser-
tions with silylated diazoacetate esters (Scheme 1).
Diazo compounds carrying silyl substituents have been
known for some time. Thus, trimethylsilyldiazo-
methane4 cyclopropanates olefins in the presence of
PdCl2 or CuCl.6 Some time ago, we observed enan-
5
tioselective olefin cyclopropanations with trimethylsilyl-
diazomethane in the presence of [R2{(2S)-mepy}4] with
ee’s of up to 54%. However, owing to problems
encountered in the attempted desilylation of the cyclo-
propanes, this research was not continued.7 In the
absence of catalysts trimethylsilyldiazomethane affords
aziridines with imines.8 Aziridines are also formed upon
transition metal-catalyzed decomposition of trimethyl-
silyldiazomethane9 and enantioselectivities of up to 72%
ee have been reported.10 The photolysis of ethyl dia-
zo(trimethylsilyl)acetate in the presence of simple
olefins has been reported by Scho¨llkopf et al. in 1969.11
However, only a few isolated studies concerning the
transition metal-catalyzed decomposition of silylated
diazoacetates have been carried out. Maas et al. investi-
gated the diastereoselectivity of the intermolecular
olefin cyclopropanation of silylated diazoacetate esters
in the presence of Ru(I)-catalysts, and a preference for
2. Results and discussion
2.1. Synthesis of cyclohexyl diazo(triorganylsilyl)-
acetates
The diazo esters 2a–c and 3a,b were prepared by treat-
ment of the appropriate cyclohexyl diazoacetates (1a–
c)1,16 with trialkylsilyl triflate and ethyl diiso-
propylamine in ether at −78°C.17 They were isolated in
yields varying from 83 to 94%. The dimethylphenylsilyl
derivative 2d, in turn, was synthesized by treatment
of 1a with (dimethylphenyl)silyl chloride in the presence
of LDA. The compound was highly labile, and de-
composed partially upon attempted purification
(chromatography on SiO2).
* Corresponding author. E-mail: paul.muller@chiorg.unige.ch
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00208-8

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P. Mu¨ller et al. / Tetrahedron: Asymmetry 14 (2003) 1503–1510
Scheme 1.
Table 1. [Rh2(OAc)4]-catalyzed intramolecular CH inser-
tion of cyclohexyl diazo(triethylsilyl)acetates 2a and 3a,ba
2.2. Decomposition of cyclohexyl diazo(triethylsilyl)-
acetates 2a and 3a,b
Compound
Solvent, T (°C)
Time
Yield (%)
Initially, the insertions were carried out with 2a and the
cis- and trans-t-butyl derivatives 3a,b under the condi-
tions reported by Marsden, i.e. with [Rh2(OAc)4] in
refluxing benzene (Table 1). The reactions proceeded
sluggishly and only in moderate yields to afford the
corresponding lactones 4a, 6 and 8, respectively. The
stereochemistry at the ring junction was established via
desilylation with TBAF which afforded the known
lactones 9a,b and 10b.1 In all cases, only insertion into
the equatorial CH bond was observed, i.e. the trans-lac-
tones 4a and 6 were formed exclusively from 2a, and
3a, and the cis- lactone 8 from 3b. This contrasts with
the behavior of the unsilylated diazoester 1a which,
upon diazo decomposition with [Rh2(OAc)4] yields a
mixture of trans- and cis-lactones 9a and 10a.
2a
2a
2a
3a
3b
C6H6, 80
PhCH3, 25
CH2Cl2, 25
C6H6, 80
C6H6, 80
15 h
42
33
61
34
21
4 days
1 day
15 h
15 h
a With 2% of catalyst.
blocked 4-t-butylcyclohexyl diazo acetates, the trans
isomer 3a, in which the substituent is equatorial, yields
exclusively trans-lactone 6, while in the case of the
cis-t-butyl derivative 3b the resulting lactone 8 has a
cis-configuration at the ring junction. This is consistent
with the previously observed preferential insertion into
equatorial CH bonds of cyclohexyl diazoacetates upon
decomposition with Rh(II)-catalysts (Scheme 2).
The formation of trans-lactone 4a from 2a necessarily
involves that conformation of the cyclohexane ring
where the diazoester occupies an equatorial position.
The same conformation could in principle also lead to
a cis-lactone via insertion into an axial CH bond, as is
the case with 1a,1 but this pathway is not followed with
the triethylsilyl substituent. An axial diazoacetate
group, in turn, must result in a cis-lactone for steric
reasons. As expected, with the conformationally
The orientation of the silyl substituent in the lactones
was assigned on the grounds of the H NMR spectra or
by X-ray crystallography: Marsden has assigned the
configuration of 12 via comparison of the vicinal H-
C(1)/H-C(9) coupling constants of 11.0 Hz, consistent
with a dihedral angle of ca. 140°, and in good agree-
ment with that of 13 with 12.4 Hz. The analogous
1

P. Mu¨ller et al. / Tetrahedron: Asymmetry 14 (2003) 1503–1510
1505
Table 2. Intramolecular insertion of cyclohexyl diazo (tri-
ethylsilyl)acetate 2a in benzenea
Catalyst
T (°C)
Time
Yieldb (%)
ee (%)
[Rh2{(4S)meox}4]
[Rh2{(2S)mepy}4]
[Rh2{(4S)-bnaz}4]
80
80
80
6 h
2 days 16
5 h
15 h
2.5 h 34
1.5 h 45
1.5 h 49
2.5 h 30
21 h
2 h
1 h
0
0
0
10
62
71
02
07
13
13
40
39
19
60
59
[Rh2{(−)campha}4] 80
[Rh2{(−)-mpmt}4]
[Rh2{(−)-tbsp}4]
[Rh2{(−)-dosp}4]
[Rh2{(S)-bnp}4]
[Rh2{(R)-bnp}4]
[Rh2{(S)-ptpa}4]
[Rh2{(S)-pttl}4]
[Rh2{(S)-nttl}4]
40
80
80
80
80
80
60
80
21
50
67
68
15 h
a 2% of catalyst.
b Isolated yield.
lower enantioselectivity (40%). The proline derived cat-
alysts [Rh2{(−)-tbsp}4] and [Rh2{(−)-dosp}4] were
equally unsatisfactory both with respect to yield and
enantioselectivity.
Scheme 2.
coupling constants of 12.6 Hz in 4a and 6, respectively,
suggests the same relative configuration. In contrast, in
8 where the oxygen of the lactone occupies an axial
position on the cyclohexane ring, the dihedral angle of
H-C(1) and H-C(9) is reduced to ca. 100°, which results
in a coupling constant of 5.6 Hz. On these grounds, the
relative configuration was tentatively assigned. Unfor-
tunately, NOE experiments to confirm this assignment
were not conclusive. However, since 8 is crystalline, the
assignment was confirmed by X-ray structure analysis
on the racemic compound (Fig. 1).
The effect of temperature and solvent on the decompo-
sition of 2a was investigated with several catalysts
(Table 3). With [Rh2{(4S)-bnaz}4] an increase of tem-
perature to 110°C and a solvent change to 1,2-
dichloroethane (DCE) or trifluorotoluene had no
significant effect on the yield, although in trifluro-
toluene the ee went up to 79%. Surprisingly, however,
we found that the Ikegami-type catalysts such as
[Rh2{(S)-ptpa}4] and, in particular our recently devel-
oped [Rh2{(S)-nttl}4]18 were much more efficient than
all the other catalysts tried, and in the end reactions
could be carried out at room temperature and with
short reaction times. Yields were in the range of 74–
90%, and the enantioselectivity culminated at 66%,
slightly below the 79% ee obtained with [Rh2{(4S)-
bnaz}4] (Scheme 3).
That [Rh2(OAc)4] is only partially satisfactory for diazo
decomposition of silylated diazoacetates has been
reported by others. Despite this, we have screened a
variety of chiral Rh(II)-catalysts for the insertion of 2a
(Table 2). The enantiomers of 4a were separated by GC
(see Section 4). The Rh(II) carboxamidate-catalysts of
Doyle, such as [Rh2{(4S)-meox}4] produced no decom-
position even at 80°C. The reportedly more reactive
[Rh2{(4S)-bnaz}4] was tested in different solvents at
elevated temperatures. Although the yields were disap-
pointing, enantioselectivities of up to 71% were
observed. Pirrung’s binol phosphate catalyst [Rh2{(R)
or (S)-bnp}4] provided low yields even at 80°C, and
The abs. configuration of 4a was determined by com-
parison of the specific rotation of the desilylated 9a
with data previously reported in the literature. The
specific rotation of authentic (1R,6S)-9a is [h]2D5=−75.0
(c 0.2, MeOH).19 The insertion product 4a resulting
from reaction of 2a with [Rh2{(S)-nttl}4] had [h]2D0=
−16.1 for 66% ee and 9a obtained via desilylation of 4a
had [h]2D0=−42.4 for 61% ee, which corresponds to
(1S,6S,9R)-configuration of 4a. Note that the Si-sub-
stituent at C(9) inverts the CIP priorities of the sub-
stituents at C(1) in going from 4a to 9a.
Some asymmetric insertions were also carried out with
3a,b. The insertions were accompanied by formation of
b-lactones 7a,b in the range of 4–5% upon decomposi-
tion of 3a and 21–27% from 3b. Their structure was
assigned on the grounds of the IR-stretching frequency
of the carbonyl group at 1796 and 1798 cm−1, respec-
1
tively, and a singlet at 2.92 in the H NMR attributed
to H-C(9). The silylated b-lactone 7b was desilylated to
afford 11b. The ee of the b-lactones 7a,b was not
determined. The results for the g-lactones are summa-
Figure 1. X-Ray crystal structure of rac-8.

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P. Mu¨ller et al. / Tetrahedron: Asymmetry 14 (2003) 1503–1510
Table 3. Effect of solvent and temperature on the intramolecular insertion of cyclohexyl diazo (triethylsilyl)acetate 2aa
Catalyst
Solvent
T (°C)
Time (h)
Yield (%)
ee (%)
[Rh2{(4S)-bnaz}4]
[Rh2{(4S)-bnaz}4]
[Rh2{(4S)-bnaz}4]
[Rh2{(S)-ptpa}4]
[Rh2{(S)-nttl}4]
[Rh2{(S)-nttl}4]
[Rh2{(S)-nttl}4]
[Rh2{(S)-nttl}4]
[Rh2{(S)-pttl}4]
[Rh2{(S)-bpttl}4]
DCE
83
110
103
103
20
40
20
20
20
20
4
3
3
2.5
1
11
4
7
48
82
87
90
76
75
74
74
79
62
16
62
56
56
61
64
66
PhCH3
PhCF3
PhCF3
C6H6
CH2Cl2
CH2Cl2
PhCH3
PhCH3
PhCH3
2
1.5
1.5
1.0
20
a With 2% of catalyst.
Scheme 3. Ligands and abbreviations of Rh(II)-catalysts.
rized in Table 4. Note that the enantioselectivity for
formation of the cis-lactone 8 tends to be generally
lower than that for 6.
product 10b ([h]2D0=−11.5) with the value available in
the literature for (1S,3R,6S)-10b {([h]2D5=−30.8 (c 0.12,
CHCl3)},12 which gives (1R,3R,6S,9R)-configuration
for 8. The abs. configuration of 6 could not be deter-
mined owing to the lack of data in the literature.
However it may reasonably be assumed to be
(1S,3S,6S,9R) in analogy to that of 4a.
The abs. configuration of 8 ([h]2D0=−18.5 for 66% ee)
obtained with [Rh2{(S)-nttl}4] was determined by com-
parison of the specific rotation of the desilylated
Table 4. Intramolecular insertion with cis- and trans-t-butylcyclohexyl diazo(triethylsilyl)acetate 3a,ba
Compound
Catalyst
Solvent
T (°C)
Yield (%)
ee (%)
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
[Rh2{(4S)-bnaz}4]
[Rh2{(R)-bnp}4]
[Rh2{(4S)-ptpa}4]
[Rh2{(S)-pttl}4]
[Rh2{(S)-nttl}4]
[Rh2{(S)-bpttl}4]
[Rh2{(4S)-bnaz}4]
[Rh2{(4S)-ptpa}4]
[Rh2{(S)-nttl}4]
[Rh2{(S)-pttl}4]
[Rh2{(S)-bpttl}4]
C6H6
C6H6
C6H6
PhCH3
PhCH3
PhCH3
C6H6
80
80
80
20
20
20
80
80
20
20
20
6: 16
6: 18
6: 7
6: 73
6: 73
6: 63
64
24
2
77
78
69
43
13
43
66
8
8:
5
C6H6
8: 23
8: 50
8: 28
8: 42
PhCH3
PhCH3
PhCH3
a With 2% of catalyst, 2 h.

P. Mu¨ller et al. / Tetrahedron: Asymmetry 14 (2003) 1503–1510
1507
2.3. Variation of the silyl substituents of cyclohexyl
diazo(triorganylsilyl)acetates
4. Experimental
4.1. General
The trimethylsilyl- and triisopropylsilyl derivatives 2b,c
of 1a were prepared in analogy to 2a. Decomposition of
2b with [Rh2{S)-pttl}4] and [Rh2{S)-nttl}4] afforded a
ca. 4:1 mixture of trans and cis-lactones 4b and 5b with
modest enantioselectivities, from which 4b could be
separated (Table 5). This contrasts with the decomposi-
tion of 2a, where only the trans-lactone is formed. The
orientation of the silyl substituent in 4b was assigned in
analogy to that of 4a. Desilylation of the mixture
afforded 9a and 10a. No cyclization product could be
obtained from the TIPS derivative 2c, however. Ele-
vated temperatures (PhCH3, reflux) were required in
order to achieve total decomposition of 2d, but yields
of insertion products were poor. In view of the substan-
tial losses encountered during purification of 2d, some
reactions were effected without purification. The respec-
tive yields in Table 5 refer to both preparation and
decomposition of 2d. Only a little improvement could
be achieved by this procedure, however. The configura-
tion of the silyl substituent was assigned on the grounds
of the vicinal coupling constant of 12.6 Hz, as before.
Desilylation of 4d with TBAF in THF afforded 9a. The
oxidative replacement of the silyl substituent was
attempted under a large variety of conditions,20 but so
far failed, and the desired alcohol could not be isolated.
See Ref. 21
4.2. Synthesis of cyclohexyl diazo(triethylsilyl)acetates
2a–2c, 3a,b
4.2.1. General procedure. Ethyldiisopropylamine (290
ml, 1.68 mmol) followed by triethylsilyl triflate (380 ml,
1.68 mmol) in Et2O (2.5 mL) were added at −78°C to
the diazoester 1 (1.50 mmol) in Et2O (5.0 mL). The
mixture was allowed to warm up to rt, and was stirred
for 24 h. It was neutralized with Na2CO3, filtered, and
concentrated in vacuo. The crude product was purified
by flash chromatography (SiO2, pentane/AcOEt, 97:3).
4.2.2. Cyclohexyl diazo(triethylsilyl)acetate 2a. Yield
94%, yellow oil. IR (NaCl): 2937m, 2088s, 1684s,
1
1078w. H NMR (500 MHz, CDCl3): 0.74 (q, J=7.8,
6H); 0.97 (t, J=7.9, 9H); 1.23–1.29 (m, 1H); 1.32–1.46
(m, 4H); 1.50–1.55 (m, 1H); 1.67–1.73 (m, 2H); 1.83–
1.88 (m, 2H); 4.78–4.83 (m, 1H). 13C NMR (125 MHz):
3.2 (t); 7.1 (q); 23.7 (t); 25.4 (t); 31.8 (t); 42.8 (s); 73.0
(d); 169.3 (s). MS: 282 (M+, 2), 171 (48), 143 (13), 115
(100), 87 (61), 55 (30). HR MS: 282.1743
(C14H26O2N2Si+; calcd 282.1764).
4.2.3. Cyclohexyl diazo(trimethylsilyl)acetate 2b. Yield
1
68%, yellow oil. H NMR (500 MHz, CDCl3): 0.25 (s,
Table 5. Intramolecular insertion with cyclohexyl diazo-
(triorganylsilyl)acetates 2b,da
9H); 1.22–1.53 (m, 6H); 1.66–1.71 (m, 2H); 1.80–1.86
(m, 2H); 4.77–4.84 (m, 1H). 13C NMR (125 MHz): −1.4
(q); 23.6 (t); 25.4 (t); 31.8 (t); 72.8 (d); 169.0 (s).
Compound Catalyst
T (°C)/t Yield (%)
ee (%)
4.2.4. Cyclohexyl diazo(triisopropylsilyl)acetate 2c. Yield
91%, yellow oil. IR (NaCl): 2942s, 2866m, 2085s, 1684s,
1465m, 1254s, 1073w. 1H NMR (500 MHz, CDCl3):
1.13 (d, J=11.9, 18H); 1.24–1.49 (m, 8H); 1.52–1.63
(m, 1H); 1.63–1.80 (m, 2H); 1.87–1.97 (m, 2H); 4.79–
4.86 (m, 1H). 13C NMR (125 MHz): 11.5 (t); 18.3 (q);
23.9 (t); 25.4 (t); 31.9 (t); 73.3 (d); 169.7 (s). MS: 281
2b
2b
[Rh2{4S)-pttl}4]
25/2.5 h 4b: 65
5b: 17
31
27
33
0
–
–
[Rh2{(S)-nttl}4]
25/1 h
4b: 66
5b: 17
2d
2d
2d
[Rh2(OAc)4]b
[Rh2(OAc)4]
[Rh2{(S)-nttl}4]
110/2 h 4d: 29c
110/3 h 4d: 14d
25/2
4d: 34d
41
+
days
(M−C3H7 , 12), 199 (100), 131 (69), 103 (21), 101 (10),
2d
2d
[Rh2{(S)-pttl}4]
110/2 h 4d: 27d
42
43
84 (15). HR MS: 281.1724 (C14H25O2N2Si+; calcd
281.1685). Anal. calcd for C17H32O2N2Si (324.54): C,
62.92; H, 9.94; N, 8.63. Found: C, 62.81; H, 10.00; N,
8.51.
[Rh2{(4S)-bpttl}4]e 110/2.5 4d: 4d
h
a In PhCH3, 2% of catalyst.
b In PhCH3, 3% of catalyst.
c With purified 2d.
4.2.5. Synthesis of cyclohexyl diazo(dimethylphenyl-
silyl)acetate 2d. Diisopropylamine (135 mL, 0.96 mmol)
in Et2O (1.0 mL) was treated with BuLi (600 mL, 0.96
mmol) at −78°C. After 15 min the precooled (at −78°C)
diazo ester 1a (136 mg, 0.81 mmol) in Et2O (1.0 mL)
was added dropwise. After 30 min of stirring, precooled
dimethylphenylsilyl chloride (220 mL, 0.97 mmol) in
Et2O (1.0 mL) was added dropwise. After 1 h of
stirring, the mixture was warmed to rt, washed with
NaHCO3 (30 mL) which was extracted with Et2O (3×30
mL). The combined organic layers were dried (MgSO4),
filtered, and concentrated in vacuo, and the residue was
purified by flash chromatography (SiO2, pentane/
AcOEt, 98:2) to afford 2d, (370 mg, 16%). IR (neat):
2937m, 2092s, 1682s, 1257s, 1082w. 1H NMR (400
d Overall yield, two steps.
e In PhCH3, 1% of catalyst.
3. Conclusion
The present investigation shows that triorganylsilyl-
substituted alkyl diazoacetates undergo intramolecular
CH insertion in high yields and with encouraging enan-
tioselectivities, with appropriate Rh(II)-catalysts. Cur-
rent research is directed towards extension of this
methodology, in particular towards stereoselective
desilylation.

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P. Mu¨ller et al. / Tetrahedron: Asymmetry 14 (2003) 1503–1510
MHz, CDCl3): 0.56 (s, 6H); 1.29–1.42 (m, 5H); 1.48–
1.53 (m, 1H); 1.63–1.65 (m, 2H); 1.79–1.81 (m, 2H);
4.77–4.83 (m, 1H); 7.39–7.41 (m, 3H); 7.58–7.60 (m,
2H). 13C NMR (100 MHz): −2.0 (q); 22.3 (t); 25.3 (t);
31.7 (t); 42.8 (s); 73.0 (d); 127.9 (t); 133.8 (t). MS: 302
(M+, 2), 192 (36), 177 (19), 135 (100), 83 (28), 55 (31).
HR MS: 302.1470 (C16H22O2N2Si+; calcd 302.1450).
4.3.3. trans-9-(Trimethylsilyl)-7-oxabicyclo[4.3.0]nonan-
8-one 4b. Colorless oil, [h]2D0=−5.0 (c 1.00, EtOH for
1
33% ee). H NMR (500 MHz, CDCl3): 0.14 (s, 9H);
1.25–1.44 (m, 3H); 1.51 (qd, J=11.9, 3.6, 1H); 1.67–
1.79 (m, 3H); 1.89–1.96 (m, 2H); 2.18–2.21 (m, 1H);
3.62–3.68 (m, 1H). 13C NMR (125 MHz): −2.4 (q); 24.1
(t); 25.5 (t); 29.2 (t); 30.0 (t); 36.7 (d); 46.8 (d); 85.5 (d);
178.6 (s). MS: 212 (M+, 3), 197 (16), 153 (13), 122 (26),
94 (23), 73 (100), 59 (24). HR MS: 212.1213
(C11H20O2Si+; calcd 212.1232). Enantiomer separation
by GC (Lip-E, 2 min at 100°C, 1°C/min to 150°C, 10
min; ~1=49.1, ~2=52.7 min).
4.2.6. trans-4-tert-Butylcyclohexyl diazo(triethylsilyl)-
acetate 3a. Yield 88% according to Section 4.2.1; yellow
solid. IR (CHCl3): 3019m, 2094s, 1671m, 1272w, 1214s.
1H NMR (500 MHz, CDCl3): 0.76 (q, J=7.9, 6H); 0.85
(s, 9H); 0.99 (t, J=7.9, 9H); 1.11 (qd, J=13.2, 3.1, 2H);
1.30 (qd J=13.2, 3.2, 2H); 1.79–1.82 (m, 2H); 2.05 (td,
J=12.6, 4.4, 2H); 4.65–4.72 (m, 1H). 13C NMR (125
MHz): 3.2 (t); 7.0 (q); 25.3 (t); 27.5 (q); 32.3 (t); 42.9 (s);
47.0 (d); 74.0 (d); 169.4 (s). MS: 338 (M+, 1), 309 (2),
115 (100), 103 (23), 87 (37), 57 (53). HR MS: 338.2368
(C18H34O2N2Si+; calcd 338.2390).
4.3.4. (1S,6S,9R)-9-(Dimethylphenylsilyl)-7-oxabicyclo
[4.3.0]nonan-8-one 4d. The diazo decomposition was
carried out according to the general procedure (Section
4.3.1). Colorless oil. [h]2D0=−13.9 (EtOH, c 1.07, for
43% ee). IR (NaCl): 2939s, 2861m, 1760s, 1200w,
1
1069w, 1025m. H NMR (MHz, CDCl3): 0.49 (s, 3H);
0.50 (s, 3H); 1.06 (qd, J=12.3, 3.5, 1H); 1.10–1.86 (m,
7H); 1.96 (d, J=12.6, 1H); 2.15–2.19 (m, 1H); 3.65 (td,
J=11.3, 3.8, 1H); 7.36–7.42 (m, 3H); 7.57 (dd, J=7.2,
1.6, 2H). 13C NMR (500 MHz): −4.9 (q); −3.2 (q); 24.0
(t); 28.9 (t); 30.0 (t); 36.6 (t); 46.9 (d); 85.6 (d); 127.9
(d); 129.5 (d); 133.9 (fd); 136.0 (s); 178.4 (s). MS: 274
(M+, 17), 259 (29), 197 (27), 135 (100), 121 (24), 103
(26), 75 (17), 55 (14). HR MS: 274.1378 (C16H22O2Si+;
calcd 274.1389).
4.2.7. cis-4-tert-Butylcyclohexyl diazo(triethylsilyl)-acet-
ate 3b. Yield 91% according to Section 4.2.1; yellow
oil. IR (CHCl3): 3019m, 2093m, 1668m, 1266w, 1215s.
1H NMR (500 MHz, CDCl3): 0.77 (q, J=8.0, 6H); 0.87
(s, 9H); 0.99 (t, J=8.0, 9H); 1.28 (qd, J=12.6, 3.1 2H);
1.47 (tt, J=14.1, 2.8, 2H); 1.60 (dd, J=12.6, 1.8, 2H);
1.97 (td, J=15.1, 2.8, 2H); 5.09 (quint. J=2.5, 1H). 13C
NMR (125 MHz): 3.3 (t); 7.1 (q); 21.7 (t); 27.4 (q); 30.8
(t); 32.5 (s); 43.3 (s); 47.5 (d); 70.1 (d); 169.6 (s). MS:
338 (M+, 1), 309 (1), 115 (100), 103 (21), 87 (38), 57
(59). HR MS: 338.2372 (C18H34O2N2Si+; calcd
338.2390).
4.3.5. cis-9-(Trimethylsilyl)-7-oxabicyclo[4.3.0]nonan-8-
one 5b (data obtained from mixture with 4b). Colorless
1
oil, H NMR (500 MHz, CDCl3): 0.16 (s, 9H); 1.12–
1.20 (m, 1H); 1.24–1.46 (m, 2H); 1.46–1.56 (m, 2H);
1.67–1.77 (m, 2H); 1.88–1.94 (m, 2H); 2.14 (d, J=6.0,
1H); 2.16–2.23 (m, 1H); 2.29–2.35 (m, 1H); 3.62–3.67
(m, 1H); 4.33–4.35 (m, 1H). 13C NMR (125 MHz): −1.2
(q); 19.5 (t); 23.8 (t); 26.7 (t); 27.6 (t); 38.9 (d); 39.9 (d);
79.7 (d); 179.3 (s). Enantiomer separation by GC (b-
Dex, 5 min at 120°C, 1°C/min to 180°C, 20 min;
~1=45.0, ~2=46.5 min).
4.3. Diazo decomposition of cyclohexyl diazo-(triorganyl-
silyl)acetates 2a–2d, 3a,b
4.3.1. General procedure. To a suspension of catalyst
([Rh2L4], 2 mol%) under Ar was added the diazoester 2
or 3 (ca. 150 mg, 0.50 mmol) in the appropriate solvent
(2.5 mL) in 10 min at rt. The mixture was stirred for the
time and at the temperature indicated in Tables 1–5.
Progress of the reaction was monitored by TLC. After
completion of the reaction, the mixture was evaporated
and the residue purified by flash chromatography,
(SiO2, pentane/AcOEt, 97:3).
4.3.6. (1S,3S,6S,9R)-3-tert-Butyl-9-(triethylsilyl)-7-oxa-
bi cyclo[4.3.0]nonan-8-one 6. Colorless oil. [h]2D0=−0.6 (c
1.00, EtOH for 77% ee). IR (neat): 2951s, 2873m,
1757s, 1457m, 1181m, 1072m. 1H NMR: (500 MHz,
CDCl3): 0.67–0.75 (m, 6H); 0.88 (s, 9H); 0.99 (t, J=8.2,
9H); 0.99–1.08 (m, 1H); 1.12–1.27 (m, 2H); 1.49–1.56
(m, 1H); 1.77–1.86 (m, 2H); 1.94–2.01 (m, 2H); 2.21–
2.25 (m, 1H); 3.57–3.62 (m, 1H). 13C NMR (125 MHz):
2.7 (t); 7.3 (q); 25.0 (t); 27.6 (q); 29.8 (t); 32.4 (s); 33.7
(d); 46.9 (d); 47.9 (d); 85.8 (d); 179.1 (s). MS: 281
4.3.2.
(1S,6S,9R)-9-(Triethylsilyl)-7-oxabicyclo[4.3.0]-
nonan-8-one 4a. Colorless oil, [h]2D0=−16.1 (c 1.02,
+
CHCl3 for 66% ee). IR (NaCl): 2947s, 2875s, 1760s
1198w, 1135w, 1027m. H NMR (500 MHz, CDCl3):
(M−C2H5 , 100), 237 (13), 157 (25), 103 (38), 87 (31),
1
75 (31), 57 (51). HR MS: 281.1922 (C16H29O2Si+; calcd
281.1937). Enantiomer separation by GC (b-Dex, 5 min
at 140°C, 1°C/min to 180°C, 20 min; ~1=53.2, ~2=53.7
min).
0.68–0.76 (m, 6H); 0.99 (t, J=7.9, 9H); 1.23–1.45 (m,
3H); 1.52 (qd, J=12.0, 3.8, 1H); 1.77–1.81 (m, 2H);
1.83 (s, 1H); 1.90–1.96 (m, 2H); 2.20–2.23 (m, 1H);
3.63–3.68 (m, 1H). 13C NMR (125 MHz): 2.7 (t); 7.3
(q); 24.1 (t); 29.2 (t); 30.2 (t); 33.4 (d); 47.0 (d); 85.6 (d);
178.8 (s). MS: 254 (M+, 1), 225 (100), 181 (16), 153 (10),
103 (26), 75 (20), 59 (19). HR MS: 254.1687
(C14H26O2Si+; calcd 254.1702). Enantiomer separation
by GC (b-Dex, 5 min at 120°C, 1°C/min to 180°C, 20
min; ~1=52.2, ~2=52.9 min).
4.3.7.
rel-(4S,7S)-7-tert-Butyl-3-(triethylsilyl)-1-oxa-
spiro[3,5] nonan-2-one 7a. Yield 4–5%. Colorless oil. IR
1
(neat): 2951s, 2868m, 1798s, 1168m, 1080w. H NMR:
(300 MHz, CDCl3): 0.67–0.76 (m, 6H); 0.85 (s, 9H);
1.00 (t, J=8.1, 9H); 0.99–1.06 (m, 1H); 1.29–1.45 (m,
2H); 1.62–1.77 (m, 4H); 1.92–1.98 (m, 1H); 2.06–2.13

P. Mu¨ller et al. / Tetrahedron: Asymmetry 14 (2003) 1503–1510
1509
(m, 1H); 2.92 (s, 1H). 13C NMR (75 MHz): 3.9 (t); 7.3
(q); 23.3 (t); 23.7 (t); 27.4 (q); 32.3 (s); 34.9 (t); 38.6 (t);
46.5 (d); 48.7 (d); 80.0 (d); 171.5 (s). MS: 310 (M+, 1),
281 (52), 237 (100), 209 (35), 157 (10), 87 (35), 103 (49),
57 (56). HR MS: 310.2310 (C18H34O2Si+; calcd
310.2328).
4.4.3. (1R,3S,6S)-3-tert-Butyl-7-oxabicyclo[4.3.0]nonan-
8-one 9b.16 Yield 68%, white solid, [h]2D0=−42.6 (c 0.98,
1
EtOH for 89% ee). H NMR (300 MHz, CDCl3): 0.87
(s, 9H); 0.93–1.27 (m, 3H); 1.48–1.60 (m, 1H); 1.87–2.04
(m, 3H); 2.17–2.26 (m, 2H); 2.50 (dd, J=16.1, 6, 1H);
3.72 (td, J=10.9, 3.9, 1H). 13C NMR (75 MHz): 25.0
(t); 27.7 (q); 29.0 (t); 29.9 (t); 32.5 (s); 36.1 (t); 44.7 (d);
47.5 (d); 85.3 (d); 176.9 (s). Enantiomer separation by
GC (Lip-E, 2 min at 120°C, 1°C/min to 150°C, 20 min;
~1=41.8, ~2=43.1 min).
4.3.8. (1R,3R,6S,9R)-3-tert-Butyl-9-(triethylsilyl)-7-oxa-
bicyclo[4.3.0]nonan-8-one 8. White solid. Mp 68°C.
[h]2D0=−18.5 (c 1.01, EtOH for 66% ee). IR (neat):
2951s, 2868m, 1744s, 1160s, 1010m. 1H NMR (500
MHz, CDCl3): 0.66–0.78 (m, 6H); 0.83 (s, 9H); 0.84–
0.97 (m, 2H); 0.97–1.00 (t, J=8.2, 9H); 1.10–1.16 (m,
1H); 1.53–1.60 (m, 2H); 1.73–1.77 (m, 1H); 2.27–2.32
(m, 3H); 4.32–4.33 (m, 1H).13C NMR (125 MHz): 4.0
(t); 7.6 (q); 20.7 (t); 27.3 (q); 28.3 (t); 28.7 (t); 32.3 (s);
36.9 (d); 40.0 (d); 45.9 (d); 79.5 (d); 179.4 (s). MS: 310
(M+, 3), 281 (100), 237 (14), 211 (15), 137 (46), 115 (25),
103 (51), 57 (94). HR MS: 310.2315 (C18H34O2Si+; calcd
310.2328). Enantiomer separation by GC (b-Dex, 5 min
at 140°C, 1°C/min to 180°C, 20 min; ~1=53.2, ~2=53.7
min).
4.4.4. cis-7-Oxabicyclo[4.3.0]nonan-8-one 10a.16 (Data
from mixture with 9a.) Colorless oil, 1H NMR (500
MHz, CDCl3): 0.16 (s, 9H); 1.12–1.20 (m, 1H); 1.24–
1.46 (m, 2H); 1.46–1.56 (m, 2H); 1.67–1.77 (m, 2H);
1.88–1.94 (m, 2H); 2.14 (d, J=6.0, 1H); 2.16–2.23 (m,
1H); 2.29–2.35 (m, 1H); 3.62–3.67 (m, 1H); 4.33–4.35
(m, 1H). 13C NMR (125 MHz): 19.8 (t); 22.7 (t); 27.1
(t); 27.7 (t); 34.8 (t); 37.4 (d); 79.1 (d); 177.5 (s).
Enantiomer separation by GC (b-Dex, 5 min at 120°C,
1°C/min to 180°C, 20 min; ~1=45.0, ~2=46.5 min).
4.4.5. (1S,3R,6S)-3-tert-Butyl-7-oxabicyclo[4.3.0]nonan-
8-one 10b.16 Yield 52%, yellow oil. [h]2D0=−11.5 (c 1.00,
1
4.3.9.
rel-(4S,7R)-7-tert-Butyl-3-(triethylsilyl)-1-oxa-
EtOH for 64% ee). H NMR (300 MHz, CDCl3): 0.84
spiro[3,5] nonan-2-one 7b. Yield 27% with [Rh2{S)-
pttl}4]; 21% with Rh2{S)-nttl}4]; 26% with Rh2{S)-
bpttl}4]. Colorless oil. IR (neat): 2951s, 2868m, 1798s,
1168m, 1080w. 1H NMR: (300 MHz, CDCl3): 0.67–0.76
(m, 6H); 0.85 (s, 9H); 1.00 (t, J=8.1, 9H); 0.99–1.06 (m,
1H); 1.29–1.45 (m, 2H); 1.62–1.77 (m, 4H); 1.92–1.98
(m, 1H); 2.06–2.13 (m, 1H); 2.92 (s, 1H). 13C NMR (75
MHz): 3.9 (t); 7.3 (q); 23.3 (t); 23.7 (t); 27.4 (q); 32.3 (s);
34.9 (t); 38.6 (t); 46.5 (d); 48.7 (d); 80.0 (d); 171.5 (s).
MS: 310 (M+, 1), 281 (52), 237 (100), 209 (35), 157 (10),
87 (35), 103 (49), 57 (56). HR MS: 310.2310
(C18H34O2Si+; calcd 310.2328).
(s, 9H); 0.89–1.18 (m, 2H); 1.52–1.65 (m, 2H); 1.75–1.82
(m, 1H); 2.20 (d, J=16.7, 1H); 2.29–2.35 (m, 2H); 2.70
(dd, J=16.7, 6.6, 1H); 4.46–4.49 (m, 1H). 13C NMR (75
MHz): 20.6 (t); 27.3 (q); 28.3 (t); 29.0 (t); 32.3 (s); 36.2
(d); 38.9 (t); 45.6 (d); 78.9 (d); 177.6 (s). Enantiomer
separation by GC (Lip-E, 2 min at 120°C, 1°C/min to
150°C, 20 min; ~1=27.4, ~2=29.4 min).
4.4.6. rel-(4R,7R)-7-tert-Butyl-1-oxaspiro[3,5]nonan-2-
one 11b. Yield 69%, white solid. Mp=93°C. IR (neat):
2929s, 2863m, 1802s, 1202m, 1089w. 1H NMR (500
MHz, CDCl3): 0.87 (m, 9H); 1.04 (tt, J=12.2, 3.0, 1H);
1.35 (qd, J=12.9, 3.5, 2H); 1.67–1.78 (m, 4H); 2.02 (dd,
J=14.8, 4.6, 2H); 3.07 (s, 2H). 13C NMR (125 MHz):
23.2 (t); 27.4 (q); 32.4 (s); 35.9 (t); 46.5 (d); 47.3 (t); 78.4
4.4. Desilylation of 7-oxabicyclo[4.3.0]nonan-8-ones
(4a–4d, 6, 8) and spiro-lactone 7b
+
(s); 168.6 (s). MS: 152 (M−CO2 , 3), 140 (6), 122 (13),
96 (20), 95 (13), 80 (45), 67 (12), 57 (100). HR MS:
152.1569 (C11H20+; calcd 152.1565). Anal. calcd for
C12H20O2: C, 73.48; H, 10.27; found C, 73.48; H, 10.34.
4.4.1. General procedure. Tetrabutylammonium fluoride
(TBAF, 1 M in THF, 1.0 mL) was added dropwise to
the respective silane (ca. 0.5 mmol) in THF (1 mL) at
rt. After stirring for 2–4 h, H2O (2.0 mL) was added,
and the mixture was extracted with CH2Cl2. The
organic layer was dried (MgSO4) and concentrated in
vacuo. The crude product was purified by flash chro-
matography (SiO2, pentane/AcOEt, 97:3, then 95:5).
4.5. X-Ray structure of rac-8
C18−H3 34O2Si, Mr=310.6; v=0.13 mm−1, dx=1.078 g
(
cm , triclinic, P1, Z=2, a=6.7793(10), b=11.165(2),
,
c=13.662(3) A, h=111.94 (2), i=93.73(2), k=
3
,
90.28(2)°, V=956.7(5) A ; cell dimensions and intensi-
4.4.2. (1S,6S)-7-Oxabicyclo[4.3.0]nonan-8-one 9a. Yield
57%, colorless oil, [h]D20=−42.4 (c 0.93, for 61% ee). IR
(CHCl3): 2944m, 1777s, 1448w, 1191m, 1030s. 1H
NMR (500 MHz, CDCl3): 1.25–1.46 (m, 3H); 1.51–1.58
(qd, J=12.0, 3.8, 1H); 1.78–1.81 (m, 1H); 1.91–1.98 (m,
3H); 2.19–2.25 (m, 2H); 2.51 (dd, J=16.4, 6.6, 1H);
3.79 (td, J=10.4, 3.8, 1H). 13C NMR (125 MHz): 24.0
(t); 25.3 (t); 28.3 (t); 30.2 (t); 35.8 (t); 44.8 (d); 85.1 (d);
176.5 (s). MS: 141 (2), 140 (M+, 2), 139 (4), 111 (3), 96
(16), 83 (23), 68 (56), 67 (100), 55 (49). HR MS:
ties were measured at 200 K on a Stoe IPDS
diffractometer. Full-matrix least-squares refinement
based on F using weight of 1/(|2(Fo)+0.0001(Fo )) gave
2
final values R=0.041, ꢀR=0.038 and S=1.01(2) for
190 variables and 1090 contributing reflections.
Crystallographic data (excluding structure factors) for 8
have been deposited to the Cambridge Crystallographic
Data Base as supplementary publication number
CCDC 202750. Copies of the data can be obtained free
of charge on application to the CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: +44 (1223) 336-033;
e-mail: deposit@ccdc.cam.ac.uk).
+
140.0839 (C8H12O2 ; calcd 140.0837). Enantiomer sepa-
ration by GC (Lip-E, 2 min at 120°C, 1°C/min to
150°C, 20 min; ~1=34.9, ~2=35.7 min).

1510
P. Mu¨ller et al. / Tetrahedron: Asymmetry 14 (2003) 1503–1510
Chemistry; Dondoni, A., Ed.; JAI Press: London, 1993;
Acknowledgements
pp. 51–101.
5. Ayoama, T.; Iwamoto, Y.; Nishigaki, S.; Shioiri, T.
Chem. Pharm. Bull. 1989, 37, 253–256.
This work was supported by the Swiss National Science
Foundation (Projects No. 20-52581.97 and 2027-
048156) and by the European Commission for Science,
Research and Development (COST Action D12). The
authors are indebted to L. Nicolas for carrying out
parts of the experiments, A. Pinto and J.-P. Saulnier for
the NMR spectra, and D. Klink for the mass spectra.
6. Zaitseva, G. S.; Lutsenko, I. F.; Kisin, A. V.; Bakelov, Y.
L.; Lorberth, J. J. Organomet. Chem. 1988, 345, 253–262.
7. Mu¨ller, P.; Ene, D. unpublished work, cf. Ene, D. Ph.D.
Thesis, University of Geneva, Thesis No. 1995, 2783.
8. (a) Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Soey, S. E.
J. Org. Chem. 2002, 67, 2335–2344; (b) Aggarwal, V. K.;
Ferrara, M. Org. Lett. 2000, 2, 4107–4110.
9. Hori, R.; Aoyama, T.; Shioiri, T. Tetrahedron Lett. 2000,
41, 9455–9458.
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