A practical synthesis of enantiopure 4,5-dihydroisoxazole-5-carboxylic acids

Article abstract of DOI:10.1055/s-2005-921894

The 1,3-dipolar cycloaddition of a variety of aromatic and aliphatic nitrile oxides to 2,5-trans-2,5-diphenylpyrrolidine derived acrylamide and cinnamamide efficiently affords the corresponding 4,5-dihydroisoxazole-5- carboxamides in a highly regio- and s

Full text of DOI:10.1055/s-2005-921894

LETTER
2899
A Practical Synthesis of Enantiopure 4,5-Dihydroisoxazole-5-carboxylic Acids
S
ynthesis of Enant
b
iopure 4,5-D
e
ihydroisox
l
azole-5-carbo
R
xylic
A
cids os,a Eleuterio Alvarez,a Hansjörg Dietrich,b Rosario Fernández,*c José M. Lassaletta*a
a
b
c
Instituto de Investigaciones Químicas, CSIC-Use, c/ Américo Vespucio 49, Isla de la Cartuja, 41092 Seville, Spain
Bayer CropScience GmbH, Industriepark Höchst G836, 65926 Frankfurt, Germany
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apdo. de Correos 553, 41071 Seville, Spain
Fax +34(95)4460565; E-mail: jmlassa@iiq.csic.es
Received 7 September 2005
the good diastereofacial differentiation observed in relat-
ed contexts was also taken into account.8
Abstract: The 1,3-dipolar cycloaddition of a variety of aromatic
and aliphatic nitrile oxides to 2,5-trans-2,5-diphenylpyrrolidine
derived acrylamide and cinnamamide efficiently affords the corre-
sponding 4,5-dihydroisoxazole-5-carboxamides in a highly regio-
and stereoselective manner. The cycloaddition of aliphatic nitrile
oxides to the analogue methacrylamide proceeds also smoothly to
afford the expected cycloadducts in moderate yields and very high
regio- and stereoselectivity. In sharp contrast, aromatic nitrile
oxides react with the same amide to afford 5-methyl-4,5-dihy-
droisoxazole-5-carboxamides in higher yields but as near 1:1 mix-
tures of diastereoisomers. Acid hydrolysis of these products
afforded enantiopure 4,5-dihydroisoxazole-5-carboxylic acids.
a,b-Unsaturated amides 1a and 1b, readily available by
acylation of (S,S)-2,5-diphenylpyrrolidine with acryloyl
and cinnamoyl chlorides under standard conditions, were
made to react with several nitrile oxides, obtained in situ
from hydroximoyl chlorides 2–8 in the usual way9
(Scheme 1). The reaction proceeded smoothly in all cases
to give the expected adducts 9–21 in variable yields. The
results collected in Table 1 indicate the generality of the
method, illustrated by cycloadditions of both amides 1a
and 1b to aromatic (2–4, entries 1–5) and aliphatic (5–8,
entries 6–13) substrates. In addition to the excellent dias-
tereoselectivities observed in the generation of the new
stereogenic centers at C-4 and C-5, it is worth mentioning
that only trans-cycloadducts 10, 13, 15, 17, 19, and 21
were observed from cinnamoyl enamide 1b, thereby
excluding any epimerization of the products. Moreover,
the reaction proved to be highly regioselective in all cases,
a fact attributed to the repulsive steric interactions expect-
ed between the R group and the bulky 2,5-diphenylpyrro-
lidine moiety in the opposite regioisomer.
Key words: asymmetric synthesis, cycloadditions, heterocycles,
nitrile oxides, isoxazolines
The 1,3-dipolar cycloaddition is a fundamental tool for
the synthesis of a number of five-membered heterocyclic
compounds.1 As a case of particular relevance, the 1,3-di-
polar cycloaddition of nitrile oxides to alkenes provides a
straightforward route to the 4,5-dihydroisoxazole ring, a
structural motif in some biologically active compounds2
and a useful synthetic intermediate for the synthesis of a
variety of bifunctional building blocks and bioactive
compounds.1,3,4 There are a number of methodologies
available for the stereochemical control of the reaction,5
most of them based on the use of chiral auxiliaries.
Though the selective Lewis acid activation of the
dipolarophiles in the presence of nitrile oxides and the
amine bases required for its synthesis is particularly diffi-
cult, some catalytic approaches have also been reported.6
Nevertheless, there are still limitations in most cases
regarding substrate generality (in particular for aliphatic
substrates), chemical yields, regioselectivity and/or
stereoselectivity. We now wish to report the results
collected by using 2,5-trans-diphenylpyrrolidine as a suit-
able auxiliary in the stereo- and regioselective 1,3-dipolar
cycloadditions of a,b-unsaturated amides 1a–c with
nitrile oxides.
O
Ph
Ph
OH
+
Et3N, r.t.
N
O
N
N
R'
N
Et2O or CH2Cl2
R
Ph
R
Cl
O
Ph
R'
2–8
1a: R = H
9–21
1b: R = Ph
Scheme 1 1,3-Dipolar cycloaddition of a,b-unsaturated amides
1a,b.
The more challenging extension of this methodology for
the synthesis of products bearing quaternary stereogenic
centers at C-5 was also investigated by reacting substrates
2–5 and 8 with methacrylamide 1c as the dipolarophile
(Scheme 2, Table 1, entries 14–18).
In this case, a different behavior for aliphatic and aromatic
substrates was observed: the former (e.g., 5 or 8) reacted
slowly to afford products 25 and 26 in moderate yields,
but with complete regio- and diastereoselectivity (entries
17 and 18). In sharp contrast, aromatic substrates 2–4
react faster to afford cycloadducts 22–24 in higher yields
and with high regioselectivity, but with negligible de (en-
tries 14–16). A retro-cyclization path leading to a thermo-
dynamically controlled product distribution was
The 2,5-trans-diphenylpyrrolidine, available in both
enantiomeric forms from inexpensive starting materials,7
was chosen as a C2-symmetric auxiliary in order to
circumvent any consideration related to the conformation-
al free rotation around the amide C–N bond. Additionally,
SYNLETT 2005, No. 19, pp 2899–2904
0
1
.1
2
.2
0
0
5
Advanced online publication: 27.10.2005
DOI: 10.1055/s-2005-921894; Art ID: G27205ST
© Georg Thieme Verlag Stuttgart · New York

2900
A. Ros et al.
LETTER
Ph
O
Ph
O
OH
Cl
CO2H
HCl, AcOH
Me
O
Et3N
N
N
N
N
N
+
∆
Et2O or CHCl3
Ph
R
R
R'
R
O
Ph
R'
2–5, 8
1c
(R)-9: R = Ph; R' = H
(R)-27: R = Ph; R' = H, 80%
(R)-28: R = i-Bu; R' = H, 73%
(R,R)-29: R = R' = Ph, 60%
(R)-16: R = i-Bu; R' = H
(R,R)-10: R = R' = Ph
Ph
Ph
N
O
N
N
Ph
O
O
N
+
O
Ph
Ph
CO2H
Me
N
HCl, AcOH
O
N
N
O
R
R
Ph
O
∆
Me
Ph
Me
Ph
62%
Me
(R)-22
(R)-22–26
(S)-22–24
(R)-30
Scheme 2 1,3-Dipolar cycloadditions of methacrylamide 1c.
Scheme 3 Release of the chiral auxiliary.
experimentally discarded: pure (R)- and (S)-22 cycload-
ducts were heated separately under the reaction conditions
without any perceptible epimerizations.
compound (R)-27 had [a]D22 –194 (c 0.5, MeOH) and this
value was compared with reported data for (R)-27 (sample
20
of ee = 68%: [a]D –116)13 and (S)-27 (sample of
ee = 60%: [a]D +67 (c 0.4, CHCl3).14 Additionally, com-
Reductive release of the chiral auxiliary by reagents such
as LiEt3BH (amide to alcohol)10 or the Schwartz reagent
(amide to aldehyde)11 failed in our case. Hydrolysis by
HCl–AcOH, however, afforded the desired 4,5-dihy-
droisoxazole-5-carboxylic acids 27–30 (Scheme 3).
20
pound (R)-30 had [a]D –131 (c 0.14, MeOH) and the
optical rotation was compared with reported data for (S)-
30 (sample of ee = 75%: [a]D +109).13 Assuming
20
uniform reaction pathways for the cycloadditions of 2–8
to cinnamamide 1b and acrylamide 1a, the R configura-
tion of 11, 12, 14, 16, 18, and 20 and the R,R configuration
of 13, 15, 17, 19, and 21 were assigned by analogy with 9
and 10, respectively.
The absolute R,R configuration of the newly created
stereogenic centers in cycloadduct 10 was determined by
single-crystal X-ray diffraction analysis12 (Figure 1),
while that of (R)-27, (R)-30 and the parent cycloadducts
(R)-9 and (R)-22 were deduced after comparison of the
optical rotation of the former with literature data. Thus,
Table 1 1,3-Dipolar Cycloaddition of Nitrile Oxides 2–8 to Amides 1a–c: Synthesis of Isoxazolines 9–26
Entry Sub-
strate
R
Amide Solvent Product
Timea Yield
(%)b
de (%)c
>99
1
2
Ph
1a
1b
Et2O
Et2O
1 h
98
Ph
Ph
N
N
O
N
N
Ph
Ph
O
9
2
2
Ph
48 h
50 (18) >99
O
Ph
Ph
N
O
O
Ph
10
3
4
3
4
1a
1a
Et2O
Et2O
1 h
90
95
>99
>99
Cl
Cl
Ph
Cl
N
Ph
Cl
Cl
O
N
Cl
11
1 h
Ph
O
Cl
O
MeO
N
Ph
O
Cl
CO2Me
12
Synlett 2005, No. 19, 2899–2904 © Thieme Stuttgart · New York

LETTER
Synthesis of Enantiopure 4,5-Dihydroisoxazole-5-carboxylic Acids
2901
Table 1 1,3-Dipolar Cycloaddition of Nitrile Oxides 2–8 to Amides 1a–c: Synthesis of Isoxazolines 9–26 (continued)
Entry Sub-
strate
R
Amide Solvent Product
Timea Yield
(%)b
de (%)c
85 (>99)d
Cl
5
4
1b
Et2O
48 h
96
Ph
O
Cl
N
O
MeO
N
Cl
CO2Me
Ph
O
Ph
Cl
13
6
7
5
5
n-Pentyl
1a
1b
CH2Cl2
CH2Cl2
0.7 h 92
>99
Ph
Ph
O
O
N
N
N
Ph
O
14
n-Pentyl
6 d
58 (30) >99
N
Ph
O
Ph
15
16
8
9
6
6
i-Bu
i-Bu
1a
1b
CH2Cl2
CH2Cl2
1 h
7 d
72 (15) >99
Ph
Ph
O
O
N
N
N
Ph
Ph
O
O
40 (30) >99
N
Ph
17
18
10
11
7
7
i-Pr
i-Pr
1a
1b
CH2Cl2
CH2Cl2
1 h
7 d
72
50
>99
>99
Ph
N
O
N
Ph
O
Ph
O
N
N
Ph
N
O
O
Ph
19
20
12
13
8
8
Cy
Cy
1a
1b
CH2Cl2
CH2Cl2
1.2 h 90
99
Ph
N
Ph
O
6 d
60 (10) 99
Ph
N
O
N
Ph
O
Ph
21
14
2
Ph
1c
Et2O
10 d
47
0 (>99)d,e
Ph
Me
Ph
O
N
N
O
Ph
N
+
N
Ph
Ph
O
O
Me
Ph
(R)-22
(S)-22
Synlett 2005, No. 19, 2899–2904 © Thieme Stuttgart · New York

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A. Ros et al.
LETTER
Table 1 1,3-Dipolar Cycloaddition of Nitrile Oxides 2–8 to Amides 1a–c: Synthesis of Isoxazolines 9–26 (continued)
Entry Sub-
strate
R
Amide Solvent Product
Timea Yield
(%)b
de (%)c
0 (>99)f
15
16
3
1c
Et2O
4 d
98
Cl
Cl
Ph
Me
O
Ph
N
Cl
N
O
N
+
N
Ph
O
Cl
Cl
O
Cl
Me
Ph
(R)-23
(S)-23
4
1c
Et2O
4 d
90
0g
Cl
Cl
O
N
Cl
Ph
Ph
Me
N
N
O
N
+
Ph
O
Cl
CO2Me
Cl
CO2Me
O
Me
Cl
Ph
CO2Me
(R)-24
(S)-24
17
18
5
8
n-Pentyl
1c
1c
CHCl3
CHCl3
10 dh 52
>99
>99
Ph
O
N
N
Ph
O
Me
25
Cy
10 dh 50
Ph
N
O
O
N
Ph
Me
26
a For reactions performed at r.t. unless indicated otherwise.
b Yield of isolated product. In parenthesis: yield of recovered, unreacted amide 1.
c Determined by 1H NMR and 13C NMR analysis of the crude reaction mixtures.
d After column chromatography.
e The absolute configurations of (R)- and (S)-22 were assigned tentatively by analogy of their characterization data with (R)- and (S)-23.
f Pure (S)-23 was obtained by fractional crystallization.
g Inseparable mixture of diastereomers.
h Performed at 55 °C.
The absolute configuration of (S)-23 was also determined
by single-crystal X-ray diffraction15 (Figure 2), while
those of (R)- and (S)-22 were assigned tentatively by
analogy of their characterization data with (R)- and (S)-
23.
The high inductions observed for the cycloadditions of
nitrile oxides to 1a and 1b and the absolute configurations
at C-4 and C-5 can be explained as the result of the shield-
ing of the si face of the C=C double bond of the dipolaro-
phile by the neighbour phenyl group in the pyrrolidine
moiety in the preferred s-cis conformation (Figure 3).
Such a difference is anticipated in view of the higher steric
CH(b)–auxiliary interactions in the s-trans conformer.
Apparently, the high inductions and the absolute configu-
rations of the products 25 and 26 of the cycloadditions of
aliphatic nitrile oxides to 1c are also consistent with a
similar analysis, but in this case the preference for the s-
cis conformer is not clear in view of the similar steric
interactions that arise from C(b)H2–auxiliary or CH3–aux-
iliary contacts in both rotamers.
Figure 1 Crystal structure of (R,R)-10. H atoms omitted for clarity.
Synlett 2005, No. 19, 2899–2904 © Thieme Stuttgart · New York

LETTER
Synthesis of Enantiopure 4,5-Dihydroisoxazole-5-carboxylic Acids
2903
(10 mL). The mixture was stirred at r.t. and monitored by TLC.
Brine (10 mL) was added and the aqueous layer was extracted with
Et2O (3 × 15 mL). The organic layer was dried (Na2SO4), concen-
trated, and the residue was purified by flash chromatography.
Method B
Et3N (0.66 mmol, 95 mL) was added dropwise to a solution of amide
1a–c (0.22 mmol) and hydroximoyl chloride 5–8 (0.66 mmol) in
CH2Cl2 (10 mL). The mixture was treated as in method A.
Selected Data
Compound 9: mp 80–82 °C; [a]D20 –379 (c 1.09, CHCl3). 1H NMR
(500 MHz, CDCl3): d = 1.77 (dd, 1 H, J = 12.5 Hz, J = 6.5 Hz), 1.82
(dd, 1 H, J = 12.0 Hz, J = 6.0 Hz), 2.43 (m, 1 H), 2.58 (m, 1 H), 3.03
(dd, 1 H, J = 17.0 Hz, J = 11.0 Hz), 4.01 (dd, 1 H, J = 17.0 Hz,
J = 7.5 Hz), 4.83 (dd, 1 H, J = 11.0 Hz, J = 7.5 Hz), 5.55 (d, 1 H,
J = 8.5 Hz), 5.84 (d, 1 H, J = 8.0 Hz), 7.17–7.38 (m, 15 H). 13C
NMR (125 MHz, CDCl3): d = 30.5, 32.9, 36.2, 61.9, 62.6, 79.0,
125.1, 125.6, 125.8, 126.9, 127.6, 128.6, 128.9, 129.0, 130.2, 142.2,
143.4, 157.3, 167.1. MS (EI): m/z (rel. intensity) = 396 (13) [M+],
365 (47), 91 (100). HRMS: m/z calcd for C26H24N2O2: 396.1838;
found: 396.1828.
Figure 2 Crystal structure of (S)-23. H atoms omitted for clarity.
Si face: hindered attack
20
1
Compound 19: [a]D –424 (c 0.87, CHCl3). H NMR (400 MHz,
CDCl3): d = 0.93 (d, 3 H, J = 7.0 Hz), 1.07 (d, 3 H, J = 7.0 Hz), 1.73
(dd, 1 H, J = 12.5 Hz, J = 6.4 Hz), 1.78 (dd, 1 H, J = 12.5 Hz,
J = 6.4 Hz), 2.30 (m, 1 H), 2.34 (m, 1 H), 2.52–2.54 (m, 1 H), 4.48
(d, 1 H, J = 6.8 Hz), 4.94 (d, 1 H, J = 6.8 Hz), 5.49 (d, 1 H, J = 8.4
Hz), 5.78 (d, 1 H, J = 8.0 Hz), 6.91–7.30 (m, 15 H). 13C NMR (100
MHz, CDCl3): d = 19.5, 20.4, 26.9, 30.4, 32.9, 57.0, 61.9, 62.6,
86.2, 125.2, 125.4, 126.9, 127.3, 127.5, 128.0, 128.6, 128.8, 128.9,
137.3, 142.3, 143.2, 166.4, 167.6. MS (EI): m/z (rel. intensity) = 438
(14) [M+], 188 (71), 91 (100). Anal. Calcd for C29H30N2O2: C,
79.42; H, 6.89; N, 6.39. Found: C, 79.52; H, 6.75; N, 6.05.
Ph
Ph
O
N
C
R
O
O
N
H
O
H
N
N
Ph
Ph
R'
R'
R'
O
N
C
R
Re face: favored attack
Figure 3
Synthesis of Compound 27
To a solution of 9 (395 mg, 1 mmol) in AcOH (4 mL) was added 6
N HCl (2 mL) and the mixture was stirred at 100 °C for 40 h. The
mixture was then co-evaporated several times with toluene and the
In conclusion, the excellent facial discrimination by the
2,5-diphenylpyrrolidine makes it a convenient auxiliary
which very efficiently controls the stereochemical course residue was purified by flash chromatography (24:1 EtOAc–AcOH)
yielding 153 mg (80%) of 27 as a white semi-solid: [a]D20 –194 (c
of the cycloaddition reactions of amides 1a,b with nitrile
oxides, affording single diastereomers in practically all
cases. A limited success was encountered in the extension
of the methodology for the synthesis of cycloadducts
containing stereogenic centers: the cycloadditions to
methacrylamide 1c are substrate-dependent and proceed
with high selectivity for aliphatic substrates only.
20
0.45, MeOH) {lit.14 (80:20 S/R mixture): [a]D +67 (c 0.41,
CHCl3)}. 1H NMR (300 MHz, MeOD): d = 3.58 (dd, 1 H, J = 17.1
Hz, J = 6.9 Hz), 3.71 (dd, 1 H, J = 17.1 Hz, J = 11.7 Hz), 5.13 (dd,
1 H, J = 11.4 Hz, J = 6.9 Hz), 7.36–7.65 (m, 5 H). 13C NMR (75
MHz, MeOD): d = 39.9, 79.4, 128.0, 129.9, 130.1, 131.6, 157.9,
174.0. MS (EI): m/z (rel. intensity) = 191 (46) [M+], 146 (100), 118
(71), 77 (93). Anal. Calcd for C10H9NO3: C, 62.82; H, 4.74; N, 7.33.
Found: C, 62.62; H, 4.92; N, 7.28.
Compound 30: (R)-22 was hydrolysed as described for 27 and puri-
fied by flash chromatography (30:1 EtOAc–AcOH) to afford 30
(62%) as a syrup: [a]D20 –131 (c 0.14, MeOH). 1H NMR (500 MHz,
CDCl3): d = 1.76 (s, 3 H), 3.28 (d, 1 H, J = 17.0 Hz), 3.87 (d, 1 H,
J = 17.0 Hz), 7.24–7.63 (m, 5 H). 13C NMR (125 MHz, CDCl3):
d = 23.3, 45.1, 85.9, 126.9, 128.5, 128.9, 130.8, 157.2, 175.9. MS
(EI): m/z (rel. intensity) = 206 (17) [M+ + 1], 160 (91), 123 (100).
HRMS: m/z calcd for C11H12NO3: 206.0817; found: 206.0807.
Hydroximoyl chlorides 2–816 and amides 1a17 and 1c8b were synthe-
sized according to literature procedures. Compound 1b was synthe-
sized by acylation of (S,S)-2,5-diphenyl-pyrrolidine with cinnamoyl
chloride under standard conditions: [a]D20 –209.3 (c 0.73, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.71 (dd, 1 H, J = 12.0 Hz, J = 5.7
Hz), 1.79 (dd, 1 H, J = 12.0 Hz, J = 5.7 Hz), 2.36 (m, 1 H), 2.50 (m,
1 H), 5.40 (d, 1 H, J = 8.1 Hz), 5.56 (d, 1 H, J = 8.1 Hz), 6.42 (d, 1
H, J = 15.3 Hz), 7.16–7.31 (m, 15 H), 7.49 (d, 1 H, J = 15.3 Hz). 13
C
NMR (75 MHz, CDCl3): d = 30.0, 32.6, 61.7, 61.9, 118.7, 124.8,
124.9, 126.2, 127.0, 127.3, 128.0, 128.1, 128.4, 129, 134.6, 141.7,
142.4, 143.4, 164.8. MS (EI): m/z (rel. intensity) = 354 (100) [M+ +
1], 353 (65) [M+], 249 (35). HRMS: m/z calcd for C25H24NO:
354.1858; found: 354.1846.
Acknowledgment
We thank the Spanish ‘Ministerio de Ciencia y Tecnología’ (grant
CTQ2004-00290 and CTQ2004-00241) and the ‘Junta de An-
dalucía’ for financial support. A.R. thanks Bayer CropScience for a
predoctoral fellowship and the donation of chemicals.
Synthesis of 3-Alkyl-5-formyl-4,5-dihydroisoxazoles (9–25)
Method A
Et3N (1.1 mmol, 159 mL) was added dropwise to a solution of amide
1a–c (1 mmol) and hydroximoyl chloride 2–4 (1.1 mmol) in Et2O
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A. Ros et al.
LETTER
(8) (a) Kozmin, S. A.; Rawal, V. H. J. Am. Chem. Soc. 1997,
119, 7165. (b) Taber, D. F.; Gorski, G. J.; Liable-Sands, L.
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(12) Crystal data for (R,R)-10: C32H28N2O2, M = 472.56,
monoclinic, space group P21, a = 13.4615 (9) Å,
b = 10.5455 (7) Å, c = 17.8450 (12) Å, b = 101.0960 (10)°,
V = 2485.9 (3) Å3, T = 100 K, Z = 4, l (Mo Ka1) = 0.71073
Å, 30258 reflections measured, 6046 unique (Rint = 0.0296)
which were used in all calculations. The final wR(F2) =
0.0848 (all data). Full crystallographic data for this structure
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication CCDC 265218.
These data can obtained free of charge on application to
CCDC, 12, Union Road, Cambridge CB2 1EZ, UK;
fax: +44 (1223)336033; or e-mail: deposit@ccdc.cam.ac.uk.
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1998, 98, 863. Recent examples: (b) Tamai, T.; Asano, S.;
Totani, K.; Takao, K.-i.; Tadano, K.-i. Synlett 2003, 1865.
(c) Faita, G.; Paio, A.; Quadrelli, P.; Rancati, F.; Seneci, P.
Tetrahedron 2001, 57, 8313. (d) Yamamoto H., Watanabe
S., Kadotani K., Hasegawa M., Noguchi M., Kanemasa S.;
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M.-H. Tetrahedron 1997, 53, 1971. (f) Oppolzer, W.;
Kingma, A. J.; Pillai, S. K. Tetrahedron Lett. 1991, 4893.
(g) Akiyama, T.; Okada, K.; Ozaki, S. Tetrahedron Lett.
1992, 5763. (h) Rispens, M. T.; Keller, E.; De Lange, B.;
Zijlstra, R. W. J.; Feringa, B. L. Tetrahedron: Asymmetry
1994, 5, 607.
(14) Kamimura, A.; Omata, Y.; Kakehi, A.; Shirai, M.
Tetrahedron 2002, 58, 8763.
(15) Crystal data for (S)-23: C27H24Cl2N2O2, Mr = 479.38,
orthorhombic, space group P212121 (no. 19), a = 6.2026 (4)
Å, b = 15.5003 (10) Å, c = 24.4725 (16) Å, V = 2352.8 (3)
Å3, T = 173 (2) K, Z = 4, l (Mo Ka1) = 0.71073 Å, 14856
reflections measured, 5519 unique (Rint = 0. 0311) which
were used in all calculations. The final wR(F2) = 0. 0617 (all
data). Full crystallographic data for this structure have been
deposited with the Cambridge Crystallographic Data Centre
as supplementary publication CCDC 265219. These data can
obtained free of charge on application to CCDC, 12, Union
Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033; or
e-mail: deposit@ccdc.cam.ac.uk.
(6) (a) Sibi, M. P.; Itoh, K.; Jasperse, C. P. J. Am. Chem. Soc.
2004, 126, 5366. (b) Shimizu, M.; Ukaji, Y.; Inomata, K.
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(7) (a) Chong, J. M.; Clarke, I. S.; Koch, I.; Olbach, P. C.;
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(b) Aldous, D. J.; Dutton, W. M.; Steel, P. G. Tetrahedron:
Asymmetry 2000, 11, 2455.
(16) Jae Nyong, K.; Eung, K. R. J. Org. Chem. 1992, 57, 6649.
(17) Nyerges, M.; Bendell, D.; Arany, A.; Hibbs, D. E.; Coles, S.
J.; Hursthouse, M. B.; Groundwater, P. W.; Meth-Cohn, O.
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Synlett 2005, No. 19, 2899–2904 © Thieme Stuttgart · New York