Ru(II)-catalyzed asymmetric cyclopropanation using chiral diphenylphosphino(oxazolinyl)quinoline ligands

Article abstract of DOI:10.1016/S0957-4166(99)00190-1

Several chiral 8-diphenylphosphino-2-oxazolinylquinolines were synthesized starting from 2-cyano-8-hydroxyquinoline. These N,N,P-chelates were successfully employed in the Ru(II)-catalyzed asymmetric cyclopropanation reactions of diazo-alkenes. The cataly

Full text of DOI:10.1016/S0957-4166(99)00190-1

Pergamon
Tetrahedron: Asymmetry 10 (1999) 1903–1911
Ru(II)-catalyzed asymmetric cyclopropanation using chiral
diphenylphosphino(oxazolinyl)quinoline ligands
Sang-Wook Park, Jeong-Ho Son, Sung-Gon Kim and Kyo Han Ahn ∗
Department of Chemistry and Center for Biofunctional Molecules, Pohang University of Science and Technology,
San 31 Hyoja-dong, Pohang, 790-784 South Korea
Received 26 March 1999; accepted 6 May 1999
Abstract
Several chiral 8-diphenylphosphino-2-oxazolinylquinolines were synthesized starting from 2-cyano-8-
hydroxyquinoline. These N,N,P-chelates were successfully employed in the Ru(II)-catalyzed asymmetric
cyclopropanation reactions of diazo-alkenes. The catalytic system exhibited good reactivity and high thermal
stability and provided high yields in the intramolecular cyclopropanation, albeit somewhat decreased
enantioselectivities compared to known catalytic systems. A dramatic dependency of the enantioselectivity
on the substituents of the oxazoline ring was observed. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
The development of chiral ligands for transition metal catalyzed asymmetric reactions has been inten-
sively pursued with the aim of obtaining efficient catalytic systems. As an ongoing project in this area,
we have been involved in the synthesis of chiral oxazoline-containing chelates such as biferrocene-based
bis(oxazolines) 1 for Cu(I)-catalyzed asymmetric cyclopropanation reactions between diazoacetates
and alkenes.1 Although our catalytic system provided high enantioselectivities for certain substrates,
it exhibited a decreased reactivity compared to the Cu(I) catalysts of malonate-based bis(oxazolines) 2.2
When the catalytic reaction is slow, dimerization of the diazoacetates is problematic and thus low yields
result. This is particularly true in the case of less reactive substrates. Recently, Nishiyama and co-workers
have reported an efficient catalytic system, a Ru(II)–pybox complex 3.3 The ruthenium catalyst exhibited
improved trans/cis-selectivity in addition to excellent enantioselectivity in the cyclopropanation. More-
over, the corresponding Ru–carbene complex, a presumed reaction intermediate, exhibited significant
chemical stability as characterized by NMR spectroscopy.4
∗
Corresponding author. E-mail: ahn@vision.postech.ac.kr
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00190-1

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Considering the apparent stability of the ruthenium complex, we were interested in a hybrid ligand
system such as N,N,P-chelates 4. These heterochelates are reminiscent of the N,P-chelates 5, which have
been proven to be excellent ligands in several transition metal catalyzed asymmetric reactions.5 However,
chelates 4 would exhibit totally different behavior in the catalytic reactions, owing to the presence of the
central nitrogen donor. Here we wish to report an efficient synthesis of these N,N,P-chelates, starting
from readily available 8-hydroxyquinoline, and their application to the Ru(II)-catalyzed asymmetric
cyclopropanation.
2. Synthesis of 8-diphenylphosphino-2-oxazolinylquinolines DPOQ 4
2-Cyano-8-hydroxyquinoline 7, prepared from 8-hydroxyquinoline 6 by the literature procedure,6 is an
adequate starting material for the synthesis of the target molecules. The oxazoline moiety could be intro-
duced by ZnCl2-catalyzed condensation between the nitrile group and the corresponding aminoalcohols,7
and the diphenylphosphino group could be introduced by the Ni(0)-catalyzed coupling reaction between
the triflate of the hydroxyl group and diphenylphosphine.8 a This synthetic plan was realized and the
results are summarized in Scheme 1. We found that the ZnCl2-catalyzed oxazoline formation gave better
yields when the 8-hydroxyl group was converted to the corresponding triflate; otherwise, in the presence
of the free hydroxyl group, lower yields were obtained.8b In the presence of 10 mol% of ZnCl2, the
condensation of L-valinol and nitrile 8 in refluxing chlorobenzene provided the corresponding oxazoline
9a in 77% yield. Oxazoline 9a could be purified further by recrystallization from ethyl acetate–hexanes
if necessary. Similarly, oxazolines 9b and 9c were synthesized in good yields. Introduction of the
phosphino group was successfully done by the Ni(0)-catalyzed coupling reaction between oxazoline
9 and diphenylphosphine.8a Thus, treatment of the oxazoline 9a with diphenylphosphine in the presence
of 10 mol% of NiCl2(dppe) and two molar equivalents of DABCO in DMF at 80°C for 8 h gave the
corresponding DPOQ 4a in 43% isolated yield. If the reaction was carried out at 100°C as in the literature,
the coupling yield decreased. It could be purified further by recrystallization. Other DPOQs 4b and 4c
were synthesized under the same reaction conditions in similar yields.
Scheme 1.

S.-W. Park et al. / Tetrahedron: Asymmetry 10 (1999) 1903–1911
1905
3. Cyclopropanation catalyzed by Ru(II)–DPOQ complexes
Nishiyama explained the trans/cis- and enantioselectivities observed in the cyclopropanation reaction
by a face-selective approach of an olefin to the Ru–carbene complex.3 The pybox ligand has C2 symmetry
and thus only a single isomeric metal–carbene complex would be generated. In contrast, the Ru–DPOQ
system can have two diastereomeric metal–carbene complexes. Therefore, both the diastereomeric
complexes should be taken into consideration in the explanation of the selectivities (Scheme 2). The
diphenyl groups at the phosphorus atom would shield one side of the π-face of the metal–carbene
complex, providing one open quadrant for the approach of a diazo group. With those ligands optimized
for this scenario, we may expect high selectivity for the cyclopropanation. Recently, Nishiyama and co-
workers reported unsymmetrical ligands that shield only one quadrant. The catalytic system provided up
to 94% ee for the intermolecular cyclopropanation of olefins.9
Scheme 2.
We studied the Ru(II)-catalyzed asymmetric cyclopropanation of diazo-enes using DPOQ as the
ligands. Both inter- and intramolecular cyclopropanations were studied, following the experimental
procedure of Nishiyama and co-workers.3 The reaction between ethyl diazoacetate and styrene was
carried out in the presence of 2 mol% of Ru(II)–DPOQ complex, maintaining a low concentration of
styrene during the reaction (by syringe-pump addition).† Although yields were good, disappointingly
low enantioselectivities were observed (Table 1). Also, somewhat decreased trans/cis-selectivity was
observed compared to that observed with the Nishiyama catalyst. At this point, we focused our attention
on the intramolecular cyclopropanation of diazo-enes. Compared to the intermolecular cyclopropanation
reaction, relatively few catalytic systems for the corresponding intramolecular reaction have been
reported.10 Also, the enantioselectivities of the catalytic cyclopropanation reactions are known to be
greatly dependent on the substrates used. The intramolecular reaction was carried out using 5 mol%
of the catalyst. Optimal reaction conditions were determined for the reaction of diazo-ene 11.3 It was
found that the reaction proceeded well at 0°C, indicating that our catalytic system has much improved
reactivity compared to the bis(oxazoline) 1–Cu(I) complexes. The catalytic reaction proceeded at normal
concentrations (0.2 M solution), which removed the need for the syringe-pump addition of diazo
compounds. Under these conditions, side products were not observed. The enantioselectivity was greatly
dependent on the solvent used: 75% ee was observed in chloroform while 25% ee was obtained in 1,2-
dichloroethane. The results are summarized in Table 2.
†
The trans/cis-selectivity was determined by NMR analysis of the products and the enantioselectivity of each isomer was
determined by GC analysis after converting the ester products into the corresponding diastereomeric amides using (S)-α-
phenethylamine.

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Table 1
Intermolecular cyclopropanations
Table 2
Intramolecular cyclopropanations
A particularly interesting result is that, depending on the ligands used, a dramatic change in the sense
and extent of the enantioselectivity was observed. Under the same reaction conditions, the ruthenium
complex of 4c gave the (1R,5S)-isomer in 75% ee while that of 4a gave the (1S,5R)-isomer in 9% ee.
The catalytic system of 4b produced an almost racemic mixture. This is quite surprising, considering that
these ligands are structurally similar. A simple molecular modeling study for the two diastereomeric
metal–carbene complexes in Scheme 2 indicated that the sterically demanding ligand 4c causes a
significant difference in the minimized energy between the two, while 4b does not.‡ However, because
we do not know whether the stability of the metal–carbene complexes leads to the enantioselectivity or
not, a further study is necessary to provide a more convincing explanation for the observation. Several
other substrates 12–1511 were studied, but poor to moderate selectivities were observed, showing once
again a large fluctuation in the enantioselectivity depending on the substrates used (Table 3). It is notable
that the cyclopropanation of less reactive substrate 14 gave the corresponding keto-ester 19 in 60% ee
‡
MacSpartan plus® from Wavefunction, Inc. (http://www.wavefun.com) was used as the modeling program.

S.-W. Park et al. / Tetrahedron: Asymmetry 10 (1999) 1903–1911
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Table 3
Intramolecular cyclopropanationsa
and 68% yield.§ The reaction required the refluxing temperature of chloroform. This result indicates that
the catalytic system is thermally robust. A further modification including fine-tuning of the substituents
of the donor atoms in DPOQ would provide more efficient ligand systems.
In summary, we have synthesized several chiral phosphino(oxazolinyl)quinolines, starting from 8-
hydroxyquinoline. The new N,N,P-chelates are found to be potentially useful ligands in the ruthenium-
catalyzed asymmetric intramolecular cyclopropanation. A dramatic dependency of the enantioselectivity
on the substituents of the oxazoline ring was observed. A further structural modification to enhance the
enantioselectivity is under study.
4. Experimental
4.1. General
All reactions were carried out under an argon atmosphere. Solvents were dried and purified prior to use.
All the reagents were commercial products otherwise unspecified and used without further purification.
Purification by chromatography means flash column chromatography performed on silica gel (230–400
mesh). Melting points determined are uncorrected.
§
For this substrate, the Cu(I)–bis(oxazoline) 1 system did not give the reaction product.

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4.2. 2-Cyano-8-(trifluoromethanesulfonyloxy)quinoline 8
To a solution of 2-cyano-8-hydroxyquinoline (2.0 g, 1.8 mmol) and pyridine (1.1 mL, 13 mmol) in
dry dichloromethane (7 mL) at 0°C was added dropwise triflic anhydride (2.5 mL, 15 mmol), and the
resulting solution was allowed to warm to room temperature and stirred for 1 h. The mixture was treated
with a saturated aqueous NH4Cl solution and extracted with dichloromethane. The organic phase was
washed with brine, dried, and concentrated. The resulting solid was purified by chromatography (eluent:
50% dichloromethane in hexanes) to give the product (3.6 g, 11.3 mmol) in 95% yield. 1H NMR (CDCl3,
300 MHz) δ 8.45 (d, 1H, J=8.5 Hz), 7.94–7.99 (m, 1H), 7.83 (d, 1H, J=8.5 Hz), 7.78–7.75 (m, 2H); 13
C
NMR (CDCl3, 75 MHz) δ 145.9, 141.3, 138.2, 135.1, 130.3, 129.5, 128.6, 125.4, 123.7, 121.4, 117.2;
19F NMR (CDCl3, 300 MHz) δ 3.84 (reference: CF3CO2H in D2O); MS (EI) m/z 302.00 (M+, 20%).
4.3. (S)-2-(4-Isopropyl-2-oxazolin-2-yl)-8-(trifluoromethanesulfonyloxy)quinoline 9a
To a solution of nitrile 8 (2.50 g, 8.3 mmol) and zinc chloride (113 mg, 0.83 mmol) in chlorobenzene
(15 mL) at 25°C, was added dropwise a solution of L-valinol (1.28 g, 12.4 mmol) in chlorobenzene (5
mL). The reaction mixture was refluxed for 24 h. Most of the solvent was evaporated at reduced pressure,
and the residue was dissolved in dichloromethane. The organic phase was washed with a saturated
aqueous ammonium chloride solution, dried, and filtered. The filtered solution was concentrated and
the residue was purified by chromatography (20% ethyl acetate in hexanes) to give the oxazoline in 77%
yield (2.46 g, 6.3 mmol). Mp 89.5°C; [α]D24 −75.3 (c 0.17, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 8.35
(d, 1H, J=8.6 Hz), 8.27 (d, 1H, J=8.6 Hz), 7.87 (dd, 1H, J=5.8, 1.9 Hz), 7.67–7.58 (m, 2H), 4.61 (dd, 1H,
J=8.5, 1.0 Hz), 4.29 (t, 1H, J=8.5 Hz), 4.22–4.14 (m, 1H), 1.93–1.86 (m, 1H), 1.07 (d, 3H, J=6.7 Hz),
0.97 (d, 3H, J=6.7 Hz); 13C NMR (CDCl3, 75 MHz) δ 163.2, 148.7, 146.6, 140.7, 136.8, 130.4, 128.3,
127.7, 123.1, 122.2, 121.4, 73.5, 71.7, 33.4, 19.4, 18.9; 19F NMR (CDCl3, 300 MHz) δ 2.74 (reference:
CF3CO2H in D2O). Anal. calcd for C16H15F3O4N2S: C, 49.48; H, 3.89; N, 7.21. Found: C, 49.20; H,
3.93; N, 7.14.
4.4. (S)-2-(4-Phenyl-2-oxazolin-2-yl)-8-(trifluoromethanesulfonyloxy)quinoline 9b
Using a similar procedure, oxazoline 9b was prepared in 82% yield (2.3 g, 5.4 mmol), starting from
24
nitrile 8 (2.0 g, 6.62 mmol) and (S)-phenylglycinol (1.0 g, 7.28 mmol). [α]D −109.8 (c 1.05, CHCl3);
1H NMR (CDCl3, 300 MHz) δ 8.45–8.40 (m, 1H), 8.29 (d, 1H, J=8.7 Hz), 7.88 (t, 1H, J=6.4 Hz),
7.67–7.63 (m, 2H), 7.40–7.34 (m, 5H), 5.56–5.48 (m, 1H), 5.00 (dd, 1H, J=8.7, 1.7 Hz), 4.47 (t, 1H,
J=8.7 Hz); 19F NMR (CDCl3, 300 MHz) δ 3.30 (reference: CF3CO2H in D2O); MS (EI) m/z 422.1.
4.5. (S)-2-(4-tert-Butyl-2-oxazolin-2-yl)-8-(trifluoromethanesulfonyloxy)quinoline 9c
Using a similar procedure, oxazoline 9c was prepared in 83% yield (2.2 g, 5.5 mmol), starting from
24
nitrile 8 (2.0 g, 6.62 mmol) and (S)-tert-leucinol (0.985 g, 7.28 mmol). Mp 110–111°C; [α]D −28.6
1
(c 0.14, CHCl3); H NMR (CDCl3, 300 MHz) δ 8.34 (d, 1H, J=8.6 Hz), 8.24 (d, 1H, J=8.6 Hz), 7.84
(dd, 1H, J=7.9, 1.6 Hz), 7.63–7.58 (m, 2H), 4.53 (dd, 1H, J=10.3, 8.8 Hz), 4.36 (t, 1H, J=8.7 Hz), 4.15
(dd, 1H, J=10.3, 8.7 Hz), 0.98 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 163.1, 148.7, 146.5, 140.6, 136.7,
130.4, 128.3, 127.6, 123.1, 122.2, 121.4, 76.9, 70.1, 34.5, 2.64; 19F NMR (CDCl3, 300 MHz) δ 3.25
(reference: CF3CO2H in D2O). Anal. calcd for C17H17F3O4N2S: C, 50.74; H, 4.26; N, 6.96. Found: C,
50.69; H, 4.16; N, 6.74.

S.-W. Park et al. / Tetrahedron: Asymmetry 10 (1999) 1903–1911
1909
4.6. (S)-8-Diphenylphosphino-2-(4-isopropyl-2-oxazolin-2-yl)quinoline 4a
A mixture of NiCl2(dppe) (410 mg, 0.77 mmol) and diphenylphosphine (0.40 mL, 2.3 mmol) in DMF
was heated at 100°C for 30 min, and then it was cooled to 80°C. To this mixture was added a solution
of oxazoline 9a (3.0 g, 7.72 mmol) and 1,4-diazabicyclo[2.2.2]octane (1.73 g, 15.4 mmol) in DMF (10
mL) through a cannula. Additional diphenylphosphine (1.2 mL, 6.7 mmol) was added, and the resulting
mixture was stirred for 8 h at 80°C. After cooling the reaction mixture to room temperature, most of the
DMF was removed by vacuum distillation. The residue was diluted with dichloromethane and washed
successively with 5% aqueous Na2S2O3, 10% aqueous citric acid solution, and brine. The organic phase
was dried and concentrated. The residue was purified by chromatography (50% ethyl ether in hexanes)
24
1
to give the product in 43% yield (1.49 g, 3.51 mmol). Mp 161.1°C; [α]D −94.4 (c 0.23, CHCl3); H
NMR (CDCl3, 300 MHz) δ 8.16 (s, 2H), 7.79 (d, 1H, J=8.1 Hz), 7.74 (t, 1H, J=7.4 Hz), 7.39–7.29
(m, 10H), 7.28–7.22 (m, 1H), 4.45 (dd, 1H, J=8.5, 1.2 Hz), 4.15 (t, 1H, J=8.5 Hz), 4.10–4.06 (m, 1H),
1.86–1.80 (m, 1H), 1.02 (d, 3H, J=6.7 Hz), 0.90 (d, 3H, J=6.7 Hz); 13C NMR (CDCl3, 75 MHz) δ 163.8,
146.5, 141.0, 140.8, 137.84, 137.81, 137.69, 137.67, 136.89, 136.87, 134.9, 134.8, 134.7, 134.6, 134.5,
128.9, 128.7, 128.6, 128.1, 121.6, 73.3, 71.2, 33.4, 19.5, 18.8; 31P NMR (CDCl3, 121 MHz) δ −12.59
(reference: H3PO4 in D2O). Anal. calcd for C27H25ON2P: C, 76.40; H, 5.94; N, 6.60. Found: C, 76.30;
H, 5.85; N, 6.54.
4.7. (S)-8-Diphenylphosphino-2-(4-phenyl-2-oxazolin-2-yl)quinoline 4b
Using a similar procedure, ligand 4b was prepared in 46% yield (830 mg, 1.85 mmol), starting from
oxazoline 9b (1.7 g, 4.02 mmol). Mp 84°C; [α]D24 −95.4 (c 2.49, CHCl3); 1H NMR (CDCl3, 300 MHz)
δ 8.54 (d, 1H, J=8.3 Hz), 8.33–8.23 (m, 2H), 7.86 (d, 1H, J=2.1 Hz), 7.52–7.13 (m, 16H), 5.43–5.36 (m,
1H), 3.83–3.68 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 164.2, 148.3, 147.6, 139.7, 139.0, 138.5, 135.2,
134.8, 134.7, 134.6, 134.4, 129.6, 129.4, 129.2, 129.12, 129.06, 129.01, 128.8, 128.7, 128.4, 127.2,
119.5, 54.4, 48.2; 31P NMR (CDCl3): δ −10.13 (reference: H3PO4 in D2O). Anal. calcd for C30H23ON2P:
C, 78.59; H, 5.06; N, 6.11. Found: C, 78.21; H, 4.72; N, 6.18.
4.8. (S)-8-Diphenylphosphino-2-(4-tert-butyl-2-oxazolin-2-yl)quinoline 4c
Using a similar procedure, ligand 4c was prepared in 47% yield (710 mg, 1.64 mmol), starting from
24
1
oxazoline 9c (1.4 g, 3.48 mmol). Mp 74–76°C; [α]D −93.5 (c 0.23, CHCl3); H NMR (CDCl3, 300
MHz) δ 8.16 (s, 2H), 7.79 (d, 1H, J=8.0 Hz), 7.45 (t, 1H, J=7.6 Hz), 7.39–7.26 (m, 10H), 7.23–7.19
(m, 1H), 4.39 (dd, 1H, J=10.3, 1.5 Hz), 4.24 (t, 1H, J=8.5 Hz), 4.05 (dd, 1H, J=10.3, 1.5 Hz), 0.93 (s,
9H); 13C NMR (CDCl3, 75 MHz) δ 163.7, 146.5, 140.9, 140.8, 137.8, 137.7, 136.8, 134.9, 134.8, 134.7,
134.6, 134.5, 128.9, 128.8, 128.7, 128.6, 128.1, 121.7, 76.7, 69.7, 34.4, 26.4; 31P NMR (CDCl3, 121
MHz) δ −12.86 (reference: H3PO4 in D2O). Anal. calcd for C28H27ON2P: C, 76.69; H, 6.21; N, 6.39.
Found: C, 76.39; H, 6.19; N, 6.50.
4.9. Representative procedure of the intermolecular cyclopropanation
A mixture of [RuCl2(p-cymene)]2 (24 mg, 0.04 mmol) and DPOQ 4a (34 mg, 0.08 mmol) in dry
dichloromethane (15 mL) was stirred for 1.5 h at 25°C. To this ruthenium complex was added styrene
(2.3 mL, 20 mmol) using a syringe, followed by a solution of ethyl diazoacetate (456 mg, 4.0 mmol) in
dichloromethane (5 mL) for 8 h using a syringe pump. The resulting mixture was stirred for a further 8

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S.-W. Park et al. / Tetrahedron: Asymmetry 10 (1999) 1903–1911
h. The reaction mixture was concentrated and subjected to chromatography (10% ethyl ether in hexanes)
to afford trans/cis-cyclopropanecarboxylates in 59% yield (450 mg). The trans/cis-ratio was determined
by 1H NMR analysis (diagnostic peaks: 4.19 ppm (trans-isomer); 3.89 ppm (cis-isomer)). Enantiopurity
of each isomer was determined by GC analysis (column HP-1; oven temp 180°C; flow rate 1.0 mL/min):
tR: trans-isomer, 57.8 min (minor), 62.7 min (major); cis-isomer, 43.4 min (minor), 47.9 min (major)
for the corresponding amides that were prepared in 93% yield by transamidation of the products with
(S)-1-phenylethylamine in the presence of trimethylaluminum in refluxing 1,2-dichloroethane for 3 h. l-
Menthyl 2-phenylcyclopropanecarboxylates: the trans/cis-ratio was similarly determined: trans-isomer,
4.7 ppm; cis-isomer, 4.4 ppm. The enantioselectivity was determined by GC analysis (column HP-1;
oven temp 180°C, flow rate 1.0 mL/min): tR: cis-(1S,2R)-isomer, 36.3 min; cis-(1R,2S)-isomer, 37.9
min; trans-(1R,2R)-isomer, 44.1 min, trans-(1S,2S)-isomer, 46.7 min.
4.10. Representative procedure for the intramolecular cyclopropanation
A solution of [RuCl2(p-cymene)]2 (15.3 mg, 0.025 mmol) and ligand 4c (21.9 mg, 0.05 mmol) in
dry chloroform was stirred for 1.5 h at 25°C. The ruthenium complex was cooled to 0°C and treated
with a solution of 1-diazo-6-methyl-5-hepten-2-one (11) (152 mg, 1.0 mmol) in chloroform (2 mL) by
a cannula. The reaction mixture was stirred for 8 h at 0°C. The mixture was concentrated and subjected
to chromatography (10% ethyl ether in hexanes) to afford 6,6-dimethyl[3.1.0]bicyclohexan-2-one (16)
in 90% yield (112 mg). The enatiopurity of the product was determined by GC analysis (chiral column
G-TA, oven temp 110°C, flow rate 1 mL/min): tR: (1R,5S)-isomer, 8.7 min; (1S,5R)-isomer, 10.7 min.
Under similar reaction conditions other substrates were subjected to the cyclopropanation and isolated
similarly. The enantiopurity of the cyclopropanation products were similarly determined by GC analysis
using the same chiral column except for compound 19. The conditions and retention times are given as
follows: product 17 (oven temp 110°C, flow rate 1 mL/min): tR: major isomer, 17.1 min; minor isomer,
16.3 min; product 18 (oven temp 110°C, flow rate 1 mL/min): tR: major (1R,5S)-isomer, 4.4 min; minor
(1S,5R)-isomer, 5.0 min; product 20 (oven temp 140°C, flow rate 1 mL/min): tR: major (1R,5S)-isomer,
7.8 min; minor (1S,5R)-isomer, 11.5 min. The enantiopurity of compound 19 was determined by 1H NMR
analysis using a chiral shift reagent, Eu(hfc)3: one of the diagnostic peaks was the methyl carboxylate
group: δ 4.02 (minor), 4.00 (major).
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G.; Noe, M. C.; Corey, E. J. Tetrahedron Lett. 1995, 36, 8745. (d) Doyle, M. P.; Peterson, C. S.; Parker Jr., D. L. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1334. (e) Piqué, C.; Fähndrich, B.; Pfaltz, A. Synlett 1995, 491. (f) Doyle, M. P.; Peterson,
C. S.; Zhou, Q. L.; Nishiyama, H. Chem. Commun. 1997, 211.
11. The diazo compounds were synthesized according to the literature procedures. 11–13: Mori, K.; Matsui, M. Tetrahedron
1969, 25, 5013. 14: Taber, D. F.; Ruckle Jr., R. E.; Hennessy, M. J. J. Org. Chem. 1986, 51, 4077. 15: Doyle, M. P.; Austin,
R. E.; Bailey, A. S.; Dwyer, M. P.; Dyatkin, A. B.; Kalinin, A. V.; Kwan, M. M. Y.; Liras, S.; Oalmann, C. J.; Pieters, R.
J.; Protopopova, M. N.; Raab, C. E.; Roos, G. H. P.; Zhou, Q. L.; Martin, S. F. J. Am. Chem. Soc. 1995, 117, 5763.