Perfluorinated Bis(dihydrooxazole) complexes immobilized on fluorous reversed-phase silica gel as recyclable catalysts for enantioselective dielsi-alder reactions

Article abstract of DOI:10.1002/hlca.201200380

The three different perfluoroalkyl-tagged bis(dihydrooxazole)copper complexes 19-21 were synthesized and immobilized noncovalently on fluorous reversed-phase silica gel (FRPSG) by fluorous-fluorous interactions (Schemes2 and 3). These supported catalysts were successfully applied to asymmetric Diels-Alder reactions in H₂O and in CH₂Cl₂ (Schemea 4). Besides high conversion of the dienophile, we observed enantiomer excesses of up to 88% in H₂O and 97% in CH₂Cl₂, and we were able to recover and re-use these catalytic systems several times. Despite the relatively high catalyst loading, the leaching of copper was remarkably low ranging from 2.4 to 5.9 ppm.

Full text of DOI:10.1002/hlca.201200380

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Helvetica Chimica Acta – Vol. 95 (2012)
Perfluorinated Bis(dihydrooxazole) Complexes Immobilized on Fluorous
Reversed-Phase Silica Gel as Recyclable Catalysts for Enantioselective
DielsꢀAlder Reactions
by Eva M. Hensle and Willi Bannwarth*
Institut fꢀr Organische Chemie und Biochemie, Albert-Ludwigs-Universitꢁt Freiburg, Albertstr. 21,
D-79104 Freiburg (phone: þ 49-761-2036073, fax: þ 49-761-2038705,
e-mail: willi.bannwarth@organik.chemie.uni-freiburg.de)
Dedicated to Prof. Dieter Seebach on the occasion of his 75th birthday
The three different perfluoroalkyl-tagged bis(dihydrooxazole)copper complexes 19 – 21 were
synthesized and immobilized noncovalently on fluorous reversed-phase silica gel (FRPSG) by
fluorousꢀfluorous interactions (Schemes 2 and 3). These supported catalysts were successfully applied
to asymmetric DielsꢀAlder reactions in H2O and in CH2Cl2 (Scheme 4). Besides high conversion of the
dienophile, we observed enantiomer excesses of up to 88% in H2O and 97% in CH2Cl2, and we were able
to recover and re-use these catalytic systems several times. Despite the relatively high catalyst loading,
the leaching of copper was remarkably low ranging from 2.4 to 5.9 ppm.
Introduction. – Fluorous biphasic systems (FBS), originally published in a seminal
´
´
paper by Horvath and Rabai in 1994, allow for a simple catalyst recovery after catalytic
processes. This is achieved by applying a biphasic system consisting of a fluorous and an
organic solvent. Due to the perfluorinated ligands, the catalyst is located in the fluorous
phase, while the substrate and reagents are dissolved in the organic phase [1]. This
concept has been applied to numerous catalytic reactions, e.g., hydroboration of
alkenes [2a][2b], oxidation of aldehydes [2c], Wacker oxidation of alkenes [2d], and
Pd-catalyzed allylic nucleophilic substitution [2e]. Our research group has applied this
concept to CꢀC coupling reactions using perfluoro-tagged Pd-complexes (Scheme 1)
Scheme 1. Perfluoro-Tagged Phosphine Ligands and the Corresponding Pd-Complexes
ꢂ 2012 Verlag Helvetica Chimica Acta AG, Zꢀrich

Helvetica Chimica Acta – Vol. 95 (2012)
2073
[3]. In two of these Pd-complexes, i.e., in 1a and 1b, the perfluoro entities were directly
linked to the benzene rings of the ligands, whereas in complexes 1c – 1e, the electron-
withdrawing effect of the perfluoro-tag was reduced by a CH2CH2 or an OCH2 spacer,
respectively. These Pd-complexes were successfully applied in Stille coupling reactions
and could be re-used several times without significant loss in activity [3]. Furthermore,
the application was extended to Suzuki [4] and Sonogashira [5] couplings.
A disadvantage of the technology was the use of the perfluorinated solvents, which
are expensive and environmentally persistent. To circumvent the use of perfluorinated
solvents and still make use of fluorousꢀfluorous interactions, we have implemented
some time ago the concept of FRPSG-supported catalysis (FRPSG ¼ fluorous
reversed-phase silicia gel; Fig. 1). In this technology, the perfluoro-tagged catalyst is
noncovalently bound to the FRPSG by fluorousꢀfluorous interactions and directly
applied in an organic solvent. After the reaction, the catalyst is removed by filtration
and can be re-used. A similar strategy but with Teflon as solid support was pulished by
Gladysz and co-workers [6].
Fig. 1. Fluorous reversed-phase SiO2 (FRPSG)
In our previous work, we had established different perfluorinated silica gel-derived
solid supports (see 2 – 4) and had applied them successfully to a number of catalytic
processes such as Suzuki and Sonogashira reactions [7][8], ring-closing-metathesis
(RCM) reactions [9], and asymmetric hydrogenations [10].
Herein, we report on the application of the FRPSG-supported catalysis concept to
DielsꢀAlder reactions in H2O and CH2Cl2 employing perfluorinated bis(dihydroox-
azole) (box) ligands. To the best of our knowledge, only one example of a FRPSG-
supported Lewis acid as recyclable catalyst for DielsꢀAlder reactions has been reported
so far by Nishikido and co-workers, i.e., Sc[C(SO2C4F9)3]3 [11].
Results and Discussion. – The perfluoro-tagged ligands 5 – 7 employed in this study
were synthesized according to Scheme 2, starting from the enantiomerically pure
starting materials 8 – 10, which had been obtained by reduction of the corresponding
amino acids as reported [12]. Reaction of the 2-aminoethanols 8 – 10 with diethyl
methylmalonate followed by ring closure with p-toluenesulfonyl chloride (TsCl) in the
presence of N,N-dimethylpyridin-4-amine (DMAP) resulted in the corresponding
bis(dihydrooxazole) 11 – 13 in moderate to good yields [13][14]. Alkylation of these
[15] with 6-bromohexanoic acid methyl ester [16] and subsequent amide formation with
propane-1,3-diamine yielded the desired amides 14 – 16 in 47 – 79% [17]. The synthesis
of the activated N-succinimide-derived ester 18 started with the reaction of

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Scheme 2. Synthesis of the Perfluoro-Tagged box Ligands 5 – 7
a) Diethyl methylmalonate, 1108, 3 d; R ¼ Ph (R,R), 55 – 99%; R ¼ Ph (S,S), 46%; R ¼ t-Bu (S,S), 78%.
b) DMAP, Et3N, TsCl, CH2Cl2, r.t., 2 d; 11, 57 – 68%; 12, 58%; 13, 33 – 78%. c) BuLi, THF, ꢀ 788, ! 08,
6-bromohexanoic acid methyl ester, ! r.t., 2 h, reflux, 4 h; R ¼ Ph (R,R), 57 – 60%; R ¼ Ph (S,S), 66%;
R ¼ t-Bu (S,S), 43%. d) Propane-1,3-diamine, r.t., 2 d; 14, 75 – 77%; 15, 78%; 16, 69%. e) C6F13CH2CH2I,
Et2O, ꢀ 788, t-BuLi, ! 08, 30 min, ! ꢀ 788, 17, r.t., 24 h; 71 – 91%. f) 9-Borabicyclo[3.3.1]nonane (9-
BBN; 0.5m in THF), r.t., 20 h, 3m aq. NaOH, 35% aq. H2O2, r.t., 2 h; 65 – 90%. g) Disuccinimidyl
carbonate, Et3N, MeCN, r.t., 20 h; 31 – 48%. h) 18, THF, (i-Pr)2EtN, r.t., 1 h; 5, 59 – 83%; 6, 91%; 7, 70 –
75%.
trichloro(ethenyl)silane (17) and C6F13CH2CH2I [18]. A hydroboration/oxidation/
hydrolyses sequence delivered the corresponding perfluorinated hydroxysilane (not
shown in Scheme 2) [19], which was converted into the N-hydroxysuccinimide-derived
carbonate 18 by a treatment with disuccinimidyl carbonate and Et3N [20]. Finally, the
desired perfluoro-tagged ligands 5 – 7 were obtained in decent yields (59 – 91%) via
coupling of the activated 18 and the amides 14 – 16 in the presence of Hꢀnigꢃs base [21].
The noncovalent immobilization of the perfluorinated box ligands 5 – 7 on the
FRPSG 2 is outlined in Scheme 3. For the immobilization process, the perfluoro-tagged
ligands 5 – 7 were dissolved in THF, and Cu(OTf)2 was added which was followed by
FRPSG 2. Evaporation of the solvent yielded the desired immobilized air-stable
catalytic systems 19 – 21.
The envisaged DielsꢀAlder reaction of the dienophiles 22 – 24 with cyclopenta-1,3-
diene (25) for the evaluation the FRPSG-supported way of proceeding is outlined in
Scheme 4. We focused on the N-oxides and not the parent pyridinyl compounds since

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Scheme 3. Noncovalent Immobilization of the Ligands 5 – 7 on the Solid Support
Scheme 4. Enantioselective DielsꢀAlder Reactions with N-Oxides 22 – 24
a) 5 or 10 mol-% of 19 – 21, H2O, 58, 1 d. b) 10 mol-% of 19 – 21, CH2Cl2, 58, 45 min for 22, 4.5 h for 23,
and 6 h for 24.
the latter were reported to yield rather low ee values [22]. Initial experiments had
indicated that the exo-product was only obtained in minute amounts, hence, the
estimation of the ee values was carried out with respect to the endo-product. Since
fluorousꢀfluorous interactions are increasing with the polarity of the solvent, we tested
the reactions first in H2O. This would guarantee for a strong noncovalent interaction
between the support and the catalyst.
In earlier work on asymmetric hydrogenations, we had observed that silica gel or
perfluorinated silica gel had an influence on the outcome of the reactions [10]. To rule
this out for the present investigation, we performed the cycloaddition of all three
dienophiles with cyclopentadiene 25 in the presence of silica gel and perfluorinated

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silica gel 2 but without catalyst. The results (Table 1) indicated that for yet unknown
reasons, the presence of silica gel led to higher conversion rates compared to the
reactions without additive. Fortunately, this effect was not observed for the reactions in
the presence of perfluorinated silica gel 2. Hence the influence of the FRPSG 2 on the
envisaged reactions could be neglected.
Table 1. Influence of Silica Gel and Perfluorinated Silica Gel 2 on the DielsꢀAlder Reaction of 22 – 24
with 25 (control experiments) in H2O
Additive
Additive [mol-%]
Conversion [%]a)
endo/exo Ratioa)
22
23
24
–
–
10
5
10
5
44
93
93
44
43
94 : 6
95 : 5
96 : 4
94 : 6
94 : 6
b
SiO2
SiO2
2
)
)
b
2
–
–
10
5
10
5
10
51
57
14
14
95 : 5
96 : 4
96 : 4
95 : 5
95 : 5
b
b
SiO2
SiO2
2
)
)
2
–
–
10
5
10
5
3
23
19
3
76 : 24
87: 13
86 : 14
79 : 21
77: 23
b
b
SiO2
SiO2
2
)
)
2
3
a) Conversions and endo/exo ratios were determined by HPLC; they are the average of three
b
independent experiments. ) 500 ꢄ, 100 – 300 mm, 80 m2/g.
For the enantioselective DielsꢀAlder reactions of the N-oxides 22 – 24 with
cyclopentadiene 25 in H2O in the presence of 5 and 10 mol-% of the immobilized
chiral catalysts 19 – 21, the perfluoro-tagged ligands 5 – 7 were dissolved in THF,
Cu(OTf)2 and the FRPSG 2 were added, and the solvent evaporated (Scheme 3). The
reaction itself was carried out in H2O at 58 for 1 d, and after each run, the solid support
was filtered off, washed with MeCN, and re-used again. The results are summarized in
Table 2. For the Ph-substituted bis(dihydrooxazole) catalysts 19 and 20, high
conversions up to 99% and enantiomer excesses (ee) up to 88% were obtained in
the first run for all dienophiles. Surprisingly, with the t-Bu-substituted catalyst 21, lower
conversions and poor ee values were achieved. This might be an indication for the
involvement of stacking interactions in the transition state. The re-use of the
immobilized Cu-complexes was not only dependent on the catalyst but also on the
dienophile employed and was generally entailed with significantly reduced conversions
and lower ee values. The reason for this is yet unknown but might have its basis in the
limited stability of the copper complex in H2O. Being aware that the relatively high
catalyst loading might lead to a substantial leaching, we performed a reaction between
N-oxide 22 and cyclopentadiene 25 with 10 mol-% of all three FRPSG-supported
catalysts 19 – 21. Estimation of the copper values resulted in only 2.4 – 5.9 ppm of Cu in
the aqueous phase.

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Table 2. DielsꢀAlder Reactions of N-Oxides 22 – 24 with 25 in the Presence of Catalysts 19, 20, or 21 in
H2O
Catalyst
Catalyst [mol-%]
Conversion [%]a)b)
eeendo [%]a)b)
endo/exo Ratioa)
22
23
24
19
19
20
20
21
21
10
5
10
5
10
5
> 99 (53)
99 (50)
> 99 (72)
96 (60)
52
ꢀ 83 (ꢀ 40)
ꢀ 84 (ꢀ 30)
74 (43)
73 (32)
ꢀ 14
96 : 4 (95 : 5)
97: 3 (94 : 6)
97: 3 (95 : 5)
97: 3 (95 : 5)
94 : 6
47
ꢀ 14
94 : 6
19
19
20
20
21
21
10
5
10
5
10
5
99 (19)
90 (12)
93 (25)
76 (18)
24
ꢀ 75 (ꢀ 28)
ꢀ 72 (ꢀ 13)
77 (49)
75 (34)
ꢀ 10
97: 3 (96 : 4)
97: 3 (94 : 6)
97: 3 (96 : 4)
97: 3 (94 : 6)
96 : 4
18
ꢀ 7
95 : 5
19
19
20
20
21
21
10
5
10
5
10
5
89 (18)
69 (8)
77 (27)
62 (14)
5
ꢀ 86 (ꢀ 83)
ꢀ 88 (ꢀ 69)
87 (84)
88 (75)
ꢀ 5
75 : 25 (72 : 28)
75 : 25 (74 : 26)
75 : 25 (71 : 29)
74 : 26 (71 : 29)
79 : 21
3
ꢀ 4
80 : 20
a) The values in parentheses are for the second runs with the same catalyst. b) Conversions, eeendo, and
endo/exo ratios were determined by chiral HPLC, they are the average of three independent
experiments.
Since the recycling experiments in H2O were not really convincing, we decided to
switch from H2O to CH2Cl2 as reaction medium. We expected the fluorousꢀfluorous
interactions to be still high enough as to allow for a decent binding of the perfluoro-
tagged catalyst on the FRPSG. Control experiments with unmodified SiO2 and FRPSG
2 as additives to the reaction in CH2Cl2 had led to negligible conversions in the range of
2 – 5%. Fig. 2 shows the recycling properties of the chiral catalysts 19 – 21 in the
DielsꢀAlder reactions of 22 – 24 with 25. The obtained ee values are given in the legend
of the figure, and those in parentheses are for the second, third, fourth, and fifth runs
with the same catalyst. Overall, concerning recyclability and ee values, the results
looked much more promising than in H2O. Furthermore, the reactions were also
significantly faster in CH2Cl2 (45 min for 22, 4.5 h for 23, and 6 h for 24) compared to
H2O as reaction medium. High conversions and ee values were achieved for all three N-
oxides when Ph-substituted catalysts 19 and 20 were used, while the t-Bu-substituted
box complex 21 resulted again in poor enantiomer excesses. In addition, the re-usability
of 19 and 20 was found to be much better than for 21, and high ee values were obtained
even in the fifth run. Nevertheless, a decrease of conversion was observed during the
recycling experiments, and decent conversions were observed over three runs.
To shed more light on the nature of the catalytic process itself, we performed
filtration experiments of ongoing reactions in CH2Cl2. After filtration, the reaction
continued and led to the same conversion and enantiomer excess as in the reaction
without filtration. This was a clear indication that the reaction proceeded at least

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Helvetica Chimica Acta – Vol. 95 (2012)
Fig. 2. DielsꢀAlder reactions of N-oxides 22 – 24 with 25 in the presence of catalysts 19, 20, or 21 in
CH2Cl2. The ee values given below in parentheses are for the second, third, fourth, and fifth runs with the
same catalyst. N-Oxide 22: eeendo [%] with 19, ꢀ 97 (ꢀ 95, ꢀ 97, ꢀ 96, ꢀ 96); with 20, 91 (90, 92, 87, 89);
with 21, ꢀ 21 (ꢀ28). N-Oxide 23: eeendo [%] with 19, ꢀ 91 (ꢀ 92, ꢀ 86, ꢀ 90, ꢀ 78); with 20, 91 (91, 93,
84, 91); with 21, ꢀ 5 (ꢀ 9). N-Oxide 24: eeendo [%] with 19, ꢀ 94 (ꢀ 93, ꢀ 91, ꢀ 92, ꢀ 91); with 20, 91 (91,
90, 89, 89); with 21, ꢀ 4 (ꢀ2).
partially in a homogeneous fashion which is in accordance with the results obtained in
Suzuki reactions with FRPSG-supported Pd-complexes [8].
Assessment of the leaching using the same reaction as outlined above resulted in
3.3 – 5.0 ppm copper in the CH2Cl2 phase.
Conclusions. – We demonstrated that the principle of FRPSG-supported catalysts
could be extended to asymmetric bis(dihydrooxazol)copper complexes. The phenyl-
substituted FRPSG-supported perfluoro-tagged copper complexes 19 and 20 turned
out to be useful catalysts for enantioselective DielsꢀAlder reactions in H2O as well as in
CH2Cl2. Concerning recyclability, ee values, and reaction times, CH2Cl2 was superior as
reaction media and allowed for three runs with decent yields. In both solvent systems,
the leaching of copper was below 5.9 ppm.
We would like to thank the International Research Training Group (IRTG; Project No. 1038,
ꢅCatalysis and Catalytic Reactions in Organic Synthesisꢃ) for financial support. Furthermore, we would
like to thank Dr. M. Keller, Mrs. M. Schonhardt, and Mr. F. Reinbold for recording NMR spectra, Mr. C.
Warth and Dr. J. Wçrth for recording mass spectra, Mrs. A. Siegel for CHN analysis and Mrs. S. Hirth-
Walther for AAS meassurements.
Experimental Part
1. General. All reagents and solvents were of the highest purity available and were used without
further purification. CC ¼ Column chromatography. HPLC: Agilent-1050 system with binary pump,
sample changer, and diode-array detector; tR in min. Optical rotation: Perkin-Elmer-341-MC polar-
imeter; at 589 nm and 208, calculated according to the Drude equation [a]D ¼ (aexp · 100)/(c · d). NMR
Spectra: Bruker spectrometer; at 400.1 (1H), 100.6 (13C), and 235.4 MHz (19F); d in ppm rel. to Me4Si
(¼0 ppm) for 1H and rel. to CHCl3 (¼ 77.0 ppm) for 13C, resp., FCCl3 as internal standard for 19F, J in Hz.

Helvetica Chimica Acta – Vol. 95 (2012)
2079
MS: Thermo TSQ 700 or MAT 95XL (CI, HR-MS-CI) and TSQ 7000 (ESI, APCI, HR-MS-APCI); in m/
z (rel. %). Microanalysis (CHN): Vario-EL system from Elementaranalysesysteme GmbH.
2. (4R,4’R)-2,2’-Ethylidenebis[4,5-dihydro-4-phenyloxazole] (11; R ¼ Ph (R,R)), (4S,4’S)-2,2’-Ethyl-
idenebis[4,5-dihydro-4-phenyloxazole] (12; R ¼ Ph (S,S)), and (4S,4’S)-2,2’-Ethylidenebis[4-(1,1-dimeth-
ylethyl)-4,5-dihydrooxazole] (13; R ¼ t-Bu (S,S)). Diethyl methylmalonate and (2R)-phenylglycinol
(¼(bR)-b-aminobenzeneethanol), (2S)-phenylglycinol (¼(bS)-b-aminobenzeneethanol), or (2S)-tert-
leucinol (¼(2S)-2-amino-3,3-dimethylbutan-1-ol; 2.0 equiv.) were heated for 3 d to 1108. Recrystalliza-
tion from CHCl3 gave the desired diols with R ¼ Ph (R,R) (55 – 99%), R ¼ Ph (S,S) (46%), and R ¼ t-Bu
(S,S) (78%), resp. White solid.
Each diol and DMAP (0.10 equiv.) were dissolved in CH2Cl2 (0.3m), and Et3N (8.25 equiv.) was
added dropwise. Then a soln. of TsCl (2.2 equiv.) in CH2Cl2 (1.0m) was added, and the soln. was stirred at
r.t. After 2 d, the addition of 0.025m aq. HCl was followed by the extraction of the aq. phase with AcOEt
(3ꢁ). The combined org. phase was washed with aq. sat. Na2CO3 soln. and aq. sat. NaCl soln., dried
(Na2SO4), and concentrated and the residue subjected to CC (SiO2, AcOEt/EtOH 50 :1): 11 (57 – 68%),
12 (58%), and 13 (33 – 78%), resp. Slightly yellow oils.
20
20
1
Data of 11 and 12: [a] ¼ þ101.5 (11, 3.5m, CHCl3); [a] ¼ ꢀ83.1 (12, 5.3m, CHCl3). H-NMR
589
589
(CDCl3/CHCl3): 1.65 (d, 3J) ¼ 7.2, MeCH); 3.77 (q, 3J ¼ 7.2, MeCH)); 4.17 and 4.18 (dA) 4.68 and 4.69 (dB;
2 AB patterns, J(A,B) ¼ 8.4, J(A,4) ¼ 7.8, J(B,4) ¼ 10.1, 4 H, CH2(5,5’)); 5.24 and 5.25 (dd, J(4,B) ¼ 10.0,
J(4,A) ¼ 7.9, 2 H, HꢀC(4,4’); 7.26 – 7.35 (m, 10 arom. H). 13C-NMR (CDCl3/CDCl3): 15.46 (MeCH);
34.20 (MeCH)); 69.63, 69.67 (C(5,5’)); 75.40, 75.42 (C(4,4’)); 126.72, and 126.76 (2 Co); 127.66 (Cp);
128.79 (2 Cm); 142.29, 142.31 (Cipso); 167.06, 167.27 (C(2,2’)). CI-MS (NH3): 337.1 (32), 322.1 (24), 321.1
(100, [M þ 1]þ), 320.1 (23), 319.1 (15), 243.1 (11), 201.0 (27), 191.0 (14), 190.0 (15), 175.0 (41), 120.0
(17), 104.0 (50), 91.0 (12). Anal. calc. for C20H20N2O2 (320.38): C 74.98, H: 6.29, N 8.74; found: C 74.69,
H 6.31, N 8.46.
20
1
Data of 13: [a] ¼ ꢀ99.3 (4.6m, CHCl3). H-NMR (CDCl3/CHCl3): 0.87, 0.88 (s, 18 H, t-Bu); 1.48
589
(d, 3J ¼ 7.2, MeCH); 3.55 (q, 3J ¼ 7.2, MeCH); 3.83 – 3.86 (m, 2 H, HꢀC(4,4’)); 4.07 and 4.08 (dA) 4.17 and
4.18 (dB; 2 AB patterns, J(A,B) ¼ 8.7, J(A,4) ¼ 7.5, J(B,4) ¼ 10.0, CH2(5,5’)). 13C-NMR (CDCl3/CDCl3):
15.36 (MeCH); 25.74, 25.79 (Me3C); 33.81, 33.85 (Me3C); 34.12 (MeCH); 69.04, 69.05 (C(5,5’)); 75.57
(C(4,4’)); 165.42, 165.63 (C(2,2’)). APCI-MS (pos.): 282 (17), 281 (100, [M þ 1]þ). Anal. calc. for
C16H28N2O2 (280.41): C 68.53, H 10.06, N 9.99; found: C 68.12, H 10.22, N 9.58.
3. N-(3-Aminopropyl)-7,7-bis[(4R)-4,5-dihydro-4-phenyloxazol-2-yl]octanamide (14; R ¼ Ph
(R,R)), N-(3-Aminopropyl)-7,7-bis[(4S)-4,5-dihydro-4-phenyloxazol-2-yl)octanamide (15; R ¼ Ph
(S,S)), and N-(3-Aminopropyl)-7,7-bis[(4S)-4-(1,1-dimethylethyl)-4,5-dihydrooxazol-2-yl)octanamide
(16; R ¼ t-Bu (S,S)). The bis(dihydrooxazole) 11, 12, or 13 was dissolved in dry THF (0.14m), and the
mixture was cooled to ꢀ 788. After the dropwise addition of BuLi (1.1 equiv.), the soln. was stirred for
15 min at ꢀ 788. Then the mixture was warmed to 08 and stirred for an additional 15 min at ꢀ 788.
Afterwards, a soln. of 6-bromohexanoic acid methyl ester (1.1 equiv.) in dry THF (0.31m) was added
dropwise at 08. After stirring for 2 h at r.t., the mixture was heated to reflux for further 4 h. After cooling
to r.t., sat. aq. NH4Cl soln. and CH2Cl2 were added, and the org. phase was washed with H2O (2 ꢁ ). The
combined aq. phase was extracted with CH2Cl2 (3ꢁ), the CH2Cl2 phase dried (Na2SO4) and
concentrated, and the crude product purified by CC (CH2Cl2/AcOEt 4 :1 þ 0.5% Et3N): methyl esters
with R ¼ Ph (R,R) (57 – 60%); R ¼ Ph (S,S) (66%), and R ¼ t-Bu (S,S) (43%), resp. Slightly yellow oils.
Each, methyl ester and propane-1,3-diamine (12.5 equiv.) were stirred for 2 d at r.t., and then the
remaining propane-1,3-diamine was removed by bulb-to-bulb distillation. Sat. aq. NaCl soln. was added
to the residue, and the aq. phase was extracted with CHCl3/i-PrOH 8 :2 (3ꢁ). The combined org. phase
was washed with sat. aq. NaCl soln., dried (Na2SO4), and concentrated, and the crude product was
purified by CC (MeOH/aq. NH3 soln. 98 :2): 14 (75 – 77%), 15 (78%), and 16 (69%); resp. Yellow oils.
20
20
1
Data of 14 and 15: [a] ¼ þ102.6 (14, 4.0m, CHCl3); [a] ¼ ꢀ106.4 (15, 4.6m, CHCl3). H-NMR
589
589
(CDCl3/CHCl3): 1.35 – 1.46 (m, CH2(4), CH2(5)); 1.63 (s, Me(8)); 1.59 – 1.68 (m, CH2(3), CH2(6)); 1.98 –
2.09 (m, CH2(2’’)); 2.13 (t, J(2,3) ¼ 7.6, CH2(2)); 2.78 (t, J(3’’,2’’) ¼ 6.4, CH2(3’’)); 3.26 (dt, J(1’’,NH) ¼ 6.1,
J(1’’,2’’) ¼ 6.3, CH2(1’’)); 3.26 (br. s, NH2); 4.13 and 4.14 (dA) 4.65 and 4.66 (dB; 2 AB patterns J(A,B) ¼
8.4, J(A,4’) ¼ 8.1, J(B,4’) ¼ 10.0, 4 H, CH2(5’), 5.22, 5.23 (dd, J(4’,B) ¼ 10.2, J(4’,A) ¼ 7.7, 2 H, HꢀC(4’));
6.71 (t, J(NH,1’’) ¼ 6.2, NH); 7.24 – 7.35 (m, 10 arom. H). 13C-NMR (CDCl3/CDCl3): 21.55 (C(8)); 24.06

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(C(6)); 25.51 (C(5)); 29.32 (C(3)); 30.65 (C(4)); 36.44 (C(2’)); 36.46 (C(2’)); 37.22 (C(1’’)); 39.07 (C(3’’));
42.63 (C(7)); 69.44, 69.56 (C(5’)); 75.27, 75.36 (C(4’)); 126.71 (2 Co); 127.62 (Cp); 128.72, 128.74 (2 Cm);
142.35, 142.37 (Cipso); 169.73, 169.85 (C(2’)); 173.58 (C(1)). ESI-MS (pos.); 492 (30), 491 (100, [M þ 1]þ).
HR-APCI-MS (MeOH): 491.30270 ([M þ H]þ, C29H39N4O3þ ; calc. 491.30222).
1
Data of 16: H-NMR (CDCl3/CHCl3): 0.87 (s, 18 H, t-Bu); 1.32 – 1.33 (m, CH2(4) CH2(5)); 1.47 (s,
Me(8)); 1.63 (tt, J(3,2) ¼ 7.6, J(3,4) ¼ 7.4, C2(3)); 1.68 (tt, J(2’’,3’’) ¼ 6.5, J(2’’,1’’) ¼ 6.4, CH2(2’’)); 1.79 –
1.87, 1.95 – 2.01 (m, CH2(6); 2.15 (t, J(2,3) ¼ 7.6, CH2(2)); 2.51 (br. s, NH2); 2.83 (t, J(3’’,2’’) ¼ 6.4,
CH2(3’’)); 3.36 (dt, J(1’’,NH) ¼ 6.1, J(1’’,2’’) ¼ 6.2, CH2(1’’)); 3.84, 3.85 (dd, J(4’,B) ¼ 10.1, J(4’,A) ¼ 7.2,
2 H, HꢀC(4’)); 4.03 and 4.06 (dA), 4.12 and 4.13 dB; 2 AB patterns, J(A,B) ¼ 8.7, J(A,4’) ¼ 7.3, J(B,4’) ¼
10.0, 4 H, CH2(5’); 6.43 (t, J(NH,1’’) ¼ 5.6, NH). 13C-NMR (CDCl3/CDCl3): 21.48 (C(8)); 24.10 (C(6));
25.69 (C(5)); 25.79, 25.87 (Me3C); 29.56 (C(3)); 31.65 (C(4)); 33.90, 34.01 (Me3C); 36.35 (C(2’’)); 36.81
(C(2)); 37.67 (C(1’’)); 39.71 (C(3’’)); 42.40 (C(7)); 68.81, 68.84 (C(5’)); 75.35, 75.56 (C(4’)); 168.04, 168.19
(C(2’)); 173.47 (C(1)). APCI-MS (pos.): 559 (14), 464 (16), 463 (59), 452 (27), 451 (100, [M þ 1]þ).
4. 2,5-Dioxopyrrolidin-1-yl 2-[Tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silyl]ethyl Carbonate
(18). C6F13CH2CH2I (4.0 equiv.) was dissolved in dry Et2O (0.085m) and cooled to ꢀ 788. After the
dropwise addition of t-BuLi (8.0 equiv.), the soln. was warmed to 08. After 30 min at 08, the mixture was
again cooled to ꢀ 788, and 17 was added. After stirring for 24 h at r.t., H2O was added, the org. phase
washed with sat. aq. NaHCO3 soln., dried (Na2SO4), and concentrated, and the crude product purified by
CC (SiO2; pure cyclohexane): perfluorinated silane (71 – 91%). Waxy solid.
The perfluorinated silane was dissolved in dry Et2O (0.25m), and 9-BBN (3.0 equiv.) was added.
After stirring for 20 h at r.t., 3m aq. NaOH and 35% aq. H2O2 soln. were added, and the soln. was stirred
for further 2 h at r.t. before H2O was added. The aq. phase was extracted with Et2O (3ꢁ), the combined
org. phase washed with 10% aq. Na2S2O3 soln. and sat. aq. NaCl soln., dried (Na2SO4), and concentrated,
and the crude product purified by CC (cyclohexane ! cyclohexane/AcOEt 4 :1): hydroxysilane (65 –
90%). Waxy solid.
The hydroxysilane and Et3N (3.0 equiv.) were suspended in dry MeCN (0.18m), and disuccinimidyl
carbonate (1.9 equiv.) was added as a solid. After stirring for 20 h at r.t., the solvent was evaporated, the
residue dissolved in CH2Cl2, the org. phase washed with sat. aq. NaHCO3 soln. (2ꢁ), dried (Na2SO4),
and concentrated, and the crude product purified by CC (cyclohexane/AcOEt 4 :1): 18 (31 – 48%). White
solid.
1H-NMR (CDCl3/CHCl3): 0.95 – 0.99 (m, 3 CH2C6F13CH2CH2); 1.31 (t, J(2,1) ¼ 8.1, CH2(2)); 2.02 –
2.15 (m, 3 C6F13CH2CH2); 2.84 (s, CH2(3’), CH2(4’); 4.46 (t, J(1,2) ¼ 8.0, CH2(1)). 13C-NMR (CDCl3/
CDCl3): 1.65 (C6F13CH2CH2); 12.66 (C(2)); 25.35 (C6F13CH2CH2); 25.56 (C(3’), C(4’)); 67.95 (C(1));
151.53 (OC(O)O); 168.51 (C2’),C(5’)). 19F-NMR (CDCl3/CDCl3): ꢀ 126.29 to ꢀ 126.12 (6 F); ꢀ 123.28
to ꢀ 123.22 (6 F); ꢀ 122.92 (6 F); ꢀ 121.95 (6 F); ꢀ 116.19 to ꢀ 115.91 (6 F); ꢀ 80.88 to ꢀ 80.78 (9 F).
CI-MS (NH3): 1275 (11), 1274 (38), 1273 (100, [M þ NH4]þ), 836 (16), 197 (17), 180 (30).
5. 2-[Tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silyl]ethyl N-{3-{{7,7-Bis[(4R)-4,5-dihydro-4-
phenyloxazol-2-yl]-1-oxooctylamino]propyl}carbamate (5; R ¼ Ph (R,R)), 2-[Tris(3,3,4,4,5,5,6,6,7,7,8,
8,8-tridecafluorooctyl)silyl]ethyl N-{3-{{7,7-Bis[(4S)-4,5-dihydro-4-phenyloxazol-2-yl]1-oxooctylamino}-
propyl}carbamate (6; R ¼ Ph (S,S)), and 2-[Tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silyl]ethyl N-
{3-{{7,7-Bis[(4S)-4-(1,1-dimethylethyl)-4,5-dihydrooxazol-2-yl]-1-oxooctylamino}propyl}carbamate (7;
R ¼ t-Bu (S,S)). To a soln. of 18 (1.0 equiv.) in dry THF (0.01m), either 14, 15, or 16 was added. After
the addition of (i-Pr)2EtN (10.0 equiv.), the mixture was stirred for 1 h at r.t., and then sat. aq. NaHCO3
soln. was added. The aq. phase was extracted with Et2O (3ꢁ), dried (Na2SO4), and concentrated and the
crude product purified by CC (AcOEt/EtOH 40 :1): 5 (59 – 83%), 6 (91%), and 7 (70 – 75%), resp.
Colorless highly viscous oils.
20
20
Data of 5 and 6: [a] ¼ þ119.8 (5, 2.5m, CHCl3); [a] ¼ ꢀ120.7 (6, 1.7m, CHCl3). 1H-NMR
365
365
(CDCl3/CHCl3): 0.90 – 0.95 (m, 3 C6F13CH2CH2); 1.14 (t, J(2’’’,1’’’) ¼ 8.0, CH2(2’’’)); 1.35 – 1.48 (m,
CH2(4’), CH2(5’)); 1.56 (tt, J(3’,2’) ¼ 6.2, J(3’,4’) ¼ 6.2, CH2(3’)); 1.62 – 1.69 (m, CH2(6’)); 1.64 (s, Me(8’));
2.01 – 2.17 (m, CH2(2), CH2(2’), 3 C6F13CH2CH2); 3.15 (dt, J(1,NH) ¼ 6.3, J(1,2) ¼ 6.3, CH2(1)); 3.16 –
3.23 (m, CH2(3)); 4.18 (t, J(1’’’,2’’’) ¼ 8.1, CH2(1’’’)); 4.14 and 4.15 (dA), 4.66 and 4.67 (dB, 2 AB patterns,
J(A,B) ¼ 8.4, J(A,4’’) ¼ 7.7, J(B,4’’) ¼ 10.2, 4 H, CH2(5’’)); 5.22, 5.24 (dd, J(4’’,B) ¼ 10.1, J(4’’,A) ¼ 7.8, 2 H,
HꢀC(4’’)); 5.39 (t, J(NH,3) ¼ 6.8, NH); 5.88 (t, J(NH,1) ¼ 6.3, NH); 7.23 – 7.35 (m, 10 arom. H. ).

Helvetica Chimica Acta – Vol. 95 (2012)
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13C-NMR (CDCl3/CDCl3): 1.64 (C6F13CH2CH2); 12.72 (C(2’’’)); 21.64 (C(8’)); 23.94 (C(4’)); 25.4
(C6F13CH2CH2); 25.46 (C(6’)); 29.19 (C(5’)); 30.15 (C(3’)); 35.73 (C(3)); 36.43 (C(2)); 36.53 (C(2’));
37.37 (C(1)); 42.73 (C(7’)); 61.02 (C(1’’’)), 69.57, 69.66 (C(5’’)); 75.34, 75.40 (C(4’’)); 115.84, 118.02, 118.71
(CF); 126.78 (2 Co); 127.67 (Cp); 128.79 (2 Cm); 142.47 (Cipso); 156.69 (NC(O)O); 169.81, 169.90 (C(2’));
173.79 (C(1’)). 19F-NMR (CDCl3/CDCl3): ꢀ 126.27 to ꢀ 126.11 (6 F); ꢀ 123.27 to ꢀ 122.92 (6 F);
ꢀ 121.96 (6 F); ꢀ 116.20 to ꢀ 115.95 (6 F); ꢀ 80.88 to ꢀ 80.79 (9 F). ESI-MS (pos.): 1633 (19), 1632
(49), 1631 (100, [M þ 1]þ). HR-APCI-MS (MeOH): 1631.32580 ([M þ H]þ, C56H54F39N4O5Siþ;
calc.1631.32408).
365
1
Data of 7: [a] ¼ ꢀ66.4 (1.8m, CHCl3). H-NMR (CDCl3/CHCl3): 0.87 (s, 18 H, t-Bu); 0.91 – 0.96
20
(m, 3 C6F13CH2CH2); 1.15 (t, J(2’’’,1’’’) ¼ 7.8, HꢀCH2(2’’’)); 1.30 – 1.35 (m, CH2(4’), CH2(5’)); 1.46 (s,
Me(8’)); 1.59 – 1.66 (m, CH2(3’), CH2(6’)); 2.00 – 2.09 (m, CH2(2), 3 C6F13CH2CH2); 2.16 (t, J(2’,3’) ¼ 7.6,
CH2(2’)); 3.18 (dt, J(1,NH) ¼ 6.3, J(1,2) ¼ 6.1, CH2(1)); 3.29 (dt, J(3,NH) ¼ 6.2, J(3,2) ¼ 6.2, CH2(3));
3.84, 3.85 (dd, J(4’’,B) ¼ 10.3, J(4’’,A) ¼ 7.0, 2 H, HꢀC(4’’)); 4.03 and 4.06 dA, 4.12 and 4.13 dB; 2 AB
patterns, J(A,B) ¼ 8.7, J(A,4’’) ¼ 7.2, J(B,4’’) ¼ 10.1, 4 H, CH2(5’’)); 4.19 (t, J(1’’’,2’’’) ¼ 7.6, CH2(1’’’)); 5.37
(t, J(NH,1) ¼ 6.8, NH); 5.88 (t, J(NH,3) ¼ 6.5, NH). 13C-NMR (CDCl3/CDCl3): 1.65 (C6F13CH2CH2);
12.72 (C(2’’’)); 21.46 (C(8’)); 24.07 (C(4’)); 25.17 (CH2CH2C6F13CH2CH2); 25.41 (C(6’)); 25.77, 25.83
(Me3C); 29.52 (C(5’)); 30.20 (C(3’)); 33.89, 34.00 (Me3C); 35.76 (C(3)); 36.36 (C(2)), 36.72 (C(2’)); 37.39
(C(1)); 42.41 (C(7’)); 61.04 (C(1’’’)); 68.81, 68.84 (C(5’’)); 75.38, 75.57 (C(4’’)); 115.84, 118.01 (CF);
156.71 (NC(O)O); 168.03, 168.21 (C(2’’)); 173.82 (C(1’)). 19F-NMR (CDCl3/CDCl3): ꢀ 126.33 to
ꢀ 126.06 (6 F); ꢀ 123.27 to ꢀ 122.92 (6 F); ꢀ 121.96 to ꢀ 121.92 (6 F); ꢀ 116.21 to ꢀ 115.94 (6 F);
ꢀ 80.88 to ꢀ 80.79 (9 F). ESI-MS (pos.): 1593 (17), 1592 (41), 1591 (100, Mþ). HR-APCI-MS (MeOH):
1591.38620 ([M þ H]þ, C52H62N4O5F39Siþ; calc. 1591.38668).
6. Noncovalent Immobilization of the Perfluoro-Tagged Ligands 5, 6, and 7 on FRPSG 2: General
Procedure. The perfluorinated ligands 5, 6, or 7 (10 mmol) were dissolved in THF (200 ml), and a soln. of
Cu(OTf)2 (10 mmol) in THF was added followed by FRPSG 2. The solvent was evaporatated, and THF
(2 ꢁ 200 ml) was added again. Concentration of the mixture yielded the immobilized catalysts 19, 20, and
21, resp., with a loading of 10 mmol/g.
7. Control Experiments in H2O: General Procedure. Unmodified SiO2 or FRPSG 2 (25.0 mg, 10 mmol/
g, 10 mol-%, and 12.5 mg, 10 mmol/g, 5 mol-%, resp.) was taken up in H2O (495 ml), and a soln. of the
dienophile 22, 23, or 24 (0.5m in MeCN, 5.0 ml) was added. The mixture was cooled to 58 before
cyclopenta-1,3-diene (25; 6.20 ml, 4.96 mg, 75.0 mmol, 30.0 equiv.) was added. After shaking the mixture
for 24 h at 58, the SiO2 or FRPSG was filtered off and washed with MeCN (4 ꢁ 0.5 ml), and the solvent
was evaporated. The residues were dissolved in heptane/i-PrOH 85 :15 (500 ml) for adducts 26, heptane/
EtOH 80 :20 (500 ml) for adducts 27, or heptane/i-PrOH 98 :2 (500 ml) for adducts 28, and the conversions
were determined by chiral HPLC.
8. DielsꢀAlder Reactions with Immobilized Catalyst 19, 20, and 21 in H2O: General Procedure. The
catalyst 19, 20, or 21 (25.0 mg, 10 mmol/g, 10 mol-%, and 12.5 mg, 10 mmol/g, 5 mol-%, resp.) was taken
up in H2O (495 ml) in an Eppendorf reaction tube. A soln. of the dienophile 22, 23, or 24 (0.5m in MeCN,
5.0 ml) was added, and the mixture was cooled to 58 before cyclopenta-1,3-diene (25; 6.20 ml, 4.96 mg,
75.0 mmol, 30.0 equiv.) was added. After shaking the mixture for 24 h at 58, the catalyst on FRPSG was
filtered off and washed with MeCN (4 ꢁ 0.5 ml), and the solvent was evaporated. The residues of the
adducts 26, 27, and 28, resp., were dissolved and analyzed by chiral HPLC as described in Exper. 7. The
recycled immobilized catalysts 19, 20, and 21 were re-used without further purification.
9. Control Experiments in CH2Cl2: General Procedure. As described in Exper. 7, with CH2Cl2 (450 ml)
instead of H2O, unmodified SiO2 or FRPSG 2 (25.0 mg, 10 mmol/g, 10 mol-%), dienophile 22, 23, or 24
(0.05m in CH2Cl2, 50.0 ml), and cyclopenta-1,3-diene (25; 6.20 ml, 4.96 mg, 75.0 mmol, 30.0 equiv.). The
mixture was shaken for 45 min with 22, for 4.5 h with 23, and for 6 h with 24 at 58. Then, the reaction soln.
was taken off via a syringe and concentrated. The residues of the adducts 26, 27, and 28, resp., were
dissolved and analyzed by chiral HPLC as described in Exper. 7.
10. DielsꢀAlder Reactions with Immobilized Catalyst 19, 20, and 21 in CH2Cl2. General Procedure.
As described in Exper. 8, with CH2Cl2 (450 ml) instead of H2O, catalyst 19, 20, or 21 (25.0 mg, 10 mmol/g,
10 mol-%), dienophile 22, 23, or 24 (0.05m in CH2Cl2, 50.0 ml), and cyclopenta-1,3-diene (25) (6.20 ml,
4.96 mg, 75.0 mmol, 30.0 equiv.). The mixture was shaken for 45 min with 22, for 4.5 h with 23, and for 6 h

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Helvetica Chimica Acta – Vol. 95 (2012)
with 24 at 58. Then, the reaction soln. was taken off via a syringe and concentrated. The residues of
adducts 26, 27, and 28, resp., were dissolved and analyzed by chiral HPLC as described in Exper. 7. The
recycled immobilized catalysts were re-used in the subsequent run without further purification.
11. (1-Oxidopyridin-2-yl)[(1R,2S,3S,4S)-3-phenylbicyclo[2.2.1]hept-5-en-2-yl]methanone (endo-26)
and (1-Oxidopyridin-2-yl)[(1S,2S,3S,4R)-3-phenylbicyclo[2.2.1]hept-5-en-2-yl]methanone (exo-26).
HPLC (Chiralpak AD-H (0.46 cm ꢁ 25 cm), heptane/i-PrOH 85 :15, 1.0 ml/min, 30 min; l 230 nm): tR
20
11.6 þ 13.5 (exo-products), 14.1 þ 15.0 (endo-products), and 23.1 (starting material). [a] ¼ þ171.2
589
(3.2m, CHCl3); eeendo 93%. 1H-NMR (CDCl3/CHCl3): endo-26: 1.56 (dA), 1.89 (dB, AB pattern, J(A,B) ¼
8.6, J(A,4’’) ¼ 3.6, 4J(A,3’’) ¼ 1.8, J(B,4’’) ¼ J(B,1’’) ¼ 1.5, CH2(7’’)); 3.09 (m, HꢀC(3’’)); 3.35 (m,
HꢀC(4’’)); 3.39 (m, HꢀC(1’’)); 4.50 (dd, J(2’’,3’’) ¼ 5.1, J(2’’,1’’) ¼ 3.5, HꢀC(2’’)); 5.87 (dd, J(6’’,5’’) ¼
5.7, J(6’’,1’’) ¼ 2.8, HꢀC(6’’)); 6.46 (dd, J(5’’,6’’) ¼ 5.6, J(5’’,4’’) ¼ 3.2, HꢀC(5’’)); 7.17 – 7.21 (m, Hp; 7.27 –
7.36 (m, 2 Ho, 2 Hm, HꢀC(4), HꢀC(5)); 7.43 (ddd, J(3,4) ¼ 7.2, 4J(3,5) ¼ 2.7, 5J(3,6) ¼ 0.8, HꢀC(3));
8.17 (ddd, J(6,5) ¼ 6.2, 4J(6,4) ¼ 1.6, 5J(6,3) ¼ 0.7, HꢀC(6)); exo-26: 1.51 (ddd, J(A,B) ¼ 8.6, J(A,4’’) ¼ 3.6,
J(A,1’’) ¼ 1.8, HAꢀC(7’’)); 1.85 – 1.87 (m, HBꢀC(7’’)); 3.21 (m, HꢀC(4’’)); 3.24 (m, HꢀC(1’’)); 6.06 (dd,
J(6’’,5’’) ¼ 5.7, J(6’’,1’’) ¼ 2.8, HꢀC(6’’)); 6.41 (dd, J(5’’,6’’) ¼ 5.6, J(5’’,4’’) ¼ 3.2, HꢀC(5’’)); 7.54 (ddd,
J(3,4) ¼ 7.2, 4J(3,5) ¼ 2.7, 5J(3,6) ¼ 0.8, HꢀC(3)). 13C-NMR (CDCl3/CDCl3): endo-26: 46.44 (C(4’’));
46.52 (C(1’’)); 47.66 (C(7’’)); 49.20 (C(3’’)); 58.28 (C(2’’)); 125.74 (C(4)); 126.04 (Cp); 126.37 (C(5));
127.47 (C(3)); 127.69 (2 Cm); 128.49 (2 Co); 133.13 (C(6’’)); 139.95 (C(5’’), C(6)); 140.43 (Cipso); 143.97
(C(2)); 198.58 (C(1’)); exo-26: 46.99 (C(4’’)); 48.12 (C(1’’)); 48.56 (C(7’’)); 49.01 (C(3’’)); 56.80 (C(2’’));
125.60 (C(4)); 126.12 (Cp); 126.64 (C(5)); 127.57 (C(3)); 127.98 (2 Cm); 128.06 (2 Co); 131.08 (C(6’’));
136.28 (C(5’’)); 137.14 (C(6)); 147.56 (C(2)). CI-MS (NH3): 293 (10), 292 (41, [M þ 1]þ), 276 (20, [M þ
1 ꢀ O]þ), 227 (15), 226 (100, [M þ 1 ꢀ C5H6]þ), 210 (35, [M þ 1 ꢀ O ꢀ C5H6)þ], 209 (11), 185 (7). HR-
CI-MS (NH3): 292.13360 ([M þ H]þ, C19H18NOþ2 ; calc. 292.13375).
[(1R,2S,3S,4S)-3-(4-Methoxyphenyl)bicyclo[2.2.1]hept-5-en-2-yl](1-oxidopyridin-2-yl)methanone
(endo-27) and [(1S,2S,3S,4R)-3-(4-Methoxyphenyl)bicyclo[2.2.1]hept-5-en-2-yl](1-oxidopyridin-2-yl)-
methanone (exo-27). HPLC (Chiralpak AD-H (0.46 cm ꢁ 25 cm), A ¼ heptane/i-PrOH 80 :20 and B ¼
heptane/EtOH 80 :20, eluent A/B 1:3, 1.25 ml/min, 60 min; l 230 nm): tR 17.7 þ 28.8 (exo-products),
20
18.9 þ 22.9 (endo-products), 45.4 (starting material). [a] ¼ þ154.4 (3.7m, CHCl3); eeendo 93%.
589
1H-NMR (CDCl3/CHCl3): endo-27: 1.55 (dA), 1.87 (dB; AB pattern, J(A,B) ¼ 8.6, J(A,4’’) ¼ 3.6,
J(A,3’’) ¼ 1.8, J(B,4’’) ¼ J(B,1’’) ¼ 1.5, CH2(7’’); 3.03 (m, HꢀC(4’’)); 3.27 (m, HꢀC(1’’)); 3.36 (m,
HꢀC(3’’)); 3.78 (s, MeO); 4.45 (dd, J(2’’,3’’) ¼ 5.1, J(2’’,1’’) ¼ 3.4, HꢀC(2’’)); 5.87 (dd, J(6’’,5’’) ¼ 5.6,
J(6’’,1’’) ¼ 2.7, HꢀC(6’’)); 6.45 (dd, J(5’’,6’’) ¼ 5.6, J(5’’,4’’) ¼ 3.2, HꢀC(5’’)); 6.84 (d, 3J ¼ 8.7, 2 Ho); 7.23 –
7.35 (m, 2 Hm, HꢀC(4), HꢀC(5)); 7.41 (ddd, J(3,4) ¼ 7.3, 4J(3,5) ¼ 2.7, 5J(3,6) ¼ 0.8, HꢀC(3)); 8.16 (ddd,
4
J(6,5) ¼ 6.2, J(6,4) ¼ 1.5, 5J(6,3) ¼ 0.8, HꢀC(6)); exo-27: 1.84 – 1.85 (m, HBꢀC(7’’)); 3.15 (m, HꢀC(1’’));
3.22 (m, HꢀC(3’’)); 3.74 (s, MeO); 6.06 (dd, J(6’’,5’’) ¼ 5.6, J(6’’,1’’) ¼ 2.7, HꢀC(6’’)); 6.41 (dd, J(5’’,6’’) ¼
5.6, J(5’’,4’’) ¼ 3.2, HꢀC(5’’)); 6.75 (d, 3J ¼ 8.8, 2 Ho); 7.10 (d, 3J ¼ 9.0, 2 Hm); 7.52 (ddd, J(3,4) ¼ 7.3,
4J(3,5) ¼ 2.7, 5J(3,6) ¼ 0.8, HꢀC(3)); 8.14 (ddd, J(6,5) ¼ 6.2, 4J(6,4) ¼ 1.4, 5J(6,3) ¼ 0.8, HꢀC(6)).
13C-NMR (CDCl3/CDCl3): endo-27: 45.85 (C(4’’)); 46.39 (C(1’’)); 47.59 (C(7’’)); 49.45 (C(3’’)); 55.32
(MeO); 58.31 (C(2’’)); 113.88 (2 Co); 125.71 (C(4)); 126.25 (C(3)); 127.41 (C(5)); 128.58 (2 Cm); 133.01
(C(6’’)); 136.01 (Cipso); 139.92 (C(5’’)); 140.38 (C(6)); 147.53 (Cp); 157.89 (C(2)); 198.74 (C(1’)); exo-27:
47.04 (C(4’’)); 47.44 (C(1’’)); 48.48 (C(7’’)); 49.12 (C(3’’)); 55.27 (MeO); 56.99 (C(2’’)); 113.46 (2 Co);
125.52 (C(4)); 126.55 (C(3)); 127.51 (C(5)), 128.87 (2 Cm); 136.37 (C(5’’)); 137.11 (C(6’’)); 158.00 (C(2)).
CI-MS (NH3): 322 (19, [M þ 1]þ), 306 (18, [M þ 1 ꢀ O]þ), 257 (15), 256 (100, [M þ 1 ꢀ C5H6]þ), 241
(11), 240 (73, [M þ 1 ꢀ O ꢀ C5H6]þ), 239 (26), 210 (5), 185 (8). HR-CI-MS (NH3): 322.14500 ([M þ H]þ,
C20H20NOþ3 ; calc. 322.14432).
[(1R,2S,3S,4S)-3-(1,1-Dimethylethyl)bicyclo[2.2.1]hept-5-en-2-yl-(1-oxidopyridin-2-yl)methanone
(endo-28) and [(1S,2S,3S,4R)-3-(1,1-Dimethylethyl)bicyclo[2.2.1]hept-5-en-2-yl](1-oxidopyridin-2-yl)-
methanone (exo-28). HPLC: Chiralpak AD-H (0.46 cm ꢁ 25 cm, heptane/i-PrOH 98 :2, 1.0 ml/min,
60 min; l 230 nm): tR 23.2 þ 27.3 (exo-products), 31.1 þ 35.2 (endo-products), 48.8 (starting material).
20
[a] ¼ þ173.7 (2.4m, CHCl3); eeendo 93%. 1H-NMR (CDCl3/CHCl3): endo-28: 0.95 (s, t-Bu); 1.35 (dA),
589
4
1.67 (dB); AB pattern J(A,B) ¼ 8.5, J(A,4’’) ¼ 3.5, J(A,3’’) ¼ 1.7, J(B,4’’) ¼ J(B,1’’) ¼ 1.5, CH2(7’’)); 1.88
(dd, J(3’’,2’’) ¼ 6.1, 4J(3’’,A) ¼ 1.8, HꢀC(3’’)); 2.77 (ddd, J(4’’,5’’) ¼ J(4’’,A) ¼ 3.1, J(4’’,B) ¼ 1.5, HꢀC(4’’));
3.17 (m, HꢀC(1’’)); 4.14 (dd, J(2’’,3’’) ¼ 5.9, J(2’’,1’’) ¼ 3.2, HꢀC(2’’)); 5.76 (dd, J(6’’,5’’) ¼ 5.6, J(6’’,1’’) ¼

Helvetica Chimica Acta – Vol. 95 (2012)
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2.7, HꢀC(6’’)); 6.43 (dd, J(5’’,6’’) ¼ 5.6, J(5’’,4’’) ¼ 3.3, HꢀC(5’’)); 7.31 (ddd, J(4,3) ¼ J(4,5) ¼ 7.5, 4J(4,6) ¼
4
5
1.4, HꢀC(4)); 7.32 – 7.36 (m, HꢀC(5)); 7.38 (ddd, J(3,4) ¼ 7.5, J(3,5) ¼ 2.5, J(3,6) ¼ 0.8, HꢀC(3)); 8.20
4
5
(ddd, J(6,5) ¼ 6.1, J(6,4) ¼ 1.4, J(6,3) ¼ 0.6, HꢀC(6)); exo-28: 0.80 (s, t-Bu); 1.34 – 1.35 (m, HAꢀC(7’’));
1.73 (ddd, J(B,A) ¼ 8.3, J(B,4’’) ¼ J(B,1’’) ¼ 1.5, HBꢀC(7’’)); 2.64 (dd, J(2’’,3’’) ¼ 6.3, 4J(2’’,1’’) ¼ 3.0,
HꢀC(2’’)); 2.98 (mc, HꢀC(4’’)); 3.02 (mc, HꢀC(1’’)); 3.40 (dd, J(3’’,2’’) ¼ 6.3, J(3’’,A) ¼ 1.3, HꢀC(3’’));
6.16 (dd, J(6’’,5’’) ¼ 5.4, J(6’’,1’’) ¼ 2.8, HꢀC(6’’)); 6.19 (dd, J(5’’,6’’) ¼ 5.5, J(5’’,4’’) ¼ 3.1, HꢀC(5’’)); 7.50 –
7.53 (m, HꢀC(3)). 13C-NMR (CDCl3/CDCl3): endo-28: 29.03 (Me3C); 32.63 (Me3C); 44.72 (C(4’’)); 46.85
(C(1’’)); 47.93 (C(7’’)); 51.79 (C(2’’)); 53.46 (C(3’’)); 125.76 (C(4)); 126.38 (C(5)); 127.27 (C(3)); 131.53
(C(6’’)); 140.47 (C(6)); 141.50 (C(5’’)); 147.81 (C(2)); 199.64 (C(1’)); exo-28: 29.41 (Me3C); 32.69
(Me3C); 45.42 (C(4’’)); 48.4 (C(7’’)); 49.12 (C(1’’)); 52.03 (C(3’’)); 55.36 (C(2’’)); 126.89 (C(3)); 135.05
(C(5’’)); 137.04 (C(6’’)); 140.47 (C(6)); 201.11 (C(1’)). CI-MS (NH3): 273 (17), 272 (99, [M þ 1]þ), 207
(12), 206 (100, [M þ 1 ꢀ C5H6]þ), 148 (7). HR-CI-MS (NH3): 272.16440 ([M þ H]þ, C17H22NOþ2 ; calc.
272.16505).
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Received July 20, 2012