First [4 + 2] cycloadditions involving the olefinic bond of an 'aldoketeniminium salt' (= N-alk-1-enylideneaminium salt)

Article abstract of DOI:10.1002/hlca.200590154

Keteniminium triflates' (= N-alk-1-enylideneaminium trifluoromethanesulfonates; [MeN(Ts)CH=C= NR¹(R²)] ⁺TfO^-) generated in situ from N^α- tosylsarcosinamides MeN(Ts)CH₂CONR¹(R²) unexpectedly react with cyclopenta-1,3-diene and cyclohexa-1,3-diene to give Diels-Alder reactions across the C=C bond of the cumulene. The use of N ^α-tosylsarcosinamides derived from chiral pyrrolidines allows the direct preparation of trinorbornenone derivative 6 in high enantiomer purity.

Full text of DOI:10.1002/hlca.200590154

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Helvetica Chimica Acta Vol. 88 (2005)
First [4 ‡ 2] Cycloadditions Involving the Olefinic Bond of an
−Aldoketeniminium Salt×( ˆ N-Alk-1-enylideneaminium Salt)
by Florence Mahuteau-Betzera), Ping-Yu Dinga), and Le¬on Ghosez*a)b)
a) Department of Chemistry, University of Louvain, 1 Place Louis Pasteur, B-1348Louvain-la-Neuve
b) European Institute of Chemistry and Biology, 2, rue Robert Escarpit, F-33607 Pessac
(phone: ‡ 33-5-4000-2217 (2223); fax: ‡ 33-5-4000 2222; e-mail: l.ghosez@iecb.u-bordeaux.fr)
To Professor Rolf Huisgen, with admiration and respect
−Keteniminium triflates× (ˆ N-alk-1-enylideneaminium trifluoromethanesulfonates; [MeN(Ts)CHˆCˆ
‡
NR1(R2)] TfOÀ) generated in situ from Na-tosylsarcosinamides MeN(Ts)CH2CONR1(R2) unexpectedly react
with cyclopenta-1,3-diene and cyclohexa-1,3-diene to give Diels Alder reactions across the CˆC bond of the
cumulene. The use of Na-tosylsarcosinamides derived from chiral pyrrolidines allows the direct preparation of
trinorbornenone derivative 6 in high enantiomer purity.
Introduction. The unique ability of ketenes to undergo [2 ‡ 2] cycloadditions with
electron-rich olefins was discovered as early as 1908by Chick and Wilsmore [1a] and by
Staudinger and Klever [1b]. Surprisingly little attention was paid to this reaction until
the early sixties when its usefulness was demonstrated by several laboratories [2].
These studies brought about a remarkable resurgence of interest for this unusual
cycloaddition reaction which is now a major component of the armory of the synthetic
chemist [3]. Mechanistic studies among which one should especially mention the
elegant and rigorous work of Huisgen×s group in Munich provided convincing
arguments in favor of the formation of the two new s bonds in a single elementary
step [3]. Further experimental and theoretical studies provided further insight into this
unique ability of ketene to undergo concerted [2 ‡ 2] cycloadditions even with 1,3-
dienes (e.g., cyclopenta-1,3-diene) which are known to be highly reactive in Diels
Alder reactions [3]. In this context, it is interesting to mention that the reaction of
bis(trifluoromethyl)ketene with olefins or conjugated dienes was shown to involve the
reversible formation of a zwitterionic intermediate which cyclizes to give four-
membered rings with olefins or six-membered rings with conjugated dienes [4]. A
recent study claims that [2 ‡ 2] cycloadducts of ketenes to olefins could be formed by a
two-step sequence involving a [4 ‡ 2] cycloaddition and a subsequent [3,3]-sigmatropic
rearrangement [5].
−Keteniminium salts× (ˆ N-alk-1-enylideneaminium salts; R1(R2)CˆCˆ
‡
NR3(R4) XÀ) are isoelectronic to allenes and lack the free electron-pair on the
heteroatom which had been shown to give a 1,2-dipolar character to ketenes
(Scheme 1) [6]. Still they also give [2 ‡ 2] cycloadducts with olefins [3c] (for
intermolecular cycloadditions, see [7]; for intramolecular cycloadditions, see [8]).
However, their reactivity profile is somewhat different.
¹ 2005 Verlag Helvetica Chimica Acta AG, Z¸rich

Helvetica Chimica Acta Vol. 88 (2005)
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Scheme 1
Thus, the reaction of −tetramethylketeniminium salts× with s-cis-dienes exclusively
‡
yielded a [4 ‡ 2] cycloadduct involving the CˆN bond as dienophile component
(Scheme 2,a and b) [8]. On the other hand, s-trans dienes such as buta-1,3-diene or
(3E)-penta-1,3-diene only gave [2 ‡ 2] cycloadducts (Scheme 2,c), while 2,3-dimethyl-
buta-1,3-diene gave a mixture of [2 ‡ 2] and [2 ‡ 4] adducts as a result of the lower
energy barrier between the s-cis and s-trans conformations (Scheme 2,d) [9].
Scheme 2
Inter- and intramolecular cycloadditions of in situ generated −keteniminium salts×
derived from enantiomerically pure amides have been successfully used in asymmetric
syntheses [10]. Thus, our group developed a short and practical enantioselective
synthesis of prostanoid synthons involving an intramolecular [2 ‡ 2] cycloaddition
of a −keteniminium salt× as key step [11]. More recently, we described an asymmetric
[2 ‡ 2 ‡ 1] cyclopentannulation of olefins involving an enantioselective intermolecular
[2 ‡ 2] cycloaddition of −keteniminium salt× 1 to olefins followed by the regioselective
insertion of an O-atom or a CH2 group into the strained four-membered ring adduct
(Scheme 3) [12].

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Helvetica Chimica Acta Vol. 88 (2005)
Scheme 3
In the course of these investigations, we encountered the first example of a Diels
Alder reaction involving the olefinic CˆC bond of a −keteniminium salt×. We describe
here the details of these unexpected observations.
Results and Discussions. Racemic [4 ‡ 2] Cycloadducts. The slow addition of a
diluted 1,2-dichloroethane solution of cyclohexa-1,3-diene into a mixture of Na-tosyl-
protected sarcosinamide 2, triflic anhydride (ˆtrifluoromethanesulfonic anhydride),
and 2,6-di(tert-butyl)-4-methylpyridine in CH2Cl2 at room temperature followed by
hydrolysis at 808 gave a 3 :1 mixture (79% yield) of the Na-tosyl-protected amino-
bicyclo[2.2.2]heptenone 3 and the expected hydrolyzed exo-[2 ‡ 2] cycloadduct 4
(Scheme 4).
Scheme 4

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Compound 3 obviously resulted from a [4 ‡ 2] cycloaddition of the diene to the
olefinic bond of −keteniminium triflate× 5 generated in situ [7c] followed by hydrolysis
of the iminium function. The exo-configuration of the 3-[methyl(tosyl)amino] group
was assigned on the basis of the value (1.6 H) of the J(3,4) coupling constant.
With cyclopenta-1,3-diene (Scheme 5), the reaction was even more selective in
favor of the Diels Alder product. Under neutral hydrolysis, aminotrinorbornenone 6
was obtained in 69% yield, and less than 5% of the hydrolyzed [2 ‡ 2] cycloadduct was
detected in the crude mixture. The exo-configuration of the 3-[methyl(tosyl)amino]
substituent in 6 was again assigned on the basis of the value (1.5 H) of the J(3,4)
coupling constant.
Scheme 5
When the hydrolysis of the Diels Alder adduct was performed under basic
conditions, a 2 :1 mixture of exo- and endo isomers 6 and 7, respectively, was obtained in
41% yield (Scheme 5). This result was interesting as it indicated that the exo-adduct
was the kinetic product which epimerized under the basic conditions of the hydrolysis.
This unique behavior of −keteniminium salt× 5 can be most simply rationalized by
the two-step cycloaddition mechanism proposed earlier (Scheme 6) [12a]. The first step
of the reaction would lead to a homoallylic cation 8 originating from an a-exo-approach
of the two reactants. As a result of the constrained s-cis conformation of the diene, the
second CÀC bond can be formed at each end of the allylic system. In the case of
−keteniminium triflate× 5, the cyclization occurred at the less-substituted C-atom of the
CˆC bond rather than at the more-substituted N-atom.
To test this hypothesis, we attempted the reaction of cyclopenta-1,3-diene and
cyclohexa-1,3-diene with other −aldoketeniminium salts× but, in each case, we obtained
intractable mixtures of products (Scheme 7).
Scheme 6 shows that the configuration of the adducts is the result of the mode of
approach of the two reacting partners in the first step of the reaction. Since we had
observed that −N-methyl-N-tosylketeniminium salts× derived from enantiomerically
pure prolinol methyl ether or 2,5-dimethylpyrrolidine gave [2 ‡ 2] cycloadducts with

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Helvetica Chimica Acta Vol. 88 (2005)
Scheme 6
a) Less than 5% of the [2 ‡ 2] adduct corresponding to 4 in the case of addition to cyclohexadiene (see
Scheme 4).
Scheme 7
olefins with high facial selectivities, we anticipated that they should also yield [4 ‡ 2]
cycloadducts of high enantiomer purities.
Asymmetric [4 ‡ 2] Cycloadditions. We then studied the behavior of −keteniminium
salt× 10 derived from C1-symmetric amide 9 (Scheme 8). The reaction gave a 65% yield
of exo-3-aminotrinorbornenone 6. No [2 ‡ 2] cycloadduct was detected.
On the other hand, −keteniminium salt× 12 derived from C2-symmetric amide 11
yielded a 3 :1 mixture of exo- and endo-3-aminotrinorbornenones 6 and 7 (Scheme 9).
The formation of the endo-isomer 7 probably resulted from partial epimerization of the
exo-adduct during the hydrolysis of the iminium function. This step was quite slow as a
‡
result of steric hindrance around the CˆN bond.
Both amides 9 and 11 gave good yields of aminotrinorbornenones. They were
formed in high enantiomer purities (92% ee and 97% ee). Enantiomer excesses were
determined by chiral HPLC (AD column).

Helvetica Chimica Acta Vol. 88 (2005)
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Scheme 8
Scheme 9
To determine the absolute configurations, ketal 13 was prepared starting from a
chiral diol. Compound 13 could be either diastereoisomer 13a or 13b (Scheme 10). A
nuclear Overhauser effect (NOE) was observed between the Me group of the
methyl(tosyl)amino group and Me1 of 13. Only 13a could lead to such an NOE effect.
The formation of enantiomer 6 from 9 can be readily explained by the mechanism
shown in Scheme 6 (R ˆ MeOCH2 or R' ˆ MeOCH2) [12a]. The preferred approach of
the two reactants (Scheme 6) avoids steric interactions with two axial H-atoms of the
ring.
Conclusions. In summary, we reported here the first examples of Diels Alder
reactions involving the CˆC bond of a −keteniminium salt× (ˆ N-alk-1-enylideneami-
nium salt). This further emphasizes the difference of behavior of ketenes and
−keteniminium salts× as a result of the lack of a free electron pair at the heteroatom
responsible for the 1,2 dipolar character of ketenes (Scheme 1) and their unique ability
to give [2 ‡ 2] cycloadditions with conjugated dienes even when they are constrained in
a s-cis conformation favorable to a Diels Alder reaction. At this point, however, the
scope of our observations appear to be limited to −keteniminium salts× derived from Na-
tosylsarcosinamides MeN(Ts)CH2CONR1(R2).

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Helvetica Chimica Acta Vol. 88 (2005)
Scheme 10
Remarkably, the Diels Alder reactions of Na-tosylsarcosinamide 9 derived from
enantiomerically pure prolinol methyl ether are highly enantioselective giving a
trinorbornenone derivative of high enantiomer purity. A direct access to trinorborne-
nones or bicyclo[2.2.2]octenones of high enantiomer purities should be of synthetic
interest. Until now, Diels Alder routes to these bicyclic enones used ketene synthetic
equivalents as dienophiles which required several additional steps to regenerate the
carbonyl group [13]. Also trinorbornenone derivatives 6 should be easily converted
into a variety of other enantiomerically pure bicyclic systems as illustrated by a
preliminary study shown in Scheme 11 [12b] (!11 16).
Scheme 11
¡
¬
This work was generously supported by the Ministere de l×Education et de la Recherche, Communatue
¬
franÁaise de Belgique (action concertee, conventions 96/01-197) and the University of Louvain.
Experimental Part
General. All solvents were distilled before use. All reagents were reagent grade. TLC: silica gel 60F254
.
Column chromatography (CC): silica gel 40 (230 440 mm, Merck). HPLC: Millipore-Waters-600 controller,
UV-Millipore-Waters-486 detector; anal. Diacel Chiralpack-AD column for the determination of ee; tR in min.
M.p.: uncorrected. [a]D: Perkin-Elmer 241-MC polarimeter. IR Spectra: BioRad TFS-135-FT-IR spectrometer;
nÄ in cmÀ1. NMR Spectra: CDCl3 solns.; Varian Gemini-200 or -300 spectrometers at 200 or 300 MHz (1H) and

Helvetica Chimica Acta Vol. 88 (2005)
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Bruker ARX-400 at 400 MHz (1H) and 50 or 75 MHz (13C) at r.t.; chemical shifts d in ppm rel. to Me4Si
(ˆ0 ppm, 1H) or CDCl3 (ˆ 77.0 ppm, 13C); J in Hz. Mass Spectra: Finnigan MAT-TSQ-700 spectrometer; in m/z
(rel.%).
[4 ‡ 2] Cycloaddition Hydrolysis Sequence: General Procedure (G.P.). Triflic anhydride (1.2 equiv.) was
added to 0.1m sarcosinamide (1 equiv.) in 1,2-dichloroethane at 08. After 5 min, the mixture was treated over 1 h
with a 0.15m 2,6-di(tert-butyl)-4-methylpyridine (1.1 equiv.) and diene (4 equiv.) in 1,2-dichloroethane at 08.
After 3 h at r.t., the solvent was evaporated and the solid residue was taken up in a biphasic mixture of H2O and
CCl4. After 12 h at 808, the aq. layer was extracted with CCl4 (3Â). The combined org. phase was dried (MgSO4)
and evaporated and the product purified by FC (silica gel, AcOEt/cyclohexane 2 :8).
Cycloaddition of 5 with Cyclohexa-1,3-diene. According to the G.P., with 1-{2-{methyl[(4-methylphenyl)-
sulfonyl]amino}acetyl}pyrrolidine (2; 500 mg, 1.7 mmol), triflic anhydride (340 ml, 2.0 mmol), 2,6-di(tert-butyl)-
4-methylpyridine (380 mg, 1.9 mmol), and cyclohexa-1,3-diene (630 ml, 6.7 mmol): 3/4 3 :1 (408mg, 79%).
Data of (1RS,3SR,4SR)-3-[Methyl(tosyl)amino]bicyclo[2.2.2]oct-5-en-2-one (ˆ N,4-Dimethyl-N-
[(1RS,2RS,4SR)-3-oxobicyclo[2.2.2]oct-5-en-2-yl]benzenesulfonamide; 3): IR (neat): 2950, 2880, 1739, 1338,
1166. 1H-NMR (300 MHz, CDCl3): 7.71 (d, J ˆ 8.4, 2 H); 7.33 (d, J ˆ 8.4, 2 H); 6.45 (ddd, J ˆ 7.9, 6.3, 1.2, 1 H);
6.10 (ddd, J ˆ 7.9, 6.8, 1.9, 1 H); 4.28 (d, J ˆ 1.6, 1 H); 3.25 3.20 (m, 1 H); 2.95 2.80 (m, 1 H); 2.55 (s, 3 H); 2.42
(s, 3 H); 2.05 1.80 (m, 2 H); 1.40 1.15 (m, 2 H). 13C-NMR (50 MHz, CDCl3): 205.6; 143.0; 136.3; 136.1; 129.2
(2C); 127.1 (2C); 126.0; 61.1; 48.0; 38.5; 31.0; 24.5; 21.5; 19.6. EI-MS: 305 (20), 277 (100), 155 (8), 91 (24). HR-
‡
MS: 305.1083 (C16H19NO3S ; calc. 305.1086).
Data of (1RS,6SR,8SR)-8-[Methyl(tosyl)amino]bicyclo[4.2.0]oct-2-en-7-one (ˆ N,4-Dimethyl-N-
[(1RS,6SR,7RS)-8-oxobicyclo[4.2.0]oct-4-en-7-yl]benzenesulfonamide; 4): IR (neat): 2926, 1781, 1340, 1166.
1H-NMR (300 MHz, CDCl3): 7.71 (d, J ˆ 8.4, 2 H); 7.33 (d, J ˆ 8.4, 2 H); 6.05 5.95 (m, 1 H); 5.90 5.85 (m,
1 H); 4.95 (dd, J ˆ 7.5, 2.9, 1 H); 3.15 (tdd, J ˆ 9.9, 7.5, 2.9, 1 H); 2.95 2.80 (m, 1 H); 2.79 (s, 3 H); 2.43 (s, 3 H);
2.05 1.80 (m, 2 H); 1.40 1.15 (m, 2 H). 13C-NMR (50 MHz, CDCl3): 206.1; 143.7; 135.7; 129.7 (2C); 129.5;
127.4 (2C); 126.2; 76.8; 52.0; 31.7; 29.4; 21.8; 21.5; 20.6. EI-MS: 305 (4), 277 (44), 225 (12), 185 (12), 160 (100),
‡
91 (52). HR-MS: 305.1091 (C16H19NO3S ; calc. 305.1086).
Cycloaddition of 5 with Cyclopenta-1,3-diene. According to the G.P., with 2 (500 mg, 1.7 mmol), triflic
anhydride (340 ml, 2.0 mmol), 2,6-di(tert-butyl)-4-methylpyridine (520 mg, 2.5 mmol), and cyclopenta-1,3-diene
(550 ml, 6.7 mmol): 6 (340 mg, 69%).
After application of the G.P. as described above, basic hydrolysis was performed in a biphasic mixture of
Et2O and 1n aq. NaOH at r.t. during 12 h: 6/7 2.1 (200 mg, 41%).
Data of (1RS,3SR,4SR)-3-[Methyl(tosyl)amino]bicyclo[2.2.1]hept-5-en-2-one (ˆ N,4-Dimethyl-N-
[(1RS,2RS,4SR)-3-oxobicyclo[2.2.1]hept-5-en-2-yl]benzenesulfonamide; 6). IR (neat): 2963, 2917, 2853, 1753,
1340, 1160. 1H-NMR (400 MHz, CDCl3): 7.70 (d, J ˆ 8.3, 2 H); 7.30 (d, J ˆ 8.3, 2 H); 6.61 (dd, J ˆ 5.6, 2.8, 1 H);
6.21 (ddt, J ˆ 5.6, 3.2, 0.8, 1 H); 3.93 (d, J ˆ 3.5, 1 H); 3.25 3.20 (m, 1 H); 2.95 (dt, J ˆ 3.2, 1.7, 1 H); 2.78( s, 3 H);
2.42 (s, 3 H); 2.32 (dtt, J ˆ 10.2, 1.7, 0.8, 1 H); 2.24 (dddd, J ˆ 10.2, 3.5, 1.7, 1.5, 1 H). 13C-NMR (50 MHz, CDCl3):
209.0; 143.6; 135.6; 133.6; 129.7 (2C); 127.4 (2C); 58.4; 53.6; 46.8; 46.7; 33.2; 21.5. CI-MS (pos.): 292 (12): HR-
‡
CI-MS (pos.): 292.1011 (C15H17NO3S ; calc. 292.1007).
Data of (1RS,3RS,4SR)-3-[Methyl(tosyl)amino]bicyclo[2.2.1]hept-5-en-2-one (ˆ N,4-Dimethyl-N-
[(1RS,2SR,3SR)-3-oxobicyclo[2.2.1]hept-5-en-2-yl]benzenesulfonamide; 7). IR (neat): 2963, 2917, 2853, 1753,
1340, 1160. 1H-NMR (300 MHz, CDCl3): 7.73 (d, J ˆ 8.3, 2 H); 7.28 (d, J ˆ 8.3, 2 H); 6.52 (dd, J ˆ 5.5, 2.7, 1 H);
6.10 (dd, J ˆ 5.5, 4.4, 1 H); 4.36 (d, J ˆ 3.0, 1 H); 3.25 3.20 (m, 1 H); 3.09 (m, 1 H); 2.63 (s, 3 H); 2.42 (s, 3 H);
2.30 2.20 (m, 1 H); 2.01 (br. d, J ˆ 9.7, 1 H). 13C-NMR (50 MHz, CDCl3): 207.8; 143.3; 140.9; 135.9; 133.5; 129.8
‡
(2C); 127.1 (2C); 61.4; 55.0; 47.2; 45.5; 31.9; 21.5. CI-MS (pos.): 292 (12). HR-CI-MS (pos.): (C15H17NO3S ; calc.
292.1007).
Cycloaddition of 10 with Cyclopenta-1,3-diene. According to the G.P., with (2S)-2-(methoxymethyl)-1-{2-
{methyl[(4-methylphenyl)sulfonyl]amino}acetyl}pyrrolidine (9; 500 mg, 1.4 mmol), triflic anhydride (300 ml,
1.7 mmol), 2,6-di(tert-butyl)-4-methylpyridine (330 mg, 1.5 mmol), and cyclopenta-1,3-diene (490 ml,
5.6 mmol): 6 (280 mg, 65%; 92% ee). HPLC (AD, EtOH, flow 0.3 mlminÀ1, l 254 nm): tR 19.5 ((1S,3R,4R),
30.7 (1R,3S,4S)). [a]D ˆ À124.3 (c ˆ 0.59, CH2Cl2)
Cycloaddition of 12 with Cyclopenta-1,3-diene. According to the G.P., with (2R,5R)-2,5-dimethyl-1-{2-
{methyl[(4-methylphenyl)sulfonyl]amino}acetyl}pyrrolidine (11; 500 mg, 1.5 mmol), triflic anhydride (310 ml,
1.8mmol), 2,6-di( tert-butyl)-4-methylpyridine (350 mg, 1.7 mmol), and cyclopenta-1,3-diene (510 ml,
6.0 mmol): 6 (97% ee) and 7 (97% ee) (230 mg, 51%) in the ratio 3 :1. HPLC (AD, EtOH, flow 0.3 ml
minÀ1, l 254 nm): tR 19.5 (6 (1S,3R,4R)), 22.8( 7 (1S,3S,4R)), 30.7 (6 (1R,3S,4S)), and 44.5 (7 (1R,3R,4S)).

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(1S,3R,4R)-3-[Methyl(tosyl)amino]bicyclo[2.2.1]hept-5-en-2-one (1R,2R)-1,2-Dimethylethane-1,2-diyl
Acetal (ˆ N,4-Dimethyl-N-[(1S,3R,4R,4'R,5'R)-4',5'-dimethylspiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]diox-
olan]-3-yl]benzenesulfonamide; 13). A mixture of 0.02m 6 (100 mg, 0.3 mmol) in toluene, (2R,3R)-butane-
2,3-diol, and a catalytic amount of TsOH was refluxed overnight in a Dean Stark apparatus. The mixture was
cooled to r.t. and washed twice with 5% aq. NaHCO3 soln. The combined org. layer was dried (MgSO4) and
evaporated and the product purified by FC silica gel, AcOEt/cyclohexane 2 :8); 13 (60 mg, 48%). [a]D ˆ ‡45.1
(c ˆ 0.75, CH2Cl2). IR (neat): 2979, 1340, 1151. 1H-NMR (200 MHz, CDCl3): 7.65 (d, J ˆ 8.3, 2 H); 7.31 (d, J ˆ
8.3, 2 H); 6.22 (dd, J ˆ 5.7, 3.0, 1 H); 6.16 (dd, J ˆ 5.7, 3.0, 1 H); 3.98( dq, J ˆ 8.4, 6.0, 1 H); 3.88 (d, J ˆ 2.7, 1 H);
3.64 (dq, J ˆ 8.4, 6.0, 1 H); 2.89 (s, 3 H); 2.50 2.40 (m, 1 H); 2.44 (s, 3 H); 2.01 (br. s, 1 H); 1.96 (d, J ˆ 9.3, 1 H);
1.63 (br. d, J ˆ 9.3, 1 H); 1.33 (d, J ˆ 6.0, 3 H); 1.23 (d, J ˆ 6.0, 3 H). 13C-NMR (75 MHz, CDCl3): 143.0; 138.8;
136.4; 135.6; 129.6 (2C); 126.9 (2C); 113.6; 79.9; 78.4; 64.5; 49.5; 46.5; 42.4; 31.0; 21.5; 16.5; 16.4.
(1S,2S,3R,4R)-3-[Methyl(tosyl)amino]spiro[bicyclo[2.2.1]hept-5-ene-2,2'-oxirane] (ˆ N,4-Dimethyl-N-
[(1S,2S,3R,4R)-spiro[bicyclo[2.2.1]hept-5-ene-2,2'-oxiran]-3-yl]benzenesulfonamide; 14). At À 158, 2.5m BuLi
in hexanes (410 ml) was added to 0.05m trimethylsulfonium tetrafluoroborate (135 mg, 0.8mmol) in THF. After
15 min, the mixture was cooled to À 788 and treated with a soln. of 6 (200 mg, 0.7 mmol). After 15 h at r.t., the
mixture was diluted with Et2O washed twice with H2O, the org. layer dried (MgSO4), and evaporated, and the
residue purified by FC (silica gel, AcOEt/cyclohexane 2 :8): 11 (60 mg, 48%). [a]D ˆ À2.4 (c ˆ 0.42, CH2Cl2).
IR (neat): 2984, 1340, 1171. 1H-NMR (300 MHz, CDCl3): 7.66 (d, J ˆ 8.4, 2 H); 7.32 (d, J ˆ 8.4, 2 H); 6.26 (dd,
J ˆ 5.6, 3.2, 1 H); 6.16 (dd, J ˆ 5.6, 2.8, 1 H); 4.07 (d, J ˆ 1.6, 1 H); 2.93 (s, 3 H); 2.76 (d, J ˆ 4.9, 1 H); 2.74 (d, J ˆ
4.9, 1 H); 2.44 (s, 3 H); 2.36 (m, 1 H); 2.30 (s, 1 H); 2.12 (d, J ˆ 9.2, 1 H); 1.75 (dd, J ˆ 9.2, 1.6, 1 H). 13C-NMR
(75 MHz, CDCl3): 143.2; 139.9; 136.5; 135.4; 129.6 (2C); 126.9 (2C); 62.4; 56.9; 48.2; 47.0; 46.8; 43.5; 31.4; 21.4.
‡
EI-MS: 351 (84), 239 (100), 155 (44), 150 (36), 91 (52), 42 (40). HR-EI-MS: 305.1095 (C16H19NO3S ; calc.
305.1086).
Rearrangement of Spirooxirane 14. LiI (36 mg, 0.27 mmol) was added to a soln. of 14 (83 mg, 0.27 mmol) in
THF (3 ml). The mixture was heated for 2 h at 658, then cooled to r.t. and evaporated. The crude was purified by
FC (AcOEt/cyclohexane 2 :8): 15 (15 mg, 45%) and 16 (60 mg, 50%).
Data of (1S,5R)-Bicyclo[3.2.1]oct-3,6-dien-2-one (15): This compound has already been described as a
racemic mixture (CA Registry Number 1122-53-8). [a]D ˆ À5.8( c ˆ 0.12, CH2Cl2). 1H-NMR (200 MHz,
CDCl3): 7.34 (dd, J ˆ 9.7, 6.4, 1 H); 6.68( dd, J ˆ 5.3, 2.9, 1 H); 6.18( dd, J ˆ 5.3, 3.3, 1 H); 5.44 (ddd, J ˆ 9.7, 1.9,
0.8, 1 H); 3.30 (m, 1 H); 3.21 (m, 1 H); 2.54 (m, 1 H).
Data of (1S,2S,3R,4R)-2-(Iodomethyl)-3-[methyl(tosyl)amino]bicyclo[2.2.1]hept-5-en-2-ol (ˆ N-
[(1R,2R,3S,4S)-3-Hydroxy-3-(iodomethyl)bicyclo[2.2.1]hept-5-en-2-yl]-N,4-dimethylbenzenesulfonamide; 16):
[a]D ˆ ‡59.2 (c ˆ 0.52, CH2Cl2). IR (neat): 3523, 2986, 1340, 1171. 1H-NMR (200 MHz, CDCl3): 7.66 (d, J ˆ 8.3,
2 H); 7.35 (d, J ˆ 8.3, 2 H); 6.23 (dd, J ˆ 5.6, 2.9, 1 H); 6.14 (dd, J ˆ 5.6, 3.0, 1 H); 3.68( d, J ˆ 10.8, 1 H); 3.59 (d,
J ˆ 1.6, 1 H); 3.18( d, J ˆ 10.8, 1 H); 3.00 2.90 (m, 1 H); 2.93 (s, 3 H); 2.59 (br. s, 1 H); 2.45 (s, 3 H); 2.14 (d, J ˆ
9.4, 1 H); 1.63 (d, J ˆ 9.4, 1 H). 13C-NMR (50 MHz, CDCl3): 143.9; 138.3; 136.2; 136.2; 134.0; 129.9 (2C); 127.3
(2C); 78.3; 64.1; 51.2; 46.2; 45.4; 31.7; 21.5; 19.6. EI-MS: 434 (20), 306 (20), 292 (100).
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Received April 4, 2005