Diastereoselective aza-baylis-hillman reactions: synthesis of chiral α-allenlamines and 2-azetines from allenie esters

Article abstract of DOI:10.1002/ejoc.200901415

The reactivity of allenic esters towards activated N-sulfonylimines in the presence of DABCO was explored. A formal [2+2] cycloaddition of benzyl buta- -dienoate and N-aryl idenebenzenesulfonamides yielded mainly 2-methyleneazet-idines. Interestingly, a DABCO-catalysed reaction of allenoates, bearing a chiral auxiliary on the ester moiety, with N- arylidenebenzenesulfonamides led to optically active aza-Baylis-Hillman products and 2-azetine derivatives.

Full text of DOI:10.1002/ejoc.200901415

FULL PAPER
DOI: 10.1002/ejoc.200901415
Diastereoselective Aza-Baylis–Hillman Reactions: Synthesis of Chiral
α-Allenylamines and 2-Azetines from Allenic Esters
Bruna S. Santos,[a] Ana L. Cardoso,[a] Ana Matos Beja,[b] Manuela Ramos Silva,[b]
José A. Paixão,[b] Francisco Palacios,[c] and Teresa M. V. D. Pinho e Melo*[a]
Keywords: Allenes / Nitrogen heterocycles / Chiral auxiliaries / Diastereoselectivity
The reactivity of allenic esters towards activated N-sulfon-
ylimines in the presence of DABCO was explored. A formal
[2+2] cycloaddition of benzyl buta-2,3-dienoate and N-aryl-
idenebenzenesulfonamides yielded mainly 2-methyleneazet-
idines. Interestingly, a DABCO-catalysed reaction of 2,3-
allenoates, bearing a chiral auxiliary on the ester moiety,
with N-arylidenebenzenesulfonamides led to optically active
aza-Baylis–Hillman products and 2-azetine derivatives.
azetidines (Scheme 1).[8] The enantioselective aza-Baylis–
Hillman reaction of α,β-unsaturated ketones has been re-
ported,[9] whereas only one example of the asymmetric ver-
sion of the aza-Baylis–Hillman reaction of allenes with
imines is known.[10]
Introduction
2-Azetines[1,2] can be considered as enamines with a
highly strained double bond. They are difficult to prepare
and have received increasing interest in the last years be-
cause they are very versatile synthons for the preparation
of acyclic and cyclic derivatives.[3] These heterocyclic com-
pounds are mainly prepared from the corresponding four-
membered azetidines[2,3a–3c] and 1-amino-2-azetines or 3-
pyrrolines. They can also be obtained when electron-rich α-
allenyl hydrazines are treated with n-butyllithium or from
reaction of lithiomethoxyallenes with hydrazones.[4] How-
ever, preparative methods for 2- and 4-substituted 2-azet-
ines are scarce, and 2-azetinyl carboxylates specifically have
not been described.
Since the first report of Baylis and Hillman in 1972,[5]
the aza-Baylis–Hillman reaction has become an important
carbon–carbon bond-forming reaction,[6] and it is one of
the most fundamental reactions for the construction of mo-
lecular frameworks.[7] Furthermore, this synthetic method-
ology can be considered an efficient process, as it meets the
requirements of atom economy and generation of func-
tional groups. Typically, the process involves the reaction of
a Michael acceptor such as electron-deficient alkenes with
imines in the presence of Lewis bases to form highly func-
tionalized allylic amines. For example, Shi et al. proved that
allenoates can act as Michael acceptors in the aza-Baylis–
Hillman reaction to yield functionalized allenes as well as
Scheme 1. DABCO-catalysed reaction of ethyl 2,3-butadienoate
with N-tosylimine.
We have been interested in the preparation of three,[11]
four, five[12] and six-membered[13] nitrogen-containing het-
erocycles, as well as in the use of allenes as starting materi-
als for the preparation of acyclic and cyclic derivatives.[14]
In this context, we decided to further explore the reactivity
of allenes towards activated imines in the presence of
DABCO (1,4-diazabicyclo[2.2.2]octane). In particular, we
are interested in the development of asymmetric versions of
these reactions to synthesize optically active four-membered
nitrogen heterocycles.
[a] Department of Chemistry, University of Coimbra,
3004-535 Coimbra, Portugal
Results and Discussion
E-mail: tmelo@ci.uc.pt
[b] Department of Physics, University of Coimbra,
3004-516 Coimbra, Portugal
The reaction of benzyl buta-2,3-dienoate (5[15]) with N-
benzylidenebenzenesulfonamide (6[16]) and DABCO at
room temperature was explored (Scheme 2 and Table 1). By
carrying out the reaction for 1 h, 2-methyleneazetidine 7
was obtained in moderate yield (40%); aza-Baylis–Hillman
[c] Department of Organic Chemistry I, Faculty of Pharmacy,
University of the Basque Country,
Apartado 450, 01080 Vitoria, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901415.
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T. M. V. D. Pinho e Melo et al.
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adduct 9 was also isolated (25% yield). Interestingly, a new 67% yield (Table 2, Entry 2), whereas a longer reaction time
kind of four-membered heterocycle, 2-methyl-4-phenyl-1- (6 h) resulted in the formation of azetidine 11b (50% yield)
phenylsulfonamido-2-azetine-3-carboxylate (8), could also as the major product and 2-azetine 12 (5% yield; Table 2,
be detected and isolated from the same reaction (Table 1, Entry 3). The microwave-assisted reaction at 100 °C pro-
Entry 1). As far as we know, the occurrence of azetine-3- duced azetidine 11b regioselectively in 66% yield after only
carboxylates has never been reported for the reaction of 5 min (Table 2, Entry 4).
1
allenoates with imines. The H NMR spectrum of 8 shows
a signal at δ = 2.03 ppm, corresponding to the methyl
group, and a signal at δ = 4.97 ppm, corresponding to the
benzylic proton, which are in agreement with the assigned
structure. When the reaction was performed under the same
reaction conditions but with a longer reaction time (6 h), 2-
methyleneazetidine 7 and 2-azetine 8 were isolated in 35
and 5% yield, respectively (Table 1, Entry 2). However, no
evidence for the aza-Baylis–Hillman adduct was observed.
The DABCO-catalysed reaction of imine 6 and 5 was also
carried at room temperature for 1 h in the presence of 4 Å
molecular sieves and, as observed for allene 1 (Scheme 1,
vide supra),[8] azetidine 7 was obtained as the main product
together with a small proportion of aza-Baylis–Hillman ad-
duct 9 (9%); 2-azetine 8 could also be detected (Table 1,
Entry 3). Increasing the reaction time to 6 h led to the isola-
tion of 7 and 8 in 39 and 7% yield, respectively (Table 1,
Entry 4). Likewise, the microwave-mediated [2+2] annu- Scheme 3. DABCO-catalysed reaction of benzyl buta-2,3-dienoate
(5) with N-arylidenebenzenesulfonamides 2 and 10.
lation reaction produced 7 and 8 in 42 and 8.5% yield,
respectively (Table 1, Entry 5).
Table 2. DABCO-catalysed reaction of benzyl buta-2,3-dienoate (5)
with N-arylidenebenzenesulfonamides 2 and 10.
Entry
Imine
Reaction conditions
Product, Yield [%]
1
2
3
4
5
6
2
4 Å MS, r.t., 1 h
4 Å MS, r.t., 1 h
4 Å MS, r.t., 6 h
MW, 100 °C, 5 min
4 Å MS, r.t., 1 h
4 Å MS, r.t., 1 h
11a, 49
11b, 67
11b, 50; 12, 5
11b, 66
10a
10a
10a
10b
10c
11c, 59
11d, 22
Treatment of allene 5 with other imines such as 10b and
10c at room temperature for 1 h in the presence of DABCO
gave 2-methyleneazetidines 11c and 11d, respectively, as the
only products (Table 2, Entries 5 and 6).
The results described in Schemes 2 and 3 demonstrate
that the main pathway for the condensation of 5 with N-
arylidenebenzenesulfonamides in the presence of DABCO
is a formal [2+2] cycloaddition leading to 2-methyleneazet-
idines 7 and 11. This reaction was, however, accompanied
by the simultaneous formation of four-membered heterocy-
cles 8 and 12, which were also isolated.
Scheme 2. DABCO-catalysed reaction of benzyl buta-2,3-dienoate
(5) with imine 6.
Table 1. DABCO-catalysed reaction of benzyl buta-2,3-dienoate (5)
with imine 6.
Entry
Reaction conditions
Yield [%]
7
8
9
1
2
3
4
5
r.t.., 1 h
r.t.., 6 h
4 Å MS, r.t., 1 h
4 Å MS, r.t., 6 h
MW, 100 °C, 5 min
40
35
39
39
42
1
5
0.2
7
25
–
9
–
–
8.5
Next, the behaviour of optically active allenes was ex-
plored. The DABCO-catalysed reaction of chiral allenes
We then investigated the reactivity of 5 towards N-arylid- 13[18] and 16[18] with imine 6 at room temperature in the
enebenzenesulfonamides 2 and 10 in the presence of presence of 4 Å molecular sieves gave different results
DABCO (Scheme 3 and Table 2). The reaction of allene 5 (Scheme 4 and Table 3). The reaction of (1R)-(–)-10-phenyl-
with N-tosylimine 2 and DABCO at room temperature for sulfonylisobornyl buta-2,3-dienoate (13) with 6 at room
1 h gave 2-methyleneazetidine 11a in 49% yield (Table 2, temperature for 24 h afforded optically active 2-azetine 15
Entry 1). A more efficient reaction was observed when all- as the major product, and chiral α-allenylamine 14 in 31
ene 5 was treated with N-(4-nitrobenzylidene)benzenesul- and 18% yield, respectively (Table 3, Entry 1). Under the
fonamide (10a[17]). The DABCO-catalysed reaction carried same conditions but with shorter reaction times an increase
out at room temperature for 1 h gave only azetidine 11b in in the conversion and the formation of optically active 2-
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Synthesis of Chiral α-Allenylamines and 2-Azetines from Allenic Esters
azetine 15 was observed (Table 3, Entries 2 and 3). The ef- moderate yield (38%; Table 3, Entry 10). Notice that 2-azet-
fect of the temperature was also investigated. At 0 °C iden- ines 15 and 18 show identical NMR spectra but that the
tical products were formed in significantly higher overall values for the optical rotation have opposite signs, indicat-
yield (81%), although 2-azetine 15 and allene 14 were iso- ing that they are enantiomers. As far as we know, this strat-
lated in 44 and 37% yield, respectively (Table 3, Entry 4). egy represents the first example of preparation of optically
Interestingly, by lowering the temperature even further to active 2-azetines 15 and 18.
–20 °C, chiral α-allenylamine 14 was isolated as the major
product in 52% yield (Table 3, Entry 5).
The structure of allene 14 was determined by X-ray crys-
tallography (Figure 1). The absolute structure was deter-
mined by taking advantage of the significant anomalous
dispersion of sulfur at the Mo-Kα wavelength. Both Flack
analysis of the diffraction data and the results of separate
refinements of the possible enantiomers unambiguously as-
signed the S,S,S,R absolute configurations to the C5, C18,
C20 and C26 stereogenic centres, respectively. The phenyl
ring attached to S1 is disordered over two positions with
approximately 50% occupancy each.
Scheme 4. DABCO-catalysed reaction of chiral allenes 13 and 16
with N-benzylidenebenzenesulfonamide (6).
Table 3. DABCO-catalysed reaction of chiral allenes 13 and 16 with
N-benzylidenebenzenesulfonamide (6).
Figure 1. X-ray structure of 14. Some disordered atoms were omit-
ted for clarity.
Entry Allene
Reaction conditions
Product, Yield [%]
1
2
3
4
5
6
7
8
13
13
13
13
13
13
16
16
16
16
16
4 Å MS, r.t., 24 h
4 Å MS, r.t., 3 h
4 Å MS, r.t., 1 h
14, 18; 15, 31
14, 12.5; 15, 48
14, 8; 15, 45
14, 37; 15, 44
14, 52; 15, 9
15, 24
The preceding results show that the selectivity of the con-
densation of chiral allenoates 13 and 16 with 6 depends on
the choice of reaction conditions. When the reaction is done
at room temperature 2-azetines are formed as the major
product, whereas at –20 °C the α-allenylamines are formed
preferentially (Scheme 4). It is noteworthy that the presence
of a (1R)- or (1S)-10-phenylsulfonylisobornyl substituent
seems to hinder the formation of 2-methyleneazetidines
(i.e., 3, 7, 11; Schemes 1–3) as has been observed for al-
4 Å MS, 0 °C, 24 h
4 Å MS, –20 °C, 24 h
MW, 100 °C, 15 min
4 Å MS, r.t., 24 h
4 Å MS, r.t., 1 h
4 Å MS, –20 °C, 24 h
4 Å MS, –20 °C, 6 h
MW, 100 °C, 15 min
17, 9; 18, 44
17, 4; 18, 55
17, 46; 18, 12
17, 38
9
10
11
18, 16
Concerning the enantiomeric allene, the aza-Baylis–Hill- lenoates 1 and 5.
man reaction of (1S)-(+)-10-phenylsulfonylisobornyl buta- The microwave-assisted reaction of imine 6 with allenes
2,3-dienoate (16) with imine 6 at room temperature for 24 h 13 and 16 at 100 °C for 15 min afforded heterocycle 15
gave 2-azetine 18 as the major product (44% yield) and op- (Table 3, Entry 6) and 2-azetine 18 (Table 3, Entry 11),
tically active α-allenylamine 17, the enantiomer of 14, in 9% respectively. Allenes 14 and 17 were formed in less than 1%
yield (Table 3, Entry 7). By performing the reaction with a yield and could only be detected by NMR spectroscopy. On
significantly shorter reaction time (1 h), 2-azetine 18 could the other hand, a significant amount of benzenesulfon-
be obtained in higher yield (55%; Table 3, Entry 8). Carry- amide was isolated, suggesting a lack of stability of the
ing out the reaction at lower temperature (–20 °C for 24 h) products upon microwave irradiation.
led to the formation of α-allenylamine 17 (46%; Table 3,
The formation of aza-Baylis–Hillman adducts 14 and 17
Entry 9) as the major product. Efforts to reduce the reac- and 2-azetines 15 and 18 can be explained as outlined in
tion time gave α-allenylamine 17 as the only product in Scheme 5. Nucleophilic addition of DABCO to 2,3-alleno-
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T. M. V. D. Pinho e Melo et al.
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ate 19 produces zwitterionic intermediate 20, which in turn
reacts with the imine to give 21. Proton transfer gives inter-
mediate 22, which then undergoes elimination of DABCO
to give α-allenylaminealkylallene 23. A similar mechanism
was previously reported for the formation of α-allenylam-
ines.[8] The synthesis of these allenes as single stereoisomers
is explained by selective addition of the imine to 20, leading
to intermediate 21. Resonance-stabilized zwitterionic inter-
mediate 24 can also undergo proton transfer to give inter-
mediate 25. Cyclization of 25 leads to another zwitterionic
intermediate 26, which can then expel DABCO to produce
2-azetine 27. Because intermediate 21 is common to both
pathways, the chirality of both α-allenylamine and 2-azetine
is expected to originate from the same chiral allene. Alter-
natively, the 2-azetines could result from a 4-exo-dig cycliza-
tion of α-allenylamines 23. This mechanistic pathway was
ruled out, as attempts to convert α-allenylamines into the
corresponding 2-azetines were unsuccessful. In fact, treat-
ment of allene 14 with DABCO at room temperature for
24 h led only to the recovery of the starting material.
Scheme 6. DABCO-catalysed reaction of chiral allenes 13 and 16
with N-(4-nitrobenzylidene)benzenesulfonamide (10a).
We can conclude that the DABCO-catalysed reaction of
(1R)-(–)-10-phenylsulfonylisobornyl buta-2,3-dienoate with
N-arylidenebenzenesulfonamide leads to chiral products
with S configuration at the new stereogenic centre. Con-
versely, the use of (1S)-(+)-10-phenylsulfonylisobornyl
buta-2,3-dienoate gives products with R configuration. It is
noteworthy that the careful choice of reaction conditions
can be used to favour the formation of optically active acy-
clic α-allenylamines or cyclic 2-azetines.
In order to determine if the presence of the (1R)- or (1S)-
10-phenylsulfonylisobornyl substituent on the allene is re-
quired to prevent the formal [2+2] cycloaddition, the
DABCO-catalysed reaction of allene 30 bearing a sterically
demanding ester group with N-arylidenebenzenesulfon-
amides was studied (Scheme 7). The reaction of allene 30
with 6 and DABCO was carried out either at room tem-
perature or under microwave irradiation to give 2-methyl-
eneazetidine 31a and α-allenylamine 33 (Table 4, Entries 1–
4). The best results were obtained by performing the reac-
Scheme 5. Proposed mechanism for the formation of aza-Baylis–
Hillman adducts and 2-azetines.
The reaction of chiral allenes 13 and 16 with 10a in the
presence of DABCO at room temperature led, in both cases,
to the corresponding chiral α-allenylamines 28 and 29 in
moderate yield and in a selective fashion. By carrying out
this reaction at –20 °C the chiral allenes could be obtained
in higher yield (Scheme 6). Lower temperatures and the
presence of an electron-withdrawing group on the imine
may favour the formation of optically active acyclic α-allen-
ylamines over the cyclic 2-azetine derivatives. These results
could be explained by invoking the proposed mechanism
(Scheme 5). At lower temperatures or by the use of more
reactive electron-poor imines, the elimination of DABCO
to produce α-allenylamines 23 could be more favourable
than the [1,3]-prototropic rearrangement between interme-
diates 24 and 25, which leads to 2-azetines 27.
Scheme 7. DABCO-catalysed reaction of tert-butyl buta-2,3-dieno-
ate (30) with N-arylidenebenzenesulfonamides 6 and 10a.
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Synthesis of Chiral α-Allenylamines and 2-Azetines from Allenic Esters
tion at room temperature for 24 h to afford heterocycle 31a pyrroles.[19] On the other hand, strained cyclic enamines,
and allene 33 in 37 and 40% yield, respectively (Table 4, such as 2-azetines, show particularly interesting reactiv-
Entry 3). The reaction of 30 with 10a did not produce the ity.[1–3]
corresponding aza-Baylis–Hillman adduct; instead, 2-meth-
yleneazetidine 31b was formed exclusively as the major
Experimental Section
Unless otherwise noted 1H and 13C NMR spectra were recorded
in CDCl3 at 400 and 100 MHz, respectively. Mass spectra were re-
corded on an instrument operating in ESI mode.
product (Table 4, Entries 5–8). In fact, the reaction done at
room temperature for 1 h afforded azetidines 31b and 32
in 24 and 5% yield, respectively (Table 4, Entry 5). Longer
reaction times led to 2-azetidine 31b as the sole product
(47–54%; Table 4, Entries 6 and 7). The microwave-in-
duced, DABCO-catalysed reaction gave only azetidine 31b
in 48% (Table 4, Entry 8).
General Procedure for the Synthesis of Abnormal and Normal Aza-
Baylis–Hillman Adducts
Method A: To
a mixture of N-arylidenebenzenesulfonamide
(1.0 mmol), DABCO (22 mg, 0.2 mmol) and 4 Å MS (400 mg) in
toluene (2 mL) was added a solution of the corresponding allene
(1.1 mmol) in toluene (1 mL). The reaction mixture was stirred un-
der an atmosphere of nitrogen for the duration indicated in the
individual procedures. The reaction mixture was then washed with
water (3ϫ20 mL) and extracted with dichloromethane
(2ϫ20 mL). The organic layer was dried with anhydrous MgSO4,
and solvents were removed under reduced pressure. The crude
product was purified by flash column chromatography (ethyl acet-
ate/hexane).
Table 4. DABCO-catalysed reaction of tert-butyl buta-2,3-dienoate
(30) with N-arylidenebenzenesulfonamides 6 and 10a.
Entry Imine
Reaction conditions
Product, Yield [%]
1
2
3
4
5
6
7
8
6
6
4 Å MS, r.t., 1 h
4 Å MS, r.t., 6 h
4 Å MS, r.t., 24 h
MW, 100 °C, 5 min
4 Å MS, r.t., 1 h
4 Å MS, r.t., 6 h
4 Å MS, r.t., 24 h
MW, 100 °C, 5 min
31a, 24; 33, 30
31a, 21; 33, 24
31a, 37; 33, 40
31a, 35; 33, 22
31b, 24; 32, 9
31b, 47
6
6
10a
10a
10a
10a
31b, 54
Method B:
A suspension of N-arylidenebenzenesulfonamide
31b, 48
(0.5 mmol), DABCO (11 mg, 0.10 mmol) and the corresponding
allene (0.55 mmol) in toluene (3 mL) was irradiated in a microwave
reactor (CEM Focused Synthesis System, Discover S-Class) at
100 °C for 15 min. The reaction mixture was then washed with
water (3ϫ20 mL) and extracted with dichloromethane
(2ϫ20 mL). The organic layer was dried with anhydrous MgSO4,
and solvents were removed under reduced pressure. The crude
product was purified by flash column chromatography (ethyl acet-
ate/hexane).
These results have shown that 2-methyleneazetidines can
be obtained from the reaction of 30 with N-arylideneben-
zenesulfonamides. The reactivities of allene 30 and 5 are
similar. However, the use of allene 30 instead of 5 favours
the formation of α-allenylamines in the condensation reac-
tion with imine 6. On the other hand, the DABCO-cata-
lysed reaction of 30 with imine 10a gave mainly the corre-
sponding 2-methyleneazetidine, as previously observed for
the reaction of allene 5 with the same imine. The reactivities
of chiral allenes 13 and 16 are different from those shown
by allenes 5 and 30. In fact, 2-methyleneazetidines are not
formed from the reaction of the chiral allenes and N-aryl-
idenebenzenesulfonamides, which leads to optically active
aza-Baylis–Hillman products and 2-azetine derivatives. The
outcome of the reaction can be controlled by the selection
of the reaction conditions or by the nature of the imine
counterpart.
(E)-Benzyl 2-[4-Phenyl-1-(phenylsulfonyl)azetindin-2-ylidene]ethano-
ate (7), Benzyl 4-methyl-2-phenyl-1-(phenylsulfonamido)-2-azetine-3-
carboxylate (8) and Benzyl 2-[phenyl(phenylsulfonamido)meth-
yl]buta-2,3-dienoate (9): Yield (method A; r.t., 1 h): 0.2 (for 8), 39
(for 7) and 9% (for 9); Yield (method B): 8.5 (for 8) and 42% (for
7). Purification by flash chromatography (hexane/ethyl acetate, 1:4)
gave (in order of elution) 8, 7 and 9. Data for 8: Oil. IR (film): ν
˜
1
= 3134, 1715, 1623, 1401, 1166 cm–1. H NMR: δ = 2.04 (s, 3 H,
CH3), 4.98 (s, 1 H, CHPh), 5.15 (s, 2 H, CH2Ph), 7.30–7.42 (m, 10
H, Ar-H), 7.51–7.55 (m, 2 H, Ar-H), 7.59–7.63 (m, 1 H, Ar-H),
3
7.90 (d, J = 7.6 Hz, 2 H, Ar-H) ppm. 13C NMR: δ = 19.8, 48.0,
65.9, 96.3, 127.1, 128.2, 128.3, 128.6, 129.3, 133.3, 135.8, 140.5,
153.1, 168.8 ppm. MS (ESI): m/z (%) = 420 (1) [M + 1]+, 407 (3),
386 (2), 354 (21), 332 (8), 247 (1), 215 (100). HRMS (ESI): calcd.
Conclusions
for C24H22NO4S 420.12641; found 420.12776. Data for 7: Oil. IR
1
(film): ν = 1706, 1655, 1168, 1119 cm–1. H NMR: δ = 3.11 (ddd,
˜
3
4
2J = 16.8 Hz, J = 4.2 Hz, J = 2.1 Hz, 1 H, CHCH2), 3.51 (ddd,
Optically active α-allenylamines and 2-azetines were pre-
pared by using a DABCO-catalysed reaction of 2,3-al- 2J = 16.8 Hz, J = 7.0 Hz, J = 2.1 Hz, 1 H, CHCH2), 5.10 (d, J
3
4
2
2
= 12.4 Hz, 1 H, CH2Ph), 5.16 (d, J = 12.4 Hz, 1 H, CH2Ph), 5.22
(dd, 3J = 7.0, 4.2 Hz, 1 H, CHCH2), 5.92–5.93 (m, 1 H, =CH),
7.30–7.36 (m, 10 H, Ar-H), 7.41–7.46 (m, 2 H, Ar-H), 7.56–7.65
(m, 3 H, Ar-H) ppm. 13C NMR: δ = 37.5, 65.7, 66.4, 94.3, 126.8,
127.3, 128.1, 128.5, 128.7, 129.0, 129.2, 133.8, 136.2, 136.8, 137.4,
158.7, 167.0 ppm. MS (ESI): m/z (%) = 420 (100) [M + 1]+, 312
(3), 197 (5). HRMS (ESI): calcd. for C24H22NO4S 420.12641; found
lenoates, bearing a chiral auxiliary on the ester moiety, with
N-arylidenebenzenesulfonamides. The use of (1R)-(–)-10-
phenylsulfonylisobornyl buta-2,3-dienoate as a starting ma-
terial affords products with S configuration, whereas (1S)-
(+)-10-phenylsulfonylisobornyl buta-2,3-dienoate leads to
products with R configuration. The outcome of the reaction
can be controlled by carefully selecting the reaction condi-
tions or by tuning the electronic properties of the imine.
Functionalized chiral α-allenylamines have great potential
420.12491. Data for 9: Oil. IR (film): ν = 3280, 1965, 1706, 1330,
˜
2
1165 cm–1. 1H NMR: δ = 5.01 (d, J = 12.8 Hz, 1 H, CH2Ph), 5.05
(d, 2J = 12.8 Hz, 1 H, CH2Ph), 5.09 (d, 2J = 14.8 Hz, 1 H, C=CH2),
2
3
as building blocks for the synthesis of chiral pyrrolines and 5.16 (d, J = 14.8 Hz, 1 H, C=CH2), 5.36 (d, J = 10.0 Hz, 1 H,
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T. M. V. D. Pinho e Melo et al.
FULL PAPER
3
CHNH), 5.84 (d, J = 10.0 Hz, 1 H, CHNH), 7.17–7.19 (m, 2 H, (22), 291 (20). HRMS (ESI): calcd. for C25H24NO5S 450.13697;
Ar-H), 7.22–7.24 (m, 5 H, Ar-H), 7.31–7.37 (m, 5 H, Ar-H), 7.47 found 450.13744.
3
(m, 1 H, Ar-H), 7.76 (d, J = 7.6 Hz, 2 H, Ar-H) ppm. 13C NMR:
(E)-Benzyl 2-[4-(2,4-Dinitrophenyl)-1-(phenylsulfonyl)azetindin-2-yl-
δ = 55.6, 65.8, 80.4, 99.5, 125.5, 126.1, 126.8, 126.9, 127.2, 127.5,
idene]ethanoate (11d): Yield (method A; r.t., 1 h): 22%. Purification
127.5, 127.8, 131.5, 134.4, 137.9, 139.8, 164.1, 212.2 ppm. MS
by flash chromatography (hexane/ethyl acetate, 1:3 to 1:2) gave 11d
(ESI): m/z (%) = 420 (41) [M + 1]+, 263 (100), 245 (14), 215 (16).
as a yellow oil. IR (film): ν = 1709, 1665, 1536, 1345, 1118 cm–1.
˜
HRMS (ESI): calcd. for C24H22NO4S 420.12641; found 420.12603.
3
4
1H NMR: δ = 2.96 (ddd, 2J = 17.2 Hz, J = 4.4 Hz, J = 1.6 Hz, 1
2
3
4
(E)-Benzyl 2-(4-Phenyl-1-tosylazetindin-2-ylidene)ethanoate (11a):
Yield (method A; r.t., 1 h): 49%. Purification by flash chromatog-
raphy (hexane/ethyl acetate, 1:6 to 1:5) gave 11a as a white solid.
H, CHCH2), 3.74 (ddd, J = 17.2 Hz, J = 7.6 Hz, J = 1.6 Hz, 1
H, CHCH2), 5.09 (d, 2J = 12.4 Hz, 1 H, CH2Ph), 5.13 (d, 2J =
3
12.4 Hz, 1 H, CH2Ph), 5.63 (dd, J = 7.6, 4.4 Hz, 1 H, CHCH2),
M.p. 116.1–117.0 °C. IR (film): ν = 1709, 1661, 1165, 1119 cm–1. 6.06 (s, 1 H, =CH), 7.33–7.37 (m, 6 H, Ar-H), 7.62–7.66 (m, 2 H,
˜
1H NMR: δ = 2.42 (s, 3 H, CH3), 3.10 (ddd, 2J = 16.8 Hz, 3J =
Ar-H), 7.75–7.79 (m, 1 H, Ar-H), 7.87 (d, 3J = 7.6 Hz, 2 H, Ar-
H), 8.39 (d, 3J = 8.8 Hz, 1 H, Ar-H), 8.58–8.63 (m, 1 H, Ar-H),
8.98–9.00 (m, 1 H, Ar-H) ppm. 13C NMR: δ = 38.0, 62.7, 66.1,
98.0, 120.7, 127.8, 128.2, 128.3, 128.5, 128.6, 129.9, 130.4, 131.5,
134.9, 135.9, 140.5, 146.6, 147.8, 156.7, 166.2, 186.3 ppm. MS
(ESI): m/z (%) = 510 (48) [M + 1]+, 476 (39), 450 (46), 354 (75),
332 (100), 291 (52), 251 (73). HRMS (ESI): calcd. for C24H20N3O8S
4
2
3
4.4 Hz, J = 1.6 Hz, 1 H, CHCH2), 3.49 (ddd, J = 16.8 Hz, J =
6.8 Hz, 4J = 1.6 Hz, 1 H, CHCH2), 5.12–5.18 (m, 2 H, CH2Ph),
3
5.19 (dd, J = 6.8, 4.4 Hz, 1 H, CHCH2), 5.90 (s, 1 H, =CH), 7.24
3
(d, J = 8.4 Hz, 2 H, Ar-H), 7.32–7.36 (m, 10 H, Ar-H), 7.55 (d,
3J = 8.4 Hz, 2 H, Ar-H) ppm. 13C NMR: δ = 21.6, 37.5, 65.7, 66.3,
94.3, 126.8, 127.4, 128.1, 128.1, 128.5, 128.7, 128.9, 129.8, 134.4,
136.3, 137.2, 144.9, 158.8, 167.1 ppm. MS (ESI): m/z (%) = 434 510.09656; found 510.09753.
(100) [M + 1]+, 359 (4), 315 (5), 230 (3), 201 (25). HRMS (ESI):
calcd. for C25H24NO4S 434.14206; found 434.14067.
(1R)-(–)-10-Phenylsulfonylisobornyl
(S)-2-[Phenyl(phenylsulfon-
amido)methyl]buta-2,3-dienoate (14) and (1R)-(–)-10-Phenylsulfon-
ylisobornyl (S)-3-Methyl-4-phenyl-1-phenylsulfonamido-2-azetine-3-
carboxylate (15): Yield (method A; r.t., 1 h): 45 (for 15) and 8%
(for 14); yield (method A; –20 °C, 24 h): 9 (for 15) and 52% (for
14); yield (method B): 24% (for 15). Purification by flash
chromatography (hexane/ethyl acetate, 1:2) gave (in order of elu-
(E)-Benzyl 2-[4-(4-Nitrophenyl)-1-(phenylsulfonyl)azetindin-2-ylid-
ene]ethanoate (11b) and Benzyl 4-Methyl-2-(4-nitrophenyl)-1-(phen-
ylsulfonamido)-2-azetine-3-carboxylate (12): Yield (method A; r.t.,
6 h): 5 (for 12) and 50% (for 11b); yield (method B): 66% (for 11b).
Purification by flash chromatography (hexane/ethyl acetate, 1:2)
gave (in order of elution) 12 and 11b. Data for 12: Oil. IR (film):
tion) 15 and 14. Data for 15: Oil. IR (film): ν = 2959, 1711, 1318,
˜
ν = 3132, 1716, 1400, 1162 cm–1. 1H NMR: δ = 2.26 (s, 3 H, CH ),
1168 cm–1. 1H NMR: δ = 0.86 (s, 3 H), 0.92 (s, 3 H), 1.17–1.22 (m,
˜
3
4.76 (d, 2J = 12.0 Hz, 1 H, CH2Ph), 4.97 (d, 2J = 12.0 Hz, 1 H, 1 H), 1.64 (br. s, 2 H), 1.75–1.78 (m, 2 H), 1.86–1.96 (m, 2 H), 2.05
CH2Ph), 5.70 (s, 1 H, CHPh), 7.45–7.47 (m, 2 H, Ar-H), 7.51–7.56
(s, 3 H, =CCH3), 3.00 (d, 2J = 14.4 Hz, 1 H), 3.54 (d, 2J = 14.4 Hz,
3
(m, 8 H, Ar-H), 7.69–7.73 (m, 2 H, Ar-H), 8.22 (d, J = 8.8 Hz, 2 1 H), 4.76–4.78 (m, 1 H), 4.80 (s, 1 H, CHPh), 7.31–7.33 (m, 1 H,
H, Ar-H) ppm. 13C NMR: δ = 20.6, 67.0, 71.8, 120.3, 124.4, 126.9, Ar-H), 7.38–7.71 (m, 9 H, Ar-H), 7.83 (d, 3J = 7.6 Hz, 2 H, Ar-
127.4, 127.5, 128.6, 128.7, 130.1, 131.3, 139.9, 144.3, 148.1, H), 7.93 (d, 3J = 7.6 Hz, 2 H, Ar-H) ppm. 13C NMR: δ = 19.7,
163.3 ppm. MS (ESI): m/z (%) = 465 (7) [M + 1]+, 420 (66), 391
19.9, 20.3, 27.1, 29.7, 39.6, 44.1, 49.3, 49.9, 53.4, 55.2, 78.9, 96.6,
(100), 301 (49), 210 (39). HRMS (ESI): calcd. for C24H21N2O6S 126.4, 127.1, 127.7, 129.2, 129.4, 133.3, 133.5, 140.5, 141.2, 152.7,
465.10756; found 465.11148. Data for 11b: Yellow solid, m.p.
167.6 ppm. MS (ESI): m/z (%) = 606 (56) [M + 1]+, 518 (100),
138.0–140.0 °C. IR (film): ν = 1701, 1661, 1522, 1345, 1168, 401 (10), 277 (28), 197 (6). HRMS (ESI): calcd. for C33H36NO6S2
˜
1120 cm–1. H NMR: δ = 2.98 (ddd, J = 16.8 Hz, J = 4.0 Hz,4J
606.19786; found 606.19708. [α]2D0 = +33 (c = 0.75, CH2Cl2). Data
1
2
3
2
3
4
= 1.6 Hz, 1 H, CHCH2), 3.48 (ddd, J = 16.8 Hz, J = 7.2 Hz, J
for 14: White solid, m.p. 135.0–137.0 °C. IR (film): ν = 3256, 1970,
˜
2
1
= 1.6 Hz, 1 H, CHCH2), 5.03 (d, J = 12.4 Hz, 1 H, CH2Ph), 5.08
1709, 1309, 1162 cm–1. H NMR: δ = 0.67 (s, 3 H), 0.80 (s, 3 H),
(d, 2J = 12.4 Hz, 1 H, CH2Ph), 5.17 (dd, 3J = 7.2, 4.0 Hz, 1 H,
1.10–1.16 (m, 1 H), 1.47–1.60 (m, 2 H), 1.70 (br. s, 2 H), 1.81–1.86
2
2
CHCH2), 5.90 (s, 1 H, =CH), 7.27 (br. s, 5 H, Ar-H), 7.44–7.47 (m, 2 H), 2.88 (d, J = 14.0 Hz, 1 H), 3.34 (d, J = 14.0 Hz, 1 H),
3
(m, 4 H, Ar-H), 7.58–7.62 (m, 1 H, Ar-H), 7.68 (d, J = 8.4 Hz, 2 4.73 (dd, 3J = 7.6, 2.8 Hz, 1 H), 4.98 (d, 2J = 14.4 Hz, 1 H,
H, Ar-H), 8.11 (d, 3J = 8.4 Hz, 2 H, Ar-H) ppm. 13C NMR: δ = C=CH2), 5.03 (d, 2J = 14.4 Hz, 1 H, C=CH2), 5.32 (d, 3J = 9.6 Hz,
3
36.5, 63.7, 64.9, 94.7, 123.1, 126.4, 127.2, 127.6, 128.5, 133.3, 135.0,
1 H, CHNH), 6.15 (d, J = 9.6 Hz, 1 H, CHNH), 7.31–7.33 (m, 2
135.7, 143.4, 147.1, 156.5, 165.6 ppm. MS (ESI): m/z (%) = 465 H, Ar-H), 7.39–7.59 (m, 8 H, Ar-H), 7.78–7.84 (m, 4 H, Ar-H),
(100) [M + 1]+, 447 (21), 391 (12), 210 (18). HRMS (ESI): calcd.
for C24H21N2O6S 465.11148; found 465.11119.
7.92 (d, J = 7.6 Hz, 1 H, Ar-H) ppm. 13C NMR: δ = 19.6, 20.2,
27.0, 29.5, 39.3, 44.0, 49.5, 49.8, 54.9, 57.0, 78.6, 80.2, 100.3, 126.4,
126.6, 127.2, 127.6, 127.9, 128.6, 128.9, 129.1, 129.2, 132.5, 133.6,
138.9, 163.8, 213.8 ppm. MS (ESI): m/z (%) = 606 (31) [M + 1]+,
449 (18), 401 (13), 277 (100), 197 (18). HRMS (ESI): calcd. for
C33H36NO6S2 606.19786; found 606.19761. [α]2D0 = +40 (c = 0.1,
CH2Cl2).
3
(E)-Benzyl 2-[4-(4-Methoxyphenyl)-1-(phenylsulfonyl)azetindin-2-yl-
idene]ethanoate (11c): Yield (method A; r.t., 1 h): 59%. Purification
by flash chromatography (hexane/ethyl acetate, 1:3 to 1:2) gave 11c
as a yellow solid, m.p. 87.2–88.9 °C. IR (film): ν = = 1714, 1666,
˜
1248, 1090 cm–1. 1H NMR: δ = 3.11 (ddd, 2J = 16.8 Hz, 3J =
4
2
3
4.0 Hz, J = 1.6 Hz, 1 H, CHCH2), 3.49 (ddd, J = 16.8 Hz, J =
(1S)-(+)-10-Phenylsulfonylisobornyl
(R)-2-[Phenyl(phenylsulfon-
4
6.8 Hz, J = 1.6 Hz, 1 H, CHCH2), 3.80 (s, 3 H, OCH3), 5.11 (d,
amido)methyl]buta-2,3-dienoate (17) and (1S)-(+)-10-Phenylsulfon-
ylisobornyl (R)-3-Methyl-4-phenyl-1-phenylsulfonamido-2-azetine-3-
carboxylate (18): Yield (method A; r.t., 1 h): 55 (for 18) and 4%
(for 17); yield (method A; –20 °C, 24 h): 12 (for 18) and 46% (for
2J = 12.4 Hz, 1 H, CH2Ph), 5.15 (d, J = 12.4 Hz, 1 H, CH2Ph),
2
3
5.20 (dd, J = 6.8, 4.0 Hz, 1 H, CHCH2), 5.90 (s, 1 H, =CH), 6.81
(d, 3J = 8.8 Hz, 2 H, Ar-H), 7.21 (d, 3J = 8.8 Hz, 2 H, Ar-H), 7.30–
7.36 (m, 6 H, Ar-H), 7.43 (m, 2 H, Ar-H), 7.62–7.63 (m, 2 H, Ar- 17); yield (method B): 16% (for 18). Purification by flash
H) ppm. 13C NMR: δ = 37.5, 55.4, 65.7, 66.3, 94.0, 114.1, 127.2,
128.2, 128.4, 128.6, 128.8, 129.2, 133.7, 136.3, 137.7, 158.8, 160.1,
167.1 ppm. MS (ESI): m/z (%) = 450 (100) [M + 1]+, 382 (12), 359
chromatography (hexane/ethyl acetate, 1:2) gave (in order of elu-
tion) 18 and 17: Data for 18: Oil. IR (film): ν = 2958, 1714, 1317,
˜
1166 cm–1. 1H NMR: δ = 0.86 (s, 3 H), 0.92 (s, 3 H), 1.17–1.24 (m,
3254
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3249–3256

Synthesis of Chiral α-Allenylamines and 2-Azetines from Allenic Esters
1 H), 1.59–1.63 (m, 2 H), 1.75–1.76 (m, 2 H), 1.88–1.96 (m, 2 H),
2.05 (s, 3 H, =CCH3), 3.00 (d, 2J = 14.4 Hz, 1 H), 3.54 (d, 2J =
and 40% (for 33); yield (method B): 24 (for 31a) and 22% (for 33).
Purification by flash chromatography (hexane/ethyl acetate, 1:4)
gave (in order of elution) 31a and 33. Data for 31a: Oil. IR (film):
14.4 Hz, 1 H), 4.75–4.78 (m, 1 H), 4.79 (s, 1 H, CHPh), 7.30–7.33
3
(m, 1 H, Ar-H), 7.35–7.71 (m, 10 H, Ar-H), 7.83 (d, J = 7.6 Hz, ν = 1701, 1665, 1324, 1150 cm–1. 1H NMR: δ = 1.46 [s, 9 H,
˜
3
2
3
4
2 H, Ar-H), 7.93 (d, J = 7.6 Hz, 2 H, Ar-H) ppm. 13C NMR: δ = C(CH3)3], 3.09 (ddd, J = 16.7 Hz, J = 4.2 Hz, J = 2.1 Hz, 1 H,
19.7, 19.9, 20.3, 27.1, 29.7, 39.6, 44.1, 49.3, 49.9, 53.4, 55.2, 96.5,
CHCH2), 3.50 (ddd, 2J = 16.7 Hz, 3J = 7.1, 2.1 Hz, 1 H, CHCH2),
127.2, 127.7, 129.2, 129.4, 133.3, 133.5, 140.5, 141.2, 152.7, 5.21 (dd, 3J = 7.0, 4.2 Hz, 1 H, CHCH2), 5.77–5.79 (m, 1 H, =CH),
167.6 ppm. MS (ESI): m/z (%) = 606 (47) [M + 1]+, 518 (100),
277 (30). HRMS (ESI): calcd. for C33H36NO6S2 606.19786; found
606.19986. [α]2D0 = –33 (c = 0.75, CH2Cl2). Data for 17: White solid,
7.31–7.39 (m, 5 H, Ar-H), 7.44–7.49 (m, 2 H, Ar-H), 7.58–7.68 (m,
3 H, Ar-H) ppm. 13C NMR: δ = 28.3, 37.4, 66.2, 80.0, 96.7, 126.8,
127.3, 128.7, 128.9, 129.1, 133.6, 137.1, 137.5, 157.0, 166.6 ppm.
MS (ESI): m/z (%) = 408 (19) [M + Na]+, 330 (100), 312 (42),
191 (8). HRMS (ESI): calcd. for C21H23NNaO4S 408.12400; found
m.p. 135.0–137.0 °C. IR (film): ν = 3256, 1964, 1710, 1309,
˜
1161 cm–1. 1H NMR: δ = 0.68 (s, 3 H), 0.80 (s, 3 H), 1.11–1.17 (m,
1 H), 1.48–1.60 (m, 2 H), 1.70 (br. s, 2 H), 1.81–1.86 (m, 2 H), 2.88
408.12401. Data for 33: Oil. IR (film): ν = 3279, 1967, 1703, 1329,
˜
2
2
3
(d, J = 14.0 Hz, 1 H), 3.35 (d, J = 14.0 Hz, 1 H), 4.72 (dd, J = 1167 cm–1. 1H NMR: δ = 1.31 [s, 9 H, C(CH3)3], 5.01 (dd, 2J =
2
2
4
2
4
7.6, 2.8 Hz, 1 H), 4.98 (d, J = 14.4 Hz, 1 H, C=CH2), 5.03 (d, J 14.2 Hz, J = 1.2 Hz, 1 H, C=CH2), 5.09 (dd, J = 14.2 Hz, J =
3
3
= 14.4 Hz, 1 H, C=CH2), 5.31 (d, J = 9.2 Hz, 1 H, CHNH), 6.10
1.3 Hz, 1 H, C=CH2), 5.30 (d, J = 9.9 Hz, 1 H, CHNH), 5.86 (d,
(d, 3J = 9.2 Hz, 1 H, CHNH), 7.21–7.59 (m, 10 H, Ar-H), 7.78– 3J = 9.9 Hz, 1 H, CHNH), 7.21–7.26 (m, 5 H, Ar-H), 7.42–7.54
7.84 (m, 4 H, Ar-H), 7.92–7.93 (m, 1 H, Ar-H) ppm. 13C NMR: δ
= 19.6, 20.2, 27.1, 29.5, 39.3, 44.0, 49.6, 49.8, 55.0, 57.0, 78.7, 80.2,
100.5, 126.7, 127.3, 127.6, 128.6, 128.9, 129.2, 132.5, 133.6, 139.0,
163.8, 213.8 ppm. MS (ESI): m/z (%) = 606 (62) [M + 1]+, 518 (10), [M
(m, 3 H, Ar-H), 7.79–7.82 (m, 2 H, Ar-H) ppm. 13C NMR: δ =
27.8, 56.6, 80.7, 82.1, 101.5, 126.4, 127.1, 127.6, 128.3, 128.8, 132.4,
139.2, 140.8, 164.3, 212.8 ppm. MS (ESI): m/z (%) = 408 (100)
+
Na]+, 352 (14), 143 (18). HRMS (ESI): calcd. for
449 (16), 277 (100), 197 (63). HRMS (ESI): calcd. for C33H36NO6S2 C21H23NNaO4S 408.12400; found 408.12342.
606.19786; found 606.19898. [α]2D0 = –40 (c = 0.1, CH2Cl2).
(E)-tert-Butyl 2-[4-(4-Nitrophenyl)-1-(phenylsulfonyl)azetindin-2-yl-
idene]ethanoate (31b) and tert-Butyl 4-Methyl-2-phenyl-1-(phenyl-
sulfonamido)-2-azetine-3-carboxylate (32): Yield (method A; r.t.,
1 h): 24 (for 31a) and 9% (for 32); yield (method B): 48% (for 31b).
Purification by flash chromatography (hexane/ethyl acetate, 1:4)
gave (in order of elution) 32 and 31b. Data for 32: Yellow oil. IR
(1R)-(+)-10-Phenylsulfonylisobornyl
(S)-2-[Nitrophenyl(phenyl-
sulfonamido)methyl]buta-2,3-dienoate (28): Yield (method A;
–20 °C, 48 h): 52%. Purification by flash chromatography (hexane/
ethyl acetate, 1:2) gave 28 as a yellow solid, m.p. 115.0–117.0 °C.
1
IR (KBr): ν = 3265, 1966, 1707, 1522, 1347, 1165 cm–1. H NMR:
˜
δ = 0.61 (s, 3 H), 0.70 (s, 3 H), 1.09–1.12 (m, 1 H), 1.55–1.58 (m,
(film): ν = 3122, 1713, 1619, 1168 cm–1. 1H NMR: δ = 1.36 [s, 9
˜
2
2 H), 1.65 (br. s, 2 H), 1.70–1.83 (m, 2 H), 2.85 (d, J = 14.0 Hz,
H, C(CH3)3], 2.17 (br. s, 3 H, CH3), 5.68 (br. s, 1 H, CHPh), 7.39–
7.59 (m, 5 H, Ar-H), 7.75–7.80 (m, 2 H, Ar-H), 8.22–8.25 (m, 2 H,
Ar-H) ppm. 13C NMR: δ = 20.4, 28.0, 71.7, 82.9, 122.3, 124.1,
127.4, 130.1, 131.5, 132.7, 134.5, 144.4, 147.5, 148.1, 162.8 ppm.
MS (ESI): m/z (%) = 453 (27) [M + Na]+, 375 (67), 357 (100), 331
(12). HRMS (ESI): calcd. for C21H22N2NaO6S 453.10908; found
2
3
1 H), 3.25 (d, J = 14.0 Hz, 1 H), 4.85 (dd, J = 7.6, 3.2 Hz, 1 H),
2
2
4.92 (d, J = 14.4 Hz, 1 H, C=CH2), 5.06 (d, J = 14.4 Hz, 1 H,
3
3
C=CH2), 5.31 (d, J = 9.2 Hz, 1 H, CHNH), 6.18 (d, J = 9.2 Hz,
1 H, CHNH), 7.39–7.59 (m, 12 H, Ar-H), 7.77–7.79 (m, 4 H, Ar-
H), 7.87 (d, 3J = 7.2 Hz, 1 H, ArH), 8.06 (d, 3J = 8.4 Hz, 1 H,
ArH) ppm. 13C NMR: δ = 18.4, 19.1, 26.0, 28.8, 38.2, 43.0, 48.8,
54.3, 55.7, 59.4, 78.1, 79.6, 98.3, 122.7, 125.4, 126.3, 126.6, 126.8,
128.0, 128.3, 131.8, 132.7, 139.5, 140.1, 146.4, 162.8, 212.8 ppm.
MS (ESI): m/z (%) = 651 (47) [M + 1]+, 442 (46), 401 (26), 321
(96), 271 (100). HRMS (ESI): calcd. for C33H35N2O8S2 651.18293;
found 651.18424. [α]2D0 = +45 (c = 0.1, CH2Cl2).
453.10964. Data for 31b: Yellow oil. IR (film): ν = 1700, 1661,
˜
1523, 1347, 1168, 1120 cm–1. 1H NMR: δ = 1.46 [s, 9 H, C(CH3)3],
2
3
4
3.04 (ddd, J = 16.8 Hz, J = 4.2 Hz, J = 2.1 Hz, 1 H, C=CH2),
2
3
4
3.55 (ddd, J = 16.8 Hz, J = 7.3 Hz, J = 2.1 Hz, 1 H, C=CH2),
5.22 (dd, 3J = 7.3, 4.3 Hz, 1 H, CHCH2), 5.83–5.85 (m, 1 H, =CH),
7.37–7.66 (m, 5 H, Ar-H), 7.75–7.79 (m, 2 H, Ar-H), 8.20–8.23 (m,
2 H, Ar-H) ppm. 13C NMR: δ = 28.3, 37.5, 64.5, 80.4, 98.1, 124.1,
127.4, 129.5, 134.2, 136.7, 144.7, 148.0, 155.9, 166.2 ppm. (ESI):
m/z (%) = 431 (26) [M + H]+, 375 (100), 357 (97), 331 (6). HRMS
(ESI): calcd. for C21H23N2O6S 431.12713; found 431.12723.
(1S)-(–)-10-Phenylsulfonylisobornyl
(R)-2-[Nitrophenyl(phenyl-
sulfonamido)methyl]buta-2,3-dienoate (29): Yield (method A;
–20 °C, 48 h): 57%. Purification by flash chromatography (hexane/
ethyl acetate, 1:2) gave 29 as a yellow solid, m.p. 85.0–86.4 °C. IR
1
(KBr): ν = 3270, 1964, 1708, 1522, 1346, 1166 cm–1. H NMR: δ
˜
X-ray Crystallography: The structure of compound 14 was deter-
mined by taking advantage of the significant anomalous dispersion
of sulfur at the Mo-Kα wavelength. Both a Flack analysis of the
diffraction data and the results of separate refinements of the pos-
sible enantiomers unambiguously assigned the S,S,S,R absolute
configurations to the C5, C18, C20 and C26 stereogenic centres,
respectively. The phenyl ring attached to S1 is disordered over two
positions with approximately 50% occupancy each. The X-ray data
were collected with an APEX2 single-crystal diffractometer, at
298(3) K, by using graphite-monochromated Mo-Kα radiation (λ =
0.71073 Å). Intensities were recorded as full profiles of ω–θ scans.
The structures were solved by direct methods as implemented in
SHELXS97 and refined by full-matrix least-squares using
SHELXL97. Examination of the structure with PLATON con-
firmed the absence of voids that might be occupied by solvent mo-
lecules in the crystal structures. CCDC-774953 contains the supple-
mentary crystallographic data for this paper. These data can be
= 0.69 (s, 3 H), 0.77 (s, 3 H), 1.11–1.16 (m, 1 H), 1.49–1.56 (m, 2
2
H), 1.72 (br. s, 2 H), 1.77–1.89 (m, 2 H), 2.92 (d, J = 14.0 Hz, 1
2
3
H), 3.33 (d, J = 14.0 Hz, 1 H), 4.92 (dd, J = 8.0, 3.2 Hz, 1 H),
2
2
4.99 (d, J = 14.4 Hz, 1 H, C=CH2), 5.13 (d, J = 14.4 Hz, 1 H,
3
3
C=CH2), 5.38 (d, J = 9.2 Hz, 1 H, CHNH), 6.26 (d, J = 9.2 Hz,
1 H, CHNH), 7.46–7.65 (m, 12 H, Ar-H), 7.81–7.86 (m, 4 H, Ar-
H), 7.93–7.95 (m, 1 H, Ar-H), 8.13 (d, 3J = 8.8 Hz, 2 H, Ar-
H) ppm. 13C NMR: δ = 19.5, 20.1, 27.0, 29.8, 37.4, 39.2, 44.1, 49.8,
55.3, 56.7, 79.1, 80.6, 99.3, 123.7, 127.3, 127.6, 127.8, 129.3, 132.8,
133.7, 140.5, 141.2, 146.2, 147.5, 163.8, 213.8 ppm. MS (ESI): m/z
(%) = 651 (38) [M + 1]+, 494 (6), 401 (9), 277 (100). HRMS (ESI):
calcd. for C33H35N2O8S2 651.18293; found 651.18148. [α]2D0 = –40
(c = 0.1, CH2Cl2).
(E)-tert-Butyl
2-[4-Phenyl-1-(phenylsulfonyl)azetindin-2-ylidene]-
ethanoate (31a) and tert-Butyl 2-[Phenyl(phenylsulfonamido)meth-
yl]buta-2,3-dienoate (33): Yield (method A; r.t., 24 h): 37 (for 31a)
Eur. J. Org. Chem. 2010, 3249–3256
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3255

T. M. V. D. Pinho e Melo et al.
FULL PAPER
[9] a) M. Shi, L.-H. Chen, C.-Q. Li, J. Am. Chem. Soc. 2005, 127,
3790–3800; b) K. Matsui, S. Takizawa, H. Sasai, J. Am. Chem.
Soc. 2005, 127, 3680–3681; c) M.-J. Qi, T. Ai, M. Shi, G. Li,
Tetrahedron 2008, 64, 1181–1186; d) M. Shi, Y.-M. Xu, Angew.
Chem. Int. Ed. 2002, 41, 4507–4510; e) M. Shi, Y.-M. Xu, Y.-
L. Shi, Chem. Eur. J. 2005, 11, 1794–1802; f) Y.-H. Liu, L.-H.
Chen, M. Shi, Adv. Synth. Catal. 2006, 348, 973–979.
[10] B. J. Vowen, L. B. Saunders, S. J. Miller, J. Am. Chem. Soc.
2009, 131, 6105–6107.
[11] a) F. Palacios, A. M. Ochoa de Retana, J. M. Alonso, J. Org.
Chem. 2006, 71, 6141–6148; b) F. Palacios, D. Aparicio, A. M.
Ochoa de Retana, J. M. de los Santos, J. I. Gil, J. M. Alonso, J.
Org. Chem. 2002, 67, 7283–7288; c) T. M. V. D. Pinho e Melo,
C. S. J. Lopes, A. L. Cardoso, A. M. d’A. Rocha Gonsalves,
Tetrahedron 2001, 57, 6203–6208.
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Crystallographic Data for (1R)-(–)-10-Phenylsulfonylisobornyl
(S)-2-[Phenyl(phenylsulfonamido)methyl]buta-2,3-dienoate
(14):
C33H35NO6S2, M = 605.74, monoclinic, P21 with unit cell, a =
11.1501(6) Å, b = 11.3696(6) Å, c = 12.1303(6) Å, α = 90°, β = 90°,
γ = 88.851(3)°, V = 1537.48(14) Å3. It contains two molecules/unit
cell. ρcalcd. = 1.308 gcm–3, Z = 2, µ = 0.219 mm–1. R [IϾ2σ(I)] =
0.0637 and Rw = 0.1504 for 5989 independent reflections. H atoms
were placed at calculated positions and refined as riding on their
parent atoms. The phenyl ring attached to S1 is disordered over
two positions, occupancies refined to 0.546(16)/0.454(16). The dis-
ordered atoms were refined isotropically.
[12] a) J. M. de los Santos, D. Aparicio, Y. López, F. Palacios, J.
Org. Chem. 2008, 73, 550–557; b) T. M. V. D. Pinho e Melo,
C. M. Nunes, M. I. L. Soares, J. A. Paixão, A. Matos Beja, M.
Ramos Silva, J. Org. Chem. 2007, 72, 4406–4415; c) F. Palacios,
D. Aparicio, J. Vicario, Eur. J. Org. Chem. 2005, 2843; d)
T. M. V. D. Pinho e Melo, M. I. L. Soares, A. M. d’A. Ro-
cha Gonsalves, J. A. Paixão, A. Matos Beja, M. Ramos Silva,
J. Org. Chem. 2005, 70, 6629–6638; e) F. Palacios, A. M.
Ochoa de Retana, J. I. Gil, J. M. Alonso, Tetrahedron 2004, 60,
8937–8947.
[13] a) J. Vicario, D. Aparicio, F. Palacios, J. Org. Chem. 2009, 74,
452–455; b) D. Aparicio, O. A. Attanasi, P. Filippone, R. Igna-
cio, S. Lillini, F. Mantellini, F. Palacios, J. M. de los Santos, J.
Org. Chem. 2006, 71, 5897–5905; c) F. Palacios, E. Herrán, C.
Alonso, G. Rubiales, B. Lecea, M. Ayerbe, F. P. Cossío, J. Org.
Chem. 2006, 71, 6020–6030; d) F. Palacios, A. M. Ochoa de Re-
tana, J. I. Gil, R. López de Munain, Org. Lett. 2002, 4, 2405–
2408; e) T. M. V. D. Pinho e Melo, R. Fausto, A. M. d’A. Ro-
cha Gonsalves, T. L. Gilchrist, J. Org. Chem. 1998, 63, 5350–
5355.
[14] a) J. M. de los Santos, R. Ignacio, D. Aparicio, F. Palacios, J.
Org. Chem. 2009, 74, 3444–3448; b) T. M. V. D. Pinho e Melo,
A. L. Cardoso, F. Palacios, J. M. de los Santos, A. A. A. Pais,
P. E. Abreu, J. A. Paixão, A. M. Beja, M. R. Silva, Tetrahedron
2008, 64, 8141–8148; c) J. M. de los Santos, R. Ignacio, D.
Aparicio, F. Palacios, J. Org. Chem. 2007, 72, 5202–5206; d)
S. M. M. Lopes, A. Matos Beja, M. Ramos Silva, J. A. Paixão,
F. Palacios, T. M. V. D. Pinho e Melo, Synthesis 2009, 2403–
2407; e) S. M. M. Lopes, B. S. Santos, F. Palacios, T. M. V. D.
Pinho e Melo, ARKIVOC 2010, 5, 70–81; f) A. L. Cardoso,
S. M. M. Lopes, A. Matos Beja, M. Ramos Silva, J. M.
de los Santos, T. M. V. D. Pinho e Melo, F. Palacios, Tetrahe-
dron 2009, 65, 9116–9124; g) F. M. Ribeiro Laia, T. M. V. D.
Pinho e Melo, Tetrahedron Lett. 2009, 50, 6180–6182.
[15] a) Prepared by the Wittig reaction by following the general
procedure described in ref.[17] b) T. H. Lambert, D. C. W. Mac-
Millan, J. Am. Chem. Soc. 2002, 124, 13646–13647.
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra.
Acknowledgments
We would like to thank the Fundação para a Ciência e a Tecnologia
(FCT) (Project PTDC/QUI/64470/2006Ͻ/cgn) and Fundo Europeu
de Desenvolvimento Regional (FEDER) for financial support. We
acknowledge the Nuclear Magnetic Resonance Laboratory of the
Coimbra Chemical Centre (www.nmrccc.uc.pt), University of Co-
imbra for obtaining the NMR spectroscopic data.
[1] For reviews, see: a) N. De Kimpe in Comprehensive Heterocy-
clic Chemistry II (Ed.: A. Padwa), Elsevier, Oxford 1996, vol.
1, ch. 1.21; b) B. Alcaide, P. Almendros, Prog. Heterocycl.
Chem. 2003, 15, 100–102.
[2] For a recent contribution, see: S. Mangelinckx, V. V. Speyb-
roeck, P. Vansteenkiste, M. Waroquier, N. De Kimpe, J. Org.
Chem. 2008, 73, 5481–5488.
[3] a) M. E. Jung, Y. M. Choi, J. Org. Chem. 1991, 56, 6729–6730;
b) A. P. Marchand, D. Rajagopal, S. G. Bott, T. G. Archibald,
J. Org. Chem. 1994, 59, 1608–1612; c) P. R. Dave, R. Duddu,
R. Surapaneni, R. Gilardi, Tetrahedron Lett. 1998, 39, 5481–
5484; d) P. R. Dave, R. Duddu, R. Surapaneni, R. Gilardi, Tet-
rahedron Lett. 1999, 40, 443–446; e) A. C. B. Burtoloso, R. D.
Correia, Tetrahedron Lett. 2006, 47, 6377–6380; f) P. J. Steven-
seon, M. Nieuwenhuyzen, D. Osborne, ARKIVOC 2007, 11,
129–144.
[4] a) V. Breuil-Desvergnes, P. Compain, J.-M. Vatèle, J. Goré, Tet-
rahedron Lett. 1999, 40, 8789–8792; b) V. Breuil-Desvergnes, J.
Goré, Tetrahedron 2001, 57, 1951–1960; c) V. Breuil-
Desvergnes, J. Goré, Tetrahedron 2001, 57, 1939–1950.
[5] a) A. B. Baylis, M. E. D. Hillman, Ger. Offen. 1972, 2, 155,113;
[Chem. Abstr. 1972, 77, 34174q]; A. B. Baylis, M. E. D. Hill-
[16] L. C. Vishwakarma, O. D. Stringer, F. A. Davis, Org. Synth.,
Coll. Vol. 1993, 8, 546.
man, German Patent 2155113, 1972; b) K.-I. Morita, Z. Su- [17] a) Prepared by the procedure described in ref.[15] b) Z. Xu, X.
zuki, H. Hirose, Bull. Chem. Soc. Jpn. 1968, 41, 2815.
[6] For recent contributions, see: a) X. Meng, Y. Huang, R. Chen,
Org. Lett. 2009, 11, 137–140; b) T. E. Reynolds, M. S. Binkley,
K. A. Scherdt, Org. Lett. 2008, 10, 5227–5230.
Lu, J. Org. Chem. 1998, 63, 5031–5041.
[18] T. M. V. D. Pinho e Melo, A. L. Cardoso, A. M. d’A. Ro-
cha Gonsalves, J. Costa Pessoa, J. A. Paixão, A. M. Beja, Eur.
J. Org. Chem. 2004, 4830–4839.
[7] a) D. Basavaiah, R. Jaganmohan, T. Satyanarayana, Chem.
Rev. 2003, 103, 811–891; b) V. Declerck, J. Martinez, F. Lam-
aty, Chem. Rev. 2009, 109, 1–48; c) V. Singh, S. Batra, Tetrahe-
dron 2008, 64, 4511–4574.
[8] a) G.-L. Zhao, J.-W. Huang, M. Shi, Org. Lett. 2003, 5, 4737–
4739; b) G. L. Zhang, M. Shi, J. Org. Chem. 2005, 70, 9975–
9984.
[19] a) N. Morita, N. Krause, Org. Lett. 2004, 6, 4121–4123; b)
R. K. Dieter, N. Chen, H. Yu, L. E. Nice, V. K. Gore, J. Org.
Chem. 2005, 70, 2109–2119; c) R. K. Dieter, Y. Yu, Org. Lett.
2001, 3, 3855–3858; d) M. O. Amombo, A. Hausherr, H.-U.
Reissig, Synlett 1999, 1871–1873.
Received: December 4, 2009
Published Online: April 30, 2010
3256
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Eur. J. Org. Chem. 2010, 3249–3256