Reactivity trends in the reaction of alkynes with 3-oxo-camphorsulfonylimine

Article abstract of DOI:10.1515/znb-2002-0616

The regioselective addition of deprotonated alkynes (phenyl-1-propyne, propargyl ether or tetrahydropyran-protected 3-butyn-1-ol) to the imine group was identified as a competitive process to the nucleophilic addition to the keto group of (1S)-3-oxo-camphorsulfonylimine. The selectivity of the process depends on the characteristics of the nucleophile and the reaction conditions. In the case of propargyl ether it was possible to render the imine addition the main process. The structural characterization of compounds 1, 2, 6 by X-ray diffraction analysis show that the C2-C3 bond becomes longer upon nucleophilic addition to the imine group of (1S)-3-oxo-camphorsulfonylimine. This trend is believed to favour the ring opening process that undergoes the formation of the spiro type compound 7.

Full text of DOI:10.1515/znb-2002-0616

Reactivity Trends in the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
A. Mafalda Santos, M. Fernanda N. N. Carvalho, Adelino M. Galva˜o,
and Armando J. L. Pombeiro
Centro de Quı´mica Estrutural, Complexo I, Instituto Superior Te´cnico,
Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Reprint requests to Dr. M. F. N. N. Carvalho. E-mail: fcarvalho@ist.utl.pt
Z. Naturforsch. 57b, 691Ð698 (2002); received February 14, 2002
Camphor Alkyne, Nucleophilic Addition, Ring Opening
The regioselective addition of deprotonated alkynes (phenyl-1-propyne, propargyl ether
or tetrahydropyran-protected 3-butyn-1-ol) to the imine group was identified as a competitive
process to the nucleophilic addition to the keto group of (1S)-3-oxo-camphorsulfonylimine.
The selectivity of the process depends on the characteristics of the nucleophile and the reac-
tion conditions. In the case of propargyl ether it was possible to render the imine addition
the main process.
The structural characterization of compounds 1, 2, 6 by X-ray diffraction analysis show
that the C2ÐC3 bond becomes longer upon nucleophilic addition to the imine group of
(1S)-3-oxo-camphorsulfonylimine. This trend is believed to favour the ring opening process
that undergoes the formation of the spiro type compound 7.
Introduction
Results and Discussion
In the experimental conditions used for the syn-
thesis of the phenyl di-alkyne camphor derivative
(1aS,3aS,7R)-7-hydroxy-8,8-dimethyl-1a,7-bis-
(phenylethynyl)-1,1a,4,5,6,7,-hexahydro-3H-3a,6-
methano-2,1-benzisothiazole 2,2-dioxide (A, R =
Ph) [4], the reaction of (1S)-3-oxo-camphorsul-
fonylimine (B) with 3-phenyl-1-propyne afforded
the corresponding di-alkyne product 1, the mono-
alkyne species 2 and a novel type product 3,
Scheme 2 (a).
The diversity of products obtained is indicative
of the high reactivity but low selectivity of 3-phe-
nyl-1-propyne compared to phenylacetylene. For
the reaction of B with 1-hexyne it was reported
that the mono addition product (analogous to 2)
was also formed [2].
To our knowledge the propargyl to allenyl con-
version (3 in Scheme 2a) has not been identified
in the reaction of B with other alkynes. The selec-
tivity of the process is driven by the reaction con-
ditions, i.e. longer overall reaction times favour the
formation of the di-alkyne species 1, whether, as
expected, shorter reaction times lead to the forma-
tion of species 2. The alkyne to allenyl rearrange-
ment seems to be favoured by an excess of the
deprotonated alkyne, conceivably due to its basic-
ity that promotes the abstraction of a proton from
the acidic methylene group.
Combined ring opening/ring closure leading to
ring enlargement to more than six members has
high relevance for organic synthesis, in particular
that of analogues to natural products with phar-
maceutical relevance [1]. We have already found
that camphor-derived di-alkynes are suitable pre-
cursors for the synthesis of compounds with an
eight-membered ring of the taxol type. During the
reaction a six-membered ring is cleaved and an
eight-membered one is formed (Scheme 1), in a
cascade process catalysed by Pt(II) [2, 3].
Within our interest in the syntheses of camphor-
alkyne derived species able to act as precursors for
ring expansion we tried to extend to alkynes such
as 3-phenyl-1-propyne, 3-butyne-1-ol or propargyl
ether the syntheses of di-alkyne derivatives. The
results of this study are now reported.
Scheme 1. Six to eight members conversion promoted
by platinum in camphor di-alkyne derived species.
0932Ð0776/2002/0600Ð0691 $06.00 ” 2002 Verlag der Zeitschrift für Naturforschung, Tübingen · www.znaturforsch.com
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A. M. Santos et al. · Reactivity Trends on the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
Scheme 2.
In addition to the unusual alkyne to allenyl con-
version in systems involving camphor alkyne spe-
cies, the formation of compound 3 was further un-
expected in view of the fact that, in related
systems, the nucleophilic attack by the deproto-
nated alkyne was always observed [2] to occur at
the keto rather than at the imino group. However,
the regioselective nucleophilic addition to the im-
ine group was conceptually possible, due to its ac-
tivation by the sulfonyl group. The characteristics
of the nucleophiles conceivably play an important
role in the reactivity trend.
Fig. 1. Molecular structure of compound 1 in the solid
state.
The characterization of 3 relies mostly on NMR,
since no suitable crystals for X-ray analysis could The homonuclear five-membered ring of the cam-
be obtained, in contrast with 1 and 2 whose molec- phor skeleton displays a considerably strain com-
ular structures (Figs 1 and 2) have been obtained pared to compound 1, as evidenced by the smaller
by X-ray diffraction, although the quality of crys- angles in the camphor skeleton (Table 2). More-
tals in the case of compound 2 was just good over, a long C2ÐC3 bond length in compound 1
enough for comparative purposes.
The details on the crystallographic analysis are
suggests some activation towards bond breaking.
In the 1H NMR spectrum of 3 (Table 3) the evi-
displayed on Table 1 and selected bond lengths dence for the protons of the allenyl group is based
and angles are given in Table 2. on the detection of a pair of doublets (δ =6.47,
˚
The short carbon-nitrogen bond length (1.310 A) 5.92, JHH =6.2 Hz). In solution, another set of
in compound 2 sustains its double bond character. doublets with lower intensity (ca. 20%) suggests
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A. M. Santos et al. · Reactivity Trends on the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
693
Fig. 3. Optimized structures of the diasteromers M (a)
and P (b) of compound 3.
In the 13C NMR spectrum of 3 the allenyl
pattern is identified by the low field signal (δ =
204.9) attributed to the C=C=C in addition to the
signals at 94.0 and 99.5 (Table 4).
The reaction of the oxoimine B with deproto-
nated propargyl ether in a 1:2 molar ratio follows a
similar trend to that observed in the reaction with
phenylacetylene, since both the nucleophilic addi-
Fig. 2. Molecular structure of compound 2 in the solid
state.
the presence of an isomeric species. The chemical tions to the keto and the imine groups occur thus
shifts of the less abundant compound appear be- affording the di-alkyne species 4 (Scheme 2b).
tween those of the main species. They do not in- However, when a 1:1 ratio is used, the main prod-
terconvert by raising the temperature up to 50 ∞C uct is that resulting from the addition to the imine
as verified by 1H NMR and could not be separated carbon atom, compound 6. In the latter case com-
by recrystallization.
pound 5 is also formed as a minor product.
Some preliminary semi-empirical calculations
The compounds can be easily identified by IR
[5] show that there is a small energy difference spectroscopy since the di-substituted compound 4
between the M (∆Hf = Ð21.33 kcal molÐ1) and P displays intense bands in the regions of the OH,
(∆Hf = Ð25.76 kcal molÐ1) diasteromers (M and NH and CϵC stretching vibrations. In the IR
P refer to the chirality of the allene moiety, see spectrum of compound 5 a band at 1654 cmÐ1 is
Fig. 3). Since no conversion between these diaste- attributed to ν(C=N) while in the IR spectrum of
reomers is detected, a kinetic barrier between 6 the band at 1761 cmÐ1 is assigned to ν(C=O)
them must exist.
(Table 5).
Table 1. Crystallographic data for camphor derived compounds.
1
2
6
7
Formula
C28H29O3NS
459.6
C19H21NO3S
343.5
C16H19O4NS
321.5
C10H22O8NSLi
323.3
M
Crystal system
Space group
orthorhombic
P212121
9.2163(5)
12.597(1)
20.717(1)
Ð
monoclinic
P21
orthorhombic
P212121
7.1460(7)
12.519(2)
17.991(3)
Ð
orthorhombic
P212121
6.311(2)
8.163(2)
30.163(2)
Ð
˚
a [A]
7.028(8)
10.196(3)
12.190(1)
91.66(7)
873
2
1.30
1.67 (Cu)
362
1748
˚
b [A]
˚
c [A]
ꢀ [∞]
3
˚
U [A ]
2405
1610
1554
Z
4
4
4
Dc [g·cmÐ3
]
1.27
1.35
1.27
µ [mmÐ1
F(000)
]
0.12 (Mo)
976
1.83 (Cu)
704
1.80 (Cu)
624
No. refl. measured
2437
1673
2946
No. uni. refl. (Rint
R1 (I > 2σ(I))
wR2
)
1356
1025 (0.38)
0.15
0.34
941
2850 (0.07)
0.05
0.06
0.12
0.11
0.29
0.14
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694
A. M. Santos et al. · Reactivity Trends on the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
Table 2. Selected bond lengths and angles (numbering as
in Scheme 2).
In contrast with compound 3, the signals of the
methyl groups in compounds 2 and 5 coincide in
agreement with a trend also found in the related
compound derived from 1-hexyne which was pre-
viously obtained [2]. From the data in Table 3 it
seems that the chemical shift and coupling of the
methylenic groups attached to the sulfonylimine
are affected by addition to the imine group while
those of the methyl groups in the five membered
ring of the camphor skeleton are influenced by ad-
dition to the keto group. This tendency needs,
however, to be corroborated by future studies.
The X-ray diffraction analysis showed that 6
shows crystallised in space group P212121. The mo-
lecular structure (Fig. 4) of 6 displays a long
Compound
1
2
6
7
˚
Bond lengths (A)
SÐN
1.655(6) 1.693(13) 1.646(12) 1.672(3)
1.785(7) 1.781(18) 1.783(12) 1.7787(24)
1.487(8) 1.310(21) 1.423(18) 1.277(3)
1.615(9) 1.520(23) 1.589(21)
1.421(9) 1.448(18) 1.163(21) 1.252(3)
1.466(8) 1.528(21) 1.484(19)
1.479(10)
SÐC
NÐC
C2ÐC3
CÐO
CÐCϵ
CϵC
1.188(8) 1.17(24) 1.191(20)
1.155(11)
Bond angles (∞)
CÐCϵC
178.3(9) 175.5(11) 171.9(8)
˚
C2ÐC3 bond (1.589 A) in addition to a relatively
176.6(6)
177.3(13)
˚
SÐC8ÐC1
C1ÐC7ÐC4
C2ÐC1ÐC7
short CÐN (1.423 A) bond length (Table 2). The
elongation of the C2ÐC3 bond distance is also
verified in compound 1, suggesting that in both
cases there is some activation towards bond rup-
ture.
1
By H NMR the imine addition product 6 dis-
The reactivity of the deprotonated form of
plays a characteristic collapse of the signals of the the tetrahydropyranyl-protected 3-butyn-1-ol,
CH2 group attached to the sulfonylimine group HCϵC(CH2)2OC5H9O, with B resembles that of
(generally observed as a doublet or a pair of the above-mentioned alkynes in what concerns the
doublets). The tendency of the signals to collapse promotion of nucleophilic addition to the sulfonyl-
was already observed in compound 3 in which the imine group. In the reaction compound 8 was iso-
signals become separate just by 1.8 Hz (Table 3).
lated, although in a very low yield (Scheme 1c).
1
Table 3. H NMR dataa of the camphor derived species 1Ð8 (numbering as in Scheme 2).
Com-
pound
4-H (d)
5,6-H (m,
2H each)
8-H (d)
9,10-H (2s, Other CH or CH2
3H each)
Ph
Other NH
or OH
1
2.09 (5.1)
1.7Ð2.3
3.29 (2.4)
0.99, 1.44
3.57, 3.50 (s, 2H each,
15-H, 16-H
7.3Ð7.2 (m, 10H) 5.07 (s, 1H)
2.89 (s, 1H)
2
3
4
2.27 (3.3)
2.32 (5.7)
2.06 (3.4)
1.7Ð2.4
1.3Ð2.4
1.6Ð2.0
3.23, 3.12 (13.5)
3.40c
1.09, 1.08
1.08, 1.29
0.95, 1.41
3.68 (s, 2H 13-H)
7.3Ð7.2 (m, 5H)
3.15
4.88 (s, 1H)
6.47, 5.92 (2d, 2H, 6.2)b 7.3Ð7.2 (m, 5H)
3.26c
4.26, 4.23 (d, 2.4,
2H each, 14-H, 20-H)
2.46, 2.44 (t, 2.4, 1H,
16-H, 22-H)
5.4 (s, 1H)
3.9 (s, 1H)
5
6
2.29 (3.6)
2.42 (4.5)
1.7Ð2.2
1.7Ð2.4
3.23, 3.12 (13.5)
3.37c
1.09d
4.33 (s, 2H 13-H)
4.22 (d, 2.1, 2H, 14-H)
2.45 (t, 2.1, 1H, 16-H)
4.29 (s, 2H, 13-H)
4.20 (d, 2.1, 2H, 14-H)
2.45 (t, 2.1, 1H)
1.04, 1.21
5.54 (s, 1H)
9.00 (s, 1H)
7e
8h
2.82f (9.3) 2.0Ð2.7
2.30 (5.0)
1.6Ð2.5i
3.52, 3.24 (13.8)
5.03, 4.87 (11.2)
1.28, 1.30
1.30, 1.00
5.68 (s, 1H)g
3.2Ð4.2 (OCH2)
a In CDCl3, unless stated otherwise. δ values in ppm versus TMS. Multiplicity, integration and coupling constants
(Hz) in parentheses; b 11-H, 13-H. Another set of doublets at δ =6.35, 5.98 ( J =6.6 Hz) ( ca. 20%) is observed;
c coincide as a singlet. In the case of 3 two singlet signals separated by 1.8 Hz can be detected; d integrates to six
protons; e in MeOD; f triplet; g 2-H; h in CD2Cl2; i overlapped with CH2 in tetrahydropyran.
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A. M. Santos et al. · Reactivity Trends on the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
Table 4. 13C NMR dataa of the camphor derived species 1Ð8 (numbering as in Scheme 2).
695
Camphor skeleton
C-4 C-5,6 C-7 C-8 C-9,10 CϵC or
C=C=C
Others
Ph(ipso) Ph(CH)
Com- C-1 C-2
pound
C-3
CH2
1
62.3
72.5
81.9 56.4 28.3
48.8 51.2 24.0
23.5
88.4, 86.5, 25.0
136.3
128.5, 128.4,
127.9, 127.8,
126.7, 126.5
128.7, 127.8,
126.9
128.7, 127.8,
127.1
23.9
82.7, 80.6
25.2
136.0
135.4
132.6
2
3
4
64.1 194.1
73.8 55.9 27.9
23.9
47.5 50.2 21.1
21.0
88.2, 79.3
25.2
56.5
61.5
70.1 207.7 58.7 28.1
20.9
71.9
45.7 49.8 22.6
19.7
99.5, 94.0
204.9b
81.3 55.9 28.0
23.6
49.0 50.9 23.3
23.7
87.2, 85.4, 56.7c
85.1, 83.1
79.0, 78.8
75.4d, 75.2d
84.7, 83.6
78.5, 75.6
56.5c
5
64.1 193.5
73.0 55.7 27.8
23.8
47.5 50.1 21.1
20.9
57.0
56.7
6
64.7
56.8 205.0 58.2 28.8
21.5
45.1 49.5 22.4
19.6
85.3, 82.0, 56.5c
78.6, 75.4d
7e
8g
68.6 180.4 181.1 59.3 36.3
26.9
69.4
51.5 27.2
(f)
21.1
45.4 51.6 22.0
21.3
69.6 205.6 58.3 29.4
20.1
91.0,
81.4
68.3h, 63.7h,
25.8, 25.3,
24.5, 23.7
a In CDCl3 unless stated otherwise (δ values). The signals were attributed on the basis DEPT and HETCOR in the
cases of compounds 1, 3, 5, 6; b corresponds to C-12; c assigned to two carbon atoms; d attributed to CϵCH; e in
MeOD; f covered by solvent signal; g in CD2Cl2; h attributed to oxygen bonded carbon atoms.
The main product was compound 7, formed upon responsible for the stability of the compound. In
1
C2ÐC3 bond breaking of the six-membered ring the H NMR spectrum the signal at δ =9.0 is at-
of the oxoimine. In the literature there are some tributed to the bridging hydrogen.
examples of ring opening of camphor derivatives
The results herein show that nucleophilic addi-
[6Ð8] but there is only scarce evidence for related tion to the imine group of 3-oxo-camphorsulfonyl-
processes in camphorsulfonic acid derivatives. imine is a process with high probability that can
Ring rupture of an oxidized derivative of A with occur in a number of cases. Moreover, depending
formation of a spiro type compound was reported on the nucleophile, it can even become the main
before [9].
process, competing favourably with the well estab-
The characterization of 7 by X-ray diffraction lished nucleophilic addition to the vicinal car-
analysis (Fig. 5) indicates hydrogen bridging be- bonyl group.
tween the carboxylate group and the lithium tetra-
hydrate moiety (OÐO, 2,86 A), which is possibly dition to the imino group prompts the conditions
The X-ray data indicate that the nucleophilic ad-
˚
Table 5. IR dataa of the cam-
phor derived species 1Ð8.
IR (ν/cmÐ1
)
Com-
pound
OH
NH
CϵC or
C=C=C
C=O
C=N
SO2 (asym, sym)
1
2
3
4
5
6
7
8
3426
3425
3322
2240
2132
1955
2112
2121
2117
1333, 1138
1335, 1164
1306, 1142
1344, 1134
1333, 1167
1312, 1139
1316, 1163
1312, 1145
1650
1654
3177
3244
1762
1761
3409
3440
3283
3294
3590, 3490
1663, 1606 1545
1766
2119
a In KBr pellets.
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A. M. Santos et al. · Reactivity Trends on the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
Et2O) followed by the addition of oxoimine (ca.
2 equivalents relative to alkyne) in dried diethyl
ether (50 ml); (ii) addition of H2O (typically
25 ml), separation of the ether phase (needs drying
with MgSO4 followed by filtration of the drying
agent) and evaporation of the solvent afforded
compounds 1, 2, 5 and 8. Extraction of the aque-
ous solution with several portions of CH2Cl2, dry-
ing over MgSO4, filtration and evaporation of the
solvent close to dryness afford compounds 1, 3, 4,
and 6. In the case of the reaction with 3-butyn-
Fig. 4. Molecular structure of compound 6 in the solid
state.
1-ol, prior to deprotonation of the alkyne the pro-
tection of the alcohol function with pyran, to form
HCϵC(CH2)2OC5H9O, was necessary. Compound
7 was obtained from the aqueous phase.
(1aS,3aS,7R)-7-Hydroxy-1a,7-bis(3-phenyl-
1-propynyl)-8,8-dimethyl-1,1a,4,5,6,7-hexahydro-
3H-3a,6-methano-2,1-benzisothiazole 2,2-dioxide (1)
and (3aS,7R)-7-hydroxy-8,8-dimethyl-7-(3-phenyl-
1-propynyl)-4,5,6,7-tetrahydro-3H-3a,6-methano-
2,1-benzisothiazole 2,2-dioxide (2)
Fig. 5. Molecular structure of compound 7 in the solid
state.
Butyl lithium (7.9 ml, 12.6 mmol) was slowly
added to a solution of 3-phenyl-1-propyne (1.5 ml,
11.7 mmol) and the mixture was stirred for 18 h.
Oxoimine (1.06 g, 4.68 mmol) was then added and
the pale yellow suspension stirred for 46 h. Upon
addition of H2O and separation of the ether phase
the solvent was evaporated close to dryness to ob-
tain the di-alkyne derivative 1 (0.20 g, 0.44 mmol).
The main crop of 1 (1.05 g, 2.28 mmol) was ob-
tained upon extraction of the aqueous solution
with three different portions of dichloromethane
(125, 175, and 150 ml), drying over MgSO4 and
evaporation close to dryness. Total yield 58%.
Recrystallization of 1 from MeOH gave suitable
crystals for X-rays crystal structure analysis. M.p.
183.8 ð 0.1 ∞C. Ð FAB-MS (matrix 4-nitrobenzyl
that favour C2ÐC3 bond breaking. Under this hy-
pothesis the formation of compound 7 conceivably
involves compound 8 as an intermediate.
Experimental Section
(1S)-3-Oxo-camphorsulfonylimine was pre-
pared by literature methods [9, 10]. Diethyl ether
was pre-dried under sodium wire and distilled
prior to use. The alkynes were purchased from
Aldrich.
The NMR spectra were recorded on a Varian
UNITY 300 spectrometer. The IR spectra were
obtained using a BIO-RAD FTS 3000 MX. FAB
mass spectra were measured using a TRIO 2000
FISONS instrument. The optical activity was
measured using an automatic Optical Activity
ATAGO instrument.
alcohol): m/z (%) =460 (8). Ð C28H29NO3S ·
1
⁄ H2O (468.6): calcd. C 71.8, H 6.5, N 3.0, S 6.8;
2
found C 71.9, H 6.5, N 3.3, S 7.3.
Traces (ca. 1%) of compound 2 were obtained
from the residual Et2O phase by evaporation of
the solvent and recrystallized from E2O/n-pen-
tane. The yield of 2 increases to ca. 10% if the
deprotonation of the alkyne (5 h) and reaction
with the oxoimine (19 h) are carried out for
Syntheses
A general procedure was used to synthesise the shorter periods. Reasonable crystals for X-ray
camphorsulfonyl alkyne derived species 1Ð8: analysis of 2 were grown from Et2O/n-pentane. Ð
(i) deprotonation of the alkyne by n-butyl lithium FAB-MS: m/z (%) =344 (10). Ð C19H21NO3S
(ca. 1:1.1 stoichiometry ratio, using a 1.6 M solu- (343.4), calcd. C 66.4, H 6.2, N 4.1, S 9.3; found
tion in hexane, previously diluted in 10Ð15 ml of C 66.5, H 6.3, N 4.0, S 9.2.
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A. M. Santos et al. · Reactivity Trends on the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
697
(1aS,3aS)-8,8-Dimethyl-1,1a,4,5,6,7-hexahydro-
80 ml) upon evaporation of the solvent and was
3H-3a,6-methano-7-oxo-1a-(3-phenylpropadienyl)- recrystallized from Et2O/n-pentane. M.p. 115Ð
2,1-benzisothiazole 2,2-dioxide (3)
7 ∞C. Ð FAB-MS (matrix 4-nitrobenzyl alcohol):
m/z (%) =321 (5). Ð C16H19NO4S · H2O (339.4):
calcd. C 56.6, H 6.2, N 4.1, S 9.4; found C 56.5,
H 6.0, N 4.0, S 10.0.
A similar procedure to that used for the prepa-
ration of compound 1 was followed. The main
change was that a 3:1 excess of 3-phenyl-1-pro-
pyne (0.50 ml, 3.9 mmol) relatively to the oxo-
imine (0.296 g, 1.3 mmol) was used. Traces of com-
pounds 1 (5.25 mg, 0.011 mmol) and 2 (19 mg,
0.055 mmol) are detected in the Et2O phase. Com-
(S,S)-3-Aza-6,6-dimethyl-4-thia-spiro[4.4]non-
2-ene-7-carboxylate (7)
3,4-Dihydro-2H-pyran (6 ml, 64 mmol) and five
pound 3 was obtained from the CH2Cl2 layer drops of HCl (37%) were added to a solution of
(125 ml). Addition of the minimum amount of HCϵC(CH2)2OH (5 ml, 64 mmol) in Et2O (50 ml)
Et2O followed by a large excess of n-pentane (ca. and the mixture stirred for 30 min BuLi (40 ml,
100 ml) to the oily material formed upon almost 64 mmol) was then slowly added to the deproto-
complete evaporation of the solvent afforded the nated tetrahydropyran-protected 3-butyn-1-ol.
yellow compound 3 (89 mg, 0.26 mmol, 20% The suspension was stirred for ca. 2 h prior to ad-
yield). M.p. 202Ð4 ∞C. Ð FAB-MS (matrix 4-ni- dition of B (7.0 g, 31 mmol) and then allowed to
trobenzyl alcohol): m/z (%) =344 (21).
Ð
react for 12 h. Acidified water (100 cm3, with a few
4
C19H21NO3S · ⁄ CH2Cl2 (411.4): calcd. C 57.8, drops of HCl) was added and the organic phase
5
H 5.5, N 3.4, S 7.8; found C 57.8, H 5.2, N 3.3, S 7.8. separated. Traces of 8 (ca. 1%) were obtained
from the Et2O layer upon drying over MgSO4 and
evaporation of the solvent. Ð C19H27NO5S (381.5):
calcd. C 59.8, H 7.2, N 3.7, S 8.4; found C 59.8,
H 7.2, N 3.6, S 8.3.
(1aS,3aS,7R)-7-Hydroxy-1a,7-bis(4-oxa-1,6-hepta-
diyn-1yl)-8,8-dimethyl-1,1a,4,5,6,7-hexahydro-3H-
3a,6-methano-2,1-benzisothiazole 2,2-dioxide (4)
The aqueous solution was concentrated (ca.
40 ml) and left to stand for 10 days. White crystals
of 7 were obtained that were washed with ethanol/
diethyl ether (910 mg, 2.94 mmol, yield 10%).
[α]D20 =78.0 ( c =0.54 in MeOH). Ð C10H22NO8SLi
(323.3): calcd. C 37.1, H 6.9, N 4.3, S 9.9; found
C 37.1, H 6.9, N 4.2, S 9.8.
Butyl lithium (2.8 ml, 4.5 mmol) was slowly
added to a mixture of dipropargyl ether (0.46 ml,
4.4 mmol) with the oxoimine (0.50 g, 2.2 mmol)
and the mixture was stirred overnight at 20 ∞C.
Following the general procedure mentioned above
no compound could be obtained from the ether
layer. Upon several extractions of the aqueous
layer with 40 cm3 portions of CH2Cl2, drying over
MgSO4 and evaporation of the solvent, compound
4 was isolated as a pale yellow powder that was
recrystallized from Et2O/n-pentane (0.37 g,
X-ray crystallographic analyses
X-ray data were collected from white crystals of
complexes 1, 2, 6 and 7 mounted in thin-walled
glass capillaries. Data were collected at room
temperature on Enraf-Nonius MACH3 (1)
or TURBO CAD4 (2, 6, 7) diffractometers
with graphite-monochromatized MoÐKα (1) and
CuÐKα (2, 6, 7) radiation, using an ω-2θ scan
mode. Unit cell dimensions were obtained by
least-squares refinement of the setting angles of
25 reflections. The crystal data are summarized in
0.88 mmol, yield 40 %). M.p. 73Ð76 ∞C.
Ð
C22H27NO6S · H2O (433.6): calcd. C 60.9, H 6.3,
N 3.2, S 7.4; found C 60.5, H 6.6, N 3.5, S 7.3.
(1aS,3aS)-8,8-Dimethyl-1,1a,4,5,6,7-hexahydro-
3H-3a,6-methano-1a-(4-oxa-1,6-heptadiynyl)-
7-oxo-2,1-benzisothiazole 2,2-dioxide (6)
The reaction is performed analogously to the Table 1. The data were corrected11 for Lorentz-
one that afforded compound 4 but a 1:1 ratio of polarization effects, for linear decay and empiri-
propargyl ether (0.35 ml, 3.37 mmol) and oxo- cally for absorption. The heavy atom positions
imine (0.75 g, 3.30 mmol) is used. Traces of com- were located by Patterson methods using
pound 5 were obtained from the ether phase (ca. SHELXS-86 [12]. The remaining atoms were lo-
20 mg, ca. 5% yield). FAB-MS (matrix 4-nitroben- cated in successive Fourier-difference maps and
zyl alcohol): m/z (%) =322 (23). Ð C12H19NO4S refined by least squares on F2 using SHELXL-93
(321.4): calcd. C 59.8, H 6.0, N 4.4; found C 59.2, [13]. All the non-hydrogen atoms were refined
H 5.8, N 4.7.
with anisotropic thermal motion parameters. The
Compound 6 (0.42 g, 1.31 mmol, yield 40%) was hydrogen atoms bonded to carbons were included
obtained from the dichloromethane phase (5 ¥ in calculated positions, constrained to ride at fixed
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698
A. M. Santos et al. · Reactivity Trends on the Reaction of Alkynes with 3-Oxo-camphorsulfonylimine
distances of the parent carbon atom. Hydroxyl hy- Cambridge CB2 1EZ, UK
drogen atoms were located and refined. Atomic (Fax: int. code +(1223) 336-033; e-mail for in-
scattering factors and anomalous dispersion terms quiry: fileserv@ccdc.cam.ac.uk).
were as in SHELXL-93 [13]. The ORTEP draw-
ings were made with ORTEX [14] the ellipsoids
Acknowledgements
displayed with 40% probability.
Crystallographic data for the structure(s) have
been deposited with the Cambridge Crystallo- helpful discussion. This work was partially sup-
graphic Centre, CCDC-182327Ð182330. Copies of ported by the Fundac¸a˜o para a Ciencia e a Tecno-
the data can be obtained free of charge on applica- logia (FCT) through Program POCTI (Project
tion to the Director, CCDC-, 12 Union Road, 36125/QUI/2000).
We are grateful to Dr. Rudolf Herrmann for
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