Ozonolyses of Acetylenes: Trapping of α-Oxo Carbonyl Oxides by Carbonyl Compounds and Stabilization of α-Oxo Ozonides by Derivatizations

Article abstract of DOI:10.1021/jo9701795

Ozonolyses of 2-butyne (7) or of 3-hexyne (14) in the presence of carbonyl compounds (aldehydes, ketones, acid derivatives) afforded the corresponding mostly labile monocyclic α-oxo ozonides (9, 13a, 16), which could be stabilized and, hence, isolated by subsequent conversion into α-methoximino derivatives. Ozonolyses of 1,4-diacyloxy-substituted (19) and 1-acyloxy-substituted 2-butynes (27) gave bicyclic ozonides (22,31) by intramolecular [3 + 2]-cycloadditions of the corresponding carbonyl oxide intermediates (20, 29). These ozonides could also be stabilized by reactions with O-methylhydroxylamine to give O-methyloximes (23c, 32) or with diazomethane to give epoxy ozonides (25, 34).

Full text of DOI:10.1021/jo9701795

J . Org. Chem. 1997, 62, 6129-6136
6129
Ozon olyses of Acetylen es: Tr a p p in g of r-Oxo Ca r bon yl Oxid es by
Ca r bon yl Com p ou n d s a n d Sta biliza tion of r-Oxo Ozon id es by
Der iva tiza tion s
Karl Griesbaum* and Yuxiang Dong
Engler-Bunte-Institut, Bereich Petrochemie, Universita¨t Karlsruhe (TH), D-76128 Karlsruhe, Germany
Kevin J . McCullough
Department of Chemistry, Heriot-Watt University, Edinburgh EH14 4AS, U.K.
Received J anuary 30, 1997X
Ozonolyses of 2-butyne (7) or of 3-hexyne (14) in the presence of carbonyl compounds (aldehydes,
ketones, acid derivatives) afforded the corresponding mostly labile monocyclic R-oxo ozonides (9,
13a , 16), which could be stabilized and, hence, isolated by subsequent conversion into R-methoximino
derivatives. Ozonolyses of 1,4-diacyloxy-substituted (19) and 1-acyloxy-substituted 2-butynes (27)
gave bicyclic ozonides (22, 31) by intramolecular [3 + 2]-cycloadditions of the corresponding carbonyl
oxide intermediates (20, 29). These ozonides could also be stabilized by reactions with O-meth-
ylhydroxylamine to give O-methyloximes (23c, 32) or with diazomethane to give epoxy ozonides
(25, 34).
Ch a r t 1
In tr od u ction
R1CR2
O
By analogy with the mechanism of ozone olefin reac-
tions, ozonolyses of acetylenes (1) are postulated to
proceed via intermediates of types 2 and 3.1a However,
while carbonyl oxide intermediates generated by ozo-
nolyses of olefins undergo facile cycloadditions with
carbonyl compounds to give ozonides, we are not aware
of any ozonides of type 5, derived from reactions of
intermediates of type 3 with carbonyl compounds of type
4, although carbonyl compounds are produced as anoma-
lous ozonolysis products of acetylenes2 and are, thus,
present during such ozonolysis reactions. The fact that
no ozonides 5 have been found in ozonolyses of acetylenes
(1) could be due either to special properties of R-oxo
carbonyl oxides (3), such as isomerizations to give the
corresponding R-oxo 1,2-dioxiranes (6)3 or premature
decompositions by free radical pathways,4 or to the
known instability of R-oxo ozonides of type 5.1b,5
CH3C CCH3
7
8
O
O
O
O
R1
R2
R1
R2
C
C
C
O
C
C
O
C
NOCH3
O
CH3 CH3
CH3 CH3
9
10
O
C
C NOCH3
CH3COCH2OCCH3
CH3 CH3
O
O
11
12
R1
R2
9(%)
10(%)b
a
b
c
H
H
H
nd
nd
9
C6H5
12
17a
17a
12a
42a
8a
H
CH3
CH3
6
6
d
e
CH3
CH3
CH3
CH2Cl
CF3
15
9
O
f
O
R
O
O
O
O
g
(CH2)5
5
C
C
R
C
C
h
i
CH3
H
CN
37a
14
7
RC CR
R
R
23a 12b
29a 14b
OCH3
OC2H5
1
2
3
j
H
9
O
O
O
O
O
R′
R′
R′
aDetermined in the product mixture by 1HNMR analysis. bYield of isolated
products. nd = not detected.
C
C
R
O
C
C
R
O
C
R
R
O
R′
4
5
6
imino groups (methoxyimino, CH3ONd). To this end, 1:1
mixtures of an acetylene and of a carbonyl compound in
CH2Cl2 were treated with ozone at low temperatures, and
the cold crude reaction products were immediately ad-
mixed with a precooled solution of O-methylhydroxyl-
amine in methanol.
In this investigation, we have tried to get answers to
these questions by ozonizing acetylenes (1) in the pres-
ence of added carbonyl compounds (4) and by stabiliza-
tion of the anticipated R-oxo ozonides 5 by converting
their R-oxo groups into the less destabilizing6 methox-
X Abstract published in Advance ACS Abstracts, August 1, 1997.
(1) Bailey, P. S. In Ozonation in Organic Chemistry; Academic
Press: New York, (a) 1982, Vol. II, p 6; (b) 1978; Vol. I, p 153, (c) p 25.
(2) J enkins, J . A.; Mendenhall, G. D. J . Org. Chem. 1981, 46, 3997.
(3) Keay, R. E.; Hamilton, G. J . Am. Chem. Soc. 1976, 98, 6578.
(4) Pryor, W. A.; Govindan, C. K.; Church, D. F. J . Am. Chem. Soc.
1982, 104, 7563.
(5) Griesbaum, K.; Greunig, H.-J .; Volpp, W.; J ung, I. Ch. Chem.
Ber. 1991, 124, 947.
(6) Griesbaum, K.; Ball, V. Tetrahedron Lett. 1994, 35, 1163.
Resu lts
Ozonolyses of 2-butyne (7) in the presence of the
aldehydes 8a -c, of the ketones 8d -g, of the acyl cyanide
8h , and of the esters 8i and 8j followed by treatment with
O-methylhydroxylamine gave the corresponding stable
ozonides 10, which were isolated in the yields shown
1
(Chart 1). On the basis of the similarity of the H NMR
S0022-3263(97)00179-5 CCC: $14.00 © 1997 American Chemical Society

6130 J . Org. Chem., Vol. 62, No. 18, 1997
Griesbaum et al.
shift values of respective groups of corresponding ozo-
nides of types 9 and 10, ozonides 9c-j could be also
detected by 1H NMR analysis of the crude ozonolysis
products prior to the derivatization reactions. However,
of these ozonides only 9i and 9j could be isolated, whereas
9c-h decomposed during the attempted isolation. In the
crude products derived from the ozonolysis of 7 in the
presence of formaldehyde (8a ) or benzaldehyde (8b), the
corresponding ozonides 9a and 9b could not be detected,
despite the fact that the corresponding derivatives 10a
and 10b were formed. This apparent discrepancy is
ascribed to decompositions of 9a and 9b during the
yields shown and characterized by the methods described
above, including reduction to give the corresponding
products 15 and 18. Ozonolysis of 14 in the presence of
acetaldehyde (15a ) gave two isomeric ozonides 17a of
unknown stereochemistry, whereas of the ozonides 17d -f
only one isomer, each of unknown stereochemistry, was
obtained. 1H NMR analyses of the crude product mix-
tures prior to the derivatization step showed the presence
of ozonides 16b-f, of which only 16e and 16f could be
isolated. Ozonide 16a was not detected.
Ozonolyses of the acyloxy-substituted 2-butynes 19a
and 19b in the presence of acetone did not provide the
corresponding cross ozonides. Instead, we obtained ozo-
nides which had the same molecular weights as the
expected intermediates 20. This, together with the fact
that the same products were obtained by ozonolyses of
19a and 19b in the absence of acetone, was indicative of
intramolecular [3 + 2]-cycloadditions between the car-
bonyl oxide moieties and the ester carbonyl groups in
intermediates 20. A priori, such intramolecular cycload-
ditions could provide two types of bicyclic ozonides, viz.
21 and 22, depending on which of the two ester carbonyl
groups in 20 reacts with the carbonyl oxide moiety.
However, the chemical and structural evidence provided
below shows that only the ozonides 22a and 22b with a
[3.2.1] bicyclic ring structures have been selectively
obtained. The formation of the isomeric ozonides 21a and
21b is most likely to be precluded by the higher degree
of ring strain in the transition state leading to the [2.2.1]
bicyclic ring system.
1
solvent evaporation prior to the H NMR analysis. One
of the decomposition products of 9a was its acyclic, non-
peroxidic isomer 12 (7%), which had been also obtained
previously as a product of the ozonolysis of the parent
olefin of 9a , viz. 2-methyl-1-buten-3-one.3
All of the stable ozonides (10a -j) have been character-
ized by positive peroxide tests, satisfactory elemental
analyses, and their 1H, 13C, and 17O NMR spectra. Re-
ductions of ozonides 10a -j gave the corresponding com-
pounds of types 8 and 11 in nearly equimolar amounts.
Of the possible cis,trans-ozonides 10b, 10c, 10e, 10f, 10h ,
10i, and 10j, only one isomer has been obtained in each
case, but unambiguous stereochemical assignments could
not be made on the basis of the available data.
Ozonolysis of 7 in the presence of butanedione followed
by derivatization with O-methylhydroxylamine provided
ozonide 13b of unknown stereochemical identity. It was
isolated in 10% yield and characterized as described
above; its reduction gave 2 molar equiv of 11. Although
the corresponding ozonide 13a could not be detected, the
formation of 13b provides evidence for its transient
existence.
Ozonides 22a and 22b could be isolated in yields of
70% and 58%, respectively, but they underwent gradual
decomposition at room temperature. Treatment of the
crude ozonolysis products of 19a and 19b with O-meth-
ylhydroxylamine gave the corresponding stable ozonides
23a c (11%) and 23bc (9%), which were characterized by
the methods mentioned above, including reduction with
triphenylphosphine to give 24a and 24b, respectively.
Treatment of the crude ozonolysis products of 19a and
19b with hydroxylamine gave the oximes 23a d (4%) and
24bd (10%), respectively. In contrast to the monocyclic
R-oxo ozonides of types 9 and 16, the bicyclic ozonides
22 reacted also with diazomethane to give the stable
epoxy ozonides 25a (42%) and 25b (38%), respectively.
Reductions of these ozonides with triphenylphosphine
gave the expected epoxides 26a and 26b, respectively.
O
O
X
C
C
C
C
X
O
CH3 CH3 CH3 CH3
13
a
b
NOCH3
X
O
Ozonolyses of 3-hexyne (14) in the presence of one of
the carbonyl compounds 15a -f followed by treatment
with O-methylhydroxylamine gave the corresponding
stable ozonides 17 (Chart 2). They were isolated in the
The unambiguous structural assignment of ozonide
22a is based on X-ray diffraction analysis of the related
crystalline epoxy ozonide 25a (Figure 1).7 The structural
parameters obtained for 25a suggest that the bicyclic ring
system is rigid but relatively strain-free, with the 1,2,4-
trioxolane ring being constrained to an envelope confor-
mation. The configuration of the epoxy ring, which is
clearly attached to the bicyclic ring system, is consistent
with the required methylene group having been delivered
to the carbonyl group in 22a from the less hindered exo-
face.
Ch a r t 2
C2H5
O
O
R1
R2
C
O
O
R1CR2
15
C
C
C2H5
O
CH3CH2C CCH2CH3
14
16
C2H5
O
O
R1
R2
C
NOCH3
O
C
C
NOCH3
C
C
C2H5
O
C2H5 C2H5
17
18
e
a
b
c
d
f
The X-ray crystallographic study of oxime derivative
23bd (Figure 2) confirms the general structural features
of the bicyclic ozonide. There is generally good agree-
ment between corresponding structural parameters in
23bd and 25a .8 The hydroxyimino group at C(2) in 23b
has the E-configuration, thereby minimizing steric in-
teractions with the adjacent bridgehead acetoxymethyl
group.
R1
R2
CH3
CH3
CN
52a
3
H
H
H
(CH2)5
CH3 CH3
OCH3
OC2H5
71a
nd
45a
25
79a 43b 70a 36b
18 16
16(%)
17(%)b 16c
24
aDetermined in the product mixture. bYield of isolated product. nd = not
detected. cTwo stereoisomers in yields of 11% and 5%.

Ozonolyses of Acetylenes
J . Org. Chem., Vol. 62, No. 18, 1997 6131
O
O
RCOCH2C CCH2OCR
RCOCH2C CCH2OCR
O
O
O
O
O
20
19
O
O
O
O
O
R
CH2OCR
O
O
RCOCH2C
R
O
O
O
O
O
21
22
OCH3
O
O
O
R
R
CH2OCR
N
O
O
O
O
O
O
RCOCH2C CCH2OCR
NOR′
23
24
O
O
O
F igu r e 1. ORTEP diagram of the molecular structure of 25a
in the crystal. Only one of the two unique molecules is shown
for clarity. All thermal ellipsoids for non-hydrogen atoms are
represented at the 50% probability density level; hydrogen
atoms are represented as open circles of arbitrary radius.
O
O
CH2OCR
CCH2OCR
CH2OCR
CH2
C
O
CH2
O
O
O
26
a, R = C6H5; b, R = CH3; c, R′ = CH3; d, R′ = H
25
appeared in the range of δ 1.60-1.80 ppm and that there
were no signals for CH3CO groups in the range of δ 2.2-
2.3 ppm. Ozonides 32 and 34 were characterized by the
methods mentioned above, including reductions with
triphenylphosphine to give 33 from 32 and 35 from 34.
Ozonolyses of the acyloxy-substituted 2-butynes 27a
and 27b in the presence of acetone also did not provide
the corresponding cross ozonides. Instead, we obtained
the same bicyclic ozonides which were produced by
ozonolyses of 27a and 27b in the absence of acetone, viz.
31a and 31b. They were obviously formed via interme-
diates 29. Although, as evidenced by trapping with
methanol,9 intermediates 28 were also produced in
roughly the same amounts as intermediates 29, there
was no evidence for the formation of the isomeric ozonides
30. This supports our view that the lack of formation of
ozonides 21 was due to inherent ring strain in the bicyclic
[2.2.1] ring system.
O
O
RCOCH2C CCH3
RCOCH2
O
C
CCH3
O
O
28
27
O
O
O
O
O
R
CCH3
RCOCH2C CCH3
Bicyclic ozonides 31a and 31b were formed in yields
of 55% and 38%, respectively, as shown by 1H NMR
analysis of the crude reaction products. They were less
stable than ozonides 22a and 22b and, hence, were not
isolated. However, treatment of the crude reaction
products with O-methylhydroxylamine gave the stable
ozonides 32a (7%) and 32b (13%), respectively, and
treatment with diazomethane gave the stable ozonides
34a (14%) and 34b (13%), respectively.
O
O
O
29
O
O
30
O
O
O
R
CH3
R
CH3
O
O
O
O
O
NOCH3
31
OCH3
32
O
O
R
CH3
N
O
O
O
The assignments of structures 31 as opposed to 30 are
based on the fact that the signals for the CH3 groups
O
CH2
O
RCOCH2C CCH3
34
33
(7) Crystal data for 25a : C19H16O7, M ) 356.32, colorless needles,
monoclinic, space group P21/c (No. 14), a ) 14.5883(11), b ) 23.755(2),
and c ) 9.7459(7) Å, â ) 91.130(6)°, U 3376.7(4) Å3, Z ) 8, Dc ) 1.402
g cm-3, F(000) ) 1488, µ(Mo KR) ) 0.108 mm-1, graphite-monochro-
mated Mo KR λ ) 0.71073 Å, T ) 293 K. Data were collected on a
Siemens P4 diffractometer, and the structure was solved by direct
methods. Final discrepancy factors: R ) 0.056 and Rw ) 0.124. The
crystal structure consists of two independent molecules per asymmetric
unit which only differ significantly in the spatial orientation of the
phenyl group at C(4).
O
CH2OCR
CCH3
CH2
C
O
O
35
a, R = C6H5; b, R = CH3
(8) Crystal data for 23bd : C8H11NO7, M ) 233.18, colorless needles,
triclinic, space group P1 (No. 2), a ) 7.2522(7), b ) 8.8749(7), and c )
8.9885(8) Å, R ) 109.534(6), â ) 95.022(9), and γ ) 111.235(5)°, U )
493.66(8) Å3, Z ) 2, Dc ) 1.569 cm-3, F(000) ) 244, µ(Mo KR) ) 0.140
mm-1, graphite-monochromated Mo KR λ ) 0.71073 Å, T ) 293 K.
Data were collected on a Siemens P4 diffractometer, and the structure
was solved by direct methods. Final discrepancy factors: R ) 0.037
and Rw ) 0.097. The authors have deposited the atomic coordinates
for the crystal structures of 25a and 23bd with the Cambridge
Crystallographic Data Centre. The coordinates can be obtained, on
request, from the Director, the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.
The results obtained in this study show that R-oxo
carbonyl oxides 3 derived from ozonolysis of acetylenes
1 can be readily trapped by carbonyl compounds to give
monocyclic R-oxo ozonides 5 and that this reaction
competes favorably with the previously postulated forma-
tion of R-oxo dioxiranes 6.3 It appears even that R-oxo
carbonyl oxides are more reactive in [3 + 2]-cycloaddi-
tions with carbonyl compounds than simple alkyl- or aryl-
substituted carbonyl oxides derived from the ozonolysis
(9) Griesbaum, K.; Dong, Y. Liebigs Ann. 1997, 753.

6132 J . Org. Chem., Vol. 62, No. 18, 1997
Griesbaum et al.
by pyrolysis of paraformaldehyde) in 40 mL of CH2Cl2 was
ozonized at -100 °C to give 71% of acetic anhydride (δ 2.23),
17% of acetic acid (δ 2.10), 5% of butanedione (δ 2.34), and
7% of 12 (δ 2.12, 5.73).3 Derivatization at -75 °C for 5 d with
3.62 g (43.4 mmol) of O-methylhydroxylamine and 7 mL of
pyridine in 30 mL of CH3OH, precooled to -75 °C, gave 0.72
g of a residue, from which 0.30 g (9%) of 10a was isolated
(solvent: pentane/ether, 20:1).
3-(1-Me t h o xim in oe t h y l)-3-m e t h yl-1,2,4-t r io x o la n e
(10a ): colorless liquid. 1H NMR: δ 1.64 (s, 3 H), 1.87 (s, 3
H), 3.91 (s, 3 H), 5.19 (s, 1 H), 5.26 (s, 1 H). 13C NMR: δ 9.76,
20.38, 62.11, 94.60, 107.26, 154.30. 17O NMR: δ 103 (s, C-O-
C), 157 (s, N-OCH3), 283 (s) and 319 (s) (O-O). Anal. Calcd
for C6H11NO4 (161.2): C, 44.72; H, 6.88; N, 8.69. Found: C,
44.67; H, 6.65; N, 8.34.
2-Bu tyn e (7) a n d Ben za ld eh yd e (8b). A solution of 0.93
g (17.2 mmol) of 7 and 1.82 g (17.2 mmol) of 8b in 50 mL of
CH2Cl2 was ozonized at -100 °C to give 72% of acetic
anhydride (δ 2.20), 19% of acetic acid (δ 2.08), and 9% of
butanedione (δ 2.30). Derivatization at -75 °C for 5 d with
2.88 g (34.5 mmol) of O-methylhydroxylamine and 6 mL of
pyridine in 30 mL of CH3OH precooled to -75 °C gave 2.24 g
of a residue, from which 0.49 g (12%) of 10b was isolated
(solvent: pentane/ether, 20:1).
3-(1-Met h oxim in oet h yl)-3-m et h yl-5-p h en yl-1,2,4-t r i-
oxola n e (10b): colorless liquid. 1H NMR: δ 1.75 (s, 3 H),
1.97 (s, 3 H), 3.94 (s, 3 H), 6.13 (s, 1 H), 7.40-7.60 (m, 5 H).
13C NMR: δ 10.04, 20.56, 62.06, 104.15, 108.65, 128.10, 128.61,
130.69, 130.92, 155.59. 17O NMR: δ 114 (s, C-O-C), 162 (s,
N-OCH3), 312 (s, O-O). Anal. Calcd for C12H15NO4 (237.3):
C, 60.75; H, 6.37; N, 5.90. Found: C, 60.42; H, 6.19; N, 6.15.
2-Bu tyn e (7) a n d Aceta ld eh yd e (8c). A solution of 1.20
g (22.2 mmol) of 7 and 0.98 g (22.3 mmol) of 8c in 50 mL of
CH2Cl2 was ozonized at -75 °C to give 17% of 9c [δ 1.46 (d, J
) 4.9 Hz, 3 H), 1.54 (s, 3 H), 2.29 (s, 3 H), 5.36 (q, J ) 4.9 Hz,
1 H)]. Derivatization with 3.71 g (44.4 mmol) of O-methylhy-
droxylamine and 7 mL of pyridine in 40 mL of CH3OH at -20
°C for 4 d gave 0.78 g of a residue, from which 0.25 g (6%) of
10c was isolated (solvent: pentane/ether, 20:1).
F igu r e 2. ORTEP diagram of the molecular structure of 23bd
in the crystal. All thermal ellipsoids for non-hydrogen atoms
are represented at 50% probability density level; hydrogen
atoms are represented as open circles of arbitrary radius.
of olefins, since the former react readily with nonacti-
vated ketones while the latter generally do not form
ozonides with ketones.1c From a preparative standpoint,
ozonolyses of acetylenes in the presence of carbonyl
compounds open a short-path, albeit low yield synthesis
for R-oxo ozonides, since they obviate the synthesis of the
parent R-oxo olefins. Furthermore, the in-situ stabiliza-
tion of R-oxo ozonides by conversion of the R-oxo groups
into O-methyl oximes or into epoxides allow the verifica-
tion of the existence of elusive labile ozonides such as
ozonides 9a , 9b, or 13a , which could not be detected as
such in the product mixtures.
Exp er im en ta l Section
3-(1-Me t h oxim in oe t h yl)-3,5-d im e t h yl-1,2,4-t r ioxo-
la n e (10c): colorless liquid. 1H NMR: δ 1.47 (d, J ) 4.9 Hz,
3 H), 1.63 (s, 3 H), 1.89 (s, 3 H), 3.90 (s, 3 H), 5.36 (q, J ) 4.9
Hz, 1 H). 13C NMR: δ 9.67, 15.35, 20.14, 61.96, 101.48, 107.78,
155.74. 17O NMR.10 Anal. Calcd for C7H13NO4 (175.2): C,
47.99; H, 7.48; N, 8.00. Found: C, 48.27; H, 7.31; N, 8.16.
2-Bu tyn e (7) a n d Aceton e (8d ). A solution of 0.56 g (10.4
mmol) of 7 and 0.61 g (10.5 mmol) of 8d in 40 mL of CH2Cl2
was ozonized at -75 °C to give 17% of 9d [δ 1.49 (s), 1.51 (s),
1.54 (s), 2.29 (s)].5 Derivatization with 1.73 g (20.7 mmol) of
O-methylhydroxylamine and 4 mL of pyridine in 20 mL of
CH3OH at -20 °C for 4 d gave 0.35 g of a residue, from which
0.12 g (6%) of 10d was isolated (solvent: pentane/ether, 20:
1).
3-(1-Met h oxim in oet h yl)-3,5,5-t r im et h yl-1,2,4-t r ioxo-
la n e (10d ): colorless liquid. 1H NMR: δ 1.52 (s), 1.53 (s),
1.61 (s, 3 H), 1.89 (s, 3 H), 3.91 (s, 3 H). 13C NMR: δ 10.05,
21.25, 23.30, 25.51, 61.99, 107.60, 109.87, 155.53. 17O NMR.10
Anal. Calcd for C8H15NO4 (189.2): C, 50.78; H, 7.99; N, 7.40.
Found: C, 50.44; H, 8.01; N, 7.42.
2-Bu tyn e (7) a n d Ch lor oa ceton e (8e). A solution of 1.12
g (20.7 mmol) of 7 and 1.88 g (20.3 mmol) of 8e in 80 mL of
CH2Cl2 was ozonized at -75 °C to give 12% of 9e [δ 1.56 (s),
1.59 (s), 2.29 (s), 3.57, AB-system, δA 3.64, δB 3.50 (J ) 11.9
Hz)]. Derivatization with 4.42 g (52.9 mmol) of O-methylhy-
droxylamine and 9 mL of pyridine in 50 mL of CH3OH at -20
°C for 5 d gave 2.03 g of a residue, from which 0.68 g (15%) of
10e was isolated (solvent: pentane/ether, 20:1).
5-(Ch lor om eth yl)-3-(1-m eth oxim in oeth yl)-3,5-dim eth yl-
1,2,4-tr ioxola n e (10e): colorless liquid. 1H NMR: δ 1.59 (s,
3 H), 1.66 (s, 3 H), 1.90 (s, 3 H), 3.58, AB-system, δA 3.66, δB
3.50 (J ) 11.6 Hz, 2 H), 3.92 (s, 3 H). 13C NMR: δ 10.17, 18.34,
20.58, 46.42, 62.07, 108.21, 109.28, 155.47. 17O NMR.10 Anal.
Calcd for C8H14ClNO4 (223.7): C, 42.96; H, 6.31; N, 6.26.
Found: C, 43.28; H, 6.27; N, 6.42.
Gen er a l. NMR spectra: Bruker AC-250. 1H- and 13C(BB)
NMR spectra were obtained in CDCl3 with TMS as internal
reference and the 17O NMR spectra in C6D6 by using H2O as
external reference. The conditions for recording the 17O NMR
spectra and the 17O NMR data of 10c-f, 10h , and 10j have
been published elsewhere.10 Chromatographic separations:
flash chromatography on silica gel. HPLC separations: Merck-
Hitachi 655 A-11; column 3.2 × 25 cm, Li Chrosorb Si 60.
Ozon olysis P r oced u r e. A solution of the respective
acetylene and carbonyl compound in dichloromethane was
treated with ozone at low temperatures until the acetylenic
substrate had disappeared. A sample of ca. 1 mL was
removed, the solvent was evaporated at reduced pressure, and
the residue was analyzed by 1H NMR spectroscopy. The major
part of the cold ozonolysis product was admixed with a solution
of O-methylhydroxylamine and pyridine in methanol, whichs
unless mentioned otherwiseswas precooled to -20 °C, and the
mixture was kept at low temperature for several days. Then,
the solvent was evaporated at room temperature and reduced
pressure, the residue was admixed with water, and the
mixture was extracted with dichloromethane. The extract was
sequentially washed with 2 M aqueous hydrochloric acid and
an aqueous solution of sodium bicarbonate, dried with MgSO4,
filtered, and concentrated by evaporation of the solvent at room
temperature and reduced pressure. Unless mentioned other-
wise, the ozonides were isolated by flash chromatography.
Ca u tion ! An attempt to ozonize 2-butyne in pentane and
in the presence of acetone at -75 °C led to a violent explosion.
Therefore, CH2Cl2 was used as solvent in all experiments. We
assume that this prevents the precipitation of peroxidic by-
products.
2-Bu tyn e (7) a n d F or m a ld eh yd e (8a ). A solution of 1.17
g (21.7 mmol) of 7 and 2 mL of formaldehyde (freshly prepared
2-Bu tyn e (7) a n d Tr iflu or oa ceton e (8f). A solution of
1.01 g (18.7 mmol) of 7 and 2.08 g (18.5 mmol) of 8f in 70 mL
(10) Hock, F.; Ball, V.; Dong, Y.; Gutsche, S.-H.; Hilss, M.; Schlind-
wein, K.; Griesbaum, K. J . Magn. Reson. 1994, Ser. A 111, 150.

Ozonolyses of Acetylenes
J . Org. Chem., Vol. 62, No. 18, 1997 6133
of CH2Cl2 was ozonized at -75 °C to give 42% of 9f [δ 1.61 (q),
1.63 (s), 2.31 (s)]. Derivatization with 3.12 g (37.4 mmol) of
O-methylhydroxylamine and 7 mL of pyridine in 30 mL of
methanol at -20 °C for 5 d gave 0.73 g of a residue, from which
0.40 g (9%) of 10f was isolated (solvent: pentane/ether, 20:1).
3-(1-Me t h oxim in oe t h yl)-3,5-d im e t h yl-5-(t r iflu or o-
m eth yl)-1,2,4-tr ioxola n e (10f): colorless liquid. 1H NMR:
δ 1.66 (s, 3 H), 1.67 (q, J ) 1.3 Hz, 3 H), 1.89 (s, 3 H), 3.93 (s,
3 H). 13C NMR: δ 10.30, 15.73, 19.10, 62.13, 104.53 (q, J )
34 Hz), 109.45, 121.75 (q, J ) 289 Hz), 154.69. 17O NMR.10
Anal. Calcd for C8H12F3NO4 (243.2): C, 39.51; H, 4.97; N, 5.76.
Found: C, 39.79; H, 4.92; N, 5.90.
2-Bu tyn e (7) a n d Cycloh exa n on e (8g). A solution of 0.90
g (16.7 mmol) of 7 and 1.64 g (16.8 mmol) of 8g in 60 mL of
CH2Cl2 was ozonized at -75 °C to give 8% of 9g [δ 1.53 (s),
1.2-2.0 (m), 2.29 (s)]. Derivatization with 1.40 g (16.8 mmol)
of O-methylhydroxylamine and 5 mL of pyridine in 20 mL of
methanol at -20 °C for 5 d gave 1.0 g of a residue, from which
0.19 g (5%) of 10g was isolated (solvent: pentane/ether, 20:
1).
3-(1-Me t h oxim in oe t h yl)-3-m e t h yl-1,2,4-t r ioxa sp ir o-
[4.5]d eca n e (10g): colorless liquid. 1H NMR: δ 1.61 (s, 3
H), 1.30-1.90 (m, 10 H), 1.90 (s, 3 H), 3.90 (s, 3 H). 13C NMR:
δ 10.01, 21.53, 23.72, 23.88, 24.91, 33.40, 34.99, 61.96, 107.28,
110.57, 155.55. 17O NMR: δ 127 (s, C-O-C), 167 (s, N-OCH3),
308 (s, O-O). Anal. Calcd for C11H19NO4 (229.3): C, 57.63;
H, 8.35; N, 6.11. Found: C, 57.50; H, 8.27; N, 6.31.
2-Bu tyn e (7) a n d Acetyl Cya n id e (8h ). A solution of 0.60
g (11.1 mmol) of 7 and 0.76 g (11.0 mmol) of 8h in 80 mL of
CH2Cl2 was ozonized at -75 °C to give 37% of 9h [δ 1.72 (s),
1.88 (s), 2.28 (s)]. Derivatization with 1.85 g (22.2 mmol) of
O-methylhydroxylamine and 5 mL of pyridine in 20 mL of
methanol at -20 °C for 5 d gave 0.41 g of a residue, from which
0.31 g (14%) of 10h was isolated (solvent: pentane/ether, 10:
1).
5-Cya n o-3-(1-m eth oxim in oeth yl)-3,5-d im eth yl-1,2,4-tr i-
oxola n e (10h ) : colorless liquid. 1H NMR: δ 1.80 (s, 3 H),
1.86 (s, 3 H), 1.89 (s, 3 H), 3.90 (s, 3 H). 13C NMR: δ 9.77,
19.56, 20.38, 62.13, 98.63, 110.42, 116.45, 153.86. 17O NMR:
δ 134 (s, C-O-C), 166 (s, N-OCH3), 300 (s) and 322 (s) (O-
O). Anal. Calcd for C8H12N2O4 (200.2): C, 48.00; H, 6.04; N,
13.99. Found: C, 48.30; H, 5.99; N, 13.83.
2-Bu tyn e (7) a n d Meth yl F or m a te (8i). (a ) Isola tion
of 9i. A solution of 1.00 g (18.5 mmol) of 7 and 1.12 g (18.7
mmol) of 8i in 60 mL of CH2Cl2 was ozonized at -75 °C to
give 23% of 9i. The solvent was distilled off at room temper-
ature and reduced pressure, and from the residue (3 mL) 0.36
g (12%) of 9i was isolated (solvent: pentane/ether, 5:1).
3-Acetyl-5-m eth oxy-3-m eth yl-1,2,4-tr ioxola n e (9i): col-
orless liquid. 1H NMR: δ 1.65 (s, 3 H), 2.29 (s, 3 H), 3.45 (s,
3 H), 6.02 (s, 1 H). 13C NMR: δ 15.91, 24.99, 51.82, 107.60,
113.38, 203.57.
(b) Isola tion of 10i. Ozonolysis of 1.24 g (23.0 mmol) of 7
and 1.38 g (23.0 mmol) of 8i in 60 mL of CH2Cl2 at -75 °C,
followed by derivatization with 1.92 g (23.0 mmol) of O-
methylhydroxylamine and 4 mL of pyridine in 20 mL of
CH3OH at 0 °C for 4 d, gave 0.48 g of a residue, from which
0.30 g (7%) of 10i was isolated (solvent: pentane/ether, 10:1).
3-(1-Meth oxim in oeth yl)-5-m eth oxy-3-m eth yl-1,2,4-tr i-
oxola n e (10i): colorless liquid. 1H NMR: δ 1.71 (s, 3 H), 1.87
(s, 3 H), 3.45 (s, 3 H), 3.91 (s, 3 H), 6.06 (s, 1 H). 13C NMR:
δ 10.18, 18.93, 51.50, 62.10, 108.08, 113.61, 154.62. 17O
NMR: δ 37 (s, OCH3), 126 (s, C-O-C), 160 (s, N-OCH3),
303 (s, O-O). Anal. Calcd for C7H13NO5 (191.2): C, 43.98;
H, 6.85; N, 7.33. Found: C, 44.31; H, 6.65; N, 7.34.
2-Bu tyn e (7) a n d Eth yl F or m a te (8j). (a ) Isola tion of
9j. A solution of 0.64 g (12.2 mmol) of 7 and 0.91 g (12.3 mmol)
of 8j in 40 mL of CH2Cl2 was ozonized at -75 °C and worked
up as described for 9i to give 0.30 g (14%) of 9j.
methylhydroxylamine and 4 mL of pyridine in 20 mL of
CH3OH at 0 °C for 4 d, gave 1.35 g of a residue, from which
0.37 g (9%) of 10j was isolated (solvent: pentane/ether, 20:1).
5-E t h oxy-3-(1-m et h oxim in oet h yl)-3-m et h yl-1,2,4-t r i-
oxola n e (10j): colorless liquid. 1H NMR: δ 1.27 (t, J ) 7.1
Hz, 3 H), 1.71 (s, 3 H), 1.87 (s, 3 H), 3.74 (m, 2 H), 3.91 (s, 3
H), 6.08 (s, 1 H). 13C NMR: δ 10.13, 14.91, 19.09, 60.60, 62.05,
107.95, 113.26, 154.68. 17O NMR: δ 70 (s, OCH2), 130 (s,
C-O-C), 161 (s, N-OCH3), 296 (s, O-O). Anal. Calcd for
C8H15NO5 (205.2): C, 46.82; H, 7.37; N, 6.83. Found: C, 46.98;
H, 7.28; N, 6.96.
Red u ction s of Ozon id es 10a -j. A solution of ca. 20 mg
of one of the ozonides in 1 mL of CDCl3 was admixed with
excess TPP at room temperature. 1H NMR analysis after 12
h showed in each case the presence of 11 [δ 1.90 (s, 3 H), 2.36
(s, 3 H), 4.04 (s, 3 H)] and of the corresponding carbonyl
compound 8 in a ratio of ca. 1:1.
2-Bu tyn e (7) a n d Bu ta n ed ion e. A solution of 1.28 g (23.7
mmol) of 7 and 2.03 g (23.6 mmol) of butanedione in 40 mL of
CH2Cl2 was ozonized at -100 °C to give a mixture of acetic
anhydride and acetic acid. Derivatization at -75 °C for 5 d
with 3.96 g (47.4 mmol) of O-methylhydroxylamine and 8 mL
of pyridine in 30 mL of CH3OH precooled to -75 °C gave 2.80
g of a residue, from which 0.60 g (10%) of 13b has been isolated
by flash chromatography (solvent: pentane/ether, 10:1), fol-
lowed by HPLC separation (solvent: pentane/ether, 92:8).
3,5-Bis(1-m e t h oxim in oe t h yl)-3,5-d im e t h yl-1,2,4-t r i-
oxola n e (13b): colorless liquid. 1H NMR: δ 1.65 (s, 3 H),
1.92 (s, 3 H), 3.91 (s, 3 H). 13C NMR: δ 10.16, 20.07, 62.01,
108.39, 155.51. 17O NMR: δ 118 (s, C-O-C), 170 (s, N-OCH3),
305 (s, O-O). Anal. Calcd for C8H18N2O5 (246.3): C, 48.77;
H, 7.37; N, 11.38. Found: C, 48.68; H, 7.27; N, 11.41.
Red u ction of 13b. A solution of 20 mg of 13b in 1 mL of
CDCl3 was admixed with excess TPP at room temperature.
After 1 week, 11 was present as the only product of reduction.
3-Hexyn e (14) a n d Aceta ld eh yd e (15a ). A solution of
1.07 g (13.1 mmol) of 14 and 0.57 g (13.0 mmol) of 15a in 50
mL of CH2Cl2 was ozonized at -75 °C to give 35% of propionic
anhydride [δ 1.19 (t, J ) 7.4 Hz), 2.50 (q, J ) 7.4 Hz)] and
65% of paraldehyde [δ 1.38 (d, J ) 5.2 Hz), 5.06 (q, J ) 5.2
Hz)]. Derivatization with 2.17 g (26.0 mmol) of O-methylhy-
droxylamine and 5 mL of pyridine in 50 mL of CH3OH at 0 °C
for 5 d gave 1.21 g of a residue, from which 0.12 g (5%) of 17a
(isomer I) and 0.30 g (11%) of 17a (isomer II) were isolated
(solvent: pentane/ether, 30:1).
3-E t h yl-3-(1-m et h oxim in op r op yl)-5-m et h yl-1,2,4-t r i-
oxola n es (17a ). Isom er I: colorless liquid. 1H NMR: δ 0.98
(t, J ) 7.4 Hz, 3 H), 1.09 (t, J ) 7.5 Hz, 3 H), 1.45 (d, J ) 5.0
Hz, 3 H), 1.96 (m, 2 H), 2.31 (m, 2 H), 3.90 (s, 3 H), 5.45 (q, J
) 5.0 Hz, 1 H). 13C NMR: δ 7.81, 10.70, 17.51, 18.89, 28.26,
62.09, 102.20, 109.99, 157.82. 17O NMR: δ 115 (s, C-O-C),
156 (s, N-OCH3), 301 (s, O-O). Anal. Calcd for C9H17NO4
(203.2): C, 53.19; H, 8.43; N, 6.89. Found: C, 53.47; H, 8.14;
N, 6.83.
Isom er II: colorless liquid. 1H NMR: δ 1.00 (t, J ) 7.4
Hz, 3 H), 1.11 (t, J ) 7.5 Hz, 3 H), 1.48 (d, J ) 4.9 Hz, 3 H),
1.97 (m, 2 H), 2.34 (m, 2 H), 3.90 (s, 3 H), 5.35 (q, J ) 4.9 Hz,
1 H). 13C NMR: δ 7.40, 10.82, 15.52, 18.75, 27.09, 61.93,
102.16, 109.56, 160.02. 17O NMR: δ 112 (s, C-O-C), 157 (s,
N-OCH3), 302 (s, O-O). Anal. Calcd for C9H17NO4 (203.2):
C, 53.19; H, 8.43; N, 6.89. Found: C, 52.79; H, 8.31; N, 6.94.
3-Hexyn e (14) a n d Aceton e (15b). A solution of 1.61 g
(19.6 mmol) of 14 and 1.14 g (19.7 mmol) of 15b in 80 mL of
CH2Cl2 was ozonized at -75 °C to give 71% of 16b [δ 0.98 (t,
J ) 7.5 Hz, 3 H), 1.07 (t, J ) 7.2 Hz, 3 H), 1.47 (s, 3 H), 1.49
(s, 3 H), 1.86 (q, J ) 7.5 Hz, 2 H), 2.67 (m, 2 H)] and propionic
anhydride. Derivatization with 3.30 g (39.5 mmol) of O-
methylhydroxylamine and 7 mL of pyridine in 30 mL of
CH3OH at 0 °C for 6 d gave 2.28 g of a residue, from which
1.01 g (24%) of 17b was isolated (solvent: pentane/ether, 20:
1).
3-Acetyl-5-eth oxy-3-m eth yl-1,2,4-tr ioxola n e (9j): color-
less liquid. 1H NMR: δ 1.27 (t, J ) 7.1 Hz, 3 H), 1.65 (s, 3 H),
2.28 (s, 3 H), 3.74 (m, 2 H), 6.05 (s, 1 H). 13C NMR: δ 14.79,
16.00, 24.32, 60.97, 107.45, 112.97, 203.67.
(b) Isola tion of 10j. Ozonolysis of 1.08 g (20.0 mmol) of 7
and 1.48 g (20.0 mmol) of 8j in 60 mL of CH2Cl2 at -75 °C,
followed by derivatization with 1.67 g (20.0 mmol) of O-
3-E t h yl-3-(1-m et h oxim in op r op yl)-5,5-d im et h yl-1,2,4-
tr ioxola n e (17b): colorless liquid. 1H NMR: δ 1.05 (t, J )
7.5 Hz, 3 H), 1.10 (t, J ) 7.5 Hz, 3 H), 1.49 (s, 3 H), 1.55 (s, 3
H), 1.90 (q, J ) 7.5 Hz, 2 H), 2.32 (m, 2 H), 3.91 (s, 3 H). 13C
NMR: δ 7.68, 10.73, 19.12, 23.19, 25.75, 27.44, 62.00, 109.63,

6134 J . Org. Chem., Vol. 62, No. 18, 1997
Griesbaum et al.
109.84, 159.85. 17O NMR: δ 122 (s, C-O-C), 163 (s, N-OCH3),
304 (s, O-O). Anal. Calcd for C10H19NO4 (217.3): C, 55.28;
H, 8.81; N, 6.45. Found: C, 55.27; H, 8.68; N, 6.53.
3-Hexyn e (14) a n d Cycloh exa n on e (15c). A solution of
1.49 g (18.2 mmol) of 14 and 1.78 g (18.2 mmol) of 15c in 70
mL of CH2Cl2 was ozonized at -75 °C to give 45% of 16c [δ
0.98 (t, J ) 7.5 Hz, 3 H), 1.07 (t, J ) 7.2 Hz, 3 H), 1.30-1.90
(m), 1.86 (q, J ) 7.5 Hz, 2 H), 2.68 (m, 2 H)] and propionic
anhydride. Derivatization with 3.03 g (36.3 mmol) of O-
methylhydroxylamine and 6 mL of pyridine in 30 mL of
CH3OH at 0 °C for 6 d gave 2.87 g of a residue, from which
1.18 g (25%) of 17c was isolated (solvent: pentane/ether, 20:
1).
3-E t h yl-3-(1-m e t h oxim in op r op yl)-1,2,4-t r ioxa sp ir o-
[4.5]d eca n e (17c): colorless liquid. 1H NMR: δ 0.99 (t, J )
7.5 Hz, 3 H), 1.11 (t, J ) 7.5 Hz, 3 H), 1.30-1.90 (m, 10 H),
1.91 (q, J ) 7.5 Hz, 2 H), 2.32 (m, 2 H), 3.90 (s, 3 H). 13C
NMR: δ 7.74, 10.76, 19.05, 23.66, 23.95, 24.90, 27.68, 33.42,
35.08, 61.95, 109.25, 110.47, 159.65. 17O NMR: δ 120 (s,
C-O-C), 160 (s, N-OCH3), 319 (s, O-O). Anal. Calcd for
C13H23NO4 (257.3): C, 60.68; H, 9.01; N, 5.44. Found: C,
60.95; H, 8.82; N 5.74.
(b) Isola tion of 17f. A solution of 1.69 g (20.6 mmol) of 14
and 1.53 g (20.7 mmol) of 15f in 70 mL of CH2Cl2 was ozonized
at -75 °C. Derivatization with 2.58 g (30.9 mmol) of O-
methylhydroxylamine and 5 mL of pyridine in 30 mL of
CH3OH at 0 °C for 6 d gave 1.40 g of a residue, from which
0.78 g (16%) of 17f was isolated (solvent: pentane/ether, 20:
1).
5-E t h oxy-3-et h yl-3-(1-m et h oxim in op r op yl)-1,2,4-t r i-
oxola n e (17f): colorless liquid. 1H NMR: δ 1.05 (t, J ) 7.5
Hz, 3 H), 1.10 (t, J ) 7.5 Hz, 3 H), 1.26 (t, J ) 7.1 Hz, 3 H),
1.97 (q, J ) 7.4 Hz, 2 H), 2.28 (m, 2 H), 3.73 (m, 2 H), 3.91 (s,
3 H), 6.07 (s, 1 H). 13C NMR: δ 7.52, 10.51, 14.93, 19.18, 25.79,
60.71, 62.10, 110.01, 113.14, 158.73. 17O NMR: δ 69 (s, OCH2),
134 (s, N-OCH3), 173 (s, C-O-C), 304 (s, O-O). Anal. Calcd
for C10H19NO5 (233.3): C, 51.49; H, 8.21; N, 6.00. Found: C,
51.26; H, 8.19; N, 6.07.
Red u ction s of Ozon id es 17a -f. A solution of ca. 20 mg
of one of the ozonides in 1 mL of CDCl3 was admixed with
excess TPP at room temperature. 1H NMR analyses after
6-12 h showed in each case the presence of 18 [δ 0.98 (t, J )
7.5 Hz, 3 H), 1.09 (t, J ) 7.3 Hz, 3 H), 2.47 (q, J ) 7.5 Hz, 2
H), 2.80 (q, J ) 7.3 Hz, 2 H), 4.02 (s, 3 H)] and of the
corresponding carbonyl compound 15 in a ratio of ca. 1:1.
Ozon olyses of 1,4-Diben zoxy-2-bu tyn e (19a ). (a ) In th e
P r esen ce of Aceton e. A solution of 0.25 g (0.9 mmol) of 19a
and 0.10 g (1.7 mmol) of acetone in 10 mL of CH2Cl2 was
ozonized at -30 °C to give 56% of 22a .
(b) In th e Absen ce of Aceton e. A solution of 1.96 g (6.7
mmol) of 19a in 60 mL of CH2Cl2 was ozonized at -30 °C to
give 94% of 22a . The solvent was distilled off at room
temperature and reduced pressure, and from the residue (4
mL) 1.60 g (70%) of 22a was isolated.
3-Hexyn e (14) a n d Acetyl Cya n id e (15d ). A solution of
1.43 g (17.4 mmol) of 14 and 1.25 g (17.4 mmol) of 15d in 80
mL of CH2Cl2 was ozonized at -75 °C to give 52% of 16d [δ
1.08 (t, J ) 7.3 Hz, 6 H), 1.86 (s, 3 H), 2.03 (q, J ) 7.5 Hz, 2
H), 2.62 (m, 2 H)] and propionic anhydride. Derivatization
with 2.91 g (34.9 mmol) of O-methylhydroxylamine and 5 mL
of pyridine in 30 mL of CH3OH at 0 °C for 6 d gave 0.56 g of
a
residue, from which 0.12 g (3%) of 17d was isolated
(solvent: pentane/ether, 20:1).
5-Cya n o-3-et h yl-3-(1-m et h oxim in op r op yl)-5-m et h yl-
1,2,4-tr ioxola n e (17d ): colorless liquid. 1H NMR: δ 1.09 (t,
J ) 7.5 Hz, 6 H), 1.91 (s, 3 H), 2.07 (q, J ) 7.5 Hz, 2 H), 2.29
(m, 2 H), 3.90 (s, 3 H). 13C NMR: δ 7.35, 10.65, 19.09, 20.87,
26.40, 62.23, 99.19, 112.31, 116.57, 158.26. 17O NMR: δ 111
(s, C-O-C), 152 (s, N-OCH3), 316 (s, O-O). Anal. Calcd
for C10H16N2O4 (228.3): C, 52.62; H, 7.07; N, 12.27. Found:
C, 52.91; H, 7.02; N, 12.41.
3-Hexyn e (14) a n d Meth yl F or m a te (15e). (a ) Isola tion
of 16e. A solution of 1.05 g (12.8 mmol) of 14 and 0.77 g (12.8
mmol) of 15e in 60 mL of CH2Cl2 was ozonized at -75 °C to
give 79% of 16e and propionic anhydride. The solvent was
distilled off at room temperature and reduced pressure, and
from the residue (3 mL) 1.05 g (43%) of 16e was isolated.
5-Meth oxy-3-eth yl-3-p r op ion yl-1,2,4-tr ioxola n e (16e):
colorless liquid. 1H NMR: δ 1.03 (t, J ) 7.6 Hz, 3 H), 1.08 (t,
J ) 7.2 Hz, 3 H), 1.98 (q, J ) 7.6 Hz, 2 H), 2.65 (m, 2 H), 3.44
(s, 3 H), 5.98 (s, 1 H). 13C NMR: δ 6.91, 7.09, 23.42, 30.52,
52.02, 109.76, 113.31, 206.93.
(b) Isola tion of 17e. The above-described ozonolysis of 14
and 15e was repeated. Derivatization with 1.02 g (12.2 mmol)
of O-methylhydroxylamine and 2 mL of pyridine in 20 mL of
CH3OH at 0 °C for 6 d gave 1.23 g of a residue, from which
0.48 g (18%) of 17e was isolated.
3-Eth yl-3-(1-m eth oxim in op r op yl)-5-m eth oxy-1,2,4-tr i-
oxola n e (17e): colorless liquid. 1H NMR: δ 1.05 (t, J ) 7.6
Hz, 3 H), 1.10 (t, J ) 7.5 Hz, 3 H), 2.00 (q, J ) 7.5 Hz, 2 H),
2.28 (m, 2 H), 3.44 (s, 3 H), 3.91 (s, 3 H), 6.03 (s, 1 H). 13C
NMR: δ 7.49, 10.48, 19.17, 25.67, 51.68, 62.11, 110.12, 113.56,
158.62. 17O NMR: δ 61 (s, C-OCH3), 131 (s, N-OCH3), 159
(s, C-O-C), 316 (s, O-O). Anal. Calcd for C9H17NO5
(219.2): C, 49.31; H, 7.82; N, 6.39. Found: C, 49.38; H, 7.84;
N, 6.51.
5-(Be n zoxym e t h yl)-4-oxo-1-p h e n yl-2,6,7,8-t e t r a oxa -
bicyclo[3.2.1]octa n e (22a ): colorless liquid. 1H NMR:
δ
4.70, AB-system, δA 4.82, δB 4.58 (J ) 17.5 Hz, 2 H), 4.94, AB-
system, δA 4.99, δB 4.89 (J ) 13.2 Hz, 2 H), 7.30-8.20 (m, 10
H). 13C NMR: δ 56.44, 67.89, 103.89, 119.20, 126.97, 128.45,
128.48, 129.04, 129.40, 129.92, 131.08, 133.51, 165.40, 193.33.
(c) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
O-Meth yl h yd r oxyla m in e. A solution of 3.26 g (11.1 mmol)
of 19a in 70 mL of CH2Cl2 was ozonized at -30 °C. Deriva-
tization with 1.39 g (16.7 mmol) of O-methylhydroxylamine
and 3 mL of pyridine in 20 mL of CH3OH at 0 °C for 9 d gave
4.25 g of a residue, from which 0.47 g (11%) of 23a c was
isolated (solvent: pentane/ether, 9:1).
5-(Ben zoxym et h yl)-4-m et h oxim in o-1-p h en yl-2,6,7,8-
tetr a oxa bicyclo[3.2.1]octa n e (23a c): colorless solid; mp 96.5
°C. 1H NMR: δ 3.92 (s, 3 H), 4.95, AB-system, δA 5.04, δB
4.86 (J ) 16.4 Hz, 2 H), 5.05, AB-system, δA 5.09, δB 5.01 (J )
13.4 Hz, 2 H), 7.30-8.20 (m, 10 H). 13C NMR: δ 57.65, 58.72,
62.95, 104.56, 118.90, 126.81, 128.32, 128.45, 129.53, 129.96,
130.71, 130.77, 133.34, 146.91, 165.68. Anal. Calcd for
C19H17NO7 (371.4): C, 61.45; H, 4.61; N, 3.77. Found: C,
61.68; H, 4.89; N, 3.96.
Red u ction of 23a c. A solution of 20 mg of 23a c in 1 mL
of CDCl3 was admixed with excess TPP at room temperature.
1H NMR analysis after 2 d showed the presence of 24a as the
sole product of reduction [δ 4.14 (s, 3 H), 5.16 (s, 2 H), 5.45 (s,
2 H), 7.30-8.20 (m, 10 H).
(d ) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
Hyd r oxyla m in e. A solution of 2.92 g (9.9 mmol) of 19a in
60 mL of CH2Cl2 was ozonized at -30 °C. Derivatization with
1.04 g (15.0 mmol) of NH2OH‚HCl and 3 mL of pyridine in 5
mL of H2O and 30 mL of CH3OH at 0 °C for 10 d gave 4.54 g
of a residue, from which 0.15 g (4%) of 23a d was isolated
(solvent: pentane/ether, 4:1).
5-(Ben zoxym et h yl)-4-h yd r oxim in o-1-p h en yl-2,6,7,8-
tetr a oxa bicyclo[3.2.1]octa n e (23a d ): colorless solid; mp 119
°C. 1H NMR: δ 5.04, AB-system, δA 5.16, δB 4.92 (J ) 16.0
Hz, 2 H), 5.06, AB-system, δA 5.09, δB 5.03 (J ) 12.8 Hz, 2 H),
7.30-8.20 (m, 10 H). 13C NMR: δ 57.88, 58.51, 104.64, 119.01,
126.86, 128.37, 128.53, 129.31, 130.07, 130.66, 130.80, 133.58,
148.43, 166.19. Anal. Calcd for C18H15NO7 (357.3): C, 60.51;
H, 4.23; N, 3.92. Found: C, 60.76; H, 4.51; N, 4.26.
(e) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
Dia zom eth a n e. A solution of 4.27 g (14.5 mmol) of 19a in
3-Hexyn e (14) a n d Eth yl F or m a te (15f). (a ) Isola tion
of 16f. A solution of 1.18 g (14.4 mmol) of 14 and 1.07 g (14.5
mmol) of 15f in 60 mL of CH2Cl2 was ozonized at -75 °C to
give 70% of 16f and propionic anhydride. The solvent was
distilled off at room temperature and reduced pressure, and
from the residue (4 mL) 1.05 g (36%) of 16f was isolated
(solvent: pentane/ether, 6:1).
5-Eth oxy-3-eth yl-3-pr opion yl-1,2,4-tr ioxolan e (16f): col-
orless liquid. 1H NMR: δ 1.02 (t, J ) 7.6 Hz, 3 H), 1.07 (t, J
) 7.2 Hz, 3 H), 1.26 (t, J ) 7.2 Hz, 3 H), 1.98 (q, J ) 7.5 Hz,
2 H), 2.64 (m, 2 H), 3.74 (m, 2 H), 6.02 (s, 1 H). 13C NMR: δ
6.98, 7.16, 14.83, 23.60, 30.59. 61.16, 109.72, 112.90, 207.13.

Ozonolyses of Acetylenes
J . Org. Chem., Vol. 62, No. 18, 1997 6135
80 mL of CH2Cl2 was ozonized at -30 °C, and a solution of
2.8 g (66.7 mmol) of diazomethane in 200 mL of ether was
dropwise added with stirring within 30 min. Stirring was
continued for 2 h at room temperature. Then the solvent was
evaporated at room temperature, and from the residue (6.8
g), 2.17 g (42%) of 25a was isolated (solvent: pentane/ether,
6:1).
4-(Ben zoxym et h yl)-4,7-ep oxy-7-p h en yl-1,5,6,8-t et r a -
oxa sp ir o[2.6]n on a n e (25a ): colorless solid; mp 78 °C. 1H
NMR: δ 2.97 (d, J ) 3.8 Hz, 1 H), 3.27 (dd, J ) 3.8 and 1.9
Hz, 1 H), 3.76 (d, J ) 11.2 Hz, 1 H), 4.82 (dd, J ) 11.2 and 1.9
Hz, 1 H), 4.64, AB-system, δA 4.66, δB 4.62 (J ) 12.8 Hz, 2 H),
7.30-8.20 (m, 10 H). 13C NMR: δ 52.58, 54.54, 57.16, 64.29,
107.30, 118.92, 127.03, 128.34, 128.51, 129.15, 129.55, 129.89,
130.86, 133.48, 165.50. Anal. Calcd for C19H16O7 (356.3): C,
64.04; H, 4.53. Found: C, 64.09; H, 4.56.
Red u ction of 25a . A solution of 30 mg of 25a in 1 mL of
CDCl3 was admixed with excess DMS at room temperature.
1H NMR analysis after 2 h showed the presence of 26a as the
sole product of reduction [δ 3.28, AB-system, δA 3.33, δB 3.23
(J ) 4.6 Hz, 2 H), 4.76, AB-system, δA 5.09, δB 4.43 (J ) 12.5
Hz, 2 H), 4.99, AB-system, δA 5.05, δB 4.93 (J ) 17.6 Hz, 2 H),
7.30-8.20 (m, 10 H)].
continued for 2 h at room temperature. Then the solvent was
evaporated at room temperature, and from the residue (5.9
g), 1.67 g (38%) of 25b was isolated (solvent: pentane/ether,
6:1).
4-(Acet oxym et h yl)-4,7-ep oxy-7-m et h yl-1,5,6,8-t et r a -
oxa sp ir o[2.6]n on a n e (25b): colorless liquid.
1H NMR: δ
1.76 (s, 3 H), 2.13 (s, 3 H), 2.90 (d, J ) 3.9 Hz, 1 H), 3.16 (dd,
J ) 3.9 and 2.0 Hz, 1 H), 3.50 (d, J ) 11.2 Hz, 1 H), 4.56 (dd,
J ) 11.2 and 2.0 Hz, 1 H), 4.30, AB-system, δA 4.35, δB 4.25 (J
) 12.8 Hz, 2 H). 13C NMR: δ 18.24, 20.45, 52.45, 54.20, 56.59,
63.84, 106.36, 119.90, 169.75. Anal. Calcd for C9H12O7
(232.2): C, 46.56; H, 5.21. Found: C, 46.69; H, 5.24.
Red u ction of 25b. A solution of 20 mg of 25b in 1 mL of
CDCl3 was admixed with excess TPP at room temperature.
1H NMR analysis after 6 h showed the presence of 26b as the
sole product of reduction [δ 2.07 (s, 3 H), 2.16 (s, 3 H), 3.15,
AB-system, δA 3.19, δB 3.11 (J ) 4.6 Hz, 2 H), 4.46, AB-system,
δA 4.85, δB 4.07 (J ) 12.4 Hz, 2 H), 4.70, AB-system, δA 4.77,
δB 4.63 (J ) 17.6 Hz, 2 H)].
Ozon olyses of 1-Ben zoxy-2-bu tyn e (27a ). (a ) In th e
P r esen ce of Aceton e. A solution of 0.15 g (0.9 mmol) of 27a
and 0.10 g (1.7 mmol) of acetone in 10 mL of CH2Cl2 was
ozonized at -30 °C to give 44% of 31a .
Ozon olyses of 1,4-Dia cetoxy-2-bu tyn e (19b). (a ) In th e
P r esen ce of Aceton e. A solution of 0.50 g (2.9 mmol) of 19b
and 0.34 g (5.9 mmol) of acetone in 40 mL of CH2Cl2 was
ozonized at -30 °C to give 70% of 22b.
(b) In th e Absen ce of Aceton e. A solution of 0.94 g (5.5
mmol) of 19b in 50 mL of CH2Cl2 was ozonized at -30 °C to
give 81% of 22b, of which 0.70 g (58%) was isolated (solvent:
pentane/ether, 3:7).
(b) In th e Absen ce of Aceton e. A solution of 2.67 g (15.3
mmol) of 27a in 80 mL of CH2Cl2 was ozonized at -30 °C to
give 55% of 31a as shown by 1H NMR analysis [δ 1.74 (s, 3
H), 4.65, AB-system, δA 4.76, δB 3.54 (J ) 17.5 Hz, 2 H), 7.30-
7.80 (m, 5 H)].
(c) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
O-Meth ylh yd r oxyla m in e. The above experiment was re-
peated. Derivatization with 1.92 g (23.0 mmol) of O-methyl-
hydroxylamine and 4 mL of pyridine in 30 mL of CH3OH at 0
°C for 6 d gave 1.57 g of a residue, from which 0.23 g (7%) of
32a was isolated (solvent: pentane/ether, 9:1).
4-Me t h oxim in o-5-m e t h yl-1-p h e n yl-2,6,7,8-t e t r a oxa -
bicyclo[3.2.1]octa n e (32a ): colorless liquid. 1H NMR: δ 1.85
(s, 3 H), 3.91 (s, 3 H), 4.90, AB-system, δA 4.99, δB 3.81 (J )
16.5 Hz, 2 H), 7.30-7.80 (m, 5 H). 13C NMR: δ 14.98, 58.86,
62.66, 106.43, 111.85, 126.69, 128.32, 130.52, 131.52, 148.88.
Anal. Calcd for C12H13NO5 (251.2): C, 57.37; H, 5.22; N, 5.58.
Found: C, 57.23; H, 5.45; N, 5.26.
Red u ction of 32a . A solution of 20 mg of 32a in 1 mL of
CDCl3 was admixed with excess TPP at room temperature.
1H NMR analysis after 1 h showed the presence of 33a as the
sole product of reduction [δ 2.44 (s, 3 H), 4.11 (s, 3 H), 5.13 (s,
2 H), 7.30-8.10 (m, 5 H)].
(d ) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
Dia zom eth a n e. A solution of 3.91 g (22.5 mmol) of 27a in
80 mL of CH2Cl2 was ozonized at -30 °C, and a solution of
2.8 g (66.7 mmol) of diazomethane in 200 mL of ether was
added dropwise with stirring within 30 min. Stirring was
continued for 2 h at room temperature. Then the solvent was
evaporated at room temperature, and from the residue (5.20
g), 0.75 g (14%) of 34a was isolated (solvent: pentane/ether,
9:1).
4,7-E p oxy-4-m e t h yl-7-p h e n yl-1,5,6,8-t e t r a oxa sp ir o-
[2.6]n on a n e (34a ): colorless solid; mp 62 °C. 1H NMR: δ
1.51 (s, 3 H), 2.89 (d, J ) 4.2 Hz, 1 H), 3.03 (dd, J ) 4.2 and
2.0 Hz, 1 H), 3.71 (d, J ) 11.1 Hz, 1 H), 4.77 (dd, J ) 11.1 and
2.0 Hz, 1 H), 7.30-7.80 (m, 5 H). 13C NMR: δ 13.07, 52.79,
54.73, 64.00, 109.51, 118.65, 126.89, 128.34, 130.55, 130.67.
17O NMR: δ -11 (s, epoxy-O), 73 (s, C-O-CH2), 162 (s, C-O-
C), 302 (s, O-O). Anal. Calcd for C12H12O5 (236.2): C, 61.01;
H, 5.12. Found: C, 60.85; H, 4.83.
Red u ction of 34a . A solution of 20 mg of 34a in 1 mL of
CDCl3 was admixed with excess TPP at room temperature.
1H NMR analysis after 12 h showed the presence of 35a as
the sole product of reduction [δ 2.14 (s, 3 H), 3.11, AB-system,
δA 3.13, δB 3.09 (J ) 4.9 Hz, 2 H), 4.74, AB-system, δA 5.01, δB
4.47 (J ) 12.4 Hz, 2 H), 7.40-8.10 (m, 5 H)].
Ozon olyses of 1-Acetoxy-2-bu tyn e (27b). (a ) In th e
P r esen ce of Aceton e. A solution of 0.20 g (1.8 mmol) of 27b
and 0.21 g (3.6 mmol) of acetone in 10 mL of CH2Cl2 was
ozonized at -30 °C to give 20% of 31b.
5-(Ace t oxym e t h yl)-1-m e t h yl-4-oxo-2,6,7,8-t e t r a oxa -
bicyclo[3.2.1]octa n e (22b): colorless liquid. 1H NMR: δ 1.85
(s, 3 H), 2.14 (s, 3 H), 4.46, AB-system, δA 4.59, δB 4.33 (J )
17.5 Hz, 2 H), 4.58, AB-system, δA 4.65, δB 4.51 (J ) 13.1 Hz,
2 H). 13C NMR: δ 18.84, 20.44, 56.03, 67.45, 102.98, 120.33,
169.73, 193.28.
(c) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
O-Meth ylh yd r oxyla m in e. A solution of 2.05 g (12.1 mmol)
of 19b in 60 mL of CH2Cl2 was ozonized at -30 °C. Deriva-
tization with 1.51 g (18.1 mmol) of O-methylhydroxylamine
and 3 mL of pyridine in 20 mL of CH3OH at 0 °C for 5 d gave
1.14 g of a residue, from which 0.27 g (9%) of 23b was isolated.
5-(Acet oxym et h yl)-4-m et h oxim in o-1-m et h yl-2,6,7,8-
tetr a oxa bicyclo[3.2.1]octa n e (23bc): colorless liquid. 1H
NMR: δ 1.76 (s, 3 H), 2.14 (s, 3 H), 3.88 (s, 3 H), 4.68, AB-
system, δA 4.78, δB 4.58 (J ) 16.4 Hz, 2 H), 4.70, AB-system,
δA 4.75, δB 4.65 (J ) 13.3 Hz, 2 H). 13C NMR: δ 19.36, 20.53,
57.09, 58.13, 62.83, 103.59, 119.93, 146.84, 169.96. Anal.
Calcd for C9H13NO7 (247.2): C, 43.73; H, 5.30; N, 5.67.
Found: C, 43.95; H, 5.33; N, 5.86.
Red u ction of 23bc. A solution of 20 mg of 23bc in 1 mL
of CDCl3 was admixed with an excess of TPP at room
temperature. 1H NMR analysis after 4 h showed the presence
of 24b as the sole product of reduction [δ 2.05 (s, 3 H), 2.19 (s,
3 H), 4.13 (s, 3 H), 4.88 (s, 2 H), 5.16 (s, 2 H)].
(d ) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
Hyd r oxyla m in e. A solution of 5.56 g (32.7 mmol) of 19b in
100 mL of CH2Cl2 was ozonized at -30 °C. Derivatization with
3.40 g (48.9 mmol) of H2NOH‚HCl and 10 mL of pyridine in
20 mL of H2O and 50 mL of CH3OH at 0 °C for 6 d gave 1.71
g of a residue, from which 0.76 g (10%) of 23bd was isolated
(solvent: pentane/ether, 3:7).
5-(Ace t oxym e t h yl)-4-h yd r oxim in o-1-m e t h yl-2,6,7,8-
tetr a oxa bicyclo[3.2.1]octa n e (23bd ): colorless solid; mp
86.5 °C. 1H NMR: δ 1.78 (s, 3 H), 2.16 (s, 3 H), 4.69, AB-
system, δA 4.75, δB 4.63 (J ) 13.2 Hz, 2 H), 4.78, AB-system,
δA 4.90, δB 4.66 (J ) 16.4 Hz, 2 H). 13C NMR: δ 19.33, 20.63,
57.39, 57.89, 103.61, 120.04, 148.25, 170.56. Anal. Calcd for
C8H11NO7 (233.2): C, 41.21; H, 4.75; N, 6.01. Found: C, 41.07;
H, 4.81; N, 6.04.
(e) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
Dia zom eth a n e. A solution of 3.21 g (18.9 mmol) of 19b in
80 mL of CH2Cl2 was ozonized at -30 °C, and a solution of
2.8 g (66.7 mmol) of diazomethane in 200 mL of ether was
dropwise added with stirring within 30 min. Stirring was
(b) In th e Absen ce of Aceton e. A solution of 1.98 g (17.7
mmol) of 27b in 60 mL of CH2Cl2 was ozonized at -30 °C to

6136 J . Org. Chem., Vol. 62, No. 18, 1997
Griesbaum et al.
1
give 38% of 31b, as shown by H NMR analysis [δ 1.62 (s, 3
2.8 g (66.7 mmol) of diazomethane in 200 mL of ether was
added dropwise with stirring within 30 min. Stirring was
continued for 2 h at room temperature, and from the residue
(4.3 g), 0.56 g (13%) of 34b was isolated (solvent: pentane/
ether, 5:1).
H), 1.80 (s, 3 H), 4.42, AB-system, δA 4.55, δB 4.29, J ) 17.4
Hz)].
(c) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
O-Meth ylh yd r oxyla m in e. The above experiment was re-
peated. Derivatization with 2.21 g (26.5 mmol) of O-methyl-
hydroxylamine and 5 mL of pyridine in 50 mL of CH3OH at
-20 °C for 5 d gave 1.36 g of a residue, from which 0.43 g
(13%) of 32b was isolated (solvent: pentane/ether, 30:1).
4-Met h oxim in o-1,5-d im et h yl-2,6,7,8-t et r a oxa b icyclo-
[3.2.1]octa n e (32b): colorless liquid. 1H NMR: δ 1.72 (s, 3
H), 1.74 (s, 3 H), 3.88 (s, 3 H), 4.66, AB-system, δA 4.76, δB
4.56 (J ) 16.4 Hz, 2 H). 13C NMR: δ 14.79, 19.62, 58.22, 62.47,
105.51, 119.75, 148.86. 17O NMR: δ 60 (s, C-O-CH2), 156
(s, C-O-C and N-OCH3), 296 (s, O-O). Anal. Calcd for
C7H11NO5 (189.2): C, 44.45; H, 5.86; N, 7.40. Found: C, 44.42;
H, 5.79; N, 7.67.
Red u ction of 32b. A solution of 20 mg of 32b in 1 mL of
CDCl3 was admixed with an excess of TPP at room tempera-
ture. 1H NMR analysis after 12 h showed the presence of 33b
as the sole product of reduction [δ 2.03 (s, 3 H), 2.39 (s, 3 H),
4.09 (s, 3 H), 4.89 (s, 2 H)].
(d ) In Dich lor om eth a n e F ollow ed by Tr ea tm en t w ith
Dia zom eth a n e. A solution of 2.85 g (25.5 mmol) of 27b in
100 mL of CH2Cl2 was ozonized at -30 °C, and a solution of
4,7-E p oxy-4,7-d im et h yl-1,5,6,8,-t et r a oxa sp ir o[2.6]n o-
n a n e (34b): colorless solid; mp 86.5 °C. 1H NMR: δ 1.40 (s,
3 H), 1.72 (s, 3 H), 2.86 (d, J ) 4.2 Hz, 1 H), 3.00 (dd, J ) 4.2
and 2.0 Hz, 1 H), 3.48 (d, J ) 11.1 Hz, 1 H), 4.54 (dd, J ) 11.1
and 2.0 Hz, 1 H). 13C NMR: δ 12.85, 18.55, 52.58, 54.47, 63.47,
108.63, 119.50. 17O NMR: δ 2 (s, epoxy-O), 72 (s, C-O-CH2),
159 (s, C-O-C), 312 (s, O-O). Anal. Calcd for C7H10O5
(174.2): C, 48.28; H, 5.79. Found: C, 48.51; H, 5.68.
Red u ction of 34b. A solution of 20 mg of 34b in 1 mL of
CDCl3 was admixed with excess TPP at room temperature.
1H NMR analysis after 1 h showed the presence of 35b as the
sole product of reduction [δ 2.07 (s, 3 H), 2.10 (s, 3 H), 3.07 (s,
2 H), 4.46, AB-system, δA 4.79, δB 4.13 (J ) 12.4 Hz, 2 H)].
Ack n ow led gm en t. Support of this work by the
Deutsche Forschungsgemeinschaft is gratefully ac-
knowledged.
J O9701795