Unexpected remarkable stability of primary ozonides derived from alkenyl stannanes. One-pot synthesis of 1,2-diols from alkynes

Article abstract of DOI:10.1021/ol0170814

(Matrix Presented) Primary ozonides derived from alkenyl stannanes display an unusual stability and can be transformed into 1,2-diols by treatment with dimethyl sulfide and borane-methyl sulfide complex. This observation has been incorporated into the development of a novel one-pot strategy for the conversion of alkynes into 1,2-diols.

Full text of DOI:10.1021/ol0170814

ORGANIC
LETTERS
2
002
Vol. 4, No. 3
83-386
Unexpected Remarkable Stability of
Primary Ozonides Derived from Alkenyl
Stannanes. One-Pot Synthesis of
3
1,2-Diols from Alkynes
Ana M. G o´ mez,* Mar ´ı a D. Company, Seraf ´ı n Valverde, and J. Crist o´ bal L o´ pez*
Instituto de Qu ´ı mica Org a´ nica General (CSIC), Juan de la CierVa 3,
28006 Madrid, Spain
anago@iqog.csic.es (AMG)
Received November 21, 2001
ABSTRACT
Primary ozonides derived from alkenyl stannanes display an unusual stability and can be transformed into 1,2-diols by treatment with dimethyl
sulfide and borane−methyl sulfide complex. This observation has been incorporated into the development of a novel one-pot strategy for the
conversion of alkynes into 1,2-diols.
The reaction of olefins with ozone is still one of the most
popular methods for cleavage of alkenes and is commonly
used for the preparation of aldehydes, ketones, and acids.
(1,2,3-trioxolane), 1, followed by cycloreversion to carbonyl
oxide and carbonyl fragments, and recombination of the
carbonyl compound and the carbonyl oxide to produce the
final ozonide (secondary ozonide, 1,2,4-trioxolane), 2.3
The primary ozonide, produced in the first step of the
mechanism, is sometimes stable enough at low temperatures
and has been observed by NMR and IR for a variety of
1
-5
A three-step mechanism (Scheme 1) was formulated by
Scheme 1. Mechanism of Ozonolysis
3
alkenes. It was indeed from these data as well as for the
6
conversion of some primary ozonides into 1,2-diols that the
7
cyclic 1,2,3-trioxolane structure was inferred. Although there
are scarce literature reports on ozonation of heteroatom-
substituted alkenes yielding products with no cleavage of
8
the carbon chain, we are not aware of any general synthetic
method for the transformation of substituted olefins into diols
based on the reduction of primary ozonides. In this Letter
(
3) Kuczkowski, R. L. In 1,3-Dipolar Cycloadditon Chemistry; Padwa,
A.; Wiley-Interscience: New York, 1984; p 197.
4) Kuczkowski, R. L. Acc. Chem. Res. 1983, 16, 42.
(5) Kuczkowski, R. L. Chem. Soc. Rev. 1992, 21, 79.
6) Criegee, R.; Schr o¨ der, G. Chem. Ber. 1960, 93, 689. Greenwood, F.
L. J. Org. Chem. 1964, 29, 1231.. Greenwood, F. L. J. Org. Chem. 1965,
(
2
Criegee more than 50 years ago for this process, and it
(
consists of dipolar cycloaddition to form a primary ozonide
3
0, 3108.
(
1) Bailey, P. S. Ozonation in Organic Chemistry. Volume I. Olefinic
Compounds; Academic Press: New York, 1978; Vol. 39.
2) Criegee, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 745.
(7) A primary ozonide was characterized by microwave spectroscopy:
Gillies, J. Z.; Gillies, C. W.; Suenram, R. D.; Lovas, F. J. J. Am. Chem.
Soc. 1988, 110, 7991.
(
1
0.1021/ol0170814 CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/16/2002

we report on (a) the, unexpected, stability of primary
ozonides resulting from the treatment of alkenyl stannanes
with ozone (1a) (Scheme 2), (b) the transformation of the
Scheme 4. Preparation of Alkenyl Stannanes
Scheme 2. Ozonation of Alkenyl Stannanes Leading to
1
,2-Diols
3
were obtained by triethylborane-mediated addition of R SnH
to the corresponding alkynes (9) following a protocol
described by Oshima and co-workers (Scheme 4b).11
The results obtained are outlined in Table 1. In most of
the cases the corresponding 1,2-diol was obtained as the sole
reaction product, and only in two instances (entries ii and
iii) were compounds resulting from cleavage of the carbon-
carbon bond observed, although in a small percentage. These
results provide good evidence for the stability of stannyl-
substituted primary ozonides at -78 °C and also seemed to
above-mentioned 1,2,3-trioxolanes into 1,2-diols, and (c) a
novel one-pot procedure for the transformation of alkynes
into 1,2-diols.
This study originated from the observation, during the
9
course of some unrelated work underway in our laboratory,
of the transformation outlined in Scheme 3a. Ozonolysis of
Table 1. Ozonation of Alkenyl Stannanes 8 and 10a-d
Leading to 1,2-Diols
Scheme 3. Ozonolysis of Alkenyl Stannanes
compound 3, followed by reductive treatment with borane-
methyl sulfide complex, acid hydrolysis, and acetylation,
resulted in the obtention of acetate 4 with no sign of the
expected methyl cyclohexanol. A similar result was obtained
when alkenyl stannane 5 (Scheme 3b) was treated with
ozone, followed by standard reductive treatment, hydrolysis,
and acetylation, thus leading to carbasugar derivative 6.
To study the scope and generality of this process we
prepared alkenyl stannanes 8, 10a-d and submitted them
to ozonation (ozone, MeOH, -78 °C, 15 min) followed by
reductive treatment as above. Compound 8 was prepared by
radical cyclization, from an enyne precursor (7), according
10
to Stork and Mook (Scheme 4a), and alkenyl stannanes 10
(8) Vinyl sulfides: Chaussin, R.; Leriferend, P.; Paquer, D. J. Chem.
Soc., Chem. Commun. 1978, 1032. Strobel, M.-P.; Morin, L.; Paquer, D.
Tetrahedron Lett. 1980, 21, 523. Vinyl silanes: Renaud, P.; Gerster, M.;
Ribezzo, M. Chimia 1994, 48, 366. Silyloxyalkenes: Clark, R. D.;
Heathcock, C. H. Tetrahedron Lett. 1974, 523.
a
The crude reaction mixture was evaporated and the residue submitted
to acetylation (Ac2O/pyridine). b Benzyl alcohol (≈10%) was also obtained.
(9) G o´ mez, A. M.; Danel o´ n, G. O.; Valverde, S.; L o´ pez, J. C. J. Org.
Chem. 1998, 63, 9626.
384
Org. Lett., Vol. 4, No. 3, 2002

indicate that the cycloreversion step in the ozonation mech-
anism is favored for aryl-substituted olefins.
Table 3. One-Pot Syntheses of 1,2-Diols from Alkynes by
BEt -Mediated Addition of Bu SnH Followed by Ozonation and
Reductive Workup
In an effort to evaluate the stability of stannyl-substituted
primary ozonides in different solvents, we carried out the
following experiment: Ozone was bubbled through a solution
of the corresponding olefin, at -78 °C, in the solvent
indicated in Table 2, after 15 min the reaction was warmed
3
3
Table 2. Ozonation of Alkenyl Stannanes 8 and 10a, in
Different Solvents, Followed by Warming to Room Temperature
(time), Cooling at -78 °C, and Reductive Workup, Leading to
1,2-Diols and Monohydroxy Compounds
entry substrate solvent time (h) ratio diol:alcohol yield (%)
i
ii
iii
iv
v
8
8
8
8
8
8
8
8
10a
10a
10a
10a
10a
10a
10a
MeOH
MeOH
MeOH
MeOH
EtOAc
EtOAc
CH2Cl2
CH2Cl2
MeOH
MeOH
EtOAc
EtOAc
CH2Cl2
CH2Cl2
toluene
0a
0.5
2
4
0a
2
0a
2
0a
2
0a
2
0a
1:0
1:2
1:8
0:1
1:0
1:1
1:0
1:2
5:1
1:3
2:1
1:5
4:1
1:7
1:1.5
67
62
63
65
59
63
65
61
71
68
69
66
62
58
59
vi
vii
viii
ix
x
xi
xii
xiii
xiv
xv
2
0a
a
The reactions were not warmed to room temperature.
a
The crude reaction mixture was evaporated and the residue submitted
to acetylation (Ac2O/pyridine).
to room temperature and kept at this temperature for the time
shown in the table. After reductive workup, a mixture of
the corresponding diol and alcohol (where carbon-carbon
bond cleavage had taken place) was obtained and their ratio
reaction products after warming of the reaction mixture
(compare entries i, ii, iii, iv). By corollary, ozonation of
alkenyl stannanes can be driven either to the preparation of
diols or to the synthesis of compounds resulting from
ozonolytic cleavage, by changes in solvent and/or temper-
ature.
We next turned our attention to the reactions shown in
Schemes 4b and 2 (radical-mediated tin addition to an alkyne,
and ozonation of alkenyl stannanes, respectively). We
envisaged that both processes could be carried out as one-
pot operations without the need for isolation of the inter-
mediate alkenyl stannane. The only factor to be adjusted was
the solvent since toluene, which had been the solvent
1
determined by H NMR.
From the results outlined in Table 2, some conclusions
can be drawn: (a) the nature of the solvent influences
considerably the rate of cycloreversion of the primary
ozonide (compare entries i, v, ix, xi, xii, and xv), (b)
ozonolytic cleavage of the double bond in alkenyl stannanes
becomes a favored reaction pathway in certain solvents
(compare entries i and xv), and (c) the cycloreversion step
is accelerated with the temperature, and compounds resulting
from carbon-carbon bond cleavage can become the sole
(10) Stork, G.; Baine, N. H. J. Am. Chem. Soc. 1982, 104, 2321. Stork,
G.; Mook, R., Jr. J. Am. Chem. Soc. 1983, 105, 3720. Stork, G.; Mook, R.,
Jr. J. Am. Chem. Soc. 1987, 109, 2829.
3
currently used in triethylborane-catalyzed addition of Bu -
SnH to alkynes, would facilitate the unwanted cycloreversion
step (see Table 2, entry xv). After some experimentation we
(11) Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987, 109,
2
547. Nozaki, K.; Oshima, K.; Utimoto, K. Tetrahedron 1989, 45, 923.
Org. Lett., Vol. 4, No. 3, 2002
385

chose methanol as solvent for the radical addition and
ozonation. The results in Table 3 show how alkynes can be
transformed into 1,2-diols in a one-pot tandem process.
Terminal alkynes uderwent smooth tin addition in metha-
nol and give moderate yields of the corresponding 1,2-diols
upon ozonation. One example of a disubstituted alkyne (entry
vi) is also included.
Moreover, ozonation of alkenyl stannanes might then be
driven to the formation of diols or products resulting from
carbon-carbon bond breaking by changes in the temperature
and solvent. The influence of the temperature in this process
1
2
3
has already been well documented. On the other hand, the
role of the solvent in the above-mentioned process is
noteworthy. Cycloreversion of the primary ozonide is, thus,
favored in certain solvents, and this could be related with
In summary, we have reported the remarkable stability of
primary ozonides (1a) derived from alkenyl stannanes. This
stability allows the preparation of 1,2-diols from alkenyl
stannanes by ozonation followed by reductive treatment of
the primary ozonides. The procedure disclosed in this Letter
extends the scope of the vinyl radical cyclization mediated
5
the concerted, or not, nature of the process.
Additional work with primary ozonides derived from
alkenyl stannanes, as well as their detailed NMR study, is
under consideration in our laboratory and will be reported
in due course.
1
0
by the addition of stannyl radicals to triple bonds, since it
provides a method for simple functionalization of the
resulting alkenyl stannane. Furthermore this transformation
has been incorporated, together with the radical addition of
Acknowledgment. This work was supported by grants
from the Direcci o´ n General de Ense n˜ anza (Grants PB97-
1
244, PPQ2000-1330, and BQU2001-0582). M.D.C. thanks
the Comunidad Aut o´ noma de Madrid for a fellowship.
Bu
3
SnH to alkynes, in a highly useful one-pot method for
the transformation of alkynes into 1,2-diols.
Supporting Information Available: Complete experi-
mental procedures and spectroscopic and analytical data for
new compounds This material is available free of charge via
Internet at http://pubs.acs.org
(12) Representative experimental procedure: The alkyne is dissolved
in MeOH and treated with Bu3SnH in the presence of BEt3 (-78 °C); once
the starting material has dissappeared (TLC) ozone is bubbled through the
solution (15 min). Oxygen is then bubbled, to eliminate ozone from the
reaction mixture, and then BH3‚SMe2 is added. Evaporation of the solvent
and flash chromatography afforded the corresponding 1,2-diol.
OL0170814
386
Org. Lett., Vol. 4, No. 3, 2002