Ring contraction of 1,2,4,5,7,8-hexaoxa-3-silonanes by selective reduction of COOSi fragments. Synthesis of new silicon-containing rings, 1,3,5,6-tetraoxa-2-silepanes

Article abstract of DOI:10.1021/jo8023957

The reducing agents Ph3P, (C₈H₁₇)₃P, or NH₂C(S)NH₂ promote the ring contraction of nine-membered triperoxides, viz., 1,2,4,5,7,8-hexaoxa-3-silonanes, giving rise to seven-membered rings belonging to t

Full text of DOI:10.1021/jo8023957

Ring Contraction of 1,2,4,5,7,8-Hexaoxa-3-silonanes by Selective
Reduction of COOSi Fragments. Synthesis of New
Silicon-Containing Rings, 1,3,5,6-Tetraoxa-2-silepanes
Alexander O. Terent’ev,* Maxim M. Platonov, Anna I. Tursina, Vladimir V. Chernyshev,
and Gennady I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prospect,
119991, Moscow, Russia
alterex@yandex.ru
ReceiVed October 27, 2008
The reducing agents Ph3P, (C8H17)3P, or NH2C(S)NH2 promote the ring contraction of nine-membered
triperoxides, viz., 1,2,4,5,7,8-hexaoxa-3-silonanes, giving rise to seven-membered rings belonging to the
previously unknown class of monoperoxides, viz., 1,3,5,6-tetraoxa-2-silepanes, in yields from 67% to
91%. Therefore, the selective reduction of the SiOOC fragments to SiOC in molecules containing
simultaneously the COOC fragment was performed for the first time.
Introduction
various reactions of organic peroxides, because peroxides are
traditionally considered as strong oxidizers and, consequently,
the O-O bond cleavage in these compounds primarily occurs
even if molecules contain other groups capable of being reduced.
As a rule, the reduction of peroxides, for example, with H2/
Pd-C,3 thiourea,3a,4 LiAlH4,4c,5 iodine,6 NaBH4,7 or Zn/
CH3COOH,8 affords alcohols.3-8 Recently a simple one-pot
method has been reported to prepare dioxabicyclo[2.2.1]heptane
derivatives from readily available 1,2,4-trioxane frameworks,
under catalytic hydrogenation conditions over a platinum
surface.9
Methods for the selective reduction of functional groups in
molecules containing simultaneously the peroxide COOC frag-
ments, which remain intact, have been extensively developed
with the aim of preparing semisynthetic drug derivatives of
artemisinin (natural cyclic peroxide). The latter are used for
malaria treatment. In one of the early studies, the reduction was
carried out with the use of NaBH4.10 As a result, the six-
membered lactone ring in artemisinin was transformed into lactol
in good yield. The reaction of artemisinin with LiAlH4 led to
In the last decades, methods for the synthesis and reactions
of organic peroxides have been extensively developed. These
compounds have attracted much attention because many struc-
tural types of peroxides showed pronounced antimalarial1 and
antitumor activities.2 The reduction has a special place among
(1) (a) Jefford, C. W. AdV. Drug Res. 1997, 29, 271–325. (b) O’Neil, P. M.;
Posner, G. H. J. Med. Chem. 2004, 47, 2945–2964. (c) Dong, Y. Mini-ReV.
Med. Chem. 2002, 2, 113–123. (d) Borstnik, K.; Paik, Ik.-h.; Shapiro, T. A.;
Posner, G. H. Int. J. Parasitol. 2002, 32, 1661–1667. (e) Vennerstrom, J. L.;
Fu, H.-N.; Ellis, W. Y.; Ager, A. L.; Wood, J. K.; Andersen, S. L.; Gerena, L.;
Milhous, W. K. J. Med. Chem. 1992, 35, 3023–3027. (f) Dong, Y.; Matile, H.;
Chollet, J.; Kaminsky, R.; Wood, J. K.; Vennerstrom, J. L. J. Med. Chem. 1999,
42, 1477–1480. (g) Dussault, P. H.; Lee, I. Q.; Lee, H. J.; Lee, R. J.; Niu, Q. J.;
Schultz, J. A.; Zope, U. R. J. Org. Chem. 2000, 65, 8407–8414. (h) Gelb, M. H.
Curr. Opin. Chem. Biol. 2007, 11, 440–445. (i) Kim, H.-S.; Tsuchiya, K.; Shibata,
Y.; Wataya, Y.; Ushigoe, Y.; Masuyama, A.; Nojima, M.; McCullough, K.
J. Chem. Soc., Perkin Trans.1 1999, 1867-1870. (j) Kim, H.-S.; Shibata, Y.;
Wataya, Y.; Tsuchiya, K.; Masuyama, A.; Nojima, M. J. Med. Chem. 1999, 42,
2604–2609. (k) Casteel, D. A. Nat. Prod. Rep. 1999, 16, 55–73. (l) Jin, H.-X.;
Liu, H.-H.; Zhang, Q.; Wu, Y. Tetrahedron Lett. 2005, 46, 5767–5769. (m)
McCullough, K. J.; Wood, J. K.; Bhattacharjee, A. K.; Dong, Y.; Kyle, D. E.;
Milhous, W. K.; Vennerstrom, J. L. J. Med. Chem. 2000, 43, 1246–1249. (n)
Wu, Y. L.; Li, Y. Med. Chem. Res. 1995, 5, 569–586. (o) Opsenica, D.; Pocsfalvi,
G.; Juranic, Z.; Tinant, B.; Declercq, J.-P.; Kyle, D. E.; Milhous, W. K.; So`laja,
B. A. J. Med. Chem. 2000, 43, 3274–3282. (p) Iskra, J.; Bonnet-Delpon, D.;
Begue, J. P. Tetrahedron Lett. 2003, 44, 6309–6312. (q) Hamada, Y.; Tokuhara,
H.; Masuyama, A.; Nojima, M.; Kim, H.-S.; Ono, K.; Ogura, N.; Wataya, Y.
J. Med. Chem. 2002, 45, 1374–1378. (r) So`laja, B. A.; Terzic, N.; Pocsfalvi, G.;
Genena, L.; Tinant, B.; Opsenica, D.; Milhous, W. K. J. Med. Chem. 2002, 45,
3331–3336. (s) Najjar, F.; Gorrichon, L.; Baltas, M.; Andre´-Barre`s, C.; Vial, H.
Org. Biomol. Chem. 2005, 3, 1612–1614.
(2) (a) Dembitsky, V. M.; Gloriozova, T. A.; Poroikov, V. V. Mini-ReV. Med.
Chem. 2007, 7 (6), 571–589. (b) Jung, M.; Kim, H.; Lee, K.; Park, M. Mini-
ReV. Med. Chem. 2003, 3 (2), 159–165. (c) Kim, J.; Park, E. J. Curr. Med. Chem.
Anticancer Agents 2002, 2 (4), 485–537. (d) Dembitsky, V. M. Eur. J. Med.
Chem. 2008, 43, 223–251. (e) Dembitsky, V. M.; Gloriozova, T. A.; Poroikov,
V. V. Mini-ReV. Med. Chem. 2005, 5 (3), 319–336. (f) Terzic´, N.; Opsenica, D.;
Milic´, D.; Tinant, B.; Smith, K. S.; Milhous, W. K.; So`laja, B. A. J. Med. Chem.
2007, 50, 5118–5127.
10.1021/jo8023957 CCC: $40.75
Published on Web 02/02/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1917–1922 1917

Terent’ev et al.
noticeable cleavage of the peroxide bond.11 The CdO group in
artemisinin was transformed into the CH2 group with the use
of diborane, which was prepared by the one-pot method from
NaBH4-BF3 ·Et2O,12 and by successive reduction with DIBAL-H
and Et3SiH-BF3 ·Et2O.13 The ester group in the side chain of
artemisinin derivatives was selectively reduced to the aldehyde
and alcoholic group with the use of DIBAL-H.14a In addition,
the reduction of acrylic ester with DIBAL-H proceeded with
high selectivity and afforded allylic alcohol, the O-O bond of
the monoperoxyketal fragment in the polyfunctional molecule
remaining intact.14b
SCHEME 1. Reduction of 1,2,4,5,7,8-Hexaoxa-3-silonanes
1-4 Giving Rise to 1,3,5,6-Tetraoxa-2-silepanes 5-8
The selective reduction of functional groups (without reducing
the peroxide fragment) was performed with the use of LiAlH
(OBut)3,15 LiAlH4,16 and LiBH4.17 The reduction of the ester
group to the alcoholic group without reducing the 1,2-dioxane
ring in the presence of lithium aluminum hydride and lithium
borohydride was studied in detail.18 The soft and selective
reduction was found to proceed in the presence of LiBH4.
As opposed to the reduction of organic peroxides, the
reduction of organosilicon peroxides containing SiOOC20 and
SiOOSi fragments20c-e,21 was studied in much less detail. These
peroxides were reduced with the use of trialkyl- and triph-
enylphosphines as reducing agents. For example, the SiOOC
fragment was transformed into SiOC by the reaction of
norbornanone peroxysilyl ether, which was prepared by the
reaction of singlet oxygen with norbornene silyl ether, with
PPh3.20a,b Analogously, the corresponding alcohol, viz., 2-hy-
droxy-5-methoxy-2-methylindan-1-one, was synthesized from
2-(tert-butyldimethylsilylperoxy)-5-methoxyindan-1-one.20c tert-
Butyl trimethylsilyl peroxide was transformed into tert-butyl
trimethylsilyl ether by the reaction with triisopropylphosphine.20d
The reduction of SiOOC with Me3P was the key step in the
synthesis of optically active triols from the ozonolysis products
of γ-silyl allylic alcohol and their ethers.20e
The ester and azido groups were successfully reduced to the
hydroxyl and amino groups, respectively, with LiAlH4 in the
synthesis of peroxide structures having high antimalarial activity;
in these reactions the 1,2,4,5-tetraoxane ring remained intact.19
(3) (a) Adam, W.; Cueto, O.; De Lucchi, O.; Peters, K.; Peters, E.-M.; von
Schnering, H. G. J. Am. Chem. Soc. 1981, 103, 5822–5828. (b) Akbulut, N.;
Balci, M. J.Org. Chem. 1988, 53, 3338–3342. (c) Cope, A. C.; Liss, T. A.; Wood,
G. W. J. Am. Chem. Soc. 1957, 79, 6287–6292. (d) Rigaudy, J. Bull. Soc. Chim.
Fr. 1971, 144-152. (e) Gollnick, K.; Griesbeck, A. Tetrahedron Lett. 1983,
24-32, 3303–3306. (f) Xu, X.-X.; Dong, H.-Q. J. Org. Chem. 1995, 60, 3039–
3044.
(4) (a) Spivey, A. C.; Man˜as, C. G.; Mann, I. Chem. Commun. 2005, 4426–
4428. (b) Hudlicky, T.; Luna, H.; Price, J. D.; Rulin, F. J. Org. Chem. 1990, 55,
4683–4687. (c) Pearson, A. J.; Lai, Y.-S.; Lu, W.; Pinkerton, A. A. J. Org.
Chem. 1989, 54, 3882–3893. (d) Su¨tbeyaz, Y.; Sec¸en, H.; Balci, M. J. Chem.
Soc., Chem. Commun. 1988, 133, 0–1331.
(5) (a) Keana, J. F. W.; Eckler, P. E. J. Org. Chem. 1976, 41, 2625–2627.
(b) Mueller, P.; Rodriguez, D. HelV. Chim. Acta 1985, 68, 975–980.
(6) Lipner, H.; Witherspoon, L. R.; Champeaux, V. C. Anal. Chem. 1964,
36, 194–204.
(7) Suzuki, M.; Oda, Y.; Hamanaka, N.; Noyori, R. Heterocycles 1990, 30,
517–535.
(8) Bis, S. J.; Whitaker, D. T.; Johnson, C. R. Tetrahedron: Asymmetry 1993,
4, 875–878.
(9) Oger, C.; Brinkmann, Y.; Bouazzaoui, S.; Durand, T.; Galano, J.-M. Org.
Lett. 2008, 10, 5087-5090.
(10) (a) Liu, J.-M.; Ni, M.-Y.; Tu, A.-A.; Wu, Z.-H.; Wu, Y.-L.; Zhou, W. S.
(Hua Hsueh Hsueh Pao) Hua Xue Xue Bao (now often translated) Acta Chim
Sinica 1979, 37, 129-143; Chem. Abstr. 1979, 92, 94594. (b) Li, Y.; Wu, Y.-L.
Curr. Med. Chem. 2003, 10, 2197–2230.
(11) Wu, Y.-L.; Zhang, J.-L. You Ji Hua Xue (now often translated) Chin.
J. Org. Chem. 1986, 15, 4-156; Chem. Abstr. 1986, 105, 191426n.
(12) Jung, M.; Li, X.; Bustos, D. A.; ElSohly, H. N.; McChesney, J. D.;
Milhous, W. K. J. Med. Chem. 1990, 33, 1516–1518.
Results and Discussion
In the present study, the reduction of peroxides containing
simultaneously the COOC and SiOOC fragments was carried
out for the first time. The conditions were found under which
it is possible to perform the transformation 2SiOOC f 2SiOC
in cyclic peroxides, 1,2,4,5,7,8-hexaoxa-3-silonanes 1-4, with
the use of certain reducing agents, the COOC fragment and other
structural fragments of the molecules remaining intact. Nine-
membered triperoxides 1-4 are transformed into the previously
unknown seven-membered monoperoxides, 1,3,5,6-tetraoxa-2-
silepanes 5-8 (Scheme 1).
In the first step of the study, we chose the conditions and
reducing agents for the selective transformation of nine-
membered peroxides into seven-membered peroxides using the
reduction of 4a into 8a as an example. Then we examined the
applicability of these conditions to related peroxides 1-4, which
(13) (a) Avery, M. A.; Mehrotra, S.; Johnson, T. L.; Bonk, J. D.; Vroman,
J. A.; Miller, R. J. Med. Chem. 1996, 39, 4149–4155. (b) Avery, M. A.; Alvim-
Gaston, M.; Vroman, J. A.; Wu, B.; Ager, A.; Peters, W.; Robinson, B.; Charman,
W. J. Med. Chem. 2002, 45, 4321–4335.
(14) (a) Mekonnen, B.; Weiss, E.; Katz, E.; Ma, J.; Ziffer, H.; Kyle, D. E.
Bioorg. Med. Chem. 2000, 8, 1111–1116. (b) Porter, N. A.; Caldwell, S. E.;
Lowe, J. R. J. Org. Chem. 1998, 63, 5547–5554.
(15) (a) Stierle, D. B.; Faulkner, D. J. J. Org. Chem. 1980, 45, 3396–3401.
(b) Kobayashi, M.; Kondo, K.; Kitagawa, I. Chem. Pharm. Bull. 1993, 41, 1324–
1326.
(16) (a) Muellner, U.; Huefnerm, A.; Haslinger, E. Tetrahedron 2000, 56,
3893–3900. (b) Quin˜oa`, E.; Kho, E.; Manes, L. V.; Crews, P.; Bakus, G. J. J.
Org. Chem. 1986, 51, 4260–4264. (c) Dussault, P.; Sahli, A.; Westermeyer, T.
J. Org. Chem. 1993, 58, 5469–5474.
(20) (a) Jefford, C. W.; Rimbault, C. G. J. Am. Chem. Soc. 1978, 100, 6437–
6445. (b) Jefford, C. W.; Rimbault, C. G. Tetrahedron Lett. 1977, 27, 2375–
2378. (c) Einaga, H.; Nojima, M.; Abe, M. J. Chem. Soc., Perkin Trans. 1, 1999,
2507-2512. (d) Gorbatov, V. V.; Yablokova, N. V.; Aleksandrov, Yu. A.;
Ivanov, V. I. Zh. Obshch. Khim. 1983, 53, 1752-1755; J. Gen. Chem. USSR
(Engl. Transl.) 1983, 53, 1576-1578. (e) Murakami, M.; Sakita, K.; Igawa, K.;
Tomooka, K. Org. Lett. 2006, 8, 4023–4026.
(21) (a) Brandes, D.; Blaschette, A. J. Organomet. Chem. 1974, 78, 1–48.
(b) Ando, W.; Kako, M.; Akasaka, T.; Kabe, Y. Tetrahedron Lett. 1990, 31,
4177–4180. (c) Ando, W.; Kako, M.; Akasaka, T.; Nagase, S.; Kawai, T.; Nagai,
Y.; Sato, T. Tetrahedron Lett. 1989, 30, 6705–6708. (d) Akasaka, T.; Sato, K.;
Kako, M.; Ando, W. Tetrahedron 1992, 48, 3283–3292. (e) Adam, W.; Albert,
R. Tetrahedron Lett. 1992, 33, 8015–8016. (f) Wiberg, N.; Preiner, G.; Schurz,
K. Chem. Ber. 1988, 121, 1407–1412. (g) Zheng, J.-Y.; Konishi, K.; Aida, T.
Chem. Lett. 1998, 5, 453–454. (h) Dussault, P. H.; Lee, R. J.; Schultz, J. A.;
Suh, Y. S. Tetrahedron Lett. 2000, 41, 5457–5460. (i) Tamao, K.; Kumada, M.;
Takahashi, T. J. Organomet. Chem. 1975, 94, 367–376. (j) Brandes, D.;
Blaschette, A. J. Organomet. Chem. 1974, 73, 217–227. (k) Brandes, D.;
Blaschette, A. J. Organomet. Chem. 1973, 49, C6. (l) Akasaka, T.; Sato, K.;
Kako, M.; Ando, W. Tetrahedron Lett. 1991, 32, 6605–6608.
(17) (a) Tang, Y.; Dong, Y.; Karle, J. M.; DiTusa, C. A.; Vennerstrom, J. L.
J. Org. Chem. 2004, 69, 6470–6473. (b) Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou,
W.-S. Tetrahedron Lett. 1991, 32, 5785–5788.
(18) Jin, H.-X.; Liu, H.-H.; Zhang, Q.; Wu, Y. J. Org. Chem. 2005, 70, 4240–
4247.
ˇ
(19) Opsenica, I.; Opsenica, D.; Smith, K. S.; Milhous, W. K.; Solaja, B. A.
J. Med. Chem. 2008, 51, 2261–2266.
1918 J. Org. Chem. Vol. 74, No. 5, 2009

Ring Contraction of 1,2,4,5,7,8-Hexaoxa-3-silonanes
FIGURE 1. Two independent molecules of 8a in monoclinic polymorph M, showing the atomic numbering and 40% probability displacement
ellipsoids. H atoms were omitted for clarity.
FIGURE 2. Two independent molecules of 8a in triclinic polymorph T, showing the atomic numbering and 50% probability displacement spheres.
H atoms were omitted for clarity.
we have synthesized earlier22 starting from 1,1′-dihydroper-
oxydi(cycloalkyl) peroxides with ring sizes of C5-C7 and C12
and various dialkyldichlorosilanes.
Synthesis of 1,3,5,6-Tetraoxa-2-silepanes by Reduction
of 1,2,4,5,7,8-Hexaoxa-3-silonanes. Peroxide 8a was synthe-
sized from 4a in tetrahydrofuran with the use of reducing agents
of different nature, such as phosphines, phosphites, thiourea,
tetrahydrothiopyran, dimethyl sulfoxide, and metal hydrides
(Table 1). These reagents are widely used in organic synthesis,
in particular, in reactions with peroxides.
It was found that the COOSi fragment in peroxide 4a is
selectively reduced only with Ph3P, (C8H17)3P, thiourea, and,
to a smaller degree, (BuO)3P; in these reactions, the COOC
fragment remains intact. Triphenylphosphine and trioctylphos-
(22) Terent’ev, A. O.; Platonov, M. M.; Tursina, A. I.; Chernyshev, V. V.;
Nikishin, G. I. J. Org. Chem. 2008, 73, 3169–3174.
J. Org. Chem. Vol. 74, No. 5, 2009 1919

Terent’ev et al.
TABLE 1. Influence of the Nature of the Reducing Agent on the Yield of 1,3,5,6-Tetraoxa-2-silepane 8aa
a General conditions of reduction: the reducing agent (0.45 mmol) dissolved or suspended in anhydrous THF (2 mL) was added to a suspension of
4a (100 mg, 0.21 mmol) in anhydrous THF (4 mL) for 2-3 min, then the reaction mixture was stirred at 20-25 °C for 2-24 h. b With the use of Ph3P
(55 mg, 0.21 mmol) for 12 h peroxide 8a was prepared with a yield of 19% along with the mixture of products. c Thiourea (0.62 g, 0.81 mmol) was
used. d The reaction affords a large amount of cyclododecanol.
SCHEME 2. Reaction of Triphenylphosphine with
Hexaoxonane 9
phine proved to be the best reducing agents. In the presence of
these agents, 8a is produced in 86% and 80% yields, respec-
tively. The conversion of peroxide 4a upon reduction with
triphenylphosphine at 20-25 °C for 7 h is 75%; the complete
conversion requires at least 12 h. The reaction in the presence
of (C8H17)3P as the reducing agent affords the target product in
high yield, but the use of this agent complicates the experiment.
In the latter case, all steps of this reaction should be performed
under anaerobic conditions, because (C8H17)3P is rapidly
oxidized in the presence of traces of oxygen. Since triph-
enylphosphine is oxidized much more slowly than (C8H17)3P,
this compound is convenient for solving the problem under
consideration. It is much more difficult to reduce 4a with
(BuO)3P. The conversion of the starting peroxide is 5-8%, and
the yield of 8a is 5%.
Satisfactory results were obtained with the use of thiourea
for reduction of 4a. Other sulfur-containing reducing agents
(tetrahydrothiopyran and dimethyl sulfoxide) do not react with
4a at all. The reactions with strong reducing agents, such as
NaBH4 and LiAlH4, proceed nonselectively and lead to the
cleavage of all peroxide bonds.
characteristic signals for the O-P-O fragment (region ca. -50
to -70 ppm)23d were not detected. It is probable that the
insertion of the phosphine into the peroxide bond is the rate
limitating step of the SiOOC fragment reduction after which
Ph3PO rapidly eliminates with formation of the SiOC fragment.
The lack of characteristic signals for the O-P-O fragment
also makes it possible to suppose that the SiOOC fragment is
reduced without a phosphorane formation. Phosphine attack
occurs on the less crowded silyl part of the molecule likely on
the silicon-bonded oxygen. Selectivity of the SiOOC fragment
reduction in comparison with the COOC fragment is also
probably the result of formation of a weak P-Si complex, which
makes it possible to draw together reductant (phosphine) and
oxidant (peroxide fragment).
An attempt to perform the ring contraction by the reduction
of hexaoxonane 9, which is the carbocyclic analogue of
compound 4a, with triphenylphosphine failed. At room tem-
The mechanism of the fragment O-O reduction with Ph3P
in cyclic peroxides was investigated in detail.23 This reduction
generally proceeds by initial cleavage of the oxygen-oxygen
bond with formation of the O-P-O fragment. For example,
the reaction of triphenylphosphine with 2,3-dioxabicyclo-
[2.2.1]heptane resulted in the formation of a phosphorane that
perature, the conversion of 9 did not proceed within 1 day. At
higher temperature (60 °C), the conversion was virtually absent
within 2 h (Scheme 2).
Taking into account the reaction conditions found for the
synthesis of 8a, we performed the reduction of compounds 1-4
containing different substituents in the peroxide ring (spiro-fused
decomposed in the presence of water to give triphenylphosphine
oxide and trans-1,3-cyclopentanediol.23b The 31P NMR monitor-
ing of peroxide 4a reduction with Ph3P at room temperature
showed only two peaks corresponding to Ph3P and Ph3PO;
(23) (a) Clennan, E. L.; Heah, P. C. J. Org. Chem. 1984, 49, 2284–2286.
carbocycles C5-C7 and C12 at the carbon atoms; Me, Et, vinyl,
(b) Clennan, E. L.; Heah, P. C. J. Org. Chem. 1981, 46, 4105–4107. (c)
cyclohexyl, phenyl, and carbethoxypropane substituents at the
silicon atom) with the use of a small excess of triphenylphos-
phine as the reducing agent (2.2 mol per mol of 1,2,4,5,7,8-
hexaoxa-3-silonanes). The reactions were performed at room
Baumstark, A. L.; Vasquez, P. C.; Chen, Y. X. Heterocycl. Commun. 1996, 2,
35–40. (d) Clennan, E. L.; Heah, P. C. J. Org. Chem. 1982, 47, 3329–3331. (e)
Clennan, E. L.; Heah, P. C. J. Org. Chem. 1983, 48, 2621–2622. (f) Bartlett,
P. D.; Baumstark, A. L.; Landis, M. E.; Lerman, C. L. J. Am. Chem. Soc. 1974,
96, 5267–5268. (g) Balci, M. Chem. ReV. 1981, 81, 91–108.
1920 J. Org. Chem. Vol. 74, No. 5, 2009

Ring Contraction of 1,2,4,5,7,8-Hexaoxa-3-silonanes
TABLE 2. Structures and Yields of 1,3,5,6-Tetraoxa-2-silepanesa
a General reaction conditions: peroxide 1-4 (0.72 mmol) was dissolved or suspended in anhydrous THF (9-12 mL), a solution of PPh3 (1.60
mmol) in anhydrous THF (5 mL) was added for 4-6 min, and the reaction mixture was stirred at 20-25 °C for 6-42 h until the complete conversion
of peroxides 1-4 was achieved. b The yield based on the isolated product.
temperature for 6-42 h until the complete conversion of
compounds 1-4 was achieved (Table 2).
oxide OOCOO fragments of the starting nine-membered rings
(108-120 ppm). The 29Si NMR spectra are also informative.
The chemical shifts in the spectra of compounds 2a and 4a are
8.44 and 7.56 ppm, respectively; after reduction the shifts in
the spectra are -7.50 (6a) and -8.25 ppm (8a), respectively.
Since 1,3,5,6-tetraoxa-2-silepanes have been previously un-
known, it was important to obtain direct evidence for the
existence of these compounds by X-ray diffraction. The X-ray
diffraction study was carried out for compound 8a. Peroxide
8a was obtained as a crystalline powder, which contained a small
amount of single crystals suitable for X-ray diffraction. The
X-ray analysis has shown that 8a crystallizes in two polymorphic
modifications: monoclinic (M) and triclinic (T), respectively.
The solid state crystal structure of M (Figure 1) was obtained
from X-ray single-crystal diffraction data, while the crystal
structure of T (Figure 2) was determined by powder diffraction
methods.
1,3,5,6-Tetraoxa-2-silepanes 5-8 were prepared in yields
from 67% to 91%. The yield depends only slightly on the
structures of the starting compounds. The nature of the substit-
uents in the starting 1,2,4,5,7,8-hexaoxa-3-silonanes has a
substantial effect on the reaction time required to achieve the
complete conversion of 1-4. The reduction time increases with
increasing ring size of the substituent spiro-fused to the peroxide
ring. Thus, the reactions with compounds containing the C5,
C6, or C7 rings are completed in 6-12 h, whereas the reaction
time in the case of compounds containing the C12 ring increases
(in certain cases) to 42 h. The reduction time increases with
increasing bulkiness of the substituent at the Si atom. Thus,
the time of the synthesis starting from compounds containing
ethyl substituents instead of methyl groups increases by a factor
of 2 or more.
Properties and Structures of Peroxides 5-8. Peroxides
5a,b, 6a,b, and 7b are liquids. Compounds 7a and 8a-f are
solid compounds with melting points from 36 °C (7a) to 137
Conclusion
1
°C (8e). Their structures were established by H, 13C, and 29Si
It was demonstrated that the COOSi fragment in organosilicon
peroxides can be selectively reduced in molecules containing
NMR spectroscopy and elemental analysis. In the 13C NMR
spectra, the characteristic signals for the carbon atoms of the
monoperoxyacetal OCOO fragments1q,24 of the seven-membered
rings are most informative. The chemical shifts of these
fragments (105-116 ppm) are similar to those for the bisper-
(24) (a) Ito, T.; Tokuyasu, T.; Masuyama, A.; Nojima, M.; McCullough, K. J.
Tetrahedron 2003, 59, 525–536. (b) Dussault, P. H.; Eary, C. T. J. Am. Chem.
Soc. 1998, 120, 7133–7134. (c) Zmitek, K.; Zupan, M.; Stavber, S.; Iskra, J. J.
Org. Chem. 2007, 72, 6534–6540.
J. Org. Chem. Vol. 74, No. 5, 2009 1921

Terent’ev et al.
86% (82 mg, 0.18 mmol). White crystals; mp 127-129 °C (MeOH);
simultaneously the COOC fragment at the same geminal
peroxide center. The reduction of 1,2,4,5,7,8-hexaoxa-3-silo-
nanes affords 1,3,5,6-tetraoxa-2-silepanes belonging to a new
class of cyclic organosilicon peroxides. The reactions with
phosphines and thiourea proceed selectively. In the presence
of other reducing agents, such as (BuO)3P, (CH2)5S, DMSO,
NaBH4, or LiAlH4, either all peroxide groups are completely
reduced or the conversion is not observed at all.
1
Rf 0.61 (TLC, petroleum ether-EtOAc, 20:1); H NMR (300.13
MHz, CDCl3) δ 0.19 (s, 6H), 1.25-1.95 (m, 44H); 13C NMR (75.48
MHz, CDCl3) δ 0.5, 19.8, 20.1, 22.0, 22.1, 22.3, 22.4, 26.07, 26.10,
31.7, 32.2, 109.7. Anal. Calcd for C26H50O4Si: C, 68.67; H, 11.08;
Si, 6.18. Found: C, 68.81; H, 11.29; Si, 6.03.
Synthesis of 18,18-Diethyl-8,9,17,19-tetraoxa-18-siladispiro-
[6.2.6.3]nonadecane (7b). Peroxide 3b (270 mg, 0.72 mmol) was
dissolved in anhydrous THF (9 mL). Then a solution of PPh3 (420
mg, 1.60 mmol) in anhydrous THF (5 mL) was added for 4 min.
The reaction mixture was stirred at 20-25 °C for 12 h until the
complete conversion of peroxide 3b was achieved. The general
procedure for the isolation of peroxides 5-7 involved the following
steps. A solution of hydrogen peroxide (35 mg, 1.0 mmol) in Et2O
(1 mL) was added to the reaction mixture to oxidize excess
triphenylphosphine. Then the solvent was removed under reduced
pressure at room temperature. Peroxide 7b was isolated by silica
gel chromatography with use of a hexane/EA ) 20/1 mixture. The
eluent was evaporated under a pressure of 0.5-1 mmHg for 0.5 h.
Compound 7b was obtained in a yield of 83% (204 mg, 0.59 mmol).
Experimental Section
Caution: Although we have encountered no difficulties in
working with peroxides, precautions, such as the use of shields,
fume hoods, and the avoidance of transition metal salts, heating,
and shaking, should be taken whenever possible.
Influence of the Nature of the Reducing Agent on the
Yield of 1,3,5,6-Tetraoxa-2-silepane (8a, Table 1). A reducing
agent (0.45 mmol) dissolved or suspended in anhydrous THF (2
mL) was added to a suspension of 4a (100 mg, 0.21 mmol) in
anhydrous THF (4 mL) for 2-3 min. The reaction mixture was
stirred at 20-25 °C for 2-24 h. Then the solvent was evaporated
(if the precipitate was present, the mixture was initially filtered
through a thin layer of silica gel) and methanol (10 mL) was added.
The reaction mixture was cooled to -10 °C, and the precipitate
was filtered off and washed with MeOH (5 × 2 mL). Peroxide 8a
was dried under a pressure of 0.5-1 mmHg for 1 h.
1
Colorless oil; Rf 0.65 (TLC, petroleum ether-EtOAc, 20:1); H
NMR (300.13 MHz, CDCl3) δ 0.63 (q, 4H, J ) 11.4 Hz), 0.98 (t,
6H, J ) 8 Hz), 1.47-1.83 (m, 20H), 1.98-2.10 (m, 4H); 13C NMR
(75.48 MHz, CDCl3) δ 6.4, 6.7, 22.3, 22.6, 29.17, 29.21, 37.9, 39.4,
109.8. Anal. Calcd for C18H34O4Si: C, 63.11; H, 10.00; Si, 8.20.
Found: C, 63.37; H, 10.12; Si, 8.11.
Synthesis of 28,28-Dimethyl-13,14,27,29-tetraoxa-28-sila-
dispiro[11.2.11.3]nonacosane Peroxide (8a) by Reduction of
4a with Triphenylphosphine (Table 1). Hexaoxasilonane 4a (100
mg, 0.21 mmol) was suspended in anhydrous tetrahydrofuran (4
mL). Then a solution of PPh3 (120 mg, 0.45 mmol) in anhydrous
THF (2 mL) was added for 2 min. The reaction mixture was stirred
at 20-25 °C for 12 h. The general procedure for the isolation of
peroxides 8a-f involved the following steps. The solvent was
evaporated and methanol (10 mL) was added. The reaction mixture
was cooled to -10 °C, the precipitate was filtered off and washed
with MeOH (5 × 2 mL), and the product was dried under a pressure
of 0.5-1 mmHg for 1 h. Compound 8a was obtained in a yield of
Acknowledgment. This work is supported by the Program
for State Support of Leading Scientific Schools of the Russian
Federation (Grant NSh 2942.2008.3) and the Grant of the
President of the Russian Federation (Grant MK-3515.2007.3).
Supporting Information Available: 1H and 13C NMR
spectra for 1,3,5,6-tetraoxa-2-silepanes 5-8, and X-ray data for
8a. This material is available free of charge via the Internet at
http://pubs.acs.org.
JO8023957
1922 J. Org. Chem. Vol. 74, No. 5, 2009