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Gerald L. Larson
KEYWORDS Reductions, organosilane reductions, tetramethyldisiloxane, TMDS. ABSTRACT Some recent applications of several highly useful reducing capabilities of tetramethyldisiloxane, TMDS, are reviewed.
hexachloroplatinate as the catalyst. Here again the yields are excellent and in this case the reaction conditions are quite moderate. The employed platinum catalyst, though expensive, is only required in low amount (3). It was found that a synergistic effect of the two Si-H groups in the TMDS formed an intermediate Pt(IV) species 1 leading to the full reduction of the amide carbonyl moiety. Whereas the indium(III) bromide-triethylsilane reduction of N,N-
INTRODUCTION
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he hydride of organosilanes has been employed in the reductions of a vast array of organic substrates oftentimes with excellent chemoselectivity. This high degree of chemoselectivity can be credited to the weakly hydridic character of the Si-H bond along with the large variation in catalytic protocols available to carry out the reductions. A comprehensive review of the ionic and transition metalcatalyzed silane reductions has been published (1). In addition to the potential for high selectivity via the weakly hydridic silanes the organosilane reducing agents are available in a variety of forms including the popular and easily handled triethylsilane, the more sterically demanding triisopropylsilane, the specialty phenylsilane, and, finally, the more economical polymethylhydrogen siloxanes, PMHS. Symtetramethyldisiloxane, TMDS, has recently been shown to bring about several interesting and highly useful reductions, some of which are presented herein.
scheme 2.
dibenzylacetamide gave a 90% yield of the corresponding dibenzylethylamine, TMDS, under these conditions, gave only a 51% yield of the amine (4). The reduction of secondary amides to secondary amines employing the ruthenium catalyst 2 has been reported (5).
scheme 3.
scheme 5.
scheme 1.
The facile, copper (II)-triflate-catalyzed TMDS reduction of secondary amides to secondary amines in good to excellent yields is possible when a diamine ligand is employed (6). Under similar conditions using other silane reducing agents including PMHS, and triethylsilane resulted in poor yields.
ORGANIC CHEMISTRY
REDUCTIVE AMINATION OF ESTERS
In a very useful transformation it was found that the reaction of esters with tosylamides in the presence of TMDS as a reducing agent and catalyzed by the ruthenium catalyst 2 results in the formation of the tosylamide of primary or secondary amines (7). The tosyl group can be readily removed to give the desired amine. The yields in these reactions are excellent and the reaction conditions are mild. It was further shown that ethyldimethylsilane was an effective reducing component in the reaction. Interestingly, it was shown that when the alcohol portion of the ester is that of a primary or secondary alcohol the alkyl group to form the amine comes from the acid half of the ester. However, when the alcohol portion of the ester is a tertiary alcohol it is this alcohol portion that alkylates the amine, thus providing an excellent entry into tertiary alkyl-substituted amines. The reaction was extended with equal success to cyclic amines and spirocyclic amines. These conversions take advantage of both modes of reaction incorporating either the acid (cyclic amines) or the alcohol (spirocyclic amines) portion of the ester.
scheme 12.
The iron (III) pentanedionate-catalyzed reduction of aryl nitro compounds provides a high-yield, economical process for this important reduction (10, 11). The process was shown to tolerate aryl bromide, ester, carboxylic acid, cyano, and m-nitro groups. PMHS was shown to be a viable alternative to the TMDS in these reductions as well.
scheme 13.
scheme 6.
scheme 7.
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scheme 8. scheme 14.
scheme 16.
scheme 10.
ring opening of styrene oxide gives a single product with the resulting silyloxy unit located exclusively on the b-carbon, whereas the reductive ring opening of 1,2-epoxyhexane gives a mixture of the regioisomeric disiloxanes. Similar nonregioselectivity is found with the reductive ring opening of 2-methyl- and 3-methyltetrahydrofuran.
scheme 11.
scheme 17.
ORGANIC CHEMISTRY
When provided with the option of ring opening or reaction with an alcohol the reaction occurs at the alcohol. In a similar fashion the reduction of aldehydes or ketones with TMDS results in the formation of 1,3-dialkoxytetramethyldisiloxanes as does the dehydrogenative coupling of TMDS with primary or secondary alcohols. The reductive bromination of carboxylic acids is possible with the use of the TMDS as the reducing agent and bromotrimethylsilane as the bromide source. The yields of this transformation are good to excellent (17). Remarkably, the reaction conditions are tolerant of a variety of functional groups.
MICHAEL
The silane reduction of ,-unsaturated esters can occur in a Michael fashion to provide an intermediate silyl ketene acetal, which can react with an electrophile to give the -subsituted ester. This has been carried out with bis-,--unsaturated ester systems wherein one of the functional groups is reduced by the silane forming the silyl ketene acetal (or enolate) and the second serves as the electrophile producing the cyclized diester. In the presence of a chiral ligand and a copper catalyst this process has been shown to be both high yielding and highly enantioselective. The SEGPHOS ligand proved to be the most effective (18).
scheme 18.
scheme 24.
TMDS in the presence of a catalytic amount of copper (II) triflate carries out the reduction of carboxylic acids to the corresponding alcohols in moderate to good yields (15). This reagent combination was also found to reductively couple aldehydes and ketones to symmetrical ethers.
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scheme 19.
scheme 20.
The direct thioetherification of aromatic carboxylic acids has proven to be possible with the combination of TMDS and InBr3. For the direct thioetherification of aliphatic carboxylic acids the TMDS/InI3 system proved best (16). TMDS proved to be significantly better than triethylsilane or phenylsilane in these transformations.
scheme 25.
scheme 21.
scheme 22.
scheme 23.
scheme 26.
ORGANIC CHEMISTRY
the regiochemistry varies depending on the mode of protection on the hydroxyl groups (20). The 4,6-O-alkylidene glycosyl acetals are selectively cleaved at the O-C6 bond in all cases. These reductions are possible when the other hydroxyls are protected or are free.
REFERENCES
1. G. L. Larson, J. L. Fry, Ionic and Organometallic-Catalyzed Organosilane Reductions, S. E. Denmark, Ed., John Wiley and Sons, Organic Reactions, 71, pp. 1-737 (2008). Y. Sunada, H. Kawakami, et al., Angew. Chem. Int. Ed. Engl., 48, pp. 9511-9514 (2009). S. Hanada, E. Tsutsumi, et al., J. Am. Chem. Soc., 131, pp. 1503215040 (2009). N. Sakai, K. Fujii, et al., Tetrahedron Lett., 49, pp. 6873-6875 (2008). S. Hanada, T. Ishida, et al., J. Org. Chem., 72, pp. 7551-7559 (2007). S. Das, B. Join, Ket al., Chem. Commun., 48, pp. 2683-2685 (2012). T. Nishikata, H. Nagashima, Angew. Chem. Int. Ed., 51, pp. 5363-5366 (2012). S. Bower, K. A. Kreutzer, et al., Angew. Chem. Int. Ed. Engl., 35, pp. 1515-1516 (1996). S. Laval, W. Dayoub, et al.,Tetrahedron Lett., 51, pp. 2092-2094 (2010). L. Pehlivan, E. Mtay, et al., Tetrahedron Lett., 51, pp. 1939-1941 (2010). L. Pehlivan, E. Mtay, et al., Tetrahedron, 67, pp. 1971-1976 (2011). Y. Motoyama, M. Aoki, et al., Chem. Commun., 48, pp. 1574-1576 (2009). L. Pehlivan, E. Mtay, et al., Eur. J. Org. Chem., pp. 4687-4692 (2011). N. Sakai, K. Kawana, et al., Eur. J. Org. Chem., pp. 3178-3183 (2011). Y.-J. Zhang, W. Dayoub, et al, Tetrahedron, 68, pp. 7400-7407 (2012). N. Sakai, T. Miyazaki, et al., Org. Lett., 14, pp. 4366-4369 (2012). T. Moriya, S. Yoneda, et al., Org. Lett., 14, pp. 4842-4845 (2012). C. L. Oswald, J. A. Peterson, et al., Org. Lett., 11, pp. 4504-4507 (2009). P. Alvarez, R. Martin, J. Am. Chem. Soc., 132, pp. 17352-17353 (2010). Y.-J. Zhang, W. Dayoub, G.-R. Chen, M. Lemaire, Eur. J. Org. Chem. 1960-1966 (2012). S. Laval, W. Dayoub, A. Favre-Rguillon, M. Berthod, P. Demonchaux, G. Mignani, M. Lemaire, Tetrahedron Lett., 50, 70057007 (2009). K. Naumann, G. Zoun, K. Mislow, J. Am. Chem. Soc., 91, 7012-7023 (1969). L. Pehlivan, E. Mtay, D. Delbrayayelle, G. Mignani, M. Lemaire, Tetrahedron, 68, 3151-3155 (2012). M. Berthod, A. Favre-Rguillon, J. Mohamad, G. Mignani, G. Docherty, M. Lemaire, Synlett, 1545-1548 (2007). C. Petit, A. Favre-Rguillon, G. Mignani, M. Lemaire, Green Chem., 12, 326-330 (2010). C. Petit, A. Favre-Rguillon, B. Albela, L. Bonneviot, G. Mignani, M. Lemaire, Organometallics, 28, 6379-6382 (2009).
REDUCTION OF NITRILES
TMDS has been shown to reduce nitriles to primary amines in high yields under mild conditions with a stoichiometric amount of isopropyl titanate. (21) The reaction work-up involves washing the reaction mixture with aqueous hydrochloric acid and isolation of the product as the hydrochloride salt. The byproducts are a silicone gel from the TMDS and titanium dioxide from the Ti(Oi-Pr)4. The reaction was shown to be tolerant of aryl bromides and nitro groups.
scheme 27.
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scheme 28.
26.
The less expensive and more easily handled Ti(O1Pr)4/ TMDS system reduces phosphine oxides to the phosphines in very good yields and compares very well with the InBr3/ TMDS combination. In one glaring example the reduction of 1,4-bis(diphenyloxophosphino)butane is reduced with the Ti(O1Pr)4/TMDS system in 95% yield and not at all under the indium bromide-catalyzed conditions (24, 25). The mechanism of this reaction was studied and the evidence supports a single electron transfer (SET) mechanism (26).
scheme 29.
CONCLUSIONS
Recent work has shown the synthetic versatility of the readily available tetramethyldisiloxane, TMDS, in several previously difficult and important organic reductions. These findings illustrate the potential to provide cleaner, safer and, in many cases, more economical routes to functional groups important in the field of organic synthesis.