Tin hydride, reduction

Formation of carbon centered radicals tin hydride reduction of... 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

Another complication that can arise in these reactions is that a cycloaddition reaction of the radical intermediate formed in the tin hydride reduction, to an adjacent carbon-carbon double bond, can compete with the simple reduction reaction. This occurs when a five- or six-membered ring can be formed in an intramolecular cycloaddition reaction. For example, Beckwith and Lawrence96 found both five- and six-membered rings in the product when l-bromo-2,2,5-trimethylhex-l-ene was treated with tributyltin hydride (Scheme 15). 

Unfortunately, the appeal of solid phase extractions on small scale fades as the scale increases due to the cost and inconvenience of using large amounts of fluorous silica gel. Here, modified techniques to reduce the tedium of repeated extractions are attractive. For example, Crich has recently introduced the minimally fluorous selenide C6Fi3CH2CH2C6H4SeH[171. This selenol is added in catalytic quantities to tin hydride reductions of reactive aryl and vinyl radicals. The high reducing capacity of the aryl selenide suppresses undesired reactions of product radicals without suppressing the reactions of the aryl and vinyl radicals themselves. After the reaction is complete, the selenol can be recovered by a modified continuous extraction procedure. 

One of the early specialized techniques used for the study of radical reactions was the rotating sector method. The use of this technique (Fig. 6) for determining reaction kinetics was demonstrated by Melville for the gas phase polymerization of methyl methacrylate, and later by Bartlett and Swain for the liquid phase reaction, and by Carlsson and Ingold for tin hydride reductions. ... 

D. H. R. Barton, D. O. Jang, and J. C. Jaszberenyi, On the mechanism of deoxygenation of secondary alcohols by tin hydride reduction of methyl xanthates and other thiocarbonyl deri-vates, Tetrahedron Lett. 37 3991 (1990). 

One first selects a chain reaction that can be initiated photochemically and that is terminated by the recombination and disproportionation of interest. An example would be the tin hydride reduction of an alkyl bromide, which proceeds according to Scheme 5. Kinetic analysis (see p. 493) yields a relation between rate... 

Tetra-substituted tin enolates of ketones, which are otherwise difficult to prepare, can be formed via Fd-catalyzed tin hydride reduction of allyl p-ketocarboxylates (equation 102).294 Allyl (3-ketocarboxy-lates can also be transformed into a-bromo ketones using this method (equation 103).296... 

In reactions such as tin hydride reductions, excess tin hydride must be added if large amounts of initiator are employed because the initiation steps consume tin hydride. 

The tin hydride method is reductive, and the cyclic radical is almost always trapped by a hydrogen atom. In simple cyclizations, both the radical precursor and the alkene are lost during tin hydride reduction, and this sometimes results in underfunctionalized products, necessitating the introduction of extra functional groups for subsequent transformations. However, in the synthesis of simple molecules, this is often an advantage as steps to remove residual alkenes, carbonyl groups and the like, left by ionic methods of C—C bond formation, are not required. Work-up requires separation of the desired products from the tin by-products (see Section 4.1.6.2.1). 

Several recent examples of metal-promoted cyclizations of perchlorocarbonyl compounds are presented in Scheme 28, and a full paper by Weinreb is recommended as an excellent source of references to prior work in this area (including mechanistic studies on the role of the metal).127 The first two examples illustrate that the choice of substrates can dictate the types of products that are formed the initially formed y-chloro esters are stable to subsequent ionic reactions, but the ris-y-chloro acids form lactones. Interestingly, Weinreb has shown that the metal can equilibrate the cis- and /rans-y-chloro esters by reversible chlorine atom transfer. The third example128 illustrates a general feature of the atom transfer method yields at high concentration are comparable to (and sometimes better than) those provided by using tin hydride at low concentrations. Indeed, in the third example, the three chlorines on the ester provided three opportunities for cyclization during the tin hydride reduction, but 40% of the product still failed to cyclize. (Unfortunately, the tin hydride concentration was not specified.)... 

Even though radical intermediates are involved in many reductive metallations, cyclizations of alkyl radicals by reductive trapping methods are relatively uncommon. When protonated products are formed, the overall transformations are similar to a tin hydride reductions however, reductive methods may facilitate purification of the cyclic product because tin by-products are absent Two examples of simple reductive cyclizations are shown in Scheme 35. The first example illustrates that Sheffold s procedure, which uses catalytic quantities of vitamin B12 with a chemical or electrochemical coreductant, is attrac-... 

We explored other thiocarbonyl derivatives including xan-thates (e.g. 19), thionoimidazolides (e.g. 20) and thio-carbonates. The last convert a glycol such as 21a via the thiocarbonate 22 and subsequent tin hydride reduction to mainly the primary alcohol 21b. The intermediate opens in such a way as to afford the more stable radical. This reaction is readily applied to nucleosides.910... 

Since it seemed likely that a xanthate function beta to a carbon radical would eliminate to furnish a double bond, we studied the tin hydride reduction of 1,2-dixanthates.1112 This provided an efficient new synthesis of olefins which was independent of the stereochemistry of the glycol. It was particularly suitable for the conversion of protected ribosides 23 via the dixanthates 24 into the corresponding olefins 25 from which biologically important dideoxynucleosides 26 were readily obtained by hydrogenation and deprotection.13... 

Normally, esters beta to a radical are perfectly stable and do not furnish olefins and carboxyl radicals.6 This is true even for 1 where tin hydride reduction affords only 2. Clearly, conjugation with two phenyls is not a sufficient driving force for elimination. However, the driving force in the change from dihydrophenanthrene to phenanthrene would be greater and in... 

Organotin hydrides are advantageous as reductants in terms of their facile availability, stability, and reactivity. - Almost all tin hydrides are liquids, and stoichiometric tin-hydrogen bonds can be used. In general, the tin hydride reductions have been performed under radical conditions using initiators such as azobisisobutyroni-trile (AIBN), triethylborane, and UV irradiation. The reduction of organic halides and pseudohalides by tri- -... 

Sonochemistry has been applied to acceleration of the Reformatsky reaction, Diels-Alder reactions, the arylation of active methylene compounds nucleophilic aromatic substitution of haloarenes, and to hydrostannation and tin hydride reduction. " Other sonochemical applications involve the reaction of benzyl chloride and nitrobenzene, a Sr I reaction in liquid ammonia at room temperature, and Knoevenagel condensation of aromatic aldehydes. lodination of aliphatic hydrocarbons can be accelerated, and oxyallyl cations have been prepared from ot,ot -diiodoketones using sonochemistry. Sonochemistry has been applied to the preparation of carbohydrate compounds.When sonochemistry is an important feature of a chemical reaction, this fact will be noted in the reactions presented in Chapters 10-19. 

From the data in Table 20, four important points should be kept in mind. First, free radical reduction of 139 and 137 with all reducing agents, as well as the tin hydride reduction of 138 and 140, occurred with the expected loss of stereochemistry. Second, the ratio of exo-/endo-norbomane-2-D obtained from these reductions was independent of the stereochemistry of starting material. Third, almost identical ratios of exo-/ ndo-norbornane-2-D were obtained from the four starting materials. Finally, the ratio of exo-(endo-norbornane-2-D was independent of the nature of the metal. 

Castro and Kray have reduced the isomeric butenyl chlorides, using chromous sulfate (5). Again, allylic radicals were proposed as intermediates in the reaction. However, unlike the tin hydride reductions, 1-butene was obtained almost exclusively from each of the isomeric chlorides. The process has been described as occurring within a chromium complex. The preponderant formation of 1-butene from butenyl metal complexes has also been noted by others (12, 23, 46). 

Reductions at anomeric positions, both by ionic and radical mechanisms, deliver hydrogen from the axial direction. Kahne prepared the hemithio orthoester 75 from thiolactone and subjected it to tin hydride reduction, which resulted in predonunant formation of the -glycoside [116] (O Scheme 40). 

C—SeMe and the C—Cl bonds and often faster than that of the C— Br bond The reduction is highly chemoselective and leads to alcohols usually in almost quantitative yield (Scheme 161, a Scheme 164, a Scheme 168, a and b). In rare cases, however, such as when a ca n-carbon double or triple bond is present in a suitable position, the formation of a five- or six-membered ring takes place by trapping of the radical intermediate (Scheme 118). ° Tin hydride reduction has been advantageously extend (g P-hydroxy-y-alkenyl and -hydroxy-a-alkenyl selenides displayed in Scheme IM (a) and Scheme 168 (a and b) and derived from a-selenoalkyllithiums and enenones, and from 1-seleno-l-alkenyl metals and carbonyl compounds, respectively. 

Tin hydride reduction has been utilized to introduce tritium at C28 of dihydrocalysterol. " When (23R,24R,2diR)- or (23/ ,24/ ,285 )-28-bromo-23,28-cyclostigmast-5-en-3)3-ol (12) was mixed with trimethyltin chloride and treated with [ H]-sodium borohydride, formation of a C-T bond giving 13 took place. 

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