Deoxygenation Tributyltin hydride

Quebrachitol was converted into iL-c/j/roinositol (105). Exhaustive O-isopropylidenation of 105 with 2,2-dimethoxypropane, selective removal of the 3,4-0-protective group, and preferential 3-0-benzylation gave compound 106. Oxidation of 106 with dimethyl sulfoxide-oxalyl chloride provided the inosose 107. Wittig reaction of 107 with methyl(triphenyl)phos-phonium bromide and butyllithium, and subsequent hydroboration and oxidation furnished compound 108. A series of reactions, namely, protection of the primary hydroxyl group, 0-debenzylation, formation of A-methyl dithiocarbonate, deoxygenation with tributyltin hydride, and removal of the protective groups, converted 108 into 7. 

The reductive removal of the tellurium moiety from aryldichlorotellurolactones is achieved by treatment with tributyltin hydride (TBTH) in refluxing toluene. High yields are conditional on a previous careful deoxygenation of the reaction mixture. 

Barton-McCombie deoxygenation is not always stereoselective the diastereo-meric ratios strongly depends on the nature of the protecting groups and of the ester moiety. However, in 2-C-trifluoromethyl-2-deoxyfuranose, the a compound is the major product of the reaction, due to steric hindrance of this a side. In 3-C-trifluoromethyl-3-deoxyfuranose, deoxygenation by tributyltin hydride yields only the a product, if it is performed with oxalate instead of thiocarbonate. Another possibility to obtain this selectivity is to perform the reaction with 1,2,5,6-di-O-isopropylidene-a-D-glucofuranose (Figure 6.34). ... 

Typical Procedure for Deoxygenation with Tributyltin Hydride Without a Radical initiator [10]... 

J. Nicholas Kirwan, B. P. Roberts, and C. R. Willis, Deoxygenation of alcohols by the reactions of their xanthate esters with triethylsilane An alternative to tributyltin hydride in the Barton-McCombie reaction, Tetrahedron Lett., 31 (1990) 5093-5096. 

Deoxygenation of primary and secondary alcohols.1 This deoxygenation has been effected by reduction of the thiocarbonyl esters with tributyltin hydride and AIBN as the radial initiator (11, 550). A newer, milder method uses diphenylsilane in a radical chain reaction initiated by triethylborane and air. Even secondary thiono-carbonates, particularly those derived from 4-fluorophenol, are deoxygenated at 25°. 

Cyclic thiocarbonates offer another class of substrates for radical deoxygenation (Scheme 3.9b). In particular, thiocarbonates formed from a diol derived from a primary and secondary hydroxyl are of particular interest, since they can be deoxygenated regioselectively with tributyltin hydride and AIBN.53 In these cases, the secondary position is deoxygenated owing to the higher stability of secondary over primary radicals. As expected, radical reduction of thiocarbonates derived from two secondary hydroxyls leads to a mixture of deoxygenated isomers.52b 53... 

The reaction of triethylboron with oxygen is a convenient way to generate ethyl radicals at room temperature, or at lower temperatures. These conditions at room temperature in the presence of tributyltin hydride efficiently perform the Barton-McCombie deoxygenation reaction. Recently, we showed that the tin hydride could be replaced by diphenylsilane also at room temperature, for the deoxygenation of secondary alcohols.20 Many different thiocarbonyl derivatives can now be used for the Barton-McCombie reaction. Data were collected for R = Ph, />-F-C6H4, C6F5, C6C13H2 with various substrates (Scheme 2). The yields were excellent for all the secondary... 

Radical chemistry has been widely exploited for the modification of carbohydrates. In particular, tributyltin hydride-promoted deoxygenation provides a convenient method for the effective removal of hydroxyl groups without intervention of other functionalities. Stereoselective carbon-carbon bond formation at the anomeric center has also revealed its apphcability for the preparation of carbon analogues of 0-glycosides. The majority of this work has been reviewed in earlier publications and hence will not be covered in this account. Instead a selection of newer appHcations is provided here, which have been categorized according to the type of radical reaction carried out. 

Reductive radical elimination (Barton deoxygenation) of the 3, 4 -xanthate derivative of neamine (70) has been used to prepare the key intermediate 71 (compounds 70, 71) for the synthesis of the 3, 4 -dideoxyneamine analog gentamine Cia [52]. In this synthesis, a precursor possessing free hydroxyl groups at positions 3 and 4 was treated with a mixture of carbon disulfide, aqueous sodium hydroxide, and methyl iodide in DMSO to afford compound 70. Subsequent reduction of 70 with tributyltin hydride furnished the olefin 71, which affer cafalyfic hydrogenation and deprofecfion was converted to gentamine Cia. 

The stereoselective five-ring annulation is the cornerstone in a synthesis of Corey s lactone, starting from readily available 3-deoxy-1.2 5,6-di-0-isopropylidene-a-D- v7)o-hexofuranose (8)54. Treatment of the intermediate 5-hexenol with thiocarbonylbis(iniidazole) followed by reaction with tributyltin hydride (Barton deoxygenation) gives exclusively the bicyclic compound 9 with the /i-orientated methoxymcthvl substituent. The cyelization product has the correct absolute configuration for the Corey lactone, to which it can be converted in four additional steps. 

The chemistry of )9-(thiocarbonyloxy)alkyl radicals stands in complete contrast to that of the (acyloxy)alkyl radicals, with elimination, while not the rule, being the norm [I]. The difference between the acyloxy and thiocarbonyloxy series is likely a consequence of the much weaker thiocarbonyl bond and the related higher stability of sulfur-centered radicals. The method has been developed in combination with the Barton deoxygenation method (Volume 1, Chapter 1.6) as a means of converting a vicinal diol, via the dixanthate, into an alkene (Scheme 33) [60-62]. Tributyltin hydride has been the reagent of choice for this reaction but it may also be conducted with the triethylsilane/benzoyl peroxide couple [63] and, doubtless, tris(trimethylsilyl)silane. 

A very useful radical-based reaction has been developed that can be applied to alcohols. As seen in chapter 4, conversion of an alcohol such as 73 to a thionocarbonate (74), followed by treatment with tributyltin hydride under radical conditions, gives cleavage to the C—O bond to give, in this case, 75. This example is take from Beak s synthesis of (-)-dihydropinidine, and is an example of a transformation called the Barton deoxygenation or the Barton-McCombie reaction. ... 

The synthesis of 7-deoxy-L-g/ cero-D-g/Mco-heptose (19), an inhibitor of gluco-kinase and glucose 6-phosphatase, from 1,2-0-isopropylidene-D-glucuronolac-tone derivative 18 is shown in Scheme 5. The 2 -0-cyclohexylcarbamoyl disaccharide 20 (see Chapter 3 for formation) was readily converted to the corresponding xanthate which was deoxygenated with tributyltin hydride to the 2 -deoxy disaccharide 21. Radical deoxygenation with tributyltin hydride has also been use to prepare l, 6 -dideoxysucrose from the corresponding l, 6 -ditriflate. ... 

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