Alcohols secondary, deoxygenation

Allyl Alcohols. Secondary cyclic allylic alcohols are reduced with the combination of Et3SiH and ethereal LiC104, even in the presence of a tertiary alcohol (Eq. 35) or ketal function.173 Primary allylic alcohols do not undergo deoxygenation under similar conditions.173... 

Radical deoxygenation. Tosylates of primary alcohols undergo deoxygenation in 75-100% yield by treatment with Nal and Bu,SnH in DME at 80°. This radical reduction can be applied to tosylates of secondary alcohols, but the rate of reaction is slower and yields are only moderate.1... 

Deoxygenation of alcohols. Thionocarbonates or xanthates of primary or secondary alcohols are deoxygenated in 89-100% yield by radical reduction with (C2H,)jSiH and (ChH5C())202. 

Reductions. The InCIj-Bu SnH/PhjP combination (catalytic in indium) reduces acid chlorides to aldehydes." Aryl ketones and secondary benzyl alcohols are deoxygenated with hydrosilanes using InCl, as cataly.st." Deoxygenative allylation of aryl ketones occurs when allyltrimethylsilane is added. ... 

Attempts to prepare 2-butoxy-3//-azepines by heating nitro compounds with tris(di-ethylamino)phosphane in /m-butyl alcohol failed, as diethylamine, liberated by alcoholysis of the aminophosphane, reacts in preference with the alcohol (vide supra) to give the Ar,/V-di-ethyl-3//-azepin-2-amine in good yield.176 However, the deoxygenation of nitroarenes with tributylphosphane in the presence of primary and secondary alcohols furnishes 2-alkoxy-3//-azepines 98 in practicable yields.79... 

An effective deoxygenation using enantiomerically pure epoxides from primary allylic alcohols ( Sharpless epoxides ) [44] to give enantiomerically pure secondary allylic alcohols was described by Yadav [45]. This approach circumvented a kinetic resolution of secondary allylic alcohols that implies a maximum yield of 50% ( Scheme 5). 

Imidazole-A-thionocarboxylates (also called thiocarbonylimidazolides ) are intermediates in a convenient radical-induced deoxygenation of primary and secondary alcohols with tributylstannane (Barton reaction).[1],[2]... 

Selectivity could be accomplished by this method in deoxygenation of primary and secondary alcohol groups,[2] as well as effective deoxygenation of hindered secondary hydroxyl groups, especially in the carbohydrate series. ... 

An unexpected C-arylation was observed by Sherburn et al. in an attempted radical deoxygenation of a homoallylic secondary alcohol 83 via its thiocarbonyl-derivative 84 (scheme 17).1511 Thus, reaction of 84, obtained from 83 with ArOC(=S)Cl, with nBu3SnH yielded the 10-aiyl compound 87 As inter-... 

The Tafel rearrangement only occurs in acid medium. Simultaneous reduction of both carbonyl groups leads to interaction and formation of a cyclopropane. Acid catalysed cyclopropane ring opening follows to yield an a-diketone 28 which undergoes the electrochemical Clemmensen reduction step to the hydrocarbon. Side products include the two monoketones derived by partial deoxygenation of the a-diketone and the secondary alcohols from reduction of these raonoketones. Separate experiments show that the a-diketone 28 can be reduced to the hydrocarbon. 

This procedure gives good yields from secondary alcohols and, by appropriate adjustment of conditions, can also be adapted to primary alcohols.132 Scheme 5.7 illustrates some of the conditions which have been developed for the reductive deoxygenation of alcohols. 

For the formal deoxygenation (decomposition) reaction 5, there is an enthalpy of formation value for every alcohol that matches a hydroperoxide . Using our exemplary groups, R = 1-hexyl, cyclohexyl and ferf-butyl, the liquid enthalpies of reaction are —77.9, —75.0 and —65.6 kJmoR, respectively (there is no liquid phase enthalpy of formation reported for f-butyl peroxide from Reference 4). The secondary hydroperoxides enthalpies of reaction average —77 7 kJmoR. For the three instances where there are also gas phase enthalpies of formation, the enthalpies of reaction are almost identical in the gas and liquid phases. The 1-heptyl (—60.3 kJmoR ) and 1-methylcyclohexyl (—50.6 kJmoR ) enthalpies of reaction are again disparate from the 1-hexyl and tert-butyl. If the enthalpy of reaction 5 for 1-hexyl hydroperoxide is used to calculate an enthalpy of formation of 1-heptyl hydroperoxide, it is —325 kJmoR, almost identical to values derived for it above. The enthalpies of reaction for the liquid and gaseous phases for the tertiary 2-hydroperoxy-2-methylhex-5-en-3-yne are —78.2 and —80.9 kJmoR, respectively. For gaseous cumyl hydroperoxide, the enthalpy of reaction is —84.5 kJmoR. ... 

The keto group of the trisubstituted dioxanone 133 generated by ozonolysis was removed by radical deoxygenation according to the Barton-McCombie protocol [80] via the alcohols 134 and the corresponding xanthate, leading after deben-zylation to the dioxane 135 in excellent yield. After conversion to the tosylate, cleavage of the acetonide and protection of the secondary alcohol function as a TBS ether provided access to oxirane 128 by cyclization with NaH in 99% yield and in virtually diastereo- and enantiomerically pure form (de, ee > 96%). 

S. Iacono and James R. Rasmussen 57 DEOXYGENATION OF SECONDARY ALCOHOLS 3-DE0XY-l,2 5,6-DI-0-ISOPROPYLIDENE-a-D-ribo-HEXOFURANOSE... 

Deoxygenation of alcohols.2 Secondary alcohols react with 1 in the presence of pyridine or 4-dimethylaminopyridine to form thiono esters (2), which are cleaved... 

M. J. Robins, J. S. Wilson, and F. Hansske, Nucleic acid related compounds. 42. A general procedure for efficient deoxygenation of secondary alcohols. Regiospeciflc and stereoselective conversion of ribotmdeoades to 2 deoxynodeosides, J. Am. Chem. Soc. 105 4059 (1983). 

Primary alcohols can also be deoxygenated by radical chemistry [11a,lib]. However, it requires a higher temperature to break the carbon-oxygen bond in radical 13. Secondary alcohols can be conveniently deoxygenated in benzene under reflux (80°C), but primary alcohols require toluene or xylene under reflux. 

This chapter shows how radical chemistry based on thiocarbonyl derivatives of secondary alcohols can be useful in the manipulation of natural products and especially in the deoxygenation of carbohydrates. From the original conception in 1975, the variety of thiocarbonyl derivatives used has increased, but the methyl xanthate function still remains the simplest and cheapest, when other functionality in the molecule does not interfere. Otherwise, selective acylation with aryloxythiocarbonyl reagents is important. Many of the functional groups present in carbohydrates and other natural products do not interfere with radical reactions. 

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). 

A useful modification of the Barton deoxygenation of secondary alcohols involves the use of O-phenylthionocarbonates developed by Robins et al. [15]. Application of this method for the generation and cyclization of a hex-5-ynyI radical is shown is Scheme 5. The precursors are readily prepared from D-ribose by a Grignard addition, followed by selective alcohol derivatizations. The major exo-isomer has been converted into carba-a-D-ribofuranose [16]. 

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