Allyl alcohol, reactions sulfides

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Nucleophilic addition to a, -unsaturated sulfones has long been known. For example, treatment of divinyl sulfone with sodium hydroxide has been known to afford bis( -hydroxyethyl) sulfone "", while the reaction of a- and -naphthyl allyl sulfones and allyl benzyl sulfone " with alkali hydroxide or alkoxide gave -hydroxy or alkoxy derivatives. In the latter reaction, the allyl group underwent prototropy to the 1-propenyl group, which in a subsequent step underwent nucleophilic attack . Amines, alcohols and sulfides are known to add readily to a, -unsaturated sulfones, and these addition reactions have been studied widely. In this section, the addition of carbon nucleophiles to a, ji-unsaturated sulfones and the reactions of the resulting a-sulfonyl carbanions will be examined. 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

The first attempts to develop reactions offering control over the absolute stereochemistry of a chiral center, created by y-selective substitution of an achiral allylic alcohol-derived substrate, involved the use of chiral auxiliaries incorporated in the nucleofuge. The types of stereodirecting groups utilized vary, and have included sulfoximines [15], carbamates [16], and chiral heterocyclic sulfides [17-19]. 

Scheme 8 summarizes the introduction of the missing carbon atoms and the diastereoselective epoxidation of the C /C double bond using a Sharpless asymmetric epoxidation (SAE) of the allylic alcohol 64. The primary alcohol 62 was converted into the aldehyde 63 which served as the starting material for a Horner-Wadsworth-Emmons (HWE) reaction to afford an E-configured tri-substituted double bond. The next steps introduced the sulfone moiety via a Mukaiyama redox condensation and a subsequent sulfide to sulfone oxidation. The sequence toward the allylic alcohol 64 was com-... 

Reactions where NLE have been discovered include Sharpless asymmetric epoxi-dation of allylic alcohols, enantioselective oxidation of sulfides to sulfoxides, Diels-Alder and hetero-Diels-Alder reactions, carbonyl-ene reactions, addition of MesSiCN or organometallics on aldehydes, conjugated additions of organometal-lics on enones, enantioselective hydrogenations, copolymerization, and the Henry reaction. Because of the diversity of the reactions, it is more convenient to classify the examples according to the types of catalyst involved. 

Heterogeneous oxidations,1 A variety of substrates can be oxidized by this solid reagent in refluxing hexane (1.5 -24 honrs). The reaction proceeds in good yield with alcohols (85-100%), aldehydes (65-80%), and sulfides but alkenes, alkynes, epoxides, and amides arc not oxidized. Surprisingly allylic alcohols arc oxidized more slowly than saturated alcohols. 

The basic Markovnikov selectivity pattern is partially or fully overrun in the presence of neighboring coordinating groups within the olefin substrate (Section 2.2.2). Known functionalities where inversed selectivity can occur include 3-alke-noylamides (e.g. 17 reacts to give a mixture of 18 and 19, Table 3) [43], homoallyl esters and alcohols, allyl ethers (but not necessarily allyl alcohols) [44], allyl amines, allyl amides, or carbamates (cf. 20 to 21) [45], allyl sulfides [46] or 1,5-dienes [47]. As a matter of fact, aldehyde by-products are quite normal in Wacker reactions, but tend to be overlooked. 

The oxidation of alcohols to aldehydes or ketones by periodane has several advantages over chromium and DMSO-based oxidants because of its shorter reaction times, higher yields and simplified work up. There is very little overoxidation to the carboxylic acid. It is a practical reagent for the facile and efficient oxidation of benzylic and allylic alcohols. Saturated alcohols are slow in their reactions with it. It oxidizes alcohols in the presence of non-hydroxylic functional groups such as sulfides, enols, ethers, furans and 2°-amides. An example of the DMP oxidation is the oxidation of 3,4,5-trimethoxybenzyl alcohol (7.17) with 7.16 in CH2CI2 to give 94% yield of 3,4,5-trimethoxybenzaldehyde (7.18). 

The vinylogous thioacetal 33 was transformed into the a,(8-unsaturated ketone 34 upon CuOTf-mediated hydrolysis whereas the HgCl2-promoted reaction was less effective (Sch. 9) [27]. Similarly, vinyl sulfide 35, which bears an allylic alcohol, was converted into the aj3-unsaturated ketone 36 with complete regiocontrol [28]. This regioselectivity is not dependent upon the heteroatom because the vinyl ether 37 hydrolyzes to the aldehyde or ketone 38 [29]. 

A novel tandem process has been reported " for the preparation of allylic amines, ethers, and sulfides from a-bromo-a, jS-unsaturated sulfones. The process is believed to proceed via an initial conjugate addition followed by proton exchange and Ramberg-Backlund rearrangement (see Scheme 75). A new variant of the Ramberg-Backlund reaction has been described in which a, /f-epoxy sulfones (319), on treatment with base, are converted into a range of mono-, di-, and tri-substituted allylic alcohols (320). 

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