Allylic alcohols alkyl halides

Several years ago, we reported the synthesis and synthetic utility of lithium aminoborohydrides (LABs) a new class of powerful, safe, and highly selective reducing agents (2, 3). These reagents performed many of the transformations for which lithium aluminum hydride is usually used. Thus, the following reduction reactions were carried out with LABs aldehydes and ketones to alcohols, esters to alcohols, oc,P>unsaturated ketones to allylic alcohols, a,P-unsaturated esters to allylic alcohols, alkyl halides to hydro-carbons, azides to amines, and epoxides to alcohols. These reduction reactions are summarized in Figure 3. 

Table 11.1 lists some of the reaction conditions which have given prepara-tively useful yields of 3-alkylation. Entries 1-3 are typical alkylations using a magnesium salt and an alkyl halide. Even 2,3-disubstituted indoles are alkylated at C3 under these conditions (Entry 7). Entry 5 represents a more recently developed method in which an allylic alcohol and indole react in the... 

Alkylation with a vatiety of common alkyl halides oi sulfates gives stable dialkylcyanamides. However, the intermediate monoalkylated compounds usually cannot be isolated and cychc trimers or cotrimers with cyanamide ate obtained (13). The reaction can be carried out efficientiy in water or alcohol. Allyl chloride is an especially useful reagent, producing diallylcyanamide [538-08-9J (4). 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

Both cyclic and acyclic allylic cations have been produced in this way. Stable allylic cations have also been obtained by the reaction between alkyl halides, alcohols, or alkenes (by hydride extraction) and SbFs in SO2 or S02C1F. Divinylmethyl... 

Alkyl halides can be hydrolyzed to alcohols. Hydroxide ion is usually required, except that especially active substrates such as allylic or benzylic types can be hydrolyzed by water. Ordinary halides can also be hydrolyzed by water, if the solvent is HMPA or A-methyl-2-pyrrolidinone." In contrast to most nucleophilic substitutions at saturated carbons, this reaction can be performed on tertiary substrates without significant interference from elimination side reactions. Tertiary alkyl a-halocarbonyl compounds can be converted to the corresponding alcohol with silver oxide in aqueous acetonitrile." The reaction is not frequently used for synthetic purposes, because alkyl halides are usually obtained from alcohols. 

An allylic sulfenate, like 199, is known to be in equilibrium with allylic sulfoxide, like 196, although its concentration is usually low . Various allylic sulfoxides can be prepared by treatment of allylic alcohols with arenesulfenyl chlorides . Evans and coworkers prepared various allylic alcohols by treating the corresponding allylic sulfoxides with trimethyl phosphite. For example, the carbanion from a cycloalkenyl sulfoxide 201 was readily alkylated at the a-position by treatment with alkyl halide. The resulting alkylated derivative 202 was then treated with trimethyl phosphite and 3-substituted cycloalkenol was obtained. Alkylation of acyclic allylic sulfoxide 204 gave... 

Alkyl halides and triflates, alkane reduction, 27-32 alkyl halides, 28-31 a-halocarbonyl compounds, 31 vinyl and aryl halides and triflates, 32 Alkynes, alkane reduction, 45-46 Allyl acetates, reduction of, 51 Allyl alcohols ... 

Allyl halides, reduction reactions, 31 Aluminum chloride reagent/catalyst alkyl halide reduction, 30-31 secondary alkyl alcohol reduction, 14-15... 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

Evans and Uraguchi also examined the rhodium-catalyzed allylic alkylation with hard nucleophiles [31]. Aryl organozinc halides proved optimal nucleophiles for the regio- and stereospecific allylic alkylation of enantiomerically enriched unsymmetrical allylic alcohol derivatives (Tab. 10.4). The reaction occurs with net inversion of absolute... 

Type I (fast homodimerization) Terminal olefins, allylsilanes" Terminal olefins, allylsilanes," 1° allylic alcohols, ethers, and esters, " allyl boronate esters, allyl halides, alkyl-substituted allenes Terminal olefms, allyl boronate esters, 1° allylic alcohols, ethers, and esters,styrenes (no large ortho substit.), " " allyl allylsilanes, allyl sulfides, allyl phosphonates, " allyl phosphine oxides, protected allylamines ... 

Etherification. The reaction of alkyl halides with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraallyl ether is formed on reaction of D-mannitol with allyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional allyl bromide, leads to hexaallyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trimethylchlorosilane in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

Both cyclic and acyclic allylic cations have been produced in this way. Stable allylic cations have also been obtained by the reaction between alkyl halides, alcohols, or olefins (by hydride extraction) and SbF5 in SO2 or SOjCIF.26 Divinylmethyl cations27 are more stable than the simple allylic type, and some of these have been prepared in concentrated sulfuric acid.2 Arenium ions (p. 502) are important examples of this type. Propargyl cations (RCssCCR2 ) have also been prepared.29... 

Alkyl sulfates, tosylates, and other esters of sulfuric and sulfonic acids can be converted to alkyl halides with any of the four halide ions.979 Neopentyl tosylate reacts with Cl, Br, or I without rearrangement in HMPA.980 Similarly, allylic tosylates can be converted to chlorides without allylic rearrangement by reaction with LiCl in the same solvent.981 Inorganic esters are intermediates in the conversion of alcohols to alkyl halides with SOCl2, PC15, PC13, etc. (0-67), but are seldom isolated. 

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