Alcohols acetate synthetic equivalent

The target is now cyclohexanol. a secondary alcohol. The reaction of a secondary alkyl halide with hydroxide ion gives an unacceptably high amount of elimination by the E2 mechanism. A better choice is to use acetate ion as the synthetic equivalent of hydroxide ion. 

One example of this strategy is the preparation of alcohols using acetate anion as the synthetic equivalent of hydroxide ion in SN2 reactions (see Section 10.2 and Figure 10.1). 

Reaction with aUyhc alcohols (1, 271 272). The reaction of rran.v-3-penten-2-ol (1) with N, N-dimethylacetamide dimethyl acetal and/or its synthetic equivalent 1 -methoxy-l-dimcthylaminoethylene in refluxing xylene for 17 hr. gives the N,N-dimethylamide of 3-mcthyl-4-trani-hexenoic acid (2) in 80% yield. When the reaction was carried out... 

Acetals prepared from chiral diols and carbonyl compounds serve as a chiral synthetic equivalent of aldehydes or ketones. 1,3-Dioxanes synthesized from chiral 2,4-pentanediols are especially useful, and high asymmetric inductions are observed in the Lewis acid promoted reactions of a variety of organometallic compounds. After the removal of the chiral auxiliary by the oxidation and -elimination procedures, optically active alcohols are obtained. Optically active propargylic alcohols and cyanohydrins are synthesized from organosilane compounds, TMS-C CR or TMS-CN in the presence of TiCU (Scheme 24). 1 6-138 Reactive wganometals such as alkyl-lithiums, -magnesiums or -coppers also react with chiral... 

Mono- and dialkylations of malonic acid esters generally are performed in an alcoholic solution of a metal alkoxide. Alkylation of a monoalkylated malonic ester requires the presence of another equivalent of alkoxide and the appropriate alkyl halide. The alkylation works well with RCH2X (X=l, Br, OTs), PhCH2X (X=C1, Br) and even with unhindered sec alkyl bromides." Subsequent hydrolysis of the diester under acidic or basic conditions followed by heat-induced decarboxylation yields the a-alkylated carboxylic acid. Thus, dialkyl malonates are the synthetic equivalents (SE) of acetate enolate anions and can be used to obtain mono- or disubstituted carboxylic acids. 

Wasserman has completed two syntheses of recifeiolide, both employing the use of oxazoles as acetic acid dianion equivalents. The first (Scheme 1.10) utilized a route previously developed by Corey for his synthesis of 1. Cuprate 4 was alkylated and then converted to iodide 38 in a straightforward manner. Alkylation with oxazole anion 39 and removal of the THP with acid then led directly to alcohol 40. Liberation of the carboximide moiety was achieved by treatment with singlet oxygen to afford 41, which led to the isolation of synthetic 1 after an acid-mediated lactonization step, and separation of the olefin isomers. 

There are only a few known reactions where the 22,23 double bond remains intact, and these involve simple protection or deprotection to the alcohol functions of azadirachtin. For example, the acetate at C-3 can be removed with sodium methoxide in methanol at room temperature in 2.5 hours (27) (yielding 54). The hydroxyl at C-11 can be selectively monoacetylated (27, 47, 49) (acetic anhydride reflux, 15 min., giving 55), or monomethylated (27) (iodomethane, silver oxide, giving 56). The remaining two hydroxyls at C-20 and especially C-7 are much more difficult to access synthetically. Nakanishi reported that in order to methylate all three alcohols (yielding 57) it was necessary to react azadirachtin with 15 equivalents of KOH and 30 equivalents of iodomethane in DMSO (40),... 

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