Alcohols acid-mediated dehydration

The utility of the Chugaev elimination for the formation of olefins without rearrangement of the carbon skeleton can be observed upon pyrolysis of the xanthate of alcohol 14.17 The desired vinyl cyclopropane (IS) was isolated in reasonable yield (42%) along with a small amount of the rearranged xanthate. Alternatively, acid-mediated dehydration with sulphuric acid yielded a variety of rearranged products in low yield. Ester pyrolysis (of the acetate of 14) also furnished a variety of compounds, with the major product being cyclopentene 16. 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

Among the simplest of the cyclizations utilized in the formation of C-glycosides is the acid-mediated formation of ethers. Such reactions can be viewed as dehydration between two alcohol units, with the driving force for the reaction being the elimination of water. As shown in Scheme 7.98, Schmidt and Frick [242] formed the perbenzylated polyol by treating the lithiated... 

ArsBi bearing ortho methoxy groups mediates dehydrative condensation of a-monosubstituted carboxylic acids with alcohols and amines (Scheme 14.139) [288]. Macrocyclic esters can be synthesized by the ArsBi-templated reaction of diols with dicarboxylic acid derivatives [289]. The Bi-C bonds of Ar Bi are cleaved by diphenyl diselenide and ditelluride to give aryl phenyl selenides and tellurides, respectively (Scheme 14.140) [290]. The reaction of ArsBi with elemental chalcogen (E Se, Te) affords a mixture of the respective dichalcogenides (ArEEAr) and monochalcogenides (ArEAr). 

The facile acid-promoted dehydration of cobalt-complexed propargyl alcohols [18], via P-pro-ton loss from the derived cations (Scheme 4-50) offers improved chemo-, regio- and stereoselectivity vis a vis the free propargylic alcohols, with a strong preference for the more substituted ( )-ene-yne complex [151,152]. Such Co-mediated dehydration has afforded routes to enantiomerically pure manicone and normanicone (4,6-dimethyl-4-octen-3-one,... 

It was recently shown by Zhang and coworkers that Ru(PPh3)3Cl2 is a suitable catalyst for the alkylative coupling of tertiary alcohols 186 to primary alcohols 185 leading to branched alcohols 187 in 32-98% yield (Fig. 46) [258]. The reaction required the presence of a Lewis acid, such as BF3 OEt2. It mediates the dehydration of the tertiary alcohol to a 1,1-disubstituted alkene, which coordinates the ruthenium catalyst. The further course is likely to be similar to the corresponding iron- or rhodium-catalyzed reactions (see Sects. 2.8 and 6). 

Condensations of acetophenones with aliphatic aldehydes are often complicated by side reactions, although some simple cases are known to proceed in good yield (e.g. equation 84). An example of the kind of complications that may arise in such cases is seen in the reaction of acetophenone with isobutyr-aldehyde. Base-mediated reaction at low temperature gives a crude aldol that is dehydrated by heating with phosphoric acid to obtain a 3 1 mixture of a,p- and p,7-unsaturated ketones (equation 85). If the reaction is carried out under more traditional conditions, by heating an alcoholic solution of the reactants... 

The practical value of DMP as a reagent has been extended to various other synthetically useful oxidative transformations, such as the dehydration of primary alcohols under extraordinarily mild conditions [1276], synthesis of various polycyclic heterocycles via the oxidative cascade cyclization of anilides with pendant double bonds [1277], one-pot oxidative allylation of Morita-Baylis-Hillman adducts with allyltrimethylsilane promoted by DMP/Bp3-OEt2 [1278], synthesis of 2-amino-l,4-benzoquinone-4-phenylimides from anilines via DMP oxidation [1279], a-tosyloxylation of ketones using DMP and p-toluenesulfonic acid [1280] and the DMP-mediated oxidative aromatization of 1,3,5-trisubstitutedpyrazolines [1281]. 

The conversion of mevalonate (1) to isopentenyl pyrophosphate (IPP) (4) involves two consecutive phosphorylations at position 5 by successive action of mevalonate kinase (EC 2.7.4.2) and a decarboxylation and dehydration of the tertiary alcohol group by mevalonate 5-pyrophosphate decarboxylase (EC 4.1.1.33) (Fig. 18.4) (Crotean Johnson, 1985 Gershenzon and Croteau, 1990). One mole of ATP is required for each phosphorylation reaction. Mevalonate kinase converts mevalonic acid to (5/ )-phosphomevalonate (5). The second phosphorylation is catalyzed by phospho-mevalonate kinase. The subsequent decarboxylation and dehydration is mediated by the enzyme mevalonate diphosphate decarboxylase (di- or pyrophosphomevalonate decarboxylase EC 4,1.1.3.3) this enzyme requires Mg " or Mn + and ATP for activity (Beale and MacMillan, 1988 Harrison, 1988). All three of these enzymes are found in a number of plants. 

In general, these alcohol-based dehydrative A-alkylation reactions can be classified into two categories. One is the direct nucleophilic substitution of the hydroxy group by amines/amides mediated/catalyzed by Bronsted acids, Lewis acids, or TM complexes via formation of carbocation or coordinated cationic metal complexes under acidic conditions (Scheme 2) [16-20]. The famous Ritter reaction of nitriles and alcohols giving alkylated amides may be classified as one of these reactions, in which the nitriles serve as the A-nuleophile (Eq. 2) [21, 22]. 

---