Dehydration regiospecific

The role of the trimethylsilyl group is to stabilize the enolate formed in the conjugate addition. The silyl group is then removed during the dehydration step. Methyl 1-trimethylsilylvinyl ketone can be used under aprotic conditions that are compatible with regiospecific methods for enolate generation. The direction of annulation of unsymmetrical ketones can therefore be controlled by the method of enolate formation. 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

Addition of water to an unsymmetrical alkene follows Markovnikov s rule. The reaction is highly regiospecific. According to Markovnikov s rule, in the addition of water (H—OH) to alkene, the hydrogen atom adds to the least substituted carbon of the double bond. For example, 2-methylpro-pene reacts with H2O in the presence of dilute H2SO4 to form t-butyl alcohol. The reaction proceeds via protonation to give the more stable tertiary carbocation intermediate. The mechanism is the reverse of that for dehydration of an alcohol. 

The regiospecific cyclization of some glutaconic half-esters under dehydration conditions leads to 6-alkoxypyran-2-ones (82JOC1150). The reaction presumably proceeds via a carboca-tion which undergoes proton loss. The cyclic glutaconic derivative (311) gives the fused pyran-2-one (312) which has been used as precursor of various tetracyclic molecules (Scheme 89). 

Alkenes are relatively low oxidation level hydrocarbons. The most common way to prepare alkenes is to cany out the elimination of a small molecule from between vicinal carbon atoms. However, this is only a viable strategy if the regiochemistry of elimination can be controlled. That is, traditional dehydrohalo-genations or dehydrations often are regioselective but not regiospecific, so that mixtures of structurally isomeric olefins are formed. For example,... 

V-aminated end-imino (imino-bridged) compounds like 392 (86JHC1331). These products result from the addition of the reagent to the keto group without dehydration, followed by regiospecific cyclization of the secondary amino function into the vinylene group. 

Nevertheless, some notable effects have been observed in the metal-mediated activations of alkanols with larger alkyl backbones, where dehydration still persists but activation of internal C-H bonds via remote functionalization also becomes accessible. Thus, regiospecific 3,4-dehydrogenation of l,6-hexandiol/Fe+ [31] is associated with a considerable diastereoselectivity (an SE of about 3.2 can be derived from the experimental data). Similarly, 3,4-dehydrogenation of 1,8-oc-tandiol/Fe+ occurs diastereoselectively [32]. Note, however, that most complexes of the monofunctional alkanols 13 and 16 with Mn+-Co+ show negligible SEs. 

Methoxyvinyl trifluoromethyl ketones 772 underwent regiospecific cyclization with aminoguanidine to give trifluoromethyl alcohols 773, which were dehydrated to give trifluoromethylated 2-[l//-pyrazol-l-yl]pyrimidines 774 (Scheme 97) <2001S1505>. 

By controlling the reaction conditions it was possible to afford selectively the acetylation of secondary hydroxyls obtaining the triacetylderivative 13c in which there is the only free tertiary hydroxyl. Triacetylderivative 13c undergoes to dehydration by treatment with thionyl chloride in pyridine. Such reaction allows the regiospecific achievement of the only isomer 13d which has the double bond in 1,2 position. 

Then the hydroxyl at C-5 is protected by means of acetylation carried out with acetic anhydride in pyridine affording conq>ound 13g. The analysis of the H-NMR spectrum of acetyl derivative 13g allows to claim surely the regiospecificity of the dehydration reaction in fact in the acetylation reaction fi om 13f to 13g, it is showed the usual deshielding of about 1 ppm of proton whose chemical shift (6 5.15) is, of course, attributable to a not allyhc position. 

We have chosen this example to illustrate the first virtue of the Wittig reaction you know where the alkene will be in the product 64. Even if, as here, it is less stable than some other possibility (the endocyclic alkene 66 that would be formed by dehydration of the tertiary alcohol 67), the new alkene must be between the carbon atoms formerly occupied by the phosphonium ylid and the carbonyl group. This is because the last step is the regiospecific decomposition of a four-membered ring (an oxaphosphetane) 65. 

The various methods of generating o-quinone methides,4-5 including the thermal or (Lewis) acid-catalyzed elimination of a phenol Mannich base,149 150-160-161163 the thermal or (Lewis) acid-catalyzed dehydration of an o-hydroxybenzyl alcohol (ether),147-149-151-153-156-157-162-163-165-168 171-175-178-183 the thermal 1,5-hydride shift of an o-hydroxy styrene,171-173 175 178-183 the thermal dissociation of the corresponding spirochromane dimer,158 163-164,166 oxidation of substituted o-alkylphenols,152-170 and the thermal or photochemical-promoted cheletropic extrusion154-155 159 of carbon monoxide, carbon dioxide, or sulfur dioxide (Scheme 7-III), as well as their subsequent in situ participation in regiospecific, intermolecular [4 + 2] cycloadditions with simple olefins and acetylenes,147 149-151 152 153159 162-164... 

In the synthesis of pyridines it proved advantageous to make a dihydropyridine and oxidize it to a pyridine afterwards. The same idea works well in probably the most famous quinoline synthesis, the Skraup reaction. The diketone is replaced by an unsaturated carbonyl compound so that the quinoline is formed regiospecifically. The first step is conjugate addition of the amine. Under acid catalysis the ketone now cyclizes in the way we have just described to give a dihydroquinoline after dehydration. Oxidation to the aromatic quinoline is an easy step accomplished by many possible oxidants. 

In 1975, Pattenden etal. reported the first regiospecific synthesis of permethylated pulvinic acids 46 [48] and pulvinones 45 [49] by condensation of 44 with aroyl formates and aryl aldehydes, respectively, followed by dehydration (Scheme 1.5). Interestingly, Pattenden s pioneering work allowed the first total synthesis of naturally occurring pulvinones, first isolated from natural sources in 1973 [3b] but... 

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