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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,*,Pinacol Rearrangement,by yangyang,preview,Overview,History,The General Features,Synthetic Applications,Overview,The acyclic and cyclic vicinal diols, upon treatment with catalytic amount of acid, will undergo dehydration with concomitant 1,2-alkyl-, aryl- or hydride shift to afford ketones or aldehydes.,This acid-catalyzed transformation of vicinal diols is known as pinacol rearrangement.,Mechanism,The first step of the process is the pronation of one of the hydroxyl group, which results in the loss of water molecule to give a carbocation intermediate. This intermediate undergoes a 1,2-shift to give a more stable carbocation that upon the loss of proton gives the product. The pinacol rearrangement was shown to be exclusively intramolecular, and both inversion and retention were oberserved at the migrating center.,History,Using wrong conventinal atomic weight,History,Wilhelm Rudolph Fittig,(6 December 1835 19 November 1910) was a German chemist.,Fittigs work on pinnacol rearrangement was his independent research. It grow out of an interest in a readily avaible substance, acetone.,History,Justus Freiherr von Liebig (12 May 1803 18 April 1873) was a German chemist who made major contributions to agricultural and biological chemistry,.,During the years before and after the Liebig analysis, several chemists made attempts to determine the chemical nature of acetone.,History,Carl Lwig: German chemist.,(,March 17, 1803 - March 27, 1890,),. Lwig was Professor at Heidelberg, Zurich, and Breslau. He taught for nearly 60 years, discovered many bromine compounds, and founded the Silesian chemical industry.,Lwig,and Weidmann were investigating the then-popular idea that acetone was an alcohol and decided to test it by treatment of it with mentallic potassium, hoping to obtain a salt.,History,Instead, they found that the main products were mesityl oxide and phorone (resulting from what we now would call an aldol condensation). These are the same products that had previously been observed from the action of potassium hydroxide on acetone.,Lwig, C.; Weidmann, S. J.,Prakt. Chem,. 1840, 21, 64.,History,Fittig started out with the modest objective of repeating the,Lwig,-Weidmann experiment with sodium instead of potassium. Superficially, one might have expected the two experiment gave to give similar results, but that was not to be the case.,To bring Liebigs determination of the atomic composition of acetone into harmony with the conventional system of atomic weights, Fittig had to convert Liebigs formula C,3,H,6,O into the incorrect convertional formula C,3,H,3,O. So his project was in immediate trouble.,Berson, J. A.,Angew. Chem,. 2002, 41, 24.,History,Fittigs intention to make and alkylate a sodium salt from acetone might have been considered dubious in view of the failure of,Lwig,and Weidmann with the potassium enolate. However, he did find an unexpected and most interesting substance, which he isolated as large, tablet-shaped crystals and which he called paraceton. That was the substance later would be called pinacol.Fittigs name for this product, paraceton, came from his belief that it was a hydrate of a dimer of acetone.,Fittig found that heating pinacol with aqueous sulfuric acid or hydrochloric acid gave rise to a new substance now known as pinacolone.,History,Charles Friedel (12 March 1832 20 April 1899) was a French chemist and mineralogist.,History,In 1869, Friedel published that pinacol was tetramethylene glycol (,2,).,Friedel, C.,Ann. Chim. Phys.,Ser. 4 1869, 16, 310.,History,The fog surrounding all this chemistry was finally disspelled by two brilliant paper of Alexander Butlerov of St. Petersburg.,Alexander Mikhaylovich Butlerov ( ; September 15, 1828 August 17, 1886) was a Russian chemist,.,History,Butlerov, A.,Justus Liebigs Ann. Chem.,1874, 174, 125.,Butlerov, A.,Justus Liebigs Ann. Chem.,1873, 170, 151.,Butlerov, A.,Justus Liebigs Ann. Chem.,1873, 170, 162.,The General Features,1) virtually any cyclic or acyclic vicinal glycol,can,undergo the rearrangement,and, depending on the substitution pattern, aldehydes and/or ketones are,f,ormed;,2) when all four substituents are identical, the rearrangement yields a single product;,3) when the four,substituents are not identical, product mixtures are formed;,Krti, L.; Czak, B.,Strategic Applications Of Named Reactions In Organic Synthesis,A. Elsevier Academic Press, 2005, 350-351.,The General Features,4) the product is usually formed,via the most stable,carbocation intermediate when the glycol substrate is unsymmetrical;,5) the reaction can be highly regioselective and,the regioselectivity is determined by the relative migratory aptitudes of the substituents attached to the carbon,adjacent the carbocation center;,6) the substituent that is able to stabilize a positive charge better (better electron donor) tends to migrate preferentially;,Krti, L.; Czak, B.,Strategic Applications Of Named Reactions In Organic Synthesis,A. Elsevier Academic Press, 2005, 350-351.,The General Features,7) the relative migratory aptitudes are: aryl H vinyl (alkenyl),t-Bu cyclopropyl 2 alkyl 1 alkyl;,8) the pinacol rearrangement can also be stereoselective especially when complex cyclic vicinal diols are involved;,9) cyclic systems may rearrange via both ring-expansion and ring-contraction and the course of the rearrangement is strongly influenced by the ring size;,Krti, L.; Czak, B.,Strategic Applications Of Named Reactions In Organic Synthesis,A. Elsevier Academic Press, 2005, 350-351.,The General Features,10) most often a cold aqueous solution of sulfuric acid (25% H,2,SO,4,) is used to effect the rearrangement; however,other acids such as perchloric acid and phosphoric acid have also been utilized;,11) besides protic acids, Lewis acids (e.g., BF,3,OEt , TMSOTf) are also used.,Krti, L.; Czak, B.,Strategic Applications Of Named Reactions In Organic Synthesis,A. Elsevier Academic Press, 2005, 350-351.,The General Features,The General Features,The General Features,1),it is generally not easy to prepare complex vicinal diols;,2) in the case of unsymmetrical substrates, the regioselective formation of only one carbocation is usually not trivial, so product mixtures are obtained;,3),side reactions such as -eliminations yielding dienes and allylic alcohols are often observed;,4) the intermediate carbocations may undergo equilibration;,Krti, L.; Czak, B.,Strategic Applications Of Named Reactions In Organic Synthesis,A. Elsevier Academic Press, 2005, 350-351.,The General Features,5) various conformational effects and neighboring group participation in cyclic systems are complicating factors.,When one of the hydroxyl groups is converted to a good leaving group, the regioselective generation of the carbocation intermediate is possible. Similarly selective generation of carbocations can be realized when 2-heterosubstituted alcohols (e.g., halohydrins, 2-amino alcohols, 2-hydroxy sulfides, etc.) are used as substrates. The pinacol-type rearrangement of these compounds is referred to as the semipinacol rearrangement, a term first coined by M. Tiffeneau. Owing to its predictability and the mild reaction conditions, the semipinacol rearrangement is almost exclusively utilized in complex molecule synthesis.,Krti, L.; Czak, B.,Strategic Applications Of Named Reactions In Organic Synthesis,A. Elsevier Academic Press, 2005, 350-351.,Synthetic Applications,Synthetic Applications,Xu, W.;Wu, S.; Zhou, L.,Org. Lett.,2013, Vol. 15, No.8,Synthetic Applications,Xu, W.;Wu, S.; Zhou, L.,Org. Lett.,2013, Vol. 15, No.8,Synthetic Applications,Xu, W.;Wu, S.; Zhou, L.,Org. Lett.,2013, Vol. 15, No.8,Thank you!,