Regiospecificity carboxylic acids

Treatment of 5//-dibenz[6,/]azepine (5, R1 = H) with an excess of butyllithium furnishes the 4,5-dilithio derivative 6, which with an equivalent of an A. A-dimethylcarboxamide undergoes regiospecific acylation at C4.206 In a similar manner, 5-acyl-5f/-dibenz[6,/]azepines, e.g. 5 (R1 = Ac), with butyllithium and carbon dioxide form dibenz[6,/]azepine-4-carboxylic acids, e.g. 7 (R1 = Ac R2 = OH).207... 

A regiospecific strategy to A-7-substituted purines 65 and its application to a library of 2,6,8-trisubstituted purines has been reported. The three-step synthetic strategy involves cyclization reactions of suitably substituted pyrimidines 63 with either a carboxylic acid or an aldehyde <06JC0410>. 

The bislactim ether method has also been applied to an intramolecular alkylation (84JOC2286) to generate stereospecifically the /3-tum-inducing element, (LL) 3-amino-2 piperidone-6-carboxylic acid as shown in Scheme 62. The efficiency of chiral induction was in the range 99.5%. It is noteworthy that there is no racemization of the intermediate bromo compound, thus proving the regiospecificity of the deprotonation. 

Sodium cyanide in DMF at 120 °C has been used for the decarboxylation of 1-substituted-4-oxoquinoline-3-carboxylic acids <94TL(35)8303>. Quinoline Reissert adducts have been epoxidized at the 3,4-bond. Its reaction with amine nucleophiles gave regiospecifically substituted 1,2,3,4-tetrahydroquinolines <95H(41)897>. Successive Claissen rearrangements of 2-(8-quinolinoxymethyl)-3-(8-quinolinoxy)-l-propene gave a product which shows excellent ability to extract heavy metal ions <95TL(36)5567>. An Eschenmoser approach has been used in a facile synthesis of monofunctional and difunctional A -substituted-4-alkylidenequinolines (54) (Scheme 39) <95S(St)56>. 

Silyl enol ethers, which are readily generated regiospecifically from ketones, can also be reduced to al-kenes, particularly by hydroboration. " Hydroboration of silyl enol ethers results in the addition of boron to the 3-c on of the double bond to afford fra/is-3-trimethylsilyloxy organoboranes, which in cyclic systems undergo anti elimination in the presence of acid to give the alkenic product (Scheme 42). A number of acids have been tested successfully, including carboxylic acids, BF3-Et20 and... 

A special category of ethers are trimethylsilyl ethers. Trimethylsilyl ethers of primary alcohols, on treatment with Jones reagent, give acids [590]. On treatment with A-bromosuccinimide under irradiation, trimethylsilyl ethers yield esters [744]. Secondary alkyl trimethylsilyl ethers are converted into ketones by oxidation with both reagents [590, 744, 981]. Oxidation with Jones reagent is regiospecific the 2-ferf-butyldimethylsilyl 11-Krf-butyldiphenylsilyl ether of 2,11-dodecanediol is oxidized only in the sterically less hindered position [590]. Trimethylsilyl ethers of tertiary alcohols are degraded by periodic acid to carboxylic acids with shorter chains [755] (equations 336-339). 

Reaction of 2-(/3-cyanoethyl)cyclohexanone benzylimide with carboxylic acid chlorides RCOCl (R = Me, Et, Pr, i-Pr, Bu, Mc2CHCH2) in benzene containing pyridine gave 47-81% N-acylenamines with high regiospecificity . ... 

Regiospecificity demands ort/zo-direction. A surprisingly effective group is a carboxylic acid C02H that acts as its lithium derivative C02Li. One equivalent of BuLi is used to make this 100 from, say picolinic acid 99, and three equivalents of LiTMP to make the C-Li derivative 101. Reaction with electrophiles such as C02 or carbonyl compounds occurs at C-3 102. 

The [ruthenium(cyclooctadienyl)2 (tributylphosphine)]- catalysed addition of carboxylic acids 250 (R = cyclohexyl, PhCH2 or CH2 = CMe) to terminal acetylenes 251 (R = Bu or Ph) results in enol esters 252 similarly, benzoic acid adds to propyne in the presence of a rhodium catalyst to yield 2-(benzoyloxy)propene (253) regiospecifically. ... 

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