Bromides oxidative decarboxylation

A related method for conversion of carboxylic acids to bromides with decarboxylation is the Hunsdiecker reaction.276 The usual method for carrying out this transformation involves heating the carboxylic acid with mercuric oxide and bromine. 

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

Seebach and coworkers demonstrated that tetrahydroisoquinoline pivala-mides 75 containing a stereogenic center at the 3-position can be used in dias-tereoselective alkylations [66]. After dilithiation of the acid with 2 equivalents of f-BuLi, the resulting organolithium was quenched with alkyl halides, such as Mel and benzyl bromide, to afford products 76 in ca. 80% yield, Eq. (5). Oxidative decarboxylation followed by amine deprotection provided 77 with ers greater than 97 3. 

The Hunsdiecker process has the disadvantage of requiring dry silver salts. As a consequence, other methods have been sought, and it has been found that some carboxyhc acids undergo oxidative decarboxylation on formation of mercury (Hg), lead (Pb), or copper (Cu) salts. For example, cyclopropane carboxyhc acid, on treatment with bromine (Br2) in the presence of red mercury(II) oxide (HgO), yields hydrogen bromide (HBr), carbon dioxide (CO2), and bromcxyclopropane (cyclopropyl bromide) as shown in Equation 9.84. 

A number of other syntheses of coniine have been effected, of which that of Diels and Alder is of special interest. The initial adduct of pyridine and methyl acetylenedicarboxylate, viz., tetraraethylquinolizine-1 2 3 4-tetracarboxylate (IX) on oxidation with dilute nitric acid is converted into methyl indolizinetricarboxylate (X). This, on hydrolysis and decarboxylation, furnishes indolizine, the octahydro-derivative (XI) of which, also known as octahydropyrrocoline, is converted by the cyanogen bromide method (as applied by Winterfeld and Holschneider to lupinane, p. 123) successively into the broraocyanoamide (XII), cyanoaraide (XIII) and dZ-coniine (XIV). A synthesis of the alkaloid, starting from indolizine (pyrrocoline) is described by Ochiai and Tsuda. ... 

To complete the section on the synthesis of 4,4 -bipyridines, we summarize the methods reported for the preparation of some substituted 4,4 -bi-pyridines and 4,4 -bipyridinones. These methods are closely analogous to syntheses already discussed for some of the isomeric bipyridines. Thus the Hantzsch reaction using pyridine-4-aldehyde, ethyl acetoacetate, and ammonia gives 3,5-di(ethoxycarbonyl)-1,4-dihydro-2,6-dimethyl-4,4 -bipyridine, which after oxidation, followed by hydrolysis and decarboxylation, afforded 2,6-dimethyl-4,4 -bipyridine. Several related condensations have been reported. Similarly, pyridine-4-aldehyde and excess acetophenone gave l,5-diphenyl-3-(4-pyridyl)pentane-l,5-dione, which with ammonium acetate afforded 2,6-diphenyl-4,4 -bipyridine. Alternatively, 1-phenyl-3-(4-pyridyl)prop-2-enone, A-phenacylpyridinium bromide, and ammonium acetate gave the same diphenyl-4,4 -bipyridine, and extensions of this synthesis have been discribed. Condensation of pyridine-4-aldehyde with malononitrile in the presence of an alcohol and alkaline catalyst produced compounds such as whereas condensations of... 

Formerly, benzoic acid was produced by the decarboxylation of phthalic anhydride. Oxidation of acetophenon, benzyl bromide, and toluene with sulfur and water has been described in the literature, but are not commercially feasible routes of synthesis. Carboxylation of benzene with carbon dioxide is not practical due to the instability of benzoic acid at the required reaction conditions [8]. 

Compound 287, which is obtained from 7V-carbethoxymethyl-2-methyl-pyridinium bromide and diethyl mesoxalate, undergoes base-catalyzed cyclization to betaine 288 which is readily converted to the quinolizinium-3-olate 286 (R = COjEt, = COjH). Decarboxylation of this compound (286 R = COjEt, R = CO2H) by cupric oxide and quinoline at 180-190 C gives the unsubstituted betaine (286 R = R = Quinolizinium-3-... 

Since we have already made compounds like 2 in chapter 25 from P-keto-esters, it makes sense to use the same strategy here. Addition of ethylene oxide 3 to the enolate of 5 gives the lactone 6 directly and treatment with HBr accomplishes decarboxylation and formation of the bromide 7 in one pot.1 Vogel2 uses the chloroketone to make 1 R=H in 82% yield by this method with NaOH for the base. 

Vanadium(V)-mediated intramolecular coupling of 90 furnished the dibenzocyclooctadiene diester 91 (45% yield), which underwent sequential oxidations at the benzylic C-8 position (via the bromide and the alcohol) to install the requisite keto group. Saponification of both esters in 92 followed by decarboxylation at 200°C furnished keto-acid 89, which was treated with formaldehyde as described above to give racemic steganone 12 and eventually steganacin 2. From a later report [109] and the work of Raphael, it seems obvious that under the decarboxylation conditions 89 was produced in an equimolar mixture with its atropisomer... 

---