Allylation with Decarboxylation

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

Although outside the scope of this section, the concurrent development of the Pd-catalyzed allylation of /3-ketocarboxylic acids via the formation and decomposition of allyl /3-ketocarboxylates is noteworthy (Sects. V.2.1.1 and V.2.1.2). The mechanism shown in Scheme 4, which involves (i) oxidative addition of allyl /3-ketocarboxylates, (ii) decarboxylation, and (iii) intermolecular enolate allylation was proposed and experimentally supportedUnfortunately, a-allylation with y-disubstituted allyl derivatives, such as geranyl carboxylates, proceeds in low yields, and there are some indications that the reaction may lack some specificity features, for example, stereospecificity of the allylic moiety. 

AlClg added in small portions at 5° in a stream of dry Ng to a stirred suspension of dimethylchloromethylamine in 1,2-didilorethane, stirring continued 0.5 hr. with ice-cooling, allowed to warm to room temp, and l,l-bis-(4-dimethylaminophenyl)-ethylene in 1,2-didilorethane added dropwise, then heated 8 hrs. at 70° with stirring in a Ng-stream dimethyl-[3,3-bis-(4-dimethylaminophenyl)allyl]amine. Y 90%. F. e. s. H. Bohme and W. Fresenius, Ardi. Pharm. 305, 601 (1972) without AICI3, also from cinnamic acids with decarboxylation, s. ibid. 305, 610. 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

Hydrogenolysis of the diallyl alkylmalonate 757 with formic acid in boiling dioxane affords the monocarboxylic acid 758. Allyl ethyl malonates are converted into ethyl carboxylates[471]. The malonic allyl ester TV-allylimide 759 undergoes smooth deallylation in refluxing dioxane to give the simple imide 760(472]. The allyl cyanoacetate 761 undergoes smooth decarboxylation to give... 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

When ethyl trifluoroacetylacetate is treated with an allylic alkoxide, tran-sesterification is followed by ester enolate Claisen rearrangement m a process that on decarboxylation yields stereospecifically the tnfluoromethyl ketone product [22] (equation 19)... 

Dibenzo[/>,rf]thiopyrylium tetrafluoroborate (1) reacts with ethyl lithiodiazoacetate at — 120 C to form the diazo compound 2 which, with dimeric ( 3-allyl)chloropalIadium at 20 C, gives ethyl dibenzo[ ,d]thiepin-6-carboxylate (3), via a carbene intermediate.5 Compound 3 is quite stable the ethoxycarbonyl group can be hydrolyzed by alkali and decarboxylated to give the corresponding parent compound 4 in good yield. 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

A convenient way of obtaining secondary amines without contamination by primary or tertiary amines involves treatment of alkyl halides with the sodium or calcium salt of cyanamide NH2—CN to give disubstituted cyanamides, which are then hydrolyzed and decarboxylated to secondary amines. Good yields are obtained when the reaction is carried out under phase-transfer conditions. The R group may be primary, secondary, allylic, or benzylic. 1, co-Dihalides give cyclic secondary amines. 

Co-adsorption experiments show a complex role of the nature and concentration of chemisorbed ammonia species. Ammonia is not only one of the reactants for the synthesis of acrylonitrile, but also reaction with Br()>nsted sites inhibits their reactivity. In particular, IR experiments show that two pathways of reaction are possible from chemisorbed propylene (i) to acetone via isopropoxylate intermediate or (ii) to acrolein via allyl alcoholate intermediate. The first reaction occurs preferentially at lower temperatures and in the presence of hydroxyl groups. When their reactivity is blocked by the faster reaction with ammonia, the second pathway of reaction becomes preferential. The first pathway of reaction is responsible for a degradative pathway, because acetone further transform to an acetate species with carbon chain breakage. Ammonia as NH4 reacts faster with acrylate species (formed by transformation of the acrolein intermediate) to give an acrylamide intermediate. At higher temperatures the amide may be transformed to acrylonitrile, but when Brreform ammonia and free, weakly bonded, acrylic acid. The latter easily decarboxylate forming carbon oxides. 

With the A-ring unit readily available, we directed our attention to the formation of the B-ring. At first, we duplicated the five step scheme reported in Sih s strigol synthesis involving 1) esterification of the acid 14, 2) allylic bromination with N-bromo 8 ucc i n imi d e (NBS) to 15, 3) condensation with the sodium salt of dimethyl malonate to 16, 4) alkylation with methyl bromoacetate to 17, and 5) acid catalyzed hydrolysis and decarboxylation to the acid 18. 

The chiral center would be installed from either Unear carbamate 15 or branched carbamate 16 via the asymmetric addition of malonate anion to the 7i-allyl Mo complex reported by Trost et al. [11] to afford the branched chiral malonate derivative 17. Decarboxylation of 17 should provide the mono-carboxylic acid 18. Masa-mune homologation with 18 affords our common precursor 14. Linear carbamate 15 was obtained from the corresponding cinnamic acid, and branched 16 was prepared in one pot from the corresponding aldehyde. 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

The substitution, with cyclic amines, of a 4-fluoro atom in 50 (R= Et, R1 = F) was unsuccessful at 80-120 °C, probably because of the presence of an acidic CH2 group at position 3 <1995T11125>. 3-Decarboxylated products 50 (R = Et) were prepared from 49 (R = Et) under different reaction conditions (Equation 7) < 1995T11125>. Direct conversion of 49 (R= Et R1 = Et, allyl) to acid 50 (R = H, R1 = F) was achieved in a boiling mixture of AcOH-conc. HC1 <1995T11125>. 

The complex also undergoes a variety of addition reactions with reagents such as methyl iodide, hydrochloric acid, benzoyl chloride, and allyl chloride.8 In a reaction similar to that of the decarboxylation of aldehydes, the complex will abstract CS from carbon disulfide to give the irans-thiocarbonyl complex rans-RhClCS[P(C8H6)5]2.9... 

The ring-opening of the cyclopropane nitrosourea 233 with silver trifiate followed by stereospecific [4 + 2] cycloaddition yields 234 [129]. (Scheme 93) Oxovanadium(V) compounds, VO(OR)X2, are revealed to be Lewis acids with one-electron oxidation capability. These properties permit versatile oxidative transformations of carbonyl and organosilicon compounds as exemplified by ring-opening oxygenation of cyclic ketones [130], dehydrogenative aroma-tization of 2-eyclohexen-l-ones [131], allylic oxidation of oc,/ -unsaturated carbonyl compounds [132], decarboxylative oxidation of a-amino acids [133], oxidative desilylation of silyl enol ethers [134], allylic silanes, and benzylic silanes [135]. 

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