Decarboxylation cyclic

Oxidation of cyclic secondary amines such as pyrrolidine (351) and piperidine (353) with iodosobenzene in water leads to lactams 352 and 354, respectively (88TL6913, 88TL6917) (Scheme 90). Similar oxidation of 2-piperidinecarboxylic acid and 2-pyrrolidinecarboxylic acid is accompanied by decarboxylation. Cyclic tertiary amines 355, 357, and 359 (Eq. 48) are likewise oxidized to the corresponding lactams. Other examples include phencyclidine (360) to A-(l-phenylcyclohexyl)piperidone (361), N-(cyanocyclohexyl)piperidine (362) to A-(l-cyanocyclohexyl)piperidone (363) (Scheme 91), and 1,2,3,4-tetrahydroisoquinoline to 1,2,3,4-tetrahy-droisoquinolinone (Eq. 49). 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

The formation of 1-and 2-aIkenes can be understood by the following mechanism. In the presence of formate anion, the 7r-allylpalladium complex 572 is converted into the 7r-allylpalladium formate 573. The most interesting feature is the attack of the hydride from formate to the more substituted side of the (T-allylic system by the cyclic mechanism shown by 574 to form the 1-alkene 575[367]. The decarboxylation and hydride transfer should be a concerted... 

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]. 

Some of these compounds are used as potential intermediates for the preparation of 4,7-dioxo-4,5,6,7-tetrahydrothiazolo[4,5d]pyridazines (78). The diesters (77) are hydrolyzed under appropriate conditions to free acids (79), whose monopotassium salts (80) yield the cyclic anhydrides (81) under the influence of thionylchloride. Pyrolysis of 79, Rj = a-thienyl, results in its decarboxylation to 82. 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

In contrast to other acids, anhydrous hydrogen fluoride does not cause hydroly SIS and decarboxylation of the malonic acid residues in these reactions [5]. It is a good reagent for the cyclization of a-benzamidoacetophenones to 2,5 diphenyl-oxazoles [6] (equation 7) The same reaction with concentrated sulfuric acid gives cyclic product with only a 12% yield [6]... 

Rearrangements of vinylogous urethanes to vinylogous carbonic acids and decarboxylation are other interesting enamine rearrangements which may be synthetically useful in the formation of cyclic enamines (623,624). 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

Selective hydrolysis of the 3-carboxylate with 6N-HCl/AcOH was unsuccessful and instead the 4-carboxylate hydrolyzed to the corresponding acid, however, heating of 432 at 50 °C caused its hydrolysis and decarboxylation in one step. Subsequent reaction with either MnO or DDQ gave 433. The fluorine atom at 8-position could be replaced by cyclic amines to give the 8-pyrrolyl or 8-[l-methyl-4-piperazinyl] derivatives 436 which upon hydrolysis using either acidic or basic conditions afforded the... 

Decarboxylation is not a general reaction of carboxylic acids. Rather, it is unique to compounds that have a second carbonyl group two atoms away from the —COoH. That is, only substituted malonic acids and /3-keto acids undergo loss of CC>2 on heating. The decarboxylation reaction occurs by a cyclic mechanism and involves initial formation of an enol, thereby accounting for the need to have a second carbonyl group appropriately positioned. 

The malonic ester synthesis can also be used to prepare cydoalkane-carboxvlic acids. For example, when 1,4-dibromobutanc is treated with diethyl malonate in the presence of 2 equivalents of sodium ethoxide base, the second alkylation step occurs intrcunotecidariy to yield a cyclic product. Hydrolysis and decarboxylation then give cvclopentanecarboxylic acid. Three-, four-, five-. 

The three-step sequence of 0) enolate ion formation, (2) alkylation, and (3) hydrolvsis/decarboxylation is applicable to all /Tketo esters with acidic a hydrogens, not just to acetoacetic ester itself. For example, cyclic /3-keto esters such as ethyl 2-oxocycIohexanecarboxylate can be alkylated and decarboxy-lated to give 2-substituted cyclohexanones. 

The cyclic /3-keto ester produced in a Dieckmann cyclization can be further alkylated and decarboxylated by a series of reactions analogous to those used in the acetoacetic ester synthesis (Section 22.7). For example, alkylation and subsequent decarboxylation of ethyl 2-oxocyclohexanecarboxylate yields a 2-alkylcvclohexanone. The overall sequence of (1) Dieckmann cyclization, (2) /3-keto ester alkylation, and (3) decarboxylation is a powerful method for preparing 2-substituted cyclohexanones and cyclopentanones. 

Michael reactions and, 895 Beta-keto ester, 851 alkylation of, 859-860 cyclic, 892-893 decarboxylation of, 857, 860 Michael reactions and. 895 pKd of, 852 synthesis of, 892-893 Beta-lactam antibiotics, 824-825 Beta oxidation pathway, 1133-1137 mechanism of, 1133-1136 Beta-pleated sheet (protein), 1038 molecular model of, 1039 secondary protein structure and, 1038-1039 Betaine, 720 Bextra. structure of, 544 BHA, synthesis of, 629 BHT, synthesis of. 629 Bicycloalkane. 129 Bijvoet. J. M., 299 Bimolecular, 363... 

The approach makes use of a bipyrroledicarbaldehyde 54 and a tripyrranedicarboxylic acid 55 which are condensed with subsequent decarboxylation in the presence of acid and oxygen. The presence of oxygen, as in many other syntheses of porphinoid macrocycles, is necessary to adjust the oxidation level of the chromophore which is in sapphyrins a 2271-aromatic cyclically conjugated system. Many sapphyrins 56 with different substitution patterns have been synthesized according to this general scheme. As in all McDonald-type condensations at least one of the components has to be symmetric because otherwise mixtures of constitutional isomers would be formed. 

Malonic acid and its derivatives, which would give four-membered cyclic anhydrides, do not give this reaction when heated but undergo decarboxylation (12-38) instead. 

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. 

In order to account for the nonvolatility, infusibility, and limited solubility, Leuchs postulated polymerization of the ground type cyclic compound, as indicated by the subscript x in his formula given above. It is now well established that linear polypeptides are produced on decarboxylation of the N-carboxyanhydrides of a-amino acids, and under favorable conditions the chain length may be fairly large. Leuchs favored the view that strained rings, i.e., those of other than five or six... 

Asymmetric hydrogenation of a cyclic enamide (Approach B) had very sparse literature precedents [7]. It should also be noted that preparation of these cyclic imines and enamides is not straightforward. The best method for the synthesis of cyclic imines involves C-acylation of the inexpensive N-vinylpyrrolidin-2-one followed by a relatively harsh treatment with refluxing 6M aqueous HC1, which accomplishes deprotection of the vinyl group, hydrolysis of the amide, and decarboxylation (Scheme 8.6) [8]. 

A palladium(O) species nicely catalyzes the Grob-type decarboxylative ring-opening reaction of cyclic carbonate 67 (Eq. 17) [38,39]. 

The question of the stability of the biomolecules is a vital one. Could they really have survived the tremendous energies which would have been set free (in the form of shock waves and/or heat) on the impact of a meteorite Blank et al. (2000) developed a special technique to try and answer this question. They used an 80-mm cannon to produce the shock waves the shocked solution contained the two amino acids lysine and norvaline, which had been found in the Murchison meteorite. Small amounts of the amino acids survived the bombardment , lysine seeming to be a little more robust. In other experiments, the amino acids aminobutyric acid, proline and phenylalanine were subjected to shock waves the first of the three was most stable, the last the most reactive. The products included amino acid dimers as well as cyclic diketopiperazine. The kinetic behaviour of the amino acids differs pressure seems to have a greater effect on the reaction pathway than temperature. As had been recognized earlier, the effect of pressure would have slowed down certain decomposition reactions, such as pyrolysis and decarboxylation (Blank et al., 2001). 

Recently, an example of cycloamylose-induced catalysis has been presented which may be attributed, in part, to a favorable conformational effect. The rates of decarboxylation of several unionized /3-keto acids are accelerated approximately six-fold by cycloheptaamylose (Table XV) (Straub and Bender, 1972). Unlike anionic decarboxylations, the rates of acidic decarboxylations are not highly solvent dependent. Relative to water, for example, the rate of decarboxylation of benzoylacetic acid is accelerated by a maximum of 2.5-fold in mixed 2-propanol-water solutions.6 Thus, if it is assumed that 2-propanol-water solutions accurately simulate the properties of the cycloamylose cavity, the observed rate accelerations cannot be attributed solely to a microsolvent effect. Since decarboxylations of unionized /3-keto acids proceed through a cyclic transition state (Scheme X), Straub and Bender suggested that an additional rate acceleration may be derived from preferential inclusion of the cyclic ground state conformer. This process effectively freezes the substrate in a reactive conformation and, in this case, complements the microsolvent effect. 

In contrast to the effect of cycloheptaamylose, cyclohexaamylose depresses the rates of decarboxylation of unionized 8-keto acids (Straub and Bender, 1972). Since conformational effects depend largely on the geometry of binding, it is not surprising to find high sensitivity to the size of the cycloamylose cavity. Apparently, the smaller cyclohexaamylose cavity cannot accomodate the cyclic transition state for acidic decarboxylations. 

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 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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