Heterocyclic compounds addition reactions

Not surprisingly, carbonyl compounds are excellent reaction partners for the ester enolates 104. Since the primary adducts are only isolable in singular cases and the subsequent ring opened products (y-lactols) are very versatile precursors for synthesis of heterocycles, these addition reactions as well as those of electrophiles with a S = C unit will be discussed in a separate paragraph (see section 4.6). 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Addition nomenclature, 1, 37 Addition reactions heterocyclic compounds reviews, 1, 70 Additives... 

Soon after the discovery of the addition reaction between diene-ophiles and dienes which now bears their names, Diels and Alder extended their investigations to include potential heterocyclic dienes. In 1929 the first compound investigated, furan, was observed to combine with maleic anhydride, like butadiene in a typical Diels-Alder reaction, across the 2,5-positions yielding a 1 1 molar adduct... 

The reactions of carbenes, which are apparently unique in displaying electrophilic character in strongly basic solutions, include substitution, addition to multiple bonds, and co-ordination with lone pairs of electrons to form unstable ylides. This last reaction is of obvious relevance to a consideration of the reactions of heterocyclic compounds with carbenes and will be summarized. 

The heterocyclic telluride 32 is susceptible to oxidation-addition reactions and readily adds halogen atoms under a treatment with halogens or sulfuryl chloride (93MI1). Compounds 34 were obtained in almost quantitative yields. 

The reaction of benzyl radicals wdth several heterocyclic compounds W as more extensively studied by Waters and Watson, " - who generated benzyl radicals by decomposing di-tert-butyl peroxide in boiling toluene. The products of the reaction with acridine, 5-phenyl-acridine, 1 2- and 3 4-benzacridine, and phenazine were studied. Acridine gives a mixture of 9-benzylacridine (17%) (28) and 5,10-dibenzylacridan (18%) (29) but ho biacridan, w hereas anthracene gives a mixture of 9,10-dibenzyl-9,10-dihydroanthracene and 9,9 -dibenzyl-9,9, 10,10 -tetrahydrobianthryl. This indicates that initial addition must occur at the meso-carbon and not at the nitrogen atom. (Similar conclusions were reached on the basis of methylations discussed in Section III,C.) That this is the position of attack is further supported by the fact that the reaction of benzyl radicals with 5-... 

Heterocyclic compounds have in most cases been hydroxylated by modified forms of Fenton s reagent. For instance, EDTA or pyrophosphate have been added to the system to complex the ferrous ions. It has been shown in the reactions of bcnzenoid compounds, however, that addition of complexing agents does not affect the distribution of isomers obtained by Fenton s reagent,and therefore the hydroxyl radical must still be the hydroxylating species. 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

Huisgen has reported in 1963 about a systematic treatment of the 1,3-dipolar cycloaddition reaction as a general principle for the construction of five-membered heterocycles. This reaction is the addition of a 1,3-dipolar species 1 to a multiple bond, e. g. a double bond 2 the resulting product is a heterocyclic compound 3. The 1,3-dipolar species can consist of carbon, nitrogen and oxygen atoms (seldom sulfur) in various combinations, and has four non-dienic r-electrons. The 1,3-dipolar cycloaddition is thus An +2n cycloaddition reaction, as is the Diels-Alder reaction. 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

Azides add to double bonds to give triazolines. This is one example of a large group of reactions ([3-l-2]-cycloadditions) in which five-membered heterocyclic compounds are prepared by addition of 1,3-dipolar compounds to double bonds (see Table 15.3). These are compounds that have a sequence of three atoms A—B—C,... 

As already described for the all-carbon-Diels-Alder reaction, a hetero-Diels-Alder reaction can also be followed by a retro-hetero-Diels-Alder reaction. This type of process, which has long been known, is especially useful for the synthesis of heterocyclic compounds. Sanchez and coworkers described the synthesis of 2-aminopyridines [48] and 2-glycosylaminopyridines 4-144 [49] by a hetero-Diels-Alder reaction of pyrimidines as 4-143 with dimethyl acetylenedicarboxylate followed by extrusion of methyl isocyanate to give the desired compounds (Scheme 4.30). This approach represents a new method for the synthesis of 2-aminopyridine nucleoside analogues. In addition to the pyridines 4-144, small amounts of pyrimidine derivatives are formed by a Michael-type addition. 

Monomeric compounds (x = 1) containing M=E double bonds remained unknown until Power and Roesky et al. reported in 2001 on the synthesis of the first monomeric iminoalane and -gallane by oxidative addition of an organoazide to a sterically encumbered low-valent A1(I) compound 4 This reaction type has been shown previously to yield heterocyclic compounds by use of sterically less hindered [Cp Al]4.145 Very recently, von Hanisch and Hampe synthesized the first GaAs compound featuring a Ga=As double bond5 (Scheme 19, Figs. 41 and 42). 

An independent synthesis of 120 was achieved by O-benzylation of 2,5-anhydro-D-gluconamide33 however, undesirable side-reactions made this alternative approach impractical. Compound 120 was subsequently transformed into a C-/3-D-arabinofuranosylated heterocycle by way of a 1,3-dipolar addition-reaction of the 1-diazo intermediate 122 to dimethyl acetylenedicarboxylate (see Section IV,2). 

Addition of Heterocyclic Compounds Stereocontrolled nucleophilic addition of heterocyclic compounds to chiral nitrones is of great synthetic importance in the synthesis of natural and biologically active compounds. In these reactions, the nitrone group serves as an amino group precursor and the heterocycle furnishes the formyl group (from thiazole) (192, 195, 214, 215, 579) or the carboxyl group (fromfuran) (194-196, 580-584) (Scheme 2.149). 

Nitrogen-containing heterocyclic compounds, including 1,2,3,4-tetrahydroqui-noline, piperidine, pyrrolidine and indoline, are also popular hydrogen donors for the reduction of aldehydes, alkenes, and alkynes [75, 76]. With piperidine as hydrogen donor, the highly reactive 1-piperidene intermediate undergoes trimer-ization or, in the presence of amines, an addition reaction [77]. Pyridine was not observed as a reaction product. 

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