Heterocycles, acylation carbonylation

Review papers have covered (81RCR336 84KGS579) the field of rotational isomerism in carbonyl-containing derivatives of five-membered aromatic heterocycles. This article aims to report a critical account of the results appearing in the literature concerning conformational information on heterocyclic acyl derivatives. 

Although many carbonyl derivatives act as acyl cation equivalents, R(C=0)" in synthetic chemistry, the inherent polarity of the carbonyl group makes it much more difficult to find compounds that will act as equivalents of acyl anions, R(C=0) . Since the 1960s, major progress has been made in this area, and there are now a wide variety of compound types that can react in this way. As in so many areas of organic chemistry, heterocyclic compounds take pride of place and form the basis of many of the most useful methods. In recent years there has been particular interest in developing chiral acyl anion equivalents that will show high... 

A -Acyl salts of nitrogen heterocycles phosphorylate in the hetero-ring, rather than at the carbonyl group, to give, for example, (25). The addition of dialkyl phosphites to ynamines has been reported. The products... 

The direct carbonylation of heterocycles with CO and olefins proceeds efficiently. The reaction of pyridine, CO, and 1-hexene in the presence of Ru3(CO)12 at 150 °C gives a-acylated pyridines (Equation (84)).111,llla A number of olefins including ethene and 1-eicosene can be used in this carbonylation reaction. 

An a-allenic sulfonamide undergoes Pd-catalyzed carbonylative cyclization with iodobenzene, affording a mixture of isomeric heterocycles (Scheme 16.12) [17]. The coupling reaction of an allene with a PhCOPdl species takes place at the allenyl central catrbon to form a 2-acyl-Jt-allylpalladium complex, which is attacked by an internal sulfonamide group in an endo mode, affording a mixture of isomeric heterocycles (Scheme 16.13). 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Dimethylbisthiomalonic acid (120), when treated with an acylated enol, produced intermediate 121 thietanediones 122 and 123 then were formed by elimination of thioketone and acetic acid (see Eq. 12). Similarly, cyclobutane-l,l-bisthiolcarboxylic acid gave 123, a previously unknown sulfur analog of malonic anhydride, (Eq. 12). Thermolysis of 120 also results in the formation of the four-membered heterocycles in addition to carbonyl sulfide, hydrogen sulfide, and thiocarbonic acid. ... 

Hydrazinolysis products obtained from oxazolones 528 are versatile synthetic intermediates and can be further elaborated to a variety of different heterocycles depending on the substituents and on the experimental conditions. For example, N-aminoimidazolones 529, isolated from reaction of 528 and hydrazine, have been acylated ° or condensed with carbonyl compounds to produce 530 and 531, respectively. On the other hand, ring-opening 528 with hydrazine affords a dehydroamino acid hydrazide 532. Condensation of 532 with aldehydes yields a hydrazone 533 that can be cyclized to an A -iminoimidazolone 534 (Scheme 7.168). ... 

The carbonyl group is bonded to an sp -hybridized X atom. As a general rule, a threefold barrier should characterize these compounds, and the preferred conformations of the acyl group are not easy to predict since they depend also on the heterocyclic ring conformation. Carbonyl derivatives of... 

In view of this conformational behavior and of the generally accepted properties of three-membered rings to conjugate with unsaturated groups, it seems more appropriate to consider acyl derivatives of these rings in the context of conjugated carbonyl heterocycles than in that of derivatives of saturated carbon. 

From a structural point of view, the N-acyl group in heterocyclic systems is closely related to amides, in which Jr-conjugation between the carbonyl group and nitrogen lone pair imposes a twofold barrier for rotation around the exocyclic C—N bond. The equilibrium distribution of s-cis and s-trans... 

The double bonds in certain heterocyclic compounds, such as furans, Af-acylpyrroles and A-acylindoles are also susceptible to photoaddition of carbonyl compounds to form oxetanes (equation 106) (77JHC1777). A wide range of carbonyl compounds can be used, including quinones, a-diketones, acyl cyanides, perfluorinated aldehydes and ketones and esters. A remarkable case of asymmetric induction in oxetane formation has been reported from optically active menthyl phenylglyoxylate and 2,3-dimethyl-2-butene the oxetane product obtained after hydrolysis of the ester group had an optical purity of 53% (79AG(E)868). 

However, the reactivity of phenolic hydroxy groups can be modified by a fused heterocyclic ring. Thus, hydroxy groups peri to a carbonyl group, e.g. (600), are hydrogen bonded they do not react with diazomethane, and are difficult to acylate. This allows selective reactions in polyhydroxychromones. 

The most important use of 1,3-dithianes (792) stems from their ability to function as acyl anion equivalents (794 Scheme 184). Metallation of this heterocycle followed by alkylation of the anion and cleavage of the dithiane group produces a carbonyl compound. Since such aspects of dithiane chemistry have been extensively documented (69S17 75JOC231), only a few of the more current applications of these heterocycles are highlighted. We again note here that the application of heterocycles to the synthesis of carbonyl compounds has been the sole subject of an extensive review (77H(6)73l). 

The C-acyl heterocycles do not generally form hydrates under acidic or alkaline conditions unless the five-membered ring is also substituted with a second electron-withdrawing group or, as with the trifluoroacetyl and trichloroacetyl derivatives, the carbonyl group is activated to nucleophilic attack. Such activated substituents also undergo the normal reactions with aqueous sodium hydroxide, sodium alkoxide and with amines to give the appropriate... 

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