Formation of heterocycles

Institutfur Organische Chemie, Universitdt Karlsruhe (TH), Fritz-Haber-Weg 6, D-76131, 

The intramolecular Mizoroki-Heck reaction, although it had been known since 1977, when it was first used in the synthesis of heterocycles [7], started to be explored properly only around the mid 1980s. Its large use for the preparation of carbocycles began only in the late 1980s [8]. Since then, however, there has been a tremendous increase of interest in this intramolecular cyclization, culminating in its widespread utilization in total synthesis [9], This was mostly due to the development of asymmetric versions by two major contributors, namely Overman for the construction of heterocycles [9] (Chapter 12) and Shibasaki focusing on carbocyclic systems [10] (Chapter 16). 

The formation of heterocycles by intramolecular Mizoroki-Heck reactions has been reviewed several times as a specific topic [11-16]. In this chapter, a classification by ting size has been established. The examples in the different subsections are organized according to specific substructures of the starting materials and according to types of heteroatom. 

The Mizoroki-Heck Reaction Edited by Martin Oestreich 2009 John Wiley Sons. Ltd. ISBN 978-0-470-03394-4 

The proper asymmetric synthesis of heterocycles via the Mizoroki-Heck reaction will be dealt with in Chapters 12 and 16. 

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The formation of heterocycles derived from quinones is an important synthetic technique. The reaction may be intramolecular, eg, the reaction of (92). Either nitrogen products, eg (93) (yields of 85—91% for R = H, CH, and C H ) or oxygen products (94) are obtained (92,93). Reactions with enamines have been especially important. 

A.4 Reactions with heterocyclic compounds and formation of heterocycles... 

By far the commonest reagents for the formation of heterocyclic quaternary salts are the alkyl halides, and, indeed, methiodides out-... 

The importance of the solvent, in many cases an excess of the quatemizing reagent, in the formation of heterocyclic salts was recognized early. The function of dielectric constants and other more detailed influences on quatemization are dealt with in Section VI, but a consideration of the subject from a preparative standpoint is presented here. Methanol and ethanol are used frequently as solvents, and acetone,chloroform, acetonitrile, nitrobenzene, and dimethyl-formamide have been used successfully. The last two solvents were among those considered by Coleman and Fuoss in their search for a suitable solvent for kinetic experiments both solvents gave rise to side reactions when used for the reaction of pyridine with i-butyl bromide. Their observation with nitrobenzene is unexpected, and no other workers have reported difficulties. However, tetramethylene sulfone, 2,4-dimethylsulfolane, ethylene and propylene carbonates, and salicylaldehyde were satisfactory, giving relatively rapid reactions and clean products. Ethylene dichloride, used quite frequently for Friedel-Crafts reactions, would be expected to be a useful solvent but has only recently been used for quatemization reactions. ... 

Aromatic carbon-heteroatom coupling reactions with participation and formation of heterocycles 98JCS(P1)2615. 

Formation of heterocycles in reactions with participation of stoichiometric transition metal complexes 98JCS(P1)819, 99JCS(P1)223. 

Nonlinear dependence between ee values of chiral auxiliary compound or ligand and product of reaction with participation or formation of heterocycle 98AG(E)2922. 

Intramolecular cycloaddition reactions of allylic cations with participation and/ or formation of heterocycles, mainly [4+3]-cycloaddition to furan system 97T6235. 

Metal-assisted cycloaddition in formation of heterocycles 97CRV523. 

Disposable formation of heterocycles in complex organic syntheses 98T2289. 

Metal-catalyzed hydrometallations in formation of heterocycles 98PAC1059. 

Microwave activation in phase-transfer catalysis of formation of heterocycles 99T10851. 

Novel solvent-free organic reactions using focused microwaves with formation of heterocycles 98S1213. 

Solid-state photoreactions in two-component crystals with formation of heterocycles 98S1. 

Formation of heterocycles by intramolecular catalytic asymmetric cyclopropa-nation 98T7919. 

Formation of heterocycles in reactions using organozinc reagents 96MI8. 

Use of bis(trimethylsilyl)acetamide and bis(trimethylsilyl)urea for protection and as control reagents in reactions with formation of heterocycles 98S357. 

Transition metal-catalyzed cyclizations accompanied by multiple bond migration with formation of heterocycles 98SL1. 

Miscellaneous reactions in neutral ionic liquids Kitazume et al. have also investigated the use of [EDBU][OTf as a medium in the formation of heterocyclic compounds [58]. Compounds such as 2-hydroxymethylaniline readily condense with... 

A useful route to 2,1,3-benzothiadiazoles is the F -catalyzed cyclization of l-(4-X-C6F4)-3-trimethylsilyl-l, 3-diaza-2-thiallenes [90JFC(50)359]. Fluoride ion catalysis is also used in the formation of heterocycles from pentafluorobenzoyl and -phenoxy compounds (81BCJ3447). Pentafluoro-phenylcarbonimidoyl dichloride with primary amines gave guanidines,... 

Synthesis by Formation of Heterocyclic Ring Main Features... 

Among the many applications of cyclodehydration to the formation of heterocyclic systems is the Bischler-Napieralski reaction. In this reaction, amides of the type 35 are cyclized with phosphorous oxychloride ... 

In a series of three papers, Noguchi and co-workers have reported their continuing studies on the formation of heterocycle-fused azepine systems <96X13081, 96X13097, 96X13111>. A typical example is the conversion of the aldehyde 15 into the azepines 16 and 17 (Scheme 3). Xhe reaction also proceeds with imines when the dihydroazepine prior to bridging can be isolated. Mechanistic and stereochemical aspects of the reaction have been explored. 

The reductive alkylation of DAP with acetone led to high conversions and selectivity to the dialkylated product over Al, Bl, and BS2 catalysts. The ASl catalyst, which typically has lower activity than the Al or Pt-based catalysts showed greater formation of heterocycles. These results indicate that a more active catalyst, a shorter reaction time, a higher operating temperature, or sterically hindered amines/ketones will help minimize the formation of the heterocycles. Similar high selectivities were obtained with DAP-MIBK reaction over BSl and BS2 catalysts with no heterocycles being formed. However, over Al, the undesired heterocyclic compound was over 15%. This indicates that the reaction between diamines and ketones has a significant potential to form heterocyclic compounds unless the interaction between these is kept to a minimum by the use of a continuous flow reactor as proposed by Speranza et al. (16) or by other methods. 

Nitro compounds have also been reported to undergo photocyclizations. The intermediacy of an isoxazoline in the photorearrangement of o-nitro-benzaldehyde to o-nitrosobenzoic acid is now in doubt,318 but intramolecular hydrogen abstraction by an excited nitro group in nitrobenzene derivatives can result in the formation of heterocycles. 4-tm-Butyl-3-methoxy-2,6-dinitrotoluene (384) on irradiation in methanolic sodium hydroxide solution... 

Intermolecular cyclization of allyloxycarbonylphosphines in the presence of azabisisobutyronitrile also results in the formation of heterocycles containing the P—C—O fragment (11) [Eq. (9)] (82ZN965). 

Scheme 9. Formation of heterocyclic stibino- and bismuthinoalanes by dehydrosilylation...

This chapter deals with thermal ring-closure reactions of dienes and polyenes resulting in carbocyclic compounds the formation of heterocycles is mentioned only occasionally. The account is highly selective, concentrating on recent work, since two comprehensive general reviews have appeared1,2. Other pertinent reviews are cited at appropriate places in the text. 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

By analogy with the intramolecular insertion of phenylthiocarbenes, the reaction of (oo-oxido)diazoalkanes 93 resulted in the formation of cycloalkenes 94.38 However, the reaction was proven to proceed not via a carbene route b but a nitrene route a as shown in Scheme 26. The nitrene route is supported by the formation of heterocyclic products 98 and 99.39 This insertion reaction was used in the cydization step to the cyclopentene ring formation of isocarbacycline 97.40... 

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