Halides hetero aromatic

A couple of years ago we have disclosed a new mode of alkyne activation towards isomerization as a detouring outcome of the Sonogashira coupling. As a result of coupling electron deficient (hetero)aryl halides (or a,p-unsaturated p-halo carbonyl compounds) 11 and aryl propargyl alcohols 12 a new access to 1,3-di (hetero)aryl propenones 13, i.e., chalcones, was established (Scheme 9) [77, 78]. The scope for electron deficient (hetero)aromatic halides 11 is fairly broad and even organometallic complexes like 13c can be synthesized by this sequence. 

Besides the mild conditions and excellent chemo- and regioselectivity the scope of this one-pot coupling-cycloaddition isoxazole synthesis is fairly broad. Due to acid chlorides as halide coupling partners, amines and hydroxy groups inevitably need to be protected prior to the reaction. Therefore, the use of acid chlorides 7 is principally limited to (hetero)aromatic compounds and derivatives without ot-hydrogen atoms. As an exception, the cyclopropyl group is tolerated as a... 

The reaction of aryl halides with copper(I) alkynides is known as the Castro reaction (equation 3). The reaction has proved to be particularly important in the synthesis of a wide range of tolan and hetero-aromatic alkynes. Vinyl and allenic halides"" can also be used and several reviews of the reaction have been published. " ... 

In the field of (hetero)aromatic photochemistry substitution reactions are also quite useful. The two most useful classes are the SrnI reaction [16] and SnI reaction [17], involving respectively the aromatic radical anion and the aryl cation as the key intermediates. In the former case, (generally photoinduced) electron transfer generates the radical anion of an aryl halide. With less strongly bonded derivatives (usually iodides) the intermediate cleaves to an aryl radical that gives the new product via a chain process (see Scheme 2.6). 

The dehalogenation of aryl halides was efficiently performed in refluxing THF using a catalytic combination composed of Ni /IMes/i-PrONa. IMes was the most effective NHC, compared to IPr, SIPr, SIMes, ITol, SITol, or ItBu, for the dehalogenation of functionalized aryl chlorides, bromides, iodides and polyhalogenated (hetero)aromatic compounds [eqn (10.2)]. 

The cross-coupling alternative yields halide salts as co-products. During the preparation of aryl halides from the aromatic ring and dihalogen also one equivalent of halide salt is produced and thus there is further room for improvement if we could directly substitute a hydrogen atom by the hetero atoms mentioned ... 

Electrochemical reduction of aromatic halides and subsequent intramolecular reaction of the resulting aromatic cr-radical with another aromatic ring have also been shown to be applicable to formation of a six membered hetero-ring containing nitrogen, though the products are not always directly related with natural alkaloids 33). 

Likewise, upon CIR of electron-deficient (hetero)aryl halides 11 and (hetero)aryl propargyl alcohols 12, and subsequent addition of amidinium salts 32, 2,4,6-trisubstituted pyrimidines 89 can be obtained in a consecutive three-component reaction in good yields (Scheme 48) [241]. Interestingly, in all cases the aromatic products 89 are found and not the expected dihydropyrimidines, regardless whether the reaction has been performed under an anaerobic or an aerobic atmosphere. Therefore, it can be assumed that the presence of the transition metal catalysts is beneficial for a terminal aromatizing dehydrogenation. 

Interestingly, the mild reaction conditions of the CIR are fully compatible with the Stetter reaction. As a result a sequence of transition metal, base and organoca-talysis can be easily conceived. Upon CIR of electron-deficient (hetero)aryl halides 11 and (hetero)aryl propargyl alcohols 12, and after subsequent addition of aliphatic or aromatic aldehydes 92 and catalytic amounts of thiazolium salt 93 1,4-diketones 94 are obtained in moderate to excellent yields in a one-pot procedure (Scheme 50) [259, 260]. For aromatic aldehydes the catalyst precursor of choice is 3,4-dimethyl-5-(2-hydroxyethyl) thiazolium iodide (93a) (R = Me), and for aliphatic aldehydes 3-benzyl-4-methyl-5-(2-hydroxyethyl)-thiazolium chloride (93b) (R = CH2Ph) is applied. 

Lithiobenzothiophenes can be generated, and reacted with electrophiles, if the temperature is kept low. Direct deprotonation of benzothiophenes follows the usual pattern for five-membered heterocycles and takes place adjacent to the hetero atom, and in concord with this pattern, metal-halogen exchange processes favour a 2- over a 3-halogen. 2-Trialkylstannylbenzofurans are useful for palladium-catalysed coupling with aromatic halides. ... 

Carbopalladation of Arynes by Arylpalladium Complexes Pd-Catalyzed Annulation Reactions of Arynes. Whereas the Pd-catalyzed annulation of alkynes by aiyl halides has proven to be an effective method for the construction of a wide variety of hetero- and carbocycles similar carbopalladation of arynes were unprecedented until Larock and Zhang reported the synthesis of flu-oren-9-ones 115 through the annulation of arynes by o-haloarenecarboxaldehydes (Scheme 12.57) [100]. Larock s group has also developed a Pd-catalyzed annulation of arynes by 2-halobiaryls, affording polycyclic aromatic and hetCToaromatic compounds such as 116 from simple starting materials. Larock and Cheng have independently reported the related double annulation of arynes by simple aryl halides as an efficient route to functionalized triphenylenes (Scheme 12.57) [101]. 

Abstract The selective catalytic activation/functionalization of sp C-H bonds is expected to improve synthesis methods by better step number and atom economy. This chapter describes the recent achievements of ruthenium(II) catalysed transformations of sp C-H bonds for cross-coupled C-C bond formation. First arylation and heteroarylation with aromatic halides of a variety of (hetero)arenes, that are directed at ortho position by heterocycle or imine groups, are presented. The role of carboxylate partners is shown for Ru(II) catalysts that are able to operate profitably in water and to selectively produce diarylated or monoarylated products. The alkylation of (hetero)arenes with primary and secondary alkylhalides, and by hydroarylation of alkene C=C bonds is presented. The recent access to functional alkenes via oxidative dehydrogenative functionalization of C-H bonds with alkenes first, and then with alkynes, is shown to be catalysed by a Ru(ll) species associated with a silver salt in the presence of an oxidant such as Cu(OAc)2. Finally the catalytic oxidative annulations with alkynes to rapidly form a variety of heterocycles are described by initial activation of C-H followed by that of N-H or O-H bonds and by formation of a second C-C bond on reaction with C=0, C=N, and sp C-H bonds. Most catalytic cycles leading from C-H to C-C bond are discussed. 

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