Synthesis of starting materials

Reactions of this type include the major early methods used by Debus,22 Radziszewski,23 Weidenhagen,24 and Maquenne.25 All these suffer from deficiencies such as difficulty of synthesis of starting materials, low yields, and, more often than not, from the formation of mixtures of products which require tedious separation. Among recent modifications26 27 of the Maquenne method is the preparation of dialkyl 4,5-imidazole dicarboxylates in yields of 45-65 % by treatment of a dialkyltartrate dinitrate with either an aliphatic aldehyde or a formaldehyde precursor, in the presence of ammonium ions at pH 3.5-6.5. 

The structural novelty and various biological activities elicited by this compound prompted the synthesis of 138 by different workers following different strategies. Some of the successful reports are described here. Banwell et al. reported the synthesis of ( )-aiphanol (154) based on the standard procedures of Stermitz s modification (124). A mixture of ( )-138, its regioisomer (157), and their stereoisomers 158 and 159 was obtained by treatment of the stilbene, piceatannol (144), and 4-hydroxy-3,5-dimethoxyciimamyl alcohol (156) with silver carbonate in ace-tone-benzene (755). The reaction steps for the synthesis of starting materials 144 and 156, and their oxidative coupling steps are shown in Schemes 9a, 9b, and 9c. 

Although all of these methods suffered from deficiencies (difficulties of synthesis of starting materials, low yields, and more often than not the formation of mixtures of products requiring tedious separation procedures), they still find ample application for the preparation of many C-substituted imidazoles (e.g. 4-alkyl, 4,5-dialkyl, 2,4,5-trialkyl). The old Debus (or Radziszewski) method is still useful for preparing such compounds as 4-methyl- (132) and 2,4-dimethyl-imidazoles (133) using pyruvaldehyde (Scheme 71). However, alkaline fission of the pyruvaldehyde can result in a mixture of products. When pyruvaldehyde is treated alone with aqueous ammonia there are three main products (132), (133) and 2-acetyl-4-methylimidazole. Reversed aldol condensations cause degradation of the pyruvaldehyde, and subsequent cyclization of the fragments as in Schemes 71 and 72 accounts for the products. 

Figure 19-5. Synthesis of starting material 6-benzyloxy-3,5-dihydroxy-...

After the structure of the bacterial cell wall became known, it was possible to determine the chemistry of its biosynthesis. For convenience the steps involved will be divided into three stages synthesis of starting materials (precursors), transfer of precursors to membrane-bound anchor, and polymerization of the netlike cell wall by cross-linking outside the cytoplasmic membrane. 

The author is indebted to Richard Gencarelli for his assistance and synthesis of starting materials and to Uniroyal Chemical for permission to publish this work. 

In contrast to the alkynylation of acidic C-H bonds which can also be achieved using alkynyliodonium salts, the direct C-H functionalization of aromatic compounds or olefins has never been realized with this class of reagents so far. However, after several unsuccessful attempts using palladium or copper catalysts and alkynyliodonium salts for the alkynylation of heterocycles, Waser and Brand reported in 2009 the first efficient alkynylation of indoles using TIPS-EBX 52 and AuCl as catalyst (Scheme 18) [117]. With indole, selective C3-aIkynylation was obtained. The reaction was tolerant to many functional groups such as bromides, acids, or alcohols. The method was already used in the synthesis of starting materials for Friedel-Crafts reactions of aminocyclopropanes [118] and for hydroamidation to access indole c -enamides [119]. In 2010, Nevado and de Haro demonstrated that alkynylation was also possible using directly terminal propiolic ester derivatives and (diacetoxyiodo)benzene as co-oxidant [120]. 

Synthesis of starting material of the reaction in original paper. 

Scheme 1.32) [156]. Cu(II)-promoted intramolecular [2+2] cycloaddition of 1,4-diallenes 202 yielded bicyclooactadienes 204 however, under uncatalyzed thermal conditions, the authors noted that the formal [3,3]-sigmatropic rearrangement product, [4]dendralene 203, was formed m 50% yield. If optimized, this presents a nice method to form unsymmetrical [4]dendralenes, but relies on a lengthy synthesis of starting materials. 

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