Amines as Building Blocks

SCHEME 3.17 Palladium-catalyzed synthesis of l-allyl-2-alkynylbenzenes and o-aUylbiaryls. 

The same group reported shortly after the use of potassium bisulfite as a convenient equivalent of sulfur dioxide for the coupling with aryl iodides or bromides and hydrazines. A wide range of aryl A-aminosulfonamides were prepared in good yields using Pd(OAc)2/PtBu3 as the catalyst [43]. 

2 Amines in Reactions Based on Buchwald Hartwig Aminativn A number of strategies of indole derivatives 

Based on the aforementioned amination process, Xi developed a one-pot synthesis of 2-alkynylindoles 36 involving the multicomponent coupling of o-bromo-(2,2-dibromovinyl)ben-zenes 35, arylamines, and terminal alkynes. The reaction is proposed to proceed through a Pd-catalyzed Sonogashira coupling leading to a monoalkynylated product XIV, followed by an intermolecular Buchwald-Hartwig amination to XV and a 

SCHEME 3.18 Palladium-catalyzed carbocyclization of aryl iodides, bicyclic alkenes, and arynes. Synthesis of annulated 9,10-dihydro-phenanthrenes. 

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A further development in the coumarin series is the use of derivatives of 3-phenyl-7-aminocoumarin ((13) where R, R = Cl or substituted amines) as building blocks for a series of light-stable brighteners for various plastics and synthetic fibers, and, as the quatemi2ed compounds, for brightening polyacrylonitrile (62). 

The same nucleophilic substitution chemistry can be manipulated by means of microwave irradiation to afford a variety of cyclic amines as building blocks in natural product syntheses via double V -alkylation of primary amines (Scheme 11). The protocol circumvents the difficulty associated with running multi-step reactions to assemble Y -aryl azacycloalkanes and avoids the use of expensive metal catalysts in building aryl C-N bonds. Further, reactive functional groups, such as carbonyl, ester, and hydroxyl, remain unaffected under these mild reaction conditions. The V-alkylation reaction is now extended to hydrazines as well. ... 

Selectivity and reactivity of mixed anhydrides toward primary and secondary aliphatic and aromatic amines has been studied in details [42, 43] (equation 22) Fluorocarboxyhc acids and then denvahves are used as building blocks m condensa non reactions widi dmucleophihc species for the synthesis of fluoroalkyl-subshtuted lieteroaromahc systems [S 9, 40, 44, 45, 46, 47 4S] (equations 20 21, and 23)... 

Many pharmacologically active compounds have been synthesized using 5-bromoisoquinoline or 5-bromo-8-nitroisoquinoline as building blocks.6 7 8 9 10 11 The haloaromatics participate in transition-metal couplings 81012 and Grignard reactions. The readily reduced nitro group of 5-bromo-8-nitroisoquinoline provides access to an aromatic amine, one of the most versatile functional groups. In addition to N-alkylation, TV-acylation and diazotiation, the amine may be utilized to direct electrophiles into the orthoposition. 

The dicyanoaurate anion [Au(CN)2] is one of the most simple molecules that show aurophilic interactions,2282-2284 and thus has been used as building blocks to obtain supramolecular structures as in the complexes of Cu11 with [Au(CN)2]- and different amines.2285-2 7 It has been found that solutions of K[Au(CN)2] in water and methanol exhibit a strong photoluminescence.2288 Also... 

The discovery of this lead compound as a potent PDF inhibitor was a result of an integrated combinatorial and medicinal chemistry approach based on the proposed generic PDF inhibitor structure. This focused chemical library was designed by Chen et al. [79], and was prepared using solid-phase parallel synthesis in which 22 amines and 24 amino acids were used as building blocks, as outlined in Scheme 23. 

Computational methods described in this work are tested using a tripeptoid combinatorial library described by Zuckermann et al. (35). These authors described chemical structures of 24 amines used as building blocks for the pep-toid synthesis. The common Markush structure of tripeptoids is shown in Fig. 3 where R1, R2, and R3 are the alkyl portions of primary amines used as building blocks. The structures of the building blocks are shown in Fig. 4 and we followed the abbreviations used in the original publication. 

Because of its bulky, inflexible, and hydrophobic side chain, terf-leucine (2-amino-3,3-dimethylbutanoic acid, Tie) is an important amino acid used as template or catalyst compound in asymmetric synthesis and in peptidic medicinal compounds. L-Tle has attracted much attention as a key component of newly emerged drugs or as building block of ligands, catalysts, and auxiliaries for asymmetric synthesis. It is synthesized in ton-scale by reductive amination of trimethylpyruvic acid by means of LeuDH from Bacillus stearothermophilus with very high yield and excellent optical purity [153]. NADH, which is consumed during the reaction, can be regenerated by FDH from C. boidinii (Fig. 35). 

Borylated ferrocenes have been exploited by Wagner as building blocks for the assembly of macrocycles and coordination polymers (Scheme 15). Treatment of the diborylated ferrocene l,L-fc(BMe2)2 with the bifunctional aromatic amines pyrazine and 4,4 -bipyridine, respectively, led to spontaneous and reversible formation of (89) and related ferrocenylborane polymers.The polymeric nature of... 

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