1,2,3-triazoles, fully substitute

Fully substituted triazoles were synthesized via the four-component coupling reaction of the unactivated silylacetylenes 50, two equivalents of allyl carbonates 5b, and trimethylsilyl azide 42 in the presence of a Pd(0)-Cu(I) bimetallic catalyst (Scheme 18) [54], Various trisubstituted 1,2,3-triazoles were obtained in good yields. The reaction most probably proceeds through the formation of alkynylcopper species 52, which on cross-coupling reaction with the 7r-allylpalladium complex 53 gives the products 51. 

The potential for sequential copper-catalyzed processes can also be illustrated in the case of formation of fully substituted 1,2,3-triazoles. In this sequence, the same copper catalyst is promoting two distinct types of catalysis [3+2]-cycloaddition and arylation via C-H activation. Each reaction type tolerates both electron-rich and -poor substrates, as well as steric hindrance, adding noteworthy breadth to this scheme. A 4-component sequence using NaNs, rather than an alkyl azide, is shown below. The diamine DMEDA (W.W -dimethylethylenediamine) is used to stabilize the copper catalyst. 

As 1,4-disubstituted 1,2,3-triazoles are usually prepared through copper-catalyzed 1,3-dipolar cycloadditions of terminal alkynes with organic azides, the use of a single copper complex for a direct arylation-based sequential catalysis was probed. Thereby, a modular chemo- and regioselective synthesis of fully-substituted 1,2,3-triazoles was achieved (Scheme 9.43). Notably, the overall reaction involved the selective coupUng of four components through the formation of one C—C- and three C—N-bonds [58]. 

The most commonly apphed method to determine a SPAAC reaction rate constant is by NMR [1]. To this end, a cyclooctyne and an azide are mixed in a deuterated solvent and formation of product is quantified by integration of diagnostic peaks of the formed triazole product. Given the fact that the triazole ring itself is fully substituted, other diagnostic protons in the product with a unique, non-... 

S.2.2.3 MCRs Involving Triazol-5-ylidenes as Key Components MCRs involving triazol-5-ylidenes V are more difficult as a result of the diminished nucleophiUcity of these carbenes compared with previously described thia-zol-2-ylidenes II and imidazol-2-yUdenes ID. However, the importance of triazole moieties in relevant organic compounds has encouraged the use of triazole carbenes as key components in MCRs. To this aim, the reaction of triazol-5-ylidene V, DMAD, and different aromatic aldehydes provided fully substituted furanone derivatives 25 [21]... 

SCHEME 7.12 Nonsequential cascade synthesis of fully substituted triazoles. 

The Ruthenium-Catalyzed Azide-Alkyne Cycloaddition (RuAAC) complements the well-established CuAAC reaction, as the formation of 1,5-substituted triazoles (instead of 1,4-substituted 1,2,3-triazoles) can be achieved with high regioselectivity. In contrast to the CuAAC reaction, triazoles that are synthesized via RuAAC reaction can be formed from terminal as well as internal alkynes. This offers the possibility of the formation of fully-substituted triazoles. 

Copper(I) chloride can be an effective catalyst in multicomponent reactions, such as in the synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydrop3nimidine-2-(l//)-ones, the synthesis of quinoline derivatives (eq 69), and the synthesis of fully substituted triazoles. The use of CuCl as an additive is also reported in cross-metathesis reactions leading to significant turnover enhancement. ... 

Ackermann L, Potukuchi HK (2010) Regioselective syntheses of fully-substituted 1,2,3-triazoles the CuAAC/C-H bond functionalization. Org Biomol Chem 8(20) 4503-4513... 

Later, Ru(II)-catalyzed azide-alkyne cycloaddition reaction (RuAAC) was developed for the regiospecific synthesis of isomeric 1,5-disubstituted 1,2,3-triazoles 4 (Scheme 4.1c) [3]. Unlike CuAAC reaction, which worked only on terminal alkynes, RuAAC was successfully applied to internal alkynes, thus giving access to fully substituted 1,2,3-triazole derivatives also. 

The authors supported the reaction with a possible mechanism via an iminium intermediate (Scheme 4.40). In the first step, the a,p-unsaturated ketone 102a reacts with the catalyst piperidine 103 to generate the iminium intermediate A. Cycloaddition between the iminium species A and the azide 15 generated the triazoline intermediate B, which on hydrolysis of the iminium center and subsequent air oxidation of the triazoline moiety in C resulted in the formation of the fully substituted triazole 104e. 

Tanimoto et al. described a regioselective rapid triazole synthesis at low temperature. Organic azides and propargyl cations generated by acids from alcohols 121 furnished fully substituted 1//-1,2,3-triazoles 122 (Scheme 4.46) [47]. Most reactions were reported to be performed within 5 min not only at room temperature but also at -90 °C. Both terminal and internal alkynes were acceptable, and... 

The aromaticity of 1,2,4-triazoles has been investigated and quantified using the harmonic oscillator model of aromaticity (HOMA) index, where a value of 1 is assigned to a molecule that is fully aromatic, 0 for a nonaromatic molecule, and a negative value for a molecule that is antiaromatic the data obtained were compared to other small-molecule heteroaromatics. It was determined that different tautomers of substituted and unsubstitued 1,2,4-triazoles have individual HOMA indices <2000JST(524)151>. 

This is consistent with the relative values for Dq(Ni2+) (1160 and 1170 cm-1 for 23 and 24, respectively) [36]. For 2-(l,2,4-triazol-3-yl)pyridine 26 Dq(Ni2+) is somewhat smaller,1130 cm-1, and for this and certain substituted derivatives the spin transitions in the [Fe N6]2+ derivatives are observed below room temperature [29]. This and related triazole systems are discussed more fully in chapter 5 by van Koningsbruggen. 

Hydrazones (93) derived from the condensation of various aldehydes and 3-substituted 4-amino-3-sulfonyl[l,2,4]triazoles, on oxidative cyclization, afford the corresponding fully conjugated heterocycles (95) (Table 9 and Equation (23)). 

These are not well studied. Of the six possible isomers, 82-87, only the C-C linked isomer, 4,4 -bi-l,2,3,-triazole (87), is known. It was prepared as outlined in Scheme 33 and fully characterized by spectral methods (89CB1175). Substituted derivatives have been known for some time... 

Despite its success as an anticancer drug, the mechanism by which the drug targets DNA in the body is not fully understood, although it is known that the nucleobase guanine (see Fig. 10.13) binds more readily to Pt(ll) than the other nucleobases in DNA. Among model studies reported is that of the reactions of cisplatin and three related complexes with L-histidine and 1,2,4-triazole (Nu). The ligand substitutions occur in two, reversible steps ... 

The use of AB2 monomers containing an internal triple bond as A-unit and two azides as B-units for the synthesis of hyperbranched polymers was developed by the same group (Figure 8.7) (Scheel et al., 2004). Hyperbranched polymers containing a mixture of 1,4- and 1,5-substituted triazoles were obtained, as the internal alkynes can only react via the classical thermal induced 1,3-dipolar cycloaddition reaction. However, it was possible to synthesize fully soluble products by low-temperature (45 °C) autopolymerization in bulk. The end product contains a large number of reactive azide functionalities that can be further postfunctionalized by CuAAC reaction with the desired alkyne-containing compound. 

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