Substrate, high activity

Although diselenonium-, ditelluronium- and mixed sulfonium-selenonium dications can exhibit either oxidative or electrophilic properties in reactions with nucleophiles, substitution at the onium chalcogen atom is more typical.96 Owing to the increased stability of heavier dichalcogenium-dications, they react only with highly activated substrates such as aniline and tV,A-dimethylaniline, while no reaction is observed with phenol and diphenylamine.113 Reactions of ditelluronium dications with activated aromatics are also not known (Scheme 44).114... 

A similar but conceptually distinct approach to difunctionalization of terminal alkynes consists of sequential carboboration-palladium-catalyzed cross-coupling 137 equation (33) illustrates that this method also provides alkenes of high stereochemical purity by net syn Markovnikov addition. Benzyne-contain-ing molecules can act as highly activated substrates for vicinal difunctionalizations initiated by nucleophiles 138-140 thus, nucleophilic addition-electrophilic trapping can serve as an alternative to sequential directed metallation for the production of 1,2-disubstituted and 1,2,3-trisubstituted aromatic systems (equation 34).141... 

Nitration with tetranitromethane proceeds along the ion radical route. Tetranitromethane is a smooth nitrating agent and a mild oxidizer. It is convenient for the nitration of highly activated substrates such as phenols, azulene, heterocycles in the presence of pyridine, N,N-dialkylaniline, and other bases. As shown (Morkovnik 1988), these reactions include the... 

Derivatizations in the N-terminal sequence of human angiotensinogen led to weakly active renin inhibitors 183). According to Szelke et al.l84), highly active substrate analogs with modified peptide linkage ( CH2 NH—) were formed by reduction of the CO—NH bond in Leu-Leu or Phe-Phe (Table 2). 

In 1995 Ciganek reported an intramolecular version of the Stetter reaction (Ciganek 1995). 2-Formyl phenoxycrotonates and -acrylates 137 have been shown to be highly active substrates for the Stetter reaction. The reactivity of the substrates was considerably enhanced may be due to entropic factors. The reaction also proceeds in the absence of triethy-lamine as base. The catalyst is presumably activated by DMF taking the place of the amine. 

We used triazolium salt 7 as the catalyst for the intramolecular Stetter reaction of 2-formylphenoxycrotonates 11 affording the corresponding 4-chromanones 12 [49], since these were known to be highly active substrates in the non-enan-tioselective thiazolium-catalyzed Stetter reaction [50] (Scheme 7). Apparently, the entropically favorable proximity of the reacting functionalities leads to a strong enhancement of the reactivity. 

Later in 2010, Movassaghi et al. proposed an alternative synthesis for (+)-chaetocin A (677) as well as syntheses for the epipolythiodiketopiperazines (+)-chaetoxin C (693) and (+)-12,12 -dideoxychetracin A (694) (432). These were the first reports on the preparation of high-order polysulfides. Studies have shown that the polysulfide bridge is important for the biological activity of these compotmds and that potency increases with the number of sulfur atoms incorporated (433). Therefore, the versatile construction of this scaffold might lead to highly active substrates. 

Ene reactions and carbonyl-ene reactions are synthetically interesting reactions and one of the most direct approaches for aUyl functionalizations. However, the often high activation energy for these reaction requires highly activated substrates and/or high temperatures that is a strongly limitation to these reactions. This also limits the application of in asymmetric catalysis and majority of these reactions developed so far are asymmetric Lewis acid catalyzed carbonyl-ene reactions [84]. 

Comparison of the effects of different sources of ultrasound are few and far between. An exception is a study of the copper-catalysed Ullman coupling of 2-iodonitrobenzene in DMF [45] (Scheme 3). The original reaction was first described by Rausch in 1961 [46] and uses a highly activated substrate, such that the thermal reaction only takes 60 h at 60 °C. It should be noted that this represents one of the lowest temperatures and highest yields reported for a classical Ullman reaction. 

Cyclic A-sulfinyliminium salts 72 are another new type of highly activated substrates for aluminum acetylide additions and were also introduced by Royer... 

A highly active substrate (533) has been converted into an inhibitor (534) by Burke el al. (Scheme 133). The inhibitor showed a significant inhibition of intracellular Yersinia pestis replication at a non-cytotoxic concentration. ... 

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