Tandem multicomponent

Synthesis and biological evaluation as microtubule-active agents of several tetrahydrofiiran and spiroacetal derivatives 13CMD1173. Tandem multicomponent reactions toward the des p and synthesis of novel polysubstituted imidazopyridines and imidazopyrazines as antibacterial and cytotoxic motifs 13CMD1445. 

S. Fustero, P. Bello, J. Mird, A. Sim6n, C. del Pozo, Chem.-Eur. J. 2012, 18, 10991-10997. 1,7-Octadiene-assisted tandem multicomponent cross-enyne metathesis (CEYM)-Diels-Alder reactions a useful alternative to Mori s condition. 

In general, DOS demands well-defined, selective reactions that are still able to introduce a significant degree of complexity and diversity. Multicomponent and tandem processes fit this profile very well [65, 66], and several groups have used this approach [41, 67-71]. 

Banfi L, Basso A, Guanti G, Lecinska P, Riva R (2008) Multicomponent synthesis of benzoxazinones via tandem Ugi/Mitsunobu reactions an unexpected cine-substitution. Mol Div 12 187-190... 

Banfi L, Basso A, Guanti G, Riva R (2003) Application of tandem Ugi reaction/ring-closing metathesis in multicomponent synthesis of unsaturated nine-memhered lactams. Tetrahedron Lett 44 7655-7658... 

Many of the recent advances in synthetic applications of allylic boron reagents have focused on the use of these reagents as key components of tandem reactions and one-pot sequential processes, including multicomponent reactions. The following examples briefly illustrate the range of possibilities. Most cases involve masked allylboronates as substrates, and the tandem process is usually terminated by the allylboration step. 

In view of the multicomponent nature of the tandem [4 + 2] / [3 + 2] cycloaddition, the potential for a combinatorial approach to the synthesis of nitroso acetals has been investigated on solid-phase supports. The incorporation of either the dipolarophile or the starting nitroalkene on a Wang-type resin is compatible with the tandem cycloaddition promoted at high pressures (Schemes 2.28 and 2.29). The solid-supported nitroso acetals are subsequently liberated (in moderate yields from the staring nitroalkene) upon the addition of a catalytic amount of potassium cyanide in triethylamine and methanol or by reduction with lithium aluminum hydride (LAH) (261,264). 

If both heat effects and effects of multicomponent adsorption are important, can the SSMTZ program (which can handle multicomponent effects but not effects of heat transfer) and the SSHTZ program (which can handle heat effects but is limited to binary mixtures) be used in tandem to extract mass transfer information in a quantitative manner ... 

Wu, S. T., Xia, Y. Q., and Jemal, M. (2007). High-field asymmetric waveform ion mobility spectrometry coupled with liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-FAIMS-MS/MS) multicomponent bioanalytical method development, performance evaluation and demonstration of the constancy of the compensation voltage with change of mobile phase composition or flow rate. Rapid Commun. Mass Spectrom. 21 3667-3676. 

This multicomponent reaction was used by the same group to prepare a ring-expanded analogue 114 of the marine sesquiterpenoid frondosin B through a remarkable reaction cascade [102]. An unprecedented tandem 1,7-hydrogen shift, 8 7r-electrocyclization converting 112 to 113 was proposed to explain the formation of this ring-expanded species (Scheme 8.47). 

Multicomponent tandem addition reactions have been investigated by Russell and coworkers. Addition of t-butyl radical to the allyl acrylate 70 with termination from dimethyldisulfide furnishes butyrolactone 71 as a diastereomeric mixture (remote center). However, the ring junction stereochemistry is exclusively trans [95JA3645],... 

The great majority of radical cascades involve sequences of intramolecular steps where the overall propagation is a unimolecular process (with the exclusion of the initiation and termination steps), and recent overviews are given in Refs 1-5. However, meanwhile many tandem reactions involving both intra- and intermolecular steps, as well as multicomponent tandem reactions, have been reported in the literature, which are compiled in recent reviews. " ... 

An efficient multicomponent tandem reaction has been described by Tu and co-workers [161] to access benzothiazepinones 112 in excellent yields in aqueous media. The reaction is easy to perform using inexpensive starting materials such as... 

In contrast, with its intrinsically higher selectivity, tandem mass spectrometry offers a much more effective and practical approach for multicomponent quantitation. This translates into faster method development and, ultimately, rapid and reliable multicomponent quantitation. The routine application of multicomponent quantitation to 5 or 10 compounds in a cassette can be developed in 1 or 2 days, offering typical quantitation range of 5 to 5000 ng/mL. The variability of the assay procedure ranges from 10 to 20%, which is less than the typical intersubject pharmacokinetic variability of 25 to 30%. 

JW Metzger, C Kempter, K-H Wiesmuller, G Jung. Electrospray mass spectrometry and tandem mass spectrometry of synthetic multicomponent peptide mixtures determination of composition and purity. Anal Biochem 219 261-277, 1994. 

Due to their high atom economy, multicomponent reactions have emerged with a high potential in the fine chemicals and pharmaceutical industries [41]. These reactions are usually not concerted rather, they are tandem or domino processes in which multiple reactions are combined into one synthetic operation. This significantly reduces reaction time as well as the amount of waste in comparison to an alternative multistep synthetic process. The first step produces an intermediate that need not be isolated, but it must undergo a sequence of reactions until the stable... 

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