Four center condensation

Concerted reactions, four-center, characteristics, 1, 123 Condensation reactions... 

Isotopic mixing experiments with the isomeric compounds methylacetylene (propyne) and allene showed that a four-center intermediate is important in many of their condensation reactions. The intermediate complex (C6H4D4) loses preferentially C2H2D2... 

Our historical account would be incomplete without a few words about the surprisingly original four center condensation (4CC) method of Ivar Ugi [60]. The reaction of an acylamino acid, or peptide with an amine, an aldehyde and an isonitrile leads to a peptide derivative... 

Weygand s successor, Ivar Ugi, invented the perhaps most surprising approach to peptide bond formation, the four-center-condensation (4CC) procedure. His principal coworker, D. Marquarding (1934-1982) is remembered here. 

Enders et al. [75] developed a synthesis of polyfunctionalized 3-(cyclohex-enylmethyl)-indoles 125 via a quadruple domino Friedel-Crafts-type Michael-Michael-aldol condensation reaction, in 2010. This cascade sequence is initiated by a Friedel-Crafts reaction of indole (126) by an iminium activation mode to the enal, followed sequentially by an enamine- and an iminium-mediated Michael addition. After an intramolecular aldol-condensation, four C-C bonds are formed and the domino product is constructed bearing three contiguous stereogenic centers (Scheme 10.34). 

MD studies on B and Z forms of DNA with explicit waters and explicit counterions were reported by Swamy and Clementi.i G-C and A-T decamer sequences in their B forms were surrounded by a rectangular box with 1500 water molecules and 20 K+ ions. In addition, a G-C dodecamer in its Z form with 1851 water molecules and 24 K+ ions was studied. Water molecules in these studies were four-centered MCY waters. These simulations were carried out for a total of 7 ps, with the first 3 ps serving as an equilibration period. The DNA in all cases was rigid, and only the ions and the waters were allowed to execute motions. The dynamical behavior of those ions showed them to be strongly bound to the DNA with restricted mobilities, a conclusion different from what counterion condensation theory and other simulations tend to suggest. The exploration of space by the counterions around DNA in the short time scale of this study was insufficient to permit the derivation of general conclusions about the ion mobilities, however. 

The mechanism for the HWE reaction is shown in above for an aldehyde condensation. The phosphoryl-stabilized carbanion 15 attacks the carbonyl in a stepwise manner, to give oxyanion intermediate 16, which then decomposes via a transient four-centered intermediate, 17A or 17B, to yield... 

Hirsutene (1) and A9(,2,-capnellcnc (2), the parent members of the hirsutane and capnellane families of triquinane natural products, respectively, are isomeric molecules that possess four contiguous stereogenic centers, one of which is quaternary. The linearly fused tricyclopentanoid frameworks of compounds 1 and 2 are obviously very similar, differing only with respect to the positions of the three methyl groups. An asset of Curran s tandem radical cyclization strategy is that it provides a unified entry into a wide variety of linear condensed cyclopentanoid natural products. As a result, it is possible to devise nearly identical retrosynthetic pathways for these structurally related molecules. 

Like the Strecker synthesis, the Ugi reaction also involves a nucleophilic addition to an imine as the crucial step in which the stereogenic center of an a-amino acid derivative is formed4. The Ugi reaction, also denoted as a four-component condensation (A), is related to the older Passerini reaction5 (B) in an analogous fashion as the Strecker synthesis is to cyanohydrin formation. In both the Ugi and the Passerini reaction, an isocyanide takes the role of cyanide. 

These reactions imply an aldol condensation following the initial Michael addition. Two examples in which absolute stereocontrol over three or four new stereogenic centers is achieved in a single operation illustrate the potential of these methods. 

This particular function, and also others of the metal, are also beautifully utilized in the work on the chemical synthesis of corrins (Fig. 6.2). In the synthesis of 2, a metal, Co(ll), Ni(ll) or Pd(ll), is required to stabilize the precursor 1, which would otherwise be extremely labile configurationally and constitutionally. As added bonuses, the metal ion helps to activate the methylene carbon for its attack on the iminoester carbon, and also forces the four nitrogens into a planar conformation, thereby bringing the condensation centers of rings A and B close together. This is strikingly shown by X-ray structural determination of 1. With... 

The ready condensation of sucrose with excess triphenylmethyl chloride in pyridine to a tri-trityl ether is, however, more easily explained by XV or II, which have three, instead of two (c/. I), primary alcohol groups to react selectively in the condensation. Fleury and Courtois oxidized sucrose for twenty-four hours at 14° with an excess of suitably buffered periodic acid and found that three moles of the oxidant were consumed and one mole of formic acid was eliminated. This highly selective oxidant is known to cleave unsubstituted 1,2 glycols quantitatively to two carbonyl groups and to eliminate the center carbon atom... 

The three hexanuclear clusters are mixed valency complexes of two M(III) and four M(IV) centers, and the average oxidation state of the metal is +3.67. The number of cluster valence electrons is 14, which agrees with seven M—M bonds. Relatively short M-M distances for the intra- and intertriangles suggest that the clusters can be viewed as dimers of triangular clusters. Extension of the triangle condensation would lead to higher polymers. 

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