Bond cleavage types

Fragment analysis is based on the RECAP algorithm, published in 1998 [55], This retrosynthetic combinatorial analysis starts with a collection of active molecules and then fragments these molecules using any set of retrosynthetic reactions (Figure 8.12). For example, Cisapride is cleaved into four fragments based on three different bond cleavage types. 

Another way to obtain a library of fragments is to decompose a known database of drug- or lead-like molecules by /j gMifo-retrosynthetic rules like RECAP (Retrosynthetic Combinatorial Analysis Procedure).The RECAP bond cleavage procedure consists of eleven bond cleavage types shown in Figure 7.3. This approach has several advantages ... 

For example, the acyl-aryloxo bond cleavage (type b) is shown by the reaction of Ni(cod)2 with phenyl propionate in the presence of PPhs (Scheme 3.34) or 2,2 -bipyridine [65]. The reaction products are ethylene, phenol, and (car-bonyl)nickel complex. Formation of these products is conveniently understood by initial oxidative addition of EtC(0)-0Ph followed by decarbonylation, )S-hydrogen elimination and reductive elimination, though (acyl)(aryloxo)nickel(II) intermediate is not isolated. However, such an intermediate is isolated by the selective insertion of CO into the (alkyl)(aryloxo)nickel (or palladium) complexes, which smoothly affords esters by reductive elimination promoted by electron deficient olehns. The results suggest that the oxidative addition involving C-0 bond cleavage is essentially reversible. 

Both types of processes, 7r -assisted y, -bond cleavage and P -bonding, have been invoked to operate in the phototransformations of the aldehyde-ketone (153) to products (155), (156) and (158). The conversions have been observed at room temperature in dioxane, t-butanol, ethanol and benzene using light of wavelengths 2537 A or above 3100 A or sensitization by acetophenone. The phosphorescing excited triple state of (153) is very similar to that of testosterone acetate (114), but its reactions are too rapid... 

Curvature in a Br nsted-type plot is sometimes attributed to a change in transition state structure. This is not a change in mechanism rather it is interpreted as a shift in extent of bond cleavage and bond formation within the same mechanistic pattern. Thus, Ba-Saif et al. ° found curvature in the Br nsted-type plot for the identity reactions in acetyl transfer between substituted phenolates this reaction was shown earlier. They concluded that a change in transition state structure occurs in the series. Jencks et al." caution against this type of conclusion solely on the evidence of curvature, because of the other possible causes. 

This is the reverse of the first step in the SnI mechanism. As written here, this reaction is called cation-anion recombination, or an electrophile-nucleophile reaction. This type of reaction lacks the symmetry of a group transfer reaction, and we should therefore not expect Marcus theory to be applicable, as Ritchie et al. have emphasized. Nevertheless, the electrophile-nucleophile reaction possesses the simplifying feature that bond formation occurs in the absence of bond cleavage. 

Furthermore, Cordes etal995 observed the saturation-type kinetics, strongly suggesting the formation of a complex between the polyelectrolyte and ester preceding bond cleavage reactions, as has been found for micellar catalysis11,1015. 

The crucial reaction intermediate PCHA in the HDN network of quinohne-type compounds has been clearly observed. Formation of cis-PCHA was faster than that of trans-PCHA, but isomerization was relatively rapid. The presence of H2S in the reaction stream favours the cleavage of the first C-N bond in DHQ, but slows down the C-N bond cleavage in PCHA. The presence of H2S decreases the adsorption constants of DHQ and NH.i. It is concluded that 40% of the HDN reaction of DHQ takes place through the reaction path of DHQ- THQl->OPA —>HC at 593 K and 3.0 MPa in the absence of H2S, while less than 10% takes place in the presence of H2S. 

Because of certain misconceptions with regard to the choice of solvent and the occurrence of sulfur-oxygen bond fission in hydroxylic solvents - , it is important to emphasize that one can greatly reduce the rate of this competing process by the use of weak bases. In systems which can undergo facile C—O as well as S—O bond fission, it is possible to control the type of bond cleavage by choosing the appropriate base . A remarkable illustration of this behavior is found in the ethanolysis of sulfinate 6a. In anhydrous ethanol at 90.0° with acetate ion as the added base, 6a yielded ethyl 2, 6-dimethylbenzenesulfinate plus a trace of sulfone 7a. Under the same conditions but with 2,6-lutidine the reaction was slower and sulfone 7a was the only detectable reaction product . ... 

The phosphine ligands suffer from P-C-bond cleavage, which result in the corporation of the phosphine aryl groups into an unwanted side product. This is due to the facile exchange of Ph and Ph Y between the Pd" centres and co-ordinated phosphines on an intermediates of type tranj-Pd(PPh,i)2(aryl)X ... 

The von Braun reaction (Scheme 6) is another basic reaction for C—N bond cleavage 32). Tetrahydroberberine (26) was heated under reflux with cyanogen bromide in benzene to afford the bromocyanide (28) and the unsaturated cyanide (29) through C-6—N and C-14—N bond cleavage, respectively. The C-8—N bond cleavage product was not obtained because of the steric hindrance of the methoxyl group at C-9 in SN2-type reactions 33). The... 

Although C—O bond cleavage is of little importance for transformations of protoberberines to other types of alkaloids, the selective C—O bond cleavage reaction provides access to naturally unabundant or nonnatural protoberberines from naturally abundant protoberberines such as berberine. 

In the mass spectra of all these substances (4,5,14,15,87,92,94), the molecular ions peaks are present. The base peak at m/z 58, typical for all the seco alkaloids with the N,iV-dimethylaminoethyl chain, corresponding to the CH2=N(CH3)2+ ion is observed. The main mass fragmentation under electron impact seems to involve bond cleavage between C-l and C-9. This can be evidenced by the presence of ions of the 122 and 123 type found in spectra of all compounds except for N-methylhydrastines (98, 99), where the 123 — C02 ion is formed instead. Finally, the carbonyl group absorption... 

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