Addition to n Bonds

Addition to n bonds is a second very common reaction of free radicals. Interaction of die free radical widi die 7r -electron pah causes one of die n electrons to pair up widi die unpaired electron of the free radical to produce a new bond to one of die r-bonded atoms. The remaining n electron is now unpaired and dius forms a new free-radical species. The process is often very favorable since the new a bond (70-90 kcal/mol) formed in die addition process is normally much stronger than die jt bond (60 kcal/mol) which is broken in the reaction. In the above example a new carbon-carbon a bond is formed by free-radical addition to produce a new carbon-centered free radical however, a wide variety of other free-radical species add readily to olefins. 

From these measurements it has been possible to conclude that GeH2 can insert readily into Si—H bonds but not into C—H bonds, and can undergo addition to n bonds. 

Abraham, H. W., Photogenerated Nitrene Addition to n Bonds. In Griesbeck, A. G., Mattay, J. (eds), Synthetic Organic Photochemistry, Marcel Dekker, New York, 2005, pp. 391 416. 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

The process described by transition state (4) is just the traits addition of a single bond 2-3 to n bond 4-5. Both transition states suggest inversion at C-3 since the 5-3 bond is formed from the back as the 2-3 bond is broken. 

Other interesting multicomponent sequences utilizing isocyanides have been elaborated by Nair and coworkers. In a recent example, this group exploited the nucleophilic nature of the isocyanide carbon, which allows addition to the triple bond of dimethyl acetylenedicarboxylate (DMAD) (9-90) in a Michael-type reaction (Scheme 9.19) [59]. As a result, the 1,3-dipole 9-91 is formed, which reacts with N-tosylimines as 9-92 present in the reaction vessel to give the unstable iminolactam 9-93. Subsequently, this undergoes a [1,5] hydride shift to yield the isolable aminopyrroles 9-94. In addition to N-tosylimine 9-92 and cyclohexyl isocyanide (9-89), substituted phenyl tosylimines and tert-butyl isocyanide could also be used here. 

During cycloadditions (addition of n bonds to n bonds, a subscript (n or a) preceding the number of electrons in the relevant orbital is added, for example n2s g2s g2ci etc. 

Robust peptide-derived approaches aim to identify a small drug-like molecule to mimic the peptide interactions. The primary peptide molecule is considered in these approaches as a tool compound to demonstrate that small molecules can compete with a given interaction. A variety of chemical, 3D structural and molecular modeling approaches are used to validate the essential 3D pharmacophore model which in turn is the basis for the design of the mimics. The chemical approaches include in addition to N- and C-terminal truncations a variety of positional scanning methods. Using alanine scans one can identify the key pharmacophore points D-amino-acid or proline scans allow stabilization of (i-turn structures cyclic scans bias the peptide or portions of the peptide in a particular conformation (a-helix, (i-turn and so on) other scans, like N-methyl-amino-acid scans and amide-bond-replacement (depsi-peptides) scans aim to improve the ADME properties." ... 

The lyases comprise enzyme class 4. They are enzymes cleaving C-C, C-0, C-N and other bonds by elimination, not by hydrolysis or oxidation. Lyases also catalyse addition to donble bonds. The types of reactions catalysed by lyases are decarboxylation (decarboxylase), hydration/dehydration (hydratase/dehydratase), ammonia addition/deamination (ammonia-lyase), cyanohydrin formation/cleavage (oxynitrilase),... 

Next to nucleophilic displacement, the commonest mechanistic processes in enzymatic catalysis are addition to double bonds and elimination to form double bonds. These often involve addition of a nucleophile together with a proton to a highly polarized double bond such as C=O or C=N-. In other reactions, which are discussed in Section C,2, the nucleophile attacks one end of a C=C bond that is polarized by conjugation with C=0 or C=N. 

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