Intramolecular side chains

Analogous behavior is also observed with the corresponding 3,4-dimethoxy derivatives [102] with these derivatives, however, because of the increased stability of the radical cations, in acidic solution a decrease in reactivity of three orders of magnitude for the deprotonation reaction is observed on going from MBA to the 3,4-dimethoxybenzyl alcohol radical cation (veratryl alcohol, VA). In the presence of OH the deprotonation site shifts from carbon to oxygen, as previously described for the 4-methoxy derivatives, and a dramatic increase in reactivity is observed, VA + reacting with OH with A = 1.3 x 10 M s (Table 5), a value which is lower than the diffusion limit and which, compared with that measured for MBA +, rather than the decreased O-H acidity of VA , presumably reflects the increased electron density on the aromatic system which disfavors the intramolecular (side-chain to nucleus) electron transfer eventually leading to the benzyloxyl radical. 

Cantel S, Le Chevalier IA, Scrima M et al (2008) Synthesis and conformational analysis of a cyclic peptide obtained via i to i + 4 intramolecular side-chain to side-chain azide-alkyne 1,3-dipolar cycloaddition. J Org Chem 73 5663-5674... 

In a reversal of this intramolecularized side-chain reactivity (effecting annulation of a five-membered ring to the N/C-2-position of pyridine) the Baylis-Hillman reaction of pyridine-2-aldehydes with acceptor-substituted alkenes, e.g. acrylates, in the presence of DABCO gives rise to formation of products 74, which can be cyclized to 2-substituted indolizines, e.g. indolizine-2-carboxylates 75 [54]. 

Unexpectedly, a completely different reaction took place in the oxidation of 2-(l-propenyl)phenol (111) with PdCh. Carpanone (112) was obtained in one step in 62% crude yield. This remarkable reaction is explained by the formation of o-quinone, followed by the radical coupling of the side-chain. Then the intramolecular cycloaddition takes place to form carpanone[131]. 

Proper condensed phase simulations require that the non-bond interactions between different portions of the system under study be properly balanced. In biomolecular simulations this balance must occur between the solvent-solvent (e.g., water-water), solvent-solute (e.g., water-protein), and solute-solute (e.g., protein intramolecular) interactions [18,21]. Having such a balance is essential for proper partitioning of molecules or parts of molecules in different environments. For example, if the solvent-solute interaction of a glutamine side chain were overestimated, there would be a tendency for the side chain to move into and interact with the solvent. The first step in obtaining this balance is the treatment of the solvent-solvent interactions. The majority of biomolecular simulations are performed using the TIP3P [81] and SPC/E [82] water models. 

When 1-hydroxymelatonin (19) is treated with acid, removal of its 1-hydroxy group leaves an indolyl cation (a hybrid of resonance structures 254,168, and so on) as shown in Scheme 37. If there is a subsequent intramolecular nucleophilic attack by the Ab-nitrogen atom on the side chain or if an intermolecular attack by suitable nucleophiles occurs on this intermediate cation, the birth of a new type of product can be expected. 

The intramolecular attack on the alkyl side chain is suggestive of a free-radical process. 

Propargylsilanes can also be employed in the Sakurai reaction. For example the enone 6, containing a propargylsilane side chain, undergoes an intramolecular Sakurai reaction, catalyzed by an acidic ion-exchange resin—e.g. Amberlyst-15—to give stereoselectively the bicyclic product 7 in good yield ... 

The alternate schemes that have been developed for achieving removal of the side chain similarly depend on intramolecular Interaction of some derivative of the amine with the amide oxygen to afford some easily hydrolyzed intermediate at an oxidation stage analogous to... 

Intramolecular Friedel-Crafts acylation has been observed with bonellin dimethyl ester (20).53 The reaction proceeds in contrast to corresponding porphyrins, very smoothly with concentrated sulfuric acid because the propanoic acid side chain at the sp3 center is located above the macrocyclic ring system and therefore can better fulfill the stereoelectronic requirements for the ring-closure reaction. The ring closure is accompanied by racemization in the product 21. 

An opportunity to investigate the relative leaving ability of fluorine in the same molecule was presented by the intramolecular cyclization of (25) [89JFC(43)393]. It was found that there was a greater distinction between the two possible sites than when S (i.e., side chain CH=C(C02")S [90JFC(50)229]) was the attacking nucleophile. 

The pioneering work on amphiphilic polyelectrolytes goes back to 1951, when Strauss et al. [25] first synthesized amphiphilic polycations by quaternization of poly(2-vinylpyridine) with n-dodecyl bromide. They revealed that the long alkyl side chains attached to partially quaternized poly(vinylpyridine)s tended to aggregate in aqueous solution so that the polymers assumed a compact conformation when the mole fraction of the hydrophobic side chains exceeded a certain critical value. Thus, Strauss et al. became the first to show experimentally the intramolecular micellation of amphiphilic polymers and the existence of a critical content of hydrophobic residues which may be compared to the critical micelle concentration of ordinary surfactants. They called such amphiphilic polyelectrolytes polysoaps [25],... 

More recently, Beckwith demonstrated that intramolecular Meerwein reactions are also possible if one uses an arenediazonium salt with an aliphatic side-chain in the ortho position containing a double or triple CC bond in 8-position. We will discuss them in Section 10.11. 

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