Functional derivatives nucleophilic substitution

A convenient alternative to protection relies on the incorporation of a labile moiety available for post-polymerization functionalization by nucleophilic substitution [84]. A more versatile approach incorporates a terminally halogenated alkyl substituent as a site for post-polymerization via nucleophilic substitution. Anthraquinone, amine, thiol and carboxylic acid derivatives have been prepared thereby. Complete conversion is possible [46, 47]. Irregular examples include conversion to iodo and thiol derivatives [85]. 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

The nucleophilic substitution of a halogen atom at C-5 in the isoxazole nucleus without further functional substituents is so far unknown, but recently reports appeared on the nucleophilic substitution reactions at C-5 in isoxazole derivatives with benzoyl (78 79), ester, and cyano groups (81—>80, 82) in the 4-position. ... 

Aminodebromination of 4-bromo-l//-3-benzazepin-2-amine (25) with triethylamine occurs readily and results in formation of the quaternary salt 26 (see also Section 3.2.1.5.6.), whereas attempts to effect nucleophilic substitution of bromide with primary or secondary amines gives only tarry mixtures.41 The bromo group is also resistant to displacement by azide and benz-cncthiolate but undergoes substitution with thiocyanate ion in hot dimethylformamide to give the 4-thiocyanato derivative 27 rather than the thiourea by addition at the amine function. 

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

The analytic potential energy surfaces, used for the Cl + CH3Clb and Cl + CHjBr trajectory studies described here, should be viewed as initial models. Future classical and quantum dynamical calculations of SN2 nucleophilic substitution should be performed on quantitative potential energy functions, derived from high-level ab initio calculations. By necessity, the quantum dynamical calculations will require reduced dimensionality models. However, by comparing the results of these reduced dimensionality classical and quantum dynamical calculations, the accuracy of the classical dynamics can be appraised. It will also be important to compare the classical and quantum reduced dimensionality and classical complete dimensionality dynamical calculations with experiment. 

We have intentionally selected example reactions (Figs. 29-33) that would not usually be immediately obvious to a chemist. The examples chosen have all been concerned with rearrangements of various types, since their courses are frequently difficult to predict. It remains to emphasize that the reactivity functions contained in EROS perform perfectly well with other types of reaction. This is true, for example, with reactions that a chemist could derive directly from an analysis of the functional groups in a molecule. Thus, EROS predicts addition reactions to carbonyl compounds, nucleophilic substitutions, and condensation reactions, to name just a few examples. In all these reaction types, the possibility of assigning a quantitative estimate to the reactivity at the various sites via the reactivity functions is of particular merit. It... 

Amino groups of functionally substituted phosphines easily undergo nucleophilic substitution. Mutual transitions were shown to exist for the aminomethyl derivatives of phenylphosphine (80IZV1438), acyclic compounds being transformed into cyclic ones with variation in the size of the rings [Eq. (45)]. 

Functionalized oxazines (521) and (522) were synthesized from these key intermediates by the nucleophilic substitution of bromine (in 55%-100% yields based on derivatives (520) or 20%-30% yields based on the starting nitroethane). Besides, bromo derivatives (520) are convenient starting reagents for the synthesis of functionalized oxazines (523) and (524). 

The wide scope application of this transformation arises not only from the utility of epoxide compounds but also from the subsequent regiocontrolled and stereocontrolled nucleophilic substitution (ring-opening) reactions of the derived epoxy alcohol. These, through further functionalization, allow access to an impressive array of target molecules in enantiomerically pure form. 

Preparation of the branched trisaccharide (80) was readily achieved in good yield by nucleophilic substitution of the iodo derivative (60 d), derived from (60a), with (8a) in DMF (Scheme 24) [22b]. The introduction of a thiol functionality at the anomeric position of (80) using a known procedure and the condensation of this donor with the two acceptors (59)... 

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