Substitution using nucleophilic reagents

Dienones with extended conjugadon undergo peroxy acid epoxidadon regioselecdvely at the, 8-double bond, even if it is less substituted than the a, -double bond. The epoxidadon of (112) is regio-and stereo-selective (equation 39). Attempted epoxidadon of (113a) using nucleophilic reagents furnishes polymeric materials. The epoxidadon has been carried out with MCPBA (equadon 40). ... 

The reactivities of the substrate and the nucleophilic reagent change vyhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides S l and mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further (see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process (see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods (see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

Ammonolysis of 2-chlorobenzothiazole in liquid ammonia was studied by Lemons et al. and found to be approximately first-order with respect to this substrate at the fairly high concentrations used. The actual nucleophilic reagent was, as expected, the neutral species NH3, and reaction via the amide ion NH2 arising from the autoprotolysis equilibrium [Eq. (5)] was excluded on the grounds that addition of ammonium chloride did not depress the reaction rate. In accordance with this interpretation and in connection with the existence of aromatic substitutions other than normal it is of interest that 2-chlorobenzothiazole was found to react difiFerently with sodamide, although the products were unidentified in this case. 

In nucleophilic substitution the attacking reagent (the nucleophile) brings an electron pair to the substrate, using this pair to form the new bond, and the leaving group (the nucleofuge) comes away with an electron pair ... 

Among various modifications of the side chain of stabilized ylides [13,14] can be pointed out the preparation and transformation of the phenyliodonio a-substi-tuted phosphonium yhdes (Scheme 3) [15]. These compounds represent a potentially useful class of reagents, in which the iodonium group can be further substituted by nucleophiles such as PhSLi. 

Oximes 509 can be converted to their tosylates 510, but use of a large excess of KOH converts them directly into 27/-azirincs 511 (Scheme 82) <2003JOC9105>. The benzotriazolyl moiety in azirines 511 can be substituted by nucleophiles (organomagnesium reagents, potassium phthalimides, and sodium thiophenoxide) to give disubstituted azirines 512. 

Kondo and Watanabe developed allylations of various types of aldehydes and oximes by using nucleophilic (7r-allyl)ruthenium(ll) complexes of type 154 bearing carbon monoxide ligands (Equation (29)).345 These 73-allyl-ruthenium complexes 154 are ambiphilic reagents and the presence of the carbon monoxide ligands proved to be essential to achieve catalytic allylation reactions. Interestingly, these transformations occur with complete regioselectivity only the more substituted allylic terminus adds to the aldehyde. 

Recently, a direct kinetic study on the amination of substituted phenyhnagnesium bromides using Af,Af-dimethyl O-mesitylenesulfonyl hydroxylamine 3b as amination reagent has been reported by Erdik and Ate Ulkii . Rate data, the Hammett relationship and activation entropy support an Sn2 displacement of the carbon nucleophile on the electrophilic nitrogen. These results are consistent with the competition kinetics for electrophilic amination of substituted phenyl Grignard reagents with O-methylhydroxylamine In. ... 

The radiosynthesis of p F]FDG is based on the nucleophilic substitution of a modified mannose precursor with [ F]fluoride used as the nucleophilic reagent (Fig. 3). 

Nucleophilic substitution of the chlorine atom present in 2-chlorothiepane (132) using Grignard reagents has provided a synthetic route to 2-methyl- (133) or 2-phenyl- (134) thiepanes (equation 27) (69JHC115). An a-sulfinyl carbanion (114), generated by alkyllithium attack on thiepane 1-oxide (115), was found to act as nucleophile in the synthesis of cis and trans sulfoxides of thiepane (133 equation 28) (78TL5239). Polymerization of 2-thiepanone (135) has been initiated by attack of the f-butoxide anion and concomitant liberation of a thiolate anion (Scheme 26) (64MI51700). 

Nitrogen heterocycles continue to be valuable reagents and provide new synthetic approaches such as NITRONES FOR INTRAMOLECULAR -1,3 - DIPOLAR CYCLOADDITIONS HEXAHYDRO-1,3,3,6-TETRAMETHYL-2,l-BENZISOX AZOLINE. Substituting on a pyrrolidine can be accomplished by using NUCLEOPHILIC a - sec - AM IN O ALKYL ATION 2-(DI-PHENYLHYDROXYMETHYL)PYRROLIDINE. Arene oxides have considerable importance for cancer studies, and the example ARENE OXIDE SYNTHESIS PHENANTHRENE 9,10-OXIDE has been included. An aromatic reaction illustrates RADICAL ANION ARYLATION DIETHYL PHENYLPHOSPHONATE. 

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