Nucleophilic addition reaction steric hindrance

An excellent method for converting an acid chloride to a ketone employs transition metal catalysts such as ferric chloride in conjunction with low reaction temperatures. Reaction of butylmagnesium bromide with octanoyl chloride at -60°C gave a mixture of 13% of 80, 4% of 81 (from the secondary reaction of butyl-magnesium bromide and 80), and 60% of 82. when a catalytic amount (2 mol %) of ferric chloride (FeCls) was added, however, a 76% yield of ketone 80 was obtained, along with 3% of the over alkylation product, 81.94 If the intermediate ketone is unreactive to nucleophilic substitution due steric hindrance or peculiar electronic factors (diisopropyl ketone and phenyl-rerr-butyl ketone are both sterically hindered) the ketone can usually be isolated (sec. 8.4.G for problems with hindered ketones). In many instances, however, even dry ice temperatures and reverse addition techniques give poor yields of the ketone.95... 

Sn2 and SNAr Reactions In these reactions the metal atom attacks aliphatic or aromatic carbon bonded to X, respectively. A stronger nucleophilic metal as well as a better leaving group X (I>Br>Cl>F) facilitates, whereas steric hindrance in R slows these types of oxidative addition [193, 194]. SNAr reactions are favored by electron-withdrawing substituents Y in the case of the substrates 4-YQH4X [2], Sn2 [27, 29, 89, 117, 180, 181] and SNAr [31, 33, 62-67, 95, 100, 107-109] mechanisms have been suggested frequently for zerovalent d10 complexes such as [L M] (M = Ni, Pd, Pt L=tertiary phosphine =2,3,4). For example ... 

Perchlorofulvalene is a highly reactive chlorocarbon which undergoes a variety of reactions, including dimerization and addition reactions, especially with nucleophiles. It has a unique structure4 which reflects a compromise between steric hindrance and conjugation. The method of preparation exemplifies the use of the mild dehalogenating properties of alkyl phosphites. 

Steric hindrance to nucleophile addition becomes a major problem with 6-exo-substituted cyclohexadienyliron complexes, and the outcome of these reactions is highly dependent on the size of the substi-... 

Aryl halides are relatively unreactive toward nucleophilic substitution reactions. This lack of reactivity is due to several factors. Steric hindrance caused by the benzene ring of the aryl halide prevents SN2 reactions. Likewise, phenyl cations are unstable, thus making SN1 reactions impossible. In addition, the carbon-halogen bond is shorter and therefore stronger in aryl halides than in alkyl halides. The carbon-halogen bond is shortened in aryl halides for two reasons. First, the carbon atom in aryl halides is sp2 hybridized instead of sp3 hybridized as in alkyl halides. Second, the carbon-halogen bond has partial double bond characteristics because of resonance. 

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