Nucleophilic substitution steric hindrance

Keywords fluorinated silane, transfer reagent, nucleophilic substitution, steric hindrance... 

In both cases, the bromide ion is the leaving group and is attached to a primary carbon atom. In the case of bromobutane, the carbon chain is off to one side and does not interfere with the approach of the nucleophile. However, in contrast, in the case of neo-pentylbromide, there is the large /-butyl group that obstructs the approach of the incoming nucleophile. This steric hindrance decreases the rate of SN2 substitution. 

The attack by a reagent of a molecule might be hampered by the presence of other atoms near the reaction site. The larger these atoms and the more are there, the higher is the geometric restriction, the steric hindrance, on reactivity. Figure 3-6e illustrates this for the attack of a nucleophile on the substrate in a nucleophilic aliphatic substitution reaction. 

The Peterson reaction has two more advantages over the Wittig reaction 1. it is sometimes less vulnerable to sterical hindrance, and 2. groups, which are susceptible to nucleophilic substitution, are not attacked by silylated carbanions. The introduction of a methylene group into a sterically hindered ketone (R.K. Boeckman, Jr., 1973) and the syntheses of olefins with sulfur, selenium, silicon, or tin substituents (D. Seebach, 1973 B.T. Grdbel, 1974, 1977) illustrate useful applications. The reaction is, however, more limited and time consuming than the Wittig reaction, since metallated silicon derivatives are difficult to synthesize and their reactions are rarely stereoselective (T.H. Chan, 1974 ... 

Having just learned that tertiary alkyl halides are practically inert to substitution by the Sn2 mechanism because of steric hindrance we might wonder whether they undergo nucleophilic substitution at all We 11 see m this section that they do but by a mecha nism different from 8 2... 

As crowding at the carbon that bears the leaving group decreases the rate of nude ophilic attack by the Lewis base increases A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to pre dominate and primary alkyl halides react with alkoxide bases by an 8 2 mechanism m preference to E2... 

Because of the rapid ring opening by the nucleophile, ayiridinium salts cannot usually be isolated. However, in a few cases it is possible to isolate such compounds (54), eg, at low temperatures, when the ayiridinium salts ate sparingly soluble or where there is steric hindrance to substitution. Stable ethyleneiminium salts can be prepared by reaction of ethyleneimine with acids not containing nucleophilic anions, for example HBF (55). 

It is interesting to note that the oxidation of sulphoxides by peracids is faster in alkaline than in acidic solution. This is in contrast to the oxidation of sulphides and amines with the same reagents " . The oxidation rate of ortho-substituted aryl alkyl sulphoxides with aromatic peracids is less than the corresponding meta- and para-substituted species due to steric hindrance of the incoming peracid anion nucleophiles . Steric bulk in the alkyl group also has some effect . Such hindrance is not nearly so important in the oxidation reaction carried out under acidic conditions . 

A similar reaction sequence of triisopropylphenylphosphole or mesitylphosphole (17b and 17a, respectively) with phosphorus tribromide afforded the corresponding 2-substituted products. The reaction of dibromophosphine 37 with nucleophiles followed by oxidation or hydrolysis gave phosphonic or //-phosphinic derivatives (39 or 41, respectively) (Scheme 9) [48, 49], The regioselectivity is obviously the consequence of the presence or the lack of the steric hindrance with ortho tert-butyl groups, only position 3 is available, while with the smaller triisopropyl substituent, position 2 may be the appropriate reaction site. 

The most typical and well-represented reactions involve nucleophilic substitution at the sulfonium atom (for example, hydrolysis to give monosulfoxides). This direction of attack is preferred because of the lower energy of S-S bonds and the decreased sterical hindrance at a trisubstituted sulfur atom compared with the hindrance at a tetracoordinated carbon atom. 

I. Dostrovsky, E. D. Hughes, and C. K. Ingold, XXXII. The role of steric hindrance, magnitued of steric effect, range of occurrence of steric and polar effects, and place of the Wagner rearrangement in nucleophilic substitution and elimination, Chem. Soc. 173 (1946). 

In many cases, the yields of these products are high. However, the use of /V-silylated triazoles as nucleophiles or the use of cyclic nitroso acetals (475) substituted at the C-3 atom leads to a noticeable decrease in the yield of the oximes. Therefore, steric hindrance in nitroso acetals and a decrease in nucleophilicity of A-centered nucleophiles result in an increase in the contribution of side reactions. It should be emphasized that C -nucleophiles, such as anions of nitro compounds, are not involved in coupling reactions with cyclic nitroso acetals (475). However, the products, which formally correspond to the C,C-coupling mechanism, can be prepared by the nucleophilic substitution of chlorine in compound (476 d) by a Sa/2 mechanism (Scheme 3.254, product (483c), the yield was 79%). 

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