Substitution at sp center

Combining Addition and Elimination Reactions (Substitutions at sp Centers)... 

There are several reasons why direct substitutions occur at xp -hybridized centers less readily than at sp centers. First, because there is more s character in the bond to the leaving group, this bond is stronger than the... 

The first two chapters have dealt with formation of new carbon bonds by processes in which carbon is the nucleophilic atom. The reactions considered in Chapter 1 involve attack by carbon nucleophiles at sp centers, while those discussed in Chapter 2 involved reaction at sp centers, primarily carbonyl groups. In this chapter we turn our attention to noncarbon nucleophiles. Nucleophilic substitution both at sp and sp centers is used in a variety of synthetic operations, particularly in the interconversion of functional groups. The mechanistic aspects of these reactions are treated more fully in Part A, Chapters 5 and 8. 

Such reductive ring contractions of sulfones are formally similar to two other methods capable of supplanting a sulfur atom by a carbon-carbon double bond the Ramberg-Backlundand Stevens rearrangements. The distinguishing feature of this novel approach to cyclobutenes consists in the resultant higher level of alkyl substitution at the sp -hybridized centers. 

The susceptibility or mixing coefficients, pj and pj , depend upon the position of the substituent (indicated by the index, /) with respect to the reaction (or detector) center, the nature of the measurement at this center, and the conditions of solvent and temperature. It has been held that the p/scale of polar effects has wide general applicability (4), holding for substituents bonded to an sp or sp carbon atom (5) and, perhaps, to other elements (6). The or scale, however, has been thought to be more narrowly defined (7), holding with precision only for systems of analogous pi electronic frameworks (i.e., having a dependence on reaction type and conditions, as well as on position of substitution). 

This chapter includes examples of aliphatic nucleophilic substitution at both sp and sp centers, aromatic nucleophilic substitution, E2 elimination, nucleophilic addition to carbonyl compounds, 1,4-addition to a, -unsaturated carbonyl compounds, and rearrangements promoted by base. 

Direct nucleophilic substitution at an sp -hybridized center is not likeiy under common reaction conditions. Thus, nucleophiiic substitution reactions at such centers usually are broken into two steps. (For exceptions to this hint, see Dietze, P. Jencks, W. P. J. Am. Chem. Soc. 1989, III, 5880-5886, and references cited therein. 

In step 5, direct substitution by cyanide ion at an sp center, as shown, is an unlikely process. 

The mechanism of the foregoing copper-catalyzed substitution at the sp carbon center is proposed as follows [Eq. (36) 88]. Formation of an intermediate alkylcopper RCu should play an important role, with the nucleophilic displacement of alkyl halides with this copper species being the rate-limiting step. 

Although considerable effort has been expended on asymmetric routes to the structural motif within a number of beta-blocker drugs, there has been little h-nancial reward. Through the use of a chiral equivalent of epichlorohydrin (X = Cl), a substitution reaction at the sp center followed by epoxide opening allows... 

The ring protons of substituted 2 -1,2,6-thiadiazine 1,1-dioxides located at sp carbon centers have chemical shifts in the region 4.7-8.5 d and vicinal coupling constants across the C=C bond of = 7.0-7.4 Hz <82JOC536, 85T3105). In iV-unsubstituted 1,2,6-thiadiazine 1,1-dioxides, protons at... 

Let us now examine how substituent effects in reactants influence the rates of nucleophilic additions to carbonyl groups. The most common mechanism for substitution reactions at carbon centers is by an addition-elimination mechanism. The adduct formed by the nucleophilic addition step is tetrahedral and has sp hybridization. This adduct may be the product (as in hydride reduction) or an intermediate (as in nucleophilic substitution). For carboxylic acid derivatives, all of the steps can be reversible, but often one direction will be strongly favored by product stability. The addition step can be acid-catalyzed or base-catalyzed or can occur without specific catalysis. In protic solvents, proton transfer reactions can be an integral part of the mechanism. Solvent molecules, the nucleophile, and the carbonyl compound can interact in a concerted addition reaction that includes proton transfer. The overall rate of reaction depends on the reactivity of the nucleophile and the position of the equilibria involving intermediates. We therefore have to consider how the substituent might affect the energy of the tetrahedral intermediate. 

Reaction mechanisms for hydrolysis can be classified according to the type of reaction center involved. The primary distinction is made between reaction at saturated and unsaturated centers. With respect to carbon-centered functional groups, which will be the primary focus of this chapter, hydrolysis involves reactions at sp (saturated) or sp (unsaturated) hybridized carbons. Nucleophilic reactions at sp carbons are termed nucleophilic substitution (2.7). The reaction at sp carbons is termed nucleophilic addition-elimination or acyl substitution (2.8). 

The rich nucleophilic reactivity of square-planar platinum(II) and palladium(II) complexes is well established. One of the most documented examples is the stepwise oxidative addition of aUcyl halides to organoplatinum(II) [1] and organopalladium (II) [2,3] complexes via SN2-type substitution at the sp carbon center. Additionally, electron-rich Pt centers are subject to protonation at the metal to generate Pt hydrides as the first step in the protonolysis of many platinum-carbon bonds [4—7]. With a less reactive Lewis acid such as SO2, reversible adduct formation is observed [8], and this reaction has been used in the development of sensors [9-11],... 

---