Nucleophilicity difference

The l-imino-lff-2-benzopyran (13) ring opens on treatment with nitrogen nucleophiles. Different modes of recyclisation are possible and (13) is therefore a source of a variety of -heterocycles <96AJC485>. 

The intermediate may be trapped by other nucleophiles (different from water) and diverse products may be obtained. The interception of the intermediate may occur inter- or intra-moleculary, the latter providing a helpful tool to produce a new ring system (Scheme 9, pathway 2). These reactions are sometimes referred to, respectively, as Beckmann rearrangement-addition and Beckmann rearrangement-cyclization reactions. 

The equilibrium of nucleophilic displacements favors the side with the weaker Bronsted base the stronger Bronsted base displaces the weaker Bronsted base. The rate of the displacement reaction on the C of a given substrate depends on the nucleophilicity of the attacking base. Basicity and nucleophilicity differ as shown ... 

A variation on this theme is seen in / -substitution reactions catalyzed by PLP in which, instead of the hydrolysis step, a nucleophile different from water is added to the /7-carbon, followed by reprotonation at the a-position (equation 13). 

These aspects introduce different mechanistic patterns expected for the 1,3-DC reactions, as compared with DA cycloadditions (concerted vs stepwise with some zwitterionic character). This result may again be traced to the electrophilicity difference at the ground states of the reacting pairs.39 These results suggest that the description of the reactivity and the reaction mechanism involved in the 1,3-DC processes can be systematized as in the case of the DA cycloadditions. Such a model should be able to determine the charge transfer pattern and to decide which of the partners is acting as nucleophile/electrophile in a polar process, or even to anticipate a concerted pathway in those cases where the electrophilicity/nucleophilicity difference is small. 

Sometimes basic conditions are specified, but there aren t any acidic protons. You might want to look for protons that are three bonds away from a leaving group X, e.g., H—C—C—X. If there are good nucleophiles present, then you may also need to look for electrophilic atoms. Don t forget that heteroatoms that have their octet and that bear a formal positive charge are not electrophilic Typical nucleophiles differ under basic and acidic conditions. 

This reaction has been extensively modified for various conditions (as mentioned in Section A) by using different nucleophiles, different carbonyl compounds, and different bases as catalysts. 

As shown in Scheme 5.38 for representative results, when using a-unsubstituted (3-ketoesters as nucleophiles, different organocatalysts were tested and almost no diastereoselectivity was observed, while high levels of diastereoselectivity were obtained in the case of a-substituted (3-ketoesters. Besides, other activated methyenes such as (3-nitro- and (3-cyanoesters were also shown to be efficient nucleophiles for highly diastero- and enantioselective conjugate addition to nitrostyrenes. 

In Section 11.2.2, the rate of reaction for a tertiary halide in an Sn2 reaction is shown to be prohibitively slow, due to steric hindrance in the requisite pen-tacoordinate transition state. When 2-bromo-2-methylpropane (64) is heated in anhydrous THF (no water) with KI, for example, only unreacted 65 and KI are isolated. There is no reaction (see Chapter 7, Section 7.12, for a definition of no reaction ). Many different experiments have been done with this reaction, including using different nucleophiles, different solvents, and different reaction conditions. Interestingly, when 64 is heated in water, 2-methyl-2-propanol (65) is isolated in low yield. This is clearly a substitution reaction (Br for OH), but it cannot be an S 2 reaction. The reaction occurred with a tertiary halide, which is contrary to the requirement of a high-energy pentacoordinate transition state such as 13 (see Figure 11.5). Many experiments have demonstrated that this reaction follows first-order rather than second-order kinetics and there is an intermediate in an overall two-step reaction. 

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