Amines nucleophilicity and

Table 25 The carbon-ll/carbon-14 KIEs for the SN2 reactions between several amine nucleophiles and labelled methyl iodide in acetonitrile or dimethoxyethane at 30°C and 15°C, respectively.0...

Finally, Persson et al. (1995) measured the UC/14C KIEs for the SN2 reactions between several amine nucleophiles and labelled methyl iodide in dimethoxyethane or acetonitrile at 15°C and 30°C, respectively, to determine how sterically hindered nucleophiles affects the transition state of a Menshut-kin reaction. The results in Table 25 show that all the fc11// 14-values for these reactions are large. In fact, they are all near the theoretical maximum value for these KIEs. Secondly, the KIE for the reaction with the more sterically hindered amine, 2,6-lutidine, is larger than that for the less sterically hindered... 

Fig. 11 In situ formation of amine nucleophiles and a,/S-unsaturated carboxamides that react further in thermosetting of hyperbranched dendrimer-polyanhydride nanocomposite thin films...

Many natural products are constrained by macrocyclic motifs, which are often essenhal for natural products to possess the desired biological properties. In the biosynthesis of macrocyclic NRPs and PKs, linear peptides or PKs are often mac-rocyclized by a TE domain located at the C-terminal of multi-modular synthases. For example, in the biosynthesis of the antibiotic tyrocidine A (Tyc A), a linear enzyme-bound decapephde, which is transferred from the last carrier protein (or thiolahon) domain of the Tyc A synthase, is cyclized by an intramolecular Sn2 reachon between the N-terminal amine nucleophile and the C-terminal ester, which is covalently linked to serine residual in the TE domain prior to macro-cyclization (Scheme 7.9) ([35] and references therein). 

The catalyst choice was based on several unique properties of the rare-earth Lewis acids (1) ready availability, (2) a large number of triflates with varied Lewis acidity, (3) compatibility with amine nucleophiles and (4) potential for reactions in aqueous medium. 

We began with our existing aminoadenosine and carbazolediimide structures, as both the carbazole portion of the receptor and the ribose portion of adenosine are well suited for synthetic elaboration. For the reciprocal system, each was outfitted with amine nucleophiles and active ester electrophiles for covalent coupling reactions [50]. Two amines and two p-nitrophenyl esters were prepared [(4), (45), (46) and (47), Figure 27], as well as the two templates (48) and (49) (Figure 28). Two reference templates (50) and... 

Halogen at a benzothiophene 2-position is subject to displacement with amine nucleophiles, and, more easily than halogen at the 3-position. 

Macrocyclic motifs are usually essential for the unique biological properties of natural products. In most cases, linear NRP and PK scaffolds are cyclized to form macrolactones or macrolactams prior to further post-modification. Macrocyclization is usually carried out by cyclases towards the end of elongation. For example, in the biosynthesis of the antibiotic tyrocidine A, a linear enzyme-bound decapeptide is cyclized via an intramolecular SN2 reaction between the N-terminal amine nucleophile and the C-terminal thioester, which is covalently linked to the synthase [reactions (a) and (b), Scheme 8.3] [22], This cyclase shows great versatility. Not only does it catalyze the formation of macrolactams of ring sizes from 18 to 42 atoms from... 

A number of years ago, one of the first indications that the synthetic polyammonium macrocycles would be able to go beyond simple recognition of anionic substrates was published by Lehn, Mertes, and coworkers in 1983. The excitement surrounding the discovery of this chemistry was that these simple cyclic systems could mimic the naturally occurring ATPases by catalyzing the hydrolysis of ATP at physiological pHs in aqueous solution. The utility of these simple macrocycles can be attributed to several aspects (i) they operate in water, (ii) due to their cyclic nature the hosts are polyprotonated under physiological pH conditions, (iii) one of the reaction pathways involves a covalent intermediate as a result of the presence of an amine nucleophile, and (iv) the rates of reaction are enhanced upon the addition of certain metal ions as seen for the Mg +-dependence of the ATPases. ... 

Three examples of Sn2 (substitution, nucleophilic, bimolecular) reactions are shown in Scheme 11.5. These are simple reactions from a mechanistic standpoint. They are concerted, and there is very little that can go wrong when considering the proper electron-pushing notation. These reactions fit our paradigm for predicting reactivity, because they are combinations of nucleophiles and electrophiles, whose reactivity can be predicted solely based upon electrostatic considerations. The specific reaction shown in Scheme 11.5 B is an example of the Menschutkin reaction, defined as the reaction between an amine nucleophile and an alkyl halide. Scheme 11.5 C shows the second step of the enolate alkylation reaction we described in Section 11.3. 

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