Nucleophilic addition small rings

Baldwin s rules. It is noteworthy that the EM5/EM6 ratio is reduced to a factor as small as about 2, which is less than the intrinsic entropic advantage of 5- over 6-membered ring formation. Kirby (1980) in his review lists a large number of EM data for intramolecular nucleophilic additions to carbonyl. Probably because these data derive from laboratories of chemists mainly interested in intramolecular nucleophilic catalysis and its relevance to understanding enzymic catalysis, the great majority of them refer to reactions occurring via 5- and 6-membered transition states. The only example where a 4-membered transition state is involved is (70), whose kinetics were studied... 

Steric effects on the nucleophile, aniline, were clearly evident. Rate constants for bimolecular attack of 2,6-dimethyl- 70a, 2,6-diethyl- 70b, and 3,5-dimethylaniline 70c at 308 K indicate that the ort/zo-substituted anilines react more than an order of magnitude slower at the same temperature (Table 7). Structure 70c must be able approach the reactive nitrogen more closely.42,43 A comparison of the rate constants for reaction of aniline 72c, /V-methyl- 71a and /V-phenylaniline 71b provides further evidence of steric effects although the very small rate constant for the diphenylamine could also be accounted for by reduced nucleophilicity on account of lone pair resonance into the additional phenyl ring. 

Positive p value consistent with nucleophilic addition to epoxide which increases electron density on oxygen. Small magnitude consistent with negative charge being insulated from the ring. 

The neutral 1,4- and 1,2-quinone methides react as Michael acceptors. However, the reactivity of these quinone methides is substantially different from that of simple Michael acceptors. The 1,6-addition of protonated nucleophiles NuH to simple Michael acceptors results in a small decrease in the stabilization of product by the two conjugated 7T-orbitals, compared to the more extended three conjugated 7T-orbitals of reactant. However, the favorable ketonization of the initial enol product (Scheme 1) confers a substantial thermodynamic driving force to nucleophile addition. By comparison, the 1,6-addition of NuH to a 1,4-quinone methide results in a large increase in the -stabilization energy due to the formation of a fully aromatic ring (Scheme 2A). This aromatic stabilization is present to a smaller extent at the reactant quinone methide, where it is represented as the contributing zwitterionic valence bond structure for the 4-0 -substituted benzyl carbocation (Scheme 1). The ketonization of the product phenol (Scheme 2B) is unfavorable by ca. 19 kcal/mol.1,2... 

Phenyl- and 3,5-diphenyl-substituted triazines 154 undergo to a small extent ring contraction by action of potassium amide in liquid ammonia to yield 1,2,4-triazoles 155. Again, nucleophilic addition at C-6 is presumed to facilitate ring opening (Scheme 86) (87JOC71). 

Another approach for the anionic synthesis of both bipyridine- and terpyridine-functionalized polymers is the direct reaction of PSIi with either 2,2 -bipyridine or 2,2 6, 2"-terpyri-dine, respectively. This end functionalization is proposed to proceed by nucleophilic addition of PSLi to the 6-position of the pyridine ring, followed by termination and oxidative rearomati-zation as shown in eqn [29] for terpyridine functionalization. One shortcoming of this procedure is that a large excess of terpyridine (e.g., 23-fold molar excess) is required to prevent diaddition. SEC analysis indicated that only small amounts of dimeric coupling products (up to 4.8%) are obtained under these conditions. Once again, in spite of the use of sec-butyllithium as initiator, the lower molecular weight samples... 

Only one or/Ao-aryne 533 is possible in a thiazole ring. Its intermediacy was first considered in the reaction of 4>halothiazoles (534) with methoxide ion as a possible rationale for the surprisingly similar reactivity of these compounds and the 2- and 5-halo isomers. This hypothesis was consistent with the small element effect, the rapid base-catalyzed exchange of the 5-proton, and the exclusive formation of the normal substitution product 535 as would be expected if nucleophilic addition to the aryne 533 was determined by the stability of the resulting anion 536 with the negative charge adjacent to the sulfur atom. The fact that the 5-phenyl derivative 537, which cannot form an aryne 533, reacts at a comparable rate to 534 rules out the possibility of an elimination-addition mechanism, however. 

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