Intramolecular competition reactions

The data in Table 5 show that concave pyridines 3 are able to differentiate alcohols. In synthesis, this capability is important when OH-groups within one molecule shall be differentiate. Therefore, intramolecular selectivities were also determined. Table 6 lists the results of intramolecular competition reactions for 1,2-propanediol (64) 172°, tra- Again, the small concave pyridine 3c only showed a small selectivity whereas the large concave pyridines 3d and 3r were the most selective catalysts. With a selectivity of 15 (3r), a selectivity range is reached which may be useful for applications because more than 93% of the functionalized OH-groups are primary ones. 

A special case (4) arises for intramolecular competition reactions. The product ratio gives the rate-constant ratio directly [Eq. (20]. Either a deficiency or an excess of alkylating agent may be present the reaction mixture may be analyzed at various stages of conversion to products. 

To investigate the mechanism further, a series of intramolecular competitive reactions of (difluoro)(phenyl)(4-substituted phenyl)silanes with iodobenzene were performed. As may... 

Benzoxepine formation by the 1,7-electrocyclisation of conjugated carbonyl ylides studied by Sharp was reported in last year s review. This work has now been extended in a study of the relative rates of cyclisation via intramolecular competition reactions <97JCS3025>. It has been found, for example and not unexpectedly, that the rate of cyclisation for alkenyl groups and the thiophene ring are ca. 10-20 times that for phenyl. The selectivity is unaffected by the nature of the substituent on the terminal atom of the ylide. 

A related synthesis of 3,3 -cyclopropyl oxindoles was reported by Takemoto et al. [32], Carbamoyl chloride 47, containing a cyclopropyl ring at the ortho position, undergoes a Pd-catalyzed cyclization onto the benzylic C-H bond of the cyclopropane to provide the corresponding spirooxindole 44 in 60% yield (Scheme 13). Intramolecular competition reactions investigated the chemoselectivity of the... 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

Copper(II) triflate is quite inefficient in promoting cyclopropanation of allyl alcohol, and the use of f-butyl diazoacetate [164/(165+166) = 97/3%] brought no improvement over ethyl diazoacetate (67/6 %)162). If, however, copper(I) triflate was the catalyst, cyclopropanation with ethyl diazoacetate increased to 30% at the expense of O/H insertion (55%). As has already been discussed in Sect. 2.2.1, competitive coordination-type and carbenoid mechanisms may be involved in cyclopropanation with copper catalysts, and the ability of Cu(I) to coordinate efficiently with olefins may enhance this reaction in the intramolecular competition with O/H insertion. 

In order to safely identify k0 with intramolecular carbenic reactions (e.g., k and the formation of alkene 4 in Scheme 1), product analysis should demonstrate that the yield of intramolecular products exceeds 90%, while dimer, azine, and solvent-derived (intermolecular) carbene products should be absent or minimal. If these conditions are not met, mechanistic interpretation is often ambiguous, a result that is well illustrated by the saga of benzylchlorocarbene (see below, Section IV.C). Less desirably, k0 can be corrected for competitive intermolecular carbenic reactions. Bimolecular reactions like dimerization and azine formation can be minimized by working at low carbene precursor concentrations, and careful experimental practice should include quantitative product studies at several precursor concentrations to highlight potential product contamination by intermolecular processes. 

DFT studies of the intramolecular ene-like (or the so-called 1,3-dipolar ene) reaction between nitrile oxides and alkenes show that this reaction is a three-step process involving a stepwise carbenoid addition of nitrile oxide to form a bicyclic nitroso compound, followed by a retro-ene reaction of the nitrosocyclopropane intermediate. The competitive reactions, either the intramolecular [3 + 2] cycloaddition between nitrile oxides and alkenes or the intermolecular dimerization of nitrile oxides to form furoxans, can overwhelm the intramolecular 1,3-dipolar ene reaction if the tether joining the nitrile oxide and alkene is elongated, or if substituents such as trimethylsilyl are absent (425). 

The last question still open addresses the alkynyl ketones. The reaction of 64 shows an example with a potential intramolecular competition and here it is possible to isomerize the propargyl substitutent on the ketone quantitatively without changing the 1-hexynyl substituent on the other side [125] (Scheme 1.28). From the publication it is not clear whether the isomerization is really a thermal reaction or occurs during the workup of the thermolysis reaction, for example by chromatography (compare the discussion above [110]). 

Finally, the intramolecular coupling reaction between an olefin and a pyrrole ring has been examined (Scheme 40). In this example, a 66% isolated yield of the six-membered ring product was obtained. A vinyl sulfide moiety was used as the olefin participant and the nitrogen protected as the pivaloyl amide in order to minimize the competition between substrate and product oxidation. Unlike the furan cyclizations, the anodic oxidation of the pyrrole-based substrate led mainly to the desired aromatic product without the need for subsequent treatment with acid. 

Section 2 discusses the syntheses of different classes of concave acids and bases. Convergent synthetic strategies were chosen for an easy structural variation of the reagents (modular assembly). Section 3 characterizes the concave acids and concave bases and checks whether the acid/base properties of the parent compounds benzoic acid, pyridine and 1,10-phenanthroline are conserved in the bimacrocyclic structures. In Section 4, the influence of the concave shielding on the reactivity and selectivity of the concave reagents is measured in model reactions. In principle, the concave shielding should be able to influence inter- and intramolecular competitions as well as chemoselectivity and (dia)stereoselectivity. If the reagent is chiral, enantioselectivity should also be observable. 

The above computer study suggested to investigate protonation reactions via protonated concave pyridines 3. Size selectivity was expected. In the following section (4.1) intramolecular competitions for protonations by concave pyridines 3 will be discussed. 

As the Connolly studies suggested (Sect. 3.5), protonated concave pyridines should be able to discriminate between small and large molecules. In a model reaction, a protonation reaction has therefore been examined. The protonation of nitronate ions 44 has been chosen [35] (Scheme 8). In these ions an intramolecular competition of carbon versus oxygen protonation leads to nitro (45) or flci-nitro (46) compounds. The latter ones may then be hydrolyzed by way of the Nef-reaction [36] to form carbonyl compounds 47. 

In an extremely clever study, Tanner and collaborators have estimated rate constants for fragmentation of a series of a-haloacetophenones41. These rate constants were determined by the intramolecular competition outlined in Scheme 9. Radical ion 4 was generated by reaction with l,3-dimethyl-2-phenylbenzimidazoline (DMBI). The rate constant ratio (k llc2) was determined by the relative yields of the two products 5 and 6. With the assumption that the a-substituent does not affect the magnitude of k2, was assumed to be equal to 3 x 107 s 1 (which had been measured earlier by Wipf and Wightman for the dehalogenation of p-bromoacetophenone radical anion)42. 

The relative power of DMG (Table 1), established by experiments at low temperature and short reaction times and thus crudely representative of kinetic control conditions, may vary with inter- and intramolecular competition, conditions, and sometimes results are conflicting. Nevertheless, for synthetic practice this hierarchy follows a qualitative order consistent with CIPE and serves as a useful predictive chart. For thermodynamic control conditions, the pchart of Fraser of 12 DMG [27], determined by equilibrium deprotonation using LiTMP (pka=37.8), is a guide for lithium dialkylamide DoM reactions. 

Probing mechanism of the reaction involving intramolecular competition between different isotopic species at several chemically equivalent positions, the number of equivalent sites must be taken into consideration. In the case of deuterium content at natural abundance the concentration of multiply labelled molecule is negligible and not-deuterated molecules are invisible in the 2H NMR. When reaction is taken to the completion the retained and transferred deuterium can be calculated from the 2H spectra of substrate and product. The KIE is given by ... 

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