Favor Closely Related Intermediates

Favor transforms that generate closely related intermediates. 

This elimination reaction is the reverse of acid-catalyzed hydration, which was discussed in Section 6.2. Because a carbocation or closely related species is the intermediate, the elimination step would be expected to favor the more substituted alkene as discussed on p. 384. The El mechanism also explains the general trends in relative reactivity. Tertiary alcohols are the most reactive, and reactivity decreases going to secondary and primary alcohols. Also in accord with the El mechanism is the fact that rearranged products are found in cases where a carbocation intermediate would be expected to rearrange ... 

In closely related experiments it was shown that sp C—H activation takes place reversibly within the coordinahon sphere of the electron-rich Ir(I)-diphosphine complex 58 (Scheme 6.9) to form an alkyl-amino-hydrido derivative 57 reminiscent of the CCM intermediate 24 the solid-state structure of 57 is shown in Figure 6.13 [40]. It appears that C—H activation only takes place after coordination of the amine function to the Ir(I) center (complex 58, NMR characterized). Amine coordination allows to break the chloro bridge of 59 and to augment the electron density of the metal center, thus favoring oxidative addihon of the C—H bond. Most importantly, the microscopic reverse of this C—H activation process (i.e. C—H reductive elimination) models the final step of the CCM cycle (see Scheme 6.1) indeed, the reaction of Scheme 6.10 is cleanly reversible at 373 K. 

It is therefore intriguing to understand what is the particular role of the platinum/electrolyte interface in the Kolbe synthesis favoring that reaction path—Eqs. (39a)-(39c)—which is thermodynamically disfavored and unlikely to occur. A closely related reaction whose kinetics are easier to investigate with conventional electrode kinetic methods is the anodically initiated addition of N3 radicals to olefins, discovered by Schafer and Alazrak (275). The consecutive reactions, which follow the initial generation of the reactive intermediate, an Na radical, are somewhat slower than that of the Kolbe radicals, so that their rate influences the shape and potential of the current voltage curves which can be evaluated in terms of reaction rates and rate laws. 

Proposed more than 20 years ago, the stalk intermediate—a highly curved lipid stmcture— provides the most plausible description of the initial fusion stage currently available. The related stalk-pore mechanism (23-25) of fusion is viewed favorably by most researchers. It shows the close relation between fusion and the transition from lamellar into bilayer cubic and hexagonal phases (see Fig. 4 in the section entitled Formation of nonlamellar phases in membrane lipids ). Studies on the rhombohedral phase formed in partially dehydrated lipids provide another insight into the possible structure of fusion stalks (26). 

Another closely related application of this type of chemistry is an elegant method of intramolecular disulfide formation on the solid phase using a polymer-bound version of Ellman s reagent [35]. Although similar conceptual schemes had been previously applied to solid-phase heterodimer formation [36,37] from single Cys-containing fragments, in this account the solid-phase chemistry has been especially adapted to favor intramolecular reaction and minimize irreversibly resin-bound intermediates. 

Under thermodynamically favorable PET reactions (AEe,<0), the radical ions are formed either as contact ion pair (CIP) or solvent-separated ion pair (SSIP). A closely related question is whether the primary intermediate is a SSIP or CIP. Gould et al. [11] have suggested in their recent study that in the polar solvents such as CH3CN, electron transfer quenching results in the formation of SSIP directly, and in these solvents, the fully solvated ions (SSIP) can separate to form free radical ion pairs (FRIP) [12]. Therefore, under these reaction conditions, the anion radicals are potentially less reactive with the cation radicals than in nonpolar solvents in which CIP is more important. The use of polar solvents (e.g., CH3CN and MeOH) thus facilitates ion radical chemistry [13]. 

On the other hand, the closely related platinum(ll)-catalyzed reaction of substrates with a geminal dimethyl block that prevents similar isomerizations provides contrary evidence in favor of a proto-de-metallation of an alkylplatinum intermediate (Scheme 4b) [19]. Additional evidence for protonolysis of the C-Pd... 

The mechanism for the Niementowski quinoline synthesis is presumably similar to that of the closely related Friedlander reaetion. The mechanism for the Friedlander reaction has been studied extensively" and two possible mechanistic pathways exist, as illustrated below. There is support for both pathways. Most of the evidence, however, tends to favor initial formation of the SchifTs base intermediate (13) followed by cyclization to give quinoline 15 however, the reaction conditions and structures of the reactants may influence the pathway by which the reaetion proeeeds. ... 

The anions of the HWE reagents 27a,b were reacted with the chiral monoketone 99 to afford the corresponding Z- and -olefins 100 and 101 with high diastereo-meric excesses, depending upon which enantiomer of the chiral phosphonate was employed. The olefinic products thus obtained served as key intermediates in the synthesis of prostacyclin derivatives [59, 60]. A closely related chiral reagent, 24, bearing 8-phenylnormenthol [67], both enantiomeric forms of which are readily accessible, provided an improved diastereoselectivity in favor of the -isomer 101 (Scheme 7.16). 

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