Reacting centers

A classic diagnostic use of such stereochemical requirements, due to Ruzicka, is the ring contraction induced in natural products containing the 4,4-dimethyl-5a-3 -ol system (94). The epimeric, axial 3a-alcohols (95) dehydrate without ring contraction. Barton suggested that it is necessary for the four reacting centers (hydroxyl, C-3, C-4, C-5) to be coplanar for ring contraction to occur, and this is only the case with the 3)5-alcohol. 

In 6j5-hydroxy-19-iodo steroids (Figure 12-2) the orientation of the reacting centers O—CH2—I resembles the arrangement in the transition state of an S 2 displacement reaction and consequently the activation energy for the transition (3) (4) is low. It has been suggested that the conformation... 

As pointed out by Chapman et the steric requirements of the reagents and the degree of solvation of the substrate at the reacting center should also be considered when comparing the nucleophilicities of different amines toward different substrates. The large number of factors which may be involved clearly call for much more work in this area. 

Illuminati and Marino reported an interesting example of the dependence of solvent effects on the position of the reacting center relative to the aza group. The rate constants for the reaction of 2- and 4-chloroquinoline with piperidine were compared in three different solvents, methanol, piperidine, and toluene. These data are reported in Table III. Three main points are apparent from these data (a) the different response of the two substrates to the action of the solvent, (b) the rates for 2-chloroquinoline in the three solvents tend to cluster around the highest reactivity level shown by 4-chloroquinoline in... 

The mechanism of the carbo-Diels-Alder reaction has been a subject of controversy with respect to synchronicity or asynchronicity. With acrolein as the dieno-phile complexed to a Lewis acid, one would not expect a synchronous reaction. The C1-C6 and C4—C5 bond lengths in the NC-transition-state structure for the BF3-catalyzed reaction of acrolein with butadiene are calculated to be 2.96 A and 1.932 A, respectively [6]. The asynchronicity of the BF3-catalyzed carbo-Diels-Alder reaction is also apparent from the pyramidalization of the reacting centers C4 and C5 of NC (the short C-C bond) is pyramidalized by 11°, while Cl and C6 (the long C-C bond) are nearly planar. The lowest energy transition-state structure (NC) has the most pronounced asynchronicity, while the highest energy transition-state structure (XT) is more synchronous. 

Secondary orbital interactions (SOI) (Fig. 2) [5] between the non-reacting centers have been proposed to determine selectivities. For example, cyclopentadiene undergoes a cycloaddition reaction with acrolein 1 at 25 °C to give a norbomene derivative (Fig. 2a) [6]. The endo adduct (74.4%) was preferred over the exo adduct (25.6%). This endo selectivity has been interpreted in terms of the in-phase relation between the HOMO of the diene at the 2-position and the LUMO at the carbonyl carbon in the case of the endo approach (Fig. 2c). An unfavorable SOI (Fig. 2d) has also been reported for the cycloaddition of cyclopentadiene and acetylenic aldehyde 2 and its derivatives (Fig. 2b) [7-9]. The exo-TS has been proposed to be favored over the endo- IS. 

The SOI concept is akin to the unsymmetrization of orbitals. The only difference is in the sites of the subsidiary interactions, which occur between the non-reacting centers (positions 3 and 4 in Fig. 3a) in SOI and between the reacting and non-reacting centers (sites 2 and 3 in Fig. 3b) for the unsymmetrization of orbitals (Fig. 1). The orbital phase environment around the reaction centers is a general idea... 

Lithiated cyanohydrin acetonides are potent nucleophiles. Reactive electrophiles like butyl bromide work well (Eq. 8). Less reactive electrophiles like -alkoxy-and -silyloxy bromides (Eqs. 9 and 10) also smoothly participate in alkylations. Increased steric bulk near the reacting center of the cyanohydrin acetonide is well tolerated (Eq. 11) [21]. 

In this section we focus on intramolecular functionalization. Such reactions normally achieve selectivity on the basis of proximity of the reacting centers. In acyclic molecules, intramolecular functionalization normally involves hydrogen atom abstraction via a six-membered cyclic TS. The net result is introduction of functionality at the S-atom in relation to the radical site. 

To the first of these pertain steric, inductive, catalytic or other effects responsible for the influence of reacted centers on the reactivity of neighboring centers... 

Fig. 2. Mutual relation and geometrical parameters of the reacting centers of the pair of guest molecules 11a...

Fig. 5. Stereoscopic drawing of the packing arrangement in 22 a down the plane of the reacting centers (marked by filled ellipsoids)...

Fig. 6. Relevant geometric parameters involving the reacting centers in 22 a...

The results (Figs. 21-25) show that bond-strengthening and bond-weakening effects of the substituents are also at work here. The most heavily substituted bond is broken most easily. This is specially evident in the case of [13], where Figs. 23—25 show the energetics of the rupture of each of the three bonds. Moreover, the double rotation at the reacting centers is... 

In accord with previous proposals, Pfaltz and co-workers (30) suggested that this reaction proceeds by initial formation of copper carbenoid 47 (Scheme 3). Pfaltz does not invoke a metallacyclobutane intermediate but rather suggests that nucleophilic attack of the alkene on 47 with concomitant pyramidalization at the reacting centers forms two possible transition states with stereoselectivities deter-... 

The importance of the environment of the reacting centers in high-pressure reactions has already been dealt with in connection with the determination of the reaction volume and of the activation volume, and also in connection with the... 

This may appear to be an unlikely situation to encounter until one recalls that there are a number of reactions involving two isolated and independently reacting centers. One might then anticipate that statistically A , = Ik and that Sg = l/2( + < ). These are precisely the conditions demanded by (1.91). It is worth noting that in this case the observed first-order rate constant is k2-... 

The process by which a stereochemically inactive center is converted to a specific stereoisomeric form. In most cases, the reacting center is prochiral. Such processes can occur with reactions involving an optically active reagent, solvent, or catalyst (eg., an enzyme). The reaction produced by such a process is referred to as an enantioselective reaction. In principle, use of circularly polarized light in photochemical reactions of achiral reactants might also exhibit asymmetric induction. However, reported enantioselectivities in these cases have been very small. 

Chiral aziridines having the chiral moiety attached to the nitrogen atom have also been applied for diastereoselective formation of optically active pyrrolidine derivatives. In the first example, aziridines were used as precursors for azomethine ylides (90-95). Photolysis of the aziridine 57 produced the azomethine ylide 58, which was found to add smoothly to methyl acrylate (Scheme 12.20) (91,93-95). The 1,3-dipolar cycloaddition proceeded with little or no de, but this was not surprising, as the chiral center in 58 is somewhat remote from the reacting centers... 

It would usually be assumed that abstraction/recombination reactions such as those illustrated in this section would proceed with racemization at the reacting centers. It has been reported22, however, that photocyclization of amide 1 proceeds with complete retention of absolute configuration. Racemization at the site of abstraction requires orbital rehybridization, passing through a planar intermediate. In this case rehybridization appears to be markedly slowed. This may be an electronic effect due to the heteroatom substituent on the intermediate radical, or simply a steric effect. The structure of product 2 was established by X-ray crystallographic analysis. 

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