Mechanistic course

The reaction of anmonia and amines with esters follows the sane general mechanistic course as other nucleophilic acyl substitution reactions (Figure 20.6). A tetrahedral intennediate is fonned in the first stage of the process and dissociates in the second stage. 

For the mechanistic course of the reaction the diketone 5 is assumed to be an intermediate, since small amounts of 5 can sometimes be isolated as a minor product. It is likely that the sodium initially reacts with the ester 1 to give the radical anion species 3, which can dimerize to the dianion 4. By release of two alkoxides R 0 the diketone 5 is formed. Further reaction with sodium leads to the dianion 6, which yields the a-hydroxy ketone 2 upon aqueous workup ... 

The applicability to alicyclic alcohols may be limited, since the mechanistic course via a cyclic transition state requires a suitably positioned hydrogen in order to afford the desired product. 

For a discussion of the mechanistic course of the reaction, many aspects have to be taken into account. The cisoid conformation of the diene 1, which is in equilibrium with the thermodynamically more favored transoid conformation, is a prerequisite for the cycloaddition step. Favored by a fixed cisoid geometry are those substrates where the diene is fitted into a ring, e.g. cyclopentadiene 5. This particular compound is so reactive that it dimerizes easily at room temperature by undergoing a Diels-Alder reaction ... 

For the mechanistic course of that reaction two pathways are discussed " a concerted [l,3]-sigmatropic rearrangement, and a pathway via an intermediate diradical species. Experimental findings suggest that both pathways are possible. The actual pathway followed strongly depends on substrate structure the diradical pathway appears to be the more important. 

Even if this simple, formal picture does not reflect the mechanistic course of the reaction, it allows the major diastereomer formed in a multitude of addition reactions, where the stereochemistry is determined only by stcric interactions to be predicted. 

Scheme 2.85. Stereochemical and mechanistic course of the domino threefold conjugate...

In order to further probe the mechanistic course of the above reaction, the possibility of a pinacolic intermediate was addressed. To test this hypothesis, the reaction of active uranium with benzopinacol was conducted. 

The influence of the halogen on the mechanistic course of carbanionic rearrangement of 3-hexylhalomethylenecyclobutanes (Scheme 11, X = F, Cl, Br, I) to l-halo-4-hexylcyclopentenes has been explored by studying the fate of C-labelled methylene... 

Hydroximoyl halides (4) are conveniently prepared by halogenation of the respective aldoximes (5), for which a number of halogenating agents such as chlorine (38), ferf-butyl hypochlorite, A -chlorosuccinimide (NCS) (39), or A -bromosuccin-imide (NBS) (40) have been employed. A plausible mechanistic course involves Hal addition and proton loss to give an a-halonitroso compound, often observed as a transient blue-green color, as shown for the chloro case (Scheme 6.1). 

Mechanistic aspects of alkene hydrogenation are by now known in considerable detail, but far less information is available on the mechanistic course of the alkyne hydrogenation reaction.160 In general, data on the hydrogenation of alkynes are rather limited.24... 

There is still uncertainty about the mechanistic course of this reaction. The isolation of the dibenzodisalicylide (527) from the pyrolysis of the ester (526) at 205-210 °C points to its intermediacy, since at higher temperatures it is converted into xanthone (Scheme 194). 

Martynov and RozepmaU2J have reported addition of alkaline hydrogen sulfide to occur at the carbon atom nearest the ester function in ethyl 0,/iJ diinethylglycid te. ThiB is in notable contrast to Martynov s own obeervatiotxB with amines (see section IV.4.B), which appear to add primarily to the most alkylated carbon atom of this substance (i.e. to the epoxide carbon atom furthest from the ester function). Addition of HS ions and amines may perhaps be suspected of following different mechanistic courses. 

Formation of both 1,2- and 1,4-addition products occurs not only with halogens, but also with other electrophiles such as the hydrogen halides. The mechanistic course of the reaction of 1,3-butadiene with hydrogen chloride is shown in Equation 13-1. The first step, as with alkenes (Section 10-3A), is formation of a carbocation. However, with 1,3-butadiene, if the proton is added to C1 (but not C2), the resulting cation has a substantial delocalization energy, with the charge distributed over two carbons (review Sections 6-5 and... 

Structural and energetic aspects of the ene reaction have been investigated320 using a variety of computational methods incorporating different ways of accounting for electron configuration, and the mechanistic course of Lewis acid-catalysed cycloaddi-... 

A possibility would be monomeric thymidine 3 -nietaphosphorothioate, which in the active site allowing the rotation around C-0 bond would lead to the same preferred orientation being adopted whatever the stereochemistry of the starting diester and this would then lead to a single diastereomeric product P>p -10. If this explanation is correct and hydrolysis of thymidine 3 -p-nitrophenyl- 80 phos-phate would follow the same mechanistic course, its hydrolysis in 1170 H20 containing medium in the presence of SPDE should lead to formation of P-racemic thymidine 3 160,170,180 phosphate. The work on elucidation of this hypothesis is in progress. 

Following Bergman s initial report <1984JA7272, 1986JA7346>, cyclopropane C-H activation and subsequent isomerization of the intermediate tr-cyclopropylrhodium hydride 169 to the rhodacyclobutane complex 112 has been demonstrated for a tris(pyrazolyl)borate analogue (Scheme 39), confirming that net cyclopropane oxidative addition to rhodium follows a rather unexpected indirect mechanistic course <19980M4484>. 

All of the alkenylations and arylations discussed in this section follow the common mechanism exemplified in Figure 16.18. The steps shown in Figure 16.18 may involve more than one elementary reaction, as in the case of the mechanistic course of the Ni-catalyzed C,C coupling with Grignard compounds (Figure 16.12). It should be noted that the basic sequence of steps is very much the same in Figures 16.18 and 16.12. 

The current density has a dramatic influence on the yield of 52 and reveals that more than one electrode reaction is involved in the sequence. When the current density is in the range of 2.8. 7 mA/cm2, 52 is directly obtained in about 30% yield. The rationale for the formation of 52 starts with the direct or indirect generation of phenoxyl radicals at the BDD anode. Since the used conditions will provide concentrations of oxyl spin centers, which exclude a recombination, the transformation has to follow a different mechanistic course. The anodic treatment will cause an Umpolung effect because the electron rich phenol is oxidized [110-113]. Such phenoxyl species are still electrophilic despite the liberation of a proton [114-119]. The electrophilic attack occurs at the most electron rich position of the reaction partner which provides the observed connectivity in 52 (Scheme 21). 

More recently, van der Donk and coworkers reported radical cyclizations catalyzed by vitamin B12 using titanium(III) citrate as a stoichiometric reducing agent (Fig. 69, entry 17) [330]. Here /V-allylic 2-(isopropenyl) pyrroles 290 or allyl 2-phenylallyl ethers serve as the starting material in tandem hydrocobaltation/ radical 5-exo cyclization sequences giving dihydropyrrolizine derivatives 291 or 292. The mechanistic course is not completely clear. However, it is assumed that the reactions start with an initial hydrocobaltation of the isopropenyl unit in the presence of the allylic alkene (see Sect. 5.7). The benzylic cobalt intermediate is subject to homolysis of the very weak cobalt-carbon bond and initiates the radical 5-exo cyclization. Interestingly, the fate of the cyclized radical is dependent on the... 

Nucleophilic aromatic photosubstitution reactions have been divided into five mechanistic categories17 and each of these mechanistic types has its representatives in the class of aryl halides. Which reaction pathway is followed in any particular case depends on a number of factors such as the nature of the leaving group, the presence of electron-donating or electron-withdrawing substituents on the aromatic ring, the solvent, the multiplicity and the lifetime of the reactive excited state and the presence or absence of electron donors or acceptors in the reaction medium. This renders it rather difficult to make predictions about the mechanistic course that will be followed under a given set of circumstances. 

Scheme 33. Possible mechanistic course of the Pd(ll)/Co(lll)-mediated dimerization of benzene.

Scheme 37. Proposed mechanistic course of the NO+-mediated dimerization of 1-methylnaphthalene. 14.5...

While relative acidities are extremely important to our abilities to accurately predict the mechanistic courses of organic reactions, we must recognize that in addition to acids, most heterolytic reactions involve bases as well. Furthermore, as will soon be discussed, in organic chemistry, bases generally are able to function as nucleophiles. Therefore, this chapter will serve as an introduction to the types of bases and nucleophiles that drive mechanistic organic chemistry. 

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