Nucleophilic attack types

Step 2 of the mechanism m Figure 6 12 is a nucleophilic attack by Br at one of the carbons of the cyclic bromonium ion For reasons that will be explained m Chapter 8 reactions of this type normally take place via a transition state m which the nude ophile approaches carbon from the side opposite the bond that is to be broken Recall mg that the vicinal dibromide formed from cyclopentene is exclusively the trans stereoisomer we see that attack by Br from the side opposite the C—Br bond of the bromonium ion intermediate can give only trans 1 2 dibromocyclopentane m accordance with the experimental observations... 

In contrast to electrophilic reagents, the highly -tt-deficient character of the pteridine nucleus is responsible for its vulnerability towards nucleophilic attack by a wide variety of reagents. The direct nucleophilic substitution of pteridine itself in a Chichibabin-type reaction with sodamide in diethylaniline, however, was unsuccessful (51JCS474). Pteridin-6-one, on the other hand, yielded pteridine-6,7-dione under the same conditions, via a still unknown reaction mechanism. 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

Let us focus attention on the unfavorable ring closures. Why, for example, should formation of a five-membered ring by an endo-trig process be difficult The answer is provided by a consideration of the trajectory of approach of the nucleophile." If Z is an electron-attracting conjugating group of the type necessary to activate the double bond to nucleophilic attack, the reaction would involve the LUMO of the conjugated system, a 7t ... 

A qualitative difference in the type of solvation (not simply in the strength of solvation) in a series of nucleophiles may contribute to curvature. Jencks has examined this possibility. " " An example is the reaction of phenoxide, alkoxide, and hydroxide ions with p-nitrophenyl thiolacetate, the Br insted-type plot showing Pnuc = 0.68 for phenoxide ions (the weaker nucleophiles) and Pnu = 0.17 for alkoxide ions. It is suggested that the need for desolvation of the alkoxide ions prior to nucleophilic attack results in their decreased nucleophilicity relative to the phenoxide ions, which do not require this desolvation step. 

Dehydrogenation of amino alcohols of type 40 affords even bicyclic compounds 41, the formation of which can be explained by nucleophilic attack of the hydroxyl group on the formed enamine salt (133,134). 

Electron densities, bond densities, and spin densities, as well as particular molecular orbitals may be displayed as graphical surfaces. In addition, the value of the electrostatic potential or the absolute value of a particular molecular orbital may be mapped onto an electron density surface. These maps provide information about the environment around the accessible surface of a molecule. Electrostatic potential maps show overall charge distribution, while orbital maps reveal likely sites for electrophilic and/or nucleophilic attack. Surface displays may be combined with any type of model display. 

Finally, select acetone from the molecules on screen. Here, both the LUMO and the LUMO map are available under the Surfaces menu. First, select LUMO and display it as a Solid. It describes a 7U-type antibonding ( i ) orbital concentrated primarily on the earbonyl carbon and oxygen. Next, turn off this surface (select None under the LUMO sub-menu), and then seleet LUMO Map under the Surfaces menu. Display the map as a transpareni solid. Note the blue spot (maximum value of the LUMO) directly over the carbonyl carbon. This reveah the most likely site for nucleophilic attack. 

Both the 4- and 5-positions of the pseudooxazolones are susceptible to nucleophilic attack. The reactivity of the >C=N— linkage is manifested by two types of behavior. 

When 1-hydroxymelatonin (19) is treated with acid, removal of its 1-hydroxy group leaves an indolyl cation (a hybrid of resonance structures 254,168, and so on) as shown in Scheme 37. If there is a subsequent intramolecular nucleophilic attack by the Ab-nitrogen atom on the side chain or if an intermolecular attack by suitable nucleophiles occurs on this intermediate cation, the birth of a new type of product can be expected. 

The direction of primary intermolecular nucleophilic attack at heterosubstituted acetylenes of type HC —X, where X = R2N, RO, RS, is governed by the nature of heteroatom and can be different. 

Because the anioas of nitroalkanes are stable, retro-acyladoc smoothly In the presence of a base catalyst. This type of reacdo organic synthesis." Nucleophilic attack of water or alcohol to ct-the ring cleavage v/ith the formadon of Oj-nitro acids and Oj-niti... 

The reaction processes shown in Scheme 8 not only accomplish the construction of an oxepane system but also furnish a valuable keto function. The realization that this function could, in an appropriate setting, be used to achieve the annulation of the second oxepane ring led to the development of a new strategy for the synthesis of cyclic ethers the reductive cyclization of hydroxy ketones (see Schemes 9 and 10).23 The development of this strategy was inspired by the elegant work of Olah 24 the scenario depicted in Scheme 9 captures its key features. It was anticipated that activation of the Lewis-basic keto function in 43 with a Lewis acid, perhaps trimethylsilyl triflate, would induce nucleophilic attack by the proximal hydroxyl group to give an intermediate of the type 44. 

Treatment of cyclic vinylaziridine 105 with organocuprates of the R2CuLi type proceeds in a highly syn-selective manner (Scheme 2.29) [46], The syn stereochemistry of the reaction reflects the effect of the acetonide group, which directs the nucleophilic attack to the less hindered a-face. The formation of SN2 products 109 from the cyclic (chlorovinyl)aziridine 107 can be explained by assuming a syn-SN2 ... 

The steric crowding introduced in the latter by the four ethyl substituents inhibits nucleophilic attack at platinum, so that complexes of this type tend to undergo substitution by a dissociative mechanism [89]. The complex of the more rigid ligand, 2,2, 2"-terpyridyl, Pt(terpy)Cl+, is found to be about 103 to 104 times more reactive to substitution than the dien analogue this is ascribed to steric strain [90], which is reflected in the short Pt—N bond to the central nitrogen (Pt-N some 0.03 A shorter than the other two Pt-N bonds) and N—Pt—N bond angles of 80-82°). 

A detailed mechanism of Goldschmidt s process has not been given two reaction paths are possible either proton transfer to the acid with the formation of RC(OH) (in which case the slow step would be an Aac2 Ingold mechanism) or nucleophilic attack of the carbonyl group of the acid on the protonated alcohol. The second mechanism would require an alkyl scission (A l). In more recent studies2501, it has been shown that scission in most cases is of the acyl type and particularly in the examples studied by Goldschmidt. 

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