Nucleofugal group

L. Strekowski, M. Lipowska and G. Patonay, Substitution reactions of a nucleofugal group in heptamethine cyanine dyes. Synthesis of an isothiocyanato derivative for labeling of proteins with a near-infrared chromophore, J. Org. Chem. 57.4578-4580(1992). 

Significantly, silylcuprates react with carbamates with syn stereoselectivity59, similar to their reactions with organocuprates62, whereas other nucleofugal groups, such as acetate or methanesulfonate, are displaced in an anti fashion23,27,57. Thus, both enantiomeric (or epimeric) allenes can be obtained from the same propynyl alcohol precursor. 

Not only was this result a great achievement in its own right,9 but it also stands as the primeval example11 of a most important route to many types of organic fluorides, i.e. displacement of a nucleofugal group by fluoride ion. 

H2S in the presence of NaHCO , leads to elimination of a nucleofugal group at the 2-position. However, attack at either the 2- or 6-positions may give the same results (Scheme 66) (83TL3713). 

Hydrolysis of 188 can also occur at the 4-carbon leading to 191 (Scheme 76) (Scheme 77). As in the case of 188 when the 2-position of the thiazine-4-one (194) is substituted by a nucleofugal group, the latter can also be substituted (Scheme 78) (67CB3671). 

The telluraxanthylium salts 92 readily add pyridine at position 9 to give salts 112 (89KGS691). The pyridinium cation behaves as a good nucleofugal group prone to substitution by alkoxy groups when salts 112 are treated with alcohols. 

It should be noted that the nucleofugal group in component XII (Scheme 6.83) might also be a cationic sulfonium moiety. In this circumstance the nucleophile attacking the aldehyde is a sulfur ylide. Catalytic enantioselective versions of the transformation of aldehydes to epoxides involving sulfur ylides are covered in Section 6.8. 

As mentioned in Sec. 15.2.3, benzylic radicals are obtained also from the cleavage of a nucleofugal group from the radical anion. This may lead again to benzylation, and it has been shown that irradiation of 1,4-dimethoxynaphthalene in the presence of substituted benzyl halides leads to benzylated naphthalenes (mainly in position 2) via benzyl radical/arene radical cation combination, which is analogous to the benzyl radical/radical... 

A much more deep-seated photorearrangement than in the dibenzo[2.2.2] systems occurs in the dibenzo[3.2.1] compound 55 with chloride or bromine as nucleofugal group at C-8 (equation 49)229. 9-Functionalized phenanthrenes are formed, supposedly also by way of photoinduced intramolecular electron transfer in the (triplet) excited state. 

In the S l mechanism of aromatic substitution the initiating step is the formation of a radical anion. In order to distinguish the process from the route described above (SR+N1) in which a radical cation plays a crucial role, the symbol S l has been used17. Creation of the radical anion can occur by several procedures. The reaction can be electrochemically initiated, a solvated electron in a solution of alkali metal in liquid ammonia may be involved or a radical anion may be used as the source of electrons. The most common source of electrons is, however, the nucleophile itself involved in the substitution reaction. In many cases the electron transfer from nucleophile to substrate is light-catalysed and the process is then sometimes referred to as S l Ar. Although the nucleofugic group in S l... 

All the substrates have the same nucleofugal group, and there is a correlation between the relative reactivity and the standard reduction potential (E° of ArBr or Ei/2 of the unsub-... 

When the nucleophilic centre and the nucleofugal group are in ra-position, the photo-stimulated reaction gives ultimately the ring closure product by an intermolecular followed by an intramolecular S l reaction. Thus, the reaction of the enolate ion of co- m-bromophenyl)-3,3-dimethylalkan-2-one (325) in liquid ammonia gives [m-m] cyclopha-dienones (326) (equation 194)340. 

As shown above, a number of ortho-cyclizations of azines with bifunctional reagents have been performed by substitution of two adjacent nucleofugic groups and allow the syntheses of a great variety of condensed azine derivatives. The obvious limitation of this method is that it can only be applied to those aza-aromatics which contain two good leaving groups oriented in ortho positions to each other. 

The alkylation of enolates offers one a most common way to simply introduce one carbon-carbon bond a to a carbonyl functionality. The acylation would be briefly treated as well, since the formation of the C—C bond in the final product formally represents the displacement of a nucleofugal group by the incoming nucleophilic enolate. 

In one sense, the stereochemistry at the carbon carrying the nucleofugal group X in the anti-periplanar process 5.14 can be seen as an inversion of configuration, since the electrons supplied by the C -M bond, where M stands for any electro-fugal group, flow into the n bond of the product 5.15 from the side opposite to the... 

Both nucleophilic and electrophilic attack on trigonal carbon can take place by two pathways (Fig. 5.4)—direct attack on one of the cr bonds attached to the double bond (path a), or by attack on the n bond (path b), with the formation of an ionic intermediate, followed by the loss, respectively, of a nucleofugal group X or an electrofugal group M. There are also formally unimolecular pathways, SN1 and SeI, with ionisation followed by capture by the nucleophile or electrophile, but the former is rare and the latter unknown. 

Applying this idea to the SN2 reaction, with the advantage that we can be confident that the nucleofugal group in a concerted reaction will be conjugated... 

The reactions of alkyl cuprates with allylic acetates are always stereospecifi-cally anti 5.114 —> 5.115, although the formation of racemic product shows that regiocontrol has been lost. These reactions are not mechanistically Sn2 reactions, since they involve in the first step coordination of the copper on the lower surface, followed by the formation of a re-allyl system at the same time as the acetate leaves. The delivery of the methyl group to the same surface, and equally to both ends of the allylic system, is a reductive elimination. It seems likely that the decisive step determining the stereoselectivity is that coordination of the copper anti to the nucleofugal group is needed before it will leave. 

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