Oxygen nucleophiles regioselectivity

These results are not inconsistent with literature precedents for the SnAt reaction of 2,4-difluoronitrobenzene. There are several examples of displacement with oxygen, (5) nitrogen, (P) and carbon (malonate) (10) nucleophiles. With oxygen nucleophiles, regioselectivity ranges from non-selective (1 1) to modest ortho selectivity (2-3 1). With nitrogen nucleophiles the regioselectivity varies more widely, from pura-selective (Pa) to non-selective, 9b) to ort/io-selective.(Pc,d) With stabilized carbon nucleophiles (malonate), there are reports of both para 10a) and ortho 10b) selectivity. 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

Factors that determine the regioselectivity are the deactivation of one of the two oxygen nucleophiles by stereochemically controlled dimerization of the dioxastannolane, and by equilibration of the possible isomeric products (Equation (141)).389-391... 

One of the earliest uses of palladium(II) salts to activate alkenes towards additions with oxygen nucleophiles is the industrially important Wacker process, wherein ethylene is oxidized to acetaldehyde using a palladium(II) chloride catalyst system in aqueous solution under an oxygen atmosphere with cop-per(II) chloride as a co-oxidant.1,2 The key step in this process is nucleophilic addition of water to the palladium(II)-complexed ethylene. As expected from the regioselectivity of palladium(II)-assisted addition of nucleophiles to alkenes, simple terminal alkenes are efficiently converted to methyl ketones rather than aldehydes under Wacker conditions. 

Amine nucleophiles appear generally to add by attack at the allyl ligand. Similar to oxygen nucleophiles, however, a caveat must be noted in evaluating the observed regioselectivities in that the allyl amine products are capable of rearrangement by reentry into the ir-allyl manifold. 

The regioselectivity in the methoxydefluorination reactions of difluoroquinolines has been examined.48 Studies of the substitution patterns in 2-cyano-3-nitroimidazole[l,2-a lpyridine have shown that nitrogen and oxygen nucleophiles substitute the 2-cyano group whereas sulfur nucleophiles replace the 3-nitro group.49... 

In the Au(I) catalysis of electron-poor alkynes such as 4, the catalytically active species is likely to be a cationic ligand-stabilized gold(I) Jt-complex, as in previously reported additions of oxygen nucleophiles to alkynes [5], Gold catalysts are very soft and thus carbophilic rather than oxophilic. On the basis of this assumption a plausible mechanism can be formulated as shown in Scheme 6. The cationic or strongly polarized neutral Au(I)-catalyst coordinates to the alkyne, and nucleophilic attack of the electron-rich arene from the opposite side leads to the formation of a vinyl-gold intermediate 7 which is stereospecifically protonated with final formation of the Z-olefm 8 [2, 4]. Regioselectivity is dominated by elec-... 

Acid anhydrides, being carbonyl electrophiles with polarized C=0 bonds, respond to charge tensity (they are hard electrophiles) and react well with oxygen nucleophiles. Bromine, by - jntrast, is uncharged and unpolarized (it is a soft electrophile) and reacts well with neutral nucleophiles such as alkenes (Chapter 20). Each electrophile reacts regioselectively with the part of --.e enol that suits it best. 

In substrates bearing suitable functionality that could lead to internal nucleophilic attack by an oxygen, even a carbonyl oxygen, excellent regioselectivity may occur. Equation 1.31 illustrates an example of a ketone playing such a role [27]. Such an effect can even lead to hydration at the more hindered alkyne as shown in... 

Phenyl vinyl sulfones reacted with cyclohexanone enamines 332 to afford adducts which, upon hydrolysis, gave 2-(2-phenylsulfonyl)alkylcyclohexanone 333a . However, in the reaction with phenyl styryl sulfone, two products 333b and 334 were obtained by the nucleophilic attack at the and a-carbon atoms . Steric effects, electrostatic interactions between the nitrogen atom of the enamine and the oxygen atoms of the sulfone group, and medium effects contribute to the regioselectivity of the reaction. ... 

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