Soft nucleophile

As supporting evidence, rapid isomerization of the ds- and maui-Tr-allylpal-ladium complexes 27 and 28 is catalyzed by Pd(Ph3P)4 in THF even at -15 C to give a 45 55 equilibrium mixture from either 27 or 28[29-31].. Actually, in the intramolecular reaction of soft nucleophiles of 29 and 30, a trans-ds mi.xttire (31 and 32) (1 1) was obtained from /raiw-allylic acetate 29. On the... 

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

Another reaction occurs by the attack of a soft nucleophile at the central carbon to form the 7r-allylpalladium complex 7, which undergoes further reaction with the nucleophile typical of rr-allylpalladium complexes to form the alkene 8,... 

A soft (nucleophilic) Grignard reagent has been developed (82—84). The value of this reaction is demonstrated ia acylation reactions (82). 

It was mentioned earlier that 6-halopenlclllanlc acids are resistant to nucleophilic displacement. Displacement at the 6-positlon with soft nucleophiles (e.g. halide, RS ) but not hard nucleophiles e.g. MeO , amines) can be carried out, however, on 6-trifloxy- and 6-nonafloxy-penlclllanate esters (80TL2991). Some examples are shown in Scheme 38. 

The soft-nucleophile-soft-electrophile combination is also associated with a late transition state, in which the strength of the newly forming bond contributes significantly to the stability of the transition state. The hard-nucleophile-hffld-elechophile combination inqilies an early transition state with electrostatic attraction being more important than bond formation. The reaction pathway is chosen early on the reaction coordinate and primarily on the basis of charge distributiotL... 

In fee absence of fee solvation typical of protic solvents, fee relative nucleophilicity of anions changes. Hard nucleophiles increase in reactivity more than do soft nucleophiles. As a result, fee relative reactivity order changes. In methanol, for example, fee relative reactivity order is N3 > 1 > CN > Br > CP, whereas in DMSO fee order becomes CN > N3 > CP > Br > P. In mefeanol, fee reactivity order is dominated by solvent effects, and fee more weakly solvated N3 and P ions are fee most reactive nucleophiles. The iodide ion is large and very polarizable. The anionic charge on fee azide ion is dispersed by delocalization. When fee effect of solvation is diminished in DMSO, other factors become more important. These include fee strength of fee bond being formed, which would account for fee reversed order of fee halides in fee two series. There is also evidence fiiat S( 2 transition states are better solvated in protic dipolar solvents than in protic solvents. 

Carbanions are classified as soft nucleophiles. It would be expected that they would be good nucleophiles in 8 2 reactions, and this is generally true. The reactions of aryl-. 

Replacement of iodine in (perfluoroalkyl)ethyl iodides predominates over the usual conversion to olefins when the reagent is very nucleophilic and weakly basic Soft nucleophiles like sodium thiocyanate and sodium thiolates react well in displacements [46, 47] (equation 42)... 

Although thiirene dioxides do not react with typical tertiary amines like triethylamine, they do react with the amidine 1,5-diazobicyclo-[4.3.0]-non-5-ene (DBN) to give a 1 1 adduct betaine119158 141, analogously to the reaction of thiirene dioxides with soft nucleophiles (equation 57). 

Trost and coworkers7 have reported the use of palladium(O) as a catalyst for displacement of the phenylsulfonyl group by soft nucleophiles. Thus, treatment of allyl sulfone 12 with the sodium salt of dimethyl malonate in the presence of 5 mol % of... 

In the presence of an excess of non-reducible soft nucleophile (for example PhS- or PhSe -), a new reducing species may be formed which allows in certain cases a propagation cycle (electron chain catalysis). 

As shown in this table, the metal catalysts used in the literature are mostly complexes of Ni or Cu and less often Co or Pd. For soft nucleophiles, on the left of the table, the efficiency of the nickel catalysts was already reported. Here, are presented the investigations concerning the arylation of hard nucleophiles such as amines, alcohols or hydroxide anion, using Ni, Pd and Cu catalysts. 

Fig. 23. Reactions of bromoarenes with hard (and soft) nucleophiles catalyzed by nickel, copper and palladium...

The use of chiral transition-metal complexes as catalysts for stereoselective C-C bond forming reactions has developed into a topic of fimdamental importance. The allyhc alkylation is one of the best known of this type of reaction. It allows the Pd-catalyzed substitution of a suitable leaving group in the allylic position by a soft nucleophile. 

Allylic substitutions catalysed by palladium NHC complexes have been studied and the activity and selectivity of the catalysts compared to analogous Pd phosphine complexes. A simple catalytic system involves the generation of a Pd(NHC) catalyst in situ in THF, from Pdj(dba)j, imidazolium salt and Cs COj. This system showed very good activities for the substitution of the allylic acetates by the soft nucleophilic sodium dimethyl malonate (2.5 mol% Pdj(dba)3, 5 mol% IPr HCl, 0.1 equiv. C (CO ), THF, 50°C) (Scheme 2.22). Generation of the malonate nncleophile can also be carried out in situ from the dimethyhnalonate pro-nucleo-phile, in which case excess (2.1 equivalents) of Cs COj was used. The nature of the catalytic species, especially the number of IPr ligands on the metal is not clear. 

Scheme 1.1 Mechanism for Pd-catalysed allylic substitution with soft nucleophiles.

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