Alkyl leaving groups

The ligand 2,6-di-t-butylphenoxide has been shown to undergo cyclometallation with a number of early transition metals. The reaction involves the intramolecular activation of the CH bonds of the Bu groups to generate six-membered rings. Besides alkyl leaving groups, alkylidene and benzyne functions have been shown to be potent for the activation of these normally inert C—H bonds. 

In the case of alkyl leaving groups, mechanistic studies show that a-bond metathesis pathways are active, proceeding via four-centre, four-electron transition states. In the case of unsaturated functional groups, the reaction involves addition of the CH bond across the r-component, so that the substrate hydrogen atom remains (labelling studies) within the product molecule. The cyclometallation of 2,6-dimethylphenoxide by a tantalum alkylidene ligand has also been demonstrated. ... 

The introduction of additional alkyl groups mostly involves the formation of a bond between a carbanion and a carbon attached to a suitable leaving group. S,.,2-reactions prevail, although radical mechanisms are also possible, especially if organometallic compounds are involved. Since many carbanions and radicals are easily oxidized by oxygen, working under inert gas is advised, until it has been shown for each specific reaction that air has no harmful effect on yields. 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

Dimethyl acetylenedicarboxylate (DMAD) has also been used to catalyse gramine alkylations (see Entry 7). It may function by both activating the dialkylamino leaving group and deprotonating the nucleophile[3]. 

Because the carbon-halogen bond breaks m the slow step the rate of the reaction depends on the leaving group Alkyl iodides have the weakest carbon-halogen bond and are the most reactive alkyl fluorides have the strongest carbon-halogen bond and are the least reactive... 

Nucleophilic substitution reactions of alkyl halides are related to elimination reactions m that the halogen acts as a leaving group on carbon and is lost as an anion The... 

The order of alkyl halide reactivity in nucleophilic substitutions is the same as their order m eliminations Iodine has the weakest bond to carbon and iodide is the best leaving group Alkyl iodides are several times more reactive than alkyl bromides and from 50 to 100 times more reactive than alkyl chlorides Fluorine has the strongest bond to car bon and fluonde is the poorest leaving group Alkyl fluorides are rarely used as sub states m nucleophilic substitution because they are several thousand times less reactive than alkyl chlorides... 

We saw m Section 8 2 that the rate of nucleophilic substitution depends strongly on the leaving group—alkyl iodides are the most reactive alkyl fluorides the least In the next section we 11 see that the structure of the alkyl group can have an even greater effect... 

As we have seen the nucleophile attacks the substrate m the rate determining step of the Sn2 mechanism it therefore follows that the rate of substitution may vary from nucleophile to nucleophile Just as some alkyl halides are more reactive than others some nucleophiles are more reactive than others Nucleophilic strength or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate By measuring the rate at which various Lewis bases react with methyl iodide m methanol a list of then nucleophihcities relative to methanol as the standard nucleophile has been compiled It is presented m Table 8 4... 

As crowding at the carbon that bears the leaving group decreases the rate of nude ophilic attack by the Lewis base increases A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to pre dominate and primary alkyl halides react with alkoxide bases by an 8 2 mechanism m preference to E2... 

Because halides are poorer leaving groups than p toluene sulfonate alkyl p toluene sulfonates can be converted to alkyl halides by 8 2 reactions involving chloride bro mide or iodide as the nucleophile... 

Section 8 14 Nucleophilic substitution can occur with leaving groups other than halide Alkyl p toluenesulfonates (tosylates) which are prepared from alcohols by reaction with p toulenesulfonyl chloride are often used... 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

The Williamson ether synthesis (Sec tion 16 6) An alkoxide ion displaces a halide or similar leaving group in an Sn2 reaction The alkyl halide cannot be one that is prone to elimination and so this reaction is limited to methyl and primary alkyl halides There is no limitation on the alkoxide ion that can be used... 

The product of this series of steps is an alkyl diazonium ion, and the amine is said to have been diazotized Alkyl diazonium ions are not very stable decomposing rapidly under the conditions of their formation Molecular nitrogen is a leaving group par excel lence and the reaction products arise by solvolysis of the diazonium ion Usually a car bocation intermediate is involved... 

Alkyl esters of trifluoromethanesulfonic acid, commonly called triflates, have been prepared from the silver salt and an alkyl iodide, or by reaction of the anhydride with an alcohol (18,20,21). Triflates of the 1,1-dihydroperfluoroalkanols, CF2S020CH2R can be prepared by the reaction of perfluoromethanesulfonyl fluoride with the dihydroalcohol in the presence of triethylamine (22,23). Triflates are important intermediates in synthetic chemistry. They are among the best leaving groups known, so they are commonly employed in anionic displacement reactions. 

Reactions with Acyl Garbanion Equivalents. Alkyl substituted carbanions CRXY with potential leaving groups X, Y, and acyl carbanion equivalents or CHRX (342) react with alkylboranes, providing products with mixed alkyl groups derived from both reagents. 

Synthesis. The first hiUy alkyl/aryl-substituted polymers were reported in 1980 via a condensation—polymeri2ation route. The method involves, first, the synthesis of organophosphine-containing alkyl or aryl substituents, followed by the ready oxidation of the phosphine to a phosphorane with leaving groups suitable for a 1,2-elimination reaction. This phosphorane is then thermally condensed to polymers in which all phosphoms atoms bear alkyl or aryl substituents. This condensation synthesis is depicted in Eigure 2 (5—7,64). 

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