Alkyl halides 1.1- propargyl metals

Whereas allyl, benzyl and propargyl electrophiles are among the most reactive towards Pd, Ni and other transition metals, ordinary alkyl halides and related alkyl electrophiles that are not /3, -unsaturated are among the least reactive carbon electrophiles with respect to oxidative addition to Pd or Ni. Most of the alkyl derivatives are also associated... 

Metalatlon of 2-alkynyl and 1,2-alkadienyl tetrahydropyranyl ethers furane synthesis. /-Butyllithium metalates the lithium alkoxide 1 to afford the allenyllithium compound a quantitatively. This anion reacts with alkyl halides or CH3OH to afford 2. Another metalation-alkylation protonation sequence proceeds via b to afford 3. Hydrolysis of the latter intermediate affords furanes directly. The overall sequence can be performed in one pot from a propargyl tetrahydropyranyl ether, r-butyl-lithium, and an aldehyde. ... 

Propargylic sulfides " and selenides have been metallated with n-butyllithium and lithium amide respectively, and allylated or alkylated selectively at the propargylic position (Scheme 34) with primary and secondary alkyl halides. - ... 

The reaction between alkyl halides and aluminum metal is the basis of the oldest method for the synthesis of organoaluminum compounds. For example, propargylic bromides react with aluminum in ether giving organoaluminum compounds that on treatment with acetals yield solely a-allenic ethers (equation 1)." However, the reaction of simple alkyl halides with aluminum metal requires a long reaction time. 

While the a-allylation of enolates occurs with high ee using palladium catalysts (see Section 10.2) there have been few reports on the enantioselective metal-catalysed enolate alkylation. The best results to date have been achieved by Doyle and lacobsen using the chromium(salen) complex (12.42) in the alkylation of cyclic tin enolates with a range of alkyl halides, including propargyl and benzylic hahdes... 

Before discussing in detail the nucleophilicity of metal complexes towards organic molecules it is important to appreciate the depth of reactivity types that is being considered. Predominantly the organic substrates are alkyl halides and tosylates, acyl halides, aryl halides and allyl halides together with a limited amount of information of the interactions with propargyl halides, and epoxides. 

Among other reactions, the bis-metallated species (151) derived from nitroalkanes condense with dialkyl carbonates to give comp>ounds (152), in 60—80% yield, which can serve as precursors of both a-amino-acids and a-hydroxyamino-esters as well as a-keto-esters. Oxazolin-5-ones (153) can be alkylated at the 4-position by alkyl halides in hot DMF containing HMPA and ethyldi-isopropylamine. Yields are good (60—90%) for allylic, benzylic, and propargylic halides but otherwise poor (e.g. 32% with EtI) under these conditions acid hydrolysis of the products affords substituted a-amino-acids. Mesoionic l,3-oxazol-5-ones (154), obtained from imidoyl chlorides and acyl-tetracarbonylferrates, react with alcohols to give N-acyl-a-amino-acid esters. ... 

The coupling reaction of a-keto esters with allyl, propargyl, and allenyl halides using indium metal in aqueous solvents affords a-hydroxy-y,<5-unsaturated esters (Equation (28)).197,198 1,3-Dicarbonyl compounds undergo efficient carbonyl allylation reactions in an aqueous medium through a Barbier-type reaction (Equation (29)). The reaction is general and a variety of 1,3-dicarbonyls has been alkylated using allyl bromide or allyl chloride in conjunction with indium.199... 

Alkynylmagnesium halides are less basic than the alkali metal acetylides and therefore can be applied to sensitive alkylating agents. In contrast to the alkali metal acetylides they do not react with saturated primary halides. On the other hand, they do react with allylic, propargylic and benzylic halides, but only in the presence of cuprous chloride catalysts. They also react with a-haloethers (e.g. equation 136)" . 

As well as the simple alkyl iodides and bromides, other organic halides react directly with Zn metal in polar solvents, e.g., (i) triphenylmethyl chloride in DMF, (ii) propargylic bromides in tetrahydrofuran (THF), e.g. ... 

In addition to coupling reactions that occur with aryl and vinyl nucleophiles and electrophiles, coupling reactions that occur with sp -hybridized nucleophiles or electrophiles have been developed. These reactions include those that form tertiary and quaternary stereocenters from racemic or prochiral nucleophiles, as shown in Equation 19.4. Substitution reactions at propargylic and benzylic electropliiles have also been reported, and several groups have reported in recent years progress in metal-catalyzed substitutions of alkyl electrophiles, including enantioselective substitutions of aliphatic organic halides. 

Reaction of potassium tris(pyrazolyl)borate with [Pd(Me)2(pyridazine)] or [Pd(Me)(Ph)(tmeda)] produces the anions [Pd(Me)(R)(HB pyrazolyl 3)], R = Me, Ph respectively. Treatment with wet ketone produces the Pd(IV) alkyls [Pd(Me)2(R)(HB pyrazolyl)3)]. The trimethyl product has been ciystallographically charactmsed. The net reaction is oxidation of Pd(II) by water accompanied by a methyl group transfer. Allenyl and propargyl halides add trans across the metal centres in [Pd(PPh3)4] and [Pt(PPh3)4], The isomerisation of the o- allenyl products [M(X)(CH=C=CRR )] has been studied and the crystal structure of one example has been determined. 

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