Organometallic reagents preparation

Organometallic reagents, prepared from fluorohalocarbons, including Grig-nard reagents [S2] or organolithium reagents prepared by transmetallation [80], are silylated with readily available alkylchlorosilanes (equations 70 and 71). 

Organometallic reagents prepared in situ from organomagnesium compounds... 

Different regioselectivities for the addition to azetidine-2,3-diones by organometallic reagents prepared from propargyhc bromides and Zn or In are observed. " Allenyl derivatives are produced exclusively with In in a mixture of THF and saturated NH4CI. 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Before we describe the applications of organometallic reagents to organic synthesis let us examine their preparation Organolithium compounds and other Group I organometal he compounds are prepared by the reaction of an alkyl halide with the appropriate metal... 

When planning the synthesis of a compound using an organometallic reagent or indeed any synthesis the best approach is to reason backward from the product This method is called retrosynthetic analysis Retro synthetic analysis of 1 methylcyclohexanol suggests it can be prepared by the reaction of methylmagnesmm bromide and cyclohexanone... 

Treatment of N hydroxysuccinimide with trifluoroacetic anhydnde gives N trifluoroacetoxysuccinimide quantitatively [27] Some otherwise hardly accessible trifluoroacetylated tertiary alcohols are readily prepared, though in poor yields, by reacting the appropriate anhydride with an excess of an organometallic reagent [22] (equation 11)... 

Preparation of Heterocyclic Enamines by Means of Organometallic Reagents... 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

The organometallic reagent was prepared by adding the diorganomagnesium compound to the dilithium salt of (S)-l,1 -binaph-thalcnc-2.2 -diol, itself prepared by addition of 2 equivalents of BuLi to the chiral diol. b n.r. = not reported. 

The only preparative limitation to this method is the occasional coproduction of alkenyl-boronates that presumably arise via a-elimination pathways of the ate complex generated upon addition of the organometallic reagent to the a-haloalkylboronate4,29-30. This problem is illustrated in the synthesis of 5-(rm-butyldimethylsilyloxy)-2-pentenyl-substituted dioxaborolane30. 

In order to synthesize 1,3-diphenyl-l, 3-diamines 3 containing a C2 axis of symmetry, which can be employed as auxiliaries and controller groups in asymmetric syntheses, the diastereoselective addition of organometallic reagents to racemic pyrazolines 2, prepared from cinnamaldehyde (l)23, was investigated. 

In this reaction, an/z-products 3 are formed exclusively while the yields vary depending on the metal. The organometallic reagents are prepared according to ref 16. 

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