Electrophiles Reformatsky reagents

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

Another useful application of these Reformatsky reagents is their conversion to difluaraketene silyl acetals and subsequent reaction of these ketene silyl acetals with electrophiles [86, 89, 90] (equation 59)... 

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

Fullerene (114) also acts as an electrophile towards the Reformatsky reagents. When 114 is stirred with an excess of ethyl bromoacetate (lb) and zinc under solvent-free... 

Two examples are reported here based on the reaction of Reformatsky reagents with phosphorus(III) electrophiles. In equations 67 and 68, a dichlorophosphine or a monochlorophosphine is reacted with 2 or 1 equivalents of la in the presence of zinc in refluxing benzene. Quenching of the crude unstable tertiary phosphine with H202 allows one to isolate phosphino oxides 116 and 117 in good yields, generally as stable solid compounds154. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

The homo-Reformatsky reagent derived from the benzyl ester of N-Boc protected P-iodoalanine (Ch. 5, p. 204) reacts under sonication with various electrophiles. With acyl chlorides in the presence of a palladium catalyst, protected y-keto a-amino acids are obtained without racemization (Fig. 28).i An experiment is described in Chapter 9 (p. 348). 

The formation of an organometallic reagent in the presence of an electrophilic partner is a synthetic process of historical value, illustrated by the Barbier and Reformatsky reactions. In their first versions, these processes consisted of additions to carbonyl compounds. They have now been extended to a wide variety of substrates and were reviewed in a recent book.250... 

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