Zinc ketone enolates preparation

An alternative method for the preparation of a kinetic zinc ketone enolate (123) from an arene thiol ester 121 and bis(iodozincio)methane (122) in the presence of a palladium(O) catalyst was developed by Matsubara and coworkers (equation 36) . The modest reactivity of the zinc reagent 122 makes this transformation highly chemo- and regioselective neither isomerization of the kinetic enolate 123 nor a palladium-catalyzed coupling with the thiol ester 121 could be observed. Thus, treatment of zinc enolate 123 with various aldehydes or ketones led regioselectively to one aldol product 124. The method provides access to reactive functionalized zinc enolates which are otherwise hard to obtain. 

Recently, Shchepin and coworkers described Michael addition reactions with zinc ketone enolates (144) for the preparation of chroman-2-one derivatives 146. The enolates were generated in situ from a-bromo ketones 143 by addition of excess zinc (equation 40), and subsequent conjugate addition to a, S-unsaturated ketones (145) (equation 40 ) provided chroman-2-ones (146a, b) in yields up to 82% . 

Zinc ester enolates may also be obtained by the addition of ZnX2 to lithium or sodium enolates as first described by Hauser and Puterbaugh (equation 6)P This approach has so far received little attention but similar reactions have been used to obtain zinc ketone enolates. In this regard, it should be noted that Heathcock and coworkers have shown that deprotonation reactions of ketones with zinc dialkylamide bases reach equilibrium at only about 50% conversion (equation 7). This result implies that attempts to prepare zinc enolates from solutions of amide-generated lithium enolates will be successful only when the lithium enolate is made amine-free. 

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 asymmetric Michael addition of nonstabilised ketone enolates has proved difficult, with most success achieved using 1,3-dicarbonyls as donors. However, Shibasaki and coworkers have achieved high ees in the addition of a-hydroxyketones with both aromatic Michael acceptors such as (11.32) and also cyclic enones and alkyl vinyl ketones, using bifiinctional zinc catalysts prepared from linked BINOL (11.33). These catalysts are also effective in the asymmetric aldol reaction (see Section 7.1) and incorporate two zinc atoms, one of which activates the acceptor carbonyl group and the other forms a zinc enolate with the donor. In addition, catalysts of this type have been used to good effect in the addition of P-ketoesters to cyclic enones. 

The role of stoichiometric amount of zinc compounds in the aldol reaction was studied 30 years ago (107). The first study of asymmetric zinc-catalyzed aldol reaction was carried out by Mukaiyama and co-workers the chiral zinc catalyst was prepared from diethylzinc and chiral sulfonamides and was effective in the reaction of ketene silyl ethers with aldehydes (108). Among the subsequent studies on zinc-catalyzed aldol reactions, Trost s group gave important contribution to zinc/prophenol ligand complexes (109,110). The chiral dinuclear zinc catalyst promotes the direct aldol reaction of ketones, including a-hydroxyketones, and aldehydes with excellent enantioselectivity (Scheme 17). It is proposed that one zinc metal coordinated different substrates to form zinc enolate, and another zinc metal center provided the bridge between the interaction of donor and acceptor. 

Bromide 280 (derived by bromination of silyl enol ether 270) undergoes both zinc- and cerium-mediated cleavage under mild and essentially neutral conditions, and was used to prepare the nucleoside-containing C-glycoside 282 (Scheme 73) [ 112,113], The aldehyde 281 used in this transformation was exceptionally sensitive to basic conditions which completely precluded use of a conventional enolate obtained by deprotonation of ketone 265 (Sect. 4.3.1). 

Fig. 17.49. Reductions of a-heterosubstituted ketones to a-unsubstituted ketones (see Figures 15.34 and 17.59 for the preparation of compounds A and B, respectively). Here, a ketyl is formed as a radical anion intermediate (for more details about ketyls see Section 17.4.2). The ketyl obtained from A releases a chloride ion, the ketyl resulting from B releases a hydroxide ion. In each case, an enol radical is formed thereby which picks up an electron. This leads to the formation of a zinc enolate from which the final product is generated by protonation.

Huorinated etiolates are generally difficult to form. Ishihara and coworkers used fluorovinyl phosphates, which can be prepared from a-fluoro ketones and sodium diethyl phosphite. Reaction of these fluorinated enol phosphates with a reagent prepared from lithium aluminum hydride (LiAIH4> and cop-per(II) bromide, zinc(II) chloride, tin(II) chloride or bromine afforded the enolate (Scheme 34).The reaction of the enol phosphate with the reagents mentioned above suggests that the metal cation of the enolate is an aluminum species, though its actual structure is not known at present. 

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