Acylzirconocene, ketone addition

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

The reactivity of acylzirconocene chlorides towards carbon electrophiles is very low, and no reaction takes place with aldehydes at ambient temperature. In the reaction described in Scheme 5.12, addition of a silver salt gave the expected product, albeit in low yield (22—34%). The yield was improved to 79% by the use of a stoichiometric amount of boron trifluoride etherate (BF3OEt2) (1 equivalent with respect to the acylzirconocene chloride) at 0 °C. Other Lewis acids, such as chlorotitanium derivatives, zinc chloride, aluminum trichloride, etc., are less efficient. Neither ketones nor acid chlorides react with acylzirconocene chlorides. In Table 5.1, BF3 OEt2-mediated reactions of acylzirconocene chlorides with aldehydes in CH2C12 are listed. 

It is interesting to note that the reaction of N-salicylideneaniline, which possesses a free phenolic hydroxyl group at the ortho position in the benzylidene portion, with the acylzirconocene chloride gives the a-amino ketone in 67 % yield in the absence of any additive (Scheme 5.16) [23]. Similarly, N-(p-hydroxybenzylidene)aniline reacts with the acylzirconocene chloride to give the a-amino ketone in 58 % yield. The reaction of N-(m-hydroxyben-zylidene)aniline, however, gives the a-amino ketone in just 12 % yield. Neither N-(o-MeO-benzylidenejaniline nor N-(p-MeO-benzylidene)aniline gives an appreciable amount of product in the absence of additive. 

The formation of an allenyl ketone as the sole product can be achieved by using an excess (2 equiv.) of propargyl bromide (entries 3—6, Table 5.9). Use of an increased amount (3 equiv.) of the acylzirconocene chloride in the reaction with propargyl bromide and/or tosylate yields a significant amount of a 1,4-dicarbonyl compound derived from Michael-type addition of the acylzirconocene chloride to the initially formed allenyl ketone (entry 2, Table 5.9). The Michael-type addition of acylzirconocene chlorides to allenyl ketones under Cu(I)-catalyzed conditions has been confirmed by an independent experiment (Scheme 5.31). 

Reactions of a,(3-unsaturated acylzirconocene chlorides with stable carbon nucleophiles (sodium salts of dimethyl malonate and malononitrile) at 0°C in THF afford the Michael addition products in good yields (Scheme 5.38). Direct treatment of the reaction mixture with allyl bromide in the presence of a catalytic amount of Cul -2LiCl (10 mol%) in THF at 0 °C gives the allylic ketone in a one-pot reaction. This sequential transformation implies the electronic nature of a,P-unsaturated acylzirconocene chloride to be of type E as shown in Scheme 5.37. 

Recently, Hanzawa et al. reported that, catalyzed by Cu(II), the reaction of an acylzirconium with propargyl bromide affords 1,2-allenyl ketones 428, which may undergo a further conjugate addition with acylzirconocene to give 2-methylene 1,4-diketones 429 [191],... 

Scheme 24 Regioselective 1,2- or 1,4-addition of acylzirconocenes to a,)0-unsaturated ketones...

Acylzirconocene derivatives can also be further transmetaUated by addition of a catalytic amount of a copper salt. These species behave as organocopper derivatives and undergo S 2 reactions with allyl- [36] and propargylic halides [36], but also undergo Michad-type addition with aDenyl ketones and enones [37] and finally react with acetyl chlorides [38] (Scheme 12.29). 

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