1.3- diketones Michael-type reactions

Diketones. A new synthesis of 0-diketones depends on a Michael-type reaction of lithium 1-alkynyltrialkylborates with methyl vinyl ketone in the presence of an excess of TiCl4 (equation 1). Other Lewis acids are considerably less effective. 

The titanium(IV) chloride-promoted reactions of enol silyl ethers with aldehydes, ketones, and acetals, known as Mukaiyama reaction, are useful as aldol type reactions which proceed under acidic conditions (eq (23)) [20], Enol silyl ethers also undergo the Michael type reactions with enones or p.y-unsaturated acetals (eq (24)) [21]. Under similar reaction conditions, enol silyl ethers are alkylated with reactive alkyl halides such as tertiary halides or chloromethyl sulfides (eq (25)) [22], and acylated with acid halides to give 1,3-diketones (eq (26)) [23]. 

Michael-type reactions have been achieved with baker s yeast using trifluoroethanol as the co-substrate (Scheme 5.17). These transformations probably are related to the acyloin condensation in that it has been proposed that the trifluoroethanol is initially oxidized enzymically to the aldehyde, which is then converted to a reactive acyl anion that can add to the electrophilic enone in a conjugate manner. The a, -unsaturated ketones are good Michael acceptors, leading to the corresponding y-hydroxyketones (via the diketone intermediate) in moderate yields (26-40%) and good optical purities (e.e. = 79%). The absolute configurations of the products (16) were not determined. 

Diketones can be obtained by the Michael-type reaction of trialkyl-alkynylborates with methyl vinyl ketone in the presence of TiCl4 (Scheme 5). The reactions of bis(trimethylstannyl)butadiyne with trialkylboranes also involve alkynylborates. Use of 9-BBN derivatives has advantages for the synthesis of trisubstituted ethenes from lithium alkenyltrialkylborates. Alkenylborates for such reactions can be obtained from the corresponding tosylhydrazones. ... 

A Michael-type addition has been used to insert suitable Michael acceptors (47 R = CN, COMe, C02Me/Et) between the carbonyls of benzils (48), to give a range of 1,4-diketones (49). The reaction is catalysed by cyanide (typically as B114NCN), and the aryl rings can bear substituents such as chloro or methoxy. Reminiscent of the Benzoin condensation, the reaction proceeds through an O-aroylmandelonitrile anion (50). The reaction has also been extended to C—O rather than C—C insertion benzaldehyde inserts into benzil under the same conditions to give an a-aroyloxy-ketone (51). 

The net effect of the Stork enamine sequence is the Michael addition of a ketone to an a, -unsaturated carbonyl compound. For example, cyclohexanone reacts with the cyclic amine pyrrolidine to yield an enamine further reaction with an enone such as 3-buten-2-one yields a Michael-type adduct and aqueous hydrolysis completes the sequence to provide a 1,5-diketone product (Figure 23.8). 

The nucleophilic Michael-type addition onto a,j9-unsaturated ketones is one of the most powerful reactions for carbon-carbon bond formation. This reaction which is promoted under pressure [169] is accelerated in water due to the hydro-phobic effect as already postulated (see Sect. 3). In fact, various 1,3-diketones, such as l,3-cyclopentadione,have been shown to add readily to a,j9-unsaturated ketones in good yields without any catalyst (Scheme 32) [170]. 

Organotetracarbonylferrates, [RFe(CO)4], continue to find use in organic synthesis. A new synthesis of a-diketones consists of the reaction of aldehydes with alkyl halides and [Fe(CO)s]. The aldehyde, protected as the ethylenedithioacetal, is treated with butyl-lithium and [Fe(CO)s] to generate the acyltetracarbonylferrate (25) which then reacts with the alkyl halide to give the a-diketone in an overall yield of around 60%. [RFe(CO)4] reacts with Michael-type acceptors to give the expected product in about 90% yield [equation (10)]. ... 

Variations include the use of yne-ones, when conjugate addition of the cyanoacetamide controls the regiochemistry of reaction, and 3-alkoxy-enones (i.e. the enol ethers of 1,3-diketones) when comparably, the initial Michael-type... 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a p unsaturated ketones The most common types of carbanions used are enolate 10ns derived from p diketones These enolates are weak bases (Section 18 6) and react with a p unsaturated ketones by conjugate addition... 

Transition metal catalysis of the Michael reaction of 1,3-dicarbonyl compounds with acceptor activated alkenes has been known since the early 1980 s 2>3 It is a valuable alternative to the classic base catalysis of the reaction. Because of the mild and neutral conditions, the chemoselectivity of these reactions is superior to that provided by base catalysis, since the latter suffers from various unwanted side or subsequent reactions, such as aldol cyclizations, ester solvolyses or retro-Claisen type decompositions. A number of transition metal and lanthanide compounds have been reported to catalyze the Michael reaction, but FeCb 6 H20 is one of the most efficient systems to date. A number of 3-diketones or p-oxo esters and MVK are cleanly converted to the corresponding Michael reaction products within a few hours at room... 

Highly substituted tetrahydrothiophens can also be prepared by two related routes, the first of which involves the Michael addition of mercapto-esters to benzylidene-benzoylacetonitriles in the presence of triethylamine/ The authors had expected the formation of a 3-oxotetrahydrothiophen by a Dieck-mann-type cyclization. In the second reaction the base-catalysed condensation of diketosulphides with 1,2-diketones led smoothly to tetrahydrothiophen diols rather than the expected thiophens." In both cases the products are probably resistant to dehydration due to steric crowding. 

The classical method for the introduction of a 3-oxobutyl grouping with the formation of the diketone (33) is the Michael reaction between cyclic ketones of type (31) and methyl vinyl ketone. In some cases, the product of the addition of two molecules of methyl vinyl ketone (34) is obtained as a by-product [28]. 

In the formation of ring A from unsaturated -ketones (116), still another type of side reaction is possible, the formation of derivatives of phenanthrene of type (120) [61, 62] (Scheme 72). The diketone (117) obtained in the Michael reaction may subsequently form the ions (118) or (119), leading, respectively, to the normal reaction product (121) and the byproduct (120). It is obvious that in this case propinquity to a conjugated system makes the ion (119) more thermodynamically stable and therefore the reaction is directed towards the formation of the by-product (120). 

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