Ketones with metal alkyls

As in catalytic hydrogenation, in reduction with metals alkyl pyridyl ketones make a complex picture. 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Reactions 33 and 35 constitute the two principal reactions of alkyl hydroperoxides with metal complexes and are the most common pathway for catalysis of LPOs (2). Both manganese and cobalt are especially effective in these reactions. There is extensive evidence that the oxidation of intermediate ketones is enhanced by a manganese catalyst, probably through an enol mechanism (34,96,183—185). 

C-C bonds can be formed by reaction with alkyl iodides or more usefully by reaction with metal carbonyls to give aldehydes and ketones e.g. Ni(CO)4 reacts with LiR to form an unstable acyl nickel carbonyl complex which can be attacked by electrophiles such as H+ or R Br to give aldehydes or ketones by solvent-induced reductive elimination ... 

Metalated SAMP- or RAMP-hydrazones derived from alkyl- or arylethyl ketones 3 add to arylaldehydes both diastereo- and enantioselectively. Substituted / -hydroxy ketones with relative syn configuration of the major diastereomer are obtained with de 51-80% and 70-80% ee. However, recrystallization of the aldol adducts, followed by ozonolysis, furnishes diastereo- and enantiomerically pure (lS, S )-. yn-a-mcthyl-/3-hydroxy ketones 5 in 36-51% overall yield. The absolute configuration of the aldol adducts was established by X-ray crystallographic analysis. Starting from the SAMP- or RAMP-hydrazone either enantiomer, (S,S) or (R,R), is available using this methodology16. 

The transition metal catalysed addition of a hydridosilane to a multiply-bonded system is known as hydrosilylation (1). Under such conditions, alkynes undergo clear cis-addition, so providing one of the most direct routes to vinylsilanes (Chapter 3). Hydridosilanes also add to the carbonyl group of saturated aldehydes and ketones, to produce alkyl silyl ethers. Fot example, under suitable conditions, 4-t-butylcyclohexanone (2) can be reduced with a high degree of stereoselectivity. 

The asymmetric organosilane reduction of prochiral ketones has been studied as an alternative to the asymmetric hydrogenation approach. A wide variety of chiral ligand systems in combination with transition metals can be employed for this purpose. The majority of these result in good to excellent chemical yields of the corresponding alcohols along with a trend for better ee results with aryl alkyl ketones than with prochiral dialkyl ketones. 

Still another possibility in the base-catalyzed reactions of carbonyl compounds is alkylation or similar reaction at the oxygen atom. This is the predominant reaction of phenoxide ion, of course, but for enolates with less resonance stabilization it is exceptional and requires special conditions. Even phenolates react at carbon when the reagent is carbon dioxide, but this may be due merely to the instability of the alternative carbonic half ester. The association of enolate ions with a proton is evidently not very different from the association with metallic cations. Although the equilibrium mixture is about 92 % ketone, the sodium derivative of acetoacetic ester reacts with acetic acid in cold petroleum ether to give the enol. The Perkin ring closure reaction, which depends on C-alkylation, gives the alternative O-alkylation only when it is applied to the synthesis of a four membered ring ... 

The organic analogues of the reactions to be discussed here are the borane reductions of aldehydes and ketones and the addition of metal alkyls across ketonic carbonyls, equation 15. In contrast to the ease of these organic reactions, qualitative data which has accumulated in our laboratory over the last decade demonstrates that the carbonyl group in organometallies is fairly resistant to addition across CO. For example, many stable adducts of organometallie carbonyls with aluminum alkyls are known, eq. lc, but under similar conditions a ketone will quickly react by addition of the aluminum alkyl across the CO bond. A similar reactivity pattern is seen with boron halides. 

Catalytic processes based on the use of electrogenerated nickel(O) bipyridine complexes have been a prominent theme in the laboratories of Nedelec, Perichon, and Troupel some of the more recent work has involved the following (1) cross-coupling of aryl halides with ethyl chloroacetate [143], with activated olefins [144], and with activated alkyl halides [145], (2) coupling of organic halides with carbon monoxide to form ketones [146], (3) coupling of a-chloroketones with aryl halides to give O -arylated ketones [147], and (4) formation of ketones via reduction of a mixture of a benzyl or alkyl halide with a metal carbonyl [148]. 

One problem in the anti-selective Michael additions of A-metalated azomethine ylides is ready epimerization after the stereoselective carbon-carbon bond formation. The use of the camphor imines of ot-amino esters should work effectively because camphor is a readily available bulky chiral ketone. With the camphor auxiliary, high asymmetric induction as well as complete inhibition of the undesired epimerization is expected. The lithium enolates derived from the camphor imines of ot-amino esters have been used by McIntosh s group for asymmetric alkylations (106-109). Their Michael additions to some a, p-unsaturated carbonyl compounds have now been examined, but no diastereoselectivity has been observed (108). It is also known that the A-pinanylidene-substituted a-amino esters function as excellent Michael donors in asymmetric Michael additions (110). Lithiation of the camphor... 

Whereas branched ketimines are metalated at the less substituted carbon, metalation and alkylation of unsymmetric imines leads to regioisomers2,4,27. For this reason, only symmetrical ketones and unsymmctrical ketones with one substituent having no a-hydrogens have been applied in alkylation reactions via imines (see Table 4). 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis.515 Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition-metals have also been used. Arylhydrazones are easily prepared by the treatment of aldehydes or ketones with phenylhydrazine (6-2) or by aliphatic diazonium coupling (2-7). However, it is not necessary to isolate the arylhy-drazone. The aldehyde or ketone can be treated with a mixture of phenylhydrazine and the catalyst this is now common practice. In order to obtain an indole, the aldehyde or ketone must be of the form RCOCH2R (R = alkyl, aryl, or hydrogen). 

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