Alkenyl alkyl ketones

Alkenyl alkyl ketones undergo both 1,2- and 1,4-hydroboration with 9-BBN, with preference for 1,2-addition. 

Despite the great success of the transmetalation process in the enantiose-lective arylation of ketones, its extension to allylation or alkynylation reactions failed, providing the corresponding tertiary alcohols with enantiomeric excesses never higher than 50% ee. On the other hand, more success has been found in the alkenylation of ketones. The process started with the hydrozirconation of terminal alkynes to give the corresponding alkenylzirconium intermediates, which were transmetalated by reaction, in this case, with various ketones in the presence of the HOCSAC ligand. This protocol tolerated the presence of other carbon-carbon multiple bonds on the alkyne, as well as different functionalities and achieved excellent results for alkyl ketones, a,(3-unsaturated ketones and even dialkylketones, as shown in Scheme 4.22. 

The addition of Grignard reagents or organolithiums (alkenyl, alkyl, alkynyl, allyl or aryl) to nitroenamines (281)213 was reported by Severin to afford P-substituted-a-nitroalkenes.214 b Similarly, ketone enolates (sodium or potassium), ester enolates (lithium) and lactone enolates (lithium) react to afford acr-nitroethylidene salts (294) which, on hydrolysis with either silica gel or dilute acid, afford 7-keto-a,(3-unsaturated esters or ketones (295)2l4c-d or acylidene lactones (296).214 Alternatively, the salts (294, X s CH2) can be converted to -y-ketoketones (297) with ascorbic acid and copper catalyst. 

As Table 5 indicates, alkyl aryl ketones are the best substrates for this reaction. This has also been the case for the previously developed chiral ligand systems. Nevertheless, there have been substantial improvements in enantioselectivity for the reactions of alkenyl methyl ketones and alkyl methyl ketones, using Rh-catalysts with chiral ligands 195a191, 206b207, and 207209. 

The binaphthol-modified lithium aluminum hydride reagents (BINAL-Hs) are also effective in enantioselective reduction of a variety of alkynyl and alkenyl ketones2 (Scheme 4.3b). When the reaction is carried out with 3 equivalents of (S)-BINAL-H at —100 to —78 C, the corresponding propargylic alcohol 3 and allylic alcohol 4 are obtained in high chemical yields with good to excellent levels of enantioselectivity. As is the case with aryl alkyl ketones, the alcohols with (.V)-con figuration are obtained when (S)-BINAL-H is employed. 

The Murai reaction (Scheme 4), the replacement of an ortho-CH on an aromatic ketone by an alkyl group derived from a substrate olefin, is catalyzed by a variety of Ru complexes. This C bond formation occurs via chelate directed C-H bond activation (cyclometalation) in the first step, followed by alkene insertion into RuH and reductive elimination of the alkylated ketone. In a recent example of the use of a related cyclometalation in complex organic synthesis, Samos reports catalytic arylation (Suzuki reaction) and alkenylation (Heck reaction) of alkyl segments of a synthetic intermediate mediated by Pd(II). 

Under analogous conditions, but at a lower temperature (-75 to -65°C), the anhydride 2 reacts with methyl alkyl (alkenyl, alkynyl) ketones 36 at their methyl group with the formation of compounds 37 [19-21],... 

In 2005, thiourea catalyst 7 was proved to be an efHcient and recyclable catalyst for the cyanosilylation of various ketones 6 (Table 30.2) [8]. In the reaction with 5 mol% catalyst 7, TMSCN, and an alcoholic additive, aryl-alkyl (entries 1, 3-5), alkenyl-alkyl (entries 10, 11) ketones, and cyclic ketones (entry 12) afforded adducts in high yields (91-98%) and high enantiopurities (86-98% ee). Yields for heteroaromatic analogues were lower (81-88%) but with high enantioselectivities (97-98% ee) (entries 6, 7). The substrate scope could be also extended to aldehydes... 

Various electrophiles other than iodine have been used to induce alkenyl coupling (9). Alkyl haUdes and protic acids react with alkynylborates to yield mixtures of stereoisomeric alkenylboranes. Nevertheless, oxidation of these products is synthetically useful, providing single ketones (296—298). Alcohols are obtained from the corresponding alkenylborates. 

The hydrosi(ly)lations of alkenes and alkynes are very important catalytic processes for the synthesis of alkyl- and alkenyl-silanes, respectively, which can be further transformed into aldehydes, ketones or alcohols by estabhshed stoichiometric organic transformations, or used as nucleophiles in cross-coupling reactions. Hydrosilylation is also used for the derivatisation of Si containing polymers. The drawbacks of the most widespread hydrosilylation catalysts [the Speier s system, H PtCl/PrOH, and Karstedt s complex [Pt2(divinyl-disiloxane)3] include the formation of side-products, in addition to the desired anh-Markovnikov Si-H addition product. In the hydrosilylation of alkynes, formation of di-silanes (by competing further reaction of the product alkenyl-silane) and of geometrical isomers (a-isomer from the Markovnikov addition and Z-p and -P from the anh-Markovnikov addition. Scheme 2.6) are also possible. 

Nitrogen functionality also assists the alkylation of ortho-Cr-H bonds of aromatics, as shown in Equations (10)—(12). In the case of aromatic imines, Ru3(GO)i2 exhibits a high catalytic activity.8-10 This reaction gives the alkylation product together with the alkenylation product in the reaction with triethoxyvinylsilane. Rhodium catalysts show the same activity to give the alkylation product.11,12,12a For example, the Rh(i)-catalyzed reaction of the imine of aromatic ketones with methyl acrylate... 

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... 

A variety of other powerful electrophiles add to the allylzirconium species 91, as shown in Scheme 3.26. Such reactions include the Lewis acid catalyzed addition of aryl, alkyl, or alkenyl acetals, derived from aldehydes, but not from ketones, and the addition of imi-nium species that lack p-hydrogens [56,58]. 

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