Aldehyde hydroacylation

Bosnich and coworkers reported the first example of aldehyde hydroacylation (i.e., Tischenko reaction) in the presence of a cationic Rh(I) catalyst (Scheme 2.40). The proposed mechanism occurs via C—H activation of the aldehyde, C=0 insertion,... 

Ketone hydroacylation is more challenging than the corresponding aldehyde hydroacylation presumably due to a slower rate of ketone insertion, rendering decarbonylation kinetically competent. For instance, 4-oxo-4-phenylbutanal reacts to generate the desired lactone product (59%) in addition to the decarbonylation product (40%) (Scheme 2.42) [86]. 

Transition metal complex-mediated hydroacylation of pyridine derivatives with aldehydes 99SL1. 

Related oxidation processes have been reported that allow the generation of esters directly from aryl aldehydes [6] and the hydroacylation of a-keto esters with aldehydes [7]. 

Tab. 3.27 Solvent-free hydroacylation of 1-alkenes with aldehyde.

A fast and efficient molybdenum-catalyzed asymmetric allylic alkylation under noninert conditions has been reported using MW-accelerated reaction [178]. Inter-molecular hydroacylation of 1-alkenes with aldehydes has been presented as a greener alternative to classical approach using a homogeneous catalyst in toluene. 

Based on Watanabe s intermolecular hydroacylation of olefins with aldehydes,348 Kondo and Misudo developed the first ruthenium-catalyzed hydroacylation of 1,3-dienes with aldehydes (Scheme 71). Usually, palladium-mediated hydroacylations of 1,3-dienes with aldehydes give tetrahydropyran and/or open-chain homoallylic alcohol derivatives.350 However, in the present ruthenium-catalyzed transformations, the corresponding /3,7-unsaturated... 

Rhodium( )-Catalyzed Asymmetric Hydroacylation of Olefins and Alkynes with Aldehydes I 85... 

The most significant progress that has been described to date in the area of rhodium-catalyzed asymmetric hydroacylation of olefms/alkynes with aldehydes has involved intramolecular processes that generate either cyclopentanones or cyclopentenones. Fig. 4.2 illustrates two of the more likely mechanisms for these ring-forming reactions [12, 13]. 

After extensive screening of various aldehydes to optimize the reaction conditions, it was found that aromatic aldehydes were able to serve as a carbon monoxide source, in which the electronic nature of the aldehydes is responsible for their ability to transfer CO efficiently [24]. Consequently, aldehydes bearing electron-withdrawing substituents are more effective than those bearing electron-donating substituents, with pentafluoro-benzaldehyde providing optimal reactivity. Interestingly, for all substrates tested the reaction is void of any complications from hydroacylation of either the alkene or alkyne of the enyne. Iridium and ruthenium complexes, which are known to decarboxylate aldehydes and catalyze the PK reaction, demonstrated inferior efficiency as compared to... 

The hydrative cyclization involves the formation of a ruthenium vinylidene, an anti-Markovnikov addition of vater, and cyclization ofan acylmetal species onto the alkene. Although the cyclization may occur through a hydroacylation [32] (path A) or Michael addition [33] (path B), the requirement for an electron- vithdra ving substituent on the alkene and lack of aldehyde formation indicate the latter path vay to be the more likely mechanism. Notably, acylruthenium complex under vent no decarbonylation in this instance. 

Addition of tin and mercury hydrides to unsaturated ketones 5-22 Free-radical addition of aldehydes or ketones to olefins 5-24 Hydroacylation of alkenes... 

Rhodium-catalyzed hydroacylation of appropriately substituted olefinic aldehydes gives cyclopentanone and cyclohexanone, respectively (Scheme 13) [49]. 

Keywords aldehyde, 1-alkene, hydroacylation, RhCl(PPh3)3, microwave irradiation... 

Hydroacylation of carbonyls or alkenes by aldehydes is well known. Hydroacylation of an activated ketone (85) by benzaldehyde has now been reported, giving a new asymmetric centre at the ketone carbon (86).257 In a metal-free procedure, the reaction... 

Acylmetal hydride is formed by the oxidative addition of aldehyde, and hydroacylation occurs by insertion of alkene or alkyne. The Ni-catalysed hydroacylation of internal alkyne 600 with aldehyde gave rise to the v./l-unsaturated ketone 601 [230]. The Ru-catalysed hydroacylation of cyclohexene with aldehyde 602 under CO pressure at high temperature gives the ketone 603 [231]. 

The Rh-catalyzed hydroacylation of alkynes is also possible. Reaction of salicyl-aldehyde (611) with 4-octyne using an Rh-DPPF complex gave the unsaturated ketone 612 in high yield [236],... 

An intermolecular hydroacylation of alkynes or electron-poor alkenes (e.g. CH2= CHCChMe) with /3-thioacetal-substituted aldehydes, catalysed by [(dppe)Rh]C104, has been reported to occur in acetone at 50 °C. The reaction is believed to proceed via a chelated rhodium acyl intermediate.111... 

The hydroacylation of olefins with aldehydes is one of the most promising transformations using a transition metal-catalyzed C-H bond activation process [1-4]. It is, furthermore, a potentially environmentally-friendly reaction because the resulting ketones are made from the whole atoms of reactants (aldehydes and olefins), i.e. it is atom-economic [5]. A key intermediate in hydroacylation is a acyl metal hydride generated from the oxidative addition of a transition metal into the C-H bond of the aldehyde. This intermediate can undergo the hydrometalation ofthe olefin followed by reductive elimination to give a ketone or the undesired decarbonyla-tion, driven by the stability of a metal carbonyl complex as outlined in Scheme 1. 

An interesting example is the hydroiminoacylation reaction, a good alternative to hydroacylation reactions, using aldimines as a synthetic equivalent to aldehydes (Scheme 4) [4]. The rhodium-catalyzed hydroiminoacylation of an olefin with aldimines produced a ketimine which could be further acid-hydrolyzed to give the ketone. The reaction proceeded via the formation of a stable iminoacylrhodi-um(III) hydride (this will be discussed in the mechanism section), production of which is facilitated by initial coordination of the rhodium complex to the pyridine moiety of the aldimine. This hydroiminoacylation procedure opened up the direct... 

C-H Transformation at Aldehydes and Imines Table 1. Examples for inter- and intramolecular hydroacylation. 

A primary alcohol and amines can be used as an aldehyde precursor, because it can be oxidized by transfer hydrogenation. For example, the reaction of benzyl alcohol with excess olefin afforded the corresponding ketone in good yield in the presence of Rh complex and 2-amino-4-picoline [18]. Similarly, primary amines, which were transformed into imines by dehydrogenation, were also employed as a substrate instead of aldehydes [19]. Although various terminal olefins, alkynes [20], and even dienes [21] have been commonly used as a reaction partner in hydroiminoacylation reactions, internal olefins were ineffective. Recently, methyl sulfide-substituted aldehydes were successfully applied to the intermolecu-lar hydroacylation reaction [22], Also in the intramolecular hydroacylation, extension of substrates such as cyclopropane-substituted 4-enal [23], 4-alkynal [24], and 4,6-dienal [25] has been developed (Table 1). 

The allylic activation of 1,3-dienes by Ru(COD)(COT) makes possible their hydroacylation to form /5,y-unsaturated ketones via C-H activation of aldehydes at the same metal center [117], and their selective coupling with acrylic compounds [18] (Eq. 87). 

In 1980, Miller et al. [76] reported the first example of an intermolecular hydroacylation of an aldehyde with an olefin to give a ketone, during their studies of the mechanism of the rhodium-catalyzed intramolecular cyclization of 4-pentenal using ethylene-saturated chloroform as the solvent. Later James and Young [77] reported that the reaction of propionaldehyde with ethylene can be conducted in the presence of RuCl2(PPh3)3 as the catalyst without any solvent at 210 °C, resulting in the formation of 3-pentanone in 2-4% yield (turnover number of 230) (Eq. 49). 

Later, they also reported an intermolecular hydroacylations of 1,3-dienes with aromatic aldehydes yielding the corresponding j8,y-unsaturated ketones (Eq. 51) [79]. This reaction does not require a CO atmosphere. The addition of formyl C-H bond in formic acid esters and amides to olefins and conjugate... 

Lenges CP, Brookhart M. Co(I)-catalyzed inter- and intramolecular hydroacylation of olefins with aromatic aldehydes. J Am Chem Soc 1997 119(13) 3165—3166. 

Finally, there are also some special NHC-mediated transformations that do not completely fit into the classification, such as triazolylidene-catalyzed hydroacylations (Chan and Scheldt 2006). Aldehydes can serve as hydride donors for activated ketones partly following a standard 1,2-addition of the NHC to the aldehyde, but instead of the usual carbonyl umpolung a hydride ( H-umpolung ) transfer is initiated. A related Cannizzaro-type transformation has been described for indazole-derived carbene catalysts (Schmidt et al. 2007). 

In hydroacylation reactions the C—H bond of an aldehyde is in effect added across a C=C bond ... 

Catalytic hydroacylation. Aldimines of 3-methyl-2-aminopyridine and aromatic aldehydes react with chlorotris(triphenylphosphine)rhodium(I) (1) in THF at 55 to afford products of imine C—H insertion (3). Aminals of 2-aminopyridine and aldehydes with a-hydrogens (4) similarly react with 1 to give 5 presumably, the aminals are in equilibrium with the corresponding imines under these conditions. These complexes undergo hydroacylation reactions with ethylene as illustrated for 2. The overall reaction can be performed with catalytic quantities of 1, as indicated for the reaction of 4. 

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