Hydroacylation alkynes

Alkylzirconocene thiolates, preparation, 4, 932 Alkynals, reductive cyclization, 10, 527 5-Alkynals, hydroacylation-isomerization, 10, 93 ]1 ]2-Alkyne-alkylidenes, in Ru and Os half-sandwiches,... 

Based on earlier work in Rh-catalyzed alkyne hydroacylation, the Tanaka group discovered that a rhodacycle generated upon oxidative addition of a 2-alkynylben-zaldehyde derivative underwent efficient dimerization in a formal [4 -h 2] annulation (Scheme 2.46) [92]. This strategy involves formal hydroacylation across one C=C... 

Tandem hydroacylation-isomerization of 5-alkynals catalyzed by a cationic rhodium(l)/BINAP complex was applied to the short synthesis of dihydrojasmone (Scheme 49).88... 

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]. 

Since the early 1990s, considerable progress has been achieved in the development of catalytic enantioselective intramolecular hydroacylation reactions of alkenes/alkynes that generate five-membered rings. Nonetheless, the vast majority of interesting hydroacylation reactions has not yet proven susceptible to effective asymmetric catalysis. This deficiency represents an exciting opportunity for future investigations in this... 

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... 

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... 

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). 

Research on intermolecular hydroacylation has also attracted considerable attention. The transition-metal-catalyzed addition of a formyl C-H bond to C-C multiple bonds gives the corresponding unsymmetrically substituted ketones. For the intermolecular hydroacylation of C-C multiple bonds, ruthenium complexes, as well as rhodium complexes, are effective [76-84]. In this section, intermolecular hydroacylation reactions of alkenes and alkynes using ruthenium catalysts are described. 

The cis stereochemistry of hydroacylation can be deduced from the hydroacylation of alkynes catalyzed by Ni(cod), modified with phosphanes56. Addition of aliphatic and aromatic aldehydes to 4-octyne, and various other alkynes gives 3,/J-unsaturatcd enones with a preferred E geometry (80-95%). 

Hydroacylation is especially interesting in its intramolecular version, converting unsaturated aldehydes to cyclopentanones. Numerous examples of transition metal catalyzed hydroacylations have been described, mostly with 4-alkenals of various substitution patterns. The reaction is used for the construction of starting materials in prostaglandin synthesis and the preparation of other cyclopentanoid systems. Rhodium catalysts, mainly of the Wilkinson type, are used. The steric course of hydroacylation is believed to occur in a m-addition manner. This was deduced from results of intermolecular alkyne hydroacylation56 (vide supra) and the intramolecular hydroacylation of deuterated E- and Z-isomers of 7,5-unsaturated aldehydes39-5 . 

Functionalization of unsaturated compounds. Hydroacylation of alkynes, allenes, and alkenes using 2-hydroxyaraldehydes affords aryl ketones. ... 

Other examples of microwave-assisted catalysis include allylic alkylation, both palladium catalyzed and molybdenum catalyzed. In the latter case, air stable precursor complexes could be used under non-inert conditions. Microwave-enhanced Pauson-Khand reactions have also been reported, as have hydroamination of alkynes, and metathesis of functionalized alkynes. " Recently, microwave enhancement has been applied to C-H activation reactions, for example, for the formation of functionalized heterocycles, allowing the reaction to be performed with no solvent purification and minimal precautions to exclude air. A solvent-free chelation-assisted hydroacylation... 

Although the hydroacylation reactions of simple alkynes will not generate new stereogenic centers on the alkyne moiety, nevertheless, the asymmetric intramolecular hydroacylation reactions of alkynes have emerged by applying either kinetic resolution or a desymmetrization strategy. 

Scheme 8.28 Asymmetric hydroacylation reactions of alkynes reported by Willis.

The hydroacylation of alkynals was also reported by Tanaka and Fu, who found that the Rh(I)-Tol-BlNAP system was the catalyst of choice for the hydroacylation-desymmetrization of 3-6is-alkynals 194 to give 4,4-disubstituted cyclopentenones 195 in excellent yields and high enantioselectivities. Cyclopentenones are important intermediates in the synthesis of natural products such as prostaglandins. This catalyst system was also found to be extremely effective in the kinetic resolution of racemic 3-disubstituted alkynals 196 giving the unreacted aldehyde 197a with near perfect enantioselection. 

The regioselectivity of hydroacylation of alkynes ArC=CH with substituted aldehydes RCH2CH=0, catalysed by [(nbd)2Rh]BF4, can now be controlled by the choice of the diphosphine ligand thus, DPEphos in CH2CI2 gives mainly the linear product ArCH=CH—CO—CHjR (20 1), whereas o-Pr -l,2-bis(diphenylphosphino) ethane (dppe) favours the formation of the branched isomer CH2=C(Ar)COCH2R... 

Scheme 2.47 Enantioselective [4 + 2] annulation via formal alkyne/ketone hydroacylation [92].

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