Rhodium-catalyzed hydroacylation

A recyclable system for the directed rhodium-catalyzed hydroacylation of olefins was reported using a homogeneous phenol and 4,4 -dipyridyl solvent system at 150 °C. High yields were obtained even after eight cycles and the ketone product was obtained after decantation (Equation (132)).115... 

In 1997, Bosnich discovered that Me-DUPHOS serves as a highly effective ligand for rhodium-catalyzed hydroacylations, particularly when R is a medium or small alkyl substituent (Eq. 14) [17]. Interestingly, in contrast to BINAP (Eq. 13), Me-DUPHOS furnishes lower stereoselection when the R group is a tert-butyl or TMS group (44 and... 

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

The potential for enatioselective intra-molecular hydroacylation to create an efficient pathway into dihydropyrroloindoles led to the study of rhodium catalyzed hydroacylations of N-vinylindole-2-carboxaldehydes 16. These dihydropyrrolin-doles are core structures of indole alkaloids. The high level of enantiomeric excess of this reaction comes from the chirality of the biphenyl phosphine 17. The reaction tolerated substitution throughout the indole and further reactivity of the substituted indole provided even more advanced intermediates used in synthetic chemistry. 

Figure 7 (A) Suggested reaction sequence for rhodium-catalyzed hydroacylation of C=C bonds via benzylic alcohol, (B) simultaneous hydroacylation and hydrogenation of PBD, (C) hydroacylation of PBD starting from symmetric diols, and (D) simultaneous hydroacylation and hydrogenation of PBD starting from substituted aldehydes.

However, the decarbonylation reaction can be suppressed by the use of specially tailored chelating groups. Intermolecular processes involving dienes and salicylaldehydes are now known, and are thought to proceed via a double chelation mechanism, akin to the Jun-type system. Rhodium-catalyzed reactions lead to hydroacylated products, under relatively mild conditions (Equation (134)).117... 

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]. 

Two years later, Bosnich described an extensive study of asymmetric rhodium-catalyzed intramolecular hydroacylation reactions [16]. Like Sakai, Bosnich found that Rh(l)/ BINAP is an unusually effective catalyst for this process, furnishing excellent enantioselectivity for a range of substrates (Eq. 13). Bosnich also reported thaL if the R substituent is a relatively unhindered alkyl (for example. Me) or an aromatic group, lower (< 80% ee) enantioselectivity is observed. 

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... 

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). 

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 . 

An insertion-reductive elimination sequence is involved in the rhodium-catalyzed, intramolecular hydroacylation of 4-alkenals to form cyclopentanes ... 

A series of l-benzazepin-5-ones were furnished via a rhodium-catalyzed intermolecular hydroacylation of an allyl amine onto an aryl aldehyde (14AGE3688) while a one-step synthesis of a number of tetrahydro-3-benzazepines was achieved through the palladium-mediated reaction of phenylethylamines with allenes (14JOC9578). 

Eight-membered ring ketones 25 were synthesized via the rhodium-catalyzed intramolecular hydroacylation of methylene cyclobutane derivatives 26, which involved ring opening by P-carbon elimination (Scheme 3.9) [21]. Deuteriumlabeling experiments with cis asymmetrically substituted alkylidenecyclobutanes revealed that the rearrangement included cleavage of three carbon-carbon bonds [22]. 

The reaction mechanism leading to advanced intermediate 85 starts with rhodium insertion into the aldehyde moiety. Rhodacycle formation follows to promote hydroacylation into the 4,6-diene providing cycloheptene compound 86. Then, rhodium catalyze a highly regioselective cycloisomerization reaction on the resulting triene to produce the final product 87 (Scheme 7.54 please refer also to Scheme 7.51). 

Marce P, Diaz Y, Matheu MI, Castillon S. Synthesis of d and L-carbocychc nucleosides via rhodium-catalyzed asymmetric hydroacylation as the key step. Org. Lett. 2008 10 4735-4738. 

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... 

Recent Advances in Rhodium(l)-Catalyzed Asymmetric Olefin Isomerization and Hydroacylation Reactions... 

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. 

Eilbracht et al. have developed rhodium- or ruthenium-catalyzed one-pot synthesis of cyclopentanones from allyl vinyl ether via tandem Claisen rearrangement and hydroacylation [109-111]. This protocol requires elevated temperature (140-220°C) and also requires alkyl or aryl substituents at the terminal position of the allylic double bond to prevent undesirable double bond migration in the intermediary formed, unsaturated aldehyde. 

Rhodium (I)-catalyzed cyclizations of 6-octen-l-als bearing a (4R,6R)-di-methyl-l,3-dioxane group at different positions do not lead to hydroacylation ( 7.S.3) products, but lead instead to the products of formal ene reaction reactions [1244]. 3-Substituted aldehyde 6.79 (R,R = 4R,6R-1,3-dioxolanyl) gives trcms-cyclohexanols with a high selectivity (Figure 6.68), while 2-substituted analogs cyclize to cw-cyclohexanols in lower selectivities. 

Intramolecular hydroacylation of 4-substituted pent-4-enals is catalyzed by Rh (I) complexes and leads to 3-substituted cyclopentanones. When the ligand of rhodium is (l ,2,S)-3.35 (X = CH2CH2) or even better (Ky or (S)-binap 3.43 (Ar = Ph), cycloalkanones are obtained with an excellent enantiomeric excess... 

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