Reactions hydroacylation

All three types of reactions of acyl anion equivalents presented herein have been used in domino reactions [70], The typically mild basic conditions required for benzoin, Stetter, and hydroacylation reactions make them amenable to a variety of such applications. 

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

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. 

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... 

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... 

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. 

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. 

Usually hydroacylation reactions of alkenes requires CO to suppress decarbonyla-tion of the aldehyde, but this reaction does not require CO. The key intermediate in the catalytic cycle is postulated to be a [Ru(> -al]yl)(acyl)Ln] species. 

Various other rhodium catalysts can initiate hydroacylation reactions. Thus, the indenyl complex [075-C9H7)Rh(J72-C2H4)2] is used in intermolecular hydroacylation44. Rhodium zeolites (RhNaX and RhNaY type zeolites) act as bifunctional catalysts for the synthesis of 2-methyl-3-hexanone and 4-heptanone (1 2 ratio) from propene, carbon monoxide and hydrogen53. In this case, the ketones may be formed via hydrocarbonylation (vide supra), however, according to control experiments, rhodium-free zeolites alone catalyze ketone formation from propene and butyraldehyde53. 

These latter results demonstrating intramolecular asymmetric hydroacylation reactions show promising potential for further useful applications of this method in stereoselective organic synthesis. 

The addition of an aldehyde group across an aUcene is a hydroacylation reaction. Whilst there is no hydrogen gas needed for these reactions, the process has some similarity to hydroformylation from a synthetic viewpoint, hence its mention in this chapter. In common with hydroformylations, catalytic asymmetric hydroacylations utilise enantiomerically pure rhodium complexes as catalysts. To date the catalytic asymmetric hydroacylation of alkenes has only been achieved in an intramolecular sense. 4-Substituted pentenal (2.213) and 3,4-disubstituted... 

A general catalytic cycle for an intramolecular alkene hydroacylation reaction. 

In 1983, James and co-workers disclosed the first example of enantioselec-tive intramolecular hydroacylation reaction of racemic a,a-disubstituted aliphatic aldehyde 1 when they investigated aldehyde decarbonylation reaction using a chiral Rh complex as the catalyst (Scheme 8.2). The enantioen-riched product 2 (69% ee) could be obtained via kinetic resolution, but only a low conversion was achieved. One possible reason for the low reactivity was the presence of a quaternary stereogenic center at the a-position of the carbonyl group in the substrate. 

Scheme 8.2 The first enantioselective intramolecular hydroacylation reaction via kinetic resolution reported by James.

Later, the groups of Sakai and of Tanaka and Suemune, respectively, extended the scope of the enantioselective cyclizations by employing desymmetrization of the aldehyde substrates bearing two identical terminal olefin moieties, and the cyclopentanone products with two vicinal stereo-centers, 8 or 9, could be obtained using a catalytic amount of the cationic Rh complex (5 mol%) (Table 8.2). However, if neutral Rh catalysts were employed, a high catalyst loading at 50 mol% was needed (entries 1, 2). Tanaka, Suemune, and co orkers also developed the kinetic resolution of unsymmetrical racemic diene-aldehyde 10 via a Rh-catalyzed asymmetric hydroacylation reaction (Scheme 8.5). The cyclization product could be obtained in >95% ee. ... 

The Bosnich group explored the kinetic resolution of 3-phenyl-4-pentenal 13 via an asymmetric hydroacylation reaction. Itwas found thatwhen [Rh((S)-BINAP)]C104 was utilized, the cyclization product 14 could be afforded in 51% yield and 48% ee, along with the side product 4-phenyl-4-pentenal 16... 

Table 8.1 Enantioselective hydroacylation reaction using cationic Rh catalysts reported by Bosnich.

In 2011, the Carreira group developed the Rh-catalyzed asymmetric intramolecular hydroacylation reactions of pent-4-enals 17 for the preparation of cyclopentanones 18 (Scheme 8.7). In this study, the biindane-derived phos-phoramidite/olefin ligand (R)-Ll was found to be highly efficient to promote... 

In 2005, the Morehead group applied the Rh-catalyzed asymmetric hydroacylation reaction in the synthesis of 3-substituted indanones 20 from... 

Recently, the Stanley group reported an asymmetric intramolecular hydroacylation reaction allowing a rapid access to polycyclic indole derivatives. When (5)-MeO-BIPHEP L2 was employed as a chiral ligand, the cyclization product 24, the core structure of natural product yuremamine, could be obtained with moderate to high yields and excellent enantioselec-tivity (Scheme 8.11). 

After that, the same group also reported catalytie, enantioselective hydroacylations of AT-allylindole-2-carboxaldehyes and N-allylpyrrole-2-car-boxaldehydes (Scheme 8.12)/ These hydroacylations occur smoothly to form dihydropyridoindolones and dihydroindolizinones in moderate to high yields and excellent enantioselectivity from a variety of indole and pyrrole substrates and represent the first example of highly enantioselective, transition metal-catalyzed hydroacylation reactions to form six-membered-rings in the absence of chelation assistance. 

The asymmetric intramolecular hydroacylation reaction has also found application in the synthesis of natural products. In 1999, a Rh-catalyzed asymmetric intramolecular hydroacylation reaction of functionalized 1,5-enal 27 was employed by Rousseau and Mioskowski in the formal synthesis of brefeldin A (Scheme S.IS). " ... 

The asymmetric hydroacylation reaction of 1,5-enal was employed by Castillon and co-workers in the enantioselective synthesis of carbocyclic nucleosides (Scheme 8.14). When compound 31 was treated with a cationic rhodium catalyst, the cyclie ketone 32 could be obtained with up to 95% ee. Starting from an elegantly designed substrate 33, the group of Tanaka and Suemune realized the synthesis of enantioenriched spiro[4.4]nonanediones 36 and 37 via an iterative Rh-eatalyzed asymmetric intramolecular hydroacylation reaction (Scheme 8.15). ... 

Scheme 8.15 As)nnmetric hydroacylation reaction used in the preparation of enantioenriched spiro compounds reported by Tanaka and Suemune.

Asymmetric Intermolecular Hydroacylation Reactions of Alkenes and Allenes... 

Compared with asymmetric intramolecular hydroacylation reactions of alkenes, the corresponding intermolecular versions have been relatively less developed. In 2007, Stemmier and Bolm reported the first example of enanti-oselective intermolecular hydroacylation reactions between salicylaldehydes 40 and norbornadiene-type alkenes 41 (Scheme 8.20). It was found that the diastereoselectivity of the reaction could be modulated through changing the chiral ligands. With ferrocene-based bisphosphine ligand L5, the exo-product 42a was obtained exclusively with up to 82% ee. When monodentate phos-phoramidite ligand L6 was employed, the e do-isomer 42b was obtained as major product with moderate enantioselectivity (54% ee). 

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