Asymmetric hydroacylation

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]. 

Asymmetric hydroacylation via kinetic resolution is achieved with racemic 2-methvl-2-phenyl-4-pentenal to give 15-50% (—)-(S )-2-methyl-2-phenyl-l-cyclopentanone with up to 69% ee at lower conversion rates, 5-7s. A complex of the type RhClL2 [L2 = (5,5)-2,3-bis(diphenylphos-phino)butane, Chiraphos]77 is used. The unreacted aldehyde shows an equally high enantiomeric excess of the less reactive -enantiomer. 

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... 

In 2009, Yu and co-workers wrote a comprehensive review on diastereo-selective and enantioselective C—H bond functionalization by transition metal catalysts, which presented the historical retrospective of this area in an elegant manner. Therefore, in the following sections, we will focus on the discussion of the latest achievements on the catalytic asymmetric C—H bond functionalization via a transient C—M bond (mainly contributions after 2009). The reactions will be classified according to the metal catalyst as well as the mechanistic scenario. Note that asymmetric hydroacylation and hydrovinylation, two important kinds of methods for the functionalization of aldehyde and alkene C—H bonds, will be covered in two separate chapters of this book (Chapters 8 and 9). 

Scheme 7.23 NHC-catalyzed asymmetric hydroacylation of unactivated alkenes reported by Glorius.

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... 

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

Table 8.3 Asymmetric hydroacylation of 2-formyl styrenes reported by Morehead.

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). ... 

In 2009, Tanaka and co-workers achieved Rh-catalyzed highly enantioselective intermolecular hydroacylation reactions of aliphatic aldehydes 48 with 1,1-substituted acrylamides 49 by using a cationic Rh/QuinoxP complex as the catalyst (Scheme 8.24a). Unfortunately, the reaction of simple benzaldehyde with acrylamide 49a was sluggish and the enantioselectivity was moderate, but utilizing (i ,R)-Me-DuPhos as the ligand could improve both yield and enantioselectivity (Scheme 8.24b). When cyclopentene-substituted amide 49b was subjected to the standard reaction conditions, a thermodynamically stable hydroacylation product 50b was generated with excellent diastereoselectivity (>99 1 dr) and enantioselectivity (97% ee), although dramatically reduced reactivity was observed (5% yield) (Scheme 8.24c). This report represents the first example of an asymmetric hydroacylation reaction of a trisubstituted alkene. 

Scheme 8.28 Asymmetric hydroacylation reactions of alkynes reported by Willis.

Asymmetric Hydroacylation Reactions Table 8.6 Counterion effects on reactivity. 

In addition to simple asymmetric hydroacylation of alkenes, highly efficient desymmetrization of alkenes has also been achieved by Wu and co-workers. Interestingly, the catalyst system (Rh(I)-BINAP) differentiated the enantiotopic faces of the olefins and thus the cyclopentanone products were obtained with excellent ee s. The authors also showed that neutral and cationic Rh(I)-BINAP complexes furnished dififerent products. The neutral catalyst system preferentially fiunished the cw-3,4-disubstituted cyclopentanone, and the cationic catalyst afforded the trans isomer. 

Recently, Glorius reported an elegant asymmetric hydroacylation of unactivated alkenes via carbene catalysis [24], Chromanone derivatives 70 containing an allcarbon based quaternary stereocenter could be efEciently produced from simple 2-aUyloxybenzaldehydes 69. Good yields and excellent enantioselectivity were obtained in the presence of chiral triazolium salt 68 and DBU. In addition, quantum-chemical calculations support a concerted but very asynchronous transition state (Scheme 36.18). 

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. 

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