Asymmetric Hydroacylation Reactions

A general catalytic cycle for an intramolecular alkene hydroacylation reaction. 

The follow-up studies from the groups of Sakai and of Bosnich, respectively, proved that the highly enantioselective hydroacylation could be realized 

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 

Entry R Catalyst Time (h) Yield (%) cisitrans ee (%) Config. 

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

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

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 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. 

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