Metallophosphites

Shortly after publishing the racemic cross silyl benzoin reaction, Johnson and co-workers reported an enantioselective variant ntilizing metallophosphite catalysis [48]. The lithiophosphite adds to the acyl silane and proceeds throngh the remain-... 

In a related process, Johnson and co-workers have developed an asymmetric metallophosphite-catalyzed intermolecular Stetter-hke reaction employing acyl silanes [81, 82], Acyl silanes are effective aldehyde surrogates which are capable of forming an acyl anion equivalent after a [l,2]-Brook rearrangement. The authors have taken advantage of this concept to induce the catalytic enantioselective synthesis of 1,4-dicarbonyls 118 in 89-97% ee and good chemical yields for a,p-unsaturated amides (Table 11). Enantioselectivities may be enhanced by recrystallization. 

Table 11 Sila-Stetter reaction catalyzed by metallophosphites...

Metallophosphites in covalent form (8.29) provide other examples of 3-coordinated P compounds, although they are devoid of M-P linkages and are not strictly metallophosphorus compounds (Chapter 6.8). 

A review of the asymmetric Stetter and asymmetric benzoin reactions focuses mainly on two classes of highly successful catalysts NHCs and metallophosphites. A new NHC, pyrido[l,2-a]-2-ethyl[l,2,4]triazol-3-ylidene (99), is a powerful catalyst of benzoin condensation in the presence of potassium f-butoxide. A DFT study of the mechanism suggests that the f-butanol solvent is explicitly involved. o-Phthalaldehyde chalcones (100) undergo intramolecular aldehyde-ketone crossed-benzoin condensation to naphthalenone tertiary alcohols (101) in yields up to 94%, in 20 min, using NHC catalysis. ... 

The cross-benzoin reaction between two different aldehydes typically produces a statistical mixture of products, although in some cases a single thermodynamic product predominates. A number of approaches have been developed to circumvent the limitations of the cross-benzoin reaction. In one approach, a thiamine diphosphate-dependent enzyme is used to promote a selective cross-benzoin reaction, often with high levels of asymmetric induction. In other approaches, one aldehyde coupling partner is replaced with a selective acyl donor. Cyanohydrin derivatives have proven to be ideal preformed acyl donors, and their use constitutes a stepwise benzoin condensation that is stoichiometric in cyanide. The discovery that acylsilanes can serve as cyanohydrin precursors has led to the development of a highly selective cyanide-catalyzed cross-benzoin condensation. By employing a chiral metallophosphite catalyst instead of potassium cyanide, good to excellent levels of asymmetric induction are possible. 

Chiral metallophosphites were found to be effective catalysts of the acylsilane/aldehyde cross-benzoin condensation in work reported by Johnson and co-workers. The TADDOL-derived catalyst 21 is very effective for the preparation of aryl-aryl cross benzoin products, with yields from 65-87% and enantiomeric purities from 81-91% ee. The more difficult aryl-alkyl, and alkyl-aryl cross-benzoin products can also be generated, with yields from 72-88% and enantiomeric purities from 41-73% ee. 

A highly efficient olefin hydroacylation known as the Stetter reaction resulted from the discovery that an activated olefin could intercept the putative acylanion intermediate of the classical benzoin reaction. Metal cyanides and heterocyclic carbenes are commonly employed catalysts for the Stetter reaction. Chiral heterocyclic carbenes as well as chiral metallophosphites have been developed as catalysts to provide 1,4-dicarbonyl compounds with high levels of enantiomeric purity. ... 

Despite significant research into new chiral carbene catalysts, few improvements in the direct asymmetric intermolecular addition of aldehydes to activated olefins have been possible. An innovative alternative was reported by Johnson and co-workers, who showed that chiral metallophosphite 31 could catalyze an asymmetric sila-Stetter reaction with high enantioselectivity. Due to the absence of a silyl scavenger, catalyst turnover occurs by a [l,4]-retro-Brook reaction, and the initially isolated a-silylamide product is recrystallized to improve the enantiomeric purity from 90 to 99% ee. Desilylation completes the three-step procedure to give y-ketoamide 32 in good yield and excellent enantiomeric purity. The reaction... 

Scheme 3-150. Enantioselective acylation of aldehydes, nitrones, and o yff-unsaturated amides catalyzed by chiral metallophosphites.

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