Sila-Stetter reaction

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

Scheme 9.12 The Sila-Stetter reaction, as reported by Scheidt et al.

Scheme 9.13 Mechanistic proposal for the Sila-Stetter reaction.

Lithium phosphites also can catalyze the silyl benzoin reaction of acylsilanes. Its asymmetric version is successfully achieved by a lithium phosphite derived from a homochiral diol.236 Thiazolium salt 32 effectively promotes conjugate acylation of a, 3-unsaturated carbonyls with acylsilanes in the presence of DBU (Equation (61)).237,237a The active catalyst of this sila-Stetter reaction would be a carbene species generated from 32 by deprotonation. 

Mattson AE, Bharadwaj AR, Scheldt KA (2004) The thiazolium-catalyzed Sila-Stetter reaction conjugate addition of acylsilanes to unsaturated esters and ketones. J Am Chem Soc 126 2314-2315... 

Mattson, A. E., Bharadwaj, A. R., Scheldt, K. A. The Thiazolium-Catalyzed Sila-Stetter Reaction Conjugate Addition of Acylsilanes to Unsaturated Esters and Ketones. J. Am. Chem. Soc. 2004, 126, 2314-2315. 

Scheidt et al. proved that acyl silanes can react in the same way as aldehydes in the so-called sila-Stetter reaction to eventually form 1,4-dicarbonyls in up to 75% The first intramolecular Stetter reaction was re-... 

Scheme 8.24 Sila-Stetter reactions between acylsilanes and .(l-iinsanirated ketones catalyzed hy heterocyclic nucleophilic carhenes.

The nucleophilic and electron-accepting properties of heterocyclic nucleophilic carbenes 36 were also used in combination with the electrophilic/nucleophilic character of acylsilanes via Brook rearrangement, leading to the invention of a sila-Stetter reaction by Scheidt and coworkers fScheme 6.24). The iminium structure in 37, generated by addition of the carbene catalyst 36 to the acylsilanes, promotes a Brook rearrangement to afford enol silyl ether 38. The alcohol additive present in the reaction causes desilylation to produce nucleophilic enaminol 39, which adds to a,p-unsaturated ketones to give 40. The formation of aryl ketone expels the carbene catalyst and produces 1,4-diketone 41. 

The efficiency of the Sila-Stetter reaction for the synthesis of 1,4-dicarbonyl compounds prompted us to extend this methodology to a single-flask protocol for the Paal-Knorr synthesis of furans and pyrroles [82, 83]. Finally, we also took advantage of acylsilanes to develop the 1,2-addition of carbanion equivalents to activated imines for the synthesis of a-amino ketones [84]. 

DeglTnnocenti and co-workers established in 1987 that acylsilanes could react with activated olefins in a cyanide-catalyzed sila-Stetter reaction, and recent work by Scheldt and co-workers has established the utility of thiazolylidine catalysts in this Stetter variation." The reaction is presumed to occur via a catalyst-initiated [l,2]-Brook rearrangement, which serves to provide the silylated acylanion donor intermediate 23. The use of excess 2-propanol in the reaction facilitates silyl transfer and catalyst turnover. Compared to the classical Stetter approach, this variation provides comparable yields of 1,4-diketone products from aromatic (20) and aliphatic (21) acylanion precursors. 

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... 

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