Acylsilanes, 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. 

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. 

N-Heterocychc carbenes (NHCs) derived from thiazolium salts (e.g., X) have been utihzed as catalysts in benzoin condensations, in additions of aldehydes to enones (Stetter reaction [17]) and recently in the reaction of acylsilanes with a, p-unsaturated carbonyl compounds (sila-SrEiTER reaction [18]), as exemplified in the following sequence of reactions ... 

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. 

A different approach toward highly substituted pyrroles involving a one-pot sila-Stetter/Paal-Knorr strategy was realized by Bharadwaj and Scheidt (Scheme 6.182) [343]. In this multicomponent synthesis, catalyzed by a thiazolium salt, an acyl anion conjugate addition reaction of an acylsilane (sila-Stetter) was coupled in situ with the conventional Paal-Knorr approach. Employing microwave conditions at 160 °C for 15 min, the acylsilane was combined with the cx/l-unsaturated ketone in... 

Catalytic multicomponent synthesis of highly substituted pyrroles has been described. A one-pot reaction uses DBU with the commercially available thiazolium salt 513 to produce the necessary nucleophilic zwitterionic catalyst in situ, which promotes a conjugate addition of acylsilanes (sila-Stetter) and unsaturated ketones to generate 1,4-dicarbonyl compounds in situ. Subsequent addition of various amines promotes a Paal-Knorr reaction, affording the desired polysubstituted pyrrole compounds in a one-pot process in moderate to high yields (Scheme 129) <2004OL2465>. Microwave heating dramatically reduced the reaction time (from 16 h to 30 min), but offered no improvement in yields. 

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