Aldol reactions Trityl perchlorate

During the past decades, the scope of Lewis acid catalysts was expanded with several organic salts. The adjustment of optimal counter anion is of significant importance, while it predetermines the nature and intensity of catalytic Lewis acid activation of the reactive species. Discovered over 100 years ago and diversely spectroscopically and computationally investigated [131-133], carbocations stiU remain seldom represented in organocatalysis, contrary to analogous of silyl salts for example. The first reported application of a carbenium salt introduced the trityl perchlorate 51 (Scheme 49) as a catalyst in the Mukaiyama aldol-type reactions and Michael transformations (Scheme 50) [134-142]. 

The reactions proceeded efficiently under mild conditions in short time. The silyl enol ethers reacted with the activated acetals or aldehydes at -78 °C to give predominant erythro- or threo-products [136, 137] respectively. In the same manner, the aldol reaction of thioacetals, catalyzed by an equimolar amount of catalyst, resulted in <-ketosulfides [139] with high diastereoselectivity. In the course of this investigation, the interaction of silyl enol ethers with a,]3-unsaturated ketones, promoted by the trityl perchlorate, was shown to proceed regioselec-tively through 1,2- [141] or 1,4-addition [138]. The application of the trityl salt as a Lewis acid catalyst was spread to the synthesis of ]3-aminoesters [142] from the ketene silyl acetals and imines resulting in high stereoselective outcome. 

Recently it was found that the aldol reaction of silyl enol ethers with acetals or aldehydes is effectively promoted by a catalytic amount of trityl perchlorate to give the corresponding aldols in good yields (44,45). Polymer-bound trityl perchlorate also successfully catalyzed the aldol reaction (45). 

Triphenylphosphine-Diethyl azodicar-boxylate-Lithium halides, 332 Mukaiyama aldol reaction 1-Methoxy-l, 3-bis(trimethylsilyloxy)-l, 3-butadiene, 178 Tin(II) chloride, 298 Titanium(IV) chloride, 304 Trityl perchlorate, 339 Murahashi reaction N,N-Methylphenylaminotributylphos-phonium iodide, 191... 

Aldol-type reactions. Trityl perchlorate catalyzes an aldol-type reaction between silyl enol ethers and acetals or ketals to give p-alkoxy ketones. The yields are comparable to those obtained with TiCU (6, 594). The iyn-aldol is formed predominantly ( 4 1). 

Aldol-type condensation of enol silyl ethers and acetals or orthoesters can be accontplished by the use of trimethylsilyl trifluoromethanesulfonate (TMSOTf). In these reactions, TMSOTf acts as a true catalyst and is required in 1-S ntol %. The reactions show interesting chemoselectivity in that acetals are highly reactive receptors of enol silyl ethers but the parent aldehydes and ketones do not react under these conditions (Scheme 37). Similarly, trityl perchlorate is found to be an efficient catalyst to promote the reaction between enol silyl ethers and acetals. 

Recently Mukaiyama and coworkers introduced the use of trityl salts as efficient catalysts for the aldol reaction. Using a catalytic amount of trityl perchlorate (5 mol %) and t-butyldimethylsilyl enol ethers, the anti aldols were preferentially obtained (anti 73-84%) regardless of the double bond geometry. With trityl triflate (5 mol %) and dimethylphenylsilyl enol ethers, the syn isomers are produced predominantly (syn 63-79% Scheme 1). Several variations of the catalyst system have been developed. Trityl... 

Initially, the titanium(IV) chloride-mediated aldol reaction of silyl enolates tvith aldehydes tvas investigated [20] and a catalytic amount of trityl salt 60 (e.g. trityl perchlorate) vas found to promote the aldol reaction (Eq. (27)) [35]. Whereas the original reaction is performed by using a stoichiometric amount of titanium(IV) chloride, 5-10 mol% trityl salt is sufficient to drive the aldol reaction to completion. One interesting finding in this catalytic reaction is that the silicon enolate reacts vith aldehydes to give the corresponding aldol adducts as their silyl ethers 61. 

The aldol reaction of a variety of silyl enolates and acetals in the presence of a catalytic amount (1-10 mol%) of trityl perchlorate proceeded efficiently to afford /i-methoxy ketone in high yield. In the presence of trityl tetra-fluoroborate catalyst, the reaction of dithioacetal 62 vith silyl enol ethers affords /i-ethylthio ketones 63 (Eq. (28)) [36]. 

Carbocations were discovered over 100 years ago and have been investigated in diverse ways both spectroscopically and computationally [86-88]. Although as cations they can possess strong Lewis acidic character, carbocations remain seldom represented in organocatalysis, unlike the analogous of silyl salts, for example, discussed above. The first catalytic application of a carbenium salt, the trityl perchlorate 35 (Figure 16.7), was reported for Mukaiyama aldol-type reactions and Michael transformations (Scheme 16.29) [89-97]. 

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