Aldol condensation trimethylsilyl triflate

TiIV compounds also work well at promoting cross-aldol reactions between two different aldehydes and/or ketones without prior activation or protection (Scheme 19).74 Claisen condensation and Knoevenagel condensation are promoted by TiX4, an amine, and trimethylsilyl triflate.75-77... 

In large measure, the problem associated with the execution of a stereoselective aldol condensation has been reduced to the generation of a specific enolate geometry. The recent results of Kuwajima (66a), which demonstrate that enolsilanes may be transformed into boryl enolates without apparent loss of stereochemistry (eq. [53]), should enhance the utility of vinyloxyboranes in stereoselective synthesis. The only current drawback to this procedure is associated with the presence of trimethylsilyl triflate (69), which must be removed from the reaction medium before the aldol condensation. It has recently been established that 69 is an effective catalyst for the aldol process (4). 

Mukiayama aldol reactions between silyl enol ethers and various carbonyl containing compounds is yet another reaction whose stereochemical outcome can be influenced by the presence of bis(oxazoline)-metal complexes. Evans has carried out a great deal of the work in this area. In 1996, Evans and coworkers reported the copper(II)- and zinc(II)-py-box (la-c) catalyzed aldol condensation between benzyloxyacetaldehyde 146 and the trimethylsilyl enol ether [(l-ferf-butylthio)vinyl]oxy trimethylsilane I47. b82,85 Complete conversion to aldol adduct 148 was achieved with enantiomeric excesses up to 96% [using copper(II) triflate]. The use of zinc as the coordination metal led to consistently lower selectivities and longer reaction times, as shown in Table 9.25 (Eig. 9.46). 

For some condensations with silylated substrates as starting compounds, trimethylsilyl triflate can be used as a catalyst [103, 104, 705] A typical example of such a reaction is the aldol type condensation of silyl enol ethers and acetals catalyzed by 1-5 mol% of trimethylsilyl triflate [705] (equation 53)... 

A number of methods that utilize enolsilanes directly in the aldol process with either aldehydes or acetals have been developed recently. These reactions are usually performed either in the presence of Lewis acids such as titanium tetrachloride (67) or with fluoride ion (68). Recently trimethylsilyl triflate (CF3S03SiMe3) was found to be an efficient acid catalyst for condensation... 

The cyclization of306 promoted by trimethylsilyl triflate and diisopropylethyl-amine gives ci5-dihydropyrones 307. Under these conditions methoxybutenone fails to form the aldol condensation product 305 (90TL2213). 

It catalyses the aminolysis of epoxides in an extraordinarily efficient manner in aprotic solvents (e.g. toluene, CH2CI2) with complete trans stereoselectivity and high regioselectivity [Chini et al. Tetrahedron Lett 35 433 1994], It also catalyses the trans addition of indole (at position 3) to epoxides (e.g. to phenoxymetltyloxirane) in >50% yields at 60° (42 hours) under pressure (10 Kbar) and was successfully applied for an enantioselective synthesis of (+)-diolmycin A2 [Kotsuki Tetrahedron Lett 37 3727 799(5]. Of the ten lanthanide triflates, Yb(OTf)3 gave the highest yields (> 90%, see above) of condensation products by catalytically activating formaldehyde, and a variety of aldehydes, in hydroformylations and aldol reactions, respectively, with trimethylsilyl enol-ethers in THF at room temperature. All the lanthanide triflates can be recovered from these reactions for re-use. [Kobayashi Hachiya J Org Chem 59 3590 1994.]... 

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