Silylation amine catalysis

The silylated tin compound 199, obtained from tributyltin hydride and N-bis(trimethylsilyl)propargylamine (198) in the presence of a trace of AIBN (2,2/-azobisisobutyronitrile), is a versatile reagent for the preparation of allylic amines. Treatment with aryl bromides ArBr (Ar = Ph, 4-MeOCgH4, 4-O2NC6H4 etc.) under Pd(PPh3)4 catalysis yields the silylated amines 200, which are hydrolysed by acids to the free amines 201. 199 is converted into the lithium compound 202, which is transformed into 203 by aqueous ammonium chloride and into 204 by the action of alkyl halides RX (R = Me, Et or allyl) (equation 76)204. 

Figure 8.8 Amine catalysis of silylation reaction, mechanism 2.

Diarylprolinol silyl ether catalyst was able to promote enantioselective allqrlations of a,p-unsaturated aldehydes with stabilised carbcations as electrophiles. Dienamine intermediates were trapped by the electrophile in two positions. The y-disubstituted aldehydes were not good substrates for y-substitution. However, linear unbranched and p-substituted a,p-unsaturated aldehydes preferred y-substitution. ot-Substituted aldehydes were unreactive under secondary amine catalysis (Scheme 8.45). 

The intermediate N-acylpyridinium salt is highly stabilized by the electron donating ability of the dimethylamino group. The increased stability of the N-acylpyridinium ion has been postulated to lead to increased separation of the ion pair resulting in an easier attack by the nucleophile with general base catalysis provided by the loosely bound carboxylate anion. Dialkylamino-pyridines have been shown to be excellent catalysts for acylation (of amines, alcohols, phenols, enolates), tritylation, silylation, lactonization, phosphonylation, and carbomylation and as transfer agents of cyano, arylsulfonyl, and arylsulfinyl groups (lj-3 ). 

Bronsted base catalysis is expected to operate when acid-base interaction strongly enhances the substrate nucleophilicity or deeply changes the structure favoring the reaction. The silylation of phosphorous acid with the Me3SiCl-amine system may serve as a good example [Eq. (74)] (see references cited in Ref. 273). The first two molecules of silyl chloride enter the... 

It has recently been shown that within the same reaction series the mechanism of catalysis by uncharged Lewis bases may change with variation of the structure (275). Tandem kinetic and IR hydrogen bond studies revealed that silylation reaction of a silanol catalyzed with triethylamine is first order with respect to the silanol-amine hydrogen bond complex [Eq. (75).] The same reaction was shown to be effectively catalyzed by... 

The strong catalytic effect of amines in silylation with silyl hydrides of some protic substrates, like alcohols, phenols, and carboxylic acids, is well known (for review, see Ref. 316). In this case, the amine is not likely to ionize the silicon-leaving group bond. General base catalysis has been... 

Examples of amination of oxopurines to aminopurines via silyl derivatives include conversion of inosine into adenosine with catalysis by mercury ions (76LA745), and hypoxan-thines have been converted directly into adenines with phosphoramides at 225-230 °C (69IZV655). 

The electrophile, the substitution pattern, and the silyl group can all be varied acetals and amines combine to form imines such as 162 under Lewis acid catalysis and these react in the same... 

Addition and cyclization reactions. Chiral propargylic amines are obtained from aUcynylation of imines by catalysis of the silver salt of IB. The enantiomer of phosphate ID also finds use in the addition of indole to a-acetaminostyrenes. One more catalyst for intramolecular hydroamination to form pyrrolidine derivatives is the silylated 3. The... 

Silyl ethers. By ZnClj catalysis i live trimethylsilyl ethers, but amines i... 

This overview about developments in the field of proline-catalysis unfortunately cannot take into full account the vast field of proline-derived catalysts, such as diarylprolinols, 4-silo)yprolines or proline-silyl-ether, to name only a few. These are covered in subsequent chapters of this volume. Furthermore, other great improvements have been made by using immobilised proline catalysts, such as PEG-supported proline or polyelectrolyte-bound pro-line. Going one step further, supported proline catalysts are then applicable in the striving field of continuous-flow reactions. Recent examples include aldol, a-amination reactions and Michael reactions under such conditions. ... 

Electrophilic a-amination reactions were also included in organocascade sequences. Jorgensen developed a formation of hydro) - and amino-esters in combination by aminocatalysis using diaiylprolinol silyl ether and a redox reaction followed by acyl transfer to the corresponding esters using NHC catalysis. This useful method did not require an inert atmosphere or anhydrous conditions to form the corresponding products in excellent enantioselectivities and high yield. 

SCHEME 11.3. Silyl-protected diaryl prolinol (7)-catalyzed a-amination of a-unbranched aldehydes with azodicarboxylate esters via enamine catalysis. 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

Iminium-based organocatalysis is somewhat less explored than enamine-based organocatalysis and has been mostly used in the activation of a,/S-conjugated aldehydes and ketones. Therefore, this type of catalysis has unsurprisingly been the subject of a limited number of studies under the umbrella of the metal-organic cooperative catalysis concept. In 2011, the Cdrdova group [55] reported the first enantioselective and chemoselective /3-silyl addition to a./S-unsaturated aldehydes using copper salts and chiral pyrrolidine derivatives as catalysts. As proposed, the chiral secondary amine forms an iminium salt with... 

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