Grignard reagents with iminium salts

Reaction of Grignard Reagents with Iminium Salts... 

Grignard reagents easily react with iminium salts ... 

The reaction has been extended to the preparation of ketones 1542 treatment of a dihydro-1, 3-oxazine (133) with methyl iodide forms the iminium salt 134 (0-43) which, when treated with a Grignard reagent or organolithium compound (6-35), produces 135 which can be... 

The allylation of imines with allylindium reagents in organic solvents gives the corresponding homoallylic amines.251-253 Under solvent-free conditions, the indium-mediated reaction of iV-benzylideneaniline furnishes a mixture of mono-allylated 79 and bis-allylated products 80 (Equation (56)). The bis-allylated product 80 presumably arises via a formation of an iminium salt, which is subsequently attacked by the allylindium nucleophiles. Formation of 80 is entirely suppressed by addition of allyl bromide to indium metal prior to any addition of the imine (Grignard-type reaction).254... 

Aminobenzonitriles 17 react with Grignard reagents to give the intermediate iminium salt 20, which can be readily trapped in situ by carbonyl compounds (e.g., acid chlorides, anhydrides, formates, carbonates, and oxalates) or phosgeniminium chlorides and cyclized to quinazolines. With this method various 2-unsubstituted quinazolines, 2,4-disubstituted quinazolines, and quinazolines with certain functional groups (e.g., COjEt, NMe ) in the 2-position are readily available. 

Both the silyl derivative (59) and the alcohol (60) may be used as sources of the iminium salt (61) in reactions with a wide variety of nucleophiles. In practice, it was found feasible to use Grignard reagents for reaction with the silyl derivative, while TiC was effective in promoting attack on the carbinol amine by weaker nucleophiles. The process is shown in Scheme 24 using the addition of indole as an example. 

Preformed iminium salts have been used extensively in organic synthesis. The facility of the condensation is a function of iminium salt substitution. Treatment of formaldehyde-derived methyl(methylene)ammonium halides (or trifluoroacetates) (46) with Grignard and lithium reagents results in the high yield formation of dimethylaminomethyl-containing compounds (47). Subsequent oxidation or alkylation of these products has been employed to generate terminal alkenes (48 Scheme 7). As expected, addition yields are modest for the mote-hindered iminium salts derived frrom other aldehydes and are somewhat lower for those derived from cyclic ketones. ... 

Iminium salts bearing a labile trimethylsilyl group can be generated in situ and undergo nucleophilic addition (see Sections 1.12.4.2 and 1.12.7.3). Bis(trimethylsilyl)methoxymethylamine (75), for example, has been used as a formaldehyde equivalent for the preparation of primary amines. Cyclic imines, such as 3,4-dihydroquinolines, react with trimethylsilyl triflate (TMS-OTf) to provide reactive labile iminium salts (55), which condense with picoline anions. The addition of nonstabilized Grignard and organolithium reagents to acyclic aromatic ketimines and aldimines, however, is often not facilitated by the presence of TMS-OTf ... 

E)-l-Chloro-3-(N,N-dimethylamino)-1-arylprop-l-enes are conveniently prepared from aryl chloropropeniminium salts by reduction with sodium cyanoborohydride.75 Those iminium salts also undergo 1,2-addition of Grignard reagents (Scheme 32). N,N-Dialkylaminomethyl arenes can be obtained by the reaction of... 

C.iii. Reaction with Nitriles. Nitriles are carboxylic acid derivatives and react with Grignard reagents (also sec, 8.2.C).l Initial attack generates an intermediate iminium salt that can be hydrolyzed (with loss of ammonia) to the corresponding ketone. HO The best yields are obtained with aryl nitriles, and this is illustrated... 

Aminals. Allylic and propargylic aminals when treated with Tf20 afford iminium salts, which react with Grignard reagents to afford allylic and propargylic amines (eq 76). ... 

There is another important method by which a cyano group can be converted to an amino group. When a nitrile reacts with a nucleophilic organometallic such as a Grignard reagent, addition to the acyl carbon generates an iminium salt (1.59). 

---