Imines desilylation

Compared to the cyclic ketones, the coupling of aliphatic aldehydes to prepare 3-substituted indoles was less successful, except for phenyl acetaldehyde, which afforded 3-phenyl indole 83 in 76% yield (Scheme 4.22). The lack of imine formation or the instability of the aliphatic aldehyde towards the reaction conditions may be responsible for the inefficiency of these reactions. Therefore, a suitable aldehyde equivalent was considered. With the facile removal of a 2-trialkylsilyl group from an indole, an acyl silane was tested as a means of preparing 3-substituted indoles. Indeed, coupling of acetyl trimethylsilane with the iodoaniline 24 gave a 2 1 mixture of 2-TMS-indole 84 and indole (85) in a combined 64% yield. Evidently, the reaction conditions did lead to some desilylation. Regardless, the silyl group of 84 was quantitatively removed upon treatment with HC1 to afford indole (85). 

Synthetic work commenced with evaluation of an azomethine ylide dipole for the proposed intramolecular dipolar cycloaddition. A number of methods exist for the preparation of azomethine ylides, including, inter alia, transformations based on fluoride-mediated desilylation of a-silyliminium species, electrocyclic ring opening of aziridines, and tautomerization of a-amino acid ester imines [37]. In particular, the fluoride-mediated desilylation of a-silyliminium species, first reported by Vedejs in 1979 [38], is among the most widely used methods for the generation of non-stabilized azomethine ylides (Scheme 1.6). 

Hydrosilylation of imine compounds was also an efficient method to prepare amines. The hydrosilylation product TV-silylamines can readily be desilylated upon methanol or water treatment, yielding the corresponding amines. The amines can be converted to their corresponding amides by subsequent acyl anhydride treatment. The first attempt to hydrogenate prochiral imines with Rh(I) chiral phosphine catalysts was made by Kagan102 and others. These catalysts exhibited low catalytic activity, and only moderate ee was obtained. 

Further methods [205] successfully employed to synthesize fuUeropyrroUdines include acid-catalyzed [213] or thermal [214] desilylation of trimethylsilyl amino derivatives, tautomerization of a-aminoesters of immonium salts [215] and imines [216, 217], reaction with aldehydes in the presence of aqueous ammonia [218], reaction with oxazolidinone [204] or photochemical reaction with some amino derivatives [219-223], The reaction with amino acids and aldehydes was also carried... 

Other examples of functionalized thiocarbonyl ylides that have been generated by the desilylation method are those bearing an imino group (49) (see Scheme 5.7). These ylides readily undergo [3 + 2] cycloaddition with aromatic aldehydes to afford l,3-thioxolane-2-imines of type 24 (X = RiN). The reaction with ketones is sluggish, however, and the cycloadducts are obtained in very low yield. 

Alkynyl azomethine ylides containing an aryl bridge have been shown to undergo cyclization. Thus, tautomerization of imine (137) afforded an azomethine ylide which cyclized to give two diastereomeric dihydropyrroles and traces of aromatized product (Scheme 42).56 The activated cyclic ylide (138), generated via the desilylation route, underwent cyclization to afford dihydropyrrole (139) in 42% yield.67b The structure of (139) is closely related to erythramine. The structurally related non-stabilized azomethine ylide (140) did not cyclize, tautomerizing to the corresponding enamine instead. 

Conceptually, quatemarization of a /V-(silylmethyl)imine with an halide would give the desired ylid. In reality, various means have been shown to induce quatemarization and desilylation of these imines. 

Triazines are trimers of unstable imines and may serve as imine precursors. Treatment of trimer of A1-pyrrol ine with a trimethylsilylmethyl triflate gives trimethylsilylmethyl-imonium triflate which may be desilylated by cesium fluoride, providing an ylid suitable for 1,3-dipolar cycloaddition reactions and constmction of the hexahydro-pyrrolizine framework.386 This strategy has been applied to prepare trachelanthamidine, supinidine and isoretronecanol alkaloids.387... 

Silyl triflates may also be used as the catalyst to the same goal. In both cases, conjugated base induces desilylation to create the ylid (compare with the action of tetrabutylammonium fluoride on the same imine which led to the anion see Section VI.B.6.a).333,391... 

Destlylation. Anhydrous cesium fluoride desilylates trimethylsilylmethyl-sulfonium, trimethylsilylmethylammonium, and trimethylsilylmethylphosphonium salts at room temperature to produce ylides, which undergo various useful transformations. Use of potassium fluoride-18-crown-6 or a tetraalkylammonium fluoride gives products in low yield in these reactions. The trimethylsilylmethyl-onium salts are prepared by alkylation of sulfides, amines, imines, and phosphines with (trifluoromethanesulfonylmethyl)trimethylsilane (1). 

PjTToles have also been subjected to [4 + 2] cycloadditions of benzynes. A(-Trimethylsilylpynole (512) is particularly suitable for such additions subsequent mild desilylation furnished 1,4- hydronaphthalen-1,4-imines, e.g. (514), in yields ranging from 30 to 53% (Scheme 120). ... 

The A -unsubstituted nonstabilized azomethine ylides generated from the desilylation of A -[(trimethylsilyl)methyl]-iminium triflates [1384, R = H, R = Ph R R = (CH2)s, (CH2)20(CH2)2] cycloadd to strongly polarized sulfonyl-imines 1385 (Ar = Ph, 4-CIC6H4, 4-O2NG6H4) to produce the corresponding A -imidazolines, for example, 1387, together with the initial cycloadducts 1386 (Scheme 358) <2001H(55)243>. 

In 1979 Vedejs and Martinez reported a terse communication on a new concept for the generation of nitrogen, sulfur, and phosphorus ylides. Their method consists of initial alkylation of the heteroatom of amines, imines, sulfides, or phosphines with trimethylsilylmethyl triflate, and subsequent desilylation of the resulting salts with fluoride ion (79JA6452). For the... 

Though a sequence of N-alkylation of imines and subsequent deprotonation at the (X position, instead of N-silylmethylation and desilylation, would seem to be an even more useful and general method for the generation of azomethine ylides, both the N-alkylation and the selective deprotonation are tricky processes (75JOC2048). The difficulty involved in the alkylation and deprotonation method discussed previously (86CRV941) increases the synthetic importance of the silylmethylation and desilylation method. 

Type 4 and 5 alkyl complexes also catalyze the regioselective hydrogenation of acyclic imines (190 psi of H2, 90 °C, TOF = 0.40 h ) [147]. The stoichiometric reaction of A -benzylidene(trimethylsilyl)imine with 4(Sm CH(SiMc3)2) yielded a desilylated Cp 2Sm-imine-amido complex with a four-membered Sm(NSi-Me3)(CPh)N=CHPh chelate ring which converts further to Se-symmetric... 

The imine nitrogen must attack the acetylene 68 and the resulting enolate desilylate the imine cation 69 to trap the diene as 70. No tautomerism to an enamine is possible. This intermediate is desilylated with fluoride to give the diene 67 in remarkably good yield. 

Desilylation. The powerful desilylation ability of BU4NF makes it useful for generating various carbanion equivalents. Synthetic exploitations of this reactivity include access to homoallylamines from imines and an allylsilane, to p-hydroxy-a-diazoalkanoic esters from a-silyl-a-diazoacetic esters and aldehydes, and a-fluorovinylation of carbonyl compounds by 1-fluoro-l-methyldiphenylsilylsilylethylene. Benzyne is formed by treatment of phenyl 2-trimethylsilylphenyliodonium triflate" with BU4NF. 

An interesting variation of the aza-Corey-Chaykovsky reaction provides a pathway to difluoromethyl-substituted aziridines. Reduction of trifluoromethylimine 143 with magnesium in the presence of chlorotrimethylsilane gave the enamine 144. Treated with dimethyloxosulfonium methylide in DMSO, 144 hrst underwent desilylation and tautomerization to produce imine 145, which then afforded aziridine 146 via the aza-Corey-Chaykovsky reaction in 92% yield. 

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