A-Silylimines

Special cases concerning the reactivity of intermediate 331 with electrophiles involve the use of A -silylimine or epoxides. In the first case, aminoalcohol 333 was prepared, which was easily cyclized (thionyl chloride followed by basic treatment) to the corresponding substituted tetrahydroisoquinoline 334 (Scheme 98) . ... 

Polymer-supported azomethine ylids generated from a-silylimines through a 1,2-silatropic shift, are shown to be versatile reagents suitable for the synthesis of libraries of pyrrolidine derivatives after 1,3-dipolar cycloaddition with a series of dipolarophiles. Effectively substituents R1, R2 and dipolarophiles A=B and A=B can be chosen to get the desired adduct.146... 

Condensation reactions between the lithium dianion of (S)-ethyl 3-hydroxybutyrate (127 R = OH) and cinnamaldimine (128), in connection with the synthesis of thienamycin, have been reported independently by three groups Georg et Cainelli et a/. " and Hart and Ha. Their results are summarized in Scheme 27 and Table 17 (entries 1-3) analogous reactions of dianion (127) with A -silylimines are discussed in Section 4.1.3.3.1. Of the four possible diastereomeric 3-lactams (129)-(132) that can be produced in this reaction, the two that prevail, (129) and (130), contain the predicted relative stereochemistry at C-3 and C-T. Subsequent inversion of the hydroxy groups of (129) and (130) led to intermediates which constituted formal total syntheses of thienamycin. " " In addition to 3-lactams (129) and (130), trans 3-lactam (131) is sometimes isolated but cis 3-lactam (132) is never observed. The product distributions are not uniform and may reflect the different bases used or the rate at... 

Table 21 3-Lactam-fonming Reactions of A -Silylimines (193) and Enolates of 3-Substituted Ethyl and...

Cainelli, Martelli and coworkers have reported an interesting case of combined syn-anti and dia-stereofacial selectivity using chiral A/-silylimine (199), prepared in situ from (S)-O-TBDMS-lactic aldehyde (198). 2 As shown in Scheme 41, condensation of the lithium enolate of r-butyl butyrate with A -silylimine (199) affords essentially a single p-lactam (2(M)), contaminated with only 4% of the corresponding other trans diastereomeric 3-lactam. The authors propose that the high level of diastereofacial selectivity (14 1) is due to the formation of lithium chelate (201), which undergoes attack by the enolate from the least hindered ir-face of the imine. The authors do not discuss the unusual anti selectivity of this reaction. 

Salts are produced by the reaction of fluorophosphoranes with A -silylimines (94). Vinyl isocyanate reacts with phosphorus penta-chloride to give a hexachlorophosphate salt (95), which yields the phosphonic dichloride (96) on hydrolysis and distillation. Butyl cyanate reacts with phosphorus pentachloride to give two products, (97) and (98). ... 

Addition to the C=N of an imine forms the magnesium amide, which is hydrolyzed to an amine. Isolated C=N double bonds of simple imines are relatively unreactive toward organomagnesium compounds, and may instead be depro-tonated at the a-position. Oximes and other N-substituted imines may react better, although an alternative sequence can produce aziridines. Imminium ions, because of their positive charge, are more reactive, and are useful in making tertiary amines. A-Silylimines yield primary amines after hydrolysis. Grignard reagents also add to one C=N of carbodiimides to produce amidines, and to nitrones to produce hydroxylamines. Some varied examples are shown in Scheme 6. 

Finally, silicon-nitrogen bonds are also labile in the presence of electrophiles, and this concept has been used by Komatsu in development of a silylimine linker (Table 1.16, Entries 12-14). Multifunctional cleavage was achieved with a range of electrophiles. For example, treatment with TFA left a hydrogen residual at the point of attachment (Table 1.16, Entry 12), while benzoyl (Table 1.16, Entry 13) and allyl (Table 1.16, Entry 14) groups were introduced by cleavage with benzoyl chloride and allyl iodide, respectively. 

A 1,2-silatropic shift was a key step when generating resin-bound azomethine ylides from a-silylimines (Scheme 11.8). A 1,3-dipole was captured with maleimide, and a polymer-bound pyrrolidine was obtained. Acidic or alkylative cleavage of the N-Si bond released A-unsubstituted or A -substituted pyrrolidines, respectively, from the resin in a traceless manner. 

M. Komatsu, H. Okada, T. AkaM, Y. Oderaotoshi, S. Minakata, Generation and cycloaddition of polymer-supported azomethine yhde via a 1,2-silatropic shift of a-silylimines traceless synthesis of pyrrolidine derivatives. Org. Lett. 2002, 4, 3505-3508. 

Scheme 11 Asymmetric [3+2] cycloaddition of a-silylimines with Al-phenyhnaleimide...

Later on, Carretero and co-workers reported the first enantioselective procedure for the Cu(I)-catalyzed 1,3-dipolar cycloaddition involving a-silylimines as azomethine precursors to provide a variety of 5-unsubstituted a-quatemary proline derivatives in good yields with excellent levels of diastereoselectivity and enantiocontrol (Scheme 11) [23]. The use of the bulky DTBM-SEGPHOS ligand proved to be crucial for obtaining this high enantioselectivity. Moreover, a,-P-unsaturated sulfones could also be employed as dipolarophiles in this catalytic system. 

In contrast, the A -silylenamine (186) reacts in conventional fashion with acyl halides R COCl in the presence of KF to give (187), and in the same vein tris(trimethylsilyl)ketenimine when treated sequentially with an aldehyde and alkali gives (Z)-alk-2-enenitriles in good jdeld and high isomeric purity. A-Silylimines derived from non-enolizable aryl aldehydes and ketones give secondary or tertiary carbinamines respectively on reaction with organolithium compounds. ... 

A(-Silylimines display similar reactivity and stereoselectivity to A -arylimines in reactions with enolates and silyl ketene acetals their advantage is that they provide easy access to -unsubstituted p-lactams by... 

An extensive review of the synthesis of a wide variety of five-membered heterocyclic compounds, via the formal 3-1-2-cycloaddition reactions of aziridines with alkenes, alkynes, nitriles, carbonyl groups, and heterocumulenes, has been presented." Supercritical CO2 has been used as the solvent in the formal 3-1-2-cycloaddition reactions of A-benzyl- and A-cyclohexyl-2-benzoyl-3-phenylaziridines with allenoates to yield pyrrole derivatives." The Lewis acid-catalysed intramolecular formal 3-1-2-cycloaddition reactions of 2-methyleneaziridines with tethered alkenes or alkynes (23) yielded cw-octahydrocyclopenta[c]pyrroles (24) after reductive workup. The reaction mechanism proceeds in a stepwise manner via a 2-aminoallyl cation (Scheme The Cu(I)/DTBM-Segphos-catalysed 1,3-dipolar cycloaddition reactions of a-silylimines and activated alkenes yielded highly enriched 5-unsubstituted a-quaternary proline cycloadducts with excellent diastereo- and enantio-selectivities (73-99% The... 

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