N-silylimines

Allmenginger reported the preparation of Phe- /[(F)-CF=CH]-Gly in racemic form via -selective HWE reaction, yielding a-fluoroenoate 7. Conversion of the (Zs)-aldehyde 8 to N-silylimine, followed by the addition of the Grignard reagent afforded amine 9 without isomerization of the double bond (see Scheme 10.2) [13]. 

Although formation of enolizable N-silylimines is usually accompanied by isomerization to the en-amine and by deprotonation of the aldehyde precursor, N-silylimines derived from enolizable aldehydes have nevertheless been reported by Cainelli, Panunzio and coworkers to condense with enolates (Table 20 entries 15-17). The temperature at which the N-silylimine is generated, -30 C, may be critical since nonenonolizable N-silylimines are normally generated at -70 °C. Condensations with enolizable N-silylimines, like those with nonenolizable N-silylimines, are stereoselective and produce mainly cis 3-lactams. The yields (30-40%), however, are lower. 

Zinc enolates of (V -bissilylglycine esters, according to van Koten and coworkers, condense with N-silylimines with high anti selectivity (Table 20 entries 18-20). °° These results parallel those previously described in Section 4.1.3.2.2.i using N-ary - and A/-alkyl-imines and are consistent with a C(Z,E)t transition state. Reactions of N-silylimines are slightly less anti selective, however, than those of N-aryl- and A/-alkyl-imines. Retroaldolization prior to cyclization has been cited as a possible cause for the erosion in stereoselectivity based on the slow rates of cyclization found in the reactions of entries 19 and 20. 

Condensations of N-silylimines with silyl ketene acetals have been reported by Colvin and coworkers using Znh as catalyst (Scheme 42 Table 22). Interestingly, titanium tetrachloride, the catalyst of... 

Table 22 Reactions of Silyl Ketene Acetals (202) with N-Silylimines (203) Catalyzed by Znh ...

Figure 8 Proposed open transition states involved in silyl ketene acetal-N-silylimine additions ...

Cainelli, Martelli and coworkers have reported an interesting case of combined syn-anti and dia-stereofacial selectivity using chiral N-silylimine (199), prepared in situ from (S)-O-TBDMS-lactic aldehyde (198).157 As shown in Scheme 41, condensation of the lithium enolate of r-butyl butyrate with /V-silylimine (199) affords essentially a single (3-lactam (200), 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. 

Sodium trihydridocyanoborate Prim, amines from N-silylimines a-Aminocarboxylic acid esters... 

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