Silyl imidate

Another variation of the Madelung synthesis involves use of an O-alkyl or O-silyl imidate as the C2 electrophile. The mechanistic advantage of this modification stems from avoiding competing N-deprotonation, which presumably reduces the electrophilicity of the amide group under the classical conditions. Examples of this approach to date appear to have been limited to reactants with a EW substituent at the o-alkyl group[15,16]. 

A mechanistic proposal, which is based on the mthenium-catalyzed dehydration reaction reported by Nagashima and coworkers [146], is shown in Scheme 44. Reaction of a primary amine with hydrosilane in the presence of the iron catalyst affords the bis(silyl)amine a and 2 equiv. of H2. Subsequently, the isomerization of a gives the A,0-bis(silyl)imidate b and then elimination of the disiloxane from b produces the corresponding nitrile. Although the disiloxane and its monohydrolysis product were observed by and Si NMR spectroscopy and by GC-Mass-analysis, intermediates a and b were not detected. 

As compared with amides, where oxygen is the most nucleophilic atom, the silyl imidates are more nucleophilic at nitrogen. 

The reaction with valerolactam 24 was also investigated, with surprising results. The reaction with BSTFA gave the silyl lactam 78 rather than the silyl imidate 25, as shown in Scheme 3.33. Subsequent reaction with DDQ gave a C-N adduct 79... 

In the early 1990s, FTIR was being evaluated at Merck for the in situ monitoring of reactions. This new technology was expected to provide a powerful means to study a reaction as well as a method for analytical control in production [28]. Both silyl imidate formation and the reaction with DDQ could be conveniently monitored by FTIR, as shown in Figure 3.13. Silyl imidate formation was indicated by the appearance of an absorbance at 1667.5 cm4 with concomitant disappearance of the absorbance corresponding to BSTFA at 1324.0cm-1. A new absorbance... 

It is also possible to form novel polysilazanes by dehydrocyclodimerization of the ammonolysis product of CH3SiHCl2, or coammonolysis products of this silane with other chlorosilanes.33 Ring compounds that contain the desired Si and N atoms may also be used as starting materials, followed by hydrolysis, thermolysis, polymerization, or copolymerization to convert them into silazane-type materials. Examples are cyclic bis (silyl) imidates, /V-acylcyclosilazoxanes, /V-arylcyclosilazoxanes, and A,A,-diarylcyclosilazanes.34... 

Early attempts to extend the halolactonization procedure to yield lactams gave cyclic imidates instead, but several approaches favor lactam products. These include working with silyl imidates, imidate esters or oxazolines, using sulfonylcarbamates or other acidic amides or by using hydroxyl-amine derivatives with increased nucleophilicity due to the a-effect. Lactams can also be favored as a consequence of steric requirements. In a few cases, amines can be cyclized to cyclic amines many lead references are given in a recent report on cyclic hydroxylamines such as (64). Veiy recent work has provided a fairly general iodolactamization procedure from unsaturated amides, trimethylsilyl triflate and iodine (Scheme 89). ... 

The enantioselective Miehael addition of a,p-unsaturated p-silyl imides to aminocyanoacetate derivatives was also deseribed by the Jaeobsen group. ° With (S,S)-[(salen)Al]20 ent-4 as the eatalyst, the reaetion of (AT-p-methox-ybenzylamino) eyanoaeetate to allyldimethylsilyl imide proceeded well, affording the y-lactam in 87% yield, 9 1 dr, and 98% enantiomeric excess. Notably, with lactam in hand, the total synthesis of (+)-lactacystin could be accomplished in 12 additional steps (Seheme 19.24). 

Scheme 19.24 Asymmetric Michael additions of aminotyanoacetate derivatives to a,p-unsaturated p-silyl imides catalysed by [(salen)Al]20.

In the above radical reaction, the 6-endo cyclization product was unexpected and indicates that there exists an equilibrium between the desired Af-silylation and the undesired 0-silylation products. For the 0-silyl imidate, the C-C s-cis conformer must be favored over the s-trans conformer in order to avoid the steric interaction between vinyl group and the TBDMS group (eq 35). The Si NMR spectrum provided further evidence for the silyl group scrambling and indicated a rapid iV-silyl/O-silyl equilibration since a single peak at S 13.38 ppm was observed which is the averaged value of chemical shifts for an 0-silyl imidate (5 19.6 ppm) and an Af-silyl amide (3 8.7 ppm). 

Chiral Auxiliary Chemistry The introduction of a sulfur atom to alkanes through a C—H activation is currently limited to enolizable C—H bonds such as a-sulfeny-lation of carbonyl compounds. Although there are other synthetic routes to a-sulfenylated carbonyl compounds, the preparation of chiral compounds has relied on the chiral auxiliary-assisted diastereoselective thioalkylation. In 1985, Paterson et al. reported that the chiral (9-silylated imide enolates 385 of Evans oxazolidinone could be sulfenylated with high diastereoselectivities by phenylsulfenyl chloride (Scheme 46.44). ... 

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