Formaldehyde imines

Difluoroamine reacts with primary and secondary amines to give alkanes (32). With imines, a variety of products are obtained depending on the structure of the imine. The three types of compounds obtained are diazirines (I), a-haloazo compounds (II), and a-fluoroalkylidine-hydrazines (III) (138, 139). The reaction of HNF2 with formaldehyde imines or negatively substituted aromatic imines yields diazirines in fair yield as the principal product, whereas with imines derived from aliphatic aldehydes the reaction gives a mixture of the corresponding diazirine derivative and a-fluoroazo compound. 

Monoalkylation of primary amines.1 A two-step sequence for this reaction involves conversion of the amine to the N-(cyanomethyl)amine (2) by reaction with chloroaceto-nitrile or with formaldehyde and KCN. Reaction of 2 with an organolithium or a Grignard reagent generates an unstable formaldehyde imine (a) that reacts with a second equivalent of the organometallic reagent to form a secondary amine (3). 

The propensity of formaldehyde imines (22) to trimerize to give hexahydro-l,3,S-triazines (24) has limited their synthetic utility. Sekiya and cowoikers and Bestmann et alP have shown that iV, -bis(tri-methylsilyl)methoxymethylamine (75) is a useful synthetic equivalent of formaldehyde imine. Treatment... 

Of the various imines known to condense with active methylene compounds, a-arylimines have been the most widely used, especially in earlier work, because of their stability, ease of preparation and the absence of enolizable protons. Aliphatic imines containing enolizable protons have broader synthetic applications but their use is more restricted because they are prone to deprotonation and self aldol type condensations. As will be discussed, new methods utilizing Lewis acids and the less basic boron enolates have been devised to overcome the problem of deprotonation. Other innovations that have extended the scope of imine condensations include in situ methods for the preparation of elusive formaldehyde imines (CH2=NR2> and the utilization of A/-heterosubstituted imines (N = Si, O and S) for the synthesis of primary Mannich bases and A(-unsubstituted 3-lactams, available via hydrolysis or reduction of the N—X bond. 

The reaction of allyl organometallics (8) with achiral aldimines (9) is the simplest combination of reactants, stereochemically, and affords (except in the case of formaldehyde imines) homoallylamines (10) containing one stereocenter (equation 2). These reactions, which typify the general scope of allyl organo-metallic-imine reactions are surveyed in Table 2. Reactions of allyl-borane, -titanium and -aluminum reagents are not shown in Table 2, only because they have been reported in reactions with chiral imines and are discussed in Sections 4.3.2.1.2 and 4.3.2.2. 

Acetyl chloride has been used as a ketene precursor to prepare P lactams unsubstituted at C3. Unsubstituted imine fragments pose special difficulties in the Staudinger reaction. Formaldehyde imines are difficult to prepare and handle, and generally p-lactams unsubstituted at C4 are not readily accessible. By contrast, formaldehyde hydrazones are more stable and can be used in place of the unstable imines in the Staudinger reaction to afford 4-unsubstituted P-lactams. ... 

Imines are generally less electrophilic than the corresponding aldehyde but this diminished level of activity can be countered by suitable activation with Lewis acids. Formaldehyde imines are generally stable only at low temperatures and are best formed in situ. However, there are exceptions like Eschenmoser s salt 20. This methylene iminium salt is a relatively stable solid that is now commercially available. The utility of this reagent was illustrated in the Mannich reaction of corrin 19 with 20 to generated 21. 

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