Amines isonitriles from

Acetylated Meldrum s acid 172 and a-aminoesters 173 have been used as the building blocks to prepare the substituted imidazoles 174, which are then cyclized to give optically active dihydro products 175 <20030L3907> (Scheme 7). A modified four-component LJgi reaction has been used to prepare dihydro products 177 from the intermediate functionalized imidazole 176, isonitriles, and amines (Equation 24) <2005EJ04670>. 

Selected examples of the synthesis of isonitriles from primary amines... 

A synthesis of arylamidines" from ArBr, f-butyl isonitrile, and amines is promoted by Pd(OAc)2 or PdCly in combination with dppf and CS2CO3. 

Tin-mediated-radical cyclization of isonitriles provides a useful strategy for the preparation of indoles (Fukuyama reaction).90 This radical cyclization is used for synthesis of 6-hydroxy-indole-3-acetic acid, which is the aromatic subunit of Nephilatoxin. The requisite isonitriles are prepared from nitroarenes via amines (Eq. 10.66).91... 

The question of the constitution of hydrocyanic acid has already been considered (p. 139). Here it need only be remarked that the isonitriles are converted by hydrolysis into primary amines and formic acid no carbon monoxide is produced, although from the formula this might be expected. The reason for this is to be sought in the fact that the first stage in the reaction consists in the addition of water to the two free valencies of the carbon atom. The reaction must therefore be formulated thus ... 

Although the extraction of primary amines from a basic medium with chloroform is an inadvisable procedure, on account of the formation of trace amounts of the pungent isonitriles, the specific synthesis of isonitriles by the two-phase reaction of primary amines with chloroform is unreliable. However, the application of the phase-transfer technique [e.g. 1 -5] for the controlled release of dichlorocarbene facilitates the synthesis of isonitriles in relatively high yields (Table 7.12). 

The four components required for the key Ugi reaction are simple aldehydes and amines such as isopropylamine and isobutyraldehyde, isonitrile 85 and a-(bromomethyl)acrylic acid and derivatives (86). Isonitrile 85 was synthesized from tyrosamine in three straightforward steps [94]. 

The multicomponent Ugi-type condensation of aldehydes, secondary amines, azide, and polystyrene-bound isonitriles has been reported to yield tetrazoles in acceptable yields (Entry 9, Table 15.20). Tetrazoles have also been prepared from... 

As the isonitriles are rapidly hydrolyzed to amines and formic acid, an extraction step with hydrochloric acid is normally sufficient in practice to remove these impurities from a desired nitrile product. 

To address the purification issue, which frequently is a bottle-neck in the fast microwave chemistry, a solid-phase catch and release methodology was utilized in a two-component, two-step synthesis of l-alkyl-4-imidazolecarboxylates [45]. In the first step, a collection of isonitriles 25 was immobilized onto a solid support by the reaction with the commercially available N-mclhyl aminomethylated polystyrene 26. Subsequent treatment with various amines brought about simultaneous derivatization and release of the desired imidazoles 27 back into solution. Significantly, only derivatized material was released from the resin, thus ensuring high purity of the desired product. Both steps of the reaction were substantially accelerated by microwave dielectric heating, resulting in the overall reaction time reduction from 60 hours to 70 minutes (Scheme 18). 

Apart from the unique adduct 5150, in which two plumbylene moieties are bridged by a MgBr2(thf)4 molecule viaBr —> Pb interactions [Pb—Br 296.4(2) pm], and few cyclopen-tadienyl derivatives where chelating amines interact with the two-valent tetrel atom62, unsupported adducts of Lewis bases with tetrylenes have been restricted to carbene-type bases so far. However, only donor carbenes, such as Arduengo carbenes, isonitriles or ylids, form simple adducts with dative C —> E interactions (Table 8). Carbenes or analogous species which also exhibit a substantial acceptor ability form multiple bonds instead (see Section III). 

The Ugi reaction produces a-amino acid amides from four components (isonitrile, carboxylic acid, aldehyde, and amine) in a one-pot reaction. With glycosylamines and ZnCl2 as promoting Lewis acid, a-amino acid amides are obtained [13,45] with excellent stereoselectivity in these reactions. For example, the galactosylamine 2 gave Ugi product 30 with formic acid as carboxylic component and various aldehydes and isonitriles in high yields and a diastereoselectivity of 19 1 in favor of the D-amino acid amides 30 (Scheme 20). 

---