Lithiated isonitriles

They are very unstable and must be generated at temperatures ranging between —100 and —120 °C, whereas lithiated amidines 683 can be kept in solution at —78 to — 20 °C989. Lithiated isonitriles 684 are also very unstable species990. 

Lithiated isonitriles have been treated with oxirans to give 3-hydroxyalkyl isonitriles (305) these have been hydrolysed to 3-amino alcohols, and cyclized to oxazines (306). From oxetane, 4-hydroxyalkyl isonitriles were obtained and these were cyclized to oxazepines in low yield (Scheme 142). ... 

For further investigations f-BuNC, which is isolobal to CO, was used. With PhLi and t-BuLi, the characteristic vibrational mode of the lithium isonitrile adduct (2135 cm ) was observed at a lower wavenumber than that of the free isonitrile (2179 cm ). Unfortunately, n-BuLi did not undergo complexation. As indicated by the C=N stretching vibrational mode at 1510 cm, only f-BuLi—CN—R reacted further to afford the lithiated Schiff base up to —20°C (equation 2) . ... 

A similar cyclization can result from lithiation of an isonitrile lithiation of 553 requires two equivalents of LDA and the organolithium 554 can either be trapped with other electrophiles at low temperature or warmed to give an indole 555 (Scheme 219) . It is quite clear that isonitriles activate purely by conjugation, and indeed they promote deprotonation of methyl groups para to an isonitrile just as well as ortho. The ease with which isonitriles can be made from formamides suggests that these methods could be rather more widely used than they are. 

Further derivatives of amines in which the a-C,H groups are sufficiently acidic to enable metalation are carbamates [235,238-240] (Scheme 5.26), imides[241], N-nitroso amines [59,242], ureas [201,243], some N-phosphorus derivatives [212, 214, 226, 244, 245], N-(2-pyridyl)amines (Scheme 5.26), and isonitriles [59]. A potential side reaction in the examples in Scheme 5.26 is the lithiation of the arene this is, in fact, observed with an isomeric dipyridopyrazine (last reaction, Scheme5.26). 

Formation of the racemate of the oxazole 196 was effected by Schollkopf s method addition of lithiated methyl isonitrile to the amide function of 201 (102, 103). The most efficient dimerization of seco acid derivatives 196-196b entailed... 

Carboxylation of lithiated carbanions of isonitriles with [ C] carbon dioxide (Vaalburg et al. 1976 Bolster et al. 1986a Hamacher and Hanus 1989) is an alternative synthetic approach to racemic amino acids labeled in the carboxylic position. Labeling in the 3-position (or P in the case of aromatic amino acids) can be achieved by alkylation using aliphatic or aromatic alkyl halides (Langstrom and Stridsberg 1979 Kilbourn et al. 1984 Antoni and Langstrom 1987). 

Magnesiation. Lithium magnesiates have proven to be effective in the deprotonation of the 2-position of oxazole to furnish the 2-Mg adduct. Similar to the lithiated species, the resulting met-alated compound exists in equilibrium between the ring-closed heterocycle and the ring-opened isonitrile. However, the former proved to be more reactive and amenable to Kumada-type coupling (eq 19). ... 

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