Lithiomethyl isocyanide

Benzylisoquinolines,2 A short synthesis of the benzylisoquinoline (4) involves reaction of lithiomethyl isocyanide with 2 equivalents of piperonal (1) to give, after acetylation, the oxazoline 2, formed via a 2-lithiooxazoline. The remaining steps are outlined in equation (I). 

I URANES Dimethylformamidc dimethyl acetal. Lithiomethyl isocyanide. 1-Nilro-l-(phenyllhio)propene. Organo-aluminum compounds. 

Reaction with lactones.1 Under controlled conditions and in DMF as solvent lithiomethyl isocyanide reacts with lactones to form alcoholic oxazoles (equation I). 

Reaction of Lithiomethyl Isocyanide with Hexyl Bromide, Oxirane, and Cyclohexanone (Note 1)... 

Ohba s group employed this methodology in two different synthetic strategies for preparing 372, a key intermediate in their synthesis of (-)-normalindine 374 (Scheme 1.102). Acylation of lithiomethyl isocyanide with A-Boc-L-alanine methyl ester gave 370 that was deprotected and alkylated with 2-(3-indolyl)ethyl bromide... 

Vedejs and Barda adapted Schollkopf s methodology " and prepared an indole-oxazole C-D-E model fragment, which was subsequently incorporated into a more advanced C-D-E-G-1 fragment. 4-Benzyloxyindole was converted to 1496 in four steps and excellent overall yield (Scheme 1.383, p. 337). Treatment of 1496 with lithiomethyl isocyanide produced a 2 1 mixture of the acylisocyanide (not shown) and 1497. Reaction of this mixture with PPTS cleanly provided the C-D-E model fragment, 1497. The triflate 1497a was then prepared in three straightforward steps. 

Wenkert and co-workers prepared a series of 5-alkenyl-substituted oxazolium salts and investigated their intramolecular Diels-Alder reactions as a means to construct alkaloids (Scheme 1.427). The starting oxazoles 1662a-c, 1663, and 1664 were prepared from an acyclic methyl ester and lithiomethyl isocyanide. Methylation of 1662a-c, 1663, and 1664 with methyl trillate then afforded the corresponding iV-methyloxazolium salt quantitatively. The oxazolium salts 1665, 1666, and 1667 were stable for up to 3 h at 90°C. 

Besides the formation of oxazole derivatives, Schollkopf and the others have successfully extended the a-alkali metalated isocyanides to the formation of the chain-extended primary amines, 2-oxazolines, 2-thiazoline-4-carboxylic esters," 2-imidazolines, 2-pyrrolines and pyrroles, thiazoles, 2-imidazolin-5-ones," 2-imidazolinones," etc. For example, a simple reaction between lithiomethyl isocyanide with two equivalents of piperonal followed by acetylation of the intermediate with acetic anhydride affords the corresponding oxazoline. ... 

A -Substituted (o-isocyanophenyl)acetamides (98), prepared by the addition of o-(lithiomethyl)phenyI isocyanide to isocyanates, are cyclized by CU2O catalyst to give indoles and/or l,3-benzodiazepin-4-ones (99) formation of the latter is favoured by less bulky R groups. " ... 

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