Isocyanides reactions with Grignard reagents

Methoxyphenyl isocyanide, 41, 103 Methyl crotonate, reaction with -butyl Grignard reagent and cuprous chloride, 41, 63... 

Grignard reagents fail to react with dihydro-1,3-oxazines unsubstituted at C-2, but n-butyllithium in diethyl ether yields 2-butyltetrahydro-l,3-oxazines. However, the reaction is solvent-dependent and in THF the ring is opened to give isocyanides (69TL5151). 

Acid-catalyzed iminium ion 57 fonnation is followed by isocyanide 54 addition and capture of the remaining nitrilium ion 58 by the carboxylate of 56 to generate compound 59. A rapid O N acyl transfer takes then place in order to obtain dipeptide 60 as a mixture of epimers at C4. Although the control of the stereochanistry of the newly formed stereocenter still remains a problan of the Ugi reaction, it nicely demonstrates the force of the Ugi MCR, as all of the carbon atoms needed are successively assanbled in a single step [22], Mannich-type 4CR are often used for the synthesis of natural products. One example is the synthesis of the alkaloid ( )-roelactamine 65 (Scheme 6.6). The reaction of piperonal 61 with methylamine, Grignard reagent 62, and acid chloride 63 results in the formation of amide 64, which... 

---