Two Cycles with One Catch: Hydrazine in Ugi 4‑CR and Its Postcyclizations

Isocyanide-based
multicomponent reactions (IMCR) are by far the
most versatile reactions that can construct relatively complex molecules
by one-pot synthesis. More importantly, the development of post IMCR
modifications significantly improves the scaffold’s diversity.
Here, we describe the use of N-Boc protected hydrazine
together with α-amino acid derived isocyanides in the Ugi tetrazole
reaction and its post cyclization under both acidic and basic conditions.
The cyclization in acidic conditions was conducted in a one pot fashion,
which give 7-aminotetrazolopyrazinone (6) and tetrazolotriazepinone
(7) cyclic products. The post cyclization under basic
condition could selectively afford Boc-protected 7-aminotetrazolopyrazinone
(8) products in yield of 38–87%.