ChemInform Abstract: Rhodium‐Catalyzed N‐tert‐Butoxycarbonyl (Boc) Amination by Directed C—H Bond Activation.

Abstract

N‐tert‐Butoxycarbonyl azide (BocN3) was shown to be an efficient and economic source for the directed introduction of N‐Boc protected amino groups into the thiophene and benzene nucleus. Yields for the amination of 2‐pyridin‐2‐ylthiophenes (10 examples) were 52–88%. For the amination of the respective benzenes (10 examples) yields between 54% and 99% were recorded with an improved reactivity observed for substrates that bear an electron‐withdrawing group. The reaction was applied to short total syntheses of the indoloquinoline alkaloids quindoline and cryptolepine. The facile removal of the Boc protecting group was the key to the success of the syntheses. The scope of the reaction was extended to a C(sp3)H bond amination and to the amination of 2‐phenyloxazoline. For the amination of 2‐pyridin‐2‐ylbenzene a kinetic deuterium isotope effect of 2.0 was determined.

Transition Metal-Catalyzed C–H Amination: Scope, Mechanism, and Applications

“…175 Recently, Bach used a deprotectable amidating reagent, tert-butoxycarbonyl azide, in the total synthesis of quindoline and cryptolepine. 176 Lu reported a selective mono-or bisamination of 2-phenylpyridine in the reaction with aryl azides in water. 177 The mechanistic details were thoroughly investigated by the same research group.…”

Directing group strategies in rhodium-catalyzed C–H amination

“…The efficient and cost-effective introduction of N -Boc-protected amino groups into the thiophene and benzene nucleus was demonstrated using N-tert -butoxycarbonyl azide (BocN 3 ) (Scheme 11). 29 The amination of 2-pyridin-2-ylthiophenes produced 52%–88% yields. The reactivity of substrates with an electron-withdrawing group was observed to be improved from the 54% to 99% yields for amination of the respective benzenes.…”