Synthesis of 5-Amino-2,5-dihydro-1H-benzo[b]azepines Using a One-Pot Multibond Forming Process.

Rapid access to allylic trichloroacetimidates bearing a 2-allylaminoaryl group from readily available 2-iodoanilines combined with a one-pot multibond forming process has allowed the efficient synthesis of a series of 5-amino-2,5-dihydro-1H-benzo[b]azepines. The potential of these compounds as synthetic building blocks was demonstrated by the preparation of a late-stage intermediate of the hyponatremia agent, mozavaptan.

Silver(I)-Catalyzed Iodination of Arenes: Tuning the Lewis Acidity of N-Iodosuccinimide Activation.

A mild and rapid method for the iodination of arenes that utilizes silver(I) triflimide as a catalyst for activation of N-iodosuccinimide has been developed. The transformation was found to be general for a wide range of anisole, aniline, acetanilide, and phenol derivatives and allowed the late-stage iodination of biologically active compounds such as PIMBA, a SPECT imaging agent of breast cancer, and (-)-IBZM, a dopamine D2 receptor antagonist. The method was also modified for the radioiodination of arenes using a one-pot procedure involving the in situ generation of [(125)I]-N-iodosuccinimide followed by the silver(I)-catalyzed iodination.

Synthesis of Allylic Amide Functionalized 2H-Chromenes and Coumarins Using a One-Pot Overman Rearrangement and Gold(I)-Catalyzed Hydroarylation.

A four-step synthesis of allylic trichloroacetimidates bearing a 2-proparyloxyaryl group has been developed from readily available 2-hydroxybenzaldehydes, and these have been used for the preparation of allylic amide derived 2H-chromenes using an Overman rearrangement and a 6-endo-dig hydroarylation. High yields of the 2H-chromenes were achieved using a stepwise approach involving an Overman rearrangement under thermal conditions followed by a hydroarylation reaction with a gold(I) triflimide catalyst. An alternative method where both reactions were performed as a one-pot process was also developed and instead used a gold(I) chloride catalyst activated by silver(I) hexafluoroantimonate for the cycloisomerization step. The allylic amide derived 2H-chromenes were converted to the corresponding coumarin analogues by a pyridinium dichromate (PDC)-mediated chemoselective allylic oxidation.

One-Pot Synthesis of 5-Amino-2,5-dihydro-1-benzoxepines: Access to Pharmacologically Active Heterocyclic Scaffolds.

A one-pot multibond-forming process involving a thermally mediated Overman rearrangement and a ring closing metathesis reaction of allylic trichloroacetimidates bearing a 2-allyloxyaryl group has been developed for the synthesis of 5-amino-substituted 2,5-dihydro-1-benzoxepines. Chemoselective reduction and functionalization of these compounds allowed access to a range of pharmacologically active 5-amino-2,3,4,5-tetrahydro-1-benzoxepine scaffolds.