Synthesis of Azabicyclo[3.1.1]heptenes Enabled by Catalyst-Controlled Annulations of Bicyclo[1.1.0]butanes with Vinyl Azides.

Bridged bicyclic scaffolds are emerging bioisosteres of planar aromatic rings under the concept of "escape from flatland". However, adopting this concept into the exploration of bioisosteres of pyridines remains elusive due to the challenge of incorporating a N atom into such bridged bicyclic structures. Herein, we report practical routes for the divergent synthesis of 2- and 3-azabicyclo[3.1.1]heptenes (aza-BCHepes) as potential bioisosteres of pyridines from the readily accessible vinyl azides and bicyclo[1.1.0]butanes (BCBs) via two distinct catalytic annulations. The reactivity of vinyl azides tailored with BCBs is the key to achieving divergent transformations. TiIII-catalyzed single-electron reductive generation of C-radicals from BCBs allows a concise (3 + 3) annulation with vinyl azides, affording novel 2-aza-BCHepe scaffolds. In contrast, scandium catalysis enables an efficient dipolar (3 + 2) annulation with vinyl azides to generate 2-azidobicyclo[2.1.1]hexanes, which subsequently undergo a chemoselective rearrangement to construct 3-aza-BCHepes. Both approaches efficiently deliver unique azabicyclo[3.1.1]heptene scaffolds with a high functional group tolerance. The synthetic utility has been further demonstrated by scale-up reactions and diverse postcatalytic transformations, providing valuable azabicyclics including 2- and 3-azabicyclo[3.1.1]heptanes and rigid bicyclic amino esters. In addition, the related sp2-hybridized nitrogen atom and the similar geometric property between pyridines and corresponding aza-BCHepes indicate that they are promising bioisosteres of pyridines.

Metal-free ß,γ-C(sp3)-H difunctionalization of propanols: DMP-initiated asymmetric spirocyclopropanation.

A DMP-initiated metal-free effective ß,γ-asymmetric spirocyclopropanation of propanols strategy using oxidative iminium activation is described. This process has been realized by a synergistic amine-catalyzed one-pot cascade oxidation-Michael addition cyclopropanation for "one-pot" access to various spirocyclopropyl propionaldehydes/propanols from diverse 3-arylpropanols and α-brominated active methylene compounds under mild conditions and with high enantioselectivity (ee up to >99%).

High atomic utilization conversion of ethers into furancarbaldehydes via an ether oxidation iminium-ion activation cascade strategy.

A novel organocatalytic one-pot cascade ether oxidation iminium-ion activation strategy for the synthesis of naphtho[2,1-b]furan-1-carbaldehyde and benzofuran-3-carbaldehyde from high atomic utilization transformation of aryl allyl ethers has been developed. Its synthetic application will provide a new ether oxidation iminium-ion activation cascade tool for the efficient synthesis of complex molecules.

One-pot three-component access to 5-hydroxyindoles based on an oxidative dearomatization strategy.

A one-pot three-component reaction based on an oxidative dearomatization strategy has been performed to provide facile access to 5-hydroxyindole derivatives through a ZnI2-catalyzed tandem process. The multi-unit reactions for the construction of a new C-C bond and two C-N bonds are simple and efficient under mild conditions, and the yield of the target product is as high as 91%.