Organocatalysed three-component modular synthesis of BN isosteres and BN-2,1-azaboranaphthalenes via Wolff-type rearrangement

[2,1]-Azaboranaphthalenes represent unique boron-nitrogen (BN) isosteres of naphthalenes, attracting interest for the development of molecules with enhanced therapeutic potency. The existing synthetic strategies are generally two-component reactions with harsh conditions. Here we report an organocatalysed three-component modular synthesis of ring-fused BN isosteres and BN-2,1-azaboranaphthalenes following ring expansion of unstrained cyclic ketones (n = 4-8) via Wolff-type rearrangement. The strategy used 2-formylarylboronic acid as a C-B surrogate and TMSN3 as an exogenous single nitrogen source, allowing the de novo rapid synthesis of BN isosteres by forging C-C, C-N and B-N bonds under a single operation. The developed method proved to be compatible with a broad substrate scope (58 examples), including cyclic ketones and diverse heterocycles, which afforded 1C ring-expanded [2,1]-azaborines.The reaction was also effective with acyclic ketones, yielding BN naphthalene isosteres. Control experiments and density functional theory study dictate the plausible reaction pathways following [1,2]-C-C/C-H shift, analogous to Wolff rearrangement.