biostudies-literatureSingh ADST | Science and Engineering Research BoardDST | Science and Engineering Research Board (SERB)Anusandhan National Research Foundation92-100https://www.ebi.ac.uk/biostudies/studies/S-EPMC12768968biostudies-literatureUnknown18(1)[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 scoNature chemistryOrganocatalysed three-component modular synthesis of BN isosteres and BN-2,1-azaboranaphthalenes via Wolff-type rearrangement.PMC12768968CRG/2018/002147Kant RSingh AGrellier MKumar RfalseOrganocatalysed 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 sco2026-01-01T00:00:00Z2026 Jan2026-06-06T10:51:03.363Z2026-05-29T03:12:01.897ZS-EPMC127689684092594410.1038/s41557-025-01938-1