Denitrogenative Carbon Skeleton Cleavage and Reorganization of Pyridines by a Trinuclear Titanium Polyhydride Complex

Xiaoxi Zhou; Shaowei Hu; Qingde Zhuo; Gen Luo; Takanori Shima; Zhaomin Hou

doi:10.1021/jacs.5c11238

Denitrogenative Carbon Skeleton Cleavage and Reorganization of Pyridines by a Trinuclear Titanium Polyhydride Complex

J Am Chem Soc. 2025 Nov 12;147(45):41462-41471. doi: 10.1021/jacs.5c11238. Epub 2025 Oct 31.

Authors

Xiaoxi Zhou¹, Shaowei Hu², Qingde Zhuo³, Gen Luo⁴, Takanori Shima^{1

3}, Zhaomin Hou^{1

3}

Affiliations

¹ Organometallic Chemistry Laboratory, RIKEN Pioneering Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
² College of Chemistry, Beijing Normal University, Beijing 100875, China.
³ Advanced Catalysis Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
⁴ Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China.

PMID: 41171174
DOI: 10.1021/jacs.5c11238

Abstract

Selective skeletal transformations of aromatic N-heterocycles are of fundamental interest and practical importance but remain a formidable challenge due to their pronounced aromatic stability. Herein we report an unprecedented denitrogenative carbon skeleton cleavage and reorganization of pyridines mediated by the trinuclear titanium polyhydride complex [(Cp'Ti)₃(μ₃-H)(μ-H)₆] (Cp' = C₅Me₄SiMe₃). The reactions of 2-R-, 3-R-, and 4-R-substituted pyridines (R = Me, Et, ⁱPr, ^tBu, Ph) with this titanium hydride complex at 160 °C uniformly yield the denitrogenated 3-R-substituted pentadienyl complexes [(Cp'Ti)₃{μ₃-η¹:η²:η²:η¹-CHCHC(R)CHCH}(μ-H)(μ₃-N)]. Isolation and characterization of key intermediates reveal that the pyridine skeleton can be fragmented into combinations of [N]^3-, [CHC(R)CHCH]^4-, and [CH₂]^2- units or [NC(R)CHCH]^4- and [CHCH]^2- groups depending on the sterics and positions of the R substituents. Upon heating to 160 °C, recombination of the hydrocarbon fragments leads to the thermodynamically favored [CHCHC(R)CHCH]^5- framework. These transformations proceed via multiple steps involving C-H, C-C, and C-N bond cleavages as well as C-H and C-C bond re-formations. This work underscores the unique capability of multinuclear titanium hydride clusters to mediate skeletal cleavage and reorganization of aromatic N-heterocycles, offering a new strategy for heterocycle-to-hydrocarbon molecular editing.