Enantioselective palladium-catalyzed carbonylation of gem-dibromoalkenes to chiral benzo[7]annulenes
Abstract
Chemo- and enantioselective mono-debrominative functionalization of 2,2-disubstituted 1,1-dibromoalkenes to access tetrasubstituted vinyl bromides remains a formidable challenge, owing to competitive double functionalization and the difficulty in achieving enantiocontrol when the gem-dibromoalkenyl moiety embodies a prochiral plane. Herein, we report a palladium-catalyzed asymmetric monocarbonylation of conformationally rigid, prochiral benzo[7]annulene-based gem-dibromoalkenes, furnishing inherently chiral tetrasubstituted benzo[7]annulene derivatives with excellent yields (up to 97%) and high enantioselectivities (up to 98:2 er). Notably, the inclusion of simple acid additives enables a switchable pathway divergence to double debrominative carbonylation, delivering inherently chiral trisubstituted vinyl carboxylic acids with equally good chemo- and enantiocontrol. This protocol is also applicable to unsymmetric gem-dibromoalkene substrates, affording the corresponding products with synthetically useful yields and enantioselectivities. Mechanistic studies, supported by DFT calculations, reveal that the acid-induced formation of a key alkylidene carbene-Pd-H species is pivotal for the pathway switch, followed by enantioselective carbene insertion into the Pd-H bond and subsequent CO insertion. This work not only provides a modular and divergent route to both tri- and tetrasubstituted inherently chiral benzo[7]annulene scaffolds, but also represents the first asymmetric desymmetrization of planarly prochiral gem-dibromoalkenes via palladium catalysis.
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BibTeX
@article{luo2026enantioselective,
title = {{Enantioselective palladium-catalyzed carbonylation of gem-dibromoalkenes to chiral benzo[7]annulenes}},
author = {Yu Luo and Xilong Wang and Yuanhang Zhang and Shuang Luo and Qiang Zhu},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78226-0},
url = {https://www.nature.com/articles/s41467-026-78226-0},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Enantioselective palladium-catalyzed carbonylation of gem-dibromoalkenes to chiral benzo[7]annulenes
AU - Yu Luo
AU - Xilong Wang
AU - Yuanhang Zhang
AU - Shuang Luo
AU - Qiang Zhu
PY - 2026
DA - 2026/10/03
JO - Nature Communications
DO - 10.1038/s41467-026-78226-0
UR - https://www.nature.com/articles/s41467-026-78226-0
AB - Chemo- and enantioselective mono-debrominative functionalization of 2,2-disubstituted 1,1-dibromoalkenes to access tetrasubstituted vinyl bromides remains a formidable challenge, owing to competitive double functionalization and the difficulty in achieving enantiocontrol when the gem-dibromoalkenyl moiety embodies a prochiral plane. Herein, we report a palladium-catalyzed asymmetric monocarbonylation of conformationally rigid, prochiral benzo[7]annulene-based gem-dibromoalkenes, furnishing inherently chiral tetrasubstituted benzo[7]annulene derivatives with excellent yields (up to 97%) and high enantioselectivities (up to 98:2 er). Notably, the inclusion of simple acid additives enables a switchable pathway divergence to double debrominative carbonylation, delivering inherently chiral trisubstituted vinyl carboxylic acids with equally good chemo- and enantiocontrol. This protocol is also applicable to unsymmetric gem-dibromoalkene substrates, affording the corresponding products with synthetically useful yields and enantioselectivities. Mechanistic studies, supported by DFT calculations, reveal that the acid-induced formation of a key alkylidene carbene-Pd-H species is pivotal for the pathway switch, followed by enantioselective carbene insertion into the Pd-H bond and subsequent CO insertion. This work not only provides a modular and divergent route to both tri- and tetrasubstituted inherently chiral benzo[7]annulene scaffolds, but also represents the first asymmetric desymmetrization of planarly prochiral gem-dibromoalkenes via palladium catalysis.
SN - 2041-1723
ER -