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. 2020 Sep 22;11(41):11307-11314.
doi: 10.1039/d0sc03409f. eCollection 2020 Nov 7.

Controlling cyclization pathways in palladium(ii)-catalyzed intramolecular alkene hydro-functionalization via substrate directivity

Xin Wang  1   2 , Zi-Qi Li  1 , Binh Khanh Mai  3 , John A Gurak Jr  1 , Jessica E Xu  1 , Van T Tran  1 , Hui-Qi Ni  1 , Zhen Liu  1 , Zhonglin Liu  1 , Kin S Yang  1 , Rong Xiang  2 , Peng Liu  3 , Keary M Engle  1
Affiliations

Controlling cyclization pathways in palladium(ii)-catalyzed intramolecular alkene hydro-functionalization via substrate directivity

Xin Wang et al. Chem Sci. .

Abstract

We report a series of palladium(ii)-catalyzed, intramolecular alkene hydrofunctionalization reactions with carbon, nitrogen, and oxygen nucleophiles to form five- and six-membered carbo- and heterocycles. In these reactions, the presence of a proximal bidentate directing group controls the cyclization pathway, dictating the ring size that is generated, even in cases that are disfavored based on Baldwin's rules and in cases where there is an inherent preference for an alternative pathway. DFT studies shed light on the origins of pathway selectivity in these processes.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Background and synopsis of current work.
Scheme 2
Scheme 2. Mechanistic experiments.
Scheme 3
Scheme 3. General depiction of a plausible reaction mechanism.
Fig. 1
Fig. 1. Computed energy profile of the 5-exo-trig cyclization of 1b (see ESI for energy profiles of 4-, 6-, and 7-exo-trig cyclizations of 1a, 1c, and 1d).
Fig. 2
Fig. 2. Activation free energies of syn-nucleopalladation transition states relative to IM1 and strain energies of the N-heterocycles.
Fig. 3
Fig. 3. Greater steric repulsions in the syn-nucleopalladation transition state TS2d to form a seven-membered ring.
See this image and copyright information in PMC

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