4,8‐Disubstituted Bicyclo[3.3.1]nona‐2,6‐dienes as Chiral Ligands for Rh‐Catalyzed Asymmetric 1,4‐Addition Reactions

Abstract

C2‐symmetric chiral diene ligands based on 4,8‐endo,endo‐disubstituted bicyclo[3.3.1]nona‐2,6‐diene framework have been designed and synthesized. The rhodium complexes of the dienes, which were obtained in a few straightforward steps from enantiomerically pure bicyclo[3.3.1]nonane‐2,6‐dione, exhibited excellent catalytic activity and high enantioselectivity (up to 96 % ee) in the conjugate addition reaction of arylboronic acids to cyclic enones under mild reaction conditions with high atom efficiency.

Fine‐Tuning the Bicyclo[3.3.1]nona‐2,6‐diene Ligands: Second Generation 4,8‐Substituted Dienes for Rh‐Catalyzed Asymmetric 1,4‐Addition Reactions

“…Indeed, rhodium complex with 4,8-bis(benzyloxy) diene 2 b, which emerged as a champion ligand, exhibited excellent catalytic activity and high enantioselectivity (up to 96 % ee) in the asymmetric arylation of cyclic enones 4 with arylboronic acids 5. [9] Nevertheless, conformational analysis of 2 b (vide infra) and inspection of the X-ray structure of [RhCl(2 b)] 2 revealed that 4,8-benzyloxy side chains are rather conformationally flexible and distant from the catalytically active center (for details, see Supporting Information, Figure S1).…”

“…[1] The pioneering reports on the application of bicyclic dienes in the asymmetric rhodium and iridium-catalyzed reactions by Hayashi [2] and Carreira [3] spurred intense research effort directed towards the synthesis and study of novel steering ligands. A variety of structurally diverse dienes based on bicyclo [2.2.1]heptadiene, [2,4] bicyclo [2.2.2]octadiene, [3,4c,5] bicyclo [3.3.0]octadiene [6] and propelladiene, [7] bicyclo [3.3.1]nonadiene, [8,9] dicyclopentadiene, [10] cyclooctadiene, [11] as well as acyclic [12] frameworks have been developed. Ligands of this type have been found to be particularly effective in the asymmetric rhodium-catalyzed conjugate addition of boronic acids to α,β-unsaturated carbonyl compounds and arylation of imines.…”

“…To this end, we have reported synthesis of C 2 -symmetric 4,8-endo,endo-disubstituted bicyclo [3.3.1]nona-2,6-diene chelating ligands and demonstrated their utility in the asymmetric rhodium-catalyzed 1,4-addition of boronic acids to cyclic enones. [9] In contrast to the common tactics, which involves manipulation of steering substituents at the vinylic positions, our approach to tuning the chiral environment around the diene-coordinated Rh atom relied on the functionalization of the ligand skeleton at the allylic positions. In comparison with the parent bicyclo [3.3.1]nona-2,6-diene, [25] the 4,8-bis(alkoxy) congeners displayed enhanced levels of enantioselectivity, thus demonstrating the beneficial effect of 4,8endo,endo-substitution on asymmetric induction.…”

Enantioselective Ring Opening of meso‐Epoxides with Silicon Tetrachloride Catalyzed by Pyridine N‐Oxides Fused with the Bicyclo[3.3.1]nonane Framework

“…The latter in our previous work has been successfully used as a key building-block for the synthesis of related enantiomerically pure structures, [20] self-assembling supramolecular tectons, [21] and ligands for asymmetric catalysis. [22] The initial synthetic strategy to access pyridine derivatives involved the use of exocyclic enones, such as 3,7-dibenzylidenebicyclo[3.3.1]nonane-2,6-dione (5), [23] as Michael acceptors. However, the Kröhnke annulation reaction [24] of 5 with the corresponding Kröhnke salt derived from 2Ј,4Ј,6Ј-trimethoxyacetophenone (6a) failed to produce desired bis(pyridine) derivative 8a.…”

Synthesis, Molecular Structure, and Chiroptical Properties of Dibenzylidene Derivatives of Bicyclo[3.3.1]nonane and Brexane

“…As a consequence, chiral bicyclo[3.3.1]nonanes have attracted considerable attention as targets for organic synthesis. 5 Interest in the bicyclononane derivatives is also related to their application in structural studies, 6 asymmetric catalysis, 7,8 and supramolecular chemistry. 9 The chirality and molecular shape of the bicyclo[3.3.1]nonane framework has been proven to be particularly suitable for design of monomers with specific molecular shape and inherent geometric features responsible for controlled self-assembly of a wide range of supramolecular structures.…”