Synthesis of Highly Enantioenriched Propelladienes and their Application as Ligands in Asymmetric Rh-Catalyzed 1,4-Additions

Abstract

The first synthesis of highly enantioenriched [4.3.3]propelladienes is reported. The novel bridged bicyclo[3.3.0] dienes were applied as steering ligands in the rhodium-catalyzed asymmetric arylation of cyclic enones. The catalytic system showed high catalytic activity, and the 1,4-adducts were obtained in good to excellent yields (46-99%) with enantioselectivities up to 96% ee.

Selectivity in Ring‐Closing Metathesis: Synthesis of Propellanes and Angular Aza‐tricycles

“…One of the triallyl derivatives (8 d) has been synthetically transformed by Suzuki-Miyaura crosscoupling reaction to generate the trifluorophenylsubstituted propellane and aza-tricylic derivatives. The structures of RCM products have been confirmed by catalytic hydrogenation and one of the structures (16) was supported by single-crystal X-ray diffraction studies. This methodology may be extended for the synthesis of kopsia indole alkaloids and erythrina alkaloids (Figure 1).…”

“…(Scheme 1b). [16] However, to the best of our knowledge, there are no reports on the formation of both scaffolds from a common starting material. This work mainly focuses on the selective formation of propellanes over aza-tricycles.…”

“…Fischer indolization and Grignard reactions are used as key steps to prepare the substrates required for RCM. [16] However, to the best of our knowledge, there are no reports on the formation of both scaffolds from a common starting material. [15] More specifically, this method is applicable for the synthesis of compounds containing quaternary carbon centers, present in several naturally occurring alkaloids ( Figure 1).…”

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

“…To test this hypothesis, conformational analysis of the selected ligands 2 a-b, 3 aa-ba, 3 fa and 3 ha was performed using MMFF94 force field, followed by further geometry optimization at the B3LYP/6-31G(d) level. [26] Analysis of 2 a-b revealed that (ap, ap)-, (-sc, ap)-and (-sc, -sc)conformers with alkoxy groups synclinal (sc) and antiperiplanar (ap) to C 4(8) À C 3 (7) bonds are close in energy and thus comparably populated (Figures S2-S3). Steric hindrance imposed even by the smallest exo-substituents, such as methyl groups in 3 aa, is sufficient to significantly affect conformational mobility of the 4,8-endo,endo side chains.…”

“…[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.…”