Palladium-catalyzed asymmetric annulation between aryl iodides and racemic epoxides using a chiral norbornene cocatalyst

Abstract

Herein, we describe our initial development of an asymmetric Pd-catalyzed annulation between aryl iodides and racemic epoxides for synthesis of 2,3-dihydrobenzofurans using a chiral norbornene cocatalyst. A series of enantiopure ester-, amide- and imide-substituted norbornenes have been prepared with a reliable synthetic route. Promising enantioselectivity (42–45% ee) has been observed using the isopropyl ester-substituted norbornene (N1*) and the amide-substituted norbornene (N7*).

Catalytic Atroposelective Catellani Reaction Enables Construction of Axially Chiral Biaryl Monophosphine Oxides

“…To validate the feasibility of our conjecture and continue our long-term interest in boron chemistry, [58][59][60][61][62][63] 1-iodonaphthalene (1a), (2-bromo-3-methylphenyl)diphenylphosphine oxide (2a), and phenylboronic acid were first chosen as model substrates for the assembly of axially chiral monophosphine oxides. First, enantiopuresubstituted NBEs were prepared according to literature procedures 50,51 ; unfortunately, after careful condition screening (see Supporting Information Table S1 for details), only n-propyl ester NBE L3 demonstrated reactivity to deliver the desired axially chiral product in 57% NMR yield (48% isolated yield) with 98% ee, due to various Suzuki reaction side products (see Supporting Information for details). Considering alkenes are widely used in the Catellani reaction as the third component and the incorporation of a C=C bond will increase functionality of the final products, we employed styrene (3a) to replace phenylboronic acid in the model reaction.…”

“…Based on the previous reports on Pd/NBE-catalyzed aryl halide-involved three-component Catellani reaction [50][51][52][53][54][55][56] and our experience on catalytic asymmetric construction of atropisomeric biaryls, 59 reaction mechanism and atroposelectivity of the reported Pd-catalyzed Catellani reaction. As shown in Figure 2, the reaction starts from a solvent coordinated Pd species CP1, which can react with iodonaphthalene reactant 1a through an oxidative addition process via transition-state TS1 with an activation free energy of 8.6 kcal/mol.…”

“…In Gu et al's elegant work, 49 the chirality installation took place in the last cross-coupling step involving an achiral palladium (Pd) species. Motivated by the recent progress in Pd/norbornene (NBE) cooperative catalysis in which the functionalization of both ortho-and ipso-carbons of the starting arylhalides could be readily achieved, [50][51][52][53][54][55][56] especially the recent Pd/chiral NBE catalysis which has been successfully employed in asymmetric synthesis, 50,51 we envisioned a strategy for the establishment of optically active atropisomeric biaryl monophosphine oxides using a Pd/chiral NBE catalytic system from aryl iodide and a phosphine oxide-containing aryl bromide via the axially chiral Pd(II) intermediate in Figure 1c. Further trapping by the terminating nucleophile will render a modular platform for the divergent synthesis of enantioenriched biaryl atropisomers (Figure 1c).…”

Catellani Reaction: An Enabling Technology for Vicinal Functionalization of Aryl Halides by Palladium(0)/Norbornene Cooperative Catalysis

“…Subsequently, asymmetric control of the reaction was enabled by the chiral version of NBE co-catalyst. [53] Scheme 19 ortho-Alkylation of aryl iodides via epoxides In 2018, Zhou described the efficient use of epoxides for the ortho alkylation and ipso Heck cascade reaction (Scheme 19b). [54] Furthermore, the isochroman scaffold (38), usually found in many bioactive natural products, could be furnished by an oxa-Michael addition.…”

Recent Advances in Synthetic Strategies to 2,3-Dihydrobenzofurans

“…The Dong group then developed an asymmetric version of this annulation using enantiopure NBE cocatalyst. 77 A series of enantiopure ester-, amide-, and imide-substituted NBEs were also prepared. Moderate enantioselectivity (42-45% ee) was observed using an isopropyl ester substituted NBE and an amide-substituted norbornene.…”