Asymmetric Synthesis of P-Stereogenic Phosphinic Amides via Pd(0)-Catalyzed Enantioselective Intramolecular C–H Arylation

Abstract

The palladium-catalyzed enantioselective intramolecular C-H arylation of N-(2-haloaryl)-P,P-diphenylphosphinic amides furnishes P-stereogenic phosphine oxide derivatives in 61-99% yield with 88-97% ee. The catalyst generated in situ from a TADDOL-derived phosphoramide ligand and Pd(dba)2 is optimum in terms of yield and enantioselectivities.

Rhodium(III)‐Catalyzed Enantiotopic C−H Activation Enables Access to P‐Chiral Cyclic Phosphinamides

“…[ and tBuOK were inferior to K 2 CO 3 (entries [8][9][10]. Solely potassium phosphate gave as imilar enantioselectivity,b ut as lightly reduced reactivity.A mong several oxidants screened, silver carbonate proved to be the reagent of choice (entries 11 and 12).…”

“…[6] Methods for their preparation comprise the formation and separation of diastereomeric mixtures,a sw ell as other resolution techniques. [8] However, these are often limited in their scope,and additional methods enabling access to different substitution patterns would be of high synthetic value. [8] However, these are often limited in their scope,and additional methods enabling access to different substitution patterns would be of high synthetic value.…”

“…[7] More-recent approaches involve desymmetrization reactions and catalytic asymmetric methods. [8] However, these are often limited in their scope,and additional methods enabling access to different substitution patterns would be of high synthetic value.…”

Pd-catalyzed enantioselective C–H arylation of phosphinamides with boronic acids for the synthesis of P-stereogenic compounds

“…(1)). Soon after, Duan et al, Liu et al, and Tang et al disclosed independently the asymmetric intramolecular C-H/C-Br arylation of other phosphorus variants through a Pd (0) to Pd (II) cycle, [65][66][67] wherein chiral phosphoramidites or phosphines were employed as effective chiral ligands (Scheme 1, Eq. (2) and (3)).…”

Rhodium‐Catalyzed Enantioposition‐Selective Hydroarylation of Divinylphosphine Oxides with Aryl Boroxines

“…[1,2] One of the most extensively studied reactions for their catalytic asymmetric synthesis is the desymmetrization of symmetrically substituted phosphine oxides RP(O)AA,w here one of the two enantiotopic substituents A is converted into ad ifferent substituent B while leaving the other A substituent unchanged (Scheme 1a). [4] One drawback of such asymmetric transformations is the overreaction of RP(O)AB resulting in RP(O)BB,which is achiral. [4] One drawback of such asymmetric transformations is the overreaction of RP(O)AB resulting in RP(O)BB,which is achiral.…”