Pd-Catalyzed Asymmetric C–H Bond Activation for the Synthesis of P-Stereogenic Dibenzophospholes

Abstract

Pd-catalyzed asymmetric C−H bond activation for the synthesis of P-stereogenic dibenzophospholes was efficiently achieved via two types of catalytic systems. Chiral phosphoric amides/acids as ligands provided the products with up to 5:95 er, and (R)-segphos as ligand resulted in enantioselectivities of up to 98:2.

Chiral Catalysts for Pd0‐Catalyzed Enantioselective C−H Activation

“…[79] In addition to using SegPhosa sachiral ligand for the synthesis of P-stereogenic compounds through aryl desymmetrization (see Scheme 34), Duan and co-workersr eported the use of ac hiral base in combination with an achiral phosphine (Scheme 48). [94] They observed high levels of stereoinduction for unsubstitutedB INOL-derived acids and amides in combination with the well-defined Pd(PCy 3 ) 2 complex, and showed that, in this case, increasing the sterich indranceo nt he bi-naphthyl scaffold had an egative impact on the enantioselectivity.F urthermore, the phosphine ligand did not have am ajor influence on the enantioselectivity,a sa ne .r.o f9 1:9w as observed when using Pd(CH 3 CN) 2 Cl 2 as the Pd source and without added phosphine. Further optimization of the reaction conditions showedt hat a1 :1 combination of A 3 and A 8 resulted in as ignificant enhancement of the enantioselectivity,a nd that the catalyst loading could be reduced.…”

“…In addition to using SegPhos as a chiral ligand for the synthesis of P‐stereogenic compounds through aryl desymmetrization (see Scheme 34), Duan and co‐workers reported the use of a chiral base in combination with an achiral phosphine (Scheme 48). [94] They observed high levels of stereoinduction for unsubstituted BINOL‐derived acids and amides in combination with the well‐defined Pd(PCy 3 ) 2 complex, and showed that, in this case, increasing the steric hindrance on the binaphthyl scaffold had a negative impact on the enantioselectivity. Furthermore, the phosphine ligand did not have a major influence on the enantioselectivity, as an e.r.…”

“…In 2017 and 2019, the groups of Cui and Xu [93] and Duan [94] developed a procedure for the enantioselective construction of P‐stereogenic dibenzophospholes 77 (Scheme 34). Although very similar, these two approaches employed different diphosphine ligands, that is, ( S , S )‐Me‐Duphos in the report by Cui and Xu and ( R )‐Segphos in the work by Duan, which both afforded high enantioselectivities, although a somewhat higher functional group tolerance was demonstrated by the latter ( 77 d , 77 f ).…”

Efficient Synthesis of P-Chirogenic Compounds Enabled by Chiral Selenide-Catalyzed Enantioselective Electrophilic Aromatic Halogenation

“…To avoid the consumption of stoichiometric amounts of chiral reagents, asymmetric catalytic methods such as metal-catalyzed asymmetric couplings [12][13][14][15][16][17][18][19][20] and desymmetrization of prochiral phosphorus molecules have been developed. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Particularly, desymmetrization methods have been a more focus lately. Typical examples include transition metalcatalyzed intra-and intermolecular C-H functionalization, [22][23][24][25][26][27][28] Mo-and Ru-catalyzed ring-closing metathesis, 29,30 Rh-catalyzed cycloaddition and hydroarylation, 31,32 Au-catalyzed intramolecular hydroetherification, 33 Nheterocyclic carbene (NHC)-catalyzed esterification, 34 Tm-catalyzed intermolecular sulfenylation, 35 and cinchona alkaloid-catalyzed allylic alkylation reaction.…”

Enantioselective Pd0‐Catalyzed C(sp2)–H Arylation for the Synthesis of Chiral Warped Molecules

“…At the transition state of this step, both the ligand and the base are coordinated to the metal center. Therefore, a chiral ancillary ligand [5] and/or a chiral base [6,7] may be used to bring in stereocontrol over the reaction. To induce a more organized transition state, and thereby to provide higher enantioselectivities in challenging cases, we recently developed a new family of chiral bifunctional phosphine-carboxylate ligands (Scheme 1 a).…”