Palladium‐Catalyzed Asymmetric Benzylic Alkylation of Active Methylene Compounds with α‐Naphthylbenzyl Carbonates and Pivalates

Abstract

A Pd/(R)-H8 -BINAP-catalyzed asymmetric benzylic alkylation of active methylene compounds has been developed. The reaction proceeds without the use of an external base, and the starting racemic diarylmethyl carbonates are converted into the optically active coupling products which contain the benzylic chiral stereocenter by a dynamic kinetic asymmetric transformation (DYKAT). Additionally, with suitable carbonates bases, the same palladium catalysis allows the corresponding pivalates to be adopted in the same DYKAT process.

Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles

“…Outstanding studies by the groups of Fiaud, Kwano, and Tunge provided some resolution to this restriction; however, the generation of enantioenriched products remains a major challenge. Focusing on the generation of stereochemistry at the electrophilic carbon atom, noteworthy contributions from Fiaud and Hirano/Murai have described the use of secondary benzyl electrophiles in reactions that proceed by partial kinetic resolution or by a dynamic kinetic asymmetric transformation (DYKAT), respectively . To address stereochemical induction at the nucleophilic carbon atom, Trost and Czabaniuk reported the highly enantioselective benzylation of cyclic prochiral azlactone and 3‐aryl oxindole nucleophiles using primary benzylic carbonates and phosphates (Figure b) .…”

“…Focusing on the generation of stereochemistry at the electrophilic carbon atom, noteworthy contributions from Fiaud and Hirano/Murai have described the use of secondary benzyl electrophiles in reactions that proceed by partial kinetic resolution or by a dynamic kinetic asymmetric transformation (DYKAT), respectively. [4,5] To address stereochemical induction at the nucleophilic carbon atom, Trost and Czabaniuk reported the highly enantioselective benzylation of cyclic prochiral azlactone and 3-aryl oxindole nucleophiles using primary benzylic carbonates and phosphates (Figure 1 b). [6] Although few in number, these remain the most effective Pd-catalyzed benzylic alkylation methods available.…”

Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles

“…Outstanding studies by the groups of Fiaud, Kwano,a nd Tu nge provided some resolution to this restriction; [3] however, the generation of enantioenriched products remains am ajor challenge.F ocusing on the generation of stereochemistry at the electrophilic carbon atom, noteworthy contributions from Fiaud and Hirano/Murai have described the use of secondary benzyl electrophiles in reactions that proceed by partial kinetic resolution or by ad ynamic kinetic asymmetric transformation (DYKAT), respectively. [4,5] To address stereochemical induction at the nucleophilic carbon atom, Tr ost and Czabaniuk reported the highly enantioselective benzylation of cyclic prochiral azlactone and 3-aryl oxindole nucleophiles using primary benzylic carbonates and phosphates (Figure 1b). [6] Although few in number, these remain the most effective Pd-catalyzed benzylic alkylation methods available.…”

“…[14] Whereas p-extended electrophiles functioned effectively,s imple monocyclic benzylic phosphates were unreactive,p resumably owing to the aforementioned energy required for dearomatization. [2][3][4][5][6] Pfp esters derived from alkylacetic acids are also unreactive within this cooperative catalysis framework.…”

Palladium‐Catalyzed Suzuki–Miyaura Cross‐Coupling of Secondary α‐(Trifluoromethyl)benzyl Tosylates

“…[5] Theg reatest breadth of scope and utility is arguably demonstrated by nickel catalysts, [6] with both stereospecific [7] and stereoconvergent variants known. [8] Palladium-catalyzed cross-coupling reactions with secondary electrophiles are comparatively far less well developed, [9] which is aconsequence of the relatively low rate of oxidative addition and the undesired competing b-hydride elimination. [10] In particular,e xamples of palladium-catalyzed Suzuki-Miyaura cross-couplings of secondary electrophiles are rare.…”