Chiral Catalysts for Pd⁰‐Catalyzed Enantioselective C−H Activation

Abstract

In the past few decades, processes that involve transition-metal catalysis have represented am ajor parto f the synthetic chemist'st oolbox. Recently,t he interesth as shifted from the well-established cross-coupling reactions to CÀHb ond functionalization, thus making it ac urrent frontier of transition-metal-catalyzed reactions. Constant progress in this field has led to the discoveryo fe nantioselective methods to generate and control various types of stereogenic elements, thereby demonstrating its high value to generate scalemic chiral molecules.The present review is dedicated to enantioselective Pd 0-catalyzed CÀHa ctivation,w hich may be considered as an evolution of Pd 0-catalyzed cross-couplings, with af ocus on the different chiral ligands and catalysts that enable theset ransformations.

Design of Chiral NHC‐Carboxylates as Potential Ligands for Pd‐Catalyzed Enantioselective C−H Activation

“…[53] ( . 13 C-NMR is consistent with literature data. [53] N 2 -Formyl-N-[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]-L -valinamide (11).…”

“…The resulting mixture was stirred at 25°C for 16 h. The mixture was diluted with CH 2 Cl 2 and washed with sat. 13 C-NMR spectrum is consistent with literature data. [53] ( .…”

“…The combined organic phases were dried over Na 2 SO 4 , filtered, and concentrated under reduced pressure. Methyl 2-(Bromomethyl)benzoate (13). NBS (1.77g, 10.0 mmol, 1.00 equiv.)…”

“…After these initial reports, diverse enantioselective transformations proceeding through Pd 0 -catalyzed C(sp 3 )À H activation were published. [13] Different classes of chiral ligands, including phosphoramidites, [14] phosphines, [15,16] phosphonites, [17] diazaphospholidines, [18] and NHCs [11] were employed in order to reach a high enantioselectivity for different classes of products. Alternatively, the use of a chiral base in combination with an achiral ligand is also able to deliver enantioselectivity in Pd 0 / Pd II catalyzed C(sp 3 )À H arylation.…”

“…The following chiral column from Daicel Chemical Industries was used: OJ-H (Chiralcel®) in 4.6 × 250 mm size. residual peaks 1 H δ 7.26 ppm,13 C δ 77.16 ppm), deuterated acetonitrile (residual peaks 1 H δ 1.94 ppm, 13 C δ 1.32 ppm) or deuterated dichloromethane (residual peaks 1 H δ 5.32 ppm, 13 C δ 54.00 ppm) unless otherwise noted. Data are reported in parts per million [ppm] as follows: chemical shift, multiplicity (s = singlet…”