Chiral Dirhodium(II) Catalysts with Orthometalated Aryl Phosphine Ligands:  Synthesis and Application for Enantioselective C−H Insertion of α-Diazo Ketones

Abstract

Racemic dirhodium(II) complexes derived from orthometalated aryl phosphines, Rh 2 (O 2 -CCH 3 ) 2 (pc) 2 (pc ) orthometalated phosphine, with head-to-tail arrangement) (1-7), are isolated as pure enantiomers by conventional resolution methods. They are the first examples of dirhodium(II) chiral catalysts without chiral ligands. These compounds have been used in the cyclization of R-diazo ketones; the influence of catalyst and substrate on enantioselectivity is studied. Results are compared with those obtained for reactions catalyzed by Rh 2 (protos) 4 and Rh 2 (protos) 2 (pc) 2 [ProtosH (8) ) N-(4-methylphenylsulfonyl-L-proline] (9-22). Only catalysts 1-7 afford a high level of enantioselectivity in the synthesis of carbocycles from R-diazo ketones.

Catalytic asymmetric C–H insertion reactions of α-diazocarbonyl compounds

“…64,163,164 Improvements in both yields and enantioselectivity were noted upon changing from an electron-donating (X = OMe) to an electron-withdrawing (X = Cl) aromatic substituent for aryl diazoacetate precursors, 67,163,165,166 as had previously been noted in intramolecular C-H insertion studies. 93,107 As seen in Scheme 16, insertion is favoured at positions α to oxygen, 62,167,168 with the same preference also holding true for insertion adjacent to nitrogen, 63,65,124,164,169,170 and at benzylic 64,171 and allylic 20,[172][173][174] sites. The use of hydrocarbon solvents (hexane, 2,2-dimethylbutane) for intermolecular C-H insertion processes has also been found to increase asymmetric induction, compared with the use of polar solvents, 64,173,175 a trend also observed for asymmetric cyclopropanation reactions.…”

“…107,113 Chiral copper(I)-bis(oxazoline) and ortho-metalated rhodium(II) catalysts have also shown some success in this area, 31,93,114 but the enantioselectivities obtained with these complexes have been moderate.…”

“…Moderate-to-good asymmetric induction was reported by Lahuerta and co-workers for the Rh 2 (O 2 CMe) 2 (PC) 2 -catalysed C-H insertion of α-diazoketone 44 (Table 7, entries a-f). 93 The electronic effects of the diazo substrates were of central importance in this study. Addition of an electronwithdrawing substituent (X = F, Cl) to the phenyl ring was shown to correspond to an increase in enantioselectivity (Table 7, entry a vs. b and d), while addition of an electrondonating group (X = OMe) provided no significant improvement in enantiocontrol (Table 7, entry a vs. f).…”

“…These complexes were subsequently shown to be effective catalysts for the asymmetric C-H insertion reactions of α-diazoketones, 93 producing cyclopentanone products with enantioselectivity as high as 74% ee, representing a significant improvement on previous attempts at enantiocontrol in the decomposition of α-diazoketones. 2 A new series of biscyclometalated Rh(II) compounds of general formula Rh 2 (OOCR) 2 (PC) 2 .…”

Chiral Molecules Containing Metal–Metal Bonds

“…Reaction with ProtosH (N-4-methylphenylsulfonyl-L-proline, see Scheme 4) yields (R,S)-cisRh 2 (C 6 H 4 PPh 2 ) 2 (Protos) 2 ·2H 2 O and the diastereoisomers are easily separated by column chromatography using silica gel and elution with a mixture of CH 2 Cl 2 /Et 2 O. [20] Many analogs using a great variety of substituted phosphanes have also been synthesized. These compounds have applications in enantioselective C-H insertion of α-diazo ketones and other catalyzed reactions.…”