Enantioselective Borohydride Reduction Catalyzed by Cobalt Complexes: Discovery, Analysis, and Design for a Halogen-Free System

Abstract

On the basis of a study on the enantioselective version of the oxidation-reduction hydration catalyzed by bis(1,3-diketonato)cobalt complexes, the highly enantioselective borohydride reduction of carbonyl compounds was developed in the presence of a catalytic amount of an optically active cobalt(II) complex catalyst. The experimental and theoretical studies on the mechanistic insight of this reaction revealed that the key reactive intermediate of borohydride reduction catalyzed by ketoiminatocobalt(II) complexes would be the dichloromethyl-cobalt hydride with a sodium cation, which was generated from chloroform and sodium borohydride. The theoretical simulation of various axial groups in active cobalt complex catalysts predicted that the cobalt-carbene complexes could be employed as efficient catalysts. The newly designed complexes generated from cobalt complex and methyl diazoacetate made it possible to catalyze the enantioselective borohydride reduction in a completely halogen-free solvent.

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

“…Salen-type ligands also provided cobalt complexes active toward the hydration of styrenes (Figure ). In this case, a chiral nonracemic catalyst ( 417 ) could catalyze the formation of enantioenriched products such as ( R )- 418 (82% ee), a result that was used to question the involvement of a free radical when the C–O bond was formed . However, this result was not reproducible in 250 batches.…”

“…92 In this case, a chiral non-racemic catalyst ( 417 ) could catalyze the formation of enantioenriched products such as (R) - 418 (82% ee ), a result that was used to question the involvement of a free radical when the C-O bond was formed. 436 However, this result was not reproducible in 250 batches. More disturbingly, when the reductant was changed to sodium borohydride, the opposite sense in enantioselection was obtained leading to (S) - 418 .…”

Mild olefin formation via bio-inspired vitamin B12 photocatalysis

“…We found this low isomerization activity interesting, as we expected that the system should behave similarly to that of Shenvi in the presence of olefins, especially as borohydride reductants have been shown to generate cobalt hydride species in Co(Salen) frameworks. 46 …”

Large-Scale Carbonyl Reductions in the Pharmaceutical Industry

“…Although not yet reported on large scale, the combinations of NaBH 4 and chiral cobalt complexes, or NaBH 4 or LiBH 4 and chiral Lewis acid ( l )-TarB–NO 2 boronic ester, have potential for future process applications of reagent-controlled, asymmetric ketone reduction.…”