Surprisingly facile C–H activation in the course of oxime-directed catalytic asymmetric hydroboration

Abstract

Deuterium-labeling studies carried out in conjunction with investigations into the directed catalytic asymmetric hydroboration of unsaturated oxime ethers reveal a surprisingly facile ortho-metallation or σ-bond metathesis pathway that that diverts the expected course of CAHB to a tandem C-H activation/hydroboration reaction pathway.

Synthesis of Chiral Tertiary Boronic Esters by Oxime‐Directed Catalytic Asymmetric Hydroboration

“…Whereas rhodium‐catalyzed hydroboration of 3 led to some γ‐borylation, the yield of 4 (after oxidation) was low, and the enantioselectivity was poor. The major side reactions are ortho ‐borylation of the benzophenone‐derived oxime with concomitant alkene reduction . We now report that the corresponding acetone‐derived oxime ethers are excellent substrates for oxime‐directed CAHB; for example, 5 a underwent oxime‐directed CAHB/oxidation to give 6 a in good yield (71 %) and with high levels of asymmetric induction (95:5 e.r.).…”

“…[5] Foro ur initial attempts at oxime-directed CAHB,w e employed benzophenone-derived allylic oxime ethers,such as 3.Whereas rhodium-catalyzed hydroboration of 3 led to some g-borylation, the yield of 4 (after oxidation) was low,and the enantioselectivity was poor.T he major side reactions are ortho-borylation of the benzophenone-derived oxime with concomitant alkene reduction. [6] We now report that the corresponding acetone-derived oxime ethers are excellent substrates for oxime-directed CAHB;for example, 5a underwent oxime-directed CAHB/oxidation to give 6a in good yield (71 %) and with high levels of asymmetric induction (95:5 e.r.). Furthermore,t he borylated intermediate is at ertiary boronic ester arising from Re-face b-borylation;i n contrast, carbonyl-directed CAHB of 1 proceeds by Si-face gborylation.…”

“…The major side reactions are ortho -borylation of the benzophenone-derived oxime with concomitant alkene reduction. [6] We now report that the corresponding acetone-derived oxime ethers are excellent substrates for oxime-directed CAHB; for example, 5a undergoes oxime-directed CAHB/oxidation to give 6a in good yield (71%) and with high levels of asymmetric induction (95:5 er). Furthermore, the borylated intermediate is a tertiary boronic ester arising from re -face β–borylation; in contrast, carbonyl-directed CAHB of 1 proceeds via si -face γ–borylation.…”

Synthesis of Chiral Tertiary Boronic Esters by Oxime‐Directed Catalytic Asymmetric Hydroboration

“…[1,2] Our research has instead focused on the directed CAHB of b,g-unsaturated amide and ester substrates.T he carbonyl moiety controls the regioselectivity of the rhodium-catalyzed addition of simple achiral boranes, such as pinacolborane (pinBH), and chiral phosphite and phosphoramidite ligands control the p-facial selectivity.A variety of chiral primary and secondary boronic esters are readily synthesized. [6] We now report that the corresponding acetone-derived oxime ethers are excellent substrates for oxime-directed CAHB;for example, 5a underwent oxime-directed CAHB/oxidation to give 6a in good yield (71 %) and with high levels of asymmetric induction (95:5 e.r.). after oxidation of the intermediate g-borylated amide.…”

“…[4] Neufeldt and Sanford also recently reported the oxime-directed palladium-catalyzed dioxygenation of an adjacent alkene. [6] We now report that the corresponding acetone-derived oxime ethers are excellent substrates for oxime-directed CAHB;for example, 5a underwent oxime-directed CAHB/oxidation to give 6a in good yield (71 %) and with high levels of asymmetric induction (95:5 e.r.). [6] We now report that the corresponding acetone-derived oxime ethers are excellent substrates for oxime-directed CAHB;for example, 5a underwent oxime-directed CAHB/oxidation to give 6a in good yield (71 %) and with high levels of asymmetric induction (95:5 e.r.).…”