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

Abstract

Chiral boronic esters are useful intermediates in asymmetric synthesis.W eh ave previously shown that carbonyl-directed catalytic asymmetric hydroboration (CAHB) is an efficient approach to the synthesis of functionalized primary and secondary chiral boronic esters.W en ow report that the oxime-directed CAHB of alkyl-substituted methylidene and trisubstituted alkene substrates by pinacolborane (pinBH) affords oxime-containing chiral tertiary boronic esters with yields up to 87 %a nd enantiomeric ratios up to 96:4 e.r. The utility of the method is demonstrated by the formation of chiral diols and O-substituted hydroxylamines,t he generation of quaternary carbon stereocenters through carbon-carbon coupling reactions,a nd the preparation of chiral 3,4,4-trisubstituted isoxazolines.Catalytic asymmetric hydroboration (CAHB) has attracted renewed interest for the synthesis of chiral organoboronates. Many of the successful applications exploit the reaction of vinyl arene substrates. [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. [3] Fore xample,u nder the conditions specified in Scheme 1, methylidene derivative 1 undergoes regioselective CAHB on the alkene Si face to afford chiral hydroxyamide 2 with 96:4 e.r. after oxidation of the intermediate g-borylated amide.Encouraged by the success of carbonyl-directed CAHB, we are exploring the effectiveness of other potential directing groups.O xime functionality has been used in conjunction with av ariety of transition-metal catalyst systems to direct metalation reactions,m ost frequently to direct ortho-CÀH activation of aromatic substrates but increasingly for C(sp3)À Ha ctivation as well. [4] Neufeldt and Sanford also recently reported the oxime-directed palladium-catalyzed dioxygenation of an adjacent alkene. [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. It seems likely that the contrasting regio-and stereochemical outcomes observed with 1 versus 5aare...

Review for chiral-at-metal complexes and metal-organic framework enantiomorphs

“…(3) Metal-centered chiral catalysts may enrich and simplify the preparation of chiral products and attract interest in asymmetric synthesis. In fact, as an important alternative toward carbon, silicon is attractive in synthesis, materials, and medicinal chemistry, with the enantioselectivity installed in the silicon groups [14,69,70]. The principle and general consideration of silicon chirality is the same as that for carbon.…”

“…Similarly, various salts of the coordination complex, named as Hexol, were also obtained [10]. Some chiral metal complexes with chiral ligands have been reported [11][12][13][14], a little different to the chiral-at-metal complexes discussed hereafter. The examples in Figs.…”

Enantioselective Rh-Catalyzed Hydroboration of Silyl Enol Ethers

“…), 5 and the ones with a directing group (X = DG). 6 Catalytic enantioselective hydroborations of heteroatom-substituted alkenes are rarely explored (X = B, N, Si, P, S), 7 and the heteroatom-substituted alkenes employed previously typically have a conjugated electron-withdrawing group. For example, Sand P-substituted alkenes participated in the asymmetric hydroboration in the form of α,β-unsaturated sulfones 7g and phosphonates, 7f respectively.…”

Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross‐Coupling

“…[2] In this regard, notable advances in catalytic conjugate borylation [3] [Eq. (2)],a nd directed hydroboration [5] [Eq. (2)],a nd directed hydroboration [5] [Eq.…”