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

Abstract

Chiral boronic esters are useful intermediates in asymmetric synthesis. We have previously shown that carbonyl-directed catalytic asymmetric hydroboration (CAHB) is an efficient approach to the synthesis of functionalized primary and secondary chiral boronic esters. We now report 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% and enantiomer ratios up to 96:4 er. The utility of the method is demonstrated by the formation of chiral diols and O-substituted hydroxylamines, the generation of quaternary carbon stereocenters via carbon-carbon coupling reactions, and the preparation of chiral 3,4,4-trisubstituted isoxazolines.

Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross‐Coupling

“…1), allylic borylation 4 (eq. 2), and directed hydroboration 5 (eq. 3) have facilitated the construction of tertiary boronic esters from appropriately functionalized precursor substrates.…”

Asymmetrische Synthese sekundärer und tertiärer Boronsäureester

“…Mit b,g-ungesättigten Amiden als Substrate entwickelte Takacs eine Methode,d ie mit hervorragender Regio-und Stereokontrolle einen Zugang zu b-Borylamiden ermçglicht. [32] Tang und Mitarbeiter entwickelten auch eine amidgesteuerte asymmetrische Hydroborierung von a-Arylenamiden. [30,31] Unter Ausnutzung der Oximfunktion zur Steuerung des Hydroborierungsprozesses entwickelte Takacs außerdem eine bedeutende Methode zur Synthese tertiärer Boronsäureester,b ei der die erwartete anti-Markownikoff-Selektivitätd urch die dirigierende Oximgruppe außer Kraft gesetzt wurde.…”

Enantioselective γ-borylation of unsaturated amides and stereoretentive Suzuki–Miyaura cross-coupling

“…1–3 Consequently, an assortment of enantioselective routes for their preparation are under active development. 4–19 We have focused on the rhodium-catalyzed catalytic asymmetric hydroboration (CAHB) of β,γ-unsaturated amides, 20 esters, 20 a and oxime ethers 21 for the preparation of functionalized chiral boronic esters. For example, disubstituted alkenes such as ( E )- 1 undergo highly enantioselective β-borylation by pinacolborane (pinBH) when catalyzed by the combination of ( R )- L1 with [Rh(nbd) 2 BF 4 ] ( i.e.…”