Catalytic Asymmetric Synthesis of Chiral Tertiary Organoboronic Esters through Conjugate Boration of β-Substituted Cyclic Enones

• Published in: Journal of the American Chemical Society Vol. 131; no. 33; pp. 11664 - 11665
• Main Authors: Chen, I-Hon, Yin, Liang, Itano, Wataru, Kanai, Motomu, Shibasaki, Masakatsu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.08.2009; Amer Chemical Soc
• Subjects: Alkenes - chemistry; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Esters - chemistry; Ketones - chemistry; Physical Sciences; Science & Technology; Stereoisomerism; Substrate Specificity; QUATERNARY STEREOGENIC CENTERS; ENANTIOSELECTIVE SYNTHESIS; CONSTRUCTION; ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; BOND FORMATION; ALPHA; TRISUBSTITUTED ENONES; ADDITIONS; ARYL ALUMINUM REAGENTS; DIBORON
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja9045839

The first catalytic enantioselective conjugate boration of β-substituted cyclic enones was developed to produce enantiomerically enriched tertiary organoboronates. The optimized asymmetric catalyst includes a QuinoxP*-CuO t Bu complex generated from CuPF6(CH3CN)4 and LiO t Bu. In situ generated LiPF6 significantly increased product yield. The enantioselectivity, however, was almost constant irrespective of the alkali metal used (Li, Na, or K). Moreover, a protic additive, which was essential in the previous Cu-catalyzed enantioselective boration to linear β-monosubstituted substrates (Yun’s reaction), was not necessary. The substrate scope was broad, and high to excellent enantioselectivity was produced using both β-aromatic and aliphatic (linear and branched)-substituted cyclic enones with five-, six-, and seven-membered ring sizes. Due to the synthetic versatility of organoboron compounds, a variety of new chiral building blocks containing a chiral tetrasubstituted carbon was synthesized based on this methodology. Specifically, a one-pot three-component reaction from α,β-substituted cyclic enone, bis(pinacolato)diboron (PinB-BPin: 2), and an aldehyde proceeded with a high level of enantio- and diastereocontrol. These chiral building blocks are difficult to access using other methods.