Catalytic asymmetric synthesis of chiral tertiary organoboronic esters through conjugate boration of beta-substituted cyclic enones.
The first catalytic enantioselective conjugate boration of beta-substituted cyclic enones was developed to produce enantiomerically enriched tertiary organoboronates. The optimized asymmetric catalyst includes a QuinoxP*-CuO(t)Bu complex generated from CuPF(6)(CH(3)CN)(4) and LiO(t)Bu. In situ generated LiPF(6) 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 beta-monosubstituted substrates (Yun's reaction), was not necessary. The substrate scope was broad, and high to excellent enantioselectivity was produced using both beta-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 alpha,beta-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.
Chen
I-Hon
IH
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo113-0033, Japan.
Yin
Liang
L
Itano
Wataru
W
Kanai
Motomu
M
Shibasaki
Masakatsu
M
D000475:Alkenes / Q000737:chemistry*; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000475:Alkenes; D001896:Boron Compounds; D004952:Esters; D007659:Ketones