Complete diastereodivergence in asymmetric 1,6-addition reactions enabled by minimal modification of a chiral catalyst.
Catalytic systems that allow selective generation of any diastereomer of a reaction product bearing multiple stereocentres through minimal modification of a single catalyst scaffold remain elusive, particularly for carbon-carbon bond formations requiring simultaneous control of multiple selectivity factors. Here, we report a catalyst-directed pinpoint inversion of diastereochemical preference in the 1,6-addition of azlactones to δ-aryl dienyl carbonyl compounds with full control over other selectivities preserved. This rigorous diastereodivergence is enabled by the slight structural adjustment of a chiral iminophosphorane catalyst, providing access to all the stereoisomers with high regio-, distereo- and enantioselectivity. The utility of this method is demonstrated in the facile stereodivergent preparation of densely functionalized proline derivatives. The experimental and computational elucidation of the origin of the diastereodivergence is also reported.
Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya 464-8601, Japan.
Daisuke
0000-0002-6584-797X
D
Uraguchi
Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya 464-8601, Japan.
Ken
K
Yoshioka
Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya 464-8601, Japan.|CREST, Japan Science and Technology Agency (JST), Nagoya University, Nagoya 464-8601, Japan.
Takashi
T
Ooi
D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D008956:Models, Chemical; D015394:Molecular Structure; D009930:Organic Chemicals / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D009930:Organic Chemicals; D002244:Carbon