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. 2020 Dec 8;12(5):1937-1943.
doi: 10.1039/d0sc05276k.

Kinetic resolution of racemic allylic alcohols via iridium-catalyzed asymmetric hydrogenation: scope, synthetic applications and insight into the origin of selectivity

Affiliations

Kinetic resolution of racemic allylic alcohols via iridium-catalyzed asymmetric hydrogenation: scope, synthetic applications and insight into the origin of selectivity

Haibo Wu et al. Chem Sci. .

Abstract

Asymmetric hydrogenation is one of the most commonly used tools in organic synthesis, whereas, kinetic resolution via asymmetric hydrogenation is less developed. Herein, we describe the first iridium catalyzed kinetic resolution of a wide range of trisubstituted secondary and tertiary allylic alcohols. Large selectivity factors were observed in most cases (s up to 211), providing the unreacted starting materials in good yield with high levels of enantiopurity (ee up to >99%). The utility of this method is highlighted in the enantioselective formal synthesis of some bioactive natural products including pumiliotoxin A, inthomycin A and B. DFT studies and a selectivity model concerning the origin of selectivity are presented.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Kinetic resolution via asymmetric hydrogenation.
Scheme 1
Scheme 1. Double stereo-differentiation.
Scheme 2
Scheme 2. Gram-scale kinetic resolution and concise synthesis of the chiral building block of 15(R)-pumiliotoxin A.
Scheme 3
Scheme 3. Enantioselective formal total synthesis of inthomycin A and B.
Fig. 2
Fig. 2. Origin of selectivity depicting: (a) steric environment around Ir. (b) Quadrant model illustrating the matched and mismatched allylic alcohol. (c) 3D quadrant model.
Fig. 3
Fig. 3. Calculated relative energy profile.

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