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. 2019 Nov 25;11(3):851-855.
doi: 10.1039/c9sc04534a.

Catalytic asymmetric hydrogenation of (Z)-α-dehydroamido boronate esters: direct route to alkyl-substituted α-amidoboronic esters

Yazhou Lou  1 , Jun Wang  1 , Gelin Gong  1 , Fanfu Guan  1 , Jiaxiang Lu  1 , Jialin Wen  1   2 , Xumu Zhang  1
Affiliations

Catalytic asymmetric hydrogenation of (Z)-α-dehydroamido boronate esters: direct route to alkyl-substituted α-amidoboronic esters

Yazhou Lou et al. Chem Sci. .

Abstract

The direct catalytic asymmetric hydrogenation of (Z)-α-dehydroamino boronate esters was realized. Using this approach, a class of therapeutically relevant alkyl-substituted α-amidoboronic esters was easily synthesized in high yields with generally excellent enantioselectivities (up to 99% yield and 99% ee). The utility of the products has been demonstrated by transformation to their corresponding boronic acid derivatives by a Pd-catalyzed borylation reaction and an efficient synthesis of a potential intermediate of bortezomib. The clean, atom-economic and environment friendly nature of this catalytic asymmetric hydrogenation process would make this approach a new alternative for the production of alkyl-substituted α-amidoboronic esters of great potential in the area of organic synthesis and medicinal chemistry.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Selected inhibitors containing chiral alkyl-substituted α-amidoboronic acids.
Scheme 1
Scheme 1. Approaches towards the synthesis of chiral alkyl-substituted α-aminoboronic esters.
Scheme 2
Scheme 2. Synthetic route to (Z)-α-dehydroamino boronates.
Scheme 3
Scheme 3. Scale-up synthesis and synthetic utility.
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