Catalytic Asymmetric Hydroboration (CAHB) can provide access to a variety of versatile chiral secondary and tertiary boronic esters. Recently, the Takacs group has explored different dimensions of the rhodium-catalyzed variant of CAHB by pinacolborane focusing on the reactions of amide-, oxime ether- and phosphonate-directed unsaturated substrates using rather simple BINOL- and TADDOL-derived chiral phosphonates and phosphoramidites. Herein, we report the successful CAHB of a new class of substrates, acyclic N-acyl allylamines. These afford chiral amine derivatives bearing γ-boronic ester functionality in yields up to 90% with 98:2 enantioselectivity. The nature of the N-acyl group is important; higher selectivity was observed with a benzyloxy carbonyl (Cbz) or phthalimide as the amine protecting group compared to N-acetyl or N-tert-butoxycarbonyl (Boc) derivatives. In some cases, the major enantiomer obtained is independent of starting alkene geometry, thus revealing that rhodium-catalyzed E/Z-alkene isomerization occurs prior to borylation. In addition, we will discuss the new use of Rh(I)-hydride and Rh(I)-boryl pre-catalysts as alternatives to common cationic Rh(I) salts. Reaction profile kinetic analysis (RPKA) and isotope labeling experiments will be discussed, and in selected cases, stereospecific transformations of the newly generated C–B bond is used to access pharmaceutical drugs highlighting the utility of these chiral synthons.

Asymmetric synthesis of γ-borylated amines via rhodium: Catalyzed hydroboration of allylamine derivatives

ACS Fall 2021

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